National Formulary of India

NFI

4th Edition 2011

Government of India Ministry of Health & Family Welfare

INDIAN PHARMACOPOEIA COMMISSION Ministry of Health & Family Welfare Government of India
I NFI-2011

2011, Indian Pharmacopoeia Commission Application for reproduction should be made to The Secretary-Cum-Scientific Director INDIAN PHARMACOPOEIA COMMISSION Sector-23, Raj Nagar, Ghaziabad-201 002, India Tel: (91-120)-2783401 Fax: (91-120-2783311 Website: [Link] [Link]: ipclab@[Link] ISBN-978-93-81238-02-8

NFI 4th Edition

On behalf of : Produced & published by : Government of India Ministry of Health & Family Welfare Indian Pharmacopoeia Commission Government of India, Ministry of Health & Family Welfare Sector 23, Raj Nagar, Ghaziabad-201 002 PMS Arts & Communications 1-A, Suraj Kund Road Pehladpur, New Delhi 110 044

Designed and printed at :

Price: Inland

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Contents
Preface...............................................................................................V Acknowledgements ......................................................................... IX List of Medicines in NFI .................................................................... XI Common Abbreviations ................................................................ XXIII General Advice to Prescribers ......................................................XXVI 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. Analgesics, Antipyretics, Non-Steroidal Anti-Inflammatory Drugs ......................................................... 3 Antacids and Antiulcer Drugs ................................................ 15 Antiallergics and Drugs used in Anaphylaxis.......................... 25 Anti-Alzheimer and Anti-Parkinsonism Drugs........................ 39 Anticonvulsants/Antiepileptics .............................................. 51 Antidiarrhoeals and Laxatives ................................................ 71 Antidotes and Substances Used in Poisoning ........................ 81 Antiemetics............................................................................ 97 Anti-Infectives ...................................................................... 105 Antimigraine Drugs .............................................................. 235 Antineoplastics and Immunosuppressives .......................... 243 Antiseptics and Disinfectants .............................................. 271 Cardiovascular Drugs ........................................................... 279 Dermatological Drugs .......................................................... 347 Diagnostic Agents ............................................................... 369 Dialysis Fluids....................................................................... 377 Disease Modifying Anti-Rheumatic Drugs (DMARDs) and Drugs for Gout............................................. 381 Diuretics............................................................................... 393 Drugs in Osteoporosis.......................................................... 403 Drugs for Anaesthesia.......................................................... 409 Drugs for Inflammatory Bowel Disease ............................... 427 Drugs for Myasthenia Gravis ............................................... 433 Drugs for Respiratory Diseases ............................................ 439 Hormones, Contraceptives and Related Drugs .................... 459 Immunologicals ................................................................... 509 Muscle Relaxants ................................................................. 535

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27. 28. 29. 30.

Ophthalmological Preparations ........................................... 543 Psychotherapeutic Drugs ..................................................... 565 Solutions Correcting Water, Electrolyte and Acid Base Disturbances ............................................................... 593 Vitamins, Minerals and Antianaemic Drugs......................... 603

Appendices
Appendix 1: Antimicrobial Resistance ......................................... 625 Appendix 2: Calculation of Electrolytes ...................................... 628 Appendix 3: Common Laboratory Parameters ............................ 632 Appendix 4: Disposal of unused/Expired Pharmaceutical Products ........................................ 637 Appendix 5: Drugs and Poisons Information Centres in India ..... 642 Appendix 6: Drug Interactions a. Drug-Alcohol Interactions ................................. 643 b. Drug-Contraceptive Interactions ....................... 645 c. Drug-Drug Interactions...................................... 648 d. Drug Food Interactions ................................... 696 Appendix 7: Drugs used in Special Conditions a. Hepatic Impairment .......................................... 701 b. Lactation............................................................ 710 c. Pregnancy.......................................................... 720 d. Renal Impairment.............................................. 722 Appendix 8: National Health Programmes (NHPs) ...................... 726 Appendix 9: National Immunization Schedule ............................ 727 Appendix 10: Pharmacogenetics................................................... 728 Appendix 11: Pharmacovigilance Programme of India ................. 732 Appendix 12: Pictograms .............................................................. 733 Appendix 13: Principles of Dose Calculation in Special Conditions a. Paediatrics ......................................................... 734 2 b. Geriatrics ............................................................ 737 Appendix 14: Storage of Drugs ..................................................... 739 Appendix 15: Therapeutic Drug Monitoring ................................. 745 Index ................................................................................ 748

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Preface
The first, second and third editions of National Formulary of India (NFI) were published in 1960, 1966 and 1979 respectively by the Ministry of Health, Govt. of India. In the past 3 decades there has been vast expansion in the range of new drugs and their formulations. To address the need of publication of an updated version of NFI, Ministry of Health and Family Welfare, Govt. of India vide their Notification No. [Link].X.11035/2/06DFQC dated 8th May, 2008 assigned this mandatory responsibility to the Indian Pharmacopoeia Commission (IPC), Ghaziabad and hence the NFI is being published by the IPC on behalf of the Govt. of India, Ministry of Health and Family Welfare. For this purpose, an Apex Body and a Core Group with the following composition were constituted: Chairman: Secretary, Ministry of Health and Family Welfare, Govt. of India

Apex Body (in alphabetical order)

1. Dr Nitya Anand, Ex-Director, CDRI, Lucknow 2. Mr L. C. Goyal, Additional Secretary & DG (CGHS), Ministry of Health and Family Welfare, Govt. of India 3. Prof. Y. K. Gupta, Head, Department of Pharmacology, All India Institute of Medical Sciences, New Delhi 4. Dr A. K. Panda, Joint Secretary (Regulation), Ministry of Health and Family Welfare, Govt. of India 5. Mr Debasish Panda, IAS, Joint Secretary (Human Resource), Ministry of Health and Family Welfare, Govt. of India 6. Mr Sanjay Prasad, Director, Ministry of Health and Family Welfare, Govt. of India 7. Mr P. D. Sheth, Vice-President, The International Pharmaceutical Federation, The Hague, The Netherlands 8. Dr G.N. Singh, Secretary-cum-Scientific Director, Indian Pharmacopoeia Commission, Ghaziabad 9. Dr Surinder Singh, Drugs Controller General of India, New Delhi 10. Prof. B. Suresh, Chairman, Scientific Body, Indian Pharmacopoeia Commission, Ghaziabad

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Core Group (in alphabetical order)

1. Mr A. K. Adhikari, Chief, Pharmacy Services, St. Stephens Hospital, Delhi 2. Prof. Praveen Aggarwal, Department of Emergency Medicine, All India Institute of Medical Sciences, New Delhi 3. Dr Veena Gupta, Consultant, Department of Radiotherapy, Safdarjung Hospital, New Delhi 4. Prof. Y. K. Gupta, Head, Department of Pharmacology, All India Institute of Medical Sciences, New Delhi 5. Prof. S. K. Kabra, Paediatric Pulmonology Division, Department of Paediatrics, All India Institute of Medical Sciences, New Delhi 6. Prof. G. C. Khilnani, Department of Medicine, All India Institute of Medical Sciences, New Delhi 7. Dr Jai Prakash, Principal Scientific Officer, Indian Pharmacopoeia Commission, Ghaziabad 8. Mr P. D. Sheth, Vice-President, The International Pharmaceutical Federation, The Hague, The Netherlands 9. Dr G. N. Singh, Secretary-cum-Scientific Director, Indian Pharmacopoeia Commission, Ghaziabad 10. Prof. Pramil Tiwari, Head, Department of Pharmacy Practice, National Institute of Pharmaceutical Education & Research, Mohali, Punjab, India

The Criteria for Inclusion of Drugs in NFI:

Drugs in National List of Essential Medicines 2011, India Drugs used in National Health Programmes Drugs listed in Indian Pharmacopoeia Drugs not covered but recommended by panel of experts Any drug (s) considered appropriate by the IPC

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NFI Review Process

To fulfil the mandate of publishing the NFI, the following process has been adopted: Policy Framework by Apex Body WHO Model Formulary - taken as zero draft Review by Core Group Modification to Indian Context suggested by Subject Review Committee Review by Core Group and Apex Body Pre-Print Version Release for Public Comments Review and Incorporation of Public Comments Adoption for NFI

Subject Review Committee (in alphabetical order)

The manuscript was reviewed and the contents updated to suit Indian context by the Subject Review Committee. 1. Dr Hemant Singh Bhadauria, Pharmacology, All India Institute of Medical Sciences, New Delhi 2. Dr Arun Kumar Dahiya, Pharmacology, All India Institute of Medical Sciences, New Delhi 3. Dr Aman Goyal, Pharmacology, All India Institute of Medical Sciences, New Delhi 4. Dr Sheffali Gulati, Pediatric Neurology, All India Institute of Medical Sciences, New Delhi 5. Dr Pooja Gupta, Pharmacology, All India Institute of Medical Sciences, New Delhi 6. Dr Madhur Gupta, WHO-India (Country Office), New Delhi 7. Dr Nirmal Gurbani, SMS Medical College, Jaipur 8. Dr Ashish Kakkar, Pharmacology, All India Institute of Medical Sciences, New Delhi 9. Dr V. Kalaiselvan, Indian Pharmacopoeia Commission, Ghaziabad VII NFI-2011

10. Dr D.B.A. Narayana, Delhi Pharmaceutical Trust 11. Dr Biswa Mohan Padhey, Pharmacology, All India Institute of Medical Sciences, New Delhi 12. Mr S. Prabu, Indian Pharmacopoeia Commission, Ghaziabad 13. Dr Jai Prakash, Indian Pharmacopoeia Commission, Ghaziabad 14. Dr Aarohan Pruthi, Pharmacology, All India Institute of Medical Sciences, New Delhi 15. Dr R.K. Sanghavi, Indian Drugs Manufacturers Association, Mumbai 16. Dr Sudhir Chandra Sarangi, Pharmacology, All India Institute of Medical Sciences, New Delhi 17. Dr P.G. Shrotriya, Elite Pharma Consultancy Services, Ahmedabad 18. Ms Sreeja PV, Indian Pharmacopoeia Commission, Ghaziabad 19. Dr Pramil Tiwari, National Institute of Pharmaceutical Education and Research, Mohali, Punjab, India 20. Mr S. S. Venkatakrishnan, Thiruvananthapuram, Kerala 21. Dr Rakesh Yadav, Cardiology, All India Institute of Medical Sciences, New Delhi NFI is not a regulatory document. Physicians are supposed to use their professional judgement. Inclusion/Exclusion of monographs in NFI is a dynamic process. The drugs contained in NFI have been chosen for rational and economic prescribing. NFI would serve as a guidance document to medical practitioners, pharmacists, nurses, medical and pharmacy students, and other healthcare professionals and stakeholders in healthcare system. The feedback from stakeholders is invited

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Acknowledgements
We are pleased to present the 4th Edition of National Formulary of India. It has materialized after a gap of 3 decades. During this period, there have been tremendous advancements in therapeutic strategies and newly available drugs. This edition incorporates the changes based on the current knowledge. Valuable inputs that emerged during the meetings of the Core Group and the inputs received in responce to the pre-print version circulated have given this edition a unique feature by incorporating value added informations. The Commission is greatly indebted to the Members of the Core Group and the Subject Review Experts from diverse fields who consented to review the manuscript of the Formulary. The services of all these experts are appreciated. The inspiration and the historical perspective were made available by Dr Nitya Anand, Dr Harkishan Singh, and Dr B. D. Miglani with close involvement of Mr P. D. Sheth, VicePresident, FIP. The initial inputs in the form of list of drugs to be incorporated was compiled based on drugs available in IP and NLEM at a short notice by Dr Pramil Tiwari and his team. The Commission is especially indebted to Mr P. D. Sheth for providing the infrastructural facilities required to carry out this work uninterruptedly. During the preparation of pre-print version, important guidance was received from Mr Duncan Enright of BNF. We are thankful to Dr Richard Laing and Dr Suzanne Hill at WHO Geneva and Dr Krisantha Weerasuria at WHO-SEARO for their suggestions, support and encouragement. Thanks are due to Dr P. Venugopal for his participation and guidance. Mr P. D. Sheth engaged a technical team consisting of Mr S. C. Bhasin, Mr M. Ahmed Khan and Mr Syed Jalal Q. Rahman in the initial compilation of the NFI. Dr Jai Prakash, Principal Scientific Officer, Indian Pharmacopoeia Commission played a major role in every step in bringing out the NFI. He was ably supported by other members mainly Dr V. Kalaiselvan, Mr S. Prabu, Ms Sreeja PV, Mrs Puja Rajput and Mr Munesh Bindal in coordinating and contributing in updating the manuscript of NFI. Special thanks go to the members who prepared Appendices which have added value to this fourth edition of NFI. Prof. Y. K. Gupta deserves a special mention for his crucial role in preparing and enriching the contents of the formulary by closely coordinating with his colleagues throughout the course of preparation of this Formulary. IX NFI-2011

This National Formulary has been adopted from the WHO Model Formulary and thoroughly updated for its content, especially keeping in view the end user in India for which we wish to thank profusely Dr Y. K. Gupta, Dr Praveen Aggarwal, Dr Sheffali Gulati and the Resident Clinicians team of Dr Y. K. Gupta of the Department of Pharmacology Dr Pooja Gupta, Dr Biswa Mohan Padhy, Dr Ashish Kakkar, Dr Aarohan Pruthi, Dr Arun Kumar Dahiya, Dr Aman Goyal and Dr Hemant Singh Bhadauria at the All India Institute of Medical Sciences, New Delhi. We are grateful to Dr B. D. Miglani and Mr S. L. Nasa for their strong recommendation to bring out the National Formulary containing the much needed information for physicians, nurses and pharmacists on the uses and doses of drugs. The Commission is highly appreciative of the encouragement and support received from Mr L. C. Goyal, Additional Secretary & DG (CGHS), Mr Debasish Panda, Joint Secretary (HR), Dr A. K. Panda, Joint Secretary (Regulation), Mr Sanjay Prasad, Director (Drugs) and Dr Surinder Singh, DCG (I) and other officials of Ministry of Health & Family Welfare. The Commission appreciates the comments offered on the pre-print version of NFI by the stakeholders. The inputs received from the institutions, state governments and stakeholders have helped to shape the 4th Edition. Their names figure on website of the Commission ([Link]). The Commission acknowledges the significant contribution of Prof. Y. K. Gupta and his team in critically analysing the comments received on pre-print version of NFI from stakeholders. Last but not the least, IPC also places on record thanks to the services of IPC employees, its scientific body members and other subject experts who from time to time provided their valuable inputs. Dr G. N. Singh Secretary-cum-Scientific Director Indian Pharmacopoeia Commission

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List of Medicines in NFI

S. No. Medicines 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 Abacavir Abciximab Acetazolamide Acetylsalicylic Acid Actinomycin D Activated Charcoal Acyclovir Adenosine Adrenaline (Epinephrine) Albendazole Albumin Alendronate Allopurinol Alpha Interferon Alprazolam Alteplase Aluminium Hydroxide Amikacin Amiloride Aminophylline Amiodarone Amitriptyline Amlodipine Amodiaquine Amoxycillin Amphotericin B Ampicillin Arteether Artemether Artesunate L- Asparaginase Atenolol Atorvastatin Atracurium Besylate Page No. 211 317 545 4 248 84 230 292 28,561 168 323 404 389 248 566 318 18 196 396 447 293 571 304 182 114 156 117 182 183 184 257 281 342 535

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S. No. Medicines 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 Atropine Azathioprine Azithromycin Baclofen Barium Sulphate Beclomethasone Benzathine Benzyl Penicillin Benzyl Benzoate Benzyl Penicillin Betamethasone Betaxolol Biperiden Bisacodyl Bleaching Powder Bleomycin Bromocriptine Budesonide Bupivacaine Busulphan Calamine Calcium Disodium Edetate Calcium Gluconate Capreomycin Carbamazepine Carbimazole Cefazolin Cefixime Cefoperazone Cefotaxime Ceftazidime Ceftriaxone Centchroman (Non-steroidal oral contraceptive) Cephalexin Cetrimide Chlorambucil Chloramphenicol Chlorhexidine

Page No. 88 266 118 536 373 448 119 365 120 354 546 45 75 276 249 46 449 417 250 355 84 607 196 55 505 121 122 122 123 124 125 462 126 272 250 127 272

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S. No. Medicines 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 Chloroquine Chloroxylenol Chlorpheniramine Chlorpromazine Cinnarizine Ciprofloxacin Cisplatin Clarithromycin Clindamycin Clobazam Clofazimine Clomifene Clomipramine Clonazepam Clonidine Clopidogrel Clotrimazole Cloxacillin Coaltar Codeine Colchicine Cyclophosphamide Cycloserine Cyclosporine Cytosine Arabinoside (Cytarabine) Danazol Dapsone Desferrioxamine Mesylate Dexamethasone Dextran 40 Dextromethorphan Diazepam Diclofenac Dicyclomine Didanosine Diethylcarbamazine Digoxin

Page No. 178 276 28 577 29 128 251 130 131 56 189 495 588 57 304 319 158 132 360 10 389 252 197 267 252 482 189 88 30 324 456 57 5 429 213 153 295

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S. No. Medicines 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144 145 Dihydroergotamine Diloxanide Furoate Diltiazem Dimercaprol (BAL) Dithranol Dobutamine Domperidone Donepezil Dopamine Doxorubicin Doxycycline Efavirenz Emtricitabine Enalapril Ergometrine Erythromycin Erythropoietin Escitalopram Esmolol Ethambutol Ethinylestradiol Ethyl Alcohol Etoposide Ezetimibe Factor VIII Concentrate Factor IX Complex (Coagulation Factors II, VII, IX, X) Concentrate Famotidine Fenofibrate Fexofenadine Fluconazole Flucytosine Flumazenil Flunarizine Fluorescein 5-Fluorouracil Fluoxetine Fluphenazine

Page No. 239 106 282 89 361 337 98 40 338 253 134 218 214 305 498 135 616 572 283 198 471 273 254 342 327 326 18 343 31 158 159 91 236 370 255 572 578

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S. No. Medicines 146 147 148 149 150 151 152 153 154 155 156 157 158 159 160 161 162 163 164 165 166 167 168 169 170 171 172 173 174 175 176 177 178 179 180 181 182 Folinic Acid Formaldehyde Fosphenytoin Framycetin Furazolidone Furosemide Gabapentin Galantamine Gamma Benzene Hexachloride Gemcitabine Gentamicin Gentian Violet Glibenclamide Gliclazide Glimepiride Glucagon Glucose Glipizide Glutaraldehyde Glycerol Glyceryl Trinitrate Griseofulvin Haloperidol Halothane Heparin Homatropine Hormone Releasing IUD Hydralazine Hydrochlorothiazide Hydrocortisone Hydroxy Ethyl Starch Hypertonic Saline Ibuprofen Imatinib Imipramine Indinavir Insulin

Page No. 255 276 59 136 72 339 59 40 366 256 137 273 489 490 490 491 595 490 277 600 283 160 580 411 320 561 468 307 308 32 325 596 6 257 573 222 492

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S. No. Medicines 183 184 185 186 187 188 189 190 191 192 193 194 195 196 197 198 199 200 201 202 203 204 205 206 207 208 209 210 211 212 213 214 215 216 217 218 219 Insulin Zinc Intraperitoneal Dialysis Solution Iodine Iopanoic Acid Ipratropium Iron Dextran Iron Salts Isoniazid Isophane Insulin Isoprenaline Isosorbide Dinitrate Isosorbide-5-Mononitrate Isotretinoin Isoxsuprine Ispaghula IUD Containing Copper Ivermectin Kanamycin Ketamine Ketoconazole Lactulose Lamivudine Lamotrigine Latanoprost Leflunomide Levetiracetam Levocetirizine Levonorgestrel Levothyroxine Lidocaine (Lignocaine) Lithium Carbonate Loperamide Lorazepam Losartan Magnesium Hydroxide Magnesium Sulphate Mannitol

Page No. 492 378 505 373 450 620 618 198 492 297 285 284 362 501 75 468 153 199 412 161 76 214 59 547 384 60 32 464 506 298 586 73 568 309 19 61 398

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S. No. Medicines 220 221 222 223 224 225 226 227 228 229 230 231 232 233 234 235 236 237 238 239 240 241 242 243 244 245 246 247 248 249 250 251 252 253 254 255 256 Mebendazole Medroxyprogesterone Mefenamic Acid Meglumine Iotroxate Melphalan Memantine Menadione Sodium Sulphate 6-Mercaptopurine Meropenem Metformin Methadone Methotrexate Methyldopa Methylene Blue (Methylthioninium Chloride) Methyl Prednisolone Metoclopramide Metoprolol Metronidazole Mexiletine Miconazole Midazolam Miltefosine Mitomycin Mometasone Montelukast Morphine Mycophenolate Mofetil Nalidixic Acid Naloxone Nelfinavir Neostigmine Nevirapine Niclosamide Nicotinic acid Nifedipine Nitrazepam Nitrofurantoin

Page No. 169 465 7 374 257 41 332 258 139 493 590 259 310 92 480 421 286 106 298 352 421 172 259 451 452 11 434 141 93 224 435 219 169 343 311 568 142

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S. No. Medicines 257 258 259 260 261 262 263 264 265 266 267 268 269 270 271 272 273 274 275 276 277 278 279 280 281 282 283 284 285 286 287 288 289 290 291 292 293 Nitrous Oxide Noradrenaline Norethisterone Norfloxacin Nystatin Ofloxacin Olanzapine Omeprazole Ondansetron Oral Rehydration Salts Oseltamivir Oxcarbamazepine Oxygen Oxytetracycline Oxytocin Paclitaxel Pancuronium Pantoprazole Paracetamol D-Penicillamine Pentamidine Pentazocine Pheniramine Phenobarbitone Phenoxymethyl Penicillin (Penicillin V) Phenylephrine Phenytoin Physostigmine Pilocarpine Pioglitazone Potassium Chloride Potassium Permanganate Povidone Iodine Pralidoxime (2-PAM) Praziquantel Prednisolone Primaquine

Page No. 413 33 466 143 162 144 581 20 100 593 224 62 413 554 499 260 538 21 8 90 173 12 34 62 145 562 63 547 548 494 597 277 273 93 228 35 180

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S. No. Medicines 294 295 296 297 298 299 300 301 302 303 304 305 306 307 308 309 310 311 312 313 314 315 316 317 318 319 320 321 322 323 324 325 326 327 328 329 330 Procainamide Procaine Benzyl Penicillin (Procaine Penicillin G) Procarbazine Prochlorperazine Proguanil Promethazine Propofol Propranolol Propyliodone Protamine Pyrantel Pamoate Pyrazinamide Pyridostigmine Quinidine Quinine Raloxifene Ramipril Ranitidine Rifampicin Ritonavir Rivastigmine Roxithromycin Salbutamol Salicylic Acid Saquinavir Senna Sildenafil Silver Sulfadiazine Sodium Bicarbonate Sodium Chloride Sodium Lactate Sodium Nitrite Sodium Nitroprusside Sodium Stibogluconate Sodium Thiosulphate Sodium Valproate Spironolactone

Page No. 299 146 261 101 181 423 414 236 375 333 170 200 436 300 185 405 311 21 190 225 41 147 452 363 226 76 484 349 597 598 599 94 313 174 95 65 340

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S. No. Medicines 331 332 333 334 335 336 337 338 339 340 341 342 343 344 345 346 347 348 349 350 351 352 353 354 355 356 357 358 359 360 361 362 363 364 365 366 367 368 Stavudine Streptokinase Streptomycin Strontium Ranelate Succinyl Choline Chloride Sulfasalazine Sulphacetamide Sulphadiazine Sumatriptan Tacrine Tacrolimus Tamoxifen Telmisartan Tenofovir Terazosin Terbutaline Testosterone Tetracaine Tetracycline Thalidomide Theophylline Thiopental Timolol Tinidazole Tolnaftate Topiramate Tramadol Tranexamic acid Trifluoperazine Trihexyphenidyl (Benzhexol) Trimethoprim Tropicamide Urea Urokinase Vancomycin Verapamil Vigabatrin Vinblastine

Page No. 215 320 203 405 540 387 555 148 240 42 268 261 313 216 314 454 483 559 149 261 454 415 549 107 163 66 13 327 582 48 150 370 364 321 151 289 67 263

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S. No. Medicines 369 370 371 372 373 374 375 376 377 Vincristine Warfarin Water for Injection Xylometazoline Zanamivir Zidovudine (AZT) Zinc Oxide Zolpidem Zonisamide

Page No. 264 334 599 558 227 217 357 569 67

FIXED DOSE COMBINATIONS S. No. Medicines 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 Amoxycillin + Clavulanic acid Benzoic Acid + Salicylic Acid Calcium Carbonate + Vitamin D3

Page No. 116 351 606 133 462 449 596 138 221 221 47 223 501 348 146 201 202 202 203 185 204 221

Cotrimoxazole (Trimethoprim and Sulphamethoxazole) 'Ethinylestradiol + Levonorgestrel and Ethinylestradiol + Norethisterone Formoterol + Fluticasone propionate Glucose + Sodium Chloride Imipenem + Cilastatin Lamivudine + Nevirapine + Stavudine Lamivudine + Zidovudine Levodopa + Carbidopa Lopinavir + Ritonavir Mifepristone + Misoprostol Neomycin + Bacitracin Piperacillin + Tazobactam Rifampicin + Isoniazid Rifampicin + Isoniazid + Ethambutol Rifampicin + Isoniazid + Pyrazinamide Rifampicin + Isoniazid + Pyrazinamide + Ethambutol Sulfadoxine + Pyrimethamine Thiacetazone + Isoniazid Zidovudine + Lamivudine + Nevirapine

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IMMUNOLOGICALS S. No. Medicines 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Anti-D Immunoglobulin (Human) Antitetanus Immunoglobulin (Human) Antivenom Sera BCG Vaccine Diphtheria Antitoxin Diphtheria, Pertussis and Tetanus (DPT) Vaccine Haemophilus Influenza Type B Vaccine Hepatitis A Vaccine Hepatitis B Vaccine Influenza Vaccine Measles Vaccine Polio Vaccine (OPV/IPV) Rabies Immunoglobulin Rabies Vaccine Rubella Vaccine Tetanus Vaccine

Page No. 511 512 514 524 512 524 525 525 526 526 527 528 513 528 529 530 369 531 531 532

Tuberculin Purified Protein Derivative (Tuberculin PPD) Typhoid Vaccine Varicella Vaccine Yellow Fever Vaccine

VITAMINS S. No. Medicines 1 2 3 4 5 6 7 8 9 10 11 12 Ascorbic Acid (Vitamin C) Cyanocobalamin (Vitamin B12) Ergocalciferol (Vitamin D2) Folic Acid Hydroxocobalamin Methylcobalamin Nicotinamide Phytomenadione Pyridoxine Riboflavin Thiamine Vitamin A

Page No. 606 616 607 619 620 609 610 332 610 611 612 612

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Common Abbreviations
ACE ACE Inhibitors ADR AE AIDS ARB BCG BNF BP BSA CAPD CD4 CDSCO CIOMS CMV COPD COLD CR CSF DCGI DMARDs DOTS DT DPT EMEA ER FDA FDC GCP GERD GFR G-6-PD Angiotensin Converting Enzyme Angiotensin Converting Enzyme Inhibitors Adverse Drug Reaction Adverse Event Acquired Immuno Deficiency Syndrome Angiotension Receptor Blocker Bacillus Calmette Guerin British National Formulary British Pharmacopoeia Body Surface Area Continuous Ambulatory Peritoneal Dialysis Cluster of Differentiation 4 Central Drugs Standards Control Organization Council for International Organization of Medical Sciences Cytomegalo Virus Chronic Obstructive Pulmonary Disease Chronic Obstructive Lung Disease Controlled Release Cerebrospinal Fluid Drugs Controller General (India) Disease Modifying Anti-Rheumatic Drugs Directly Observed Treatment Shortcourse Dispersible Tablet/Diphtheria Tetanus Diphtheria Pertussis Tetanus European Medicines Evaluation Agency Extended Release Food and Drug Administration Fixed Dose Combination Good Clinical Practice Gastroesophageal Reflux Disease Glomerular Filtration Rate Glucose-6-Phosphate Dehydrogenase

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HAART HD HIV HPA HT ICMR INR IP IPC IPV IU LFT MAO MD MDR mEq MI mMol MMR MOHFW MR NLEM NFI NRHM NSAIDs NS ODT OPV PFS PK/PD PD PvPI SC SL SLE SR SWI

Highly Active Anti-Retroviral Therapy Hemodialysis Human Immunodeficiency Virus Hypothalamic Pituitary Adrenal Axis Hormone Therapy Indian Council of Medical Research International Normalized Ratio Indian Pharmacopoeia Indian Pharmacopoeia Commission Inactivated Poliomyelitis Vaccine International Units Liver Function Test Mono Amine Oxidase Mouth Dissolving Multi Drug Resistance MilliEquivalent Myocardial Infarction Millimole Measles, Mumps and Rubella Ministry of Health and Family Welfare Modified Release National List of Essential Medicines National Formulary of India National Rural Health Mission Non-Steroidal Anti-Inflammatory Drugs Normal Saline Oral Dispersible Tablet Oral Polio Vaccine Pre-Filled Syringes Pharmacokinetic/Pharmacodynamic Peritoneal Dialysis Pharmacovigilance Programme of India Subcutaneous Sublingual Systemic Lupus Erythematosus Sustained Release Sterile Water for Injection

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SSRI TDM USP WHO W/V W/W

Selective Serotonin Reuptake Inhibitor Therapeutic Drug Monitoring United States Pharmacopoeia World Health Organization Weight/Volume Weight/Weight

*
Schedule H:

Drugs listed in National List of Essential Medicines 2011, India List of substances that could be sold by retail on the prescription of a Registered Medical Practitioner only (Prescription Drugs). List of drugs for which the retailer is to preserve prescription for a period of two years. List of drugs that could be dangerous to take except under medical supervision.

Schedule X: Schedule G:

Notes: 1. Wherever Schedule H and X are stated it means that the drug is specified in that Schedule of Drugs and Cosmetics Rules, 1945. 2. Substances specified in Schedule H or Schedule X shall not be sold by retail except on and in accordance with the prescription of a Registered Medical Practitioner and in the case of substances specified in Schedule X, the prescriptions shall be in duplicate, one copy of which shall be retained by the licensee for a period of two years. 3. The supply of drugs specified in Schedule H or Schedule X to Registered Medical Practioners, Hospitals, Dispensaries and Nursing Homes shall be made only against the signed order in writing which shall be preserved by the licensee for a period of two years.

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General Advice to Prescribers

1. Rational Approach to Therapeutics
Drugs should only be prescribed when they are necessary, and in all cases the benefit of administering the medicine should be considered in relation to the risks involved. Bad prescribing habits lead to ineffective and unsafe treatment, exacerbation or prolongation of illness, distress and harm to the patient, and higher cost. The Guide to Good Prescribing (WHO, Geneva; 1994) provides important tools for training in the process of rational prescribing. The following steps will help prescribers to follow the rational approach to therapeutics.

1 Define the Patients Problem

Whenever possible, making the right diagnosis is based on integrating many pieces of information: the complaint as described by the patient; a detailed history; physical examination; laboratory tests; X-rays and other investigations. This will help in rational prescribing, always bearing in mind that diseases are evolutionary processes.

2 Specify the Therapeutic Objective

Doctors must clearly state their therapeutic objectives based on the pathophysiology underlying the clinical situation. Very often physicians are required to select more than one therapeutic goal for each patient.

3 Selecting Therapeutic Strategies

The selected strategy should be agreed with the patient; this agreement on outcome, and how it may be achieved, is termed concordance. The selected treatment can be non-pharmacological and/ or pharmacological; it also needs to take into account the total cost of all therapeutic options.

a. Non-Pharmacological Treatment
It is very important to bear in mind that the patient does not always need a medicine for treatment of the condition. Very often, health problems can be resolved by a change in lifestyle or diet, use of physiotherapy or exercise, provision of adequate psychological support, and other non-pharmacological treatments; these have the same importance as a prescription medicine, and instructions must be written, explained and NFI-2011 XXVI

monitored in the same way.

b. Pharmacological Treatment
Selecting the Correct Group of Drugs Knowledge about the pathophysiology involved in the clinical situation of each patient, pharmacokinetics and pharmacodynamics of the chosen group of drugs, are fundamental principles for rational therapeutics. Selecting the Medicine from the Chosen Group The selection process must consider benefit/risk/cost information. This step is based on evidence about maximal clinical benefits of the medicine (efficacy) for a given indication with the minimum production of adverse effects (safety). It must be remembered that each medicine has adverse effects and it is estimated that up to 10% of hospital admissions in industrialized countries are due to adverse effects. Not all medicine-induced injury can be prevented but much of it is caused by inappropriate selection of drugs. In cost comparison between drugs, the cost of the total treatment and not only the unit cost of the medicine must be considered. Verifying the Suitability of the Chosen Pharmaceutical Treatment for Each Patient The prescriber must check whether the active substance chosen, its dosage form, standard dosage schedule and standard duration of treatment are suitable for each patient. Medicine treatment should be individualized to the needs of each patient. Prescription Writing The prescription is the link between the prescriber, the pharmacist (or dispenser) and the patient so it is important for the successful management of the presenting medical condition. Giving Information, Instructions and Warnings This step is important to ensure patient compliance and is covered in detail in the following chapter (Refer 2.11. Adherence (compliance) with medicine treatment). Monitoring Treatment Evaluation of the follow up and the outcome of treatment allow the stopping of it (if the patients problem is solved) or to reformulate it when necessary. This step gives rise to important information about the effects of XXVII NFI-2011

drugs contributing to building up the body of knowledge of pharmacovigilance, needed to promote the rational use of drugs.

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2. Factors Affecting Medicine Response

2.1. Variation in Dose
Success and effectiveness of medicine therapy depends not only on the correct choice of medicine but also on the correct dose regimen. Unfortunately, treatment frequently fails because either the dose is too small or it is too large that it produces adverse effects amongst other factors. The concept of a standard or average adult dose for every medicine is fir mly rooted in the mind of most prescribers. After the initial dose ranging studies on new drugs, manufacturers recommend a dosage that appears to produce the desired response in the majority of subjects. These studies are usually done on healthy, young male volunteers, rather than on older men and women with illnesses and of different ethnic and environmental bac kgrounds. The use of standard doses in the marketing literature suggests that standard responses are the rule, but in reality there is considerable variation in medicine response. There are many reasons for this variation such as medicine formulation, body weight and age, variation in pharmacokinetics (absorption, distribution, metabolism and excretion), variation in pharmacodynamics, disease variables, environmental and genetic variables, adherence to instructions and adverse effects and interactions etc. Some of them are described below.

2.2. Formulation
The type of drug formulation is an important factor affecting its response, apart from its lipid solubility and so many other factors. Pharmaceutical dosage forms such as tablets, capsules, emulsions, ointments, injectables, liposomes etc provide a mechanism for safe, effective, accurate, and convenient delivery of drugs to the target site. Poorly formulated drugs may fail to disintegrate or dissolve. Enteric-coated drugs are particularly problematic, and have been known to pass through the gastrointestinal tract intact. Some drugs like digoxin or phenytoin have a track record of formulation problems, and dissolution profiles can vary not only from manufacturer to manufacturer but also from batch to batch manufactured by the same manufacturer. Lately, biogeneric products (off patent biopharmaceuticals) have also been available in the pharmaceutical market. The production of biogenerics involves complex processes.

2.3. Body Weight and Age

Although the concept of varying the dose with the body weight or age of children has a long tradition, adult doses have been XXIX NFI-2011

assumed to be the same irrespective of size or shape. Yet adult weights vary two to threefold, while a large fat mass can store large excess of highly lipid soluble drugs compared to lean patients of the same weight. Age changes are also important. Adolescents may oxidize some drugs relatively more rapidly than adults, while the elderly may have reduced renal function and eliminate some drugs more slowly.

2.4. Sex
Females usually require smaller doses than males. Iron preparations and other haematinics are exceptions to this rule because of the blood lost by women during menstruation. There is a possibility that males metabolize benzodiazepines, estrogen containing preparations and salicylate at a faster rate than females.

2.5. Route of Administration

It governs the speed and intensity of drug response. The indications for a drug may vary when route of administration varies. Example: Magnesium sulphate when administered orallyacts as a purgative, when administered topically- decreases swelling on sprained joints, and when administered intravenously- CNS depression and hypotension occur.

2.6. Tolerance
The therapeutic effects of some medications are lessened in individuals over a prolonged period of use. Thus, a patient who has been using a drug for longer time, requires a higher dose so as to obtain the same therapeutic effect as produced by the drug when taken for the first time. This is called tolerance. Opioids, benzodiazepines, 2 agonists, caffeine, cocaine, amphetamines, and barbiturates fall into this category. Crosstolerance develops when the use of one drug causes a tolerance to another. Alcoholics, barbiturate and narcotic addicts develop a cross-tolerance to sedatives and anaesthetics. These individuals require very large amounts of anaesthetics before surgical anaesthesia can be attained.

2.7. Synergistic Effect

Several drugs when combined may show synergistic action in the form of either additive or supraadditive action or potentiation. A few examples are: a) Trimethoprim + Sulphamethoxazole. b) ACE inhibitor + Angiotensin Receptor blocker + Diuretic. c) Long acting 2 agonists + Inhaled steroids (ExampleSalmeterol + Fluticasone) NFI-2011 XXX

2.8. Resistance
Development of resistance to drugs is a common problem with antimicrobial agents (antituberculosis drugs, antileprotic drugs, antimalarial drugs etc). Rational prescribing and in turn compliance by the user will prevent the emergence of resistance.

2.9. Pharmacokinetic Variables

2.9.1. Absorption
Absorption of a medicine is possible when it is present in solution form. Medicine absorption rates may vary widely between individuals and in the same individual at different times and in different physiological states. Drugs taken after a meal are delivered to the small intestine much more slowly than in the fasting state, leading to much lower medicine concentrations. In pregnancy gastric emptying is also delayed, while some drugs may increase or decrease gastric emptying and affect absorption of other drugs.

2.9.2 Distribution
Medicine distribution varies widely: fat soluble drugs are stored in adipose tissue, water soluble drugs are distributed chiefly in the extracellular space, acidic drugs bind strongly to plasma protein albumin and basic drugs to muscle cells. Hence variation in plasma albumin levels, fat content or muscle mass may all contribute to dose variation. With very highly albumin bound drugs like warfarin, a small change of albumin concentration can produce a big change in free medicine concentration and a dramatic change in therapeutic action of a medicine.

2.9.3. Metabolism
Medicine metabolic rates are determined both by genetic and environmental factors. Medicine acetylation shows genetic polymorphism, whereby individuals fall clearly into either fast or slow acetylator types. Medicine oxidation, however, is polygenic, and although a small proportion of the population can be classified as very slow oxidizers of some drugs, for most drugs and most subjects there is a normal distribution of medicine metabolizing capacity, and much of the variation is under environmental control. Also refer 2.10.2.

2.9.4. Excretion
Many drugs are eliminated by the kidneys without being metabolized. Renal disease or competitive tubular secretion of drugs can therefore slow down the excretion of certain drugs. XXXI NFI-2011

2.10. Pharmacodynamic Variables

There is significant variation in receptor response to some drugs, especially central nervous system responses, for example pain and sedation. Some of this is genetic, some due to tolerance, some due to interactions with other drugs and some due to addiction, for example, morphine and alcohol.

2.10.1. Disease Variables

Both liver and kidney disease can have major effects on medicine response, chiefly by the effect on metabolism and elimination respectively (increasing toxicity), but also by their effect on plasma albumin (increased free medicine also increasing toxicity). Heart failure can also affect metabolism of drugs with rapid hepatic clearance (for example lidocaine, propranolol). Respiratory disease and hypothyroidism can both impair medicine oxidation.

2.10.2. Environmental Factors and Genetic Factors (Pharmacogenetics)

Many drugs and environmental toxins can induce the hepatic microsomal enzyme oxidizing system (MEOS) or cytochrome P450 oxygenases, leading to more rapid metabolism and elimination and ineffective treatment. Environmental pollutants, carcinogens, tobacco smoke, alcohol, anaesthetic drugs and pesticides can also induce metabolism. Diet and nutritional status also have an impact on pharmacokinetics. For example, in infantile malnutrition and in malnourished elderly populations medicine oxidation rates are decreased, while high protein diets, charcoal cooked foods and certain other foods act as metabolizing enzyme inducers. Sedative and hypnotics induce sleep better in calm environment and when administered at night. Pharmacogenetic variation will affect the medicine response, by 4-6 fold among different individuals. All major determinants of medicine response such as transporters, metabolizing enzymes, and receptors are controlled genetically. These factors in certain cases may result in toxicity- for example toxicity caused by inhibitory effect of isoniazid on phenytoin metabolism seems to be more significant in slow acetylators of isoniazid than in those patients who metabolize the drug more rapidly. The Appendix 10 summarizes the pharmacogenetic variation, the frequency of occurrence, drugs involved and the outcome.

2.11. Adherence (Compliance) with Medicine Treatment

It is often assumed that once an appropriate medicine is chosen, the prescription correctly written and the medication correctly NFI-2011 XXXII

dispensed, that it will be taken correctly then the treatment will be successful. Unfortunately this is very often not the case, and physicians overlook one of the most important reasons for treatment failure that is poor adherence (compliance) with the treatment plan. There are sometimes valid reasons for poor adherence. The medicine may be poorly tolerated, may cause obvious adverse effects or may be prescribed in a toxic dose. Failure to adhere with such a prescription has been described as intelligent non-compliance. Bad prescribing or a dispensing error may also create a problem, and regarding which patients may have neither the insight nor the courage to question. Even with good prescribing, failure to adhere to treatment is common. Factors may be related to the patient, the disease, the doctor, the prescription, the pharmacist or the health system and can often be avoided. Low-cost strategies for improving adherence increase effectiveness of health interventions and reduce costs. Such strategies must be tailored to the individual patient. Health care providers should be familiar with techniques for improving adherence and they should employ systems to assess adherence and to determine what influences it.

2.11.1. Patient Reasons

In general, women tend to be more adherent than men, younger patients and the very elderly are less adherent, and people living alone are less adherent than those with partners or spouses. Specific education interventions have been shown to improve adherence. Patient disadvantages such as illiteracy, poor eyesight or cultural attitudes (for example preference for traditional or alternative drugs and suspicion of modern medicine) may be very important in some individuals or societies, as may economic factors. Such disabilities or attitudes need to be discussed and taken account of.

2.11.2 Disease Reasons

Conditions with a known worse prognosis (for example cancer) or painful conditions (for example rheumatoid arthritis) elicit better adherence rates than asymptomatic perceived as benign conditions such as hypertension. Doctors should be aware that in most settings less than half of patients initiated on antihypertensive medicine treatment are still taking it a year later. Similarly, in epilepsy, where events may occur at long intervals, adherence is notoriously unsatisfactory.

2.11.3 Doctor Reasons

Doctors may cause poor adherence in many ways-by failing to inspire confidence in the treatment offered, by giving too little or no explanation, by thoughtlessly prescribing too many XXXIII NFI-2011

drugs, by making errors in prescribing, or by their overall attitude towards the patient.

2.11.4. The Doctor-Patient Interaction

There is considerable evidence that this is crucial to concordance. Satisfaction with the interview is one of the best predictors of good adherence. Patients are often well informed and expect a greater say in their health care. If they are in doubt or dissatisfied they may turn to alternative options, including complementary medicine. There is no doubt that the medicine doctor has a powerful effect to encourage confidence and perhaps contribute directly to the healing process.

2.11.5. Prescription Reasons

Many aspects of the prescription may lead to non-adherence (noncompliance). It may be illegible or inaccurate; it may get lost; it may not be refilled as intended or instructed for a chronic disease. Also, the prescription may be too complex; it has been shown that the greater the number of medications the poorer the adherence, while multiple doses also decrease adherence if more than two doses per day are given. Not surprisingly adverse effects like drowsiness, impotence or nausea reduce adherence and patients may not admit to the problem.

2.11.6. Pharmacist Reasons

The pharmacists behaviour and professionalism, like the doctors, may have a positive impact, supporting adherence, or a negative one, raising suspicions or concerns. This has been reported in relation to generic drugs when substituted for brand-name drugs. Pharmacist information and advice can be a valuable reinforcement, as long as it agrees with the doctors advice.

2.11.7. The Healthcare System

The healthcare system may be the biggest hindrance to adherence. Long waiting times, uncaring staff, uncomfortable environment, exhausted medicine supplies and so on, are all common problems in developing countries, and have a major impact on adherence. An important problem is the distance and accessibility of the clinic from the patient. Some studies have confirmed the obvious, that patients farthest from the clinic are least likely to adhere to treatment in the long term.

2.12. Adverse Effects and Interactions

An Adverse Drug Reaction (ADR) may be defined as any response to a medicine which is noxious, unintended and occurs at doses normally used for prophylaxis, diagnosis, or therapy. ADRs are therefore unwanted or unintended effects NFI-2011 XXXIV

of a medicine, including idiosyncratic effects, which occur during its proper use. They differ from accidental to deliberate excessive dosage or medicine maladministration. ADRs may be directly linked to the properties of the medicine in use, the so-called A type reactions. An example is hypoglycaemia induced by an antidiabetic medicine. ADRs may also be unrelated to the known pharmacology of the medicine, the B type reactions including allergic effects, for example anaphylaxis with penicillins. Thalidomide marked the first recognized public health disaster related to the introduction of a new medicine. It is now recognized that clinical trials, however thorough, cannot be guaranteed to detect all adverse effects likely to be caused by a medicine and hence necessitating post-marketing surveillance. Health workers are thus encouraged to record and report to the National Pharmacovigilance Centre for any unexpected adverse effects with any medicine to achieve faster recognition of serious related problems. The National Regulatory Authority takes appropriate action on drugs showing serious ADRs.

2.12.1. Major Factors Predisposing to Adverse Effects

It is well known that different patients often respond differently to a given treatment regimen. For example, in a sample of 2422 patients who had been taking combinations of drugs known to interact, only 7 (0.3%) showed any clinical evidence of interactions. Therefore, in addition to the pharmaceutical properties of the medicine, the characteristics of the patients may be responsible for causing predisposition to ADRs.

2.12.2. Extremes of Age

The very old and the very young persons are more susceptible to ADRs. Drugs which commonly cause problems in the elderly include hypnotics, diuretics, non-steroidal anti-inflammatory drugs, antihypertensives, psychotropics, digoxin etc. All children, and particularly neonates, differ from adult in their response to drugs. Some drugs are likely to cause problems in neonates (for example morphine ), but are generally tolerated in children. Valproic acid is associated with increased risk of ADRs in children of all ages. Other drugs associated with problems in children include chloramphenicol (grey baby syndrome), antiarrhythmics (worsening of arrhythmias), acetylsalicylic acid (Reyes syndrome etc).

2.12.3. Intercurrent Illness

If besides the condition being treated the patient concomitantly suffers from another disease, such as kidney, liver or heart disease, special precautions may be necessary to prevent ADRs. Remember also that, apart from the above factors, the XXXV NFI-2011

genetic make-up of the individual patient may also predispose to ADRs.

2.12.4. Drug Interactions

Interactions (see Appendix 6) may occur between drugs which compete for the same receptor or act on the same physiological system. They may also occur indirectly when a medicineinduced disease or a change in fluid or electrolyte balance alters the response to another medicine. Interactions may occur when one medicine alters the absorption, distribution, metabolism or elimination of another medicine, such that the amount which reaches the site of action is increased or decreased. Medicine-medicine interactions are some of the commonest causes of adverse effects. When two drugs are administered to a patient, they may either act independent of each other, or interact with each other. Interactions may increase or decrease the effects of the drugs concerned and may cause unexpected toxicity. As newer and more potent drugs become available, the number of serious medicine interactions is likely to increase. Remember that interactions which modify the effects of a medicine may involve non-prescription drugs, non-medicinal chemical agents, and social drugs such as alcohol, marijuana, tobacco and traditional remedies, as well as certain types of food. The physiological changes in individual patients, caused by such factors as age and gender, also influence the predisposition to ADRs resulting from medicine interactions.

2.12.5. Pharmaceutical Interactions

Certain drugs, when added to intravenous fluids, may be inactivated by pH changes, by precipitation or by chemical reaction. Benzylpenicillin and ampicillin lose potency after 6-8 hours if added to dextrose solutions, due to the acidity of these solutions. Some drugs bind to plastic containers and tubing, for example diazepam and insulin. Aminoglycosides are incompatible with penicillins and heparin. Hydrocortisone is incompatible with heparin, tetracycline and chloramphenicol.

2.12.6. Adverse Effects Caused by Traditional Drugs

Patients who have been or are taking traditional herbal remedies may develop ADRs. It is not always easy to identify the responsible plant or plant constituent. For further details, refer to the Medicine and Toxicology Information Service if

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XXXVI

available and/or to suitable literature. Appendix 6d summarises the Drug Herbal/Food Interactions.

2.12.7. The Effect of Food on Medicine Absorption

Food delays gastric emptying and reduces the rate of absorption of many drugs; the total amount of medicine absorbed may or may not be reduced. However, some drugs are preferably taken with food, either to increase absorption or to decrease the irritant effect on the stomach. Appendix 6d summarises the Drug Food Interactions.

Recommendations
Review the prescription to make sure that it is correct. Spend time explaining the health problem and the reason for the medicine. Counselling of patients. Establish good rapport with the patient. Explore problems, for example difficulty with reading the label or getting the prescription filled. Encourage patients to bring their medication to the clinic, so that tablet/capsule counts etc. can be done to monitor compliance. Encourage patients to learn the names of their drugs, and review their regimen with them. Write notes for them. Keep treatment regimens simple. Communicate with other health care professionals, to develop a team approach and to collaborate on helping and advising the patient. Involve the partner or another family member in eliciting clinical history of the patient and explaining the advice. Listen to the patient. Pharmacist plays and important role as a connecting link between the physician and patient.

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Analgesics, Antipyretics, Non-Steroidal Anti-Inflammatory Drugs

1.

Analgesics, Antipyretics, Non-Steroidal Anti-Inflammatory Drugs 3

Non-Opioid, Non-Steroidal Anti-Inflammatory Drugs Opioid Analgesics 4 10

1.1 1.2

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Analgesics, Antipyretics, Non-Steroidal Anti-Inflammatory Drugs

1. Analgesics, Antipyretics, Non-Steroidal Anti-Inflammatory Drugs

Analgesics are used to relieve/reduce body pain and antipyretics are used to reduce elevated body temperature. Nonopioid analgesics are particularly suitable for relieveing or management of pain in musculoskeletal conditions whereas the opioid analgesics are more suitable for moderate to severe visceral pain. Those non-opioid analgesics which also have anti-inflammatory actions include salicylates and NSAIDs; they can reduce both pain and inflammation of chronic inflammatory disorders such as rheumatoid arthritis, but they do not alter or modify the disease process itself. For the management of rheumatoid arthritis, DMARDs (disease-modifying antirheumatic drugs) may favourably influence the outcome of the disease. The pain and inflammation of an acute attack of gout is treated with a NSAID or colchicine; a xanthineoxidase inhibitor is used for long-term control of gout. Neurogenic pain generally responds poorly to conventional analgesics; treatment can be difficult and includes the use of carbamazepine for trigeminal neuralgia and amitriptyline for diabetic neuropathy and post-therapeutic neuralgia.

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Analgesics, Antipyretics, Non-Steroidal Anti-Inflammatory Drugs

1.1 Non-Opioid, Non-Steroidal Anti-Inflammatory Drugs

Non-opioid analgesics with anti-inflammatory activity include salicylates such as acetylsalicylic acid and other nonsteroidal anti-inflammatory drugs such as ibuprofen. Non-opioid analgesics with little or no anti-inflammatory activity include paracetamol.

Acetylsalicylic Acid* (Refer Page No. 281 and 317)

Pregnancy Category-D Indications Management of mild to moderate pain such as headache, acute migraine attacks,transient musculoskeletal pain, dysmenorrhoeal pain and for reducing fever; pain and inflammation of rheumatoid arthritis; antiplatelet agent for prophylaxis of myocardial infarction, stable angina pectoris; stroke prophylaxis. TABLETS 50, 60, 75, 80, 150, 300 and 325 mg. Oral Adult- Analgesic and antipyretic including migraine attacks: 0.3 to 0.9g, 3 to 4 times a day (max. 4g daily). Acute Rheumatic fever: 4 to 6g or 75 to 100 mg/kg daily in divided doses. Antiplatelet: 75-325 mg/day . Child- Under 16 years: not recommended (can cause Reyes syndrome). Contraindications Hypersensitivity (including asthma; angioedema; urticaria or rhinitis) to acetylsalicylic acid or any other NSAID; children and adolescents under 16 years (may cause Reyes syndrome); gastrointestinal ulceration; haemophilia and other bleeding disorders; not for treatment of gout; severe renal or hepatic impairment; lactation. It is known to cause haemolytic anaemia in people who have the genetic disease- G-6-PD-deficiency. Asthma, allergic disease; impaired renal or hepatic function (Appendices 7d and 7a); lactation (Appendix 7b); pregnancy (Appendix 7c); elderly; G-6-PD-deficiency; dehydration; interactions (Appendix 6a, 6c, 6d).

Availability Dose

Precautions

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Analgesics, Antipyretics, Non-Steroidal Anti-Inflammatory Drugs

Adverse Effects

Storage

Generally mild and infrequent for lower doses, but common with anti-inflammatory doses; gastrointestinal discomfort or nausea, ulceration with occult bleeding (occasionally major haemorrhage); also other haemorrhage (including subconjunctival); hearing disturbances such as tinnitus (rarely, deafness); vertigo; confusion; hypersensitivity reactions (angioedema; bronchospasm and rash); increased bleeding time, blood disorders (particularly thrombocytopenia); rarely, oedema; myocarditis; Reyes syndrome. Store protected from moisture at a temperature not exceeding 30C.

Diclofenac
Pregnancy Category-B Indications Availability Schedule H Acute musculo-skeletal pain; arthritis; gout; spondylitis; migraine; post-operative pain. TABLETS 25 and 50 mg Plain; 75 and 100 mg SR; CAPSULES 100 mg, 100 mg CR; INJECTION 3 ml ampoule (25 mg/ml); EyE/EAR DROPS 0.1% w/v; SUPPOSITORIES 25, 50 and 100 mg; GEL 1%w/w. Oral 100 to 150 mg daily in 2 to 3 divided doses, (max 150 mg/day) maintenance by 50 to 100 mg in divided doses. Intramuscular injection 75 mg, 2 to 3 times daily. Topically Adult- Apply 1% w/w gel on to affected area 3 to 4 times daily. Instill to eye Post-operative ocular inflammation: Adult- as sodium (1% w/v), 4 times daily starting 24 h after surgery for up to 28 days. Rectal Post-operative pain. Adult- 75 to 150 mg daily in divided doses (max. 150 mg/day, inclusive of diclofenac administered through other routes). Child- 6 to 12 year: 1 to 2 mg/kg/day in divided doses for max. of 4 days. Porphyria; avoid injections containing benzyl alcohol in neonates; history of gastric ulcers, bleeding or perforation.

Dose

Contraindications

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Analgesics, Antipyretics, Non-Steroidal Anti-Inflammatory Drugs

Precautions

Adverse Effects

Storage

Additional contraindications include concomitant NSAID or anticoagulant use (including low-dose heparin); history of haemorrhagic diathesis; history of confirmed or suspected cerebrovascular bleeding; operations with high risk of haemorrhage; history of asthma; moderate or severe renal impairment; hypovolaemia; dehydration. NSAIDs should be used with caution in the elderly (risk of serious side-effects and fatalities); interactions (Appendix 6a, 6c, 6d); pregnancy (Appendix 7c); patients with coagulation disorders; hepatic, renal and cardiac impairment; history of gastrointestinal lesions. Injection site reactions; transient epigastric pain, risk of thrombotic events; toxic epidermal necrolysis; Abnormality in kidney function. Store protected from light.

Ibuprofen*
Pregnancy Category-C Indications Schedule H

Pain and inflammation in rheumatic disease and other musculoskeletal disorders including juvenile arthritis; mild to moderate pain including dysmenorrhoeal pain, headache; pain in children; acute migraine attack. TABLETS 200, 400 and 600 mg; CAPSULES 400 mg Plain, 300 mg SR; SUSPENSION 100 mg/5 ml. Oral Adult- and Child over 12 years- initially 300 to 400 mg 3 to 4 times daily, increase if necessary (max. 2.4g daily), maintenance dose of 0.6 to 1.2g daily may be adequate. Infant or Child over 3 months- 5-10 mg/kg 3 to 4 times/day, Maximum daily dose: 40 mg/kg/day. Intravenous injection and infusion Neonate- initially by intravenous injection (over atleast 5 min) 25-100 g/kg then by continuous intravenous infusion 5-40 g/ kg/h. adjusted according to response.

Availability

Dose

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Analgesics, Antipyretics, Non-Steroidal Anti-Inflammatory Drugs

Child- 1-6 months: initially by intravenous injection (over atleast 5 min) 100-200 g/kg then by continous infusion 10-30 g/h. adjusted according to response. 6 months-12 years: initially by intravenous injection (over atleast 5 min) 100-200 g/kg, adjusted according to response. Juvenile rheumatoid arthritis: 20 to 40 mg/ kg/day in 3 to 4 divided doses. Contraindications Hypersensitivity (including asthma; angioedema; urticaria or rhinitis) to acetylsalicylic acid or any other NSAID; active peptic ulceration; for treatment of pre-operative pain in the setting of coronary artery bypass graft surgery; neonates with congenital heart disease. Renal and hepatic impairment (Appendix 7a); preferably avoid if history of peptic ulceration; cardiac disease; elderly; pregnancy (Appendix 7c); lactation (Appendix 7b); coagulation defects; allergic disorders; interactions (Appendix 6a, 6c, 6d). Gastrointestinal disturbances including nausea, diarrhoea, dyspepsia, gastrointestinal haemorrhage; hypersensitivity reactions including rash, angioedema; bronchospasm; headache; dizziness; nervousness; depression; drowsiness; insomnia; vertigo; tinnitus; photosensitivity; haematuria; renal failure; fluid retention (rarely, precipitating congestive heart failure in elderly), raised blood pressure; rarely, hepatic damage; alveolitis, pulmonary eosinophilia; pancreatitis; visual disturbances; erythema multiforme (StevensJohnson syndrome); toxic dermal necrolysis (Lyell's syndrome); colitis; aseptic meningitis. Skin reactions like dermatitis. Store protected from light and moisture.

Precautions

Adverse Effects

Storage

Mefenamic Acid
Pregnancy Category-CH Indications Treatment of rheumatoid arthritis, osteoarthritis, dysmenorrhea, mild to moderate pain, inflammation, fever dental pain. TABLETS 100 mg, 250 mg, 500 mg. CAPSULES 250 mg. SUSPENSION 50 mg/5 ml. Adult

Availability Dose

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Analgesics, Antipyretics, Non-Steroidal Anti-Inflammatory Drugs

Contraindications

Precautions

Adverse Effects

Pain: 500 mg orally, followed by 250 mg every 6 hours as needed, not to exceed 7 days. Dysmenorrhea: 500 mg orally, followed by 250 mg every 6 hours starting with the onset of menses. Children Pain: 14 to 18 years: 500 mg orally followed by 250 mg every 6 hours as needed, not to exceed 7 days. Known hypersensitivity to mefenamic acid; patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs; peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery, active ulceration or chronic inflammation of the gastrointestinal tract, pre-existing renal disease, pregnancy (Appendix 7c), interactions (Appendix 6c). Hepatic effects: Borderline elevations of one or more liver function tests may occur. These laboratory abnormalities may progress, may remain unchanged, or may be transient with continuing therapy. A patient with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal liver test has occurred, should be evaluated for evidence of the development of a more severe hepatic reaction while on therapy. If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), the drug should be discontinued. Anaemia: Patients on long-term treatment should have their hemoglobin or hematocrit checked if they exhibit any signs or symptoms of anaemia. Asthma: Mefenamic acid should not be administered to patients with aspirin sensitive asthma and should be used with caution in patients with preexisting asthma. Gastrointestinal experiences includingabdominal pain, constipation, diarrhoea, dyspepsia, flatulence, gross bleeding/ perforation, heartburn, nausea, gastrointestinal ulcers, vomiting, abnormal renal function, bronchospasm, anaemia, dizziness, edema, elevated liver enzymes, headaches, increased bleeding time, pruritus, rashes, tinnitus. Store protected from light and moisture.

Storage

Paracetamol*
Pregnancy Category-B Indications Mild to moderate pain including dysmenorrhoeal pain, headache; pain relief in osteoarthritis and soft tissue lesions; pyrexia including post-immunisation pyrexia; acute migraine attack.

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Analgesics, Antipyretics, Non-Steroidal Anti-Inflammatory Drugs

Availability

TABLETS 500 and 650 mg Plain; 750 mg DT; SyRUPS/SUSPENSION 125 and 250 mg/5 ml; INJECTION 2 ml ampoule 125 mg/ml.; Intravenous infusion 500 mg and 1g. Oral Adult- 0.5 to 1g every 4 to 6 h (max. 4g, max 2g in alcoholics per day). Child- for post-immunisation pyrexia, up to 2 months: 60 mg. 3 month to 1 year: 60 to 120 mg every 4 to 6 h. 1 to 5 years: 120 to 250 mg every 4 to 6 h. 6 to 12 years: 250 to 500 mg every 4 to 6 h. Intramuscular injection Adult- 250 mg every 4 to 6 h or as required. Intravenous infusion Adult- 1g every 6 hours, maximum daily dose 4 g. Child- 15 mg/kg upto 4 times a day, maximum daily dose 60 mg/kg.

Dose

Precautions

Hepatic impairment (Appendix 7a); renal impairment; alcohol dependence; lactation (Appendix 7b); pregnancy (Appendix 7c); overdosage: chapter 7.2; interactions (Appendix 6a); G-6-PD deficiency. Rare but rashes and blood disorders reported; important: liver damage (and less frequently renal damage) following overdosage; dyspepsia. Store protected from light and moisture.

Adverse Effects

Storage

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Analgesics, Antipyretics, Non-Steroidal Anti-Inflammatory Drugs

1.2 Opioid Analgesics

Morphine is effective in relieving moderate to severe pain, particularly of visceral origin; there is a large variation in patient response. Weaker opioids such as codeine are suitable for mild to moderate pain. Morphine remains the most valuable analgesic for severe pain. In addition to pain relief it confers a state of euphoria and mental detachment; repeated administration may cause dependence and tolerance, but this should not be a deterrent in the control of pain in terminal illness. Regular use may also be appropriate for certain cases of non-malignant pain, but specialist supervision is required. In normal doses common adverse effects include nausea, vomiting, constipation and drowsiness; larger doses produce respiratory depression and hypotension. Codeine is an opioid analgesic much less potent than morphine and much less liable, in normal doses, to produce adverse effects including dependency. It is effective for mild to moderate pain but is too constipating for long-term use.

Codeine* (Refer Page No. 72)

Pregnancy Category-C Indications Availability Dose

(Controlled Medicine Under the Narcotic Drugs and Psychotropic Substances Act 1985) Schedule H Mild to moderate pain; diarrhoea; cough suppressant; irritable bowel syndrome. TABLET 10 mg; SyRUP 15 mg/5 ml. Oral day).
Adult- 30 to 60 mg every 4 h. (max. 240 mg/

Child- 1 year to 12 year: 3 mg/kg daily in divided doses.

Contraindications

Respiratory depression; obstructive airways disease; acute asthma attack; where risk of paralytic ileus; hypersensitivity; head injury; increased intracranial pressure. Hepatic impairment (Appendix 7a) and renal impairment; opioids dependence; lactation; overdosage: chapter 7.2; pregnancy (Appendix 7c); interactions (Appendix 6c); hypothyroidism; shock.

Precautions

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10

Analgesics, Antipyretics, Non-Steroidal Anti-Inflammatory Drugs

Adverse Effects

Constipation particularly troublesome in long-term use, dizziness, nausea, vomiting; difficulty with micturition; ureteric or biliary spasm; dry mouth; headaches; sweating; facial flushing; in therapeutic doses, codeine is much less liable than morphine to produce tolerance, dependence, euphoria, sedation or other adverse effects; orthostatic hypotension; respiratory depression; rhabdomyolysis; convulsions (especially in children).

Morphine* (Refer Page No. 422) (Controlled Medicine Under the Narcotic Drugs and Psychotropic Substances Act, 1985)
Pregnancy Category-C Indications Schedule H, X In severe pain (acute and chronic); myocardial infarction, acute pulmonary oedema; adjunct during major surgery and postoperative analgesia; prolonged relief of severe and intractable pain. INJECTION 10 ml ampoule (1 mg/ml, 10 mg/ ml, 15 mg/ml); TABLETS 10, 20, 30 and 60 mg. Subcutaneous or intramuscular injection
Adult- Acute pain: 10 mg every 4 h. Elderly or frail- Acute pain: 5 mg, adjust

Availability Dose

according to response (not suitable for patients having oedema).

Child- Acute pain: can be given to children in dose range of 0.2 to 0.8 mg/kg every 12 h. After 1 to 6 months: initially 100 to 200 g/ kg every 6 h, 2 to 12 years: initially 200 g/ kg every 4 h, 12 to 18 years: initially 2.5 to 10 mg every 4 h. Slow intravenous injection Adult- Acute pain: 2.5 mg every 4 h. Myocardial infarction: 10 mg (2 mg/min), followed by another 5 to 10 mg if necessary. Elderly or frail- Acute pain: reduced dose. Child- 0.1-0.15 mg/kg Subcutaneous or intramuscular injection Premedication: up to 10 mg, 1 to 1.5 h before operation. Oral or subcutaneous or intramuscular injection Chronic acute pain: 5 to 20 mg every 4 h or as per recovery (not suitable for patient having oedema).

11

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Analgesics, Antipyretics, Non-Steroidal Anti-Inflammatory Drugs

Contraindications

Acute respiratory depression, obstructive airway disease; acute alcoholism; where risk of paralytic ileus; raised intracranial pressure or head injury (interferes with respiration, also affects pupillary responses vital for neurological assessment); avoid injection in pheochromocytoma. Renal and hepatic impairment (Appendix 7a); reduce dose or avoid in elderly and debilitated; dependence (severe withdrawal symptoms if withdrawn abruptly); hypothyroidism; convulsive disorders, seizure disorder; decreased respiratory reserve and acute asthma; hypotension; prostatic hypertrophy; pregnancy (Appendix 7c) and lactation (Appendix 7b); overdosage: chapter 7.2; interactions (Appendix 6a, 6c, 6d); driving and operating machinery. Nausea, vomiting (particularly in initial stages) constipation, drowsiness, also dry mouth, anorexia; spasm of urinary and biliary tract; bradycardia/tachycardia; palpitations; decreased libido; rash, urticaria, pruritus; sweating; headache; facial flushing; vertigo; postural hypotension; hypothermia; hallucinations, euphoria, confusion, dependence; miosis; larger doses produce respiratory depression and hypotension; somnolence; sepsis, peripheral oedema. Store protected from light and moisture.

Precautions

Adverse Effects

Storage

Pentazocine
Pregnancy Category-C Indications Moderate to severe pain; pre-anaesthetic medication; colic; trauma; surgical procedures; burns. TABLETS 25 mg Plain, Combination: Paracetamol 500 mg + Pentazocine 15 mg; INJECTION 1 ml ampoule (30 mg/ml). Oral
Adult- Pentazocine 50 mg every 3 to 4 h

Availability

Dose

preferably after food (range 25 to 100 mg, max. 600 mg daily).

Child- 6 to 12 years: 25 mg.

Subcutaneous, intramuscular or intravenous injection

Adult- Moderate pain: 30 mg. Severe pain: 45 to 60 mg every 3 h to 4 h when necessary.

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12

Analgesics, Antipyretics, Non-Steroidal Anti-Inflammatory Drugs

Child (Over 1 year)- by subcutaneous or intramuscular injection: 1 mg/kg; by intravenous injection: 500 g/kg.

Contraindications

Patients dependent on opioids; arterial or pulmonary hypertension; heart failure; narcotic dependence; hypersensitivity; ischaemia; myocardial infarction. Avoid in porphyria; interactions (Appendix 6a); impaired respiratory function; pregnancy (Appendix 7c); renal or hepatic function; thyroid dysfunction; biliary tract impairment. Nausea, vomiting; euphoria, occasional hallucinations. sedation,

Precautions

Adverse Effects Storage

Store protected from light and moisture.

Tramadol*
Pregnancy Category-C Indications Availability Schedule H Moderate or severe pain, post operative pain, in patients contraindicated to NSAIDs. TABLETS 50 mg and 100 mg SR; CAPSULE 50 and 100 mg SR; INJECTION 1 and 2 ml ampoule (50 mg/ml). Adult- Moderate to severe pain: 50 to 100 mg, 4 to 6 hourly (max 400 mg/day). Post operative pain: 100 mg i.v. initially followed by 50 mg every 10 to 20 min upto max. of 250 mg in the 1st h. Maintenance dose 50 to 100 mg, 4 to 6 hourly (max 600 mg/day). Contraindications Patients with suicidal tendency; raised intracranial pressure; severe renal impairment; acute alcoholism; lactation. Renal or hepatic impairment; history of epilepsy; inflammatory or obstructive bowel disease; myasthenia gravis; hypothyroidism; adreno-cortical insufficiency; respiratory depression; prostatic hyperplasia; pregnancy (Appendix 7c). Same as other opioids, however it has less addictive potential.

Dose

Precautions

Adverse Effects

13

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Antacids and Antiulcer Drugs

2.

Antacids and Antiulcer Drugs

15

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14

Antacids and Antiulcer Drugs

2. Antacids and Antiulcer Drugs

Antacids (usually containing aluminium or magnesium compounds) can often relieve symptoms in ulcer dyspepsia and in non-erosive gastro-oesophageal reflux; they are also sometimes used in non-ulcer dyspepsia but the evidence of benefit is uncertain. Antacids are best given when symptoms occur or are expected, usually between meals and at bedtime, Liquid preparations are more effective than solids. Aluminium-and magnesium-containing antacids (for example aluminium hydroxide and magnesium hydroxide), being relatively insoluble in water, are long-acting if retained in the stomach. They are suitable antacids for most purposes. Magnesium-containing antacids have a laxative effect whereas aluminium-containing antacids may be constipating. H2-receptor antagonists heal gastric and duodenal ulcers by reducing the secretion of gastric acid as a result of histamine H2-receptor blockade; they can also relieve gastro-oesophageal reflux disease. High doses of H2-receptor antagonists have been used in the Zollinger-Ellison syndrome, but a proton-pump inhibitor is now preferred. Maintenance treatment with low doses has largely been replaced in Helicobacter pylori positive patients by eradication regimens. Maintenance treatment may occasionally be used for those with frequent severe recurrences and for the elderly who suffer ulcer complications. Treatment of undiagnosed dyspepsia with H2-receptor antagonists may be acceptable in younger patients but care is required in older patients because their symptoms may be caused by gastric cancer. H2-receptor antagonist therapy can promote healing of NSAID-associated ulcers (particularly duodenal). Treatment also reduces the risk of acid aspiration in obstetric patients at delivery (Mendelson syndrome).

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Antacids and Antiulcer Drugs

Peptic Ulcer
Ulcer disease is caused by peptic ulceration that involves the stomach, duodenum and lower oesophagus. General and inexpensive measures like introducing healthy life-style, stopping smoking and taking antacids should be promoted. The possibility of malignant disease should be considered in all patients over the age of 40 years who are suspected of having an ulcer. Gastric and duodenal ulcers are healed by 4-8 weeks treatment with H2-receptor antagonists but there is a high rate of relapse (greater than 70% over 2 years) requiring maintenance therapy. Relapses can be prevented very sucessfully by eradicating Helicobacter pylori which is causally associated with most peptic ulcers (except those related to NSAID use). Eradication of H. pylori reduces the relapse rate to about 4-8%. This is undoubtedly cost-effective compared to the alternatives of long-term maintenance therapy with low-dose H2-receptor antagonists or repeated treatment of recurrent ulcers. It is recommended that the presence of H. pylori is confirmed before starting eradication treatment, particularly for gastric ulcers. The urea breath test is used widely to test for H. pylori, but it may produce false negative results if used soon after proton-pump inhibitors or antibacterials. Eradication regimens are based on a combination of an acid-reducing (antisecretory) drug and antibiotics. The following model eradication regimen is suggested on the basis of its efficacy and simplicity (only doses suitable for adults are shown): Omeprazole 40 mg daily for 1 week plus Metronidazole 400 mg thrice daily for 1 week plus Amoxycillin 500 mg thrice daily for 1 week The decision on choosing an eradication regimen should take into account local resistance to antibacterials, cost and availability of the necessary drugs.

NSAID-Associated Ulcers
Gastrointestinal bleeding and ulceration may occur with NSAID use. To avoid this, emphasis should be on stopping NSAID use but this is not always possible. A proton-pump inhibitor may be considered for protection against NSAIDassociated gastric and duodenal ulcers. An H2-receptor antagonist may be effective for protection against NSAIDassociated duodenal ulcers only. Patients who must continue NSAID therapy after ulcer NFI-2011 16

Antacids and Antiulcer Drugs

development may take high-dose H2-receptor antagonists concomitantly, but ulcers tend to heal more slowly with H2-receptor antagonists if NSAIDs are continued. A protonpump inhibitor such as omeprazole is more effective but it is also more expensive. In patients who can discontinue NSAID therapy after ulcer development, treatment with an H2-receptor antagonist is effective, but a treatment period of up to 8 weeks may be necessary. A proton-pump inhibitor usually produces the most rapid healing. After healing, continued prophylaxis is required.

Dyspepsia
Dyspepsia covers pain, fullness, early satiety, bloating, or nausea. It can occur with gastric and duodenal ulceration and gastric cancer but most commonly it is of uncertain origin. Patients with non-ulcer dyspepsia should be advised to avoid smoking, alcohol and aggravating foods and to eat small regular meals to aid digestion. Non-ulcer dyspepsia tends to be self-limiting but antacids and H2-receptor antagonists are often used to suppress gastric acid. Effective treatment is important in the presence of severe oesophageal ulceration to prevent longer term complications such as oesophageal stricture and carcinoma.

Gastro-Esophageal Reflux Disease (GERD)

GERD (including non-erosive gastro-esophageal reflux and erosive esophagitis) is characterized by symptoms which include heartburn, acid regurgitation and sometimes difficulty in swallowing (dysphagia); esophageal inflammation (esophagitis), ulceration and stricture formation may occur and there is an association with asthma. The management of GERD includes drug treatment, lifestyle changes and, in some cases, surgery. Initial treatment is guided by the severity of symptoms and treatment is then adjusted according to response. For mild symptoms of GERD, initial management may include the use of antacids. H2-receptor antagonists suppress acid secretion and they may relieve symptoms and permit reduction in antacid consumption. Severe symptoms initially require a short-course of a proton-pump inhibitor.

Zollinger-Ellison Syndrome
Management of Zollinger-Ellison syndrome requires high dose H2-receptor antagonist treatment. The proton pump inhibitors are more effective particularly for cases resistant to other treatment but they are more expensive. 17 NFI-2011

Antacids and Antiulcer Drugs

Aluminium Hydroxide
Pregnancy Category-C Indications Availability Ulcer and non-ulcer dyspepsia; GERD; hyperphosphataemia. TABLETS 300 and 840 mg; GEL 610 mg/10 ml; In combination as Tablet/Suspension/Gel/ Syrup. Oral Adult- Dyspepsia, GERD: 1 to 2 tablets chewed 4 times daily and at bedtime or 5 to 10 ml suspension 4 times daily between meals and at bedtime. Hyperphosphataemia: 2 to 10g daily in divided doses with meals.
Child- 6 to 12 years: 5 ml up to three times daily.

Dose

Contraindications Precautions

Hypophosphataemia; undiagnosed gastrointestinal or rectal bleeding; appendicitis; porphyria; hypersensitivity to aluminium salts. Impaired renal function and renal dialysis; hepatic impairment (Appendix 7a); constipation; dehydration; fluid restriction; gastrointestinal disorders associated with decreased bowel motility or obstruction; pregnancy (Appendix 7c); interactions (Appendix 6c); oedema, cirrhosis and low sodium diets. Constipation, intestinal obstruction (large doses); hypophosphataemia with increased bone resorption, hypercalciuria and risk of osteomalacia (patients on low phosphate diet or prolonged therapy); hyperalbuminaemiaresulting in osteomalacia, encephalopathy, dementia, microcytic anaemia (in chronic renal failure treated with aluminium hydroxide as phosphate-binding agent); loss of appetite. Store protected from moisture at a temperature not exceeding 30C. Do not freeze Gel.

Adverse Effects

Storage

Famotidine*
Pregnancy Category-B Indications Availability Schedule H Duodenal or benign gastric ulcers, GERD. Zollinger-Ellison syndrome. TABLETS 10, 20, 40 & 100 mg; CAPSULES 20 & 40 mg; INJECTION 2 ml (10 mg/ml).

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Antacids and Antiulcer Drugs

Dose

Oral Benign gastric and duodenal ulceration Adult: 40 mg daily at bedtime for 4-8 weeks or 20 mg twice daily. To prevent recurrence of duodenal ulceration: 20 mg at bedtime may be taken. Gastro-oesophageal reflux disease Adult: 20 mg twice daily for 6-12 week or up to 40 mg twice daily if there is oesophageal ulceration. Maintenance dose: 20 mg twice daily may be given to prevent recurrence. Child: 1-16 yr: 1-2 mg/kg/day divided twice daily up to 40 mg twice daily. Zollinger-Ellison syndrome Adult: Initially, 20 mg every 6 hr, up to 640 mg daily if necessary. Child: 1-16 yr: 0.5-1 mg/kg/day up to 40 mg/ day, given once at bedtime or taken twice daily. Non-ulcer dyspepsia Adult: 10 mg twice daily. Heartburn Adult: 10 mg twice daily. Intravenous Benign gastric and duodenal ulceration Adult: 20 mg every 12 hr, as an injection over at least 2 minutes or as an infusion over 1530 minutes.

Contraindications Precautions

Hypersensitivity Possibility of gastric malignancy should be excluded, Impaired renal function, liver cirrhosis, pregnancy (Appendix 7c), lactation, children and elderly, interactions (Appendix 6c). Headache, dizziness, constipation, diarrhoea, nausea, vomiting, anorexia, rash, fatigue, gynaecomastia and impotence. Store protected from light, Tablets to be stored at room temperature, 15 -30C (5986F). Injection to be stored between 2-8C (36-46F).

Adverse Effects

Storage

Magnesium Hydroxide
Pregnancy Category-B Indications Availability Dose Ulcer and non-ulcer dyspepsia; GERD. TABLET 310 mg; SUSPENSION 110 ml and 340 ml (8%). Oral

19

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Antacids and Antiulcer Drugs

Adult- Dyspepsia, GERD: 5 to 10 ml repeated

according to patients needs. Severe renal impairment.

Contraindications Precautions

Renal impairment; hepatic impairment (Appendix 7a); interactions (Appendix 6c); abdominal pain. Diarrhoea; in renal impairmenthypermagnesaemia resulting in loss of deep tendon reflexes and respiratory depression with other symptoms including nausea, vomiting, flushing of skin, thirst, hypotension, drowsiness, confusion, muscle weakness, bradycardia, coma and cardiac arrest; allergic reaction. Store protected from light. Do not store Gel in refrigerator.

Adverse Effects

Storage

Omeprazole*
Pregnancy Category-C Indications Schedule H Benign gastric and duodenal ulcers; Zollinger Ellison syndrome; gastric acid reduction during gastric surgery; GERD, NSAID- induced ulcer, prophylaxis during NSAIDs treatment in patients with high risk for peptic ulceration, eradication of [Link], as preoperative medication, systemic mastocytosis and in patients not responsive to H2 blockers. TABLETS 20 and 40 mg; INJECTION 10 ml vial (40 mg/10 ml); CAPSULES 10, 20 and 40 mg. Oral Benign gastric and duodenal ulcers: 20 mg once a day for 4 weeks in duodenal ulcers, for 8 weeks in gastric ulcers, Increase to 40 mg in severe case. Maintenance for recurrent duodenal ulcers: 20 mg once daily. Prevention of relapse: 10 mg daily. NSAIDs associated gastric or duodenal ulcers or gastro-duodenal erosions: 20 mg daily for 4 weeks. Prophylaxis in case of history associated with gastric/duodenal ulcers or dyspepsia: 20 mg daily. Zollinger-Ellison syndrome: 60 mg to 120 mg/day or more, into divided doses. Gastric acid reduction during gastric surgery: 40 mg on preceding evening then 40 mg 2 to 6 h before surgery. Contraindications Precautions Hypersensitivity. Interactions (Appendix 6c, 6d); pregnancy (Appendix 7c); concomitant gastric malignancy.

Availability Dose

NFI-2011

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Antacids and Antiulcer Drugs

Adverse Effects

Nausea, abdominal pain, constipation, flatulence, diarrhoea, headache, skin rashes, subacute, myopathy, arthralgias, increased risk of hip fractures, decreased B12 absorption, hypergastrenemia, respiratory and Clostridium difficile infections, hepatic dysfunction. Store protected from light and moisture at a temperature not exceeding 30C.

Storage

Pantoprazole*
Pregnancy Category-B Indications Availability Dose Schedule H Duodenal ulcer, gastric ulcer, GERD, erosive esophagitis. TABLETS 20 and 40 mg, INJECTIONS 20 and 40 mg/vial, CAPSULES 20 and 40 mg. Oral
Adult- 40 mg once daily up to 8 weeks.

Intravenous
Adult- 40 mg twice daily.

Contraindications Precautions

Hypersensitivity. Hepatic impairment; monitor liver function; pregnancy (Appendix 7c); cyanocobalamin deficiency; tumorogenicity. Diarrhoea; pruritus; dizziness; blurred vision; vertigo. pyrexia;

Adverse Effects

Ranitidine*
Pregnancy Category-B Indications Schedule H Benign gastric and duodenal ulceration, GERD, Zollinger-Ellison syndrome, other conditions where gastric acid reduction is beneficial. Prophylaxis during NSAIDs treatment in patients with high risk for peptic ulceration, eradication of [Link], as preoperative medication, systemic mastocytosis TABLETS 150 and 300 mg. INJECTION 2 ml ampoule (25 mg/ml), SyRUP 375 mg/5 ml. Oral

Availability Dose

21

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Antacids and Antiulcer Drugs

Adult- Benign gastric and duodenal ulceration: 150 mg twice daily or 300 mg at night for 4 to 8 weeks, up to 6 weeks in chronic episodic dyspepsia and up to 8 weeks in NSAID-associated ulceration (in duodenal ulcer 300 mg can be given twice daily for 4 weeks to achieve a higher healing rate); maintenance, 150 mg at night. Prophylaxis of NSAID-induced duodenal ulcer: 150 mg twice daily. Reflux oesophagitis: 150 mg twice daily or 300 mg at night for up to 8 weeks, or if necessary 12 weeks (moderate to severe, 150 mg 4 times daily for up to 12 weeks). Long-term treatment of healed oesophagitis: 150 mg twice daily. Zollinger- Ellison syndrome: 150 mg 3 times

daily (up to 6g daily in divided doses has been used). Gastric acid reduction (prophylaxis of acid aspiration) in obstetrics: 150 mg at onset of labour, then every 6 h. Surgical procedures: 150 mg 2 h before induction of anaesthesia and also, when possible on the preceding evening.

Child- Peptic ulcer: 2 to 4 mg/kg twice daily (max. 300 mg daily).

Intramuscular injection
Adult- Benign gastric and duodenal ulceration, reflux oesophagitis, ZollingerEllison syndrome: 50 mg every 6 to 8 h. Surgical procedures: 50 mg 45 to 60 min before induction of anaesthesia.

Slow intravenous injection Benign gastric and duodenal ulceration, reflux oesophagitis, Zollinger-Ellison syndrome: 50 mg diluted to 20 ml and given over at least 2 min, may be repeated every 6 to 8 h. Surgical procedures: 50 mg 45 to 60 min before induction of anaesthesia (intravenous injection diluted to 20 ml and given over at least 2 min). Intravenous infusion Benign gastric and duodenal ulceration, reflux oesophagitis, Zollinger-Ellison syndrome: 25 mg/h for 2 h, may be repeated every 6 to 8 h. Prophylaxis of stress ulceration: initial slow intravenous injection of 50 mg diluted to 20 ml and given over at least 2 min then by continuous intravenous infusion, 125250 g/kg per h (may be followed by 150 mg twice daily by mouth when oral feeding commences). Contraindications Porphyria.

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22

Antacids and Antiulcer Drugs

Precautions

Hepatic impairment (Appendix 7a); renal impairment; lactation (Appendix 7b); middleaged or older patients and those whose symptoms change-may mask gastric cancer; interactions (Appendix 6a); pregnancy (Appendix 7c). Diarrhoea and other gastrointestinal disturbances; headache; dizziness; rash; tiredness; acute pancreatitis; bradycardia, tachycardia; AV block, confusion; depression; rarely, hallucinations (particularly in the elderly or the very ill); hypersensitivity reactions (including fever, arthralgia, myalgia, anaphylaxis); blood disorders (including agranulocytosis, leukopenia, pancytopenia, thrombocytopenia); hepatitis; agitation; visual disturbances; erythema multiforme; alopecia; gynaecomastia and impotence; malaise; somnolence. Store protected from light and moisture.

Adverse Effects

Storage

23

NFI-2011

Antiallergics and Drugs used in Anaphylaxis

3.

Antiallergics and Drugs used in Anaphylaxis

25

NFI-2011

24

Antiallergics and Drugs used in Anaphylaxis

3. Antiallergics and Drugs used in Anaphylaxis

Antihistamines are used to treat drug allergies, food allergies, insect stings and some of the symptoms of anaphylaxis and angioedema. Drug treatment and other supportive care should not be delayed in critically ill patients. Specific precipitants should be sought and if identified, further exposure avoided and desensitization considered. Drowsiness and sedation are particular disadvantages of the older antihistamines and the patient should be warned against driving or operating machinery. Other central nervous system depressants, including alcohol, barbiturates, hypnotics, opioid analgesics, anxiolytics and neuroleptics, may enhance the sedative effects of antihistamines. Since antihistamines interfere with skin tests for allergy, they should be stopped at least one week before conducting a skin test. Allergic reactions of limited duration and with mild symptoms, such as urticaria or allergic rhinitis, usually require no treatment. If on the other hand, symptoms become persistent, antihistamines constitute the mainstay of treatment. However, oral corticosteroids may be required for a few days in an acute attack of urticaria or for severe skin reactions. Oral corticosteroids are also used to relieve severe exacerbations in chronic urticaria, but long-term use should be avoided. Corticosteroids may be used topically to reduce inflammation in allergic rhinitis but should only be used systemically for this condition when symptoms are disabling.

Allergic Emergencies
Anaphylactic shock and conditions such as angioedema are medical emergencies that can result in cardiovascular collapse and/or death. They require prompt treatment of possible laryngeal oedema, bronchospasm or hypotension. Atopic individuals are particularly susceptible. Insect stings and certain foods including eggs, fish, cow's milk protein, peanuts and nuts are a risk for sensitized persons. Therapeutic substances particularly associated with anaphylaxis include blood products, vaccines, hyposensitizing (allergen) preparations, antibiotics (especially penicillins), iron injections, heparin and neuromuscular blocking drugs. Acetylsalicylic acid and other nonsteroidal anti-inflammatory drugs (NSAIDs) may cause bronchoconstriction in leukotriene25 NFI-2011

Antiallergics and Drugs used in Anaphylaxis

sensitive patients. In the case of drug allergy, anaphylaxis is more likely to occur after parenteral administration. Resuscitation facilities should always be available while injecting a drug associated with risk of anaphylactic reactions. First-line treatment of a severe allergic reaction includes administering epinephrine, keeping the airway open (with assisted respiration if necessary) and restoring blood pressure (laying the patient flat, raising the feet). Epinephrine should immediately be given by intramuscular injection to produce vasoconstriction and bronchodilation and injection should be repeated if necessary at 5-min intervals until blood pressure, pulse and respiratory function have stabilized. If there is cardiovascular shock with inadequate circulation, epinephrine must be given cautiously by slow intravenous injection of a dilute solution. Oxygen administration is also of primary importance. An antihistamine such as chlorpheniramine is a useful adjunctive treatment given after epinephrine injection and continued for 24 to 48 h to reduce the severity and duration of symptoms and to prevent relapse. An intravenous corticosteroid such as hydrocortisone has an onset of action that is delayed by several hours but should be given to help prevent later deterioration in severely affected patients. Further treatment of anaphylaxis may include intravenous fluids, an intravenous vasopressor such as dopamine, intravenous aminophylline or injected or nebulized bronchodilator, such as salbutamol.

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26

Antiallergics and Drugs used in Anaphylaxis

Steps in the Management of Anaphylaxis:

1. Sympathomimetic: Epinephrine by intramuscular injection using epinephrine injection 1 in 1000, ADULT and ADOLESCENT, 500 g (0.5 ml); INFANT under 6 months 50 g (0.05 ml); CHILD 6 months-6 years 120 g (0.12 ml), 6-12 years 250 g (0.25 ml)
Note: The above doses may be repeated several times if necessary at 5-min intervals, according to blood pressure, pulse and respiratory function

2. 3.

4.

5. 6.

If circulation inadequate, by slow intravenous injection using epinephrine injection 1 in 10,000 (given at a rate of 1 ml/min), ADULT 500 g (5 ml); CHILD 10 g/kg (0.1 ml/ kg), given over several min. Vital Functions: Maintain an open airway; give oxygen by mask, restore blood pressure (lay patient flat, raise feet) Antihistamine: such as chlorpheniramine by intravenous injection over 1 min, ADULT 10-20 mg, repeated if required (max. total dose 40 mg in 24 h) Corticosteroids: such as hydrocortisone by slow intravenous injection, ADULT 100-300 mg; CHILD up to 1 year, 25 mg; 1-5 years, 50 mg; 6-12 years, 100 mg Intravenous Fluids: start infusion with sodium chloride (0.5-1 litre during the first h) If the patient has asthma-like symptoms, give salbutamol 2.5-5 mg by nebulization or aminophylline 5 mg/kg by intravenous injection over at least 20 min.

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NFI-2011

Antiallergics and Drugs used in Anaphylaxis

Adrenaline (Epinephrine)* (Refer Page No. 561)

Pregnancy Category-C Indications Availability Dose Schedule H Severe anaphylactic reaction; severe angioedema; cardiac arrest; hemostatic agent. INJECTION 1 ml ampoule (1 mg/ml). Intramuscular injection Anaphylaxis: preferable site is the midpoint in anterior thigh [1:1000 solution]. This route should be used by specialists only with extreme care. Slow intravenous injection When there is doubt regarding adequacy of circulation and absorption from the intramuscular site; slow intravenous injection of 1:10000 (10 mg/ml) solution be injected in severely ill patients only. Contraindications Precautions Narrow angle glaucoma, organic brain damage, cardiac dilation, coronary insufficiency. Hyperthyroidism, hypertension, diabetes mellitus, heart disease, arrhythmias, cerebrovascular disease; second stage of labour; elderly; interactions (Appendix 6c); pregnancy (Appendix 7c); lactation (Appendix 7b). Epinephrine fastness, tachycardia and arrhythmias, hypertension, tremor, anxiety, sweating, nausea, vomiting, weakness, hyperglycaemia, dizziness, pulmonary oedema have all been reported; headache common. Store protected from light preferably in containers filled with nitrogen.

Adverse Effects

Storage

Chlorpheniramine*
Pregnancy Category-C Indications Schedule H,G Symptomatic relief of allergy, allergic rhinitis (hay fever); conjunctivitis; urticaria; insect stings and pruritus of allergic origin; adjunct in the emergency treatment of anaphylactic shock and severe angioedema. TABLETS 2, 4 and 6 mg; INJECTIONS 10 mg/10 ml, CAPSULE 8 mg; SyRUP 10 mg/50 ml, 100 mg/100 ml. Oral
Adult- Allergic reactions: 4 mg every 4 to 6 h (max. 24 mg daily).

Availability

Dose

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Antiallergics and Drugs used in Anaphylaxis

Child- 1 to 2 years: 1 mg twice daily. 2 to 5 years: 1 mg every 4 to 6 h (max. 12 mg daily). 6 to 12 years: 2 mg every 4 to 6 h (max. 12 mg daily)

Intramuscular or intravenous injection

Adult- Allergic reactions: 10 to 20 mg, repeated if required (max. 40 mg in 24 h).

Subcutaneous injection
Child- Allergic reactions: 87.5 g/kg, repeated if necessary up to 4 times daily.

Intravenous injection (over 1 min).

Adult- Anaphylaxis (adjunct): 10 to 20 mg. Child- Anaphylaxis (adjunct)- under 1 year: 250 g/kg. 1 to 5 years: 2.5 to 5 mg. 6 to 12 years: 5 to 10 mg.

Contraindications

Prostatic enlargement, urinary retention; ileus or pyloroduodenal obstruction; asthma; child under 1 year; hypersensitivity, narrow angle glaucoma, pregnancy (Appendix 7c), lactation (Appendix 7b). Performing works requiring utmost alertness such as vehicle driving, operating machines etc within 24 h of taking the drug should be [Link] (Appendix 7b); renal and hepatic impairment (Appendix 7a); epilepsy; interactions (Appendix 6a); atropic gastritis, elderly. Drowsiness (rarely, paradoxical stimulation with high doses, or in children or elderly), hypotension, headache, palpitations, psychomotor impairment, urinary retention, dry mouth, blurred vision, gastrointestinal disturbances; liver dysfunction; blood disorders; also rash and photosensitivity reactions, hypersensitivity reactions (including bronchospasm, angioedema, anaphylaxis); sweating and tremor, injections may be irritant; flatulence, diarrhoea. Store protected from light and moisture.

Precautions

Adverse Effects

Storage

Cinnarizine
Pregnancy Category-C Indications Schedule H Motion sickness, nausea, vomiting, vertigo and tinnitus associated with Meniere disease and other middle ear disorders, as a nootropic drug, adjunct therapy for symptoms of peripheral arterial disease.

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Antiallergics and Drugs used in Anaphylaxis

Availability Dose

TABLETS 25 & 75 mg Plain and 75 mg SR. Oral

Motion sickness Adult: 30 mg 2 hr before travel and 15 mg every 8 hr during travel if needed. Vertigo Adult: 30 mg thrice daily. Child: 5-12 year: half of adult dose. Peripheral circulatory disorders Adult: 75 mg tablets three times daily.

Contraindications Precautions

Hypersensitivity, Parkinson's children below 5 years.

disease,

Hypotension, patients should not drive or operate machinery, pregnancy (Appendix 7c), lactation, elderly, children and neonates, interactions (Appendix 6c). Drowsiness, rarely skin and hypersensitivity reactions, dry mouth, extrapyramidal symptoms sometimes associated with severe depression, muscular weakness, headache, euphoria, GI upsets, blurred vision, urinary difficulty or retention, constipation and increased gastric reflux, fatigue, hypolipidaemic effect. Store below 25C, protected from light

Adverse Effects

Storage:

Dexamethasone* (Refer Page No. 478)

Pregnancy Category-C Indications Schedule H Adjunct in the emergency treatment of anaphylaxis; short-term suppression of inflammation in allergic disorders; adrenocortical insufficiency, ocular inflammation, autoimmune disorders, rheumatic disorder, cerebral oedema, unresponsive shock, bacterial meningitis along with antibiotics. TABLETS 0.5 mg; INJECTION 2 ml vial (4 mg/ ml); CREAM 5 and 15 g (0.1% w/w). Oral Adult- 0.5 to 10 mg daily in divided doses, repeat if necessary. Child- 0.02 to 0.3 mg/kg in three or four divided doses daily.

Availability Dose

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Antiallergics and Drugs used in Anaphylaxis

Intravenous injection 4 to 10 mg every 6 h. Contraindications Untreated systemic infection (unless condition life-threatening); administration of live virus vaccines; renal failure, diabetes mellitus, psychosis, osteoporosis, pregnancy (Appendix 7c), CHF, tuberculosis, fungal infections of the eye. Increased susceptibility to and severity of infection; activation or exacerbation of tuberculosis, amoebiasis, strongyloidiasis; risk of severe chickenpox in non-immune patient (varicella-zoster immunoglobulin required if exposed to chickenpox); avoid exposure to measles (normal immunoglobulin possibly required if exposed); diabetes mellitus; peptic ulcer; hypertension; precautions relating to long-term use of corticosteroids; glaucoma, epilepsy; drug should not be abruptly withdrawn; interactions (Appendix 6c), lactation (Appendix 7b). Nausea, dyspepsia, malaise, hiccups; hypersensitivity reactions including anaphylaxis; perineal irritation after intravenous administration; adverse effects associated with long-term corticosteroid treatment; hyperglycaemia, abdominal distension, angioedema, bradycardia, acne, erythema, Cushings syndrome, oropharangeal candidiasis, hypothalamic pituitary adrenal axis suppression. Store protected from light at a temperature not exceeding 30C.

Precautions

Adverse Effects

Storage

Fexofenadine
Pregnancy Category-C Indications Availability Dose Allergic rhinitis, urticaria. TABLETS 30, 60, 120 and 180 mg; SyRUP 30 mg/5 ml. Allergic rhinitis: Adult- 120 mg once daily. Child (6-11year)- 30 mg twice daily. Urticaria and skin allergy: Adult-180 mg once daily. Child- (6 month to 2 years): 15 mg twice daily, more than 2 years: 30 mg twice daily. Schedule H

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Antiallergics and Drugs used in Anaphylaxis

Contraindications Precautions

Hypersensitivity. Bradycardia, hypokalemia, preexisting long QT interval, renal impairment, pregnancy (Appendix 7c), lactation, interactions (Appendix 6a, 6c). Dizziness, stomach discomfort, pain in extremity, back pain, vomiting, diarrhoea, upper respiratory tract infection, headache, dysmenorrhoea.

Adverse Effects

Hydrocortisone* (Refer Page No. 355, 429 and 479)

Pregnancy Category-C Indications Schedule H Adjunct in the emergency treatment of anaphylaxis; inflammatory skin conditions; inflammatory bowel disease; adrenocortical insufficiency; As acetate: rheumatology, neurology, episcleritis, sinusitis; Addisons disease, Simmonds disease, terculous meningitis; perineal trauma, joint inflammation, subaortic dermatitis. TABLETS 5, 10 and 20 mg, CREAM 10g (1% w/w), OINTMENT 1%, 2.5% w/w INJECTION 100, 200 and 400 mg/vial, (25 mg/5 ml). Intramuscular injection or slow intravenous injection or intravenous infusion
Adult-100 mg to 500 mg, 3 to 4 times in 24 h or as required.

Availability

Dose

Slow intravenous injection mg. Contraindications

Child- Up to 1year: 25 mg. 1 to 5 years: 50

Not relevant to emergency use but for contra-indications relating to long-term use; ulcers. Not relevant to emergency use but for precautions relating to long-term use, interactions (Appendix 6d), lactation (Appendix 7b), pregnancy (Appendix 7c). Adverse effects associated with long-term corticosteroid treatment; opportunistic infections.

Precautions

Adverse Effects

Levocetirizine
Pregnancy Category-B Indications Allergic rhinitis, chronic urticaria. Schedule H

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Antiallergics and Drugs used in Anaphylaxis

Availability Dose

TABLETS 5 mg; SyRUP 2.5 mg/5 ml. Oral Rhinitis, chronic urticaria: Adult & children (>12 years) - 5 mg once daily in the evening. Children (6-12 yrs) - 2.5 mg once daily. Children (6 months - 5 yrs) 1.25 mg once daily.

Contraindications

Hypersensitivity, end-stage renal disease with creatinine clearance < 10 ml/min. Not recommended for lactating mothers or children below 6 months. May impair the ability to drive or operate machinery, concurrent use of alcohol or CNS depressant drugs should be avoided, pregnancy (Appendix 7c), elderly, interactions (Appendix 6c). Somnolence, fatigue, dry mouth, nasopharyngitis have been reported in adults. Fever, cough, epistaxis and diarrhoea may occur in children <12 years. Store protected from heat, light and moisture at a temperature not exceeding 30C.

Precautions

Adverse Effects

Storage

Noradrenaline
Pregnancy Category-C Indications Availability Dose Acute hypotension, adjunct in cardiac arrest, upper gastrointestinal haemorrhage. INJECTIONS Vials (4 mg/ml, 4 mg/2 ml and 2 mg/2 ml) Parenteral Intravenous Acute hypotension Adult: 8-12 g/minute, up to 8-30 g/minute in refractory shock. Infused using a solution of 4 g/ml in glucose 5%, or sodium chloride 0.9% and glucose 5% at a rate of 2-3 ml/ minute. Adjust according to blood pressure response. Average maintenance dose: 0.5-1 ml/minute (2-4 g/minute). Infuse via a central venous catheter or into a large vein. Child: Administer at a rate of 2 g/minute. Alternatively, 2 g/m2/minute. Adjust rate according to BP response and perfusion. Elderly: Initial dose should be at low end of dose range.

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Antiallergics and Drugs used in Anaphylaxis

Upper gastrointestinal haemorrhage Adult: 8 mg in 250 ml of 0.9% sodium chloride injection via intraperitoneal route Alternatively, instill 8 mg in 100 ml of 0.9% sodium chloride solution through a nasogastric tube every hr for 68 hrs, then every 2 hrs for 46 hrs. Withdraw drug gradually. Reconstitution Dilute with 5% glucose injection, with or without sodium chloride; dilution with sodium chloride injection alone is not recommended. Contraindications Hypertension, pregnancy (Appendix 7c), patients with peripheral or mesenteric vascular thrombosis unless necessary as a life-saving procedure. During cyclopropane and halothane anaesthesia, noradrenaline is considered contraindicated because of the risk of producing ventricular tachycardia or fibrillation Monitor BP frequently during infusion, Use large vein for infusion to avoid skin necrosis, interactions (Appendix 6c). Elevation of blood pressure, bradycardia, peripheral ischemia, arrhythmias, anxiety, transient headache, respiratory difficulty, extravasation necrosis at injection site. Store protected from light, in single dose containers. Store at room temperature (25C) and protect from light. Store in tight, lightresistant containers as it is readily oxidised. Do not use if discoloured (e.g. pink, dark yellow, brown) or if there is a precipitate.

Precautions

Adverse Effects

Storage

Pheniramine*
Pregnancy Category-C Indications Availability Dose Schedule H Symptomatic relief of allergy; allergic rhinitis; urticaria. TABLETS 25 and 50 mg; INJECTION 2 ml ampoule (22.75 mg/ml); SyRUP 15 mg/ml. Oral
Adult- 25 mg, 2 to 3 times a day or 50 mg twice daily.

Intramuscular injection
Adult- 1 to 2 ml twice a day.

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Antiallergics and Drugs used in Anaphylaxis

Child- 6 months to 3 years: 0.4 to 1 ml once or twice daily. Over 4 years: 0.8 to 2 ml once or twice daily.

Contraindications

Epilepsy; pregnancy (Appendix 7c); acute asthma; acute porphyria; symptomatic prostatic hypertrophy; neonates and premature infants. Glaucoma; driving or operating machinery; asthma or severe cardiovascular disease, pregnancy (Appendix 7c), lactation. Drug abuse; CNS depression; dry mouth; blurred vision; dizziness; excitation in children. Store protected from light and moisture.

Precautions

Adverse Effects

Storage

Prednisolone* (Refer Page No. 436, 481 and 557)

Pregnancy Category-C Indications Schedule H Short-term as well as long term suppression of inflammation in allergic disorders; malignant disease; Autoimmune disease, bronchial asthma. TABLETS 5, 10, 20, 30 and 40 mg; SyRUP 1 mg/ml and 3 mg/ml; EyE DROPS 1% w/v; INJECTION 2 ml vial (40 mg/ml). Oral
Adult and Child- Initially up to 10 to 20 mg daily in divided doses (severe diseases up to 60 mg), preferably after breakfast.

Availability

Dose

Intramuscular injection Adult and Child- 25 mg to 100 mg once or twice weekly. Contraindications Untreated systemic infection; administration of live virus vaccines; hypersensitivity.

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Antiallergics and Drugs used in Anaphylaxis

Precautions

Increased susceptibility to and severity of infection; activation or exacerbation of tuberculosis, amoebiasis, strongyloidiasis; risk of severe chickenpox in non-immune patient (varicella-zoster immunoglobulin required if exposed to chickenpox); avoid exposure to measles (normal immunoglobulin possibly required if exposed); diabetes mellitus; peptic ulcer; hypertension; further precautions relating to long-term use of corticosteroids; myasthenia gravis, congestive heart failure, renal insufficiency, pregnancy (Appendix 7c), osteoporosis, glaucoma, psychological disorders, diverticulitis, interactions (Appendix 6c, 6d), lactation (Appendix 7b), hepatic impairment (Appendix 7a). Nausea, dyspepsia, malaise, hiccups; hypersensitivity reactions including anaphylaxis; supraclavicular lump, fragile skin. Store protected from light and moisture.

Adverse Effects

Storage

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Antiallergics and Drugs used in Anaphylaxis

37

NFI-2011

Anti-Alzheimer and Anti-Parkinsonism Drugs

4.

Anti-Alzheimer and Anti-Parkinsonism Drugs

Anti-Alzheimer Drugs Anti-Parkinsonism Drugs

39
39 43

4.1 4.2

NFI-2011

38

Anti-Alzheimer and Anti-Parkinsonism Drugs

4. Anti-Alzheimer and Anti-Parkinsonism Drugs

4.1 Anti-Alzheimer Drugs
Alzheimers disease is a slowly progressive neurodegenerative disorder characterized by loss of neurons and synapses in cerebral cortex and certain subcortical regions. The disease mainly affects the older population and is the most common cause of dementia (early stage). Advancing age is one of the predominant risk factors for Alzheimers disease. As the disease advances behavioural changes such as confusion, irritability and aggression, mood swings, language breakdown, long term loss of memory etc. appear. The biochemical mechanisms involved in its pathogenesis are suggested to be the accumulation of abnormally folded amyloid and proteins in the brain, involvement of inflammatory cytokines, alteration in distribution of different neurotrophic factors and expression of their receptors etc. Alzheimers Association has pointed out 10 warning symptoms for this disease which are as under: 1. Memory loss 2. Difficulty performing familiar task 3. Problems with language 4. Disorientation to time and place 5. Poor or decreased judgement 6. Problems with abstract thinking 7. Misplacing things 8. Changes in mood or behaviour 9. Changes in personality 10. Loss of initiative There is no cure for this disease, drug therapy is mainly symptomatic and palliative in nature. Following drugs are used for the treatment of Alzheimers disease:

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Anti-Alzheimer and Anti-Parkinsonism Drugs

Donepezil
Pregnancy Category-C Indications Availability Dose Schedule H For the treatment of mild to moderate Alzheimers disease. TABLETS 5 and 10 mg Plain. Oral Adult- Initially 5 mg daily in the evening. If necessary increase upto 10 mg once daily after 4-6 weeks. Extended release tablet- once daily (23 mg/ day). Maximum dose- 10 mg daily. Contraindications Hypersensitivity, severe hepatic and renal impairment, pregnancy (Appendix 7c), lactation, not recommended for children. Mechanicalintestinalobstructionorperitonitis, Recent intestinal or bladder surgery, bronchial asthma or COPD, arrhythmias, bradycardia, recent MI and hypotension, vagotonia, epilepsy, hyperthyroidism, parkinsonism, moderate renal or hepatic impairment or peptic ulcer, sick sinus syndrome. Nausea, vomiting, diarrhoea, fatigue, insomnia, muscle cramps, bradycardia, convulsions, gastrointestinal, haemorrhage, hepatitis, urinary incontinence, influenza, pruritus, increased liver transaminases. Store protected from moisture, at a temperature not exceeding 25C.

Precautions

Adverse Effects

Storage

Galantamine
Pregnancy Category-B Indications Availability Dosage: Schedule H To treat the symptoms of mild to moderate Alzheimers disease, Dementia syndrome. TABLETS 4 mg, 8 mg and 12 mg; CAPSULES ER 8, 16 and 24 mg; ORAL SOLUTION 4 mg/ml. Oral with meals For Alzheimers disease: 4 mg twice daily. For Dementia Syndrome: 8 to 12 mg twice daily. Extended Release Capsule: 16 to 24 mg once daily.

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Anti-Alzheimer and Anti-Parkinsonism Drugs

Oral Solution: Initially 4 mg twice daily, Maximum 12 mg twice daily (24 mg/day) and in hepatic/renal impairment (max. dose:16 mg/day). Contraindications Hypersensitivity to galantamine, severe kidney and liver problems, pregnancy (Appendix 7c), lactating mothers, children. Patients with asthma or lung disease, epilepsy, stomach ulcer, take plenty of fluids during treatment. Diarrhoea, nausea, anorexia and weight loss, chest pain or shortness of breath.

Precautions

Adverse Effects

Memantine
Pregnancy Category-B Indications Availability Dose Contraindications Precautions Treatment of moderate to severe dementia of Alzheimers disease. TABLETS 5 and 10 mg; CAPSULES 10 mg; ORAL SOLUTION 2 mg/ml. 5 mg once daily; (max. dose upto 20 mg/day). Hypersensitivity to memantine. Seizure, rise in urine pH results in increased plasma levels, pregnancy (Appendix 7c), lactation, children. Fatigue, pain, hypertension, dizziness, headache, constipation, vomiting, back pain, confusion, somnolence, hallucination, coughing, dyspnea, insomnia, urinary tract infections, anxiety, peripheral oedema, arthralgia.

Adverse Effects

Rivastigmine
Pregnancy Category-B Indications Availability Moderate to severe dementia. TABLETS 3 and 4.5 mg; CAPSULES 1.5, 3, 4.5 and 6.0 mg. Transdermal patches containing 9 mg in 5cm2 and 18 mg in 10cm2. Dose Contraindications Adult - Initially 1.5 mg twice daily; (max. dose 6 mg twice daily). Hypersensitivity to carbamate derivatives and severe hepatic impairment, children, lactation. Schedule H

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Anti-Alzheimer and Anti-Parkinsonism Drugs

Precautions

Renal or hepatic impairment, acid peptic disease, pregnancy (Appendix 7c), asthma, sick-sinus syndrome. Mild peripheral cholinergic effect, nausea, vomiting, anorexia, dyspepsia, asthenia, abdominal pain, depression, gastrointestinal haemorrhage, weight loss, urinary tract infections, insomnia, hallucinations, hypertension, elevated LFTs. Smaller patch associated with fewer adverse effects.

Adverse Effects

Tacrine
Pregnancy Category-C Indications Availability Dose Contraindications Mild to dementia. moderate Schedule H Alzheimers type

CAPSULES 10, 20, 30 and 40 mg. 10 mg, 4 times par day; (max. dose 40 mg 4 times par day). Hepatic impairment, hyperbilirubinaemia, bradycardia, bronchial asthma, seizures and gastro intestinal obstruction. Haematological disorders, (Appendix 7c), lactation. pregnancy

Precautions Adverse Effects

Hepatotoxicity, cholinergic side effects.

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Anti-Alzheimer and Anti-Parkinsonism Drugs

4.2 Anti-Parkinsonism Drugs

The use of pharmacotherapy will depend upon the degree of incapacity of the patient and is generally not justified until symptoms compromise working ability and social relationships; although levodopa is used in the early stages in some patients. Close supervision is then needed to ensure that treatment regimens are tolerated and that appropriate changes are made to the regimen as the disease progresses. The most effective form of therapy is a combination of levodopa and a peripheral dopa-decarboxylase inhibitor, such as carbidopa. The response to levodopa with carbidopa is a compromise between increased mobility and adverse effects. Dyskinesias may be dose limiting and increasingly frequent with increased duration of treatment. Many factors including tolerance and progression of the disease may result in complications after 2-5 years of treatment. End-of-dose deterioration occurs when there is a reduced duration of benefit from a dose, resulting in disability and dystonias. The on-off phenomenon is characterized by sudden swings from mobility to episodes of akinesia, tremor and rigidity lasting from a few minutes to several hours. Amelioration of these effects can sometimes be achieved by administering levodopa in a sustained-release preparation or in a greater number of fractionated doses throughout the day. Psychiatric symptoms inducing disruption of sleep, vivid dreams and hallucinations are characteristic adverse effects that may occur at any time, especially in the elderly and may require dose reduction or withdrawal of levodopa. Treatment for idiopathic parkinsonism is often initiated with a dopamine receptor agonist such as bromocriptine. Supplementary use of amantadine, bromocriptine or the monoamine-oxidase-B inhibitor, selegiline can be of value either to enhance the effect of levodopa or to reduce end-of-dose fluctuations and on-off effects. Anticholinergic (more correctly termed antimuscarinic) drugs such as biperiden are usually sufficient in drug-induced parkinsonism.

Drugs Used in Essential Tremor and Related Disorders:

Essential Tremor:
It can be treated with -blockers such as propranolol (120 mg daily) (chapter 13.4) which may be of value if the tremor results in physical or social disability.

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Anti-Alzheimer and Anti-Parkinsonism Drugs

Dystonias:
If no identifiable cause is found and the patient does not go into spontaneous remission, a trial of levodopa should be given to determine whether the patient has dopamineresponsive dystonia. If there is no response within three months, the drug should be withdrawn and small doses of an anticholinergic drug such as biperiden should be given. The dosage may be increased gradually and up to 16 mg daily may be tolerated. In patients who fail to respond to either levodopa or an anticholinergic, other drugs including diazepam, baclofen, carbamazepine or phenothiazines may be of value. Psychological treatments have also been used successfully in the management of dyskinesias.

Chorea:
Choreiform movements can be induced by certain drugs including levodopa, phenytoin and antipsychotic drugs. Huntingtons disease is the most common of the hereditary choreas. Drug treatment is symptomatic and does not alter the progression of the disease. The aim of therapy is to reduce dopaminergic transmission which results from excessive or enhanced cholinergic activity. Antipsychotic drugs antagonize dopamine and usually lessen the chorea temporarily. Tetrabenazine, the dopamine-depleting drug, is used to control movement disorders in Huntingtons chorea and related disorders.

Tics:
Tics which resemble choreiform movements are commonly associated with anxiety. However, in the more complex multiple tic disorder, Tourette syndrome, treatment with antipsychotic drugs may be required.

Tardive Dyskinesia:
It is associated with chronic administration of antipsychotic drugs. It is characterized by involuntary, repetitive, choreiform movement of the cheek, mouth and fingers. The first step of treatment should always be discontinuation of the antipsychotic drug or dosage reduction if the underlying psychotic disorder permits.

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Anti-Alzheimer and Anti-Parkinsonism Drugs

Biperiden
Pregnancy Category-C Indications Schedule H Medicine-induced extrapyramidal symptoms (but not tardive dyskinesias) and adjunctive treatment of parkinsonism. TABLET 2 mg; INJECTION 1 ml ampoule (5 mg/ml). Oral Adult- Medicine-induced extra-pyramidal symptoms, parkinsonism: initially 1 mg twice daily, increased gradually to 2 mg thrice daily; usual maintenance dose 3 to 12 mg daily in divided doses. Intramuscular injection or Slow intravenous injection Adult- Medicine-induced extra-pyramidal symptoms, parkinsonism: 2.5 to 5 mg repeated as necessary to max. 20 mg in 24 h. Contraindications Angle-closure glaucoma; bowel obstruction; megacolon; untreated urinary retention; prostatic hypertrophy; myasthenia gravis; gastrointestinal obstruction. Elderly; cardiovascular disease, hepatic or renal impairment; avoid abrupt withdrawal; paediatric use; pregnancy (Appendix 7c); lactation. May impair ability to perform skilled tasks, for example operating machinery, driving. Adverse Effects Drowsiness, dry mouth, constipation, blurred vision; hesitancy of micturition, dizziness, tachycardia, arrhythmias; confusion, euphoria, excitement, agitation, hallucinations and psychiatric disturbances with high dosage, especially in the elderly and other susceptible patients, may require withdrawal of treatment; impaired memory, mild postural hypotension; urinary retention. Store protected from light.

Availability Dose

Precautions

Storage

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Anti-Alzheimer and Anti-Parkinsonism Drugs

Bromocriptine*
Pregnancy Category-B Indications Availability Dose Parkinsonism. TABLETS 1.25, 2.5 and 5 mg. Oral Adult- First week 1 to 1.25 mg at night, second week 2 to 2.5 mg at night, third week 2.5 mg twice daily, fourth week 2.5 mg 3 times daily, then increasing by 2.5 mg every 3 to 14 days according to response to a usual range of 10 to 40 mg daily. Take with food. Child- Under 15 years; not recommended. Contraindications Hypersensitivity to bromocriptine or other ergot alkaloids; ischaemic heart disease; toxaemia of pregnancy and hypertension in postpartum women or in puerperium. Should not be used postpartum or in puerperium in women with high blood pressure, coronary artery disease or symptoms (or history) of serious mental disorder; monitor blood pressure carefully (especially during first few days) in postpartum women. Very rarely, hypertension, myocardial infarction, seizures or stroke (both sometimes preceded by severe headache or visual disturbances) and mental disorders have been reported in postpartum women given bromocriptine for lactation suppression-caution with antihypertensive therapy and avoid other ergot alkaloids. Discontinue immediately if hypertension, unremitting headache or signs of CNS toxicity develop. Precautions Specialist evaluation-monitor for pituitary enlargement, particularly during pregnancy, annual gynaecological assessment (postmenopausal, every 6 months), monitor for peptic ulceration in acromegalic patients; contraceptive advice if appropriate (oral contraceptives may increase prolactin concentration); avoid lactation for about 5 days if lactation prevention fails; history of serious mental disorders (especially psychotic disorders) or cardiovascular disease or Raynaud's syndrome; monitor for retroperitoneal fibrosis; porphyria; hepatic impairment; interactions (Appendix 6a, 6c, 6d). Schedule H

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Anti-Alzheimer and Anti-Parkinsonism Drugs

Hypotensive reactions may be disturbing in some patients during the first few days of treatment and particular care should be exercised when driving or operating machinery; tolerance may be reduced by alcohol. Adverse Effects Nausea, constipation, headache, drowsiness, nasal congestion; less commonly vomiting, postural hypotension, fatigue, dizziness, dyskinesia, dry mouth, leg cramps; also, particularly with high doses, confusion, psychomotor excitation, hallucinations; rarely, constrictive pericarditis, pericardial effusion, pleural effusion (may necessitate discontinuation), retroperitoneal fibrosis reported (monitoring required), hair loss and allergic skin reactions; very rarely, gastro-intestinal bleeding, gastric ulcer, vasospasm of fingers and toes particularly in patients with Raynaud's syndrome and effects like neuroleptic malignant syndrome on withdrawal, increased libido and hypersexuality also reported; conjunctival infection. Store protected from light.

Storage

Levodopa + Carbidopa*
Pregnancy Category-C Indications Availability Schedule H All forms of parkinsonism other than medicine-induced. TABLETS Levodopa 100 mg + Carbidopa 10 mg; Levodopa 100 mg + Carbidopa 25 mg; Levodopa 200 mg + Carbidopa 50 mg; Levodopa 250 mg + Carbidopa 25 mg. Oral Adult- Parkinsonism: expressed in terms of levodopa, initially 100 mg (with carbidopa 10 mg) twice daily, increased by 100 mg (with carbidopa 10 mg) every few days as necessary, to a max. of 1.5g. Optimum daily dose must be determined for each patient by careful monitoring and be taken after meals. Contraindications Concurrent use of monoamine oxidase inhibitors; undiagnosed chin lesion; lactation; psychosis; decompensated endocrine; angleclosure glaucoma; confirmed or suspected malignant melanoma.

Dose

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Anti-Alzheimer and Anti-Parkinsonism Drugs

Precautions

Pulmonary disease, peptic ulceration, cardiovascular disease (including previous myocardial infarction); diabetes mellitus, osteomalacia, open-angle glaucoma, history of melanoma (risk of activation), psychiatric illness (avoid if severe); close monitoring of hepatic, haematological, psychiatric, cardiovascular and renal function required in long-term therapy; elderly: avoid rapid dose increases; warn patients to resume normal activities gradually; avoid abrupt withdrawal; pregnancy (toxicity in animals) (Appendix 7c), lactation; interactions (Appendix 6c). Nausea, anorexia and vomiting, particularly at the start of treatment; postural hypotension at the start of treatment, particularly in elderly and those receiving antihypertensives; excessive drowsiness and sudden onset of sleep (warn patient of these effects); confusion, vivid dreams, dizziness, tachycardia, arrhythmias; reddish discolouration of body fluids; insomnia, headache, flushing, gastrointestinal bleeding, peripheral neuropathy; taste disturbances, pruritus, rash, liver enzyme changes; psychiatric symptoms including psychosis, depression, hallucinations, delusions and neurological disturbances including dyskinesias may be dose-limiting; painful dystonic spasms (end-of-dose effects) and (on-off effects) after prolonged treatment (see notes above); neuroleptic malignant syndrome, on sudden withdrawal; rarely, hypersensitivity, dyspnoea; upper respiratory infection. Store protected from light and moisture.

Adverse Effects

Storage

Trihexyphenidyl (Benzhexol)*
Pregnancy Category-C Indications Schedule H All forms of parkinsonism other than medicine-induced, control of extrapyramidal disorders caused by CNS drugs. TABLETS 2 and 5 mg; INJECTION vial 2 mg/ ml. 1 mg daily, increased gradually; usual maintenance dose 5 to 15 mg daily in 3 to 4 divided doses (max. 20 mg daily); elderly preferably lower end of range.

Availability Dose

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Anti-Alzheimer and Anti-Parkinsonism Drugs

Contraindications

Avoided in gastro-intestinal obstruction and myasthenia gravis; closed angle glaucoma; chronic pulmonary disease; sick sinus syndrome; thyrotoxicosis; tachycardia. Use with caution in cardiovascular disease, hypertension, psychotic disorders, prostatic hypertrophy, pyrexia, in those susceptible to angle-closure glaucoma and in the elderly. It should not be withdrawn abruptly in patients receiving long-term treatment. Antimuscarinics are liable to abuse. Elderly males with possible prostate hypertrophy; tardive dyskinesia; neuroleptic malignant syndrome. Use with caution in renal impairment and hepatic impairment, lactation and interactions (Appendix 6a). Constipation, dry mouth, nausea, vomiting, tachycardia, dizziness, confusion, euphoria, hallucinations, impaired memory, anxiety, restlessness, urinary retention, blurred vision and rash. Angle-closure glaucoma may occur very rarely, paralytic ileus; dilation of colon.

Precautions

Adverse Effects

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Anticonvulsants/Antiepileptics

5.

Anticonvulsants/Antiepileptics

51

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50

Anticonvulsants/Antiepileptics

5. Anticonvulsants/ Antiepileptics
Control of Epilepsy:
Treatment of seizures should always be started with a single antiepileptic drug (AED), and the choice of an anticonvulsant should be made on an individual basis. The drug of choice will depend on the primary diagnosis, seizure type, efficacy of the drug and the patients tolerance of treatment. If a drug fails to control the seizures after it has been used in full therapeutic dosage for an adequate period, or if it is not tolerated, it should be gradually substituted with another drug, with the first drug being withdrawn only when the new regimen is established. If monotherpy is ineffective, next alternative drug should be started, and try to withdraw first drug if there was no response for that drug or continue with that if there was partial response for initial drug. Initial dose of the drug of choice should be determined on the basis of the degree of urgency, the size and age of the patient. It should be increased gradually until an effective response is obtained. All antiepileptics commonly produce neurological adverse effects at higher dose ranges and patients should be monitored closely for adverse effects to help in accurate dose titration. Except for phenytoin, it is rarely, useful to measure plasma-drug concentrations as an aid to dose adjustment. Non-compliance, inappropriate dosing and overdosing is a major impediment to effective antiepileptic treatment. Patients should ideally remain under supervision throughout treatment period.

Withdrawal:
Treatment is normally continued for a minimum of two years of seizure free period. In certain circumstances like in juvenile myoclonic epilepsy, antiepileptic drugs may need to be continued throughout life, because of the high relapse rate of seizure after AED withdrawal. Withdrawal should be extended over a period of several months because abrupt withdrawal can lead to recurrence of seizure and or/status epilepticus. A general rule for duration of tapering is how many years patient had taken that particular drug, over a period of so many months it should be tapered. In patients receiving several antiepileptic drugs, only one drug should be withdrawn at a time. Many adult patients relapse once treatment is withdrawn and it may be justified to continue 51 NFI-2011

Anticonvulsants/Antiepileptics

treatment indefinitely, particularly when the patients livelihood or lifestyle can be endangered by recurrence of a seizure.

Pregnancy and Lactation:

Untreated epilepsy during pregnancy may cause harm to the fetus; there is therefore no justification for abrupt withdrawal of treatment although withdrawal of therapy may be an option if the patient has been seizure-free for at least 2 years; resumption of treatment may be considered after the first trimester. If antiepileptics are continued in pregnancy, monotherapy with the lowest effective dose is preferred, with adjustment made to take account of changes in plasma levels associated with pregnancy. There is an increased risk of birth defects with the use of anticonvulsants, particularly carbamazepine, valproate and phenytoin. However, if there is good seizure control, there is probably no advantage in changing pregnant patients antiepileptic drugs. In view of the risks of neural tube and other defects, patients who may become pregnant should be informed of the risks and referred for advice and pregnant patients should be offered counselling and antenatal screening. To counteract the risk of neural tube defects, adequate folate supplements are advised for women before and during pregnancy. In view of the risk of neonatal bleeding associated with carbamazepine, phenobarbital and phenytoin, prophylactic phytomenadione (vitamin K1 ) is recommended for the neonate and the mother before delivery. Antiepileptic drugs can be continued during lactation (see also Appendix 7b).

Driving:
Regulations are in place in many countries which may, for example, restrict driving by patients with epilepsy to those whose seizures are controlled. Further, antiepileptic drugs may cause CNS depression, particularly in the early stages of treatment and patients affected by adverse effects such as drowsiness or dizziness should not operate machinery or drive.

Choice of Antiepileptic in Management of Convulsive Disorders

Generalized Tonic-Clonic Seizures:
Phenobarbital, phenytoin and valproate are widely used in the treatment of these conditions. However, each of these drugs is associated with dose-related and idiosyncratic adverse effects and monitoring of haematological and hepatic function is routinely not advised.

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Anticonvulsants/Antiepileptics

Simple Partial and Complex Partial Seizures:

Carbamazepine, oxcarbamazepine, clobazam, lamotrigine and zonisamide are effective in partial epilepsy.

Absence Seizures:
Both ethosuximide and valproate are recommended in the treatment of absence seizures (petit mal) and are usually well tolerated. However, ethosuximide can, rarely, cause lupus erythematosus and psychoses which call for immediate, but cautious, discontinuation. Absence seizures are commonly associated with tonic-clonic seizures and valproate is preferred since it has a broad spectrum of activity.

Tonic Seizures, Atonic Seizures and Atypical Absence Seizures:

Phenobarbital or phenytoin is widely used for tonic seizures, valproate or clonazepam for atonic seizures and clonazepam for atypical absence seizures. However, tonic seizures most of the times are associated with multiple seizures types like Lennox-Gastaut syndrome (LGS), where phenytoin and phenobarbitone should be avoided as they can precipitate other type of seizures.

Myoclonic Seizures:
Valproate is widely used and most effective for juvenile myoclonic seizures. As juvenile myoclonic epilepsy is associated with a high relapse rate, it is often necessary to continue therapy indefinitely. Other myoclonic seizures are often resistant to treatment and some do not have an epileptic basis. Valproate or clonazepam can be of value in this case and other antiepileptic drugs may be useful in intractable cases. Both drugs are generally well accepted, although tolerance to clonazepam has been reported.

Infantile Spasm (Infantile Myoclonic Epilepsy):

Infantile spasms, which are often associated with severe brain damage, can be resistant to antiepileptic drugs. Drugs effective in this type of seizures are benzodiazepines (nitrazepam, clonazepam, clobazam), valproic acid, ACTH, vigabatrin, levetiracetam, topiramate, zonisamide, lamotrigine, and ketogenic diet.

Febrile Convulsions:
Sponging with tepid water and antipyretic such as paracetamol is effective in controlling the temperature. Recurrent febrile convulsions or prolonged convulsions (those lasting >5 min) are treated with diazepam, either rectally in solution or 53 NFI-2011

Anticonvulsants/Antiepileptics

by intravenous injection, or intranasal or buccal midazolam, to prevent possible brain damage. Intermittent prophylaxis, with diazepam (or clobazam) administered at the onset of fever, may prevent recurrence of febrile [Link] of antiepileptics for continuous prophylaxis is controversial; it is probably indicated in only a small proportion of children including those who already have evident neurological abnormalities, or who have had previous prolonged or focal convulsions. Phenobarbital may be used for this purpose but careful clinical monitoring and dosage adjustment are necessary in order to minimize the risk of adverse effects. Valproate can also be used.

Status Epilepticus:
Status epilepticus is a medical emergency which carries a high mortality rate. Initial management includes positioning the patient to avoid injury, supporting respiration including provision of oxygen, maintaining blood pressure and the correction of any hypoglycaemia; hypocalcemia or any other electrolyte disturbance; maintenance of the airway and assisted ventilation are crucial even when the seizures are controlled, because the drugs used in its management may cause respiratory depression. Intravenous lorazepam, midazolam are often effective in status epilepticus. Lorazepam, which acts rapidly, should be administered first and should be followed immediately by a loading dose of phenytoin which has a longer-acting effect. When cannulation is difficult or impossible, diazepam may be administered rectally as a solution (absorption from suppositories is too slow for treatment of status epilepticus). Intravenous phenobarbital is also effective but is more likely to cause respiratory depression; it is used in refractory cases but should be avoided in patients who have recently received oral phenobarbital. Rectal paraldehyde may also be used; it causes little respiratory depression and is therefore useful where facilities for resuscitation are poor. If seizures continue despite treatment, intravenous valproate, levetiracetam, midazolam infusion, propofol infusion, barbiturate coma and general anaesthesia may be required. The underlying cause must be identified and remedied in all cases.

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Carbamazepine* (Refer Page No. 585)

Pregnancy Category-D Indications Schedule H

Partial seizures with or without secondary generalisation; trigeminal neuralgia; bipolar disorder. TABLETS 100, 200 and 400 mg Plain; 100 mg DT; 200, 300 and 400 mg CR and SR; SyRUP 100 ml (100 mg/5 ml). Oral
Adult- Initially 100 and 200 mg 1 to 2 times daily increased slowly to usual dose of 400 mg to 1.2g daily in divided doses. In some cases 1.6 to 2g may be needed. Administer lower initial dose to elderly. Child- Start with 5 - 10 mg/kg/day in two to three divided doses then gradually increase at weekly intervals to a max. dose of 30-35 mg/ kg/day.

Availability

Dose

Contraindications Atrioventricular conduction abnormalities; history of bone-marrow depression; porphyria. Precautions Hepatic impairment (Appendix 7a); renal impairment; cardiac disease (see also Contraindications); skin reactions (see Adverse effects); history of blood disorders (blood counts before and during treatment); glaucoma; lactation (Appendix 7b); avoid sudden withdrawal; interactions (Appendix 6b, 6c, 6d); pregnancy (Appendix 7c). Patients or their caretakers should be told how to recognize signs of blood, liver or skin disorders and advised to seek immediate medical attention if symptoms such as fever, sore throat, rash, mouth ulcers, bruising or bleeding develop. Leukopenia which is severe, progressive and associated with clinical symptoms requires withdrawal (if necessary under cover of suitable alternative). May impair ability to perform skilled tasks, for example operating machinery, driving; see also notes above.

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Adverse Effects

Dizziness, drowsiness, headache, ataxia, blurred vision, diplopia (may be associated with high plasma levels); gastrointestinal intolerance including nausea and vomiting, anorexia, abdominal pain, dry mouth, diarrhoea or constipation; commonly, mild transient generalized erythematous rash (withdraw if worsens or is accompanied by other symptoms); leukopenia and other blood disorders (including thrombocytopenia, agranulocytosis and aplastic anaemia); cholestatic jaundice, hepatitis, acute renal failure, Stevens-Johnson syndrome (erythema multiforme), toxic epidermal necrolysis, alopecia, thromboembolism, arthralgia, fever, proteinuria, lymph node enlargement, arrhythmias, heart block and heart failure, dyskinesia, paraesthesia, depression, impotence, male infertility, gynaecomastia, galactorrhoea, aggression, activation of psychosis, photosensitivity, pulmonary hypersensitivity, hyponatraemia, oedema, disturbances of bone metabolism with osteomalacia also reported; confusion and agitation in elderly. Store protected from light and moisture.

Storage

Clobazam
Pregnancy Category-D Indications Schedule H

Add-on for refractory partial, complex and generalized seizures, add-on in West syndrome, LGS, myoclonic epilepsy, absence seizures, to cover short period of increased seizure susceptibility addition of new AED examinations overnight travel catamenial epilepsy, intermittent prophylaxis in febrile seizures. TABLETS 5, 10 and 20 mg. Oral 0.3-2.9 mg/kg/day, (average 1 mg/kg/day) single at bed time or twice daily dose.

Availability Dose

Precautions Adverse Effects

Pregnancy (Appendix (Appendix 6c).

7c),

interactions

Sedation, dizziness, hyperactivity, behavioural problem, irritability, drooling, weight gain, sleep disturbance, blurring, diplopia.

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Clonazepam
Pregnancy Category-D Indications Schedule H

Absence seizures, myoclonic seizures, akinetic seizures, panic disorder, subcortical myoclonus, adjuvant treatment of refractory epilepsy. TABLETS 0.25, 0.5, 1 and 2 mg. Adult- 0.5 - 5 mg thrice daily, initial dose should not exceed 1.5 mg/day, slow titration is recommended Maintenance dose 4-8 mg daily, Maximum dose 20 mg daily. Infants and child: Initial dose 0.01-0.03 mg/ kg/day (not to exceed 0.05 mg/kg/day) given in 2-3 divided doses. Maintenance dose 0.1-0.2 mg/kg/day in 3 divided doses. Panic disorder: Adult- Initial dose 0.25 mg twice daily, usual maintenance dose 1 mg/day, maximum dose 4 mg/day.

Availability Dose

Contraindications Hypersensitivity to benzodiazepines, acute pulmonary insufficiency, acute narrow angle glaucoma. Precautions Neonates, chronic pulmonary insufficiency, hepatic and renal dysfunction, porphyria, elderly, pregnancy (Appendix 7c), lactation (Appendix 7b), interactions (Appendix 6a, 6c); avoid sudden withdrawal. Sedation, dullness, CNS depression, ataxia, bronchial hypersecretion, abnormal eye movement, blood dyscrasias.

Adverse Effects

Diazepam* (Refer Page No. 420 and 567)

Pregnancy Category-D Indications Schedule H

Status epilepticus; emergency management of recurrent seizures; febrile convulsions; seizures associated with poisoning and medicine withdrawal; adjunct in acute alcohol withdrawal; premedication; anxiety disorders; psychosomatic behaviour disorder; spasticity. TABLETS 2, 5 and 10 mg; CAPSULE 10 mg; SUSPENSION 2 mg/ml; INJECTION 2 ml ampoule (5 mg/ml). Intravenous injection

Availability

Dose

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Adult-Treatment of status epilepticus and convulsions due to poisoning: 10 mg at the rate of 1 ml/min (5 mg) repeated if necessary after 10 min. Child-Under 12 years: 300 to 400 g/kg, repeated after 10 min if necessary. Contraindications Respiratory depression; acute pulmonary insufficiency; sleep apnoea; severe hepatic impairment; myasthenia gravis; avoid injections containing benzyl alcohol in neonates, narrow angle glaucoma; hypersensitivity to benzodiazepine. Precautions Respiratory disease, muscle weakness, history of alcohol or drug abuse, marked personality disorder; pregnancy (Appendix 7c); lactation (Appendix 7b); reduce dose in elderly or debilitated patients and in hepatic impairment (avoid if severe, Appendix 7a), renal impairment; avoid prolonged use and abrupt withdrawal; when given intravenously, facilities for reversing respiratory depression with mechanical ventilation must be at hand (see below); porphyria; interactions (Appendix 6a, 6c); blood count test on prolonged treatment. Intravenous infusion of diazepam is potentially hazardous (especially if prolonged) calling for close and constant observation and best carried out in a speciality centre with intensive care facilities. Prolonged intravenous infusion may lead to accumulation and delay recovery. May impair ability to perform skilled tasks, for example operating machinery, driving; see also notes above. Adverse Effects Drowsiness and lightheadedness the next day; confusion and ataxia (especially in the elderly); amnesia; dependence; paradoxical increase in aggression; muscle weakness; occasionally headache, vertigo, salivation changes, gastrointestinal disturbances, skin reactions, visual disturbances, dysarthria, tremors, incontinence, urinary retention; blood disorders and jaundice; hypotension and apnoea, pain and thrombophlebitis (with injection); increased appetite; weight gain. Store protected from light.

Storage

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Fosphenytoin
Pregnancy Category-D Indications Availability Dose Schedule H

Generalized tonic-clonic status epilepticus. INJECTION 2 ml vial (75 mg/ml). Adult- 15 mg/kg i.v. infusion at the rate of 100150 mg/min.

Contraindications Porphyria. Precautions Adverse Effects Uremia, hypoalbuminemia, interactions (Appendix 6b, 6c); pregnancy (Appendix 7c). Cardiovascular collapse and/or central nervous system depression, nystagmus, dizziness, pruritus, paresthesia, headache, somnolence, ataxia, hypotension.

Gabapentin
Pregnancy Category-C Indications Schedule H

Add-on drug in resistant partial seizures with or without secondary generalization, rolandic epilepsy- preferred for safety reason, first line in epilepsy patients with hepatic disease. TABLETS/CAPSULES 100 and 300 mg. Oral Initially 10 mg/kg/day, increase 10 mg/kg/day to maintenance dose 30-100 mg/kg/day, in three divided doses.

Availability Dose

Contraindications Pregnancy (Appendix 7c) Adverse Effects Somnolence, dizziness, fatigue, nystagmus, behavioral changes (<10%)-aggression, hyperexcitability, tantrum, euphoria, weight gain.

Lamotrigine
Pregnancy Category-C Indications Schedule H

Partial seizures and secondary generalised tonic-clonic seizures.

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Availability Dose

TABLETS 25, 50 and 100 mg Plain; 5, 150 and 200 mg DT. Oral Adult and Child over 12 years- 25 mg once daily for 2 weeks followed by 50 mg once daily for 2 weeks, increase by 50 to 100 mg every 1 to 2 weeks to maintenance dose of 100 to 200 mg daily. Child- Monotherapy- Inital dose 2 mg/kg/day for 2 weeks then 5 mg/kg/day for 2 weeks. max. dose 5 - 15 mg/kg/day once or twice daily. With valproic acid- Initial dose - 0.5 mg/kg/ day to max. dose of 1 - 5 mg/kg/day in single dose. With enzyme inducer- 2 mg/kg/day for 2 weeks than 5 mg/kg/day for 2 weeks. Max. 5 - 15 mg/ kg/day once or twice daily, when valproic acid added to already regimen with lamotrigine, reduce dose of lamotrigine by 25 - 50%.

Contraindications Child less than 12 years; hypersensitivity; severe hepatic and renal impairment. Precautions Monitoring of liver and renal function; abrupt withdrawal to be avoided; pregnancy (Appendix 7c) and lactation; avoid in patients who need to undertake task requiring mental alertness; patients taking sodium valproate. Skin eruptions; nausea; vomiting; headache; toxic epidermal necrosis; hepatotoxicity; leucopenia; thrombocytopenia; confusion; hallucination.

Adverse Effects

Levetiracetam
Pregnancy Category-C Indications Schedule H

Good effect difficult-to-treat idiopathic focal epilepsies of childhood, including variations such as continuous spike and wave during sleep or Landau-Kleffner syndrome (LKS), photosensitivity and myoclonus- Generalised epilepsy with photosensitivity, idiopathic epilepsy control of GTCS and Myoclonic, treatment of postanoxic and post-encephalitic myoclonic epilepsy, epileptic encephalopathiesLGS, West Syndrome, severe myoclonic epilepsy, absence seizure, rolandic epilepsy. TABLETS 250, 500 and 750 mg, SyRUP 100 mg/ ml, INJECTION 5 ml ampoule (100 mg/ml). Oral

Availability Dose

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Initial dose- 10-20 mg/kg/day, increase by 10 mg/kg/day every 1-2 week upto 40-60 mg/kg/ day in two divided doses. Intravenous injection 20-30 mg/kg at the rate of 5 mg/kg/min. Contraindications Hypersensitivity. Precautions Adverse Effects Renal disease; pregnancy (Appendix 7c). Most frequent somnolence, asthenia (dose dependent); headache, hair loss, vertigo, nausea, infection; behavioral changes such as hostility aggression, apathy, anxiety, depression, psychosis.

Magnesium Sulphate
Pregnancy Category-A Indications Prevention of recurrent seizures in eclampsia; prevention of seizures in pre-eclampsia; acute nephritis in children. INJECTION 500 mg/ml. Intravenous injection (concentration of magnesium sulphate should not exceed 20%) Prevention of seizure occurrence in eclampsia: initially 4g over 5 to 15 min, followed by infusion 1g/hr for at least 24 h after last seizure. If seizures recur, additional dose of 2g (or 4g if body weight is over 70 kg). Contraindications Not to be injected parenterally in patients with heart block or myocardial damage. Precautions Hepatic impairment (Appendix 7a); pregnancy (Appendix 7c); renal impairment; in severe hypomagnesaemia administer initially via controlled infusion device (preferably syringe pump); monitor blood pressure, respiratory rate, urinary output and for signs of overdosage (loss of patellar reflexes, weakness, nausea, sensation of warmth, flushing, drowsiness, double vision and slurred speech). Generally associated with hypermagnesaemia, nausea, vomiting, thirst, flushing of skin, hypotension, arrhythmias, coma, respiratory depression, drowsiness and confusion, loss of tendon reflexes, muscle weakness; colic and diarrhoea following oral administration; hypothermia; stupor.

Availability Dose

Adverse Effects

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Storage

Store protected from moisture.

Oxcarbamazepine
Pregnancy Category-C Indications Schedule H

Monotherapy or adjunctive therapy in the treatment of partial seizures, secondary generalzed seizure, substitution for carbamazepine can be made abruptly with an oxcarbamazepine-to-carbamazepine ratio of 300:200. TABLETS 150, 300, 450, 500 and 600 mg; SUSPENSIONS 300 mg/5 ml. Initial dose: 8-10 mg/kg/day, increasing by 8-10 mg/kg/day as tolerated at 3-7 day interval. Given in two divided doses. Maximum- 30 mg/ kg. Pregnancy (Appendix 7c); interactions (Appendix 6c). Less frequently than they do with carbamazepine (2.8% vs 6.5%), hyponatremia is more common but not clinically significant, rash, weight gain, alopecia, nausea, headache, somnolence.

Availability Dose

Precautions Adverse Effects

Phenobarbitone*
Pregnancy Category-D Indications Schedule H

Generalized tonic-clonic seizures; partial seizures; neonatal seizures; febrile convulsions; status epilepticus; sedative, hypnotic, preanaesthetic. TABLETS 30 and 60 mg; INJECTION 1 ml ampoule (200 mg/ml); SyRUP 20 mg/ml. Slow intravenous injection Status epilepticus: (dilute injection 1 in 10 with water for injections), Adult- 10 mg/kg at a rate of not more than 100 mg/min (up to max. total dose of 1 g); Child- 10-20 mg/kg at a rate of not more than 30 mg/min. Oral Adult- 60-180 mg daily at night.

Availability Dose

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Child- 1 month-12 years: 1-1.5 mg/kg twice daily, maintenance dose 2.5-4 mg/kg once/ twice daily. 12-18 years: Initially 60-180 mg twice daily, maintenance dose 60-180 mg once daily. Contraindications Absence seizures; latent porphyria. Precautions Elderly, debilitated, children (may cause behavioural changes); impaired renal function or hepatic function (Appendix 7a), respiratory depression (avoid if severe); pregnancy (see notes above; Appendix 7c); lactation (Appendix 7b); avoid sudden withdrawal; interactions (Appendix 6a, 6b, 6c); habbit forming. Sedation, mental depression, agitation, hallucination, syncope; ataxia, nystagmus; allergic skin reactions including rarely, exfoliative dermatitis, toxic epidermal necrolysis, StevensJohnson syndrome (erythema multiforme); paradoxical excitement, restlessness and confusion in the elderly; irritability and hyperactivity in children; megaloblastic anaemia (may be treated with folic acid); osteomalacia; status epilepticus (on treatment withdrawal); hypotension, bradycardia, shock; laryngospasm and apnoea (with intravenous injection); cognitive impairment; aplastic anaemia; hepatic failure; connective tissue disorder; hyperkinesias. Store protected from moisture.

Adverse Effects

Storage

Phenytoin*
Pregnancy Category-D Indications Availability Schedule H partial

Generalized tonic-clonic seizures; seizures; status epilepticus.

TABLETS 100, 150 and 200 mg Plain; 300 mg SR; CAPSULES 25 mg, 100 mg; INJECTION 2 ml ampoule (50 mg/ml); SUSPENSION 25 mg/ml. Oral or slow intravenous injection or infusion
Adult- Status epilepticus: (with regular BP and ECG monitoring) 18 mg/kg at rate not exceeding 50 mg/min as loading dose, maintenance dose of about 100 mg should be given thereafter at an interval of 6 to 8 h (dose can be reduced according to weight). Child- Status epilepticus: 20 mg/kg at a rate not exceeding 1 mg/kg/min, maintenance dose 4-7 mg/kg/day in 2 divided doses, max dose 300 mg/day.

Dose

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Contraindications Porphyria; avoid parenteral use in sinus bradycardia, sino-atrial block, second- and third-degree heart block, Stokes-Adams syndrome; pregnancy (Appendix 7c). Precautions Hepatic impairment (reduce dose; Appendix 7a); lactation (Appendix 7b); diabetes mellitus; monitor blood counts; hypotension and heart failure (caution with parenteral use); intravenous administration-resuscitation facilities must be available; injection solution alkaline (irritant to tissues); interactions (Appendix 6a, 6b, 6c); hypersensitivity; osteomalacia, it worsens myoclonus and absence seizures. Patients or their caretakers should be told how to recognize signs of blood or skin disorders and advised to seek immediate medical attention if symptoms such as sore throat, rash, mouth ulcers, bruising or bleeding develop. Leukopenia which is severe, progressive or associated with clinical symptoms requires withdrawal (if necessary under cover of suitable alternative). May impair ability to perform skilled tasks, for example operating machinery, driving; see notes above. Adverse Effects Gastric intolerance, headache, sleeplessness, agitation (during initial phase); sedation, hallucinations, confusion; blurred vision, ataxia, nystagmus, diplopia; slurred speech, cerebellar-vestibular symptoms, behavioural disorders, hyperglycaemia (may be signs of overdosage); gingival hyperplasia, acne, coarse facies, hirsutism, fever; neurological changes (peripheral neuropathy, choreiform movements, impaired cognition, increased seizure frequency); osteomalacia, rickets (associated with reduced plasma calcium levels); lymph-node enlargement; rashes (discontinue; if mild re-introduce cautiously, but discontinue if recurrence); very rarely, Stevens-Johnson syndrome (erythema multiforme), systemic lupus erythematosus, toxic epidermal necrolysis; rarely, blood disorders including megaloblastic anaemia (may be treated with folic acid), leukopenia, thrombocytopenia, agranulocytosis with or without bone marrow depression; intravenous administrationcardiovascular and CNS depression (particularly if administered too rapidly) with arrhythmias, hypotension and cardiovascular collapse, alterations in respiratory function (including respiratory collapse); dyskinesia; hepatitis, hepatic failure. Store protected from moisture at temperature not exceeding 30C.

Storage

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Sodium Valproate*
Pregnancy Category-D Indications Schedule H

Generalized tonic-clonic seizures; partial seizures; atonic seizures; absence seizures; myoclonic seizures; acute mania; migraine. TABLETS 125, 200, 250, 300 and 500 mg Plain; 200, 300 and 500 mg CR; SyRUP 200 mg/5 ml; INJECTION 100 mg/vial, 5 ml ampoule (100 mg/5 ml) CR. Oral
Adult- 600 mg daily in two divided doses (preferably after food) thereafter increase by 200 mg at 3 days interval clinical response till desired. Child- Initial dose 20 mg/kg/day, max. dose 60 mg/kg/day.

Availability

Dose

Contraindications Active liver disease, family history of severe hepatic dysfunction; pancreatitis; porphyria; hypersensitivity. Precautions Monitor liver function before and during first 6 months of therapy (Appendix 7a), especially in patients at most risk (children under 3 years of age, those with metabolic disorders, degenerative disorders, organic brain disease or severe seizure disorders associated with mental retardation, or multiple antiepileptic therapy); ensure no undue potential for bleeding before starting and before major surgery or anticoagulant therapy; renal impairment; pregnancy {important see notes above, (neural tube screening)} (Appendix 7c); lactation (see notes above; Appendix 7b); systemic lupus erythematosus; false-positive urine tests for ketones; avoid sudden withdrawal; interactions (Appendix 6a, 6c, 6d); hyperammonemia.

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Adverse Effects

Gastrointestinal irritation, nausea, increased appetite and weight gain, hyperammonaemia; ataxia, tremor; transient hair loss (regrowth may be curly); oedema, thrombocytopenia, inhibition of platelet aggregation; impaired hepatic function and rarely, fatal hepatic failure (see Precautions-withdraw treatment immediately if malaise, weakness, lethargy, oedema, abdominal pain, vomiting, anorexia, jaundice, drowsiness or loss of seizure control); sedation reported and also increased alertness; behavioural disturbances; rarely, pancreatitis (measure plasma amylase if acute abdominal pain), extrapyramidal symptoms, leukopenia, pancytopenia, red cell hypoplasia, fibrinogen reduction; irregular periods, amenorrhoea, gynaecomastia, hearing loss, Fanconi syndrome, dementia, toxic epidermal necrolysis, StevensJohnson syndrome (erythema multiforme), vasculitis, hirsutism and acne reported; hallucinations; abnormal gut; pneumonia; headache; taste perversion; polycystic ovary. Store protected from light.

Storage

Topiramate
Pregnancy Category-C Indications Schedule H

Resistant partial seizures, LGS- I.S, Generalized Tonic-Clonic Seizures (GTCS), severe myoclonic epilepsy of infancy. TABLETS 25, 50, 100 and 200 mg. Oral Initial dose: 0.5 - 1 mg/kg/day (two divided doses) increase by 0.5 - 1 mg/kg/day at 1 to 2 week intervals, maintenance dose usually 5 - 9 mg/kg/day, max.-24 mg/kg/day. For prophylaxis of migraine headache: 100 mg/ day.

Availability Dose

Precautions

Pregnancy (Appendix (Appendix 6a, 6c).

7c);

interactions

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Adverse Effects

Anorexia, weight loss, cognitive slowing and behavior changes, difficulty with memory, somnolence, dizziness, ataxia, fatigue, kidney stones (1.5%) 2-4 times higher than general population, paresthesias, liver functions- in 1% transient and mild enzymes, metabolic acidosis, Ac. myopia and sec, angle glaucoma- mostly at start, oligohydrosis, hyperthermia and sec rash, hyperammonemia and encephalopathy with concomitant valproic acid use, behavioral reactions (26%), Most frequent such as aggressiveness, hyperactivity, excitement, anxiety, obsessive behaviour, cognitive delay of various degree more in children than adults because of preexisting behavioral problems in children with drug resistant epilepsy.

Vigabatrin
Pregnancy Category-C Indications Availability Dose Infantile spasms, refractory partial seizures with or without secondary generalization. CAPSULES 500 mg. Initial dose- 40 mg/kg/day in two divided doses, increase to 80-100 mg/kg/day. In infantile spasms- Initial dose 40-50 mg/ kg/day increase by 50 mg/kg/day till spasm control or to 150-200 mg/kg/day. Pregnancy (Appendix 7c). Psychosis (5%), behavioral problems, hyperactivity (most common cause for discontinuation), confusion, fatigue, insomnia, ataxia, drowsiness, weight gain, facial oedema, GIT upset (dose related), no effect on cognition. Chronic toxicity-most serious: persistent ncentric visual field defects in 1/3rd cases (rarely, reversible with early withdrawal), many patients are asymptomatic.

Precautions Adverse effects

Zonisamide
Pregnancy Category-C Indications Schedule H

Add-on in partial seizures, primary generalized tonic clonic seizures, myoclonic epilepsy, absence seizures, LGS, infantile spasms. CAPSULES 25, 50 and 100 mg; TABLET 100 mg. Oral

Availability Dose

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Child- Initial dose - 2-4 mg/kg/day divided twice daily, with increments at 2- week intervals to 6-8 mg/kg/day and a possible maximum of 12 mg/kg/day.

Precautions Adverse Effects

Pregnancy (Appendix 7c). Drowsiness, anorexia, ataxia, fatigue (dose related), photosensitivity; cognitive effectsreversible psychotic effects, behavioral abnormalities, abnormal thinking, irritability (Do slow titration); weight loss, renal stones (mostly small); idiosyncratic-in 1.4% skin rash (including SJS, TEN), blood dyscrasias, hepatic failure; oligohidrosis and hyperthermia (more in children).

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Antidiarrhoeals and Laxatives

6.
6.1 6.2 6.3

Antidiarrhoeals and Laxatives

Antidiarrhoeal Symptomatic Drugs in Adult Laxatives Oral Rehydration

71
72 74 77

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Antidiarrhoeals and Laxatives

6. Antidiarrhoeals and Laxatives

Acute diarrhoeal diseases are a leading cause of childhood morbidity and mortality; frail and elderly patients are also at risk. In adults acute diarrhoea is the most frequent health problem of travellers and is increasingly common among HIVinfected persons. Assessment and correction of dehydration and electrolyte disturbance is the priority in all cases of acute diarrhoea. Symptomatic relief in adults may be warranted in some cases but antidiarrhoeals should never be used in children since they do not reduce fluid and electrolyte loss and may cause adverse effects. Diarrhoea persisting for longer than a month is known as chronic diarrhoea. A mild malabsorption syndrome, tropical enteropathy, is apparent in most healthy indigenous populations of tropical countries. However the majority of cases of chronic diarrhoea have non-infectious causes including gluten-sensitivity, inherited metabolic disorders or inflammatory bowel disease. Bloody diarrhoea is usually a sign of invasive enteric infection and should be treated with an appropriate anti-infective agent.

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6.1 Antidiarrhoeal Symptomatic Drugs in Adult

Codeine* (Refer Page No. 10)
Pregnancy Category-C Indications Availability Dose Schedule H Short-term symptomatic relief of acute diarrhoea in adult; pain. TABLET 30 mg. Oral
Adult- Symptomatic relief of acute diarrhoea: 30 mg 3 to 4 times daily. Child- (1-12 years) 500 g/kg 4-6 times daily.

Contraindications

Conditions where inhibition of peristalsis should be avoided; abdominal distension; acute diarrhoeal conditions such as ulcerative colitis or antibiotic-associated colitis; acute respiratory depression. Tolerance or dependence may occur with prolonged use; elderly and debilitated patients; hepatic impairment (Appendix 7a); renal impairment; lactation; overdosage: see chapter 7.2; interactions (Appendix 6c); pregnancy (Appendix 7c). Nausea, vomiting, constipation, drowsiness; respiratory depression and hypotension (large doses); dependence; difficulty with micturition; ureteric or biliary spasm; dry mouth, sweating, headache, facial flushing, vertigo, bradycardia, tachycardia, palpitations, hypothermia, hallucinations, dysphoria, mood changes, miosis, decreased libido or potency, rash, urticaria, pruritus; convulsions (large doses).

Precautions

Adverse Effects

Furazolidone
Pregnancy Category-C Indications Schedule H Giardiasis; cholera; gastrointestinal infections; protozoal or bacterial diarrhoea and enteritis; food poisoning. TABLETS 100 mg; CAPSULE 100 mg; SUSPENSION 25 mg/5 ml. Oral
Adult- 100 mg 3 to 4 times a day.

Availability Dose

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Child- 5 mg/kg body weight daily in 4 divided doses.

Contraindications Precautions

Hypersensitivity; sensitivity.

alcoholics;

primaquine

Urine colour changes to yellow after administration; orthostatic hypotension; hypoglycaemia; pregnancy (Appendix 7c); interactions (Appendix 6a, 6c). Nausea, vomitting, headache; hypotension; urticaria; dyspnea; dizziness. Store protected from light at temperature not exceeding 30C.

Adverse Effects Storage

Loperamide
Pregnancy Category-C Indications Schedule H For the control and symptomatic relief of acute nonspecific diarrhoea and chronic diarrhoea associated with inflammatory bowel disease or gastroenteritis; for reducing the volume of discharge from ileostomies. TABLET/CAPSULE 2 mg; LIQUID 1 mg/5 ml. Oral
Adult- 4 mg initially thereafter 2 mg after every motion. Child- 2 mg followed by 2 mg after every motion.

Availability Dose

Contraindications

Conditions where inhibition of peristalsis should be avoided, where abdominal distension develops, or in conditions such as active ulcerative colitis or antibioticassociated colitis. Liver disease; pregnancy: (Appendix 7c); interactions (Appendix 6c); glaucoma; Crohns disease; urinary bladder obstruction. Abdominal cramps, dizziness, drowsiness and skin reactions including urticaria; paralytic ileus and abdominal bloating also reported; constipation; headache; meteorism; nausea; dry mouth; urinary retention. Store protected from light and moisture.

Precautions

Adverse Effects

Storage

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6.2 Laxatives
A balanced diet, including adequate fluid intake and fibre is of value in preventing constipation. Before prescribing laxatives, it is important to be sure that the patient is constipated and that the constipation is not secondary to an underlying undiagnosed complaint. It is also important that the patient understands that bowel habit can vary considerably in frequency without doing harm. For example, some people consider themselves constipated if they do not have a bowel movement each day. A useful definition of constipation is the passage of hard stools less frequently than the patients own normal pattern and this should be explained to the patient since misconceptions about bowel habits have led to excessive laxative use which in turn has led to hypokalaemia and an atonic non-functioning colon. Laxatives should generally be avoided except where straining will exacerbate a condition such as angina or increase the risk of rectal bleeding as in haemorrhoids. Laxatives are of value in drug-induced constipation, for the expulsion of parasites after anthelminthic treatment and to clear the alimentary tract before surgery and radiological procedures. Prolonged treatment of constipation is rarely, necessary except occasionally in the elderly. There are many different laxatives. These include bulk-forming laxatives which relieve constipation by increasing faecal mass and stimulating peristalsis, stimulant laxatives which increase intestinal motility and often cause abdominal cramp, faecal softeners which lubricate and soften impacted faeces and osmotic laxatives which act by retaining fluid in the bowel by osmosis. Bowel cleansing solutions are used before colonic surgery, colonoscopy or radiological examination to ensure that the bowel is free of solid contents; they are not a treatment for constipation.

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Bisacodyl*
Pregnancy Category-B Indications Availability Dose Constipation. TABLETS 5 mg; SUPPOSITORIES 5 and 10 mg. Oral/Rectal Adult and child over 10 years- 5 to 10 mg daily at night. Before radiological procedure and surgery: 16 to 20 mg at night before procedure. Contraindications Intestinal obstruction (causes abdominal cramps), acute surgical abdominal conditions, acute inflammatory bowel disease, severe dehydration; faecal impaction, chronic use. Excessive use of stimulant laxatives can cause diarrhoea and related effects such as hypokalaemia; however, prolonged use may be justifiable in some circumstances; dont give antacid within 1 hour, pregnancy (Appendix 7c), inflammatory bowel disease, pre-existing heart disease or bowel disease, allergies, interactions (Appendix 6d). Tabletsgriping; suppositories-local irritation; fainting, dizziness, soreness in anal region due to suppository leakage; abdominal discomfort, electrolyte imbalance, hypokalaemia.

Precautions

Adverse Effects

Ispaghula*
Indications Availability Dose Constipation; irritable colon syndrome. GRANULES (flavoured and sweetened) 37.5 and 100g. Oral Adult- 6 teaspoonful of water or milk at night before bed time. Child- 1-3 teaspoonful in water or milk before bed time. Contraindications Precautions Intestinal obstruction; difficulty in swallowing. colonic atony;

Salt restriction; interactions (Appendix 6c).

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Adverse Effects Storage

Abdominal discomfort, gastrointestinal obstruction.

flatulence,

Store protected from light and moisture.

Lactulose
Indications Availability Dose Contraindications Precautions Adverse effects Constipation, hepatic encephalopathy. SOLUTION/SyRUP 3.35g/5 ml. 10 to 20g (15 to 20 ml/day, max 45 ml/day). Galactosemia, intestinal obstruction, patients on low galactose diet. Lactose intolerance, diabetes mellitus. Diarrhoea (dose related), nausea, vomiting, hypokalaemia; dehydration; hypernatremia; bloating and abdominal cramps.

Senna
Pregnancy Category-C Indications Availability Dose Constipation. TABLETS (containing Sennoside B-11.5 mg). Oral Adult- 2 to 4 tablets, usually at night; initial dose should be low, then gradually increased. Child- over 6 years, half the adult dose in the morning (on doctors advice). Contraindications Precautions Intestinal obstruction; abdominal symptoms. undiagnosed

Avoid prolonged use unless indicated for prevention of faecal impaction; pregnancy (Appendix 7c), lactation (Appendix 7b); hypersensitivity, undiagnosed abdominal pain, intestinal blockage. Abdominal discomfort; atonic nonfunctioning colon and hypokalaemia (with prolonged use or overdosage); red or yellow brown urine, diarrhoea, nausea, vomiting, bloating. Store protected from light and moisture.

Adverse Effects

Storage

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6.3 Oral Rehydration

Acute diarrhoea in children should always be treated with oral rehydration solution according to plan A, B or C as shown. Severely dehydrated patients must be treated initially with intravenous fluids until they are able to take fluids by mouth. For oral rehydration it is important to administer the solution in small amounts at regular intervals as indicated below.

Treatment of Dehydration:
WHO Recommendations
According to the degree of dehydration, health professionals are advised to follow one of the three management plans. Plan A: No dehydration: Nutritional advice and increased fluid intake are sufficient (soup, rice, water and yoghurt, or even water). For infants aged under 6 months who have not yet started taking solids, oral rehydration solution must be presented before offering milk. Mothers milk or dried milk must be given without any particular restrictions. In the case of mixed breast-milk/formula feeding, the contribution of lactation must be increased. Plan B: Moderate dehydration: Whatever the childs age, a 4-h treatment plan is applied to avoid short-term problems. Feeding should not therefore be envisaged initially. It is recommended that parents are shown how to give approximately 75 ml/kg of oral rehydration solution with a spoon over a 4-h period and it is suggested that parents should be watched to see how they cope at the beginning of the treatment. A larger amount of solution can be given if the child continues to have frequent stools. In case of vomiting, rehydration must be discontinued for 10 min and then resumed at a slower rate (about one teaspoonful every 2 min). The childs status must be re-assessed after 4 h to decide on the most appropriate subsequent treatment. Oral rehydration solution should continue to be offered once dehydration has been controlled, for as long as the child continues to have diarrhoea. Plan C: Severe dehydration: Hospitalization is necessary, but the most urgent priority is to start rehydration. In hospital (or elsewhere), if the child can drink, oral rehydration solution must be given pending, and even during intravenous infusion (20 ml/kg every h by mouth before infusion, then 5 ml/kg every h by mouth during intravenous rehydration). For intravenous supplementation, it is recommended that compound solution of sodium lactate (see chapter 28.2) is administered at a rate adapted to the childs age (infant under 12 months: 30 ml/kg over 1 h then 70 ml/kg over 5 h; child over 12 months: 77 NFI-2011

Antidiarrhoeals and Laxatives

the same amounts over 30 min and 2.5 h respectively). If the intravenous route is unavailable, a nasogastric tube is also suitable for administering oral rehydration solution, at a rate of 20 ml/kg every h. If the child vomits, the rate of administration of the oral solution should be reduced.

Oral Rehydration Salts*

Indications Availability Dehydration from acute diarrhoea. GLUCOSE SALT SOLUTION 5 and 37.5g. Sodium chloride Sodium citrate Potassium chloride 2.6 g/litre of water 2.9 g/litre of water 1.5 g/litre of water

Glucose (anhydrous) 13.5 g/litre of water When glucose and sodium citrate are not available, they may be replaced by Sucrose (common sugar) 27 g/litre of water Sodium bicarbonate 2.5 g/litre of water In cases of cholera, oral rehydration salts containing a higher concentration of sodium may be required to prevent hyponatraemia. Note: The solution may be prepared either from prepackaged sugar/salt mixtures or from bulk substances and water. Solutions must be freshly prepared, preferably with recently boiled and cooled water. Accurate weighing and thorough mixing and dissolution of ingredients in the correct volume of clean water is important. Administration of more concentrated solutions can result in hypernatraemia. Dose Oral 5g (single use): dissolve in water and drink; 37.5g: to reconstitute it with 1 litre of clean water.
Adult- Fluid and electrolyte loss in acute diarrhoea; 200 to 400 ml solution after every loose motion.

Precautions Adverse Effects

Renal impairment.
Vomiting-

may indicate too rapid administration; hypernatraemia and hyperkalaemia may result from overdose in renal impairment or administration of too concentrated a solution.

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Storage

Store protected from moisture in a sachet preferably made of aluminium foil containing sufficient powder for single dose or for a day treatment or for use in hospital.

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7.

Antidotes and Substances Used in Poisoning

Non specific Specific

81
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Antidotes and Substances Used in Poisoning

7. Antidotes and Substances Used in Poisoning

These notes are only guidelines and it is strongly recommended that poisons information centres (Appendix 5) be consulted in cases where there is doubt about the degree of risk or about appropriate management.

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7.1 Non specific

General Care and Non-Specific Treatment:
All patients who show features of poisoning should generally be admitted to hospital. Patients who have taken poisons with delayed actions should also be admitted, even if they appear well; delayed-action poisons include acetylsalicylic acid, iron, lithium, paracetamol, paraquat, tricyclic antidepressants and warfarin. The effects of modified-release or prolonged-release preparations are also delayed. However, it is often impossible to establish with certainty the identity of the poison and the size of the dose but information on the type and timing of poisoning may be useful for symptomatic management. Few patients require active removal of the poison. Most patients must be treated symptomatically and monitored. Particular care must be given to maintenance of respiration and blood pressure. Assisted ventilation may be required. Cardiac conduction defects and arrhythmias often respond to correction of underlying hypoxia, acidosis, or other biochemical abnormalities. Hypothermia which may develop in patients who have been unconscious for some hour is best treated by wrapping the patient in blankets to conserve body heat. Convulsions which are prolonged or recurrent may be controlled by intravenous diazepam. In some situations removal of the poison from the stomach by gastric lavage may be appropriate (see below). Activated charcoal can bind many poisons in the stomach and therefore prevent absorption. Active elimination techniques such as repeated administration of activated charcoal can enhance the elimination of some drugs after they have been absorbed (see below). Other techniques to enhance elimination of poisons after their absorption are only practical in hospital and are only suitable for a small number of patients and only to a limited number of poisons. Methods include haemodialysis and haemoperfusion. Alkalinization of urine can be used to increase the elimination of salicylates. Forced alkaline diuresis is no longer recommended.

Gastric Lavage:
The dangers of attempting to empty the stomach have to be balanced against the toxicity of the ingested poison, as assessed by the quantity ingested, the inherent toxicity of the poison and the time since ingestion. Gastric emptying is clearly unnecessary if the risk of toxicity is small or if the patient presents too late. Emptying the stomach may be of value if undertaken within 1-2 h after ingestion. The main NFI-2011 82

Antidotes and Substances Used in Poisoning

risk is with inhalation of stomach contents and gastric lavage should not be undertaken in drowsy or comatose patients without assistance of an anaesthetist so that the airway can be protected by a cuffed endotracheal tube. Gastric lavage must not be attempted after corrosive poisoning or for hydrocarbon products which could be dangerous if aspirated.

Emesis:
Induction of emesis for the treatment of poisoning is not recommended. There is no evidence that it prevents absorption of the poison and it may increase the likelihood of aspiration. Furthermore, the effects of the emetic substance may complicate diagnosis.

Prevention of Absorption:
Given by mouth activated charcoal can bind many poisons in the gastrointestinal system, thereby reducing their absorption. The sooner it is given, the more effective it is, but it may be effective for up to 1 hour after ingestion of the poison. It may be effective several hour after poisoning with modifiedrelease preparations or drugs with anticholinergic (antimuscarinic) properties. It is relatively safe and particularly useful for prevention of absorption of poisons which are toxic in small amounts, for example, antidepressants. Furthermore, repeated doses of activated charcoal enhance the faecal elimination of some drugs (that undergo enterohepatic or enteroenteric recycling) several hours after ingestion and after they have been absorbed, for example phenobarbital, theophylline.

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Activated Charcoal
Indications Availability Dose Treatment of acute poisoning. POWDER (for oral suspension), TABLETS 500 mg. Oral
Adult and child over 12years- 50g, 0.5g/kg

may be repeated every 4-6 h for upto 12-24 h.

Child- Below 12years; 1g/kg (max 50g). May be repeated every 4 h.

Contraindications

Poisoning by hydrocarbons with high potential for harm if aspirated; poisoning by corrosive substances-may prevent visualization of lesions caused by poison. Drowsy or unconscious patients-risk of aspiration (intubate before administration via nasogastric or gastric tube); not effective for poisoning with alcohols, clofenotane (dicophane, DDT), cyanides, malathion and metal salts including iron and lithium. Black stools; vomiting, constipation or diarrhoea; pneumonitis-due to aspiration. Store protected from moisture.

Precautions

Adverse Effects Storage Pregnancy Category-B Indications Availability Dose

Calcium Disodium Edetate

Lead poisoning (acute and chronic) and lead encephalopathy. AMPOULE 5 ml (200 mg/ml). Intravenous injection Lead poisoning without encephalopathy: 1000 mg/m2/day as continous infusion for 5 days. Lead encephalopathy: 1500 mg/m2/day by continous intravenous infusion in 5% dextrose or 0.9% NaCl (Final Concentration of edentate < 500 mg/100 ml), starting 4 h after first dose of BAL and after an adequate urine flow is established. Infusion is continued for 5 days.
Intramuscular injection to be used if fluid overload is a concern.

1000 mg/m2/day divided into equal doses spaced 8 to 12 h apart. Lignocaine or procaine should be added to the injection to minimize pain at the injection site.

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Contraindications Precautions

Anuria; patients with active renal disease or hepatitis; pregnancy (Appendix 7c). Ensure adequate urine output, pre-existing mild renal disease; patients with lead encephalopathy and cerebral edema may experience a lethal increase in intracranial pressure following intravenous infusion, the intramuscular route is preferred for these patients. Renal tubular toxicity which may lead to acute renal failure, fever, chills, lacrimation, increased prothrombin time, pain at intramuscular injection site; hypotension; cardiac rhythm irregularities; thirst; headache; fatigue; malaise; urinary frequency; glycosuria; proteinuria; microscopic hematuria; histamine-like reactions.

Adverse Effects

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7.2 Specific
Paracetamol Overdosage:
Paracetamol in a dose of 10-15g or 150 mg/kg of paracetamol taken within 24 h may cause severe hepatocellular necrosis and less frequently renal tubular necrosis. The only early features of poisoning, nausea and vomiting, usually settle within 24 h. Persistence beyond this time, often with the onset of right subcostal pain and tenderness, usually indicates the development of liver damage which is maximal 3-4 days after ingestion. In spite of a lack of significant early symptoms, patients who have taken an overdose of paracetamol should be transferred to hospital urgently. Administration of activated charcoal should be considered if paracetamol in excess of 150 mg/kg or 12g, whichever is smaller, is thought to have been ingested within the previous hour. N-Acetylcysteine or N-methionine protect the liver if given within 10-12 h of ingesting paracetamol. Acetylcysteine, given intravenously is most effective within 8 h of overdosage, but is effective for up to and possibly beyond 24 h. Alternatively, methionine may be given by mouth provided the overdose was ingested within 10-12 h and the patient is not vomiting. However, acetylcysteine is the preferred treatment. Concurrent use of activated charcoal and specific oral antidotes should be avoided. In remote areas methionine should be given, since administration of acetylcysteine outside hospital is not generally practicable. Once the patient is in hospital the need to continue antidote treatment can be assessed from plasma-paracetamol concentrations.

Opioid Analgesic Overdosage:

Opioids cause varying degrees of coma, respiratory depression and pinpoint pupils. Naloxone is a specific antidote indicated if there is coma or bradypnoea. Naloxone has a shorter duration of action than many opioids so close monitoring and repeated injections are required depending on respiratory rate and depth of coma; naloxone may alternatively be given by intravenous infusion. The effects of some opioids such as buprenorphine are only partially reversed by naloxone. Acute withdrawal syndromes may be precipitated by the use of naloxone in patients with a physical dependence on opioids or in overdosage with large doses; a withdrawal syndrome may occur in neonates of opioid-dependent mothers. NFI-2011 86

Antidotes and Substances Used in Poisoning

Organophosphate and Carbamate Poisoning:

Organophosphates are absorbed through the bronchi and intact skin as well as from the gastrointestinal tract. Initial treatment of organophosphate or carbamate poisoning includes prevention of further absorption by emptying the stomach by gastric lavage, moving patient to fresh air supply, removing contaminated clothing and washing contaminated skin. A clear airway must be maintained. Organophosphates inhibit cholinesterases and thus prolong the effects of acetylcholine. Toxicity depends on the particular compound involved and onset after ingestion, skin exposure may be delayed. Atropine will reverse the muscarinic effects of acetylcholine and is used (in conjunction with oximes such as pralidoxime) with additional symptomatic treatment. Additional treatment for carbamate poisoning is generally symptomatic and supportive. Atropine may be given but may not be required because of the rapidly reversible type of cholinesterase inhibition produced (oximes should not be given).

Iron Poisoning and Iron and Aluminium Overload:

Mortality from iron poisoning is reduced by specific therapy with desferrioxamine which chelates iron. Before administration of desferrioxamine the stomach should be emptied by gastric lavage (with a wide-bore tube) within 1 h of ingesting a significant quantity of iron or if radiography reveals tablets in the stomach. Desferrioxamine is also used to diagnose and treat chronic iron overload. It is used in the diagnosis of aluminium overload and to treat aluminium overload in patients with endstage renal failure undergoing maintenance haemodialysis.

Heavy Metal Poisoning:

Heavy metal poisoning may be treated with a range of antidotes including dimercaprol, penicillamine, potassium ferric hexacyanoferrate and Sodium calcium edetate. Penicillamine is also used to promote excretion of copper in Wilsons disease.

Methaemoglobinaemia:
Methylthioninium chloride can lower the levels of methaemoglobin in red blood cells and is used in the treatment of methaemoglobinaemia. In large doses, it may cause methaemoglobinaemia and therefore methaemoglobin levels should be monitored during treatment.

Cyanide Poisoning:
Cyanide poisoning may be treated with Sodium nitrite followed by Sodium thiosulphate. 87 NFI-2011

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Atropine* (Refer Page No. 419 and 560)

Pregnancy Category-C Indications Schedule H Organophosphate and carbamate poisoning; premedication; antispasmodic; as mydriatic; cycloplegic refraction procedures. INJECTION 1 ml ampoules and 50 ml vial (0.6 mg/ml). Intramuscular and intravenous injection
Adult- 1.8 - 3.0 mg intravenous bolus followed by doubling dose every 3 to 5 minutes depending upon response. End-point for atropinization include clear chest with no wheeze, systolic BP >80mm Hg, pulse >80 beats/min., pupils no longer pinpoint and dry axillae. Following that infusion of atropine at 10-20 % of total initial dose required/hour; may require boluses during infusion. Child-20-30 g/kg schedule as above.

Availability Dose

initially

with

same

Contraindications

In myasthenia gravis (but may be used to decrease muscarinic side-effects of anticholinesterases), paralytic ileus, pyloric stenosis and prostatic enlargement; reflux oesophagitis; unstable cardiac rhythm. Elderly, Down syndrome; angle-closure glaucoma; myasthenia gravis; prostatic enlargement; pyrexia; lactation (Appendix 7b); interactions (Appendix 6a); pregnancy (Appendix 7c). Constipation, transient bradycardia (followed by tachycardia, palpitation and arrhythmias), reduced bronchial secretions, urinary urgency and retention, dilatation of the pupils with loss of accommodation, photophobia, dry mouth, flushing and dryness of the skin. Occasionally, confusion (particularly in the elderly), nausea, vomiting and giddiness; very rarely, angle-closure glaucoma may occur.

Precautions

Adverse Effects

Desferrioxamine Mesylate*
Pregnancy Category-C Indications Acute iron poisoning; chronic iron overload; aluminium overload; primary hemochromatosis. INJECTION 5 ml and 10 ml vial (500 mg/vial). Continuous intravenous infusion

Availability Dose

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Adult and Child- Begin with 5 mg/kg/h, increasing over 15 minutes if tolerated to 15 mg/kg/h, to minimize the risk of hypotension. After 1 to 2 h reduce to 3-4 mg/kg/h for the next 22-23 hrs (max dose is 100 mg/kg over 24 hrs). Patients with cardiovascular collapse: 5 mg/ kg/h (up to max. of 80 mg/kg in 24 h.) Chronic iron overload: Intramuscular 500 to 1000 mg daily, in addition 2g by intravenous infusion with each unit of blood transfused. Contraindications Precautions Severe renal (Appendix 7c). disease; pregnancy

Renal impairment; eye and ear examinations before and at 3-month intervals during treatment; aluminium encephalopathy (may exacerbate neurological dysfunction); children under 3 years (may retard growth); lactation; interactions (Appendix 6c). Anaphylaxis; flushing, urticaria, hypotension, shock (especially if given by too rapid intravenous infusion); gastrointestinal disturbances; fever, headache, arthralgia, myalgia; arrhythmias; renal impairment; blood disorders; neurological disturbances including neuropathy, paraesthesia and dizziness; convulsions; Yersinia and mucormycosis infections; visual disturbances (including lens opacity and retinopathy) and hearing loss; rash; rarely, growth retardation (in young children); rarely, acute respiratory distress syndrome; pain on intramuscular or subcutaneous injection; local irritation on prolonged subcutaneous infusion; reddishbrown discolouration of urine. Store protected from light in refrigerator (2-8C). Do not freeze.

Adverse Effects

Storage

Dimercaprol (BAL)*
Pregnancy Category-C Indications Acute poisoning by antimony, arsenic, bismuth, copper gold, mercury and possibly thallium; adjunct (with sodium calcium edetate) in lead poisoning. OILy INJECTION 2 ml ampoule (50 mg/ml). Intramuscular injection

Availability Dose

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To be administerd by deep intramuscular injection only Lead poisoning: Adults-4 mg/kg every 4 h for 5 days. Child- 75 mg/m2 every 5 h for 5 days. Arsenic poisoning: 3 mg/kg every 4 h for 48 h and then twice a day for 7-10 days. Mercury poisoning: 5 mg/kg followed by 2.5 mg/kg every 12-24 h for upto 10 days Contraindications Not indicated for iron, selenium or cadmium poisoning; severe hepatic impairment (unless due to arsenic poisoning); hypertension; tellurium poisoning, peanut allergy, G-6-PD deficiency. Hypertension; renal impairment (discontinue or use with extreme caution if renal failure occurs during treatment); any abnormal reaction such as hyperpyrexia should be assessed; elderly; pregnancy (Appendix 7c); lactation, alkalinize urine to pH of 7.5-8.0 using sodium bicarbonate. Hypertension, tachycardia; malaise, nausea, vomiting, abdominal pain, salivation, lacrimation, sweating, burning sensation in the mouth, throat and eyes; feeling of constriction in throat and chest; headache, muscle spasms, tingling of the extremities; fever in children; local pain and abscess at injection site, iron toxicity potentiation. Store protected from light.

Precautions

Adverse Effects

Storage

D-Penicillamine* (Refer Page No. 385)

Pregnancy Category-D Indications Schedule H Poisoning by heavy metals, particularly lead and copper; Wilsons disease; severe rheumatoid arthritis. CAPSULE/TABLET 250 mg. Oral (given before food) Adult- 1 to 2g daily in three divided doses starting with 250 mg OD and gradually increasing to full dose over 2-3 weeks.
Child- 20 mg/kg/day administered in 3-4 divided doses, initiating treatment at 25% of this dose and gradually increasing to full dose over 2-3 weeks to minimize adverse reactions. Continue till blood lead levels <45 g/dl.

Availability Dose

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Contraindications

Hypersensitivity; lupus erythematosus; gold or antimalarial drug; penicillamineinduced agranulocytosis; aplastic anaemia; thrombocytopenia, pregnancy, lactation (for rheumatoid arthritis). Monitor throughout treatment including blood counts and urine tests; renal impairment; immunosuppressive treatment; avoid oral iron within 2 h of a dose; hepatic impairment; pregnancy (Appendix 7c). In Wilsons disease, consider withdrawal if platelet count falls below 120 000/mm3 or white blood cells below 2500/mm3 or if 3 successive falls within reference range (can restart at reduced dose when counts return to reference range but permanent withdrawal necessary if neutropenia or thrombocytopenia recur). In Wilsons disease warn patient to tell doctor immediately if sore throat, fever, infection, non-specific illness, unexplained bleeding and bruising, purpura, mouth ulcers or rashes develop.

Precautions

Adverse Effects

Initially nausea (less of a problem if taken with food and on retiring), anorexia, fever; taste loss (mineral supplements not recommended); blood disorders including thrombocytopenia, neutropenia, agranulocytosis and aplastic anaemia; proteinuria, rarely, haematuria (withdraw immediately); haemolytic anaemia, nephrotic syndrome, lupus erythematosuslike syndrome, myasthenia gravis-like syndrome, polymyositis (rarely, with cardiac involvement), dermatomyositis, mouth ulcers, stomatitis, alopecia, bronchiolitis and pneumonitis, pemphigus, Goodpasture syndrome and Stevens-Johnson syndrome also reported; male and female breast enlargement reported; rash early in treatment (usually allergic-may need temporary withdrawal), late rashes (reduce dose or withdraw treatment).

Flumazenil*
Pregnancy Category-C Indications Antidote for benzodiazepine overdose, reversal of sedative effects produced by benzodiazepenes administered during general anaesthesia or diagnostic or therapeutic procedures. INJECTION 0.1 mg/ml.

Availability

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Dose

Adult- 0.2 mg (2 ml) administered over 30 seconds, i.v, repeat 0.3 mg and 0.5 mg at 1-2 minute intervals. Not more than 3 mg over one hour. Child- 10 g/kg, i.v, for 2 doses.

Contraindications

Epilepsy, neuromuscular blockade, hypersensitivity to benzodiazepines, patients of suspected tricyclic antidepressant overdose, raised intracranial pressure. History of seizures, panic attack, alcohol drug dependence, bleeding disorder, liver disease, head injury, respiratory depression, pregnancy (Appendix 7c). Convulsions, fatigue, injection site pains, increased sweating, facial erythema, raised intracranial pressure, agitation, dizziness, abnormal vision, may cause complete heart block, flushing, transient increase in blood pressure and heart-rate.

Precautions

Adverse effects

Methylene Blue (Methylthioninium Chloride)*

Pregnancy Category-C Indications Availability Dose Acute methaemoglobinaemia. INJECTION 10 mg/ml. Intravenous injection Methaemoglobinaemia caused by high dosage of prilocaine infusion: 1-2 mg/kg intravenously over 5 minutes, followed immediately by a fluid flush of 15-30 ml to minimize local pain. May be repeated in 3060 minutes. Maximum dose: 7 mg/kg. Contraindications Severe renal impairment; methaemoglobinaemia due to chlorate or induced by sodium nitrite in treatment of cyanide poisoning; affects ability to drive machinery. G-6-PD deficiency-may cause haemolytic anaemia; monitor blood methaemoglobin throughout treatment; pregnancy (Appendix 7c); lactation. Nausea, vomiting, abdominal pain, chest pain, headache, dizziness, confusion, profuse sweating; hypertension or hypotension reported; haemolytic anaemia-in G-6-PD deficiency; methaemoglobinaemia-with high dosage; bluish skin discolouration; blue saliva, urine and faeces.

Precautions

Adverse Effects

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Storage

Store protected from light in an airtight container.

Naloxone*
Pregnancy Category-B Indications Availability Dose Schedule X Opioid overdosage; postoperative respiratory depression. INJECTION 0.4 mg/ml. Intravenous injection Subcutaneous or intramuscular route (if i.v. route is not feasible but the dose is same, can be given oral as well). Adult- Opioid poisoning: Start with 0.4 to 2 mg (at all ages) as intravenous bolus, Repeat every 2 minutes if no response to a total of 10 mg. Once response occurs start infusion of naloxone at 2/3rd the total loading dose given every hour with continous monitoring for reccurence of respiratory depression. May require additional bolus during infusion. Child- Opioid poisoning: 10 g/kg, followed by 100 g/kg if there is no response. Contraindications Precautions Hypersensitivity. Physical dependence on opioids or other situations where acute withdrawal syndrome may be precipitated (see above); lactation; cardiovascular disease; pregnancy (Appendix 7c). Nausea, vomiting, sweating-may also be due to opioid withdrawal. Store protected from light in an airtight container.

Adverse Effects Storage

Pralidoxime (2-PAM)*
Pregnancy Category-C Indications Schedule H Adjunct to atropine in the treatment of organophosphate poisoning and anticholinesterase overdosage used in the treatment of myasthenia gravis (mg), respiratory depression or severe muscle weakness due to carbamate poisoning.

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Availability Dose

INJECTION i.v infusion 500 mg/20 ml, 1g/20 ml (as chloride and iodide salt). For Chloride salt, 30 mg/kg i.v. over 15-20 minutes followed by infusion at 8-10 mg/ kg/h. To be continued 12-24 hours after atropine is no longer required. For Iodide salt, dose is about 30% higher than chloride salt. Child- 25 to 50 mg/kg, diluted to 5% concentration in NS and infused over 5-30 minutes. May be repeated after one h, then every 6 to 12 h. Severe poisoning: Adult- 500 mg/h via continuous infusion. max.- 12g/24 h. Child- 9 to 19 mg/kg/h. For anticholinesterase overdose in MG: Adult- 1-2g i.v. initially, then 250 mg every 5 minutes. Child (0-18 years)- 15-25 mg/kg by slow i.v (up to 1 g). Maintainance dose- (< 12 years) 15-50 mg/ kg i.v every 5 minutes (up to 250 mg).

Contraindications

Carbamate poisoning and organophosphates without anticholinesterase activity; hypersensitivity to the drug. Impaired renal function; large doses can cause neuromuscular blockade, myasthenia gravis; atropinization occur faster on concurrent use with atropine; paediatrics; allergies; pregnancy (Appendix 7c). Headache, nausea; blurred vision, drowsiness, dizziness, impaired accommodation, tachycardia, hyperventilation, muscular weakness; transient elevation in SGOT and/ or SGPT levels; laryngospasm and rigidity. Store protected from moisture.

Precautions

Adverse effects

Storage

Sodium Nitrite*
Pregnancy Category-C Indications Cyanide poisoning (together with Sodium thiosulphate).

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Availability Dose

INJECTION 30 mg/ml (10 ml). Intravenous injection (over 5 to 20 min) Adult-300 mg at 2.5-5.0 mg/minute. Child- 4 to 10 mg/kg (max 300 mg) at 5 mg/ minute.

Note: Prepare as 3% solution of Sodium nitrite in Water for Injections (30 mg/ml) at the time of administration. Contraindications Precautions Methaemoglobinaemia; hemolytic anaemia; G-6-PD deficiency. Monitor plasma methaemoglobin levels; severe cardiovascular or cerebrovascular disease; hypotension; pregnancy (Appendix 7c). Nausea, vomiting and abdominal pain, vasodilatation resulting in syncope, hypotension, tachycardia, flushing, headache; methaemoglobinaemia; cyanosis, dyspnoea, tachypnoea.

Adverse Effects

Sodium Thiosulphate* (Refer Page No. 352)

Pregnancy Category-C Indications Prophylactically with prolonged use of nitro prusside to prevent cyanide toxicity, cyanide poisoning (together with Sodium nitrite); pityriasis versicolor; skin disease. INJECTION 250 mg/ml; 500 mg/ml (50 ml). Intravenous injection (over 10 min).
Adult- 12.5g intravenously over 10-30 minutes may be repeated at half the initial dose at 1-2 hours. Child- 500 mg/kg intravenously over 10-30 minutes may be repeated at half the initial dose at 1-2 hours (12.5g maximum)

Availability Dose

Contraindications Adverse Effects

Hypersensitivity; pregnancy (Appendix 7c). Irritation; urticaria; hypotension; burning; stinging on application.

Note: Freshly prepare by dissolving Sodium thiosulphate IP in Water for Injections.

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8.

Antiemetics

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Antiemetics

8. Antiemetics
Antiemetics are drugs effective against nausea and vomiting. They are typically used to treat motion sickness and the side effects of opioid analgesics, general anaesthetics and chemotherapy induced nausea and vomiting in cancer patients either alone or in combination. They act on the brain by preventing the stimulation of the vomiting centre (chemoreceptor trigger zone-CTZ). Some medications act on the gut by speeding up the rate at which the stomach empties and help to facilitate the quick transit of food through intestine (prokinetic action). Classification: 5-HT3 receptor antagonists block serotonin receptors in the central nervous system and gastrointestinal tract: Ondansetron, Granisetron, Dolasetron etc. Dopamine D2-receptor antagonists act in the brain: Domperidone, Metoclopramide, Mosapride etc. Antihistamines or H1- histamine receptor antagonists: Diphenhydramine, Promethazine etc. Benzodiazepines: Midazolam, Lorazepam etc. Anticholinergics: Scopolamine, Hyoscine, Dicyclomine etc. Steroids: Dexamethasone etc. Metoclopramide has antiemetic properties and also stimulates upper gastrointestinal motility. It is effective against nausea and vomiting associated with gastrointestinal disorders or migraine, following surgery and chemotherapy and is also effective against radiation-induced nausea and vomiting. Combining metoclopramide with corticosteroids (such as dexamethasone) can improve its antiemetic effect in chemotherapy-induced nausea and vomiting. Metoclopramide may be useful in the management of gastro-oesophageal reflux and gastroparesis, as well as preoperatively in the prevention of aspiration syndromes. It is also used to facilitate intubation of the small bowel during radiographic examinations. It is not effective in the prevention or treatment of motion sickness. Metoclopramide may cause acute dystonic reactions with facial and skeletal muscle spasms and oculogyric crisis. These reactions are most common in the young (especially girls and young women) and the elderly; they occur shortly after the start of treatment and subside within 24 h of drug withdrawal. Promethazine is a phenothiazine derivative. In addition to D2 97 NFI-2011

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dopaminergic blockade it has pronounced histamine H1 and muscarinic receptor blocking properties. It is effective in the prevention and treatment of vertigo and motion sickness. Promethazine may be useful in the prevention and treatment of postoperative and drug-induced nausea and vomiting. It has limited effect on chemotherapy-induced mild to moderate emesis.

Domperidone*
Schedule H Indications Nausea and vomiting from any cause in adult, epigastric senses of fullness; upper abdominal distress; non ulcer dyspepsia; migraine. TABLETS 5 and 10 mg; SyRUP 30 ml (1 mg/ ml); CAPSULE 30 mg. Oral Adult- 10 to 20 mg 3 to 4 times a day Child- 0.3 to 0.6 mg/kg TDS. Contraindications Hypersensitivity; prolactinoma, hepatic impairment; where increased gastrointestinal motility harmful; pregnancy; gastro intestinal haemorrhage; intestinal obstruction. Children; renal impairment, interactions (Appendix 6c); history of breast cancer; allergies; pheochromocytoma; i.v. administration can lead to hypokalaemia and cardiac arrhythmias. Rarely, gastro-intestinal disturbances (including cramps) and hyperprolactinaemia; very rarely, extrapyramidal effects and rashes; headache; dizziness; dry mouth; nervousness; flushing. Store protected from light and moisture.

Availability Dose

Precautions

Adverse Effects

Storage

Metoclopramide* (Refer Page No. 421)

Pregnancy Category-B Indications Schedule H Nausea and vomiting in gastrointestinal disorders and treatment with cytotoxics or radiotherapy; gastro-oesophageal reflux disease; gastroparesis; premedication and postoperatively; aid to gastrointestinal intubation; nausea and vomiting in migraine; diabetic gastric stasis.

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Availability Dose

TABLETS 10 and 15 mg; INJECTION 2 ml ampoule (5 mg/ml); SyRUP 30 ml (1 mg/ml). Oral or intramuscular injection or Slow intravenous injection Adult- Nausea and vomiting, gastroesophageal reflux, gastroparesis: (over 1 to 2 min for slow intravenous injection), 10 mg 3 times daily. 15 to 19 years (under 60 kg) 5 mg 3 times daily. Aid to gastrointestinal intubation: 20 mg as a single dose 5 to 10 min before examination; Adolescent (15 to 19 years), 10 mg. Child- Up to 1 year (up to 10 kg) 1 mg twice daily; 1 to 3years (10 to 14 kg) 1 mg 2 to 3 times daily; 3 to 5 years (15 to 19 kg) 2 mg 2 to3 times daily; 5 to 9 years (20 to 29 kg) 2.5 mg 3 times daily; 9 to 14 years (30 kg and over) 5 mg 3 times daily (usual max. 500 g/ kg daily, particularly for children and young adult). Slow intravenous injection only Adult- Premedication: 10 mg as a single dose.

Contraindications

Gastrointestinal obstruction, haemorrhage or perforation, 3-4 days after gastrointestinal surgery; convulsive disorders; pheochromocytoma; hypersensitivity. Elderly, children and young adults; hepatic impairment (Appendix 7a); renal impairment (Appendix 7d); pregnancy (Appendix 7c); may mask underlying disorders such as cerebral irritation; avoid for 3-4 days after gastrointestinal surgery; lactation (Appendix 7b); interactions (Appendix 6a); Parkinsons disease; epilepsy; depression; porphyria; driving or operating machines; hypertension; cirrhosis; congestive heart failure. Extrapyramidal symptoms (especially in children and young adults; see notes above); tardive dyskinesias on prolonged use; hyperprolactinaemia; drowsiness, restlessness, dizziness, headache, diarrhoea, depression, hypotension and hypertension reported; rarely, neuroleptic malignant syndrome; rashes, pruritus, oedema; cardiac conduction abnormalities following intravenous administration; rarely, methaemoglobinaemia (more severe in G-6PD deficiency); galactorrhoea; amenorrhoea; bradykinesia; gynaecomastia; insomnia. Store protected from light and moisture.

Precautions

Adverse Effects

Storage

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Ondansetron*
Pregnancy Category-B Indications Schedule H Postoperative nausea and vomiting, chemotherapy and/or radiotherapy induced nausea and vomiting. TABLETS 4 and 8 mg; INJECTION 2 and 4 ml ampoule (2 mg/ml); DROPS 2 mg/5 ml; SyRUP 2 mg/5 ml; SUSPENSION 1 mg/5 ml. Oral Prevention of post-operative nausea and vomiting: Adult 16 mg, 1 h before induction of anaesthesia. Nausea and vomiting associated with cancer chemotherapy: Adult- 24 mg as a single dose taken 30 min before start of single day chemotherapy. Child (4-11 yrs)- 4 mg tablets 3 times a day; continue for 1-2 days after completion of chemotherapy. Parenteral Post-operative nausea and vomiting: Adult- 4 mg by i.m or slow i.v as a single dose. Prevention of chemotherapy-induced nausea and vomiting: Adult- single 32 mg i.v dose infused over 15 min begining 30 min before start of emetogenic chemotherapy. Contraindications Precautions Hypersensitivity. Moderate to severe liver impairment; pregnancy (Appendix 7c), lactation; hypersensitivity to other selective 5-HT3 receptor antagonists, subacute intestinal obstruction; cardiac disease, electrolyte abnormalities, QT interval prolongation (avoid concomitant administration of drugs that prolong QT interval), interactions (Appendix 6c). Headache, constipation or diarrhoea, dizziness; flushing, hypersensitivity reaction, anaphylaxis/anaphylactoid reactions, angioedema; bronchospasm, hypotension, laryngeal edema, urticaria, hiccups, oculagyric crisis.

Availability

Dose

Adverse Effects

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Prochlorperazine
Pregnancy Category-C Indications Availability Dose Nausea and vomiting. TABLETS 3 and 5 mg; INJECTION 1 ml ampoule (2.5 mg/ml). Oral and intravenous injection
Adult- Nausea, vomiting acute attack: initially

Schedule H

20 mg then 20 mg every 2 h. Prevention; 5 to 10 mg 2 to 3 times daily. Child- (over 10 kg only). Oral: 0.4 mg/kg/day in 3-4 divided doses. Intravenous injection: 0.13 mg/kg/day in 3-4 divided doses. Adult- Labyrinthine disorder: 5 mg 3 times daily increased to 30 mg daily in divided doses that decrease after meal to 5 to 10 mg daily. ChildLabyrinthine recommended. disorder Not

Intravenous injection: 0.13 mg/kg/day in 3-4 divided doses. Contraindications Comatose states, CNS depression and pheochromocytoma. Most antipsychotics are best avoided during pregnancy; hypersensitivity; prolactin dependant tumors.

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Precautions

Patients with hepatic impairment, renal impairment, cardiovascular disease, Parkinsons disease (may be exacerbated by antipsychotics), epilepsy (and conditions predisposing to epilepsy), depression, myasthenia gravis, prostatic hypertrophy, or a susceptibility to angle-closure glaucoma. Caution is also required in severe respiratory disease and in patients with a history of jaundice or who have blood dyscrasias (perform blood counts if unexplained infection or fever develops). Caution should be taken in elderly, who are particularly susceptible to postural hypotension and to hyper- or hypothermia in very hot or cold weather. Serious consideration should be given before prescribing these drugs for elderly patients. As photosensitisation may occur with higher dosages, patients should avoid direct sunlight; extrapyramidal syndrome; pregnancy (Appendix 7c); interactions (Appendix 6a). Less sedating; extrapyramidal symptoms, particularly dystonias, more frequent; respiratory depression may occur in susceptible patients; amenorrhoea; blurred vision; cholestatic jaundice; neuroleptic malignant syndrome; leucopenia; agranulocytosis. Store protected from light and moisture.

Adverse Effects

Storage

Promethazine* (Refer Page No. 423)

Pregnancy Category-C Indications Schedule G Nausea, vomiting, labyrinthine disorders, motion sickness; premedication; allergic rhinitis; vasomotor rhinitis. TABLETS 10 and 25 mg; SyRUP 60 ml (5 mg/5 ml); INJECTION 2 ml ampoule (25 mg/ml). Oral Nausea and vomiting (including postoperative): 12.5 to 25 mg, repeated at intervals of not less than 4 h (usual max., 100 mg in 24 h). Motion sickness, prevention: 20 to 25 mg at bedtime on night before travel, repeated on day of travel if necessary.
Child- Motion sickness, prevention; 2 to 5 years: 5 mg at night and on day of travel, if necessary. 5 to 10 years: 10 mg at night and on day of travel, if necessary.

Availability Dose

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Intramuscular injection or Slow intravenous injection Nausea and vomiting (including postoperative); (diluted to 2.5 mg/ml in water for injection); 12.5 to 25 mg, repeated at intervals of not less than 4 h (usual max., 100 mg in 24 h). Contraindications Precautions Porphyria; hypersensitivity; hypokalaemia. coma;

Prostatic hypertrophy; urinary retention; glaucoma; hepatic disease (Appendix 7a); epilepsy; elderly and children (more susceptible to adverse effects); lactation (Appendix 7b); pregnancy (Appendix 7c); interactions (Appendix 6a). May impair ability to perform skilled tasks, for example operating machinery, driving.

Adverse Effects

Drowsiness, dizziness, sedation (but paradoxical stimulation may occur, especially with high doses or in children and elderly); headache, psychomotor impairment; urinary retention, dry mouth, blurred vision, gastrointestinal disturbances; hypersensitivity reactions, rashes, photosensitivity reactions; jaundice; blood disorders; cardiovascular adverse effects-after injection; venous thrombosis at site of intravenous injection; pain on intramuscular injection; somnolence; torticollis; tinnitus; leucopenia; thrombocytopenia, agranulcytosis; apnoea; angioneurotic edema. Store protected from light and moisture.

Storage

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9.
9.1 9.2 9.3 9.4 9.5 9.6 9.7 9.8 9.9 9.10 9.11 9.12

Anti-Infectives
Antiamoebic, Antigiardiasis and Antitrichomoniasis Drugs Antibacterial Drugs Antifilarial Drugs Antifungal Drugs Anthelminthics Anti-Leishmaniasis Drugs Antimalarial Drugs Antimycobacterial Drugs Antipneumocystosis and Antitoxoplasmosis Drugs Antiretrovirals

105
105 109 152 155 164 171 175 187 206 207

Antischistosomals and Antitrematode Drugs 228 Antiviral Drugs 230

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9. Anti-Infectives
9.1 Antiamoebic, Antigiardiasis and Antitrichomoniasis Drugs
Amoebiasis:
Amoebic dysentery is caused by Entamoeba histolytica. It is transmitted by the faeco-oral route and infection is usually caused by ingestion of cysts from contaminated food and drink. Asymptomatic carriers are common in endemic areas. In non-endemic areas, sympto mless carriers should be treated with a luminal amoebicide which will reduce the risk of transmission and protect the patient from invasive amoebiasis. Diloxanide furoate is most widely used, but other compounds, including clefamide, etofamide and teclozan, are also effective. Treatment with diloxanide furoate is regarded as successful if stools are free of E. histolytica for one month. Several specimens should be examined in evaluating response to treatment. Symptomatic (invasive) amoebiasis may be classified as intestinal or extra-intestinal. Intestinal amoebiasis is either amoebic dysentery or non-dysenteric amoebic colitis. Extraintestinal amoebiasis most commonly involves the liver, but may involve the skin, genito-urinary tract, lung and brain. Invasive amoebiasis is more likely in malnutrition, immunosuppression and pregnancy. Amoebic dysentery may take a fulminating course in late pregnancy and the puerperium; treatment with metronidazole may be life saving. In less severe infection, metronidazole should, if possible, be avoided in the first trimester. All patients with invasive amoebiasis require treatment with a systemically active compound such as metronidazole, ornidazole and tinidazole followed by a luminal amoebicide in order to eliminate any surviving organisms in the colon. Combined preparations are useful. In severe cases of amoebic dysentery, tetracycline given in combination with a systemic amoebicide lessens the risk of superinfection, intestinal perforation and peritonitis. Hepatic abscesses should be lanced by needle aspiration.

Giardiasis:
Giardiasis is caused by Giardia intestinalis and is acquired by oral ingestion of Giardia cysts. Giardiasis can be treated with tinidazole in a single dose or with another 5-nitroimidazole 105 NFI-2011

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such as metronidazole ; both are highly effective and should be offered when practicable to all infected patients. Family and institutional contacts should also be treated. Larger epidemics are difficult to eradicate because of the high proportion of sympto mless carriers and because excreted cysts can survive for long periods outside the human host.

Trichomoniasis:
Trichomoniasis is an infection of the genito-urinary tract caused by Trichomonas vaginalis and transmission is usually sexual. In women it causes vaginitis although some are asymptomatic. It is usually asymptomatic in men but may cause urethritis. Patients and their sexual partners should be treated with metronidazole or other nitroimidazole.

Diloxanide Furoate*
Schedule H Indications Amoebiasis (asymptomatic carriers in nonendemic areas; eradication of residual luminal amoebae after treatment of invasive disease with other drugs). TABLET 500 mg. Oral Adult- 500 mg every 8 h for 10 days. Child- 20 mg/kg body weight daily in three divided doses for 10 days. Contraindications Precautions Adverse Effects Storage Lactation (Appendix 7b); systemic amoebiasis. Pregnancy (defer treatment until after first trimester). Flatulence; occasionally vomiting, pruritus and urticaria; furred tongue. Store protected from light.

Availability Dose

Metronidazole* (Refer Page No. 140)

Pregnancy Category-B Indications Schedule H Invasive amoebiasis and giardiasis; trichomoniasis; tissue nematode infections; bacterial infections; Helicobacter pylori eradication; ulcerative gingivitis.

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Availability

TABLETS 200 and 400 mg; SUSPENSION 200 mg/5 ml; INJECTION 500 mg in 100 ml infusion. Oral
Adult- Amoebiasis: 400 to 800 mg three times a day for 5 to7 days. Giardiasis: 200 mg three times a day for 7 to 10 days. Child- 35 to 50 mg/kg body weight in amoebiasis and 10 to 15 mg/kg body weight in giardiasis.

Dose

Intravenous injection
Adult- 500 mg every eight h up to 7 days. Child- (Below 12 years) 7.5 mg/kg body weight.

Contraindications

Chronic alcohol dependence; neurological disease, blood dyscrasias, first trimester of pregnancy. Disulfiram-like reaction with alcohol; hepatic impairment and hepatic encephalopathy (Appendix 7a); pregnancy (Appendix 7c); see also notes above); lactation (Appendix 7b); clinical and laboratory monitoring in courses lasting longer than 10 days; interactions (Appendix 6a, 6c, 6d); prolonged use may result in fungal or bacterial superinfection, phenobarbitones, history of seizure disorder. Nausea, vomiting, unpleasant metallic taste, furred tongue and gastrointestinal disturbances; rarely, headache, drowsiness, dizziness, ataxia, darkening of urine, erythema multiforme, pruritus, urticaria, angioedema and anaphylaxis; abnormal liver function tests, hepatitis, jaundice; thrombocytopenia, aplastic anaemia; myalgia, arthralgia; peripheral neuropathy, epileptiform seizures; leukopenia on prolonged or high dosage regimens; anorexia, glossitis, dryness of mouth. Store protected from light and moisture. Store injection in a single dose container.

Precautions

Adverse Effects

Storage

Tinidazole
Pregnancy Category-C Indications Schedule H Amoebiasis, trichomoniasis and giardiasis, anaerobic infections, necrotising ulcerative gingivitis, bacterial vaginosis, H. pylori associated peptic ulcers, abdominal surgery prophylaxis.

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Availability

TABLETS 300 and 500 mg, 1g; INJECTION 400 ml infusion (2 mg/ml); SUSPENSION 75 mg/5 ml, 150 mg/5 ml. Oral Anaerobic infections: Adult- 2g on first day, followed by 1g daily or 0.5g twice daily for 5-6 days. Amoebiasis: Adult- 1.5 - 2g daily as a single dose for 3 - 6 days. Child- 30-50 mg/kg daily as a single dose for 3 days. Trichomoniasis and giardiasis: Adult- 2g as a single dose. Child- 50 to 75 mg/kg as a single dose. Parenteral Bacterial vaginosis and ulcerative gingivitis: Adult- 2g as a single dose parenterally. Anaerobic infections: Adult- Initially 800 mg/400 ml infused i.v. at a rate of 10 ml/minute followed by 800 mg daily. Abdominal surgical prophylaxis: Adult- 2.0g as single i.v. infusion 12 h prior to surgery.

Dose

Contraindications

Hypersensitivity to nitroimidazole derivatives, first trimester of pregnancy (Appendix 7c), lactation, blood dyscrasias, porphyria; interactions (Appendix 6a). Seizures, peripheral neuropathy, CNS disease, disulfiram-like reaction with alcohol. Similar to metronidazole. Store protected from light and moisture.

Precautions Adverse effects Storage

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9.2 Antibacterial Drugs

Beta-Lactams:
Beta-lactam antibiotics including penicillins, cephalosporins and carbapenems share a common structure; they are bactericidal, their mechanism of action resulting from inhibition of peptidoglycan, a mucopeptide in bacterial cell walls. Benzylpenicillin and phenoxymethylpenicillin are active against susceptible strains of Gram-positive bacteria and Gram-negative bacteria, spirochaetes and actinomycetes, but are inactivated by penicillinase and other beta-lactamases. Benzathine benzylpenicillin and procaine benzylpenicillin are long-acting preparations which slowly release benzylpenicillin on injection. A range of penicillins with improved stability to gastric acid and penicillinases have been produced by substitution of the 6-amino position of 6-aminopenicillanic acid. Cloxacillin is an isoxazoyl penicillin which is resistant to staphylococcal penicillinase. Broad-spectrum penicillins such as ampicillin are acid-stable and active against Gram-positive and Gram-negative bacteria, but are inactivated by penicillinase. Beta-lactamase inhibitors such as clavulanic acid are often necessary to provide activity against beta-lactamases produced by a wide range of both Gram-negative and Grampositive bacteria. Cephalosporins are classified by generation, with the first generation agents having Gram-positive and some Gramnegative activity; the second generation drugs have improved Gram-negative activity and the third generation cephalosporin have a wider spectrum of activity, although may be less active against Gram-positive bacteria than first generation drugs, but they are active against Gram-negative Enterobacteriaceae and Pseudomonas aeruginosa. Carbapenems are semisynthetic derivatives of Streptomyces cattleya. They have a broad spectrum of activity and are stable to most penicillinases. They should be reserved for severe infections resistant to other antibiotics. Penicillins may cause encephalopathy due to cerebral irritation. This rare, but serious adverse effect may result from very high doses or in severe renal failure. Penicillins should not be given by intrathecal injection because they can cause encephalopathy which may be fatal.

Hypersensitivity:
The most important adverse effect of penicillins is hypersensitivity which causes rashes and, occasionally anaphylaxis, which can be fatal. A careful history should be taken with regard to 109 NFI-2011

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previous allergic reactions. If rash develops, another antimicrobial should be substituted. Allergic reactions to penicillins occur in 1-10% of exposed individuals, while anaphylactic reactions occur in fewer than 0.05% of treated patients. Individuals with a history of anaphylaxis, urticaria or rash immediately after penicllin administration are at risk of immediate hypersensitivity to penicillin. These individuals should not receive penicillin, rather a cephalosporins or another beta-lactam antibiotic may be used. Patients who are allergic to one penicillin will be allergic to them all because the hypersensitivity is related to the basic penicillin structure and about 10% of penicillin-sensitive patients will be allergic to cephalosporins and other beta-lactams. Individuals with a history of a minor rash (a non-confluent rash restricted to a small area of the body) or a rash occurring more than 72 h after penicillin administration are possibly not allergic to penicillin and in these individuals a penicillin should not be withheld unnecessarily for a serious infection; however, the possibility of an allergic reaction should be borne in mind and facilities should be available for treating anaphylaxis.

Ampicillin, Amoxycillin, Amoxycillin with Clavulanic Acid and Cloxacillin:

Ampicillin is active against certain Gram-positive and Gramnegative organisms. It is used to treat a wide range of infections including otitis media, respiratory-tract and urinarytract infections and gonorrhoea due to susceptible bacteria. However, ampicillin is inactivated by penicillinases including those produced by Staphylococcus aureus and by common Gram-negative bacilli such as Escherichia coli; many strains of Haemophilus influenzae, Moraxella catarrhalis, Neisseria gonorrhoeae and Salmonella and Shigella spp. are resistant. There are geographical variations in the incidence of resistance and an awareness of local patterns is important. In some areas, oral use should be restricted to treatment of Shigella infections; it is given in an oral dose of 1g every 6 h for 7-10 days. Amoxycillin has a similar spectrum of activity to ampicillin, but is also inactivated by penicillinases. However, it is better absorbed after oral administration than ampicillin and higher plasma and tissue levels are achieved. Amoxycillin is preferred to ampicillin for the treatment of some infections including otitis media and respiratory-tract and urinary-tract infections. Clavulanic acid is a beta-lactamase inhibitor. It has no significant antibacterial activity but in combination with Amoxycillin widens Amoxycillins spectrum of activity and allows its use against Amoxycillin-resistant strains of bacteria. It is used in respiratory-tract, genito-urinary and abdominal infections, cellulitis, animal bites and dental infections. NFI-2011 110

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Cloxacillin is used to treat infections due to penicillinase-producing staphylococci which are resistant to benzylpenicillin. It is acid-stable and may therefore be given by mouth as well as by injection. These antibiotics may also be administered with an aminoglycoside to increase their spectrums of activity. The penicillin and aminoglycoside should not be mixed before or during administration, because loss of aminoglycoside activity can occur on mixing.

Benzylpenicillin and Phenoxymethylpenicillin:

Benzylpenicillin remains an important and useful antibiotic but it is inactivated by bacterial beta-lactamases. It is effective for many streptococcal (including pneumococcal), gonococcal and meningococcal infections and also for anthrax, diphtheria, gas gangrene, leptospirosis, tetanus and treatment of Lyme disease in children. Pneumococci, meningococci and gonococci often have decreased sensitivity to penicillin and benzylpenicillin is no longer the first choice for pneumococcal meningitis. Benzylpenicillin is given by injection as it is inactivated by gastric acid and absorption from the intestinal tract is low. Depot preparations are used when therapeutic concentrations need to be sustained for several h. Benzathine benzylpenicillin or procaine benzylpenicillin provides a tissue depot from which the drug is slowly absorbed over a period of 12 hour to several days. They are the preferred choice for the treatment of syphilis or yaws. Phenoxymethylpenicillin is suitable for oral administration; it has a similar spectrum of activity but is less effective than benzylpenicillin. It should not be used for serious infections because absorption can be unpredictable and plasma concentrations variable.

Cephalosporins and Imipenem with Cilastatin:

Ceftazidime and ceftriaxone are third generation cefalosporins. Ceftriaxone is used for serious infections such as septicaemia, pneumonia and meningitis; it is used as a reserve antimicrobial to treat meningitis due to Streptococcus pneumoniae in some areas where penicillin resistance is found. Ceftazidime is active against Pseudomonas aeruginosa and other Gram-negative bacteria; it is used in the treatment of pseudomonal infections and in some areas is restricted to use only where gentamicin resistance is high. Imipenem is a broad-spectrum antibiotic. As it is partially 111 NFI-2011

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inactivated by enzymatic activity in the kidney, it is administered with cilastatin which inhibits the renal metabolism of imipenem. It is active against many aerobic and anaerobic Gram-positive and Gram-negative bacteria; in some areas it is reserve agent for the treatment of infections due to Acinetobacter spp. and P. aeruginosa, which are resistant to other more usual treatments.

Quinolones:
Ciprofloxacin is active against both Gram-positive and Gramnegative bacteria. It is particularly active against salmonella, shigella, campylobacter, neisseria, Bacillus anthracis and pseudomonas. It is also active against chlamydia and some mycobacteria. Most anaerobic organisms are not susceptible. Ciprofloxacin is used with doxycycline and metronidazole to treat pelvic inflammatory disease. Nalidixic acid is an older quinolone effective in uncomplicated urinary-tract infections and, in the treatment of shigella in areas where it remains susceptible.

Tetracyclines:
Doxycycline is a tetracycline and is a broad-spectrum antibiotic effective for conditions caused by chlamydia, rickettsia, brucella and the spirochaete, Borrelia burgdorferi (Lyme disease). It is the preferred tetracycline since it has a more favourable pharmacokinetic profile than tetracycline. It is deposited in growing bone and teeth causing staining and occasionally dental hypoplasia. It should not be given to children under 8 years or pregnant women; in some countries, use in children under 12 years is contraindicated.

Aminoglycosides:
Aminoglycosides including gentamicin are bactericidal and active against some Gram-positive and many Gram-negative organisms including Pseudomonas aeruginosa. Aminoglycosides are not absorbed from the gut and must therefore be given by injection for systemic infections. Excretion is mainly by the kidney and accumulation occurs in renal impairment. Use of gentamicin should be restricted to trained health personnel and care must be taken to ensure correct dosage and duration of treatment are not exceeded, because most adverse effects are dose related. The most important adverse effects are ototoxicity and nephrotoxicity and they are most common in the elderly and in patients with renal impairment. These groups and, if possible, all patients should be monitored for ototoxicity by audiometry. If there is impairment of renal function the dose interval must be increased; in severe renal impairment, the dose should also be reduced. Serum concenNFI-2011 112

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tration monitoring avoids both excessive and subtherapeutic concentrations and can prevent toxicity and ensure efficacy. If possible serum concentrations should be monitored in all patients, but must be measured in infants, the elderly, in obesity, in cystic fibrosis, in high-dosage regimens, in renal impairment, or if treatment lasts for longer than 7 days. For most infections, doses of up to 5 mg/kg daily in divided doses are used if renal function is normal; higher doses are used occasionally for serious infections. Loading and maintenance doses are based on the patients weight and renal function (for example, using a nomogram) with adjustments based on plasma gentamicin concentration.

Chloramphenicol:
Chloramphenicol is a potent broad-spectrum antibiotic. It is associated with serious haematological adverse effects and should be reserved for the treatment of severe infections, particularly those caused by Haemophilus influenzae and typhoid fever. The oily suspension should be reserved for use in situations of catastrophic epidemics of meningococcal meningitis occurring mainly in sub-Saharan Africa, during which the medical services are overwhelmed by the epidemic and in which the overwhelming scale of the epidemic precludes any other form of antimicrobial therapy.

Macrolides:
Erythromycin is a macrolide; it has an antibacterial spectrum that is similar but not identical to penicillin and is used as an alternative in penicillin-allergic patients. It is effective in respiratory infections, whooping cough, legionnaires disease and campylobacter enteritis. Azithromycin is more active than erythromycin against some Gram-negative organisms such as Chlamydia trachomatis. The concentration and persistance of azithromycin is much higher in the tissue than in plasma; a single dose of azithromycin is used in the treatment of uncomplicated genital chlamydia and trachoma. Azithromycin is not recommended if there is a possibility of gonorrhoea because macrolide resistance emerges rapidly when it is used in this setting.

Metronidazole:
Metronidazole has high activity against anaerobic bacteria and protozoa. Metronidazole by the rectal route is an effective alternative to the intravenous route when oral administration is not possible.

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Nitrofurantoin:
Nitrofurantoin is bactericidal in vitro to most Gram-positive and Gram-negative urinary-tract pathogens and it is used to treat acute and recurrent urinary-tract infections. It is also used prophylactically in chronic urinary-tract infections. Sulfonamides and Trimethoprim: The usefulness of sulfonamides is limited by an increasing incidence of bacterial resistance. For many indications they have been replaced by antibiotics that are more active and safer. Sulfadiazine is used in the prevention of rheumatic fever recurrence. Sulfamethoxazole is used in combination with trimethoprim because of their synergistic activity. In some countries, indications for the use of this combination have been restricted. The treatment of Pneumocystis carinii infections must only be undertaken with specialist supervision where there are appropriate monitoring facilities. Trimethoprim is also used alone for respiratory-tract infections and, in particular, for urinary-tract infections.

Vancomycin:
Vancomycin is not significantly absorbed from the gastrointestinal tract and must be given intravenously for systemic infections which cannot be treated with other effective, less toxic antimicrobials. It is used to treat serious infections due to Gram-positive cocci including methicillin-resistant staphylococcal infections, brain abscess, staphylococcal meningitis and septicaemia.

Amoxycillin*
Pregnancy Category-B Indications Schedule H Urinary-tract infections, upper respiratorytract infections, bronchitis; pneumonia; otitis media; dental abscess; osteomyelitis; Lyme disease in children; endocarditis prophylaxis; post-splenectomy prophylaxis; gynaecological infections; gonorrhoea; Helicobacter pylori eradication. TABLETS 250 mg, 500 mg; KID TABLETS 125, 250 mg; CAPSULES 250, 500 mg; DRy SyRUP 125 and 250 mg per 5 ml; INJECTION 1 ml ampoule (100 mg/ml), 250 mg/vial; DROP 10 ml (100 mg/ml). Oral Adult- 250 mg every 8 h, double in severe infection.

Availability:

Dose

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Otitis media: 1g every 8 h. Enteric fever: 2 to 4g daily in divided doses for 14 to 21 days. Intramuscular injection 500 mg every 8 h. Intravenous injection or infusion 500 mg every 8 h, increase to 1g every 6 h in case of severe infection. Child up to 10 years- 125 mg every 8 h, double in severe infections. Otitis media: 40 mg/kg body weight daily in three divided doses. Enteric fever: 50 to 100 mg/kg body weight in three divided doses for 14 to 21 days. Intramuscular injection 50 to 100 mg/kg body weight in divided doses. Intravenous injection or infusion 50 to 100 mg/kg body weight in divided doses. Contraindications Precautions Hypersensitivity to penicillins (see notes above). History of allergy; renal impairment; erythematous rashes common in glandular fever, chronic lymphatic leukaemia and possibly HIV infection; lactation (Appendix 7b); interactions (Appendix 6b, 6c, 6d); possibility of super infection with mycotic pathogens, mononucleosis, hepatic impairment (Appendix 7a); pregnancy (Appendix 7c). Nausea and vomiting, diarrhoea; rashes (hypersensitivity or toxic response, may be serious reaction-discontinue treatment); hypersensitivity reactions including Stevens Johnson syndrome, urticaria, angioedema, anaphylaxis, serum sickness-like reactions, haemolytic anaemia, interstitial nephritis; rarely, antibiotic-associated colitis; neutropenia, thrombocytopenia, coagulation disorders; rarely, central nervous system disorders including convulsions associated with high doses or impaired renal function; mucocutaneous candidiasis, with discolouration; agitation.

Adverse Effects

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Storage

Tablet, Capsule and Oral suspension: Store protected from moisture at a temperature not exceeding 30C. Injection: Store protected from moisture in a sterile, tamper evident container sealed so as to exclude micro-organisms at temperature not exceeding 30C.

Amoxycillin + Clavulanic acid*

Pregnancy Category-B Indications Schedule H Treatment of infections caused by susceptible organisms, sinusitis, otitis media, dental abcesses, severe respiratory tract infections, urinary tract infections, skin and soft tissue infections, surgical prophylaxis. TABLETS Amoxycillin 500 mg 250 mg 875 mg 200 mg + + + + + Clavulanic acid 125 mg 125 mg 125 mg 28.5 mg (DT)

Availability

CAPSULS Amoxycillin + Clavulanic acid 500 mg + 125 mg 250 mg + 125 mg SUSPENSION Amoxycillin + 200 mg + 125 mg + 250 mg + INJECTION Amoxycillin 250 mg 1g 125 mg 500 mg Dose Oral Upper and lower respiratory tract infections, sinusitis, otitis media, skin and soft tissue infections, susceptible infections: Adult- 250-500 mg every 8 hours or 500-750 mg every 12 hours. Child- 125-250 mg every 8 hours; Children weighing <40 kg: 20-40 mg/kg/day in divided doses every 8 hours; Infants <3 months: up to 30 mg/kg/day in divided doses every 12 hours. Dental abcesses: Adult- 3 g as a single dose, followed by a second dose 8 hours later. + + + + + Clavulanic acid 28.5 mg/5 ml 31.25 mg/5 ml 62.5 mg/5 ml Clavulanic acid 50 mg 200 mg 25 mg 100 mg

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Severe or recurrent respiratory tract infections: Adult-3 g twice daily. Child (2-6 years)- 5 ml twice daily; (7-12 years)- 10 ml twice daily before meals, upto 14 days (dose should be specified in terms of strength). Parenteral Susceptible infections and surgical prophylaxis: Adult- 500 mg every 8 hr. In severe infections, dose may be increased to 1 g every 6 hours, upto 14 days. Can be given via i.m or slow i.v over 3-4 minutes or i.v infusion over 30-60 minutes. Child: <10 years: 50-100 mg/kg/day in divided doses. Contraindications Precautions Hypersensitivity to penicillins, infectious mononucleosis, jaundice. Renal impairment, hepatic dysfunction, patients on anticoagulant therapy, pregnancy (Appendix 7c), lactation, interactions (Appendix 6c). GI upset, mycosis, rash, nausea, vomiting, anaphylaxis, cholestatic jaundice, blood dyscracias, toxic epidermal necrolysis, convulsions, exfoliative dermatitis, Stevens Johnson syndrome, angioedema, hepatitis, tooth discolouration. Store protected from moisture at a temperature not exceeding 30C.

Adverse Effects

Storage

Ampicillin*
Pregnancy Category-B Indications Schedule H Mastoiditis; gynaecological infections; septicaemia; peritonitis; endocarditis; meningitis; cholecystitis; osteomyelitis; respiratory tract infection. TABLETS 125 and 250 mg; CAPSULES 250, 500 mg and 1g; DRy SyRUP 125 and 250 mg/5 ml; INJECTION 100, 250 and 500 mg/ vial. Oral Adult- 250 mg to 1g every 6 h at least 30 min before food. Urinary tract infection Adult- 500 mg every 8 h.

Availability

Dose

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Children under 10 years- Half of adult dose. Intramuscular and intravenous injection or infusion 500 mg every 4 to 6 h. Listeria meningitis (in combination with antibiotics); by intravenous infusion 2g every 4h for 10 to 14 days. Child- Half of the adult dose. Listeria meningitis (in combination with antibiotics); infants 1 to 3 months; 50 to 100 mg/kg body weight every 6 h. 3 months to 12 years; 100 mg/kg body weight every 76 h (max 12g daily). Contraindications Precautions Hypersensitivity to penicillins (see notes above). History of allergy (see notes above); renal impairment (Appendix 7d); erythematous rashes common in glandular fever, acute or chronic lymphocytic leukaemia and cytomegalovirus infection; lactation (Appendix 7b); interactions (Appendix 6b, 6c, 6d); pregnancy (Appendix 7c). Nausea and vomiting, diarrhoea; rashes, high fever (hypersensitivity or toxic response-may be serious reaction, discontinue treatment); hypersensitivity reactions including urticaria, angioedema, anaphylaxis, serum sicknesslike reaction, haemolytic anaemia, interstitial nephritis (see also notes above); rarely, antibiotic-associated colitis; neutropenia, thrombocytopenia, coagulation disorders; sore tongue; asthma. Tablets, Capsule, Oral suspension: Store protected from moisture and light at a temperature not exceeding 30C. Injection: Store protected from light in a sterile tamper evident container sealed so as to exclude micro-organisms at a temperature not exceeding 30C.

Adverse Effects

Storage

Azithromycin*
Pregnancy Category-B Indications Schedule H Uncomplicated genital chlamydial infections and trachoma.

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Availability

TABLETS 100, 250 and 500 mg; CAPSULES 250 and 500 mg; INJECTION 500 mg/vial DRy SyRUP 100, 200 mg/5 ml. Oral Adult- 500 mg once daily for 3 days or 500 mg on first day then 250 mg once daily for 4 days. Child- over 6 months: 10 mg/kg body weight once daily for three days. Body weight 15 to 20 kg: 200 mg once daily for 3 days; body weight 26 to 35 kg: 300 mg daily for 3 days. Uncomplicated genital chlamydia infection and non-gonococcal infection: 500 mg once daily for 7 days.

Dose

Contraindications Precautions

Hepatic impairment (Appendix hypersensitivity to erythromycin.

7a);

Pregnancy (Appendix 7c) and lactation (Appendix 7b); renal impairment, prolongation of QT interval (ventricular tachycardia reported); interactions (Appendix 6c, 6d); exacerbation of symptoms of myasthenia gravis; impaired hepatic function. Fewer gastrointestinal effects as compared to erythromycin, also anorexia, dyspepsia, constipation; dizziness, headache, drowsiness; photosensitivity; hepatitis, interstitial nephritis, acute renal failure, asthenia, paraesthesia, convulsions and mild neutropenia reported; rarely, tinnitus, hepatic necrosis, hepatic failure and taste disturbances; flatulence, somnolence, angioedema; eczema, pharyngitis; arthalgia, conjunctivitis. Store protected from moisture.

Adverse Effects

Storage

Benzathine Benzyl Penicillin*

Indications Mild to moderate infections of upper respiratory tract due to susceptible streptococci, Syphilis, prophylaxis of rheumatic fever. INJECTABLE units/2 ml. SUSPENSION1200,000

Availability Dose

Streptococcal URTI: 1.2 million unit (>27 kg) single dose (deep IM inj) after sensitivity test (AST); 0.6 million unit (<27 kg) single dose (deep IM inj) AST.

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Secondary prophylaxis of Rheumatic fever: 1.2 million unit (> 27 kg) single dose (deep IM inj) after sensitivity test (AST) every 21 days; 0.6 million unit (<27 kg) single dose (deep IM inj) AST every 15 days. Syphilis: Primary, secondary, or early latent: Single dose of 2.4 million Unit IM; Late latent (or latent of uncertain duration), cardiovascular, or benign tertiary: 2.4 million Unit IM weekly for 3 weeks. Contraindications Precautions Hypersensitivity, neurosyphilis. Hypersensitivity to cephalosporins or/ and penicillins, elderly, infants, asthma, kidney disease, lactation (Appendix 7b); interactions (Appendix 6c). Hypersensitivity reactions such as exfoliative dermatitis, pain at injection site, thrombophlebitis of injected vein, diarrhoea, nausea, joint pain, angioedema, serum sickness like reactions; haemolytic anaemia, interstitial nephritis.

Adverse effects

Benzyl Penicillin
Pregnancy Category-B Indications Schedule H Mild to moderate infections of upper respiratory tract due to susceptible streptococci, syphilis, prophylaxis of rheumatic fever. INjECTABLE SUSPENSION- 6, 12, 24 Lac units; INjECTABLE SUSPENSION- 1200,000 units/2 ml. Streptococcal URTI: 1.2 million unit (>27 kg) single dose (deep IM inj) after sensitivity test (AST); 0.6 million unit (<27 kg) single dose (deep IM inj) AST. Secondary prophylaxis of Rheumatic fever: 1.2 million unit (>27 kg) single dose (deep IM inj) after sensitivity test (AST) every 21 days; 0.6 million unit (<27 kg) single dose (deep IM inj) AST every 15 days. Syphilis: Primary, secondary, or early latent: Single dose of 2.4 million Unit IM; Late latent (or latent of uncertain duration), cardiovascular, or benign tertiary: 2.4 million Unit IM weekly for 3 weeks. Contraindications Hypersensitivity, neurosyphilis.

Availability

Dose

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Precautions

Hypersensitivity to cephalosporins or/ and penicillins, elderly, infants, asthma, renal impairment (Appendix 7d), lactation (Appendix 7b); pregnancy (Appendix 7c). Hypersensitivity reactions such as exfoliative dermatitis, pain at injection site; thrombophlebitis of injected vein, diarrhoea, nausea, joint pain, angioedema, serum sickness like reactions, haemolytic anaemia, interstitial nephritis. Store protected from moisture at a temperature not exceeding 30C.

Adverse Effects

Storage

Cefazolin
Pregnancy Category-B Indications Schedule H Respiratory tract infection; urinary tract infection; skin and soft tissue infection; biliary tract infection; bone and joint infection; endocarditis; septicaemia; preoperative prophylaxis. INJECTION 125, 250, 500 mg and 1g/vial. Intramuscular and intravenous injection Adult- 1 to 4g daily in 2 to 3 divided doses. Child- 50 to 100 mg/kg body weight every 6 h. Contraindications Precautions Hypersensitivity and cephalosporin; colitis; lactation; pregnancy (Appendix 7c). Renal function impairment (Appendix 7d); over growth of non-susceptible organism; interactions (Appendix 6c). Eosinophilia; diarrhoea; fever; convulsions; neutropenia, anaphylaxis, phlebitis, oral candidiasis, leucopenia; transient rise in SGOT and SGPT and alkaline phosphatase. Store protected from light and moisture at a temperature not exceeding 30C. The constituted solution should be stored protected from light and used within 24 hours when stored at a temperature not exceeding 30C or within 4 days when stored between 2 to 8C.

Availability Dose

Adverse Effects

Storage

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Cefixime*
Pregnancy Category-B Indications Schedule H Otitis media, respiratory tract infections, uncomplicated UTIs, effective against infections caused by Enterobacteriaceae, H. influenza species. TABLETS 50, 100, 200 and 400 mg; CAPSULES 100 and 200 mg; SyRUP/SUSPENSION 50 mg/5 ml, 100 mg/5 ml. Adult- 200-400 mg/day as a single dose or in two divided doses. Child- (more than 6 months) 8 mg/kg/day as a single dose or two divided doses. Uncomplicated gonorrhea: Adult- 400 mg as a single dose. Contraindications Precautions Hypersensitivity to cephalosporins. History of allergy to penicillins, renal failure (Appendix 7d) or patients undergoing continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD), gastrointestinal disease, pregnancy (Appendix 7c), lactation, interactions (Appendix 6c). Diarrhoea, pseudomembranous colitis, loose or frequent stools, abdominal pain, nausea, dyspepsia; hypersensitivity reactions. Store protected from light and moisture at a temperature not exceeding 30C.

Availability

Dose

Adverse Effects

Storage

Cefoperazone
Pregnancy Category-B Indications Schedule H Urinary, biliary, respiratory, skin soft tissue infections, meningitis, septicemias, Pseudomonas, Salmonella typhi, B. fragilis infections. INJECTIONS 0.25, 1.0, 2.0 g/vial. 25-100 mg/kg/day in 2-3 divided doses. Hypersensitivity, interactions (Appendix 6a).

Availability Dose Contraindications

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Adverse Effects

Anaphylaxis, fever, skin rashes; nephritis; granulocytopenia, and hemolytic anaemia, hypoprothrombinaemia and bleeding disorders.

Cefotaxime*
Pregnancy Category-B Indications Schedule H Infections due to sensitive Gram positive and Gram negative bacteria such as bacteraemia, cellulites, intra-abdominal infections, gonorrhoea, bone or joint infections, skin and skin structure infections, urinary tract infections, septicaemias, surgical prophylaxis, endometritis, life threatening resistant/hospital acquired infections, infections in immuno-compromised patients, Haemophilus epiglottitis and meningitis. INJECTION 125, 250, 500 mg, and 1g/vial. Susceptible infections: 12g by i.v or i.m injection, 8 12 hourly. Max.-12 g/day. Child- 50-100 mg/kg/day. Surgical prophylaxis: 1g by i.v or i.m injection, 30-90 minutes before procedure. Gonorrhoea: 0.51g by i.m injection, as a single dose. Septicaemia, meningitis: Adult- 2g i.v, 6-8 hourly for 14-28 days. Neonates- 50 mg/kg daily in 24 divided doses may be increased to 150200 mg/kg daily in severe infections. Child- 100150 mg/kg daily in 24 divided doses increased up to 200 mg/kg daily in very severe infections. Contraindications Precautions Renal disease (Appendix 7d); hypersensitivity to cephalosporins. Impaired kidney or liver disease, colitis; history of penicillin allergy; pregnancy (Appendix 7c), lactation; diabetes. Local inflammation or pain at injection site; thrombocytopenia, eosinophilia, leukopenia; pseudomembranous colitis, moniliasis, diarrhoea, candidiasis, decreased urination; seizures, headache, nausea and vomiting; jaundice; Stevens Johnson syndrome. Store protected from light at a temperature not exceeding 30C.

Availability Dose

Adverse effects

Storage

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Ceftazidime*
Pregnancy Category-B Indications Schedule H Infections due to sensitive bacteria, especially those due to Pseudomonas spp. and including those resistant to aminoglycosides. INJECTION 250, 500 mg, 1g and 2g vial. Deep intramuscular injection and infusion and intravenous

Availability Dose

Adult- 1g every 8 h or 2g every 12 h. Severe infections: 2g every 12 h or 3g every 12 h (1g single dose by intravenous route). Immunocompromised or meningitis patients: 150 mg/kg body weight daily in 3 divided doses (max 6g daily) given by i.v route only. Elderly- Usual max dose of 3g daily. Child- Up to 2 months; 25 to 60g/kg body weight in two divided doses. Over 2 months: 30 to 100 mg/kg body weight in 2 to 3 divided doses. Contraindications Precautions Cephalosporin hypersensitivity; porphyria. Penicillin sensitivity; renal impairment; lactation (Appendix 7b); false positive urinary glucose (if tested for reducing substances) and false positive Coombs test; interactions (Appendix 6b, 6c); pregnancy (Appendix 7c); fall in prothrombin activity, colitis. Diarrhoea, nausea, vomiting, abdominal discomfort, headache; rarely, antibioticassociated colitis (particularly with higher doses); allergic reactions including rashes, pruritus, urticaria, serum sickness-like reaction, fever and arthralgia and anaphylaxis; erythema multiforme, toxic epidermal necrolysis reported; transient hepatitis, cholestatic jaundice; eosinophilia and blood disorders (including thrombocytopenia, leukopenia, agranulocytosis, aplastic anaemia and haemolytic anaemia); reversible interstitial nephritis; nervousness, sleep disturbances, confusion, hypertonia and dizziness; phlebitis, angioedema, myoclonia, candidiasis, transient elevation of blood urea and serum creatinine. Store in sterile containers sealed so as to exclude micro-organisms protected from moisture at a temperature not exceeding 30C.

Adverse Effects

Storage

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Ceftriaxone*
Pregnancy Category-B Indications Schedule H Serious infections due to sensitive bacteria, including septicaemia, pneumonia and meningitis; surgical prophylaxis; prophylaxis of meningococcal meningitis; gonorrhea; bone and joint infection. INJECTION 125, 250, 500 mg, 1g and 2g vial. Intramuscular and intravenous injection or infusion Adult- Urinary tract infection, pneumonia, pelvic inflammatory disease, prophylaxis of surgical infections and meningitis: 4g initially once daily for 10 days or up to 72 h after fever disappears. Typhoid: 4g daily for two days followed by 2g daily for next two days. 1 to 2g daily is used for any other type of condition. Child- Meningitis: 75 to 100 mg/kg body weight for 7 to 9 days. Typhoid: 5 mg/kg body weight for 7 days. 50 to 75 mg/kg body weight is used in case of any other condition (max 2g/day). Contraindications Cephalosporin hypersensitivity; porphyria; neonates with jaundice, hypoalbuminaemia, acidosis or impaired bilirubin binding. Penicillin sensitivity; severe renal impairment; hepatic impairment if accompanied by renal impairment (Appendix 7a); premature neonates; may displace bilirubin from serum albumin; treatment longer than 14 days, renal failure, dehydration or concomitant total parenteral nutrition-risk of ceftriaxone precipitation in gallbladder; lactation (but appropriate to use, see Appendix 7b); pregnancy (Appendix 7c); false positive urinary glucose (if tested for reducing substances) and false positive Coombs test; interactions (Appendix 6b, 6c); phrophylactic indication, patients with impaired vit K synthesis, monitoring of prothrombin time is recommended.

Availability Dose

Precautions

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Adverse Effects

Diarrhoea, nausea and vomiting, abdominal discomfort, headache; antibiotic-associated colitis (particularly with higher doses); allergic reactions including rashes, pruritus, urticaria, serum sickness-like reactions, fever and arthralgia and anaphylaxis; erythema multiforme, toxic epidermal necrolysis reported; transient hepatitis and cholestatic jaundice; elevation of SGOT and SGPT; eosinophilia and blood disorders (including thrombocytopenia, leukopenia, agranulocytosis, aplastic anaemia and haemolytic anaemia); reversible interstitial nephritis, hyperactivity, nervousness, sleep disturbances, confusion, hypertonia and dizziness; calcium ceftriaxone precipitates in urine (particularly in very young, dehydrated, or those who are immobilized) or in gall bladder-consider discontinuation if symptomatic; rarely, prolongation of prothrombin time, pancreatitis; local reaction, hypersensitivity. Store protected from light at a temperature not exceeding 30C.

Storage

Cephalexin*
Pregnancy Category-B Indications Schedule H Respiratory tract infections; otitis media; skin and skin structure infections; genitourinary tract infection; bone infection. CAPSULES/TABLETS 125, 250 and 500 mg; 125 mg Kid tablets; 250 mg DT; DRy SyRUP 125 and 250 mg/5 ml. To be given preferably on empty stomach. Adult- 250 mg every 6 h or 500 mg every 8 to 12 h, increased to 1 to 1.5g every 6 to 8 h for severe infections. Prophylaxis of severe urinary infection: 125 mg at night. tract

Availability

Dose

Child- 25 mg/kg body weight daily in divided doses doubled for severe infections (max. 100 mg/kg body weight daily); Under 1year: 125 mg every 12 h; 1 to 5 years: 125 mg every 8 h; 5 to 12 years: 250 mg every 8 h. Contraindications Cephalosporin hypersensitivity.

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Precautions

Sensitivity to beta-lactam antibacterials (avoid if history of immediate hypersensitivity reaction, renal impairment; lactation; false positive urinary glucose (if tested for reducing substances) and false positive Coombs' test; poor nutritional state; pregnancy (Appendix 7c). Diarrhoea and rarely, antibiotic-associated colitis (more likely with higher doses), nausea and vomiting, abdominal discomfort, headache; allergic reactions including rashes, pruritus, urticaria, serum sickness-like reactions with rashes, fever and arthralgia and anaphylaxis; StevensJohnson syndrome, toxic epidermal necrolysis reported; disturbances in liver enzymes, transient hepatitis and cholestatic jaundice; other side-effects reported include eosinophilia and blood disorders (including thrombocytopenia, leucopenia, agranulocytosis, aplastic anaemia and haemolytic anaemia); reversible interstitial nephritis, hyperactivity, nervousness, sleep disturbances, hallucinations, confusion, hypertonia and dizziness; dyspnoea, colitis, increased blood urea, creatinine, alkaline phosphatase, bilirubin, LDH. Store protected from light and moisture at a temperature not exceeding 30C.

Adverse Effects

Storage

Chloramphenicol* (Refer Page No. 551)

Pregnancy Category-C Indications Schedule H Severe life-threatening infections, particularly those caused by Haemophilus influenzae and typhoid fever; cerebral abscess; mastoiditis; relapsing fever; gangrene; granuloma inguinale; listeriosis; severe melioidosis; plague; psittacosis; tularaemia; Whipples disease; septicaemia; empirical treatment of meningitis; ocular infection. CAPSULES 250 and 500 mg; SyRUP 125 mg/5 ml; INJECTION 250 and 500 mg/vial. Oral, intramuscular or intravenous injection or infusion Adult- 50 mg/kg body weight in four divided doses (can be doubled in very severe infections, septicaemia, meningitis, reduce as soon as clinically indicated). Child- Haemophilus epiglotitis and pyrogenic meningitis: 50 to 100 mg/kg body weight daily in divided doses (can be doubled in severe infections, reduce as soon as clinically indicated).

Availability Dose

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Contraindications

Pregnancy (Appendix 7c); porphyria; blood dyscrasias, preexisting bone marrow depression; hypersensitivity; patients receiving radiation therapy. Avoid repeated courses and prolonged use; reduce dose in hepatic impairment (Appendix 7a) and severe renal impairment; blood counts required before and during treatment; monitor plasma concentrations in neonates (see below); lactation (Appendix 7b); interactions (Appendix 6c); regular blood count; over growth of non-susceptible organism may occur; seizure disorders. Bone marrow depression-reversible and irreversible aplastic anaemia (with reports of leukaemia), anaemia, leukopenia and thrombocytopenia; nocturnal haemoglobinuria; peripheral neuritis and optic neuritis; nausea, vomiting, diarrhoea, dry mouth, stomatitis, glossitis; headache, depression; hypersensitivity reactions including, rashes, fever, angioedema and rarely, anaphylaxis; grey baby syndrome (vomiting, greenish diarrhoea, abdominal distension, hypothermia, pallid cyanosis, irregular respiration, circulatory collapse) may follow excessive doses in neonates with immature hepatic metabolism; also reported in infants born to mothers treated in late pregnancy; ocular irritation, angioneuretic edema. Capsule: Store protected from moisture. Syrup and Injection: Store protected from light and moisture.

Precautions

Adverse Effects

Storage

Ciprofloxacin* (Refer Page No. 552)

Pregnancy Category-C Indications Schedule H Gastroenteritis-including cholera, shigellosis, travellers diarrhoea, campylobacter and salmonella enteritis; typhoid; gonorrhoea; chancroid; legionnaires disease; meningitis (including meningococcal meningitis prophylaxis); respiratory-tract infectionsincluding pseudomonal infections in cystic fibrosis, but not pneumococcal pneumonia; urinary-tract infections; bone and joint infections; septicaemia; anthrax; skin infections; prophylaxis in surgery. TABLETS 100, 250, 500 and 750 mg; INFUSION 50, 100 and 200 ml (2 mg/ml). Oral

Availability Dose

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Adult- Urinary tract infection, respiratory tract infection: 250 to 500 mg, twice daily. Severe respiratory tract infections: up to 750 mg twice daily (however in acute uncomplicated cystitis in women 100 mg twice daily for three days). Chronic prostatitis: 500 mg twice daily for 28 days. Gonorrhoea: 500 mg as a single dose. Child- Not recommended. Intravenous infusion (30 to 60 min) Adult- Urinary tract infection, ENT infection, skin, soft tissue and bone infection, joint infection, gastrointestinal tract infection, severe systemic infection, gonorrhea, surgical prophylaxis and septicaemia; 100 to 200 mg twice daily by slow intravenous injection or infusion. Contraindications History of tendon disorders related to quinolone use; exposure to strong sunlight, hypersensitivity to quinolones derivatives; tizanidine therapy. History of epilepsy or conditions that predispose to seizures, G-6-PD deficiency, myasthenia gravis (risk of exacerbation), pregnancy (Appendix 7c), lactation (Appendix 7b), children or adolescents (see below); avoid exposure to excessive sunlight (discontinue if photosensitivity occurs); rarely, tendon damage-discontinue at first sign of pain or inflammation and rest affected limb; hepatic impairment; renal failure (Appendix 7d); avoid excessive alkalinity of urine and ensure adequate fluid intake as there is risk of crystalluria; interactions (Appendix 6c); cerebral arteriosclerosis, anxiety, paranoia, erythema, blistering. Use In Children. Ciprofloxacin causes arthropathy in the weight-bearing joints of immature animals and is therefore generally not recommended in children and growing adolescents. However, the significance of this effect in humans is uncertain and in some specific circumstances short-term use of ciprofloxacin in children may be justified. Ciprofloxacin is used for pseudomonal infections in cystic fibrosis (for children over 5 years) and for treatment and prophylaxis of anthrax. May impair ability to perform skilled tasks, for example operating machinery, driving.

Precautions

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Adverse Effects

Nausea, vomiting, dyspepsia, abdominal pain, flatulence, diarrhoea (rarely, antibiotic-associated colitis), dysphagia, tremor, hyperglycaemia, headache, dizziness, sleep disorders, rash (rarely, erythema multiforme (Stevens-Johnson syndrome) and toxic epidermal necrolysis) and pruritus; vasculitis, erythema nodosum, petechiae, haemorrhagic bullae; less frequently anorexia, increase in blood urea and creatinine; drowsiness, restlessness, asthenia, depression, confusion, hallucinations, convulsions, paraesthesia; photosensitivity, hypersensitivity reactions including fever, urticaria, angioedema, arthralgia, myalgia and anaphylaxis; blood disorders (including eosinophilia, leukopenia, thrombocytopenia), altered prothrombin time; disturbances in vision, taste, hearing and smell, tinnitus; tenosynovitis; tachycardia, oedema, syncope, hot flushes and sweating; if psychiatric, neurological or hypersensitivity reactions (including severe rash) occur discontinue; arthralgia. Eye drops and Tablet: Store protected from light. Injection: Store protected from light at a temperature not exceeding 30C. The container should not be allowed to freeze.

Storage

Clarithromycin
Pregnancy Category-C Indications Schedule H For the treatment of bacterial infections (pharyngitis/tonsillitis, sinusitis, bronchitis, pneumonia, uncomplicated skin and skin structure infections) caused by H. influenzae, M. catarrhalis, M. pneumoniae, S. pneumoniae, C. pneumoniae, S. aureus, S. pyogenes, Mycobacterium avium and Mycobacterium intracellulare. TABLETS 250 and 500 mg ; 125 mg DT. SUSPENSION 125 mg/5 ml Dose Oral Adult- 250 mg to 500 mg twice a day for 7 to 14 days increase in severe infections to 500 mg every 12 h up to 14 days. Child- Body weight under 8 kg: 7.5 mg/kg body weight twice daily; 8 to 11 kg: 62.5 mg twice daily; 30 to 40 kg: 250 mg twice daily. Contraindications Hypersensitivity cephalosporin. to clarithromycin;

Availability

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Precautions

Neonate under 2 weeks (risk of hypertrophic pyloric stenosis); predisposition to QT interval prolongation (including electrolyte disturbances, concomitant use of drugs that prolong QT interval); avoid in porphyria; hepatic impairment; renal impairment; pregnancy (not known to be harmful) (Appendix 7c); lactation (only small amounts in milk); interactions (Appendix 6c); myasthenia gravis. Nausea, vomiting, abdominal discomfort, diarrhoea (antibiotic-associated colitis reported); less frequently urticaria, rashes and other allergic reactions; reversible hearing loss reported after large doses; cholestatic jaundice, pancreatitis, cardiac effects (including chest pain and arrhythmias), myasthenia-like syndrome, Stevens-Johnson syndrome, toxic epidermal necrolysis also reported, dyspepsia, tooth and tongue discolouration, smell and taste disturbances, stomatitis, glossitis and headache; less commonly hepatitis, arthralgia and myalgia; rarely, tinnitus; very rarely, pancreatitis, dizziness, insomnia, nightmares, anxiety, confusion, psychosis, paraesthesia, convulsions, hypoglycaemia, renal failure, leucopenia and thrombocytopenia; on intravenous infusion, local tenderness, phlebitis. Store protected from moisture.

Adverse Effects

Storage

Clindamycin*
Pregnancy Category-B Indications Schedule H Respiratory tract infections, penicillin resistant staphylococcal infections and many anaerobes such as bacteroides, skin, soft tissue and dental infections. TABLETS/CAPSULES 150 & 300 mg; SyRUP 4 ml (150 mg/ml); INJECTION 2 ml (150 mg/ ml); CREAM/GEL/OINTMENT 10g (1%w/w); LOTION 25 ml (1%w/v). Oral Serious anaerobic infections Adult: 150-300 mg 6 every hr; for more severe infection: 300 to 450 mg every 6 hr. Child: 2-4 mg/kg every 6 hr; for more severe infection: 3-6 mg/kg every 6 hr; 10 kg: 37.5 mg every 8hr. Prophylaxis of endocarditis 600 mg 1 hr before dental procedure.

Availability

Dose

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Intravenous/Intramuscular Serious anaerobic infections Adult: 0.6-2.7 g/day in 3-4 divided doses, up to 4.8 g/day for severe infections. Child: 20-40 mg/kg daily in 3-4 divided dose. Neonate: 15-20 mg/kg daily in 3-4 divided dose Toxic shock syndrome Adult: 900 mg every 8 hr along with penicillin G or ceftriaxone. Pelvic inflammatory disease Adult: 900 mg every 8 hr along with gentamicin. Vaginal Bacterial vaginosis As pessary or 2% cream: 100 mg once nightly for 3-7 days. Topical Acne As 1% preparation: Apply twice daily. Contraindications Hypersensitivity, meningitis as it has less penetration into CNS, pseudomembranous colitis. Hepatic and renal impairment, pregnancy and lactation, GI disease, elderly, atopic patients, regular monitoring of blood counts, in conjuction with antibiotic therapy, pregnancy (Appendix 7c), interactions (Appendix 6c). Urticaria, rashes, contact dermatitis, exfoliative and vesiculous dermatitis, local irritation abdominal pain, oesophagitis, nausea, vomiting, diarrhoea, jaundice and liver abnormalities, eosinophilia, erythema multiforme, thrombophloebitis, gasping syndrome (premature infants and neonates) due to preservative benzoyl alcohol in parenteral formulation, pseudomembranous colitis, azotemia, oliguria, proteinuria. Store protected from moisture

Precautions

Adverse Effects

Storage

Cloxacillin
Pregnancy Category-B Indications Schedule H Multibacillary (MB) leprosy; type 2 lepra reactions; gram positive infection including resistant staphylococci. CAPSULES 250 and 500 mg; INJECTION 250 and 500 mg/vial; DRy SyRUP 125 mg/5 ml. Oral

Availability Dose

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Adult- 250-500 mg every 6 h at least 30 min. before food. Osteomyelitis; upto 8g daily in 2 to 3 divided doses. Surgical prophylaxis; 1 to 2g at induction thereafter up to 4 further doses each of 500 mg may be given every 6 h. Slow intravenous injection or infusion Adult- Surgical prophylaxis; 1 to 2g at induction thereafter up to 4 further doses each of 500 mg may be given every 6 h. Child- High risk procedures; Under 2 years; quarter adult dose. 2 to 10 years; half adult dose. Contraindications Precautions Hypersensitivity to penicillins (see notes above). History of allergy (see notes above); renal and hepatic impairment (Appendix 7a); heart failure; lactation (Appendix 7b); pregnancy (Appendix 7c). Nausea and vomiting, diarrhoea; hypersensitivity reactions including urticaria, fever, joint pain, rashes, angioedema, anaphylaxis, serum sickness-like reactions, haemolytic anaemia, interstitial nephritis (see also notes above); neutropenia, thrombocytopenia, coagulation disorders; antibioticassociated colitis; hepatitis and cholestatic jaundice-may be delayed in onset; electrolyte disturbances; pain, inflammation, phlebitis or thrombophlebitis at injection sites. Store protected from moisture at a temperature not exceeding 30C.

Adverse Effects

Storage

Cotrimoxazole*

(Trimethoprim + Sulphamethoxazole) Pregnancy Category-C Indications Schedule H Urinary-tract infections; respiratory-tract infections including bronchitis, pneumonia, infections in cystic fibrosis; melioidosis; listeriosis; brucellosis; granuloma inguinale; otitis media; skin infections; Pneumocystis carinii pneumonia. TABLETS (TMP + SMZ) 80 mg + 400 mg and 160 mg + 800 mg; SUSPENSION 40 mg TMP + 200 mg SMZ/5 ml. Adult- 1 to 2 tablets twice daily for 7-14 days (160 + 800 mg). Child- Suspension 5 ml twice daily (40 + 200 mg). infant 2.5 ml.

Availability

Dose

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Contraindications

Hypersensitivity to sulfonamides or trimethoprim; porphyria; marked liver parenchymal damage, blood dyscrasias, severe renal insufficiency. Renal impairment; hepatic impairment (avoid if severe; Appendix 7a); maintain adequate fluid intake (to avoid crystalluria); avoid in blood disorders (unless under specialist supervision); monitor blood counts and discontinue immediately if blood disorder develops; rash-discontinue immediately; predisposition to folate deficiency, elderly; asthma; G-6-PD deficiency; lactation (Appendix 7b); avoid in infants under 6 weeks; elderly.; pregnancy (Appendix 7c); interactions (Appendix 6c). Nausea, vomiting, diarrhoea, headache; hypersensitivity reactions including rashes, pruritus, photosensitivity reactions, exfoliativedermatitisanderythemanodosum; rarely, erythema multiforme (StevensJohnson syndrome) and toxic epidermal necrolysis; systemic lupus erythematosus, myocarditis, serum sickness; crystalluriaresulting in haematuria, oliguria, anuria; blood disorders including granulocytopenia, agranulocytosis, aplastic anaemia, purpuradiscontinue immediately; also reported, liver damage, pancreatitis, antibiotic-associated colitis, eosinophilia, cough and shortness of breath, pulmonary infiltrates, aseptic meningitis, depression, convulsions, ataxia, tinnitus, vertigo, dizziness, hallucinations and electrolyte disturbances; megaloblastic anaemia due to trimethoprim; elevation of transaminase and bilirubin; skin rashes. Store protected from light and moisture. Suspension should not be allowed to freeze.

Precautions

Adverse Effects

Storage

Doxycycline* (Refer Page No. 178)

Pregnancy Category-D Indications Schedule H Respiratory-tract infections, including pneumonia and chronic bronchitis; urinary-tract infections; syphilis; chlamydia, mycoplasma and rickettsia; prostatitis; lymphogranuloma venereum; pelvic inflammatory disease (with metronidazole); Lyme disease; brucellosis (with rifampicin); leptospirosis, scrub typhus and travellers diarrhoea; psittacosis; cholera; melioidosis; plague; anthrax; Q fever; Treatment of acute malaria caused by P. malariae and susceptible P. falciparum; P. vivax and P. ovale (followed by primaquine to eliminate intrahepatic forms); prophylaxis of malaria for pregnant women and non-immune individuals at risk.

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Availability Dose

TABLETS/CAPSULES 100 and 200 mg; SyRUP 25 mg/5 ml. Oral Severe infections including refractory urinary tract infection: 200 mg daily. Early syphilis: 100 mg twice daily for 14 days. Latent syphilis: 200 mg twce daily for 28 days. Uncomplicated genital Chlamydia, nongonococcal urethritis: 100 mg twice daily for 7 days. Child- Only if alternate antibacterial cannot be given 5 mg/kg body weight in two divided doses.

Contraindications

Pregnancy (Appendix 7c); children (see notes above); porphyria; systemic lupus erythematosus; hypersensitivity to tetracycline. Avoid exposure to sunlight or sunlampsphotosensitivity reported; renal impairment; hepatic impairment (Appendix 7a); lactation (Appendix 7b); interactions (Appendix 6a, 6b, 6c 6d); predisposition to candidiasis. Gastrointestinal disturbances; anorexia, erythema (discontinue treatment); photosensitivity; hypersensitivity reactions; headache and visual disturbances; hepatotoxicity, blood disorders, pancreatitis and antibiotic-associated colitis reported; staining of growing teeth and occasional dental hypoplasia; erythematous rashes, nasophryngitis, sinusitis, increased blood glucose levels, haemolytic anaemia, neutropenia. Store protected from light and moisture at a temperature not exceeding 30C.

Precautions

Adverse Effects

Storage

Erythromycin*
Pregnancy Category-B Indications Schedule H Alternative to penicillin in hypersensitive patients; pneumonia; legionnaires disease; syphilis; chancroid; chlamydia; nongonococcal urethritis; prostatitis; lymphogranuloma venereum; campylobacter enteritis; relapsing fever; diphtheria and whooping cough prophylaxis upper respiratory tract infection, acne vulgaris, sycosis, vulgaris.

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Availability

TABLETS 125, 250 and 500 mg plain; 125 DT; SyRUP 125 mg/5 ml; OINTMENT 2 and 3% w/w; CREAM 3% w/w. Oral Adult and child over 8 years- 250 to 500 mg every 6 h or 0.5 to 1g every 12 h upto 4g daily in severe infections. Child- 1 month to 2 years; 12.5 mg/kg body weight every 6 h; 2 to 8 years 250 mg every 6 h (doses doubled for severe infections). Early syphilis: 500 mg three times daily for 14 days.

Dose

Contraindications Precautions

Hypersensitivity to erythromycin or other macrolides; porphyria; myasthenia gravis. Hepatic impairment (Appendix 7a) and renal impairment (Appendix 7d); prolongation of the QT interval (ventricular tachycardia reported); pregnancy (Appendix 7c); (not known to be harmful); lactation (Appendix 7b); interactions (Appendix 6c). Nausea, vomiting, abdominal discomfort, diarrhoea and (antibiotic-associated colitis); urticaria, rashes and other allergic reactions (rarely, anaphylaxis); reversible hearing loss after large doses; cholestatic jaundice, cardiac effects (including chest pain and arrhythmias), myasthenialike syndrome, erythema multiforme (Stevens-Johnson syndrome) and toxic epidermal necrolysis; burning sensation, itching, anorexia. Store protected from light at a temperature not exceeding 30C.

Adverse Effects

Storage

Framycetin*
Schedule H Indications Bacterial skin infections, burns, ENT infections, surgical infections, traumatic injury, conjunctivitis, blepharitis. CREAM 1% - 5, 15 and 40g; DROPS 5 ml (0.5%); DRESSING 1%; POWDER 15g. Topical Skin infections: Adult- as 1% dressing.

Availability Dose

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Ophthalmic Blepharitis along with conjunctivitis: Adult- as 0.5 % ointment, apply 2-3 times daily. Otitis externa Adult- 0.5% drops. Contraindications Tuberculosis, glaucoma, perforated tympanic membrane, fungal, viral or resistant bacterial infections of eye, hypersensitivity. Pregnancy, ototoxicity due to systemic absorption may occur if applied on large areas in children, elderly and patients with renal failure, avoid prolonged use, interactions (Appendix 6c). Ototoxicity, gastrointestinal symptoms, inflammation, transient irritation, contact dermatitis, burning sensation, pruritus. Store protected from light and moisture at a temperature not exceeding 30C. If the material is sterile, the container should be tamper-evident and sealed so as to exclude micro-organisms.

Precautions

Adverse effects

Storage

Gentamicin* (Refer Page No. 553)

Pregnancy Category-C Indications Schedule H Pneumonia; cholecystitis; peritonitis; septicaemia; acute pyelonephritis; prostatitis; skin infections; pelvic inflammatory disease; endocarditis; meningitis; listeriosis; tularaemia; brucellosis; plague; surgical prophylaxis; ocular bacterial infection. EyE DROPS 0.3% w/v, CREAM 15g (0.1% w/w); INJECTION 2 ml ampoule (40 mg/ml), 2 and 10 ml vials (40 mg/ml). Intravenous infusion Once daily dose regime; 5 to 7 mg/kg body weight, then adjust as per serum gentamicin concentration. Intramuscular or slow intravenous injection over at least 3 min. Multiple daily dose regimen: 3 mg/kg body weight divided into 8 hly doses.

Availability

Dose

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Child- 2 weeks to 12 years; 2 mg/kg body weight 8 hly. Contraindications Precautions Myasthenia gravis. Renal impairment (Appendix 7d), infants and elderly (dosage adjustment and monitor renal, auditory and vestibular function and serum-gentamicin concentrations); avoid prolonged use; conditions characterized by muscular weakness; significant obesity (monitor serum-gentamicin concentration closely and possibly reduce dose); see notes above; interactions (Appendix 6c); purulent discharge, discontinue if pain/inflammation becomes aggravated; pregnancy (Appendix 7c). Vestibular and auditory damage, nephrotoxicity; rarely, hypomagnesaemia on prolonged therapy; antibiotic-associated colitis, also nausea, vomiting, rash; bacterial/ fungal corneal ulcers, ocular burning or irritation, thrombocytopenia, joint pain. Store protected from moisture if it is intended for use in the manufacture of parenteral preparations.

Adverse Effects

Storage

Imipenem + Cilastatin
Pregnancy Category-C Indications Schedule H Severe aerobic and anaerobic Gram-positive and Gram-negative infections in hospital -acquired infections (not indicated for CNS infections), including infections caused by resistant Pseudomonas and Acinetobacter species. INJECTION Imipenem 125 mg 250 mg 500 mg 1g 2g + + + + + + Cilastatin 125 mg vial 250 mg vial 500 mg vial 1g vial 2g vial

Availability

Dose

Intravenous infusion in terms of imipenem Adult- 2g daily in 2 to 3 divided doses. Less susceptible organism may be given up to 3 to 4 divided doses (max 4g daily). Surgical prophylaxis: 1g for induction, repeated every three h, supplemented in high risk surgery by doses of 500 mg for 8 to 16 h. Child- 3 months and older: 60 mg/kg body weight in four divided doses. Over 40 kg: adult dose.

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Contraindications

Hypersensitivity to beta-lactam antibiotics; local anaesthetics of the amide type and in patients with severe shock or heart block. Renal impairment; CNS disorders, such as epilepsy; lactation (Appendix 7b); interactions (Appendix 6c); pregnancy (Appendix 7c). Nausea, vomiting, diarrhoea; antibioticassociated colitis; taste disturbances; tooth or tongue discolouration, hearing loss; blood disorders, (decreased haematocrit, increased prothrombin time) positive Coombs test; allergic reactions including rash, pruritus, urticaria, erythema multiforme (Stevens-Johnson syndrome), fever, anaphylactic reactions, rarely, toxic epidermal necrolysis, exfoliative dermatitis; myoclonic activity, convulsions, confusion and mental disturbances; slight increase in liver enzymes and bilirubin, rarely, hepatitis; increase in serum creatinine and blood urea; red coloration of urine in children; erythema, pain and induration and thrombophlebitis at injection sites; bone marrow depression. Store protected from moisture in a single dose or multi dose container.

Precautions

Adverse Effects

Storage

Meropenem
Pregnancy Category-B Indications Schedule H Nosocomial infection like septicemia, febrile neutropenia, intraabdominal and pelvic infection etc caused by cephalosporins resistant bacteria, meningitis, cystic fibrosis. INJECTIONS 0.125, 0.250, 0.5, 1 g/vial. Adult- 0.5-2 g or 10-40 mg/kg by slow i.v injection 8 hourly. Neonate (less than 7 days)- 20 mg/kg 12 hourly. 7-28 days- 20 mg/kg 8 hourly. 1-3 months- 10 mg/kg 8 hourly. > 3 months- 10- 20 mg/kg 8 hourly. Meningitis: Adult- 2g 8 hourly. Child- (> 3 months)- 40 mg/kg 8 hourly. Contraindications Hypersensitivity.

Availability Dose

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Precautions

Renal insufficiency, neurological disorders, prolonged use of meropenem may result in overgrowth of nonsusceptible organisms, pregnancy (Appendix 7c), lactation, history of hypersensitivity to other -lactam antibiotics; interactions (Appendix 6c). Inflammation at the injection site; nausea, vomiting, headache, rash; diarrhoea, thrombophlebitis, anaphylaxis, pseudomembranous colitis, disturbances in LFTs.

Adverse Effects

Metronidazole* (Refer Page No. 106)

Pregnancy Category-B Indications Schedule H Anaerobic bacterial infections including gingivitis, pelvic inflammatory disease, tetanus, peritonitis, brain abscess, necrotizing pneumonia, antibiotic-associated colitis, leg ulcers and pressure sores and surgical prophylaxis; bacterial vaginosis; tissue nematode infections; trichomonal vaginitis, amoebiasis and giardiasis; Helicobacter pylori eradication. TABLETS 200 and 400 mg; SUSPENSION 200 mg/5 ml; INJECTION 100 ml infusion (5 mg/ ml). Oral Adult- Amoebiasis: 400 to 800 mg every 8 h for 5 to 7 days. GiardiasisL: 200 mg three times a day for 7 to 10 days or intravenous injection 500 mg 8 hly for 7 days. Child- Amoebiasis: Below 12 years; 7.5 mg/ kg body weight. 12 years and above; 35 to 50 mg/kg body weight daily in three divided doses. Contraindications Precautions Chronic alcohol dependence; first trimester of pregnancy. Disulfiram-like reaction with alcohol; hepatic impairment and hepatic encephalopathy (Appendix 7a); lactation (Appendix 7b); clinical and laboratory monitoring in courses lasting longer than 10 days; interactions (Appendix 6a, 6c, 6d); pregnancy (Appendix 7c); phenobarbitone, history of blood dyscrasias.

Availability

Dose

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Adverse Effects

Nausea, vomiting, unpleasant metallic taste, furred tongue and gastrointestinal disturbances; rarely, headache, drowsiness, dizziness; ataxia; darkening of urine, erythema multiforme; pruritus, urticaria, angioedema and anaphylaxis; abnormal liver function tests, hepatitis, jaundice; thrombocytopenia, aplastic anaemia, myalgia, arthralgia; peripheral neuropathy, epileptiform seizures, leukopenia on prolonged or high dosage regimens; paresthesia. Store protected from light and moisture. Store injection in a single dose container.

Storage

Nalidixic Acid
Pregnancy Category-C Indications Availability Dose Schedule H Urinary-tract infections; shigellosis. TABLETS 250, 500 mg and 1g; SUSPENSION 300 mg/5 ml. Oral Adult- 1g every 6 h for 7 days. Reduced in chronic infection to 600 mg every 6 h. Child- Over 3 months: max 50 mg/kg body weight in divided doses, in prolonged therapy, reduced to 30 mg/kg body weight daily. Contraindications Precautions Hypersensitivity; children <3 years age, porphyria; convulsive disorder. History of epilepsy or conditions that predispose to seizures; G-6-PD deficiency; myasthenia gravis (risk of exacerbation); pregnancy (Appendix 7c); lactation (Appendix 7b); avoid exposure to excessive sunlight (discontinue if photosensitivity occurs); rarely, tendon damage-discontinue at first sign of pain or inflammation and rest affected limb; porphyria; hepatic impairment; renal impairment; false positive urinary glucose (if tested for reducing substances); monitor blood counts, renal and liver function if treatment exceeds 2 weeks; interactions (Appendix 6c); cerebroarterial sclerosis.

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Adverse Effects

Nausea, vomiting, dyspepsia, abdominal pain, diarrhoea (rarely, antibiotic-associated colitis), headache, dizziness, weakness, sleep disorders; rash (rarely, erythema multiforme (Stevens-Johnson syndrome) and toxic epidermal necrolysis) and pruritus; less frequently anorexia, increase in blood urea and creatinine; metabolic acidosis; drowsiness, restlessness, asthenia, depression, confusion, hallucinations, convulsions, paraesthesia, raised intracranial pressure, cranial nerve palsy; photosensitivity, hypersensitivity reactions including fever, urticaria, angioedema, arthralgia, myalgia and anaphylaxis; blood disorders (including eosinophilia, leukopenia, thrombocytopenia); disturbances in vision, taste, hearing and smell; also isolated reports of tendon inflammation and damage (especially in the elderly and in those taking corticosteroids); haemolytic anaemia, renal failure, interstitial nephritis and hepatic dysfunction (including hepatitis and cholestatic jaundice); if psychiatric, neurological or hypersensitivity reactions (including severe rash) occur, discontinue. Store protected from light and moisture.

Storage

Nitrofurantoin*
Pregnancy Category-B Indications Availability Dose Urinary-tract infections; cystitis. TABLETS 50, 100 and 200 mg. Adult- 50 mg every 6 h with food for 3-7 days. Child- Over 3 months: 3 mg/kg body weight daily in four divided doses. Severe chronic recurrent infections: 100 mg every 6 h with food for 7 days, discontinue or reduce dosage in case of nausea. Contraindications Impaired renal function; infants less than 3 months; G-6-PD-deficiency including lactation of affected infants (Appendix 7b); pregnancy, at term (Appendix 7c); porphyria; anuria, oliguria, labour and delivery, neonates; interactions (Appendix 6a, 6d). Schedule H

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Precautions

Pulmonary disorders or hepatic impairment (Appendix 7a); monitor lung and liver function on long-term therapy (discontinue if lung function deteriorates); neurological or allergic disorders; anaemia; diabetes mellitus; elderly and debilitated; vitamin B and folate deficiency; false positive urinary glucose (if testing for reducing substances); urine may be coloured yellow or brown. Dose-related gastrointestinal disorders, nausea; hypersensitivity reactions including urticaria, rash, sialadenitis, pruritus, angioedema; anaphylaxis reported; rarely, cholestatic jaundice, hepatitis, exfoliative dermatitis; erythema multiforme, pancreatitis, arthralgia; blood disorders; pulmonary reactions (pulmonary fibrosis; possible association with lupus erythematosus-like syndrome); peripheral neuropathy; benign intracranial hypertension; transient alopecia; dyspepsia, dizziness, nystagmus. Store protected from light and moisture.

Adverse Effects

Storage

Norfloxacin
Pregnancy Category-C Indications Schedule H Uncomplicated gonorrhea; chronic bacterial prostatitis; complicated UTI; gastroenteritis; conjunctivitis. TABLETS 200, 400, 800 mg; 100 mg DT; SUSPENSION 100 mg/5 ml. Oral Urinary tract infection and upper respiratory tract infections: 200 to 400 mg daily preferably in the morning. Increase if necessary in upper urinary tract infection to 400 mg twice daily. Uncomplicated gonorrhea: 400 mg as a single dose. Uncomplicated genital chlamydia infections, non-gonococcal urethritis: 400 mg daily in single dose for 7 days or divided doses for 7 days. Contraindications History of hypersensitivity, tendinitis.

Availability Dose

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Precautions

Should be used with caution in patients with a history of epilepsy or conditions that predispose to seizures, in G-6-PD deficiency, myasthenia gravis (risk of exacerbation), in renal impairment; during lactation. Exposure to excessive sunlight should be avoided (discontinue if photosensitivity occurs). Quinolones may induce convulsions in patients with or without a history of convulsions; taking NSAIDs at the same time, organ system assessment, haemolytic reaction, pregnancy (Appendix 7c). Nausea, vomiting, dyspepsia, abdominal pain, diarrhoea (rarely, antibiotic-associated colitis), headache, dizziness, sleep disorders; rash (rarely, Stevens-Johnson syndrome and toxic epidermal necrolysis) and pruritus. Less frequent side-effects include anorexia, increase in blood urea and creatinine; drowsiness, restlessness, asthenia, depression, confusion, hallucinations, convulsions, tremor, paraesthesia, hypoaesthesia; photosensitivity, hypersensitivity reactions including fever, urticaria, angioedema, arthralgia, myalgia and anaphylaxis; blood disorders (including eosinophilia, leucopenia, thrombocytopenia); disturbances in vision, taste, hearing and smell. The drug should be discontinued if psychiatric, neurological or hypersensitivity reactions (including severe rash) occur; rash, heart burn, abdominal cramps, irritability. Store protected from light and moisture.

Adverse Effects

Storage

Ofloxacin*
Pregnancy Category-C Indications Schedule H Acute uncomplicated cystitis, community acquired pneumonia, acute exacerbation of chronic bronchitis. TABLETS 100, 200 and 400 mg; SyRUP 30 ml (50 mg/5 ml, 100 mg/5 ml); INJECTION 100 ml (2 mg/ml); EyE DROPS 0.3% w/v. Oral Community acquired pneumonia: Adult- 400 mg twice daily for 10 days. Pelvic inflammatory disease: Adult- 400 mg twice daily for 14 days. Complicated UTI: Adult- 200 mg twice daily for 10 days.

Availability

Dose

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Parenteral Complicated UTI: Adult- 200 mg daily by i.v infusion over atleast 30 minutes, max. 400 mg twice infused over at least 1 h. Septicaemia, lower respiratory tract infection: Adult- 200 mg twice daily by i.v infusion over at least 30 minutes, max. 400 mg twice daily infused over at least 1 h. Bacterial corneal ulcer: Adult- 0.3%, 1-2 drops every 30 minutes. Ophthalmic Bacterial conjunctivitis: Adult- 0.3%, 1-2 drops every 2-4 h. Child- >1year, 1-2drops every 2-4 h. Contraindications Precautions Hypersensitivity. Patients with epilepsy, kidney disease, tendon problem, nervous system problem, liver disease (Appendix 7a), limit alcohol intake, pregnancy (Appendix 7c); lactation (Appendix 7b). Sinus tachycardia, hallucination, Stevens Johnson syndrome, seizure; dizziness, headache, nausea, vomiting, diarrhoea; insomnia, pruritus, photosensitivity. Tablets: Store protected from light and moisture. Eye Drops: Store protected from light.

Adverse effects

Storage

Phenoxymethyl Penicillin (Penicillin V)

Pregnancy Category-B Indications Schedule H Streptococcal pharyngitis; otitis media; erysipelas; mouth infections; secondary prophylaxis of rheumatic fever; postsplenectomy prophylaxis. TABLETS 125 and 250 mg. Adult- 500 mg every 6 hour increased to 750 mg every 6 h in severe cases. Child- up to 1 year: 62.5 mg every 6 h. 1 to 5 years: 125 mg every 6 h. 6 to 12 years: 250 mg every 6 h. Contraindications Hypersensitivity to penicillins (see notes above); serious infections (see notes above).

Availability Dose

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Precautions

History of allergy (see notes above); lactation (Appendix 7b); pregnancy (Appendix 7c); interactions (Appendix 6c); cross sensitivity with cephalosporins may occur. Hypersensitivity reactions including urticaria, serum sickness reaction; joint pain, rash, angioedema, anaphylaxis (see notes above); nausea and diarrhoea; epigastric distress, skin eruptions; haemolytic anaemia. Store protected from moisture.

Adverse Effects

Storage

Piperacillin + Tazobactam
Pregnancy Category-B Indications Availability Schedule H Nosocomial pneumonia, infections following burns, urinary tract infections. INJECTIONS Piperacillin 4g +Tazobactam 0.5g Piperacillin 2g + Tazobactam 0.25g, Piperacillin 1g +Tazobactam 0.0125g. 4.5g (Piperacillin 4g + Tazobactam 0.5g) every 6 h for 7-14 days. Hypersensitivity to penicillins. Pregnancy (Appendix 7c), lactation; prolonged treatment may increase super infections, interactions (Appendix 6c). Hypersensitivity reactions like rash, fever, bronchospasm, vasculitis, serum sickness, exfoliative dermatitis, Stevens-Johnson syndrome, and anaphylaxis. Store below 25C.

Dose Contraindications Precautions

Adverse Effects

Storage

Procaine Benzyl Penicillin (Procaine Penicillin G)

Pregnancy Category-B Indications Schedule H Syphilis; anthrax; childhood pneumonia; diphtheria carrier state; cellulitis; mouth infections; bites. VIALS 5 and 10 lac units. Intramuscular and intravenous injection or infusion AdultStreptococcal infection and pyroderma: single dose 12 lac units. Syphilis: 24 lac units every week for three weeks. Rheumatic fever: 12 lac units every 3 to 4 weeks.

Availability Dose

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Contraindications Precautions Adverse Effects

Hypersensitivity to penicillins (see notes above); intravascular injection. History of allergy (see notes above); renal failure; pregnancy (Appendix 7c). Hypersensitivity reactions including urticaria, fever, joint pains, rashes, angioedema, anaphylaxis, serum sickness-like reaction, haemolytic anaemia, interstitial nephritis (see also notes above); neutropenia, thrombocytopenia, coagulation disorders and central nervous system toxicity (associated with high doses and severe renal failure); Jarisch-Herxheimer reaction (during treatment for syphilis and other spirochaete infections, probably due to release of endotoxins); rarely, non-allergic (embolictoxic) reactions; pain and inflammation at injection site. The constituted solution should be used immidiately after preparation but in any case within the period recommended by the manufacturer.

Storage

Roxithromycin
Pregnancy Category-B Indications Schedule H Susceptible infections; pneumonia, acute bronchitis, sinusitis, pharyngitis, tonsillitis, genital infection. TABLETS 150 and 300 mg; SUSPENSION 50 mg/ml; DROPS 10 ml (25 mg/ml). Adult- 150 mg twice a day at least 15 min before meals. Child- 5 to 8 mg/kg body weight in two divded doses for not more than 10 days. Contraindications Precautions Concomitant use with ergot alkaloid type compounds. Hepatic dysfunction; paediatrics (reduce dose); interactions (Appendix 6d); pregnancy (Appendix 7c). Diarrhoea; vomiting; nausea; transient rise in liver transaminase; skin rash; gastralgia. Store protected from light and moisture.

Availability Dose

Adverse Effects Storage

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Sulphadiazine*
Pregnancy Category-C Indications Schedule H Prevention of recurrences of rheumatic fever; toxoplasmosis; prophylaxis of meningococcal infections. TABLET 500 mg. Oral Adult- 500 mg twice a day. Child- Up to 8 years: 125 mg twice daily. 8 to 12 years: 250 mg twice daily. Contraindications Hypersensitivity to sulfonamides; porphyria; severe renal hepatic impairment, blood dyscrasias, elderly. Hepatic impairment (avoid if severe; Appendix 7a); renal impairment; maintain adequate fluid intake (to avoid crystalluria); avoid in blood disorders (unless under specialist supervision); monitor blood counts and discontinue immediately if blood disorder develops; rashesdiscontinue immediately; predisposition to folate deficiency; elderly; asthma; G-6-PD deficiency; lactation (Appendix 7b); avoid in infants under 6 weeks; interactions (Appendix 6d); pregnancy (Appendix 7c). Nausea, vomiting, diarrhoea, headache; hypersensitivity reactions including rashes, pruritus,photosensitivityreactions,exfoliative dermatitis and erythema nodosum; rarely, erythema multiforme (Stevens-Johnson syndrome) and toxic epidermal necrolysis; systemic lupus erythematosus, myocarditis, serum sickness; crystalluria-resulting in haematuria, oliguria/anuria; blood disorders including granulocytopenia, agranulocytosis, aplastic anaemia, purpura-discontinue immediately; also reported, liver damage, pancreatitis, antibiotic-associated colitis, eosinophilia, cough and shortness of breath, pulmonary infiltrates; aseptic meningitis, depression, ataxia, tinnitus, vertigo, dizziness, hallucinations, and electrolyte disturbances; convulsions, hypoprothrombinemia, methaemoglobinemia, anorexia, pancreatitis. Store protected from light and moisture.

Availability Dose

Precautions

Adverse Effects

Storage

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Tetracycline (Refer Page No. 555)

Pregnancy Category-D Indications Schedule H Rocky Mountain spotted fever; typhus; Q fever; rickettsial pox; tick fever caused by Rickettsiae; respiratory tract infections caused by Mycoplasma pneumonia; chlamydia infection; nongonococcal urethritis; chancroid; plague; tularemia; cholera; brucellosis; bartonellosis; granuloma inguinale; haemophilus and kleibsella infections; psittacosis. CAPSULES/TABLETS 250 and 500 mg. Adult- 250 mg every 6 h, increase to 500 mg every 6 to 8 h in severe infections. Non-gonococcal urethritis: 500 mg every 6 h for 7 to 14 days (21 days if failure or relapse after course is seen). To be taken with plenty of fluid while sitting or standing. Child- 25 to 50 mg/kg body weight, daily in three divided doses. Avoid in children below 8 years. Contraindications Deposition of tetracyclines in growing bone and teeth (by binding to calcium) causes staining and occasionally dental hypoplasia and they should not be given to children under 12 years, or to pregnant (Appendix 7c) or lactating women (Appendix 7b). However, doxycycline may be used in children for treatment and post-exposure prophylaxis of anthrax when an alternative antibacterial cannot be given (unlicensed indication). With the exception of doxycycline and minocycline, the tetracyclines may exacerbate renal failure and should not be given to patients with kidney disease; hypersensitivity; interactions (Appendix 6c, 6d) Used with caution in patients with hepatic impairment or those receiving potentially hepatotoxic drugs. Tetracyclines may increase muscle weakness in patients with myasthenia gravis and exacerbate systemic lupus erythematosus; antacids and aluminium, calcium, iron, magnesium and zinc salts decrease the absorption of tetracyclines; milk also reduces the absorption of tetracyclines, demeclocyclines and oxytetracycline; cerebrovascular sensitisation, maculopapular rashes, increased blood urea nitrogen, anaemia.

Availability Dose

Precautions

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Adverse Effects

Nausea, vomiting, diarrhoea (antibioticassociated colitis reported occasionally), dysphagia and oesophageal irritation. Other rare side-effects include hepatotoxicity, pancreatitis, blood disorders, photosensitivity (particularly with demeclocycline) and hypersensitivity reactions (including rash, exfoliative dermatitis, Stevens-Johnson syndrome, urticaria, angioedema, anaphylaxis, pericarditis). Headache and visual disturbances may indicate benign intracranial hypertension (discontinue treatment); bulging fontanelles have been reported in infants; anaemia. Store protected from light and moisture.

Storage

Trimethoprim
Pregnancy Category-C Indications Availability Dose Schedule H Urinary-tract infections; bronchitis. Refer cotrimoxazole above. Oral Adult- 200 mg every 12 h. Child- 1 month to 12 years: 4 mg/kg body weight (max. 200 mg) every 12 h. 6 weeks to 6 months: 25 mg every 12 h. Contraindications Precautions Blood disorders; porphyria; hypersensitivity. Renal impairment; lactation (Appendix 7b); predisposition to folate deficiency; elderly; blood counts on long-term therapy (but practical value not proven); neonates (specialist supervision required); pregnancy (Appendix 7c). Rashes, pruritus; depression of haematopoiesis; gastrointestinal disturbances including nausea and vomiting; rarely, exfoliative dermatitis and toxic epidermal necrolysis, photosensitivity and other allergic reactions including angioedema and anaphylaxis; aseptic meningitis; erythema, multiforme, elevation of transaminase and bilirubin. Store protected from light and moisture.

Adverse Effects

Storage

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Vancomycin*
Pregnancy Category Oral Capsules- B Parenteral Formulation- C Indications Schedule H

Methicillin-resistant staphylococcal pneumonia; staphylococcal meningitis; endocarditis prophylaxis (with gentamicin). TABLETS 500 mg; INJECTION 250 mg, 500 mg and 1g/vial; CAPSULE 125 and 250 mg. Adult- 1 to 1.5g every 12 h. Elderly over 65 years; 500 mg every 12 h or 1g once daily. Child- Over 1 month; 15 mg/kg body weight every 8 h (max. 2g daily).

Availability Dose

Note: Oral for antibiotic associated colitis, 125 mg every 6 h for 7 to 10 days. Not very common therapy. Contraindications Precautions Allergy to hypersensitivity. corn/corn products,

Avoid rapid infusion (risk of anaphylactoid reactions, see Adverse effects); rotate infusion sites; renal impairment (Appendix 7d); elderly; history of deafness-avoid; plasma-vancomycin concentration measured after 3 or 4 doses (earlier if renal impairment), blood counts, urinalysis and renal function tests-use only in hospital setting; monitor auditory function and plasma-vancomycin concentrations in elderly or in renal impairment; lactation (Appendix 7b); pregnancy (Appendix 7c); interactions (Appendix 6c); Pseudomembranous colitis. Nephrotoxicity including renal failure and interstitial nephritis; ototoxicity (discontinue if tinnitus occurs); blood disorders; nausea, chills, fever, eosinophilia, anaphylaxis, rashes, including exfoliative dermatitis, erythema multiforme (Stevens-Johnson syndrome), toxic epidermal necrolysis and vasculitis; phlebitis; on rapid infusion, severe hypotension (with shock, cardiac arrest), wheezing, dyspnoea, urticaria, pruritus, flushing of the upper body (red man syndrome), pain and muscle spasm of back and chest; hypotension, pruritus, haematopoitic flebitis. Store in an air tight container protected from light.

Adverse Effects

Storage

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9.3 Antifilarial Drugs

Loiasis:
Loiasis is an infection with the filarial nematode Loa loa and is transmitted by the biting of tabanid fly Chrysops. Diethylcarbamazine is effective against both adult worms and larvae; a single weekly dose is normally effective as prophylaxis. During individual treatment, particularly of persons with heavy microfilaraemia (>50 000 microfilariae/ml blood), a condition simulating meningoencephalitis occasionally occurs. This probably results from sludging of moribund microfilariae within cerebral capillaries. The frequency of meningoencephalitis associated with diethylcarbamazine therapy of loiasis is reported as 1.25%, with a mortality rate of about 50% in affected patients; treatment with diethylcarbamazine should be stopped at the first sign of cerebral involvement (and specialist advice sought). Permanent cerebral damage is common among patients who survive and this possibility should be considered when deciding on treatment. Treatment of heavily infected patients should thus begin at low dosage and corticosteroid and antihistamine cover should be provided for the first 2 to 3 days.

Lymphatic Filariasis:
Lymphatic filariasis is caused by infection with Wuchereria bancrofti (bancroftian filariasis), Brugia malayi or B. timori (brugian filariasis). Occult filariasis (tropical pulmonary eosinophilia) is a clinical variant of W. bancrofti infection. Individual treatment with diethylcarbamazine which has both microfilaricidal and macrofilaricidal activity is effective. Total cumulative dosages of 72 mg/kg are generally recommended for Wuchereria bancrofti infections with half this dose used for Brugia malayi and B. timori infections. In all cases treatment is best initiated with smaller doses for 2-3 days to avoid the danger of immunological reactions. Rigorous hygiene to the affected limbs with adjunctive measures to minimize infection and promote lymph flow is important for reducing acute episodes of inflammation. In communities where filariasis is endemic, annual administration of single doses of albendazole 400 mg with either diethylcarbamazine (6 mg/kg) or ivermectin (200 g/kg) is effective for interrupting transmission; this treatment is continued for at least 5 years. Trials in India and China have shown that the consistent use for 6-12 months of table salt containing diethylcarbamazine 0.1% can eliminate W. bancrofti; a concentration of 0.3% for 3-4 months may be required where B. malayi is endemic. NFI-2011 152

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Diethylcarbamazine*
Indications Treatment of loiasis; prophylaxis of loiasis in temporary residents in endemic areas; tissue nematode infections; lymphatic filariasis; toxocariasis. TABLETS 50 and 100 mg; SyRUP 5 mg/ml and 120 mg/5 ml. Oral
Adult and child- 11 mg/kg body weight

Availability Dose

daily in three divided doses on the first day. Thereafter increase gradually to 6 mg/kg body weight given after food daily for two to three days. Hookworm infection: treat for 21 days. Filariasis: 2 mg/kg body weight is given three times a day for 3 to 4 weeks. 1 mg/kg body weight for an adult of 50 kg. Treatment may be repeated once after 6 months. Pregnancy (delay treatment until after delivery); infants, elderly, debilitated (usually excluded from mass treatment programmes; see also Precautions); cardiac disease, hypersensitivity, impaired renal function. Renal impairment; cardiac disorders; other severe acute diseases-delay diethylcarbamazine treatment until after recovery; risk of meningoencephalitis in severe infection (see notes above). Headache, dizziness, drowsiness, nausea and vomiting; immunological reactions, within a few hour of the first dose, subsiding by fifth day of treatment and including fever, headache, joint pain, dizziness, anorexia, malaise, nausea and vomiting, urticaria and asthma in asthmatics (similar to Mazzotti reaction), induced by disintegrating microfilariae; microencephalitis (with heavy microfilaraemia, see notes above); reversible proteinuria; enlargement of lymph nodes. Store protected from moisture.

Contraindications

Precautions

Adverse Effects

Storage

Ivermectin
Pregnancy Category-C Indications Nematodal infections such as ascariasis, trichuriasis, strongyloidiasis, enterbiasis, lymphatic filariasis, scabies and pediculosis. TABLETS 3, 6, 9 and 12 mg; INJECTION 10 ml (0.1% w/v).

Availability

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Dose

Oral Strongyloidiosis: 200 g/kg of body weight once daily for 1-2 days. Lymphatic filariasis: 400 g/kg of body weight simple annual dose for 4-6 years. Scabies and pediculosis: 150-200 g/kg of body weight single oral dose highly effective. Second dose may be required 7-10 days later.

Contraindications

Hypersensitivity, CNS disorders, pregnancy, meningitis, trypanosomiasis, seizures, contraindicated to children below the age of < 5 years old or under 15 kg body weight. Concurrent Loa Loa infection, impaired blood-brain barrier function, pregnancy (Appendix 7c), lactation, hepatic, cardiovascular, renal or pulmonary disease, anaemia, coagulation disorder, severe asthma, interactions (Appendix 6c). Nausea, vomiting, constipation, abdominal pain and fatigue, rash, arthralgia, fever, myalgia, asthenia, hypotension, tachycardia, edema, lymphadenopathy, sore throat, cough, headache, somnolence, transient eosinophilia, dizziness, diarrhoea, pruritus, orthostatic hypotension, lymph-node tenderness, rare but serious adverse effects such as marked disability and encephalopathies in patients coinfected with heavy burdens of Loa microfilaria.

Precautions

Adverse Effects

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9.4 Antifungal Drugs

Fungal infections can be superficial or systemic. Superficial infections affect only the skin, hair, nails or mucous membranes whereas systemic fungal infections affect the body as a whole. Systemic fungal infections are sometimes caused by inhalation, ingestion or inoculation of primary pathogens and sometimes by opportunistic invasion of commensals in patients with lowered host resistance. They are increasing in prevalence not only because of the pandemic of HIV infection, but also because of the rise in illicit intravenous drug use in many countries and greater use of broad spectrum antibiotics and invasive medical procedures. In immunodeficient patients systemic fungal infections are often disseminated. Amphotericin B is a lipophilic polyene antibiotic; it is fungistatic against a broad spectrum of pathogenic fungi, including Candida spp., Aspergillus spp., Cryptococcus neoformans, Histoplasma capsulatum, Blastomyces dermatitidis, Coccidioides immitis, Paracoccidioides brasiliensis, Mucor, Absidia and Phicopes spp.; it is active against algal Prototheca spp. and against the Leishmania protozoa. It is used for the empirical treatment of serious fungal infections and is used in conjunction with flucytosine to treat cryptococcal meningitis and systemic candidosis. Amphotericin B has to be administered parenterally as there is little or no absorption from the gastrointestinal tract; amphotericin B is liable to cause nephrotoxicity. Duration of therapy varies with the initial severity of the infection and the clinical response of the patient. In some infections a satisfactory response is only obtained after several months of continuous treatment. Intrathecal infusion has been used successfully in patients with meningeal coccidioidomycosis. Fluconazole an orally active synthetic imidazole derivative, possesses fungistatic activity against dermatophytes, yeasts and other pathogenic fungi. It is widely used in the treatment of serious gastrointestinal and systemic mycoses as well as in the management of superficial infections. Fluconazole is also used to prevent fungal infections in immunocompromised patients. Flucytosine, is a synthetic fluorinated pyrimidine with a narrow spectrum of antifungal activity, particularly against Cryptococcus and Candida spp. In susceptible fungi, it is converted to 5-fluorouracil by cytosine deaminase. Flucytosine is myelosuppressive and plasma concentrations above 75 g/ml are associated with myelotoxicity. 155 NFI-2011

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Griseofulvin is a fungistatic antibiotic derived from Penicillium griseofulvum with selective activity against the dermatophytes causing ringworm, Microsporum canis, Trichophyton rubrum and T. verrucosum. It has no activity against pityriasis versicolor or candida infections. Griseofulvin is deposited selectively in keratin precursor cells of skin, hair and nails where it disrupts the mitotic apparatus of fungal cells thus preventing fungal invasion of newly-formed cells. It is unsuitable for prophylactic use. Close attention should be given to hygiene and to possible reservoirs of reinfection in clothing, footware and bedding. Nystatin, a polyene antifungal antibiotic derived from Streptomyces noursei, is effective against infections caused by a wide range of yeasts and yeast-like fungi. It is poorly absorbed from the gastrointestinal tract and it is not absorbed from the skin or mucous membranes when applied topically. It is used for the prophylaxis and treatment of candidosis. Potassium iodide aqueous oral solution is a clear liquid with a characteristic, strong salty taste. It is effective against sporotrichosis and subcutaneous phycomycosis, which are fungal infections caused by Sporothrix schenckii and Basidiobolus haptosporus respectively. In subcutaneous sporotrichosis, amphotericin B is often effective in patients unable to tolerate iodides. Itraconazole, by mouth has been tried as an alternative to potassium iodide in both cutaneous and extracutaneous sporotrichosis. In phycomycosis, fluconazole may be effective.

Amphotericin B*
Pregnancy Category-B Indications Schedule H Life-threatening fungal infections including histoplasmosis, coccidioidomycosis, paracoccidioidomycosis, blastomycosis, aspergillosis, cryptaococcosis, mucormycosis, sporotrichosis and candidiasis; visceral and mucocutaneous leishmaniasis unresponsive to pentavalent antimony compounds; severe meningitis, perioral candidiasis. VIALS 10, 25, 50 and 100 mg plain, 50 mg/ vial (liposomal). Intravenous infusion (plain)

Availability Dose

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Adult- Systemic fungal infection: 250 g/kg body weight daily, increase gradually 1 mg/ kg body weight if tolerated (max 1.5 mg/kg body weight daily) or alternate days. Child- Same as for Adult based on body weight.

Intravenous (liposomal) For fever in neutropenic patients: 3 mg/kg/ day, max. dose 5 mg/kg/day i.v. For cryptococcal meningitis: 3-4 mg/kg, max. 6 mg/kg, i.v. once daily. Visceral leismaniasis: Immunocompetent patients: 3 mg/kg. Immunocompromized patients: 4 mg/kg. Contraindications Toxic effects must be weighed against benefits. Regular kidney, liver function tests and blood counts must be conducted; lactation; antineoplastic therapy. Close medical supervision throughout treatment and initial test dose required (see note, below); renal impairment (Appendix 7d); pregnancy (Appendix 7c); hepatic and renal function tests; blood counts and plasma electrolyte monitoring; corticosteroids (avoid, except to control reactions); lactation; avoid rapid infusion (risk of arrhythmias); interactions (Appendix 6c); geriatric use. Anaphylaxis occurs rarely, with intravenous amphotericin B and a test dose is advisable before the first infusion. The patient should be observed for about 30 min after the test dose. Adverse Effects Fever, headache, anorexia, weight loss, nausea and vomiting, malaise, diarrhoea, muscle and joint pain, dyspepsia and epigastric pain; renal function disturbances including hypokalaemia, hypomagnesaemia and renal toxicity; blood disorders; cardiovascular toxicity (including arrhythmias); neurological disorders (including peripheral neuropathy); abnormal liver function (discontinue treatment); rash; anaphylactoid reactions (see above); pain and thrombophlebitis at injection site; respiratory failure. Store in a tightly closed container between 2 to 8C, protected from light.

Precautions

Storage

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Clotrimazole*
Pregnancy Category-B Indications Schedule H Vulvo-vaginal candidiasis, trichomoniasis, vaginitis, non-specific vaginitis, mixed vaginal infection, Gram-positive and Gram-negative bacterial infection, infective leucorrhoeas; prevention of athletes foot and ringworm disease of skin folds. PESSARIES/VAGINAL TABLETS 100 and 200 mg; CREAM 1% w/w; POWDER 75g; LOTION 50 ml.
Adult- Pessaries/vaginal tablets: 100 mg pessary/vaginal tablet to be inserted into vagina at night before going to bed as deep as possible for consecutive 6 to 7 days or 200 mg for 3 consecutive night before going to bed or 500 mg single dose. ChildPessaries/vaginal tablets: not recommended. Cream: Rub on affected area 2 to 3 times by applying in thin layer and rubbing, continue for 14 days after healing.

Availability

Dose

Contraindications Precautions Adverse Effects

Ophthalmic use; hypersensitivity. Avoid contact with eyes, (Appendix 7c) and lactation. pregnancy

Local irritation, burning sensation and itching, abnormal liver function, unpleasant mouth sensation. Store protected from light and moisture. Do not crush pessaries.

Storage

Fluconazole*
Pregnancy Category-C Indications Schedule H Systemic mycosis including histoplasmosis, non-meningeal coccidioidomycosis, paracoccidioidomycosis and blastomycosis treatment and, in AIDS and other immunosuppressed patients, prophylaxis of cryptococcal meningitis; oesophageal and oropharyngeal candidiasis, vaginal candidiasis and systemic candidiasis.

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Availability Dose

TABLETS/CAPSULES 50, 100, 150 and 200 mg; EyE DROPS 5 ml (0.3% w/v). Adult- Mucosal: 50 to 100 mg daily for 14 to 30 days. Vaginal: 150 mg as a single dose. Oral: systemic loading dose of 400 mg on first day and thereafter 200 to 400 mg once daily for at least 28 days. Prophylaxis of fungal infection: 50 to 100 mg once daily.

Contraindications

Sensitivity to primaquine; infants below 1 year of age; alcohol; coadministration of cisapride, terfenadine. Renal impairment (Appendix 7d); lactation (Appendix 7b); monitor liver functiondiscontinue if signs or symptoms of hepatic disease (risk of hepatic necrosis; Appendix 7a); interactions: (Appendix 6b, 6c); pregnancy (Appendix 7c); immunocompromised patients. Nausea, vomiting, abdominal pain; flatulence, diarrhoea; headache, taste disturbance, hepatic disorders, dizziness, seizures, alopecia, pruritus; rash (withdraw treatment); angioedema, anaphylaxis, bullous lesions, toxic epidermal necrolysis and erythema multiforme (Stevens-Johnson syndrome) reported (skin reactions more common in AIDS); hyperlipidaemia, leukopenia, thrombocytopenia, hypokalaemia. Stor in an airtight container.

Precautions

Adverse Effects

Storage

Flucytosine
Pregnancy Category-C Indications Schedule H Adjunct to amphotericin B (or fluconazole) in cryptococcal meningitis; adjunct to amphotericin B in systemic candidiasis; septicemia, pulmonary infection. CAPSULE 250 mg; INFUSION 2.5g in 250 ml. Oral
Adult- 250 mg four times a day for not more than 7 days. Intravenous infusion- over 20 to 40 min;

Availability Dose

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Adult and Child- 200 mg/kg body weight daily in four divided doses.

Contraindications Precautions

Renal impairment; elderly; blood disorders, pregnancy (Appendix 7c); hypersensitivity. Elderly; renal impairment; also the use with amphotericin B (both nephrotoxic); liverand kidney function tests and blood counts required (weekly in renal impairment or in blood disorders); lactation (Appendix 7b); interactions (Appendix 6c); pregnancy (Appendix 7c). Rash, nausea, vomiting and diarrhoea; alterations in liver function tests; less frequently, confusion, hallucinations, convulsions, headache, sedation, vertigo; blood disorders including leukopenia, potentially fatal thrombocytopenia and aplastic anaemia; cardiac arrest, myocardial toxicity, dyspnoea, azotemia, ataxia, hypoglycemia. Store protected from light.

Adverse Effects

Storage

Griseofulvin*
Pregnancy Category-C Indications Fungal infections of the skin, scalp, hair and nails where topical treatment has failed or is inappropriate; athletes foot. TABLETS 125, 250, 375 and 500 mg; CAPSULES 125 mg. Oral
Adult- 500 mg once a day or in divided doses, in severe infections dose may be doubled. Reduce when response occurs. Administer with meals. Child- Under 50 kg: 10 mg/kg body weight once daily or divided doses with meals.

Availability Dose

Contraindications

Severe liver disease (Appendix 7a); pregnancy (Appendix 7c) (avoid pregnancy during and for 1 month after treatment; men should not father children within 6 months of treatment; porphyria; systemic lupus erythematosus and related disorders.

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Precautions

Pre-existing hepatic insufficiency (closely monitor hepatic function throughout treatment); blood disorders (monitor blood count weekly during first month of treatment); lactation; interactions (Appendix 6a, 6b, 6c, 6d); avoid exposure to sunlight/ artificial light. May impair ability to perform skilled tasks, for example operating machinery, driving.

Adverse Effects

Headache, nausea, vomiting, diarrhoea, rashes, dizziness, fatigue reported; dry mouth and angular stomatitis; leukopenia, agranulocytosis; proteinuria reported; photosensitivity; lupus erythematosus, toxic epidermal necrolysis, erythema multiforme; serum sickness, angioedema; peripheral neuropathy; confusion and impaired coordination. Store in a well closed container.

Storage

Ketoconazole
Pregnancy Category-C Indications Schedule H Malassezia fulliculitis dermatophytosis and chronic conditions which cannot be treated topically; infections resistant to fluconazole; blastomycosis, candidiasis, chromomycosis. TABLETS 200 mg; CREAM 2% and 5% w/w; SOLUTION 2%w/v; LOTION 2%w/v.
Adult- 200 to 400 mg daily once preferably after food. Child- (Over 2 years) 3.3 to 6.6 mg/kg body weight once daily after food.

Availability Dose

Local application- 3 to 4 times daily, apply thoroughly. Contraindications Precautions Hepatic impairment; lactation; concomitant use with cisapride. Predisposition to adrenocortical insufficiency; avoid in porphyria; pregnancy (Appendix 7c); interactions (Appendix 6a, 6c), hepatotoxicity

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Potentially life-threatening hepatotoxicity reported very rarely,; risk of hepatotoxicity greater if given for longer than 14 days. Monitor liver function before treatment, then on weeks 2 and 4 of treatment, then every month. Avoid or use with caution if abnormal liver function tests (avoid in active liver disease) or if history of hepatotoxicity with other drugs. Adverse Effects Nausea, vomiting, abdominal pain; pruritus; less commonly diarrhoea, headache, dizziness, drowsiness and rash; very rarely, fatal liver damage (see Hepatotoxicity above), dyspepsia, raised intracranial pressure, adrenocortical insufficiency, erectile dysfunction, menstrual disorders, azoospermia (with high doses), gynaecomastia, thrombocytopenia, photophobia and alopecia.

Nystatin*
Pregnancy Category-C Indications Availability Dose Schedule H Oral, oesophageal, intestinal, vaginal and cutaneous candidiasis. TABLETS 5,00,000 units; OINTMENT 3g (100000 IU). Oral
Adult- Intestinal candidiasis: 5,00,000 units every six h, doubled in severe infections. Child- 1 month to 12 years: 1,00,000 units 4 times daily, immunocompromised children may require higher doses up to 5,00,000 units.

Topical application Dissolve one tablet in glycerine and apply locally 3 to 4 times. Intravaginal Insert one tablet deep into vagina before bed time once at night. Contraindications Hypersensitivity.

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Precautions

Lactation; discontinue if sensitivity develops, teratogenic effect, should not be used for the treatment of systemic, oral, intravaginal or ophthalmic infections; preganacy (Appendix 7c). Nausea, vomiting, diarrhoea at high doses; oral irritation and sensitization; rash and rarely, erythema multiforme (StevensJohnson syndrome); eczema, burning. Store protected from light and moisture.

Adverse Effects

Storage

Tolnaftate
Pregnancy Category-C Indications Availability Dose Contraindications Precautions Ringworm infections, athletes foot. CREAM 10% w/w.; OINTMENT- 10 % w/w. SOLUTION- 10% w/v. Rub sufficient quantity gently into affected area 2-3 times daily. Hypersensitivity, deep infections. Avoid contact with eyes and mucous membranes; mixed infections. Discontinue if irritation occurs on application, pregnancy (Appendix 7c). Stinging, irritation, sensitization.

Adverse Effects

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9.5 Anthelminthics
Cestode Infections:
Cestode infections (tapeworms) include intestinal taeniasis and cysticercosis, hymenolepiasis (dwarf tapeworm), diphyllobothriasis and echinococcosis (hydatid disease). Cysticercosis is a systemic infection caused by the larval form (cysticercus) of Taenia solium. Neurocysticercosis occurs when the infection involves the brain. In man, echinococcosis is due to the larval stage of Echinococcus granulosus or E. multilocularis. The larvae (oncospheres) develop by expansion (cystic echinococcosis) or tumour-like infiltration (alveolar echinococcosis), respectively, in the liver, lungs, or other organs.

1. Diphyllobothriasis:
In diphyllobothriasis, niclosamide or praziquantel in a single dose is highly effective. Hydroxocobalamin and folic acid supplements may also be required.

2. Echinococcosis:
In echinococcosis, surgery (or, if this is not possible, a technique such as puncture-aspiration-injection-reaspiration) is the treatment of choice for operable cystic disease due to Echinococcus granulosus but chemotherapy with benzimidazoles, such as mebendazole and albendazole, may be of value as adjunctive therapy. Alveolar echinococcosis due to E. multilocularis requires both surgery and long-term treatment with either mebendazole or albendazole to inhibit spread of the infection. In animal studies, albendazole and mebendazole have been found to be teratogenic. They are contraindicated for the treatment of cestode infections in pregnancy; pregnancy should be excluded before treatment with albendazole (non-hormonal contraception during and for 1 month after treatment). For single-dose or short-term use in pregnancy.

3. Hymenolepiasis:
In hymenolepiasis, praziquantel is more effective than niclosamide, although resistance to praziquantel has been reported. Repeated treatment may be necessary to cure intense infections or to eliminate the parasite within a family group or institution.

4. Taeniasis:
In taeniasis, praziquantel is well tolerated and extensively absorbed and kills adult intestinal taenia worms in a single NFI-2011 164

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dose. Praziquantel also kills T. solium cysticerci when taken for 14 days in high doses. It thus offers the prospect of a cure for neurocysticercosis, which has been treatable only by surgery, anti-inflammatory corticosteroids and anticonvulsants. However, because dying and disintegrating cysts may induce localized cerebral oedema, treatment with praziquantel must always be undertaken in a hospital setting. In addition, a corticosteroid is usually given to reduce the inflammatory response. Albendazole also kills neurocysticerci when given daily for one month; a corticosteroid or an antihistamine is also given to reduce any inflammatory reaction. The longerestablished niclosamide acts only against the adult intestinal worms. Cestode infections due to T. solium, occurring during pregnancy should always be treated immediately (with praziquantel or niclosamide, but not with albendazole) because of the risk of cysticercosis.

Intestinal Nematode Infections:

Intestinal nematode infections include ascariasis, capillariasis, enterobiasis, hookworm infection, strongyloidiasis, trichostrongyliasis and trichuriasis.

1. Ascariasis:
Ascariasis is an infection, usually of the small intestine, caused by Ascaris lumbricoides (roundworm). Single doses of levamisole or pyrantel are effective; the broad-spectrum anthelminthics, albendazole or mebendazole are also effective.

2. Capillariasis:
Capillariasis is caused by infection of the intestine with Capillaria philippinensis. Prolonged treatment with mebendazole or albendazole offers the only prospect of cure.

3. Enterobiasis:
Enterobiasis is an infection of the large intestine caused by Enterobius vermicularis (pinworm, threadworm). All household members should be treated concurrently with a single dose of mebendazole, albendazole or pyrantel. Since reinfection readily occurs, at least one further dose should be given 2-4 weeks later. Piperazine is also effective but must be taken regularly for at least 7 consecutive days.

4. Hookworm Infections:
Hookworm infections are caused by Ancylostoma duodenale (ancylostomiasis) and Necator americanus (necatoriasis); they are a major cause of iron-deficiency anaemia in the tropics and sub-tropics. Ideally all cases of hookworm infection should be treated. However, when this is impracticable, priority should be given to women in second- and third-trimester of 165 NFI-2011

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pregnancy, children and debilitated patients. In hookworm, broad-spectrum anthelminthics are preferred wherever other nematode infections are endemic. Both mebendazole and albendazole are effective. In animal studies, albendazole and mebendazole have been found to be teratogenic. There is some evidence to suggest that the use of mebendazole in pregnancy is not associated with an increased incidence of adverse effects on the fetus. However, neither mebendazole nor albendazole should be used during the first trimester of pregnancy to treat nematode infections. Both drugs are contraindicated for the treatment of cestode infections in pregnancy. Levamisole is effective in the treatment of mixed Ascaris and hookworm infections and pyrantel has been highly effective in some community-based control programmes, although several doses are often needed to eliminate Necator americanus infection. Patients with iron-deficiency anaemia caused by hookworm infection require supplementary iron salts and should receive ferrous sulphate (200 mg daily for adults) for at least 3 months after the haemoglobin concentration of 12g/100 ml is obtained.

5. Strongyloidiasis:
Strongyloidiasis is an infection of the small intestine caused by Strongyloides stercoralis. All infected patients should be treated. Ivermectin in a single dose of 200 g/kg or 200 g/ kg/day on two consecutive days is the treatment of choice for chronic strongyloidiasis but it may not be available in all countries. Albendazole 400 mg once or twice daily for 3 days is well tolerated by both adults and children aged over 2 years and it may eradicate up to 80% of infections. Mebendazole has also been used but, to be effective, it must be administered for longer periods as it has a limited effect on larvae and hence the prevention of autoinfection.

6. Trichostrongyliasis:
Trichostrongyliasis is an infection of the small intestine caused by Trichostrongylus spp. In symptomatic trichostrongyliasis, a single dose of pyrantel (10 mg/kg) or albendazole (400 mg) is effective.

7. Trichuriasis:
Trichuriasis is an infection of the large intestine caused by Trichuris trichiura (whipworm). Chemotherapy is required whenever symptoms develop or when faecal samples are found to be heavily contaminated (up to 10,000 eggs per gram). A single dose of albendazole (400 mg) or mebendazole (500 mg) can be effective in mild to moderate infections; severe infecNFI-2011 166

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tions require a 3-day course.

Tissue Nematode Infections:

Tissue nematode infections include angiostrongyliasis, anisakiasis, cutaneous larva migrans, dracunculiasis, trichinellosis and visceral larva migrans.

1. Angiostrongyliasis:
Angiostrongyliasis is caused by infection with the larvae of the rat lungworm, Parastrongylus cantonensis (Angiostrongylus cantonensis). Symptomatic treatment pending spontaneous recovery is often all that is required.

2. Anisakiasis:
Anisakiasis is caused by infection with seafood containing larvae of Anisakis, Contracaecum or Pseudoterranova spp. In anisakiasis, anthelminthic treatment is rarely, necessary. Prevention is dependent upon informing communities of the hazards of eating raw or inadequately prepared salt-water fish; and early evisceration of fish after capture and freezing of seafood at -20C for at least 60 h before sale.

3. Cutaneous Larva Migrans:

Cutaneous larva migrans (creeping eruption) is caused by infection with larvae of animal hookworms, usually Ancylostoma braziliense and A. caninum which infect cats and dogs. Albendazole in a single dose of 400 mg is effective.

4. Dracunculiasis:
Dracunculiasis (dracontiasis, guinea-worm infection) is caused by infection with Dracunculus medinensis, acquired through drinking water containing larvae that develop in small freshwater crustaceans. Metronidazole (25 mg/kg daily for 10 days, with a daily max. of 750 mg for children) provides rapid symptomatic relief. It also weakens the anchorage of the worms in the subcutaneous tissues and they can then be removed by traction. However, since it has no effect on the larvae of pre-emergent worms, it does not immediately prevent transmission.

5. Trichinellosis:
Trichinellosis (trichinosis) is caused by infection with the larvae of Trichinella spiralis. Each case of confirmed or even suspected trichinellosis infection should be treated in order to prevent the continued production of larvae. In both adults and children, mebendazole (200 mg daily for 5 days), albendazole (400 mg daily for 3 days) and pyrantel (10 mg/kg daily for 5 days) are all effective. Prednisolone (40-60 mg daily) may be needed to alleviate the allergic and inflammatory symptoms. 167 NFI-2011

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6. Visceral Larva Migrans:

Visceral larva migrans (toxocariasis) is caused by infection with the larval forms of Toxocara canis and less commonly, T. cati (which infect dogs and cats). Treatment should be reserved for symptomatic infections. A 3 week oral course of diethylcarbamazine kills the larvae and arrests the disease, but established lesions are irreversible. To reduce the intensity of allergic reactions induced by dying larvae, dosage is commonly commenced at 1 mg/kg twice daily and raised progressively to 3 mg/kg twice daily (adults and children). Ocular larva migrans occurs when larvae invade the eye, causing a granuloma which may result in blindness. In order to suppress allergic inflammatory responses in patients with ophthalmic lesions, prednisolone should be administered concurrently, either topically or systemically.

Albendazole*
Pregnancy Category-C Indications Schedule H Echinococcus multilocularis and E. granulosus infections prior to or not amenable to surgery; neurocysticercosis; nematode infections; filariasis; ascariasis, hookworm infections, strongyloidiasis, enterobiasis, trichuriasis, trichostrongyliasis and capillariasis; cestode infections; tissue nematode infections. CHEWABLE/PLAIN TABLET 150, 200, 400 mg & 1.5g; CAPSULE 400 mg; ORAL SUSPENSION 200 mg/5 ml; SyRUP 200 mg/5 ml; DROPS 10 ml (200 mg/ml) Oral
Adult and child above 2 years- 400 mg daily

Availability

Dose

as a single dose.

Strongyloidiasis, taeniasis and H. nana infection: 400 mg once daily is given for 3 consecutive days. Hydatid disease: 400 mg twice daily with meals for 28 days (therapy may be repeated after 14 days in three cycles).
Child- 1 to 2 years: 200 mg as a single dose.

Contraindications

Pregnancy, adequate measures must be taken for non-hormonal contraceptive during and one month after therapy; hypersensitivity. Pregnancy (see notes above and Appendix 7c); liver impairment, increased intracranial pressure; seizures; monitor blood count and liver function.

Precautions

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Adverse Effects

Gastrointestinal discomfort; headache; adverse effects associated with use in cestode infections; reversible alopecia; leucopenia, neurocystecercosis; Stevens Johnson syndrome. Store protected from light.

Storage

Mebendazole
Pregnancy Category-C Indications Schedule H Echinococcus granulosus and E. multilocularis infections before surgery or not amenable to surgery; nematode infections. TABLET 100 mg; ORAL SUSPENSION 100 mg/5 ml. Oral
Adult and child over 2 years- Threadworm

Availability Dose

infection: 100 mg single dose. If re-infection occurs second dose may be needed after 2 weeks. Whip worm, roundworm and hookworm infection: 100 mg twice daily for 3 days. Pregnancy; lactation; hypersensitivity; patients with CNS disorders. Pregnancy (Appendix 7c; see also notes above); lactation; interactions (Appendix 6c, 6d); expulsion of ascaris from mouth or nose; monitor blood count or hepatic function. Gastrointestinal disturbances; headache and dizziness; adverse effects associated with use in cestode infections; abdominal pain, diarrhoea; rashes, urticaria, angioedema. Store protected from light and moisture.

Contraindications Precautions

Adverse Effects

Storage

Niclosamide
Pregnancy Category-B Indications Availability Dose Schedule H Taenia saginata, T. solium, Hymenolepis nana and Diphyllobothrium latum infections. TABLETS 500 mg and 1g. Oral
Adult- 1g (2 tablets) chewed and swallowed with water on empty stomach. Followed by another dose of 1g one h later. Brisk purgative after 2 h of last dose is recommended.

H. nana infection: 2g daily after food on first day thereafter 1g for next 6 days.

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Contraindications

Hypersensitivity; purgative must be given after two h to clear bowel since ova in dead segments are not cleared without purgative. Infection may recur if purgative is not given. Chronic constipation (restore regular bowel movement before treatment); give antiemetic before treatment; not effective against larval worms; pregnancy (Appendix 7c). Nausea; retching; abdominal pain; lightheadedness; pruritus; anorexia, emesis, perianal itching. Store protected from light and moisture.

Precautions

Adverse Effects

Storage

Pyrantel Pamoate
Pregnancy Category-C Indications Schedule H Ascariasis; hookworm infections; enterobiasis; trichostrongyliasis; tissue nematode infection. TABLET 250 mg; ORAL SUSPENSION 250 mg/ml. Oral 11 mg/kg (max 1g) in a single dose (given for 2 consecutive days in case of heavy hookworm infestation). Contraindications Precautions Hepatic diseases. Pregnancy (Appendix 7c; lactation; liver disease (reduce dose); severe malnutrition, anaemia, concurrent administration with piperazine. Mild gastrointestinal disturbances; headache; dizziness; drowsiness; insomnia; rash and elevated liver enzymes. Store protected from light at temperature not exceeding 30C.

Availability Dose

Adverse Effects

Storage

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9.6 Anti-Leishmaniasis Drugs

Leishmaniasis is caused by the parasitic protozoa Leishmania. It can be categorized as visceral, cutaneous or mucocutaneous. It may be a self-limiting localized skin lesion but may range from this to disseminated progressive disease. In endemic areas there is usually a reservoir of disease in a mammalian host and the usual vectors are sandflies.

Visceral Leishmaniasis:
Visceral leishmaniasis (kala-azar) is caused by Leishmania donovani and L. infantum (Old World) and by L. chagasi (New World) and it is usually responsive initially to the pentavalent antimony compounds, meglumine antimoniate or Sodium stibogluconate. Both dosage and duration of treatment need to be adjusted according to the clinical response. Patients are considered to be clinically cured when no parasites are detected in splenic or bone marrow aspirates. However, biopsies should be repeated after 3 and 12 months since relapse is frequent. Antimonials combined with allopurinol, pentamidine isothionate and amphotericin B have been used with success in patients in relapse who have become unresponsive to antimonials alone.

Cutaneous Leishmaniasis:
Cutaneous leishmaniasis comprises two conditions. The Old World variety is caused by L. tropica, L. major, L. infantum and L. aethiopica. The New World variety is caused by L. amazonensis, L. mexicana, L. peruviana, L. guyanensis, L. panamensis and L. braziliensis. These conditions are characterized by a cell-mediated reaction of varying intensity at the site of inoculation. The New World variety tends to be more severe and slower to heal. Infections caused by L. major, L. mexicana, L. tropica and L. peruviana, are responsive to intralesional injections of antimonial compounds. Mild lesions can often be left to heal spontaneously. However, it is preferable to treat L. tropica infections with a view to reducing transmission since humans seem to be the only host. When the lesion is inflamed or ulcerated or when obstruction of lymphatic drainage or destruction of cartilage creates a risk of serious disfigurement or disability, antimonials should be administered systemically as well as locally. Infections due to L. braziliensis and the less common L. panamensis should be treated with antimonials because of the risk of mucosal involvement. L. aethiopica is less responsive at conventional doses and the sores should be left to heal spontaneously if there is no evidence of diffuse cutaneous involvement. L. 171 NFI-2011

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guyanensis infections should be treated with pentamidine

Mucocutaneous Leishmaniasis:
Mucocutaneous leishmaniasis is caused by L. braziliensis and L. panamensis. In this form of the disease the primary lesions do not heal and spread to the mucosa may occur. It usually responds to antimonials and, when relapses occur, more extended courses of treatment are often successful. Patients who still fail to respond should receive amphotericin B or pentamidine isothionate, although neither treatment is highly satisfactory. Because of resistance to antimonials, L. aethiopica infections should be treated with pentamidine from the outset until complete healing occurs. Emergency use of corticosteroids may be needed to control pharyngeal or tracheal oedema produced by severe inflammation resulting from antigens liberated from dead parasites during the early phase of treatment. Antibiotics may also be needed to treat secondary infections and plastic surgery offers the only means of ameliorating disfiguring scars.

Diffuse Cutaneous Leishmaniasis:

Diffuse cutaneous leishmaniasis usually occurs following infection with L. amazonensis, L. aethiopica or L. mexicana and is usually treated with antimonial compounds, but relapses must be expected and repeated courses of pentamidine isothionate may be needed until clinical immunity is established.

Miltefosine
Pregnancy Category-X Indications Schedule H As directly observed therapy (DOT) of visceral Leishmaniasis caused by Leishmania donovani. CAPSULES 10 mg, 50 mg Oral Adult- (>12 years): Weighing >25 kg: 100 mg/day, twice a day, after meals for 28 days. <25 kg: 50 mg/day, after meals for 28 days Child (2-11 years): 2.5 mg/kg daily after meals for 28 days, i.e., 50 mg once daily. Contraindications Children below 2 years, patients with HIV, newborns, pregnancy (Appendix 7C) and lactation.

Availability Dose

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Precautions

Avoid contact with eyes, kidney or liver impairment, may impair ability to drive or operate machinery. Nausea and vomiting, GI irritation, diarrhoea, constipation, ocular, hepatic, renal toxicity, skin rash, leukocytosis, thrombocytosis Store in a cool place, protected from light and moisture.

Adverse Effects

Storage

Pentamidine*
Pregnancy Category-C Indications Availability Dose Schedule H Leishmaniasis; African trypanosomiasis; Pneumocystis carinii pneumonia. INJECTION 200 and 300 mg Vials. Deep intramuscular injection. 3 to 4 mg/kg body weight on alternate days to a max. of 10 injection. Course may be repeated if necessary. Contraindications Precautions Severe renal impairment. Risk of severe hypotension following administration (establish baseline blood pressure and administer with patient lying down); monitor blood pressure during administration and treatment period; hypertension; hypoglycaemia or hyperglycaemia; hepatic impairment; leukopenia, thrombocytopenia, anaemia; immunodeficiency-if acute deterioration in bone marrow, renal or pancreatic function, interrupt or discontinue treatment; renal impairment; pregnancy-in potentially fatal visceral leishmaniasis, pregnancy (Appendix 7c); lactation (Appendix 7b); history of asthma. Nephrotoxicity; acute hypotension-with dizziness, headache, breathlessness; tachycardia and syncope following rapid intravenous injection; hypoglycaemiamay be followed by hyperglycaemia and type I diabetes mellitus; pancreatitis; also hypocalcaemia, gastrointestinal disturbances; confusion, hallucinations; arrhythmias; thrombocytopenia, leukopenia, abnormal liver function tests; hyperkalaemia; rash, Stevens-Johnson syndrome, reported; pain, local induration, sterile abscess and muscle necrosis at injection site; night sweat, diarrhoea, nausea, anaemia, wheezing, bad taste, anxiety, insomnia, miscarriage, erythema. Store protected from moisture in a single dose container.

Adverse Effects

Storage

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Sodium Stibogluconate*
Indications Availability Dose Leishmaniasis/Kala-azar. INJECTION vial 30 ml (0.33g equivalent to total antimony 100 mg/ml). 4 to 6g for full course. Slow intravenous infusion 20 mg/kg/day. Contraindications Precautions Severe kidney disorders; lactation. Provide protein-rich diet throughout treatment and, if possible, correct iron and other nutritional deficiencies; renal and hepatic impairment; monitor cardiac, renal and hepatic function-reduce dose or withdraw treatment if abnormalities occur; pregnancyin potentially fatal visceral leishmaniasis, treat without delay; intravenous injections must be given slowly over 5 min (to reduce risk of local thrombosis) and stopped if coughing or substernal pain; mucocutaneous disease (see below); treat intercurrent infection (for example pneumonia); lactation; ECG monitoring. Successful treatment of mucocutaneous leishmaniasis may induce severe inflammation around lesions (may be life-threatening if pharyngeal or tracheal involvement)-may require corticosteroids. Adverse Effects Anorexia, nausea, vomiting, abdominal pain, ECG changes (possibly requiring dose reduction or withdrawal), headache, lethargy, myalgia; raised liver enzymes; renal function impairment; coughing and substernal pain (see Precautions); rarely, anaphylaxis, fever, sweating, flushing, vertigo, bleeding from nose or gum, jaundice, rash; pain and thrombosis on intravenous administration; pain on intramuscular injection; phlebotoxicity, metallic taste in mouth, dizziness. Store protected from moisture.

Storage

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9.7 Antimalarial Drugs

Human malaria, which is transmitted by female anopheline mosquitoes (and rarely, by congenital transmission, transfusion of infected blood or use of contaminated syringes among drug addicts), is caused by four species of plasmodial parasites. Plasmodium vivax is the most extensively distributed and causes much debilitating disease. P. falciparum is also widespread and causes the most severe infections which are responsible for nearly all malaria-related deaths. P. ovale is mainly confined to Africa and is less prevalent, while P. malariae, which causes the least severe but most persistent infections, also occurs widely. Certain tissue forms of P. vivax and P. ovale which persist in the liver for many months and even years are responsible for the relapses characteristic of malaria. Such latent forms are not generated by P. falciparum or P. malariae. Recrudescence of these infections results from persistent blood forms in inadequately treated or untreated patients.

Treatment of Malaria:
Blood schizonticides, which suppress malaria by destroying the asexual blood forms of the parasites, are the mainstay of the treatment of acute malaria and some are used for prophylaxis. They include the 4-aminoquinolines (example amodiaquine and chloroquine), the related arylaminoalcohols (example mefloquine and quinine) and artemisinin and its derivatives (example artemether and artesunate). Blood schizonticides are not active against intrahepatic forms and therefore they do not eliminate infections by P. vivax and P. ovale. Some antimetabolites act synergistically when given in combination. For example, pyrimethamine in combination with a sulfonamide (sulfadoxine) or sulfone and some antibiotics (for example doxycycline) are blood schizonticides. Because they act more slowly, these substances are of little value when used alone. The tetracyclines are used primarily as adjuncts to quinine where multiple-drug-resistant P. falciparum is prevalent. Chloroquine, a rapidly acting schizonticide, is well tolerated, safe and inexpensive. It should be used to treat malaria wherever the parasites remain susceptible. P. malariae and P. ovale remain fully sensitive to chloroquine. A 3-day course of chloroquine by mouth is sufficient to eliminate susceptible P. falciparum infections because effective plasma-chloroquine concentration is sustained for several weeks. If subsequent relapse occurs in P. ovale and P. vivax infections primaquine should be administered, after a second course of chloroquine, to eliminate the intrahepatic infection. 175 NFI-2011

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Amodiaquine is an alternative to chloroquine for the treatment of uncomplicated P. falciparum infection; but crossresistance with chloroquine exists in some areas. It should preferably be used as part of combination therapy with other antimalarials, for example artesunate. Hepatitis and blood disorders were reported when amodiaquine was used for prophylaxis of malaria; patients should be told how to recognise the symptoms of these conditions and advised to seek medical help if they occur. The combination of sulfadoxine with pyrimethamine is recommended for the treatment of malaria only in areas of high chloroquine resistance. A single dose of sulfadoxine with pyrimethamine is usually sufficient to eliminate infection; quinine should also be given for 3 days in patients in whom quinine may accelerate reduction of parasitaemia and in those at risk of fulminating disease. Because sulfonamides are associated with a risk of haemolysis and methaemoglobinaemia in the newborn, quinine is preferred to treat chloroquine-resistant malaria during pregnancy. Mefloquine is generally well tolerated, although, some adverse effects have been reported (see notes). However, because of the danger of the emergence of mefloquine-resistant strains of P. falciparum and because of its potential toxicity, it should be used only following either microscopic or careful clinical diagnosis of P. falciparum infections that are known or strongly suspected to be resistant to chloroquine or sulfadoxine with pyrimethamine. Quinine, given orally, should be reserved for P. falciparum infections likely to be unresponsive to other drugs. Doxycycline, which is an effective oral schizonticide, should be given in combination with quinine except in pregnant women and children under 8 years. In multi-drug resistant malaria, preparations of artemisinin or its derivatives (artemether or artesunate) offer the only prospect of cure. They should not be used in the first trimester of pregnancy. For the treatment of multi-drug resistant falciparum malaria oral artesunate may be an effective antimalarial. It should always be given in combination with mefloquine. Parenteral artemether or artesunate, whose use is restricted, are effective alternatives to quinine for the treatment of severe falciparum malaria and are preferred in areas where decreased efficacy of quinine has been documented. To ensure radical cure following parenteral treatment with artemether or oral treatment with artesunate, a full therapeutic dose of mefloquine should be given. A fixed-dose oral formulation of artemether with lumefantrine has recently become available and is recommended for the treatment of uncomplicated falciparum malaria in areas with significant resistance. The combination is not for use in pregnancy or lactation. NFI-2011 176

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Prophylaxis Against Malaria:

No drug regimen gives assured protection to everybody and indiscriminate use of antimalarials can increase the risk of inducing resistance. Chloroquine, which is usually well tolerated at the required dosage, is preferred where P. falciparum remains fully sensitive. The combination of proguanil with chloroquine may overcome mild chloroquine resistance. Chloroquine must be started 1 week before exposure and be continued in pregnant women until after delivery and for at least 4 weeks after the last risk of exposure in the case of non-immune individuals. This is sufficient to ensure elimination of P. falciparum and P. malariae, but not of P. vivax and P. ovale, whose residual hepatic forms survive. Mefloquine may be used for prophylaxis in areas of high risk or where multiple-drug resistance has been reported. Where possible prophylaxis should be started 2-3 weeks before travel to enable any adverse reactions to be identified before exposure (over three-quarters of adverse reactions occur by the third dose) and should be continued for 4 weeks after last exposure. Mefloquine may be used for prophylaxis during the second and third trimesters. It should be used in early pregnancy only if alternative drugs are either not available or unlikely to be effective and when it is impracticable for the woman to leave the endemic area. Proguanil, a predominantly tissue schizonticide with little blood schizonticidal activity, is a causal prophylactic agent since it is active against pre-erythrocytic intrahepatic forms, particularly of P. falciparum. The latent persistent liver forms of P. ovale and P. vivax are unresponsive. However, there is evidence that it may be effective against P. vivax only immediately after the initial infection. P. falciparum resistance to proguanil or related compounds may occur in malaria endemic areas and particularly where it has been employed in mass prophylaxis. Proguanil is used for prophylaxis with chloroquine in areas where there is resistance to chloroquine but a low risk of infection as it may give some protection against and may alleviate symptoms if an attack occurs. Proguanil and chloroquine may also be used prophylactically in areas of high risk or multi-drug resistance as a second choice where mefloquine is not appropriate. There is no evidence that proguanil is harmful in prophylactic doses during pregnancy. Because of the vulnerablility of pregnant women to falciparum malaria, it should be used at full prophylactic dosage wherever the disease is prevalent and likely to be responsive to proguanil, if chloroquine is not available or with chloroquine, if the latter alone is unlikely to be effective. 177 NFI-2011

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9.7.1 Drugs for Prophylaxis Chloroquine* (Refer Page No. 383)

Pregnancy Category-D Indications Treatment of acute malaria caused by P. malariae and susceptible P. falciparum; P. vivax and P. ovale (followed by primaquine to eliminate intrahepatic forms); prophylaxis of malaria for pregnant women and nonimmune individuals at risk; rheumatic disorders. TABLETS 250 and 500 mg; INJECTION 10 and 30 ml (40 mg/ml); SUSPENSION 50 mg/ml. Oral Adult- Immediately 600 mg, after 6 h 300 mg followed by 300 mg daily for 2 days. Child- 10 mg/kg body weight followed by 5 mg/kg body weight after 6 h, thereafter once a day for 2 days. Intramuscular injection Adult- 10 ml followed by 5 ml after 6 h. Thereafter 5 ml daily for two days. Child- 5 mg/kg body weight administered every 12 h followed by oral therapy. Contraindications Severe haematologic distress or gastrointestinal distress; eye dysfunction; liver disease. If patient continues to deteriorate after chloroquine-suspect resistance and administer quinine intravenously as emergency measure; hepatic impairment; renal impairment (Appendix 7d); pregnancy (but in malaria, benefit considered to outweigh risk; Appendix 7c); lactation (Appendix 7b); may exacerbate psoriasis; neurological disorders (avoid for prophylaxis if history of epilepsy); may aggravate myasthenia gravis; severe gastrointestinal disorders; G-6-PD deficiency; avoid concurrent therapy with hepatotoxic drugs; interactions (Appendix 6c, 6d).

Availability Dose

Precautions

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Adverse Effects

Headache, gastrointestinal disturbances; also convulsions; visual disturbances (retinopathy associated with long-term, high dose therapy or inappropriate selfmedication); depigmentation or loss of hair; rashes; pruritus-may become intolerable; bone-marrow suppression; hypersensitivity reactions such as urticaria and angioedema; atrioventricular block (may be result of inappropriate self-medication); porphyria and psoriasis in susceptible individuals. Store protected from light.

Storage

Doxycycline* (Refer Page No. 134)

Pregnancy Category-D Indications Schedule H Supplement to quinine in treatment of multiple-medicine resistant P. falciparum malaria (where quinine resistance, in cases of hypersensitivity to sulfonamides); shortterm prophylaxis of multiple-medicine resistant P. falciparum malaria; bacterial infections. CAPSULES/TABLETS 50, 100, 150 and 200 mg; SyRUP 25 mg/5 ml. Oral Adult- 200 mg on the first day then 100 mg daily. Severe infections including refractory urinary tract infection: 200 mg daily can be used. Early syphilis: 100 mg twice daily for 14 days and for latent syphilis 200 mg twice daily for 28 days is used. Uncomplicated genital Chlamydia, nongonococcal urethritis: 100 mg twice daily for 7 days. Child- Only if alternate antibacterial cannot be given 5 mg/kg body weight in two divided doses. Contraindications Pregnancy (Appendix 7c); children under 8 years; porphyria; systemic lupus erythematosus; prolonged exposure to sunlight, severe hepatic dysfunction. Avoid exposure to sunlight or sunlampsphotosensitivity reported; renal impairment; hepatic impairment (Appendix 7a); lactation (Appendix 7b); interactions (Appendix 6c).

Availability Dose

Precautions

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Adverse Effects

Gastrointestinal disturbances; anorexia; erythema (discontinue treatment); photosensitivity; hypersensitivity reactions; headache and visual disturbances; hepatotoxicity, blood disorders, pancreatitis and antibiotic-associated colitis reported; staining of growing teeth and occasional dental hypoplasia; nasopharyngitis, reduced tibular growth rate, diarrhoea, sinusitis. Store protected from light and moisture at a temperature not exceeding 30C.

Storage

Primaquine*
Indications Radical cure of P. vivax and P. ovale malaria (after chloroquine therapy to eradicate erythrocytic forms), elimination of gametocytes of P. Falciparum, malaria prophylaxis. TABLETS 2.5, 7.5 and 15 mg. Radical treatment Adult- 15 mg daily for 14 days, may be increased to higher dose. Child- 250 g/kg daily for 14 days. Malaria prophylaxis Adult- 30 mg once daily; Child- 0.5 mg/kg once daily (to be started 1-2 days before travel and continue for 7 days after departure from malaria endemic area). Gametocidal treatment of P. falciparum malaria (after standard blood schizontocide therapy). Adult and Child- 50050 g/kg as a single dose. Contraindications Precautions Hypersensitivity, granulocytopenia, pregnancy, lactation, children below 1 year. Patients with history of granulocytosis/ methaemoglobinaemia, G-6-PD deficiency, monitor Hb levels, blood counts routinely and withdraw if signs of haemolysis or methaemoglobinaemia occur; lactation (Appendix7b). Nausea, vomiting, abdominal cramps, haemolytic anaemia in G-6-PD deficient patients; rarely, leukopenia, agranulocytosis, leukocytosis, methaemoglobinaemia and cardiac arrythmias.

Availability Dose

Adverse effects

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Storage

Store protected from moisture.

Proguanil
Pregnancy Category-B Indications Availability Dose Schedule H With chloroquine, prophylaxis of malaria in areas of low resistance. TABLET 100 mg. Oral Prophylaxis Adult- Preferably 200 mg once daily, start 1 to 2 days before entering endemic area and continue for 4 weeks after leaving. Child- (11-20 kg) - 25 mg once daily; (21-30 kg)- 50 mg once daily; (31-40 kg)- 75 mg once daily; more than 40 kg- 100 mg once daily. Treatment Adult and child- over 40 kg; 100 mg once daily. Child- Up to 1 year: 25 mg; 1 to 4 years; 50 mg; 5 to 8 years: 100 mg; 9 to 14 years: 150 mg; above 14 years: 200 mg. Contraindications Precautions Use in areas of known resistance to either proguanil or pyrimethamine. Renal impairment; pregnancy (folate supplements required, Appendix 7c); lactation. Mild gastric intolerance, diarrhoea; occasional mouth ulcers and stomatitis; skin reactions and hair loss reported; rarely, hypersensitivity reactions such as urticaria and angioedema. Store protected from light and moisture.

Adverse Effects

Storage

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9.7.2 Drugs for Curative Treatment Amodiaquine

Schedule H Indications Availability Dose Treatment of uncomplicated malaria caused by P. falciparum. TABLET 200 mg; SUSPENSION 50 mg/5 ml. Oral
Adult- Prophylaxis: 300 mg once weekly, start one week before entering endemic area and continue for 4 weeks after leaving. Infant- up to 12 weeks, body weight under 6

kg: 37.5 mg once weekly, 1 year body weight 6 to 10 kg: 75 mg once weekly.

Child- 1 to 4 years, body weight 10 to 16 kg: 11 to 12.5 mg once weekly. 4 to 8 years: body weight 16 to 25 kg: 150 mg once a week. 8 to 13 years, body weight over 45 kg: adult dose is used.

Contraindications Precautions

Hepatic impairment (Appendix 7a); blood disorders, retinopathy. Pregnancy and lactation; G-6-PD deficiency; avoid concurrent therapy with hepatotoxic drugs. Patients and their caretakers should be told how to recognize the signs of blood disorders and advised to seek medical attention as soon as possible if symptoms such as fever, sore throat, rash, mouth ulcers, purpura, bruising or bleeding develop. They should also be told how to recognize signs of hepatitis and advised to seek medical attention if symptoms such as anorexia, abnormal weight loss, asthenia, abdominal pains, fever, nausea or vomiting develop.

Adverse Effects

Blood disorders including leukopenia and agranulocytosis; hepatitis; gastrointestinal disturbances, visual disturbances (retinopathy associated with long-term, high-dose therapy); rarely, rash, pruritus, skin pigmentation, neuromyopathy.

Arteether
Pregnancy Category-C Indications Availability Schedule H Complicated falciparum malaria; chloroquine resistant malaria; cerebral malaria. INJECTION 2 ml ampoule (150 mg/2 ml).

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(Arteether is an ethyl derivative of dihydroartimisinin. It is a mixture of and arteether in a 30:70 ratio) Dose Contraindications Adverse reactions Storage Adult- 150 mg daily i.m. injection, once daily for 3 consecutive days. Hypersensitivity to artemisinin derivatives; preganacy (Appendix 7c). It is clinically very well tolerated without any significant side effects; neurological or biochemical. Store protected from light in tamper evident container so as to avoid contamination by micro-organisms.

Artemether
Pregnancy Category-C Indications Availability Dose Schedule H Treatment of severe P. falciparum malaria in areas where evidence is there that quinine is ineffective; multi drug resistant malaria. CAPSULE 40 mg; INJECTION 1 ml ampoule (80 mg/ml, 160 mg/2 ml). Oral Adult- 160 mg in two divided doses on first day followed by 80 mg once a day for next four days. Intramuscular injection Adult- 80 mg twice a day for 3 days. Child- 1.6 mg/kg body weight twice a day followed by 1.6 mg/kg body weight once a day for 4 days, alternatively 1.6 mg/kg body weight twice a day for 3 days. Contraindications Precautions First trimester of pregnancy (Appendix 7c); hypersensitivity. Electrolyte disturbances, concomitant use with other drugs known to cause QT-interval prolongation; hepatic impairment; renal impairment; monitor patients unable to take food (greater risk of recrudescence); interactions (Appendix 6c); lactation (Appendix 7b). Dizziness may impair ability to perform skilled tasks, for example operating machinery, driving.

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Adverse Effects

Headache, nausea, vomiting, abdominal pain, diarrhoea; dizziness, tinnitus, neutropenia, elevated liver enzyme values; cardiotoxicity (after high doses); neurotoxicity-in animal studies; decrease in reticulicyte count. Store protected from light and moisture.

Storage

Artesunate*
Pregnancy Category-C Indications Availability Dose Schedule H Treatment of uncomplicated P. falciparum malaria in areas of multiple drug resistance. TABLET 25, 50 & 60 mg; INJECTION 50, 60, 1000 & 2000 mg/vial. Oral Adult- total oral dose 600 mg can be divided into two 50 mg tablets twice a day on first day thereafter 50 mg twice a day for next 4 days. Child- half adult dose. Intramuscular injection 60 mg twice daily. Contraindications Precautions First trimester of pregnancy (Appendix 7c); hypersensitivity. Risk of recurrence if used alone in nonimmune patients; hepatic/renal insufficiency, pregnancy (Appendix 7c), lactation, paediatrics. Dizziness may impair ability to perform skilled tasks, for example operating machinery, driving. Adverse Effects Headache, nausea, vomiting, abdominal pain, diarrhoea, dizziness, tinnitus, neutropenia, elevated liver enzyme values; ECG abnormalities, including prolongation of QT interval; temporary suppression of reticulocyte response and induction of blackwater fever reported; neurotoxicity-in animal studies. Store protected from light and moisture.

Storage

Chloroquine* (Refer Page No. 178 and 383) Doxycycline* (Refer Page No. 134 and 179)

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Quinine*
Pregnancy Category-X Indications Availability Multiple drug resistant P. falciparum malaria. TABLETS 100, 150, 300 and 600 mg; SUSPENSION 150 mg/5 ml; INJECTION 1 and 2 ml ampoule (300 mg/ml). Oral Adult- 300 to 600 mg every 8 h in divided doses for 5 to 7 days. Child- 25 mg/kg body weight every 8 h in divided doses for 5 to 7days. Intravenous infusion for patients unable to swallow tablets Loading dose 900 mg to 1.4g infused over 4 h, then 300 to 600 mg every 8 h infused over 4 h. Contraindications Haemoglobinuria; optic neuritis; tinnitus; quinine resistant falciparum, pregnancy (Appendix 7c), lactation, prolonged QT interval. Atrial fibrillation, conduction defects, heart block; monitor for signs of cardiac toxicity and blood glucose levels (with intravenous use); renal impairment (Appendix 7d); G-6PD deficiency; may aggravate myasthenia gravis; interactions (Appendix 6d). Cinchonism (tinnitus, headache, blurred vision, temporary blindness, altered auditory acuity, nausea, diarrhoea, hot and flushed skin, rashes, confusion); hypersensitivity reactions including angioedema; rarely, haemorrhage and asthma; hypoglycaemia (especially after parenteral administration); renal damage (culminating in acute renal failure and anuria); blood disorders; cardiovascular, gastrointestinal and CNS effects; very toxic in overdosage-immediate medical attention required; acute haemolytic anaemia. Store protected from light.

Dose

Precautions

Adverse Effects

Storage

Sulfadoxine + Pyrimethamine*
Pregnancy Category-C Indications Schedule H Treatment of malaria due to susceptible P. falciparum in areas of high chloroquine resistance and in patients who have not responded to chloroquine; additionally quinine may be given for 3 days.

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Availability

TABLETS Sulfadoxine 500 mg + Pyrimethamine 25 mg; SUSPENSION 5 ml (500 mg sulfadoxine+25 mg pyrimethamine). Oral Adult- Prophylaxis: one tablet once a week. Treatment: 2 tablets in single dose. Child- Under 4 years: half a tablet. 4 to 8 years: one tablet. 9 to 14 years: two tablets single dose. Prophylaxis: Under 4 years 1/4th tablet. 4 to 8 years: half tablet. 9 to 14 years: 3/4th tablet once a week.

Dose

Contraindications

Hypersensitivity to sulfonamides or pyrimethamine; severe hepatic or renal impairment (except where no alternative treatment available); blood dyscrasias, neonates, megaloblastic anaemia and folate deficiency. Avoid in blood disorders-unless specialist supervision; discontinue immediately if blood disorder occurs; rash, sore throat, mouth ulcers, or shortness of breathwithdraw treatment; G-6-PD deficiency; predisposition to folate deficiency; hepatic impairment (Appendix 7a); pregnancy (Appendix 7c); lactation (Appendix 7b); interactions (Appendix 6c). Rashes, pruritus, slight hair loss; rarely, erythema multiforme (Stevens-Johnson syndrome) and toxic epidermal necrolysis; gastrointestinal disturbances including nausea, vomiting, stomatitis; rarely, hepatitis, leukopenia, thrombocytopenia, megaloblastic anaemia and purpurawithdraw treatment; fatigue, headache, fever, polyneuritis, also reported; pulmonary infiltrates such as eosinophilic or allergic alveolitis-if symptoms of cough or shortness of breath-withdraw treatment. Store protected from light and moisture.

Precautions

Adverse Effects

Storage

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9.8 Antimycobacterial Drugs

9.8.1 Antileprosy Drugs
Leprosy is a chronic mycobacterial infection due to Mycobacterium leprae, which is a slow-growing intracellular bacillus that infiltrates the skin, peripheral nerves, the nasal and other mucosa and the eyes; it affects people of all ages and both sexes. The incubation period between infection and appearance of leprosy is normally between 2 to 10 years, but may be up to 20 years. It is transmitted from person-to-person when bacilli are shed from the nose; most individuals have natural immunity and symptoms are suppressed. For treatment purposes patients may be classified as having paucibacillary (PB) or multibacillary (MB) leprosy. The 2 forms may be distinguished by skin smears, but facilities are not always available to process them and their reliability is often doubtful. In practice, most leprosy programmes classify and choose a regimen based on number of skin lesions; these are PB leprosy (1-5 skin lesions) and MB leprosy (more than 5 skin lesions). Drugs used in the treatment of leprosy should always be used in combination; this is essential to prevent the emergence of resistance. Rifampicin is now combined with dapsone to treat PB leprosy and rifampicin and clofazimine are now combined with dapsone to treat MB leprosy. The WHO Programme for the Elimination of Leprosy currently provides, free of charge, oral multidrug therapy in colour-coded blister packs (MDT blister packs) to improve patients adherence to treatment. Any patient with a positive skin smear should be treated with the MDT regimen for MB leprosy. The regimen for PB leprosy should never be given to a patient with MB leprosy. If diagnosis classification in a particular patient is not possible the MDT regimen for MB leprosy must be used. Lepra reactions are episodes of sudden increase in the activity of leprosy and are often accompanied by neuritis; reactions must always be treated promptly to prevent permanent nerve damage and disability. Leprosy multidrug therapy should continue during a lepra reaction without interruption. This reduces the frequency and severity of lepra reactions. Type 1 lepra reactions, or reversal reactions, are delayed hypersensitivity reactions and may occur in either PB or MB leprosy. If there is no nerve damage, type 1 reactions may be treated with analgesics such as acetylsalicylic acid or paracetamol. If there is nerve involvement corticosteroids, such as oral prednisolone should be used in addition to analgesics. The type 2 lepra reaction, also known as erythema nodosum 187 NFI-2011

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leprosum (ENL), is an antibody response to dead leprosy bacteria and occurs only in MB leprosy. Therapy for type 2 reactions may include analgesics, such as acetylsalicylic acid or paracetamol and a corticosteroid, such as oral prednisolone. In patients not responding to a corticosteroid, clofazimine may be used. Severe type 2 lepra reactions should be treated under medical supervision in hospital. If a patient does not respond to lepra reaction treatment within 6 weeks or seems to become worse, the patient must be sent immediately to the nearest specialist centre. Neuritis may occur during or independently of lepra reactions. It can be successfully treated with a 12-week course of oral prednisolone; if patients do not respond, specialist centre treatment is required.

Treatment Regimens:
The recommended regimen for paucibacillary leprosy in adults (50-70 kg) is rifampicin 600 mg once monthly and dapsone 100 mg daily. Children aged 10-14 years may be given rifampicin 450 mg once monthly and dapsone 50 mg daily. Appropriate dose adjustments are required for younger children. For example, dapsone 25 mg daily and rifampicin 300 mg once a month. Treatment is continued for 6 months for PB leprosy. The recommended regimen for MB leprosy in adults (50-70 kg) is rifampicin 600 mg and clofazimine 300 mg, both given once a month together with clofazimine 50 mg and dapsone 100 mg, both daily. Children aged 10-14 years may be given rifampicin 450 mg and clofazimine 150 mg, both once a month together with clofazimine 50 mg every other day and dapsone 50 mg daily. Appropriate dosage adjustments are required for younger children. For example, dapsone 25 mg daily, clofazimine 50 mg twice a week and clofazimine 100 mg and rifampicin 300 mg once a month. Treatment is continued for 12 months for MB leprosy. For patients who cannot take rifampicin because of allergy, other diseases, or rifampicin-resistant leprosy and for patients who refuse to take clofazimine, there are alternative regimens which incorporate ofloxacin and minocycline

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Clofazimine*
Pregnancy Category-C Indications Availability Dose Schedule H MB leprosy; type 2 lepra reactions. TABLETS 25, 50, 100 mg; CAPSULES 50 and 100 mg. Oral
Adult- 300 mg spread over a week. Sulfone

resistant cases: 600 mg weekly preferably after meal. Lepra reaction: 200 mg daily for 3 weeks or as required.

Child- 1 to 2 mg/kg body weight daily or 4 to

6 mg/kg body weight once a month.

Contraindications Precautions

Pregnancy (Appendix 7c), lactation, renal and hepatic impairment. Pre-existing gastrointestinal symptoms (reduce dose, increase dose interval or discontinue if symptoms develop during treatment); liver and renal impairment; may discolour soft contact lenses; paediatrics, elderly, interactions (Appendix 6d). Reversible discolouration of skin, hair, cornea, conjunctiva, tears, sweat, sputum, faeces and urine; dose-related gastrointestinal symptoms including pain, nausea, vomiting and diarrhoea; severe mucosal and submucosal oedema, with prolonged treatment with high doses-may be severe enough to cause subacute small-bowel obstruction (see also Precautions); pruritus, ichthyosis, elevated blood sugar, diminished vision, dizziness, eosinophillic enteropathy. Store protected from moisture.

Adverse Effects

Storage

Dapsone*
Pregnancy Category-C Indications Availability Dose Schedule H PB and MB leprosy; acne vulgaris, dermatitis, pneumocystic pneumonia. TABLETS 25, 50 and 100 mg; GEL 5% w/w. Oral

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Adult- Leprosy: 50 to 100 mg daily depending upon body weight. Dermatitis herpetiformis: start with 50 mg daily and increase up to 400 mg till full response is obtained; dose reduced to minimum maintenance level as soon as possible. Child- 1 to 2 mg/kg body weight as minimum dose to start with, increased weekly so that at the end of 7th week patient is receiving max. dose.

Contraindications Precautions

Hypersensitivity to sulfones; severe anaemia; porphyria. Anaemia (treat severe anaemia before therapy and monitor blood counts during treatment); susceptibility to haemolysis including G-6-PD deficiency (including lactation affected infants); lactation (Appendix 7b); porphyria; interactions (Appendix 6c); hyperbilirubinemia, methaemoglobinemia; renal impairment (Appendix 7d); pregnancy (Appendix 7c). On long-term treatment patients and their caretakers should be told how to recognize blood disorders and advised to seek immediate medical attention if symptoms such as fever, sore throat, rash, mouth ulcers, purpura, bruising or bleeding develop.

Adverse Effects

Haemolysis and methaemoglobinaemia; allergic dermatitis (rarely, including toxic epidermal necrolysis and the Stevens-Johnson syndrome); rarely, hepatitis and agranulocytosis; dapsone syndrome resembling mononucleosis-rare hypersensitivity reaction with symptoms including rash, fever, jaundice and eosinophilia; gastrointestinal irritation; tachycardia, headache, nervousness, insomnia, blurred vision, paraesthesia, reversible peripheral neuropathy and psychoses reported; increase in reticulocytes, vertigo; pancreatitis; renal papillary necrosis; anorexia. Store protected from light.

Storage

Rifampicin* (Refer Page No. 200)

Pregnancy Category-C Indications Availability Schedule H PB leprosy; MB leprosy; tuberculosis. CAPSULES 150, 300, 450 and 600 mg; TABLETS 150, 300, 350, 450, 500, 600 and 750 mg; SyRUP 100 mg/5 ml.

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Dose

Oral Adult- 450 to 600 mg single dose before breakfast. Child- 10 to 20 mg/kg body weight daily.

Contraindications Precautions

Hypersensitivity; jaundice; patients with earlier drug induced liver disease. Reduce dose in hepatic impairment (Appendix 7a); liver function tests and blood counts required in liver disorders, alcohol dependency, elderly and on prolonged therapy; renal impairment (if dose above 600 mg daily); lactation; porphyria; discolours soft contact lenses; advise patients on oral contraceptives to use additional means; interactions (Appendix 6b, 6c, 6d); pregnancy (Appendix 7c).

Note: Resumption of rifampicin treatment after a long interval may cause serious immunological reactions, resulting in renal impairment, haemolysis, or thrombocytopenia-discontinue permanently if serious adverse effects occur Patients or their caretakers should be told how to recognize signs of liver disorders and advised to discontinue treatment and seek immediate medical attention if symptoms such as persistent nausea, vomiting, malaise or jaundice develop. Adverse Effects Severe gastrointestinal disturbances including anorexia, nausea, vomiting and diarrhoea (antibiotic-associated colitis reported); headache, drowsiness; rashes, fever, influenza-like syndrome and respiratory symptoms, collapse, shock, haemolytic anaemia, acute renal failure and thrombocytopenic purpura-m ore frequent with intermittent therapy; alterations of liver function-jaundice and potentially fatal hepatitis (dose-related, do not exceed max. daily dose of 600 mg); oedema, muscular weakness and myopathy, exfoliative dermatitis, toxic epidermal necrolysis, pemphigoid reactions, leukopenia, eosinophilia and menstrual disturbances; urine, tears, saliva and sputum coloured orange-red; cerebral haemorrhage, visual disturbances. Store protected from light and moisture.

Storage

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9.8.2 Antituberculosis Drugs

Tuberculosis is a chronic infectious disease caused primarily by Mycobacterium tuberculosis or sometimes by M. bovis. Infection is usually due to inhalation of infected droplet nuclei with the lung generally being the first organ affected, but the primary infection is usually asymptomatic. Infection and inflammatory responses resolve with the development of acquired immunity. Surviving bacteria may become dormant or in susceptible patients, progress to active primary disease; dormant organisms may produce disease and this often occurs if immune status is altered. Tuberculosis is the most prevalent infectious disease of adults and causes 26% of avoidable adult deaths in the developing world. More than 80% of tuberculosis cases are pulmonary (PTB). At least 30% of patients who are infected with HIV will also develop active tuberculosis. The increase in resistant strains and poor compliance of dosage regimen which may contribute to resistance and treatment failure has led to the development of regimens with directly supervised treatment. Directly observed treatment short-course (DOTS) therapy which lasts for 6 or 8 months, given under direct observation is one of the most important components of the WHO strategy against tuberculosis. Simplified drug regimens and intermittent therapy have been introduced to improve compliance. WHO does not generally recommend twice weekly regimens. If a patient receiving a twice weekly regimen misses a dose of tablets, the missed dose represents a bigger fraction of the total number of treatment doses than if the patient was receiving a three times weekly or daily dose regimen. Therefore, there is a greater risk of treatment failure with twice weekly regimens. Fixeddose combination tablets incorporating 2 or more drugs are also used to improve compliance and decrease medication errors; they should be used unless one of the components cannot be given because of resistance or intolerance. Modern short-course therapy is usually in 2 phases. The initial phase (2 months) involves the concurrent use of at least 3 drugs to reduce the bacterial population rapidly and prevent drug-resistant bacteria emerging. The second continuation phase (4-6 months) involves fewer drugs and is used to eliminate any remaining bacteria and prevent recurrence. Direct observation of therapy is considered essential to ensure compliance in the initial phase and also useful in the continuation phase if patients are receiving rifampicin. Five antituberculosis drugs, isoniazid, rifampicin, pyrazinamide, streptomycin (which are bactericidal) and ethambutol NFI-2011 192

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(which is bacteriostatic) are used in various combinations as part of WHO-recommended treatment regimens; thiacetazone is used only if ethambutol cannot be used. In supervised regimens change of drug regimen should be considered only if the patient fails to respond after 5 months of DOTS. Isoniazid, rifampicin and pyrazinamide are components of all antituberculosis drug regimens currently recommended by WHO. Unsupervised and alternative regimens as set out in the following tables may be administered as specified. Additional reserve antituberculosis drugs (amikacin, p-aminosalicylic acid, capreomycin, ciprofloxacin, cycloserine, ethionamide, kanamycin, levofloxacin and ofloxacin ) for the treatment of multidrug-resistant tuberculosis should be used in specialized centres adhering to WHO standards for TB control. Worldwide, an important predisposing cause of immunosuppression leading to tuberculosis is human immunodeficiency virus (HIV) infection; it increases susceptibility to primary infection and increases the reactivation rate of tuberculosis. Preventative antituberculosis therapy of such persons is recommended. Chemoprophylaxis with isoniazid can prevent the development of clinically apparent disease in persons in close contact with infectious patients and also prevent the reactivation of previously dormant disease in other persons at high risk particularly those who are immunodeficient. Where the disease remains highly prevalent routine immunization of infants within the first year of age with BCG vaccine is cost-effective. However, there is no evidence that BCG will protect children older than 15 years of age. Infants born to HIV-positive mothers should be vaccinated during the first year of life, provided they have no clinical signs suggestive of HIV. The tuberculin test has limited diagnostic value. A positive tuberculin test indicates previous exposure to mycobacterial antigens through infection with one of the tubercle bacilli, or BCG vaccination. The tuberculin test does not distinguish between tuberculosis and other mycobacterial infection, between active and quiescent disease, or between acquired infection and seroconversion induced by BCG vaccination.

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Recommended 6-Month Treatment Regimens for Tuberculosis1

Drug Isoniazid Rifampicin Pyrazinamide together with Streptomycin3 15 mg/kg daily or Ethambutol2 Isoniazid Rifampicin Pyrazinamide together with Streptomycin3 15 mg/kg 3 times weekly or Ethambutol
1

Initial phase (2 months) Continuation phase (4 months) 5 mg/kg daily 10 mg/kg daily 25 mg/kg daily 5 mg/kg daily 10 mg/kg daily

15 mg/kg daily 10 mg/kg 3 times weekly 10 mg/kg 3 times weekly 10 mg/kg 3 times weekly 10 mg/kg 3 times weekly 35 mg/kg 3 times weekly

30 mg/kg 3 times weekly

Unless otherwise indicated, doses are suitable for both adults and children

Not suitable for children

Recommended 8-month treatment regimen for tuberculosis1 Drug Initial phase (2 months) Isoniazid 5 mg/kg daily Rifampicin 10 mg/kg daily Pyrazinamide 25 mg/kg daily together with Ethambutol3 15 mg/kg daily or Streptomycin2 15 mg/kg daily
1

Continuation phase (6 months) 5 mg/kg daily

15 mg/kg daily4

Unless otherwise indicated, doses are suitable for both adults and children 2 Streptomycin always replaces ethambutol in meningeal TB 3 Not suitable for children under 5 years 4 Thiacetazone (2.5 mg/kg daily) may be used (only if ethambutol cannot be given) in combination with isoniazid in the continuation phase; risk of severe toxicity, particularly in HIVinfected individuals NFI-2011 194

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Category I: New pulmonary disease (smear-positive or smear-negative with extensive involvement of parenchyma), concomitant severe HIV disease and new severe extra-pulmonary disease Initial phase1 (antibacterials administered daily or 3 times weekly): isoniazid + rifampicin + pyrazinamide + ethambutol (or streptomycin) for 2 months Continuation phase1 (antibacterials administered daily or 3 times weekly): isoniazid + rifampicin for 4 months (or isoniazid + ethambutol for 6 months but less effective than isoniazid + rifampicin) Category II: Previously treated smear-positive pulmonary disease which has relapsed, or failed to respond, or if treatment was interrupted Initial phase1 (antibacterials administered daily or 3 times weekly): isoniazid + rifampicin + pyrazinamide + ethambutol + streptomycin for 2 months then: isoniazid + rifampicin + pyrazinamide + ethambutol for 1 month Continuation phase1 (antibacterials administered daily or 3 times weekly): isoniazid + rifampicin + ethambutol for 5 months Category III: New smear-negative pulmonary disease (other than in Category I) and less severe extra-pulmonary disease Initial phase1 (antibacterials administered daily or 3 times weekly): isoniazid + rifampicin + pyrazinamide + ethambutol3 for 2 months Continuation phase1 (antibacterials administered daily or 3 times weekly): isoniazid + rifampicin for 4 months (or isoniazid + ethambutol for 6 months but less effective than isoniazid + rifampicin) Category IV: Chronic and multi-drug-resistant tuberculosis (MDR-TB) (smear-positive despite supervised re-treatment)4 specially designed standardized or individualized regimens recommended Treatment regimens by category of tuberculosis diagnosis 1 Drug intake should be directly observed in patients who are smear positive during the initial phase and always when rifampicin is given 2 Drug sensitivity testing recommended before prescribing Category II treatment in failure cases; patients with MDR-TB should be prescribed Category IV regimen 3 Omit ethambutol in initial phase if disease is not complicated by cavitary disease or concomitant HIV disease and in patients infected with fully susceptible bacilli or young children with primary tuberculosis 4 Early culture and sensitivity testing recommended for contacts of patients with MDR-TB 195 NFI-2011

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Amikacin*
Pregnancy Category-D Indications Schedule H Short-term treatment of serious infections due to susceptible strains of Gram-negative bacteria, including Pseudomonas species, Escherichia coli, species of indole-positive and indole-negative Proteus, Providencia species, Klebsiella, Enterobacter, Serratia species and Acinetobacter (Mima-Herellea) species. INJECTION 10 ml vial (100 mg/2 ml), 2 ml vial (250 mg/2 ml), (500 mg/2 ml). Intramuscular or intravenous injection or infusion Adult- 15 mg/kg body weight daily in two divided doses, increased to 22.5 mg/kg body weight daily in three divided doses in severe infections. (max 1.5g daily for 10 days, max. cumulative dose is 15g). Child- 15 mg/kg body weight daily in two divided doses. Neonates- loading dose is 10 mg/kg body weight followed by 15 mg/kg body weight in two divided doses. Contraindications Precautions Myasthenia gravis; hypersensitivity. Pregnancy (Appendix 7c), renal impairment (Appendix 7d); neonates, infants and elderly; cross allergenicity. Vestibular and auditory damage, nephrotoxicity; rarely, hypomagnesaemia on prolonged therapy, antibiotic-associated colitis, stomatitis; also reported, nausea, vomiting, rash, blood disorders; acute muscular paralysis; albuminuria; azotemia.

Availability Dose

Adverse Effects

Capreomycin
Pregnancy Category-C Indications Availability Dose Schedule H Tuberculosis, in combination with other first line drugs for tuberculosis. INJECTION 0.5, 0.75 and 1g/vial. Deep intramuscular injection Adult- 1g daily for 2 to 4 months (not more than 20 mg/kg body weight). Then 1 to 2g 2 to 3 times each week, in case of renal impairment reduce the dose in accordance with creatinine clearance.

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Contraindications Precautions

Not for paediatric use; hypersensitivity to capreomycin. Renal impairment; hepatic impairment; auditory impairment; monitor renal, hepatic, auditory and vestibular function and electrolytes; pregnancy (teratogenic in animals; Appendix 7c) and lactation; interactions (Appendix 6c). Hypersensitivity reactions including urticaria and rashes; eosinophilia; leucocytosis or leucopenia, rarely, thrombocytopenia; changes in liver function tests; nephrotoxicity, electrolyte disturbances; hearing loss with tinnitus and vertigo; neuromuscular block after large doses, pain and induration at injection site. Store protected from moisture temperature not exceeding 25C. at a

Adverse Effects

Storage

Cycloserine
Pregnancy Category-C Indications Availability Dose Schedule H Tuberculosis resistant to first-line drugs. CAPSULE/TABLET 250 mg. Oral Adult- Initially 250 mg every 12 h for 2 weeks, increase according to blood concentration and response to 500 mg every 2 h. Child- Initially 10 mg/kg body weight daily adjusted to blood concentration and response. Contraindications Severe renal impairment; epilepsy; depression, severe anxiety, psychotic states, alcohol dependence; porphyria; hypersensitivity. Reduce dose in renal impairment (avoid if severe); monitor haematological, renal and hepatic function; lactation; discontinue or reduce dose if allergic skin reactions or CNS toxicity occur, pregnancy (Appendix 7c). Mainly neurological, including headache, dizziness, vertigo, drowsiness, tremor, convulsions, confusion, psychosis, depression (discontinue or reduce dose if symptoms of CNS toxicity); rashes, allergic dermatitis (discontinue or reduce dose); megaloblastic anaemia; changes in liver function tests; heart failure at high doses reported. Store at a temperature not exceeding 30C (tablets). Store protected from moisture (capsules).

Precautions

Adverse Effects

Storage

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Ethambutol *
Pregnancy Category-C Indications Availability Dose Schedule H Tuberculosis, in combination with other drugs. TABLETS 200, 400, 600, 800 mg and 1g. Oral Adult- 15 mg/kg body weight as a single dose, retreatment with 25 mg/kg body weight as a single dose for two months, thereafter reduce to 15 mg/kg body weight. Given as combination therapy with other anti-tubercular drugs. Child- Same as for Adult. Do not use under 3 years. Contraindications Optic neuritis; children under 5 years-unable to report symptomatic visual disturbances; severe renal impairment; hypersensitivity. Visual disturbances-ocular examination recommended before and during treatment (see note below); reduce dose in renal impairment (Appendix 7d) and monitor plasma concentration; elderly; pregnancy (Appendix 7c) (not known to be harmful); lactation.

Precautions

Note: Patients should report visual disturbances immediately and discontinue treatment; children who are incapable of reporting symptomatic visual changes accurately should be given alternative therapy, as should, if possible, any patient who cannot understand warnings about visual adverse effects Adverse Effects Optic neuritis-reduced visual acuity and red/ green colour blindness (early changes usually reversible, prompt withdrawal may prevent blindness); peripheral neuritis-especially in legs; gout; rarely, rash, pruritus, urticaria, thrombocytopenia; pulmonary infiltrates gastrointestinal upset. Store protected from moisture.

Storage

Isoniazid*
Pregnancy Category-C Indications Availability Dose Schedule H Tuberculosis, in combination with other drugs; tuberculosis prophylaxis also. TABLETS 100 and 300 mg. Oral

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Adult- 3 to 5 mg/kg body weight up to 300 mg as single dose daily. Child- 10 to 15 mg/kg body weight as a single dose, not to exceed 300 mg/day. Contraindications Precautions Drug-induced Hepatic Disease. Hepatic impairment (monitor hepatic function; Appendix 7a); malnutrition, chronic alcohol dependence, chronic renal failure (Appendix 7d); diabetes mellitus and HIV infection-prophylactic pyridoxine 10 mg daily required because risk of peripheral neuritis; epilepsy; slow acetylator status (increased risk of adverse effects); history of psychosis; pregnancy (Appendix 7c) (not known to be harmful); lactation (Appendix 7b); porphyria; interactions (Appendix 6a, 6c, 6d). Patients or their caretakers should be told how to recognize signs of liver disorder and advised to discontinue treatment and seek immediate medical attention if symptoms such as nausea, vomiting, malaise or jaundice develop. Adverse Effects Gastrointestinal disorders including nausea and vomiting, diarrhoea and pain, also constipation, dry mouth; hypersensitivity reactions including fever, rashes, joint pain, erythema multiforme, purpura usually during first weeks of treatment; peripheral neuropathy; blood disorders including agranulocytosis, haemolytic anaemia, aplastic anaemia; optic neuritis, toxic psychoses and convulsions; hepatitis (especially over age of 35 years and regular users of alcohol)-withdraw treatment; also reported systemic lupus erythematosuslike syndrome, pellagra, hyperreflexia, difficulty with micturition, hyperglycaemia and gynaecomastia; memory impairement, elevated serum transaminase, rheumatic syndrome, pyridoxine syndrome. Store protected from light.

Storage

Kanamycin
Pregnancy Category-D Indications Tuberculosis; hepatic resistant gonorrhoea, infections. Schedule H coma; chronic penicillin bacterial

Availability Dose

INJECTION Vial 500, 750 mg and 1g. Intramuscular and intravenous injection Adult- 1g daily as a single dose.

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Child- 6 to 15 mg/kg body weight daily in divided doses, 8 to 12 h (slow injection), usual duration of therapy 7 to 10 days. Contraindications Precautions Adverse Effects Storage Lactation; pregnancy (Appendix hypersensitivity; renal impairment. 7c);

Myasthenia gravis; renal impairment; elderly patients with neuromuscular disorder. Nephrotoxicity; ototoxicity; urticaria; neuromuscular malabsorption syndrome. skin rash; blockade;

Store protected from light and moisture.

Pyrazinamide*
Pregnancy Category-C Indications Availability Dose Schedule H Tuberculosis, in combination with other drugs. TABLETS 300, 500 and 750 mg; 1 and 1.5g; SUSPENSION 100 ml (5%). Oral Adult and Child- 20 to 35 mg/kg body weight as a single dose (max. 3g daily). Contraindications Precautions Severe hepatic impairment; porphyria. Hepatic impairment (monitor hepatic function; (Appendix 7a); renal impairment (Appendix 7d); diabetes mellitus (monitor blood glucose-may change suddenly); gout; pregnancy (Appendix 7c) and lactation; hypouricemia. Patients or their caretakers should be told how to recognize signs of liver disorder and advised to discontinue treatment and seek immediate medical attention if symptoms such as persistent nausea, vomiting, malaise or jaundice develop. Adverse Effects Hepatotoxicity including fever, anorexia, hepatomegaly, splenomegaly, jaundice, liver failure; nausea, vomiting; arthralgia; gout; sideroblastic anaemia; rash, photosensitivity; porphyria, dysuria, thrombocytopenia, hyperplasia, myalgia. Store in single dose containers protected from light and moisture.

Storage

Rifampicin* (Refer Page No. 190)

Pregnancy Category-C Indications Schedule H Tuberculosis, in combination with other drugs.

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Availability Dose

CAPSULE 150, 300, 350, 450, 500, 600 and 750 mg; SUSPENSION 100 mg/5 ml. Oral Adult- 450 to 600 mg as a single dose before breakfast. Child- 10 to 20 mg/kg body weight daily, same dose for meningococcal carriers but for 4 days.

Contraindications Precautions

Hypersensitivity; jaundice. Reduce dose in hepatic impairment (Appendix 7a); liver function tests and blood counts required in liver disorders, alcohol dependency, elderly and on prolonged therapy; renal impairment (if dose above 600 mg daily); lactation; porphyria; discolours soft contact lenses; advise patients on oral contraceptives to use additional means; interactions (Appendix 6b, 6c, 6d); pregnancy (Appendix 7c); cerebral haemorrhage, visual disturbances.

Note: Resumption of rifampicin treatment after a long interval may cause serious immunological reactions, resulting in renal impairment, haemolysis, or thrombocytopenia-discontinue permanently if serious adverse effects occur Patients or their caretakers should be told how to recognize signs of liver disorders and advised to discontinue treatment and seek immediate medical attention if symptoms such as persistent nausea, vomiting, malaise or jaundice develop. Adverse Effects Severe gastrointestinal disturbances including anorexia, nausea, vomiting and diarrhoea (antibiotic-associated colitis reported); headache, drowsiness; rashes, fever, influenza-like syndrome and respiratory symptoms, collapse, shock, haemolytic anaemia, acute renal failure and thrombocytopenic purpura-more frequent with intermittent therapy; alterations of liver function-jaundice and potentially fatal hepatitis (dose related; do not exceed max. dose of 600 mg daily); oedema, muscular weakness and myopathy, exfoliative dermatitis, toxic epidermal necrolysis, pemphigoid reactions, leukopenia, eosinophilia and menstrual disturbances reported; urine, tears, saliva and sputum coloured orange-red. Store protected from light and moisture.

Storage

Rifampicin + Isoniazid
Pregnancy Category-C Indications Tuberculosis. Schedule H

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Availability

TABLETS/CAPSULES Rifampicin + Isoniazid 60 mg + 30 mg 100 mg + 100 mg 100 mg + 300 mg 100 mg + 50 mg 150 mg + 100 mg 150 mg + 75 mg 300 mg + 150 mg 450 mg + 300 mg 600 mg + 300 mg Adult- One tablet daily before breakfast. Combined preparation usually not suitable for use in children; see under Rifampicin and Isoniazid; pregnancy (Appendix 7c). Store protected from moisture.

Dose Precautions

Storage

Rifampicin + Isoniazid + Ethambutol

Pregnancy Category-C Indications Availability Tuberculosis. TABLETS Rifampicin 150 mg 150 mg 450 mg 450 mg 100 mg 300 mg CAPSULES Rifampicin 225 mg + + + + + + + Isoniazid 275 mg 75 mg 300 mg 225 mg 50 mg 150 mg + + + + + + + Ethambutol 275 mg 275 mg 800 mg 825 mg 800 mg 550 mg Schedule H

+ Isoniazid + Ethambutol + 150 mg + 400 mg

Dose Precautions Storage

One tablet daily before breakfast in accordance with dose of individual drugs. Pregnancy (Appendix 7c). Store protected from moisture.

Rifampicin + Isoniazid + Pyrazinamide

Pregnancy Category-C Indications Schedule H Tuberculosis, in combination with other drugs.

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Availability

TABLETS/CAPSULES Rifampicin + Isoniazid 60 mg + 30 mg 100 mg + 50 mg 150 mg + 100 mg 450 mg + 300 mg 120 mg + 80 mg 225 mg + 150 mg 150 mg + 100 mg 450 mg + 300 mg Oral

+ + + + + + + + +

Pyrazinamide 150 mg 300 mg 500 mg 1000 mg 250 mg 750 mg 375 mg 1500 mg

Dose

Adult- One tablet daily before breakfast. Contraindications Combined preparation not suitable for use in children; see Rifampicin, Isoniazid and Pyrazinamide; pregnancy (Appendix 7c). Store protected from moisture.

Storage

Rifampicin + Isoniazid + Pyrazinamide + Ethambutol

Pregnancy Category-C Indications Availability Tuberculosis. TABLETS Rifampicin+Isoniazid+Pyrazinamide+ Ethambutol 150 mg + 100 mg + 500 mg + 800 mg 225 mg + 150 mg + 750 mg + 400 mg 150 mg + 75 mg + 400 mg + 275 mg 150 mg + 100 mg + 500 mg + 267 mg 450 mg + 300 mg + 1500 mg + 800 mg 600 mg + 300 mg + 800 mg + 1100 mg 1450 mg + 225 mg + 1200 mg + 825 mg Dose Oral Adult- One tablet daily before breakfast. Precautions Storage Pregnancy (Appendix 7c). Store protected from moisture. Schedule H

Streptomycin*
Pregnancy Category-D Indications Availability Dose Schedule H Tuberculosis, in combination with other drugs. INJECTION vial 750 mg and 1g. Deep intramuscular injection. Adult- 0.75g to 1g daily.

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Elderly- 0.5g daily. Child- 20 to 40 mg/kg body weight daily. Contraindications Precautions Hearing disorders; myasthenia pregnancy (Appendix 7c). gravis;

Children-painful injection, avoid use if possible; renal impairment (Appendix 7d), infants and elderly (dosage adjustment and monitor renal, auditory and vestibular function and plasma streptomycin concentrations); interactions (Appendix 6c). Vestibular and auditory damage, nephrotoxicity; hypersensitivity reactionswithdraw treatment; paraesthesia of mouth; rarely, hypomagnesaemia on prolonged therapy; antibiotic-associated colitis; also, nausea, vomiting, rash; rarely, haemolytic anaemia, aplastic anaemia, agranulocytosis, thrombocytopenia; pain and abscess at injection site. Store protected from moisture.

Adverse Effects

Storage

Thiacetazone + Isoniazid
Pregnancy Category-C Indications Availability Schedule H Tuberculosis, in combination with other drugs. TABLETS Thiacetazone + Isoniazid 150 mg + 300 mg 37.5 mg + 750 mg Oral Adult- One tablet daily before breakfast. Contraindications See Isoniazid; hepatic impairment; renal impairment; HIV infection-thioacetazone associated with high incidence of serious, sometimes fatal cutaneous hypersensitivity reactions, including exfoliative dermatitis. See Isoniazid; determine efficacy and toxicity of thiacetazone-geographical differences; hypersensitivity reactions-withdraw treatment; Pregnancy (Appendix 7c). SeeIsoniazid;thiacetazonecausesthefollowingnausea, vomiting, diarrhoea; hypersensitivity reactions including conjunctivitis, vertigo, rashes; fatal exfoliative dermatitis, acute hepatic failure reported; also, agranulocytosis, thrombocytopenia and aplastic anaemia. Store protected from light and moisture.

Dose

Precautions

Adverse Effects

Storage

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DOTS (Directly Observed Treatment, Short Course)

The WHO-recommended Directly Observed Treatment, Short Course (DOTS) strategy was launched formally as Revised National TB Control Programme in India in 1997 after pilot testing from 1993-1996. Since then DOTS has been widely advocated and successfully applied. (Revised National TB Control Policy) DOTS is the most effective strategy available for controlling TB. The five key components of DOTS are a) Political commitment to control TB; b) Case detection by sputum smear microscopy examination among symptomatic patients; c) Patients are given anti- TB drugs under the direct observation of the health care provider/community DOT provider; d) Regular, uninterrupted supply of anti-TB drugs; and e) Systematic recording and reporting system that allows assessment of treatment results of each and every patient and of whole TB control programme. Responsibility of ensuring regular and complete treatment of the patient lies with the health system. In 2006, the new stop TB strategy was recommended internationally by WHO. The components of the new stop TB strategy are the following: 1. Pursue high quality DOTS expansion and enhancement 2. Address TB/HIV, MDR-TB and other challenges 3. Contribute to health system strengthening 4. Engage all health care providers 5. Empower people with TB and communities 6. Enable and promote research DOTS involves treatment with combination of drugs -Rifampicin 300 mg + Isoniazid 150 mg + Pyrazinamide 800 mg + Ethambutol 550 mg, given thrice weekly. Twice weekly therapy can also be given but it is not recommended since it does not have margin for error and missing even one dose makes the therapy ineffective.

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9.9 Antipneumocystosis and Antitoxoplasmosis Drugs

Pneumocystosis:
Pneumocystis carinii is classified as a protozoan although there is evidence to suggest that it is probably a fungus. Pneumocystis carinii pneumonia is probably acquired by the airborne route. In otherwise healthy persons it rarely, produces signs of infection. However, it is a frequent cause of opportunistic infection in immunosuppressed, debilitated or malnourished patients; it is the commonest cause of pneumonia in AIDS and the most frequent immediate cause of death in these patients. Sulfamethoxazole with trimethoprim is the treatment of choice for Pneumocystis carinii pneumonia and is also used for prophylaxis in high-risk patients; pentamidine isothionate is used in patients unresponsive to or intolerant of sulfamethoxazole with trimethoprim. The treatment of Pneumocystis carinii infections must only be undertaken with specialist supervision where there are appropriate monitoring facilities.

Toxoplasmosis:
Toxoplasmosis is caused by infection with the protozoan parasite Toxoplasma gondii. Most infections are self-limiting and do not require treatment. However, in immunodeficiency, primary infection may result in encephalitis, myocarditis or pneumonitis; impairment of immunity (such as in AIDS) in a previously infected person, may result in encephalitis or meningoencephalitis. Congenital transmission may occur if there is a primary infection in early pregnancy or if the mother is immunodeficient. Such cases often result in spontaneous abortion, fetal death or severe congenital disease. Ocular toxoplasmosis causes chorioretinitis and is often the result of a childhood infection that becomes apparent in adulthood. The treatment of choice for toxoplasmosis is pyrimethamine with sulfadiazine; a folate supplement is also given to counteract the megaloblastic anaemia associated with these drugs.

Pentamidine* (Refer Page No 175)

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9.10 Antiretrovirals
Antiretroviral drugs do not cure HIV (human immunodeficiency virus) infection; they only temporarily suppress viral replication and improve symptoms. Patients receiving these drugs require careful monitoring by appropriately trained health professionals in an adequately resourced setting. Rigorous promotion of measures to prevent new infections remains essential and its need is not diminished by the availability of antiretroviral drugs. Effective therapy requires the simultaneous use of 3 or 4 drugs; alternative regimens are necessary to meet specific requirements at start-up, to substitute for first-line regimens in cases of intolerance, or to replace failing regimens. The use of a 3- or 4-drug combination as specified in the WHO treatment guidelines is recommended. The use of fixed-dose preparations for these combinations is also recommended if the pharmaceutical quality is assured and interchangeability with the single products is demonstrated as specified by the relevant drug regulatory authority. Selection of 2 or 3 protease inhibitors from the Model List will need to be determined by each country after consideration of local treatment guidelines and experience, as well as comparative costs of available products. Low-dose ritonavir is used in combination with indinavir, lopinavir or saquinavir as a booster; ritonavir is not recommended as a drug in its own right.

Principles of Treatment:
Treatment is aimed at reducing the plasma viral load as much as possible and for as long as possible; it should be started before the immune system is irreversibly damaged. The need for early drug treatment should, however, be balanced against the development of toxicity. Commitment to treatment and strict adherence over many years are required; the regimen chosen should take into account convenience and the patients tolerance of it. The development of resistance is reduced by using a combination of 3 or 4 drugs; such combinations should have additive or synergistic activity while ensuring that their toxicity is not additive. Testing for resistance to antiviral drugs, particularly in therapeutic failure, should be considered. Women of childbearing age receiving antiretroviral therapy must have available effective contraceptive methods to prevent unintended pregnancy. Women who are taking non nucleoside reverse transcriptase inhibitors or protease inhibitors which can lower blood concentration of hormonal oral contraceptives, should be advised to use additional or alternative contraceptives. 207 NFI-2011

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Drugs used to treat HIV Infection:

Zidovudine, a nucleoside reverse transcriptase inhibitor (or nucleoside analogue), was the first anti-HIV drug introduced. Other nucleoside reverse transcriptase inhibitors include abacavir, didanosine, lamivudine, stavudine and zalcitabine. The protease inhibitors include amprenavir, indinavir, lopinavir, nelfinavir, ritonavir and saquinavir. Ritonavir in low doses is used in combination with indinavir, lopinavir or saquinavir as a booster. The small amount of ritonavir in such combinations has no intrinsic antiviral activity but it increases the antiviral activity of the other protease inhibitors by reducing their metabolism. Indinavir, nelfinavir, ritonavir and possibly saquinavir inhibit the cytochrome P450 enzyme system and therefore have a potential for significant drug interactions. Protease inhibitors are associated with lipodystrophy and metabolic effects (see below). The non-nucleoside reverse transcriptase inhibitors include efavirenz and nevirapine. They interact with a number of drugs metabolized in the liver; the doses of protease inhibitors may need to be increased when they are given with efavirenz or nevirapine. Nevirapine is associated with a high incidence of rash (including Stevens-Johnson syndrome) and occasionally fatal hepatitis. Rash is also associated with efavirenz but it is usually milder. Efavirenz treatment has also been associated with an increased plasma cholesterol concentration.

Initiation of Treatment
The time for initiating antiviral treatment is determined by the clinical stage of the HIV infection as indicated by symptoms and where available, by the CD4-cell count or total lymphocyte count; the plasma viral load, if available, is also a valuable guide for staging the disease (see Monitoring, below). Recommended initial treatment with a combination of drugs (highly active antiretroviral therapy, HAART) includes: 2 nucleoside reverse transcriptase inhibitors plus a non-nucleoside reverse transcriptase inhibitor or a third nucleoside reverse transcriptase inhibitor or a protease inhibitor which may be combined with ritonavir as booster.

Monitoring:
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HIV-related illnesses, identification of co-existing medical conditions that may influence the choice of therapy (for example, pregnancy or tuberculosis) as well as current symptoms and physical signs. The absolute minimum laboratory tests before initiating antiretroviral therapy are an HIV antibody test (in patients over 18 months of age) and a haemoglobin or haematocrit measurement. Additional basic testing should include: white blood cell count; differential cell count (to identify a decline in neutrophils and the possibility of neutropenia); total lymphocyte count; serum alanine or aspartate aminotransferase concentration to assess the possibility of hepatitis co-infection and to monitor for hepatotoxicity; serum creatinine and/or blood urea nitrogen to assess baseline renal function; serum glucose; pregnancy tests for women. Desirable supplemental tests include measurement of bilirubin, amylase and serum lipids. CD4-cell determinations are, of course, very desirable and efforts should be made to make these widely available. Viral load testing is currently considered optional because of constraints on resources.

Changing Therapy:
Deterioration of the condition (including clinical and virological changes) usually calls for replacement of the failing drugs. Intolerance to adverse effects and drug-induced organ dysfunction usually require change in therapy. The choice of an alternative regimen depends on factors such as the response to previous treatment, tolerance and the possibility of cross-resistance. If treatment fails, a new second-line regimen will be needed. If toxicity occurs, either a new second-line regimen is indicated or, if the toxicity is related to an identifiable drug in the regimen, the offending drug can be replaced with another drug that does not have the same adverse effects.

Pregnancy:
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reduce the risk of toxicity to the fetus (although the teratogenic potential of most antiretroviral drugs is unknown); prevent transmission of infection to the neonate. In pregnant women, it may be desirable to initiate antiretroviral therapy after the first trimester, although for pregnant women who are severely ill, the benefit of early therapy outweighs the potential risk to the fetus. All treatment options require careful assessment by a specialist. The use of zidovudine, lamivudine, nevirapine, nelfinavir and saquinavir are recommended for women of child-bearing potential or who are pregnant. Efavirenz should be avoided because of its potential teratogenic effect on the fetus in the first trimester. First-line treatment in pregnant women should when possible include zidovudine and lamivudine. Monotherapy with either zidovudine or with nevirapine reduces transmission of infection to the neonate (see also below), but combination antiretroviral therapy maximizes the chance of preventing transmission and represents optimal therapy for the mother. Low-dose ritonavir is required if either indinavir or saquinavir is used in pregnancy because adequate drug concentration is achieved only with ritonavir boosting. Information is lacking on the use of lopinavir with ritonavir in pregnancy. Lactic acidosis and hepatic steatosis associated with nucleoside reverse transcriptase inhibitors may be more frequent in pregnant women and therefore the combination of stavudine and didanosine should be used in pregnancy only when no alternatives are available. Protease inhibitors have been associated with glucose intolerance and pregnant women should be instructed to recognize symptoms of hyperglycaemia and to seek health care advice if they occur. Various regimens have been used to specifically prevent the transmission of HIV from mother to the neonate at term. More information is available in New Data on the Prevention of Mother-to-Child Transmission of HIV and their Policy Implications: Conclusions and Recommendations (WHO/ RHR/01.28), which reflects an inter-agency consultation, held on 11-13 October 2000.

Lactation:
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prevent viral replication and there is therefore the possibility of promoting the development of drug-resistant virus which could be transmitted to the infant. Women with HIV infection should be counselled about the risks of lactation and, where possible, they should limit or avoid lactation; in particular, lactation should be avoided where replacement feeding is acceptable, affordable, sustainable and safe. HIV-infected women should be counselled on infant feeding options and they should be supported in their choice.

Post-Exposure Prophylaxis:
Treatment with antiretroviral drugs may be appropriate following occupational exposure to HIV-contaminated material. Immediate expert advice should be sought in such cases; national guidelines on post-exposure prophylaxis for healthcare workers have been developed and local ones may also be available.

Lipodystrophy and Metabolic Effects:

Combination antiretroviral therapy, including regimens containing a protease inhibitor, is associated with redistribution of body fat in some patients (for example, decreased fat under the skin, increased abdominal fat, buffalo humps and breast enlargement). Protease inhibitors are also associated with metabolic abnormalities such as hyperlipidaemia, insulin resistance and hyperglycaemia. Clinical examination should include an evaluation of fat distribution; measurement of serum lipids and blood glucose should be considered.

9.10.1 Nucleoside/Nucleotide Reverse Transcriptase Inhibitors

In some settings it may not be possible to carry out full monitoring described under each drug entry; in such cases the level of monitoring should be determined by local guidelines (see also notes above).

Abacavir
Pregnancy Category-C Indications Availability Dose Schedule H HIV infection in combination with atleast two other antiretroviral drugs. TABLET 300 mg. Oral Adult- 300 mg twice daily or 600 mg once daily.

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Child- 3 months to 12 years: 8 mg/kg body weight every 12 h (max. 600 mg daily). Contraindications Precautions Pregnancy (Appendix 7c); lactation (Appendix 7b); hepatic dysfunction (Appendix 7a); renal disease. Hepatic impairment (see below and Appendix 7a); renal impairment; pregnancy (see notes above and Appendix 7c); lactation (Appendix 7b) (see notes above); hypersensitivity reaction; interactions (Appendix 6a). Life-threatening hypersensitivity reactions reported-characterized by fever or rash and possibly nausea, vomiting, diarrhoea, abdominal pain, lethargy, malaise, headache, myalgia and renal failure; less frequently mouth ulceration, oedema, hypotension, dyspnoea, sore throat, cough, paraesthesia, arthralgia, conjunctivitis, lymphadenopathy, lymphocytopenia and anaphylaxis (hypersensitivity reactions presenting as sore throat, influenza-like illness, cough and breathlessness identified); rarely, myolysis; laboratory abnormalities may include raised liver enzymes and creatine kinase; symptoms usually appear in the first 6 weeks, but may occur at any time; monitor for symptoms every 2 weeks for 2 months; discontinue immediately if any symptom of hypersensitivity develops and do not rechallenge (risk of more severe hypersensitivity reaction); discontinue if hypersensitivity cannot be ruled out, even when other diagnosis possible-if rechallenge necessary it must be carried out in hospital setting; if abacavir is stopped for any reason other than hypersensitivity, exclude hypersensitivity reaction as the cause and rechallenge only if medical assistance is readily available; care needed with concomitant use of drugs which cause skin toxicity. Patients should be told the importance of regular dosing (intermittent therapy may increase sensitization), how to recognize signs of hypersensitivity and advised to seek immediate medical attention if symptoms develop or before re-starting treatment. Potentially life-threatening lactic acidosis and severe hepatomegaly with steatosis reported-caution in liver disease, liver enzyme abnormalities, or risk factors for liver disease (particularly in obese women); suspend or discontinue if deterioration in liver function tests, hepatic steatosis, progressive hepatomegaly or unexplained lactic acidosis. Storage Store at a temperature not exceeding 30C.

Adverse Effects

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Didanosine*
Pregnancy Category-B Indications Availability Dose Schedule H HIV infection in combination with atleast two other antiretroviral drugs. TABLETS 100, 250 mg and 400 mg; CAPSULES 250 and 400 mg. Oral Adult- Under 60 kg: 250 mg daily in 1 to 2 divided doses. 60 kg and over: 400 mg daily in 1 to 2 divided doses, 30 min before meals or 2 h after meals. Child- 2week - 8 months: 100 mg/m2 twice daily. >8 months: 120 mg/m2 twice daily. Contraindications Precautions Hypersensitivity; pancreatitis; coadministration of allopurinol and ribavirin. History of pancreatitis (preferably avoid, otherwise extreme caution, see also below); peripheral neuropathy or hyperuricaemia (see under Adverse effects); history of liver disease (see below); renal and hepatic impairment (see Appendices 7d and 7a); pregnancy (Appendix 7c) and lactation (Appendix 7b) (see notes above); dilated retinal examinations recommended (especially in children) every 6 months, or if visual changes occur; interactions (Appendix 6c, 6d); immune reconstitution syndrome, fat redistribution, retinal changes and optic neuritis. If symptoms of pancreatitis develop or if serum amylase or lipase is raised (even if asymptomatic) suspend treatment until diagnosis of pancreatitis excluded; on return to normal values re-initiate treatment only if essential (using low dose increased gradually if appropriate). Whenever possible avoid concomitant treatment with other drugs known to cause pancreatic toxicity (for example intravenous pentamidine isothionate); monitor closely if concomitant therapy unavoidable. Since significant elevations of triglycerides cause pancreatitis monitor closely if elevated. Potentially life-threatening lactic acidosis and severe hepatomegaly with steatosis reported therefore caution in liver disease, excessive alcohol intake, liver enzyme abnormalities, or risk factors for liver disease (particularly in obese women); suspend or discontinue if deterioration in liver function tests, hepatic steatosis, progressive hepatomegaly or unexplained lactic acidosis

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Adverse Effects

Pancreatitis (see also under Precautions); peripheral neuropathy especially in advanced HIV infection-suspend (reduced dose may be tolerated when symptoms resolve); hyperuricaemia (suspend treatment if significant elevation); diarrhoea (occasionally serious); also reported, nausea, vomiting, dry mouth, asthenia, headache, hypersensitivity reactions; retinal and optic nerve changes (especially in children); diabetes mellitus, raised liver enzymes (see also under Precautions); liver failure. Store protected from light.

Storage

Emtricitabine
Pregnancy Category-B Indications Availability Dose HIV infection. CAPSULE 200 mg. Oral Adult and child over 33 kg- 200 mg once a day. Child- Under 33 kg: 6 mg/kg body weight once a day. Contraindications Precautions Lactation; hypersensitivity. Monitor patients with hepatitis B (risk of exacerbation of hepatitis); obesity, lactic acidosis, severe hepatomegaly, coinfection with hepatitis B virus; pregnancy (Appendix 7c). Gastro-intestinal disturbances (such as nausea, vomiting, abdominal pain, flatulence and diarrhoea); anorexia; pancreatitis; liver damage (see also Lactic Acidosis, above); dyspnoea; cough, headache; insomnia; dizziness; fatigue; blood disorders (including anaemia, neutropenia and thrombocytopenia); myalgia, arthralgia, rash, urticaria and fever. Lipodystrophy, abnormal dreams, pruritus and hyperpigmentation. Store protected from moisture. Schedule H

Adverse Effects

Storage

Lamivudine*
Pregnancy Category-C Indications Availability Schedule H HIV infection in combination with at least two other antiretroviral drugs. TABLETS 100, 150 and 300 mg; ORAL SOLUTION 50 mg/ml.

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Dose

Oral Adult- 150 mg twice daily administered with zidovudine. Child- 3 months to 12 years: 4 mg/kg body weight twice a day (max. 150 mg twice daily).

Contraindications Precautions

Pregnancy (Appendix 7c); lactation (Appendix 7b); hepatic dysfunction (Appendix 7a); renal disease (Appendix 7d). Renal impairment (Appendix 7d); hepatic disease (see below); pregnancy (Appendix 7c) and lactation (Appendix 7b) (see notes above); interactions (Appendix 6c). Potentially life-threatening lactic acidosis and severe hepatomegaly with steatosis reported therefore caution (particularly in obese women) in liver disease, liver enzyme abnormalities, or risk factors for liver disease; suspend or discontinue if deterioration in liver function tests, hepatic steatosis, progressive hepatomegaly or unexplained lactic acidosis. Recurrent hepatitis in patients with chronic hepatitis B may occur on discontinuation of lamivudine.

Adverse Effects

Nausea, vomiting, diarrhoea, abdominal pain; cough; headache, fatigue, insomnia; malaise, fever, rash, alopecia, muscle disorders; nasal symptoms; peripheral neuropathy reported; rarely, pancreatitis (discontinue); neutropenia, anaemia, thrombocytopenia and red-cell aplasia; lactic acidosis; raised liver enzymes and serum amylase. Store protected from moisture.

Storage

Stavudine*
Pregnancy Category-C Indications Availability Dose Schedule H HIV infection in combination with atleast two other antiretroviral drugs. TABLETS/CAPSULES 30 and 40 mg. Oral Adult- Under 60 kg: 30 mg every 12 h preferably at least 1 h before food. 60 kg and over: 40 mg every 12 h. Neonate under 2 weeks- 500 g/kg body weight.

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Child- over 2 weeks and body weight under 30 kg: 1 mg/kg body weight every 12 h. 30 kg and over: 30 mg every 12 h. Contraindications Precautions Hypersensitivity. History of peripheral neuropathy (see below); history of pancreatitis or concomitant use with other drugs associated with pancreatitis; hepatic disease (see below); renal impairment; pregnancy (Appendix 7c) and lactation (Appendix 7b) (see notes above); fat redistribution, immune reconstitution syndrome. Suspend if peripheral neuropathy developscharacterized by persistent numbness, tingling or pain in feet or hands; if symptoms resolve satisfactorily on withdrawal and if stavudine needs to be continued, resume treatment at half previous dose. Potentially life-threatening lactic acidosis and severe hepatomegaly with steatosis reported therefore caution in liver disease, liver enzyme abnormalities, or risk factors for liver disease (particularly in obese women); suspend or discontinue if deterioration in liver function tests, hepatic steatosis, progressive hepatomegaly or unexplained lactic acidosis. Adverse Effects Peripheral neuropathy (dose-related, see above); pancreatitis; nausea, vomiting, diarrhoea, constipation, anorexia, abdominal discomfort; chest pain; dyspnoea; headache, dizziness, insomnia, mood changes; asthenia, musculoskeletal pain; influenzalike symptoms, rash and other allergic reactions; lymphadenopathy; neoplasms; elevated liver enzymes (see hepatic disease, above) and serum amylase; neutropenia, thrombocytopenia. Store protected from moisture temperature not exceeding 30C. at a

Storage

Tenofovir
Pregnancy Category-B Indications Availability Dose HIV infection. TABLET 300 mg. Oral
Adult- 300 mg once daily.

Schedule H

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Contraindications Precautions

Lactation; hypersensitivity. Should be used with caution in patients with chronic hepatitis B or C (greater risk of hepatic side-effects), in hepatic impairment, in renal impairment and in pregnancy (Appendix 7c). Test renal function and serum phosphate before treatment, then every 4 weeks (more frequently if at increased risk of renal impairment) for 1 year and then every 3 months, interrupt treatment if renal function deteriorates or serum phosphate decreases; concomitant or recent use of nephrotoxic drugs; on discontinuation, monitor patients with hepatitis B (risk of exacerbation of hepatitis). Gastro-intestinal disturbances (such as nausea, vomiting, abdominal pain, flatulence and diarrhoea); anorexia; pancreatitis; liver damage; dyspnoea; cough; headache, insomnia, dizziness, fatigue; blood disorders (including anaemia, neutropenia and thrombocytopenia); myalgia, arthralgia, rash, urticaria and fever. See notes above for metabolic effects and lipodystrophy; hypophosphataemia; reduced bone density; nephrogenic diabetes insipidus and renal failure; lactic acidosis, decrease in bone mineral density, acute exacerbation of hepatitis. Store protected from moisture temperature not exceeding 30C. at a

Adverse Effects

Storage

Zidovudine (AZT)*
Pregnancy Category-C Indications Schedule H HIV infection in combination with at least two other antiretroviral drugs; monotherapy for prevention of maternal-fetal HIV transmission. TABLETS 30, 40, 100 and 300 mg; CAPSULES 100 and 300 mg; SyRUP 50 mg/5 ml. Oral
HIV infection Adult- 600 mg daily in divided doses in combination with other antiretroviral drugs. Child- 6 weeks to 12 years: 160 mg/m2 every 8 hour, max. dose 200 mg every 8 hour. Prevention of maternal-foetal HIV transmission.

Availability Dose

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Adult- 100 mg five times daily or 200 mg thrice daily or 300 mg twice daily, start treatment after 14th week of gestation until the start of labour. Prevention of HIV transmission in neonates. Child- neonates- 2 mg/kg every 6 hour for first 6 weeks of life, starting with12 hour after birth.

Contraindications

Abnormally low neutrophil counts or haemoglobin; neonates either with hyperbilirubinaemia requiring treatment other than phototherapy or with raised transaminase; life threatening allergic reactions. Haematological toxicity; vitamin B12 deficiency (increased risk of neutropenia); reduce dose or interrupt treatment if anaemia or myelosuppression; renal impairment (Appendix 7d); hepatic impairment (Appendix 7a); risk of lactic acidosis; elderly; lactation (Appendix 7b); interactions (Appendix 6c, 6d); pregnancy (Appendix 7c); myopathy, use with interferon and ribavirin based regimens in HIV/HCV coinfected patients, immune reconstitution syndrome. Anaemia (may require transfusion), neutropenia and leukopenia (all more frequent with high dose and advanced disease); also nausea and vomiting, abdominal pain, dyspepsia, diarrhoea, flatulence, taste disturbance, pancreatitis, liver disorders including fatty change and raised bilirubin and liver enzymes (see hepatic disease, above); chest pain, dyspnoea, cough; influenza-like symptoms; headache; fever; paraesthesia, neuropathy; convulsions; dizziness; somnolence, insomnia; anxiety; depression; malaise; anorexia; asthenia; myopathy; myalgia; pancytopenia, thrombocytopenia; gynaecomastia; urinary frequency; rash, pruritus, pigmentation of nail, skin and oral mucosa. Store protected from light and moisture.

Precautions

Adverse Effects

Storage

9.10.2 Non-Nucleoside Transcriptase Inhibitor

In some settings it may not be possible to carry out full monitoring described under each drug entry; in such cases the level of monitoring should be determined by local guidelines (see also notes above).

Efavirenz*
Pregnancy Category-D Schedule H

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Indications Availability Dose

HIV infection in combination with at least two other antiretroviral drugs. TABLETS/CAPSULES 200, 400 and 600 mg. Oral Adult- 600 mg once a day. Child- Over 3 years 13 to 14 kg body weight: 200 mg once a day. 15 to 19 kg body weight: 250 mg once a day; 25 to 32.5 kg body weight: 400 mg once a day; over 40 kg body weight: adult dose.

Contraindications

Pregnancy (see notes above and (Appendix 7c); substitute nevirapine for efavirenz in pregnant women or women for whom effective contraception cannot be assured); hypersensitivity. Hepatic impairment (avoid if severe; Appendix 7a); severe renal impairment; lactation (Appendix 7b) (see notes above); elderly; history of mental illness or substance abuse; interactions (Appendix 6b, 6c); psychiatric symptoms. Rash, usually in the first 2 weeks, is the most common adverse effect; discontinue if severe rash with blistering, desquamation, mucosal involvement or fever; if rash mild or moderate, may continue without interruption-rash usually resolves within 1 month.

Precautions

Adverse Effects

Rash including Stevens-Johnson syndrome (see also above); dizziness, headache, insomnia, somnolence, abnormal dreams, fatigue, impaired concentration (administration at bedtime especially in the first 2-4 weeks reduces CNS effects); nausea; less frequently vomiting, diarrhoea, hepatitis, depression, anxiety, psychosis, amnesia, ataxia, stupor, vertigo; also reported raised serum cholesterol, elevated liver enzymes (especially if seropositive for hepatitis B or C), pancreatitis. Store protected from light.

Storage

Nevirapine*
Pregnancy Category-C Indications Schedule H HIV infection, in combination with at least two other antiretroviral drugs; prevention of mother-to-child transmission in HIV-infected patients. TABLET/CAPSULE 200 mg; ORAL SUSPENSION 100 mg/5 ml. Oral

Availability Dose

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Adult- 200 mg once a day for 14 days, if tolerated and no rash is observed then increase to 200 mg two times a day. Child- 2 months to 8 years: 4 mg/kg body weight once a day for 14 days, if tolerated and no rash is observed increase to 4 mg/kg body weight two times a day. Contraindications Precautions Acute porphyria; severe hepatic impairment; post-exposure prophylaxis; breast feeding. Hepatic impairment (see below and Appendix 7a); history of chronic hepatitis (greater risk of hepatic adverse effects), pregnancy (Appendix 7c) and lactation (Appendix 7b); interactions (Appendix 6b, 6c). Potentially life-threatening hepatotoxicity including fatal fulminant hepatitis reported usually occurring in first 8 weeks; monitor liver function before long-term treatment then every 2 weeks for 2 months then after 1 month and then every 3-6 months; discontinue permanently if abnormalities in liver function tests accompanied by hypersensitivity reaction (rash, fever, arthralgia, myalgia, lymphadenopathy, hepatitis, renal impairment, eosinophilia, granulocytopenia); suspend if severe abnormalities in liver function tests but no hypersensitivity reaction-discontinue permanently if significant liver function abnormalities recur; monitor patient closely if mild to moderate abnormalities in liver function tests with no hypersensitivity reaction. Rash, usually in first 8 weeks, is most common adverse effect; incidence reduced if introduced at low dose and dose increased gradually; discontinue permanently if severe rash or if rash accompanied by blistering, oral lesions, conjunctivitis, swelling, general malaise or hypersensitivity reactions; if rash mild or moderate may continue without interruption but dose should not be increased until rash resolves. Patients should be told how to recognize hypersensitivity reactions and advised to seek immediate medical attention if symptoms develop. Adverse Effects Rash including Stevens-Johnson syndrome and rarely, toxic epidermal necrolysis (see also Precautions above); hepatitis or jaundice reported (see also Precautions above); nausea, vomiting, abdominal pain, diarrhoea, headache, drowsiness, fatigue, fever; hypersensitivity reactions (may involve hepatic reactions and rash, see Precautions above); anaphylaxis, angioedema, urticaria also reported; granulocytopenia. Store protected from light and moisture at a temperature not exceeding 30C.

Storage

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9.10.3 Combinations Lamivudine + Nevirapine + Stavudine*

Pregnancy Category-C Indications Availability HIV infection. TABLETS Lamivudine 40 mg 150 mg 150 mg 100 mg + + + + + Nevirapine 10 mg 40 mg 30 mg 30 mg + + + + + Stavudine 70 mg 200 mg 200 mg 200 mg Schedule H

Dose

Adult- One tablet twice daily. Patients with body weight less than 50 kg, 2 mg/kg body weight two times a day. Child- 3 months to 12 years; half adult dose is given two times a day.

Precautions Storage

Pregnancy (Appendix 7c). Store protected from moisture at temperature not exceeding 25C for DT. a

Lamivudine + Zidovudine*
Pregnancy Category-C Indications Availability Dose HIV infection. TABLET lamivudine + zidovudine 150 mg + 300 mg. Adult- 2 tablets three times a day or as prescribed. Child- Half the adult dose. Precautions Storage Pregnancy (Appendix 7c). Store protected from moisture. Schedule H

Zidovudine + Lamivudine + Nevirapine*

Schedule H Indications Avaialbility: Dose HIV infection. TABLETS Zidovudine 300 mg + Lamivudine 150 mg + Nevirapine 200 mg. Adult- 2 tablets three times a day. Child- Half adult dose.

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9.10.4 Protease Inhibitors

In some settings it may not be possible to carry out full monitoring described under each drug entry; in such cases the level of monitoring should be determined by local guidelines (see also notes above).

Indinavir*
Pregnancy Category-C Indications Schedule H HIV infection in combination with two nucleoside reverse transcriptase inhibitors and usually with low-dose ritonavir booster. TABLET/CAPSULE 400 mg. Oral Adult- 800 mg every 8 h with water, 1 h before or 2 h after meals. Child- 4 to 17 years: 500 mg every 8 h. Safety and efficacy is not established in patients less than 4 years. Contraindications Precautions Pregnancy; concurrent use of cisapride; alprazolam; midazolam. Hepatic impairment (Appendix 7a); ensure adequate hydration to reduce risk of nephrolithiasis; diabetes mellitus; haemophilia; pregnancy (see notes above and Appendix 7c); lactation (Appendix 7b) (see notes above); metabolism of many drugs inhibited if administered concomitantly; interactions (Appendix 6c, 6d); hyperbilirubinemia, tubulo-interstitial nephritis. Nausea, vomiting, diarrhoea, abdominal discomfort, dyspepsia, flatulence, pancreatitis, dry mouth, taste disturbances; headache, dizziness, insomnia; myalgia, myositis, rhabdomyolysis, asthenia, hypoaesthesia, paraesthesia; hyperglycaemia; anaphylactoid reactions, rash (including Stevens-Johnson syndrome), pruritus, dry skin, hyperpigmentation, alopecia, paronychia; interstitial nephritis, nephrolithiasis (may require interruption or discontinuation; more frequent in children), dysuria, haematuria, crystalluria, proteinuria, pyuria (in children); hepatitis, transient hyperbilirubinaemia; blood disorders including neutropenia, haemolytic anaemia; lipodystrophy and metabolic effects, see notes above; hydronephrosis. Store protected from light and moisture at a temperature not exceeding 30C.

Availability Dose

Adverse Effects

Storage

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Lopinavir + Ritonavir
Pregnancy Category-C Indications Availability Dose Schedule H HIV infection in combination with two other antiretroviral drugs. CAPSULE/TABLET Lopinavir + Ritonavir 200 mg + 50 mg. Adult and child with body surface area 1.4 m2, body weight 40 kg and over- 2 tablets twice daily. Child over 2 years with body weight 40 kg and body surface area 0.5 to 0.9 m2 - 2 tablets (Lopinavir 100 mg + Ritonavir 25 mg), twice daily. Body surface area 0.9 to 1.4 m2 - 3 tablets twice daily. Note: Ritonavir increases effect of lopinavir; low dose in combination does not have intrinsic antiviral activity. Contraindications Precautions Hypersensitivity; avoid concomitant use with ergot derivatives. Hepatic impairment-avoid if severe; renal impairment; haemophilia; pregnancy (see notes above and (Appendix 7c); lactation (see notes above and Appendix 7b); diabetes mellitus. Signs and symptoms suggestive of pancreatitis (including raised serum amylase and lipase) should be evaluated-discontinue if pancreatitis diagnosed. Adverse Effects Diarrhoea, nausea, vomiting, colitis, abdominal discomfort, asthenia, headache, insomnia; rash; less frequently, dry mouth, hepatic dysfunction, pancreatitis (see also Precautions), dyspepsia, dysphagia, oesophagitis, influenza-like syndrome, appetite changes; hypertension, palpitations, thrombophlebitis, vasculitis, chest pain, dyspnoea, agitation, anxiety, ataxia, hypertonia, confusion, depression, dizziness, dyskinesia, paraesthesia, peripheral neuritis, somnolence; Cushing syndrome, hypothyroidism, sexual dysfunction, anaemia, leukopenia, dehydration, oedema, lactic acidosis; arthralgia, myalgia, abnormal vision, otitis media, taste disturbances, tinnitus; acne, alopecia, dry skin, pruritus, skin discolouration, nail disorders, sweating; lipodystrophy and metabolic effects (see notes above); raised bilirubin and lowered sodium, low platelet and low neutrophil counts also reported in children; myocardial infarction, loss of taste.

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Storage

Store protected from moisture at a temperature not exceeding 30C for tablets and store protected from moisture in refrigerator (2 to 8C) for capsules.

Nelfinavir*
Pregnancy Category-B Indications Availability Dose Schedule H HIV infection in combination with two other antiretroviral drugs. TABLET 250 mg. Adult- 750 mg thrice daily. Child- 3 to 13 years: initially 25 to 30 mg/kg body weight three times a day (max. 1.25 g) or 50 to 55 mg/kg body weight twice daily. Not recommended under 3 years. Contraindications Moderate to severe liver disease; concurrent use of alprazolam; midazolam; lactation; hypersensitivity. Hepatic and renal impairment; diabetes mellitus; haemophilia; pregnancy (Appendix 7c) and lactation (Appendix 7b) (see notes above); interactions (Appendix 6b, 6c, 6d); HIV cross resistance, immune reconstitution syndrome. Diarrhoea, nausea, vomiting, flatulence, abdominal pain; rash; reports of elevated creatine kinase; hepatitis; pancreatitis; neutropenia; hypersensitivity reactions including bronchospasm, fever, pruritus and facial oedema, lipodystrophy and metabolic effects, see notes above; backpain, myopathy, anxiety, sleep disorder, kidney calculus, QT prolongation. Store protected from light.

Precautions

Adverse Effects

Storage

Oseltamivir
Pregnancy Category-C Indications Availability Dose Schedule X Influenze A, B and its subtypes like swine flu. CAPSULES 30, 45 and 75 mg. Oral Adult and adolescent- Prevention of influenza, over 13 years: 75 mg once daily for 10 days for post exposure prophylaxis, for up to 6 weeks in epidemics. Treatment of influenza, over 13 years: 75 mg every 12 h for 5 days.

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Child- Prevention of influenza: body weight under 15 kg: 30 mg once daily; 15 to 23 kg: 45 mg once daily; 23 to 40 kg: 60 mg once daily: above 40 kg: adult dose. Treatment of influenza: body weight under 15 kg: 39 mg every 12 h for 5 days; 15 to 23 kg: 45 mg every 12 h for 5 days; 23 to 40 kg: 60 mg every 12 h for 5 days; above 40 kg: adult dose. Contraindications Precautions Adverse Effects Hypersensitivity. Hepatic impairment; pregnancy (Appendix 7c); lactation; renal impairment. Nausea, vomiting, abdominal pain, dyspepsia, diarrhoea; headache, fatigue, insomnia, dizziness; conjunctivitis, epistaxis; rash; very rarely, hepatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis; neuropsychiatric disorders also reported (in children); cough, bronchitis, eczema, seizures, aggravation of diabetes. Store protected from moisture and light at a temperature not exceeding 30C.

Storage

Ritonavir*
Pregnancy Category-C Indications Schedule H HIV infection, as a booster to increase effect of indinavir, lopinavir or saquinavir and in combination with two other antiretroviral drugs. TABLET 100 and 250 mg; CAPSULE 100 mg; SyRUP 400 mg/5 ml. Adult- Initially 300 mg every 12 h for three days increased in steps of 100 mg every 12 h over not longer than 14 days to 600 mg every 12 h. Child- Over 2 years: initially 250 mg/m2 of body surface area every 12 h, increase by 50 mg/m2 at intervals of 2 to 3 days to 350 mg/m2 body surface area every 12 h (max. 600 mg/12 h). Contraindications Precautions Severe hepatic impairment. Hepatic impairment, diabetes mellitus; haemophilia; pregnancy (Appendix 7c) and lactation (Appendix 7b) (see notes above); interactions (Appendix 6b, 6c, 6d); PR interval prolongation, lipid disorder. Signs and symptoms suggestive of pancreatitis (including raised serum amylase and lipase) should be evaluated-discontinue if pancreatitis diagnosed.

Availability Dose

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Adverse Effects

Nausea, vomiting, diarrhoea (may impair absorption-close monitoring required), abdominal pain, taste disturbances, dyspepsia, anorexia, throat irritation; vasodilatation; headache, circumoral and peripheral paraesthesia, hyperaesthesia, dizziness, sleep disturbances, asthenia, rash, hypersensitivity reactions, leukopenia; raised liver enzymes, bilirubin and uric acid; occasionally flatulence, eructation, dry mouth and ulceration, cough, anxiety, fever, pain, myalgia, weight loss, decreased thyroxine, sweating, pruritus, electrolyte disturbances, anaemia, neutropenia, increased prothrombin time; pancreatitis (see also Pancreatitis, above); lipodystrophy and metabolic effects, see notes above; postural hypotension, abnormal stool, albuminuria. Store protected from light at temperature (2 to 8C) for capsules.

Storage

Saquinavir*
Pregnancy Category-B Indications Schedule H HIV infection in combination with two other antiretroviral drugs and usually with lowdose ritonavir booster. TABLETS 500 mg; CAPSULES 200 mg. Adult and adolescent over 16 years with low dose ritonavir, 1g saquinavir every 12 h. Hypersensitivity. Hepatic impairment (Appendix 7a); renal impairment; diabetes mellitus; haemophilia; pregnancy (Appendix 7c) and lactation (Appendix 7b) (see notes above); interactions (Appendix 6d); hyperlipidemia, lactose intolerance, fat redistribution, immune reconstitution syndrome. Diarrhoea, buccal and mucosal ulceration, abdominal discomfort, nausea, vomiting; headache, peripheral neuropathy, paraesthesia, dizziness, insomnia, mood changes, ataxia, musculoskeletal pain, asthenia; fever, pruritus, rash and other skin eruptions, rarely, Stevens-Johnson syndrome; other rare adverse effects include thrombocytopenia and other blood disorders; liver damage; pancreatitis and nephrolithiasis; reports of elevated creatine kinase, raised liver enzymes and neutropenia when used in combination therapy; lipodystrophy and metabolic effects (see notes above); cyanosis, heart murmur; decrease appetite; amnesia.

Availability Dose Contraindications Precautions

Adverse Effects

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Storage

Store protected from moisture.

Zanamivir
Pregnancy Category-B Indications Schedule X Most effective for the treatment of influenza if started within a few hour of the onset of symptoms; they are to be used within 48 h (36 h for children) of the first symptoms. CAPSULE 5 mg, powder for inhalation. Oral- powder for inhalation. Adult- minimum 10 mg (2 inhalations) inhaled; orally twice a day for 5 days. Max. 20 mg.

Availability Dose

Note: The formulation is not designed or intended to be administred by nebulization. To be used with a diskhaler device only. Precautions Adverse Effects Anaphylaxis; encephalitis; pediatric, geriatric, lactation, pregnancy (Appendix 7c). Nausea, vomiting, abdominal pain, dyspepsia, diarrhoea; headache, fatigue, insomnia, dizziness; conjunctivitis, epistaxis; rash; very rarely, hepatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis.

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9.11 Antischistosomals and Antitrematode Drugs

Schistosomiasis:
Schistosomiasis, a waterborne parasitic infection, is caused by several species of trematode worms (blood flukes). Its socioeconomic impact as a parasitic disease is outstripped only by that of malaria. Intestinal schistosomiasis is caused principally by Schistosoma mansoni as well as S. japonicum, S. mekongi and S. intercalatum. Urinary schistosomiasis is caused by S. haematobium. The latter is an important predisposing cause of squamous cell cancer of the bladder. Praziquantel has transformed the treatment of schistosomiasis and is often effective in a single dose, against all species of the parasite. It can be of particular value in patients with mixed infections and those who do not respond adequately to other drugs. It is also extremely well tolerated and well suited for mass treatment control programmes. Extensive use over several years has provided no evidence of serious adverse effects or long-term toxicity, nor has mutagenic or carcinogenic activity been shown in experimental animals. Drugs still widely used in the treatment of schistosomiasis include oxamniquine, which is effective against S. mansoni. It is preferable to delay treatment with oxamniquine in pregnant women until after delivery unless immediate intervention is essential. Due to lack of information on whether oxamniquine is excreted in breast milk, it is preferable not to administer it to nursing mothers.

Praziquantel*
Pregnancy Category-B Indications Schedule H Taenia saginata, T. solium, Hymenolepis nana and Diphyllobothrium latum infections; trematode infections, schistosomiasis. TABLETS 600 mg. Schistosomiasis: 40 mg/kg body weight is given in two divided doses 4 to 6 h apart in one day. S. japonicum infection: 60 mg/kg body weight in three divided doses in one day. Ocular cysticercosis; hypersensitivity.

Availability Dose

Contraindications

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Precautions

Pregnancy (Appendix 7c); lactation (Appendix 7b); areas endemic for cysticercosis-possible oedematous reaction; impaired renal function, cardiac irregularities. May impair ability to perform skilled tasks, for example operating machinery, driving.

Adverse Effects

Abdominal discomfort, anorexia, nausea, vomiting, malaise, headache, dizziness, drowsiness, rectal bleeding; rarely, hypersensitivity reactions, including fever, pruritus, eosinophilia (may be due to dead and dying parasites); ectopic rhythms, urticaria, erythema, convulsions. Store protected from light.

Storage

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9.12 Antiviral Drugs

Herpes and Cytomegalovirus Infections: Herpes Simplex Virus (HSV):
Acyclovir is active against herpes viruses but does not eradicate them. It is only effective if started at onset of infection; it is also used for prevention of recurrence in the immunocompromised patients. Genital lesions, oesophagitis and proctitis may be treated with oral Acyclovir. HSV encephalitis or pneumonitis should be treated with intravenous Acyclovir. Valacyclovir, a prodrug of Acyclovir, can be given by mouth as an alternative treatment for herpes simplex infections of the skin and mucous membranes (including initial and recurrent genital herpes).

Herpes Zoster Virus:

While most HIV positive patients with zoster experience only one self-limiting course, some will experience repeated episodes. Treatment should be reserved for debilitating disease and when there is high risk of serious complications, such as in advanced HIV disease. Acyclovir is the treatment of choice and it can be administered in high oral dose or in the case of lack of response to oral therapy or CNS involvement, it should be given intravenously.

Cytomegalovirus (CMV):
Parenteral antiviral ganciclovir arrests retinochoroiditis and enteritis caused by CMV in HIV infected patients. Maintenance therapy with oral ganciclovir should be given to prevent relapse of retinitis. Alternative therapy with intravenous foscarnet can be used if necessary.

Acyclovir* (Refer Page No. 550)

Pregnancy Category-B Indications Schedule H Treatment of primary genital herpes; disseminated Varicella-zoster in immunocompromised patients; Herpes simplex encephalitis; chicken pox. TABLETS Plain/DT 200, 400 and 800 mg; SUSPENSION 400 mg/5 ml; INFUSION 100 ml (after reconstitution) (250 mg); OINTMENT 5g (3%w/w); DROPS 5 ml (3% w/w); CREAM 5g (5% w/w). Oral

Availability

Dose

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AdultNon-genital herpes simplex treatment, 200 mg five times daily usually for 5 days, longer if new lesions appear during treatment or if healing is incomplete. 400 mg for immunocompromised patients or if absorption is impaired. Genital herpes simplex treatment; 200 mg 5 times daily for 5 days or 400 mg three times daily for three days. Longer if new lesions appear or healing is incomplete. Immunocompromised or HIV positive patients; 400 mg is given five times daily for 7 to 10 days during first episode or 400 mg three times a day for 5 to 10 days during recurrent injection. Herpes simplex prevention of recurrence; 200 mg 4 times daily or 400 mg twice daily reduced to 200 mg two or three times daily interrupted every 6 to 12 months. Varicella and herpes zoster; 800 mg five times daily for 7 days. Chicken pox; 800 mg five times daily for 7 to 10 days. Intravenous infusion Severe initial genital herpes, Varicella zoster, Herpes simplex infection; 5 mg/kg body weight every 8 h for five days. Child- Under 2 years; half dose. Above 2 years; adult dose. Varicella and herpes zoster; 20 mg/kg body weight (max. 800 mg) four times daily for 5 days, under 2 years 200 mg four times daily, for 2 to 5 years; 400 mg four times daily. Over 6 years; 800 mg four times daily. Chicken pox; 20 mg/kg body weight (max 800 mg) four times daily for 5 days. Contraindications Precautions Hypersensitivity; glaucoma; disease; depression. psychiatric

Maintain adequate hydration; renal impairment (Appendix 7d); lactation (Appendix 7b); pregnancy (Appendix 7c); paediatrics.

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Adverse Effects

Nausea, vomiting, abdominal pain, diarrhoea, headache, fatigue, rash, urticaria, pruritus, photosensitivity; rarely, hepatitis, jaundice, dyspnoea, angioedema, anaphylaxis; neurological reactions (including dizziness, confusion, hallucinations, drowsiness), acute renal failure; decrease in haematological indices; on intravenous infusion, severe local inflammation (sometimes resulting in ulceration), fever, agitation, tremor, psychosis and convulsions somnolence, visual abnormalities. Store tablets protected from light. For infusion: Store protected from moisture in a sterile tamper evident container sealed so as to exclude micro-organisms at a temperature not exceeding 30C.

Storage

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Antimigraine Drugs

10.
10.1 10.2

Antimigraine Drugs
For Prophylaxis For Treatment of Acute Attack

235
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10. Antimigraine Drugs

Chronic recurrent headache is associated with many disorders, both somatic and psychogenic. An accurate diagnosis must consequently be made before appropriate treatment can be initiated for migraine. Untreated migraine attacks last for several hours and sometimes for as long as 3 days. Migraine headache is frequently accompanied by episodes of gastrointestinal disturbance including nausea and vomiting. The headache may be preceded or accompanied by aura (classical migraine) which is characterised by visual disturbances such as flickering lines and fragmented vision or sensory disturbances such as tingling or numbness; rarely, hemiparesis or impaired consciousness may occur. Migraine without aura (common migraine) is the more common form occurring in about 75% of patients who experience migraine. Emotional or physical stress, lack of or excess sleep, missed meals, menstruation, alcohol and specific foods including cheese and chocolate are often identified as precipitating factors; oral contraceptives may increase the frequency of attacks. Avoidance of such precipitating factors can be of great benefit in preventing or reducing the frequency of attacks and should be addressed in detail. Women taking combined oral contraceptives who experience an onset or increase in frequency of headaches should be advised of other contraceptive measures. The two principal strategies of migraine management are treatment of acute attacks and prophylactic treatment.

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10.1 For Prophylaxis

Prophylactic treatment should be considered for patients in whom treatment of acute migraine attacks with analgesics or ergotamine is ineffective, or in whom attacks occur more than once a month, or for those with less frequent but severe or prolonged attacks. Prophylaxis can reduce the severity and frequency of attacks but does not eliminate them completely; additional symptomatic treatment is still needed. However, long-term prophylaxis is undesirable and treatment should be reviewed at 6-monthly intervals. Of the many drugs that have been advocated beta-adrenoceptor antagonists (betablockers) are most frequently used. Propranolol, a non-selective beta-blocker and other related compounds with similar profile such as atenolol are generally preferred. The potential for beta-blockers to interact with ergotamine should be borne in mind. Tricyclic antidepressants, such as amitriptyline or calcium-channel blocking drugs such as flunarizine or verapamil may be of value.

Flunarizine
Pregnancy Category-C Indications Availability Dose Prophylaxis of migraine. TABLETS/CAPSULES 5 and 10 mg. Oral Adults- 10 mg at night. Child < 40 kg- 5 mg at night. Contraindications Precautions Adverse Effects Pregnancy (Appendix 7c); lactation. Patient may have drowsiness, should not operate hazardous machines. Drowsiness; weight gain; depression; gastric pain, dry mouth; insomnia; extrapyramidal side effects. Schedule H

Propranolol* (Refer Page No. 287)

Pregnancy Category-C Indications Dose Prophylaxis of migraine. Oral Initially 40 mg 2 to 3 times a day. Maintenance dose 80 to 160 mg daily. Schedule H

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Child- 2-4 mg/kg/day Contraindications Asthma or history of obstructive airway disease; uncontrolled heart failure; Prinzmetal angina, marked bradycardia, hypotension; sick sinus syndrome, second- or third-degree atrioventricular block, cardiogenic shock, metabolic acidosis, severe peripheral arterial disease; pheochromocytoma. First-degree atrioventricular block; renal impairment; liver disease; pregnancy (Appendix 7c); lactation (Appendix 7b); portal hypertension; diabetes mellitus; myasthenia gravis; history of hypersensitivity (increased reaction to allergens, also reduced response to epinephrine (adrenaline); interactions (Appendix 6a, 6b, 6d). Bradycardia, heart failure, hypotension, conduction disorders, bronchospasm, peripheral vasoconstriction, exacerbation of intermittent claudication and Raynaud phenomenon; gastrointestinal disturbances, fatigue, sleep disturbances including nightmares; rarely; rash, dry eyes (reversible); exacerbation of psoriasis. Store protected from light and moisture.

Precautions

Adverse Effects

Storage

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10.2 For Treatment of Acute Attack

Treatment of acute attacks may be non-specific using simple analgesics, or specific using an ergot alkaloid such as ergotamine. If nausea and vomiting are features of the attack, an antiemetic drug may be given. Treatment is generally by mouth; some drugs are available as suppositories which may be administered if the oral route is not effective (poor oral bioavailability, or absorption from the gut impaired by vomiting) or not practicable (patient unable to take drugs orally). Simple analgesics including NSAIDs (nonsteroidal anti-inflammatory drugs) can be effective in mild to moderate forms of migraine if taken early in the attack; most migraine headaches respond to paracetamol, acetylsalicylic acid or NSAID such as ibuprofen or naproxen sodium. Peristalsis is often reduced during migraine attacks and, if available, a dispersible or effervescent preparation of the drug is preferred because of enhanced absorption compared with a conventional tablet. The risk of Reye syndrome due to acetylsalicylic acid in children can be avoided by giving paracetamol instead. Frequent and prolonged use of analgesics by migraine sufferers may lead to analgesic-induced headache. Ergotamine should be considered only when attacks are unresponsive to non-opioid analgesics. It is poorly absorbed when taken orally or sublingually. Rectal suppositories may offer an advantage when other routes of administration are unsatisfactory. To be fully effective ergotamine must be taken in adequate amounts as early as possible during each attack. Adverse effects limit how much ergotamine can be used in a single attack and consequently the recommended dosage should never be exceeded and at least four days should elapse between successive treatments. Even normal dosage can lead to dependence, tolerance to adverse effects and to a withdrawal syndrome on discontinuing the drug. To avoid dependence the frequency of administration should be limited to no more than twice a month. Adverse effects include nausea, vomiting, diarrhoea and vertigo; chronic ergotism is characterized by severe peripheral vasoconstriction which can lead to gangrene in the extremities. The severity of adverse effects prevents the use of ergotamine for migraine prophylaxis. An antiemetic such as metoclopramide, given as a single dose orally or by intramuscular injection at the onset of a NFI-2011 238

Antimigraine Drugs

migraine attack, preferably 10-15 min before the analgesic or ergotamine, is useful not only in relieving nausea but also in restoring gastric motility, thus improving absorption of the antimigraine drug. Products which contain barbiturates or codeine are undesirable, particularly in combination with ergotamine, since they may cause physical dependence and withdrawal headaches.

Acetylsalicylic Acid* (Refer Page No. 4, 281 and 317) Dihydroergotamine*

Pregnancy Category-X Indications Schedule H

Acute treatment of migraine headaches with or without aura and acute treatment of cluster headache episodes. TABLET 1 mg; INJECTION 1 ml Ampoule (1 mg/ml). Usually in combination with other analgesics e.g. caffeine. Adult and child over 12 years- 1 to 2 tablets at onset (max. 4 tablets in 24 h), not to be repeated at intervals of less than 4 days. Intravenous infusion Termination of an acute attack of cluster headache, migraine: Adult- 0.5 to 1 mg, 1 dose (Max: 3 mg/day or 6 mg/week).

Availability Dose

Contraindications

Peripheral vascular disease, coronary heart disease, obliterative vascular disease and Raynauds syndrome, temporal arteritis; hepatic impairment, renal impairment, sepsis; severe or inadequately controlled hypertension, hyperthyroidism, pregnancy (Appendix 7c); lactation; porphyria, ischaemic heart disease; angina pectoris. Risk of peripheral vasospasm; elderly; it should not be used for migraine prophylaxis; interactions (Appendix 6c). Warn patient to stop treatment immediately if numbness or tingling of extremities develops and to contact doctor, compromised circulation; hypertension.

Precautions

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Adverse Effects

Nausea, vomiting, vertigo, abdominal pain, diarrhoea, muscle cramps and occasionally headache provoked (usually because of prolonged excessive dosage or abrupt withdrawal); precardial pain, myocardial and intestinal ischaemia, rarely, myocardial infarction; repeated high dosage may cause ergotism with gangrene and confusion; pleural, peritoneal and heart-valve fibrosis may occur with excessive use; coronary artery vasospasm; ventricular tachycardia; altered sense of taste; rhinitis. Store protected from light.

Storage

Paracetamol* (Refer Page No. 8) Sumatriptan

Pregnancy Category-C Indications Availability Dose Acute treatment of migraine. TABLET 25, 50 and 100 mg; INJECTION 0.5 ml ampoule (6 mg/ml). Oral The recommended oral dose is 25-100 mg, repeatable after 2 hours upto a total dose of 200 mg over a 24 hour period. Parenteral 6 mg at onset subcutaneously, may be repeated once after 1 h for maximum of 2 doses in 24 hours. Contraindications Precautions Adverse Effects Ischaemic heart disease, hypertension; pregnancy (Appendix 7c); renal impairment. Ischaemic heart disease; hepatic impairment. Tightness in head and chest, paraesthesia in limbs, dizziness; rise in BP, bradycardia, sudden death, seizures. Schedule H

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Antineoplastics and Immunosuppressives

11.

Antineoplastics and Immunosuppressives

Antineoplastics Immunosuppressives

243
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11.1 11.2

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11. Antineoplastics and Immunosuppressives

11.1 Antineoplastics
Note: WHo advises that adequate resources and specialist supervision are a prerequisite for the introduction of this class of drugs. Specific expertise, diagnostic precision, individualization of dosage or special equipment are required for their proper use

The treatment of cancer with drugs, radiotherapy and surgery is complex and should only be undertaken by an oncologist. For this reason, the following information is provided merely as a guide. Chemotherapy may be curative or used to alleviate symptoms or to prolong life. Where the condition can no longer be managed with cytotoxic therapy, alternative palliative treatment should be considered. For some tumours, single-drug chemotherapy may be adequate, but for many malignancies a combination of drugs provides the best response. Examples of combination therapy include: CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) for non-Hodgkins disease; ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) for Hodgkins disease; MOPP (chlormethine, vincristine, procarbazine, prednisolone) for Hodgkins disease. Cytotoxic drugs are often combined with other classes of drugs in the treatment of malignant conditions. Such drugs include hormone agonists and antagonists, corticosteroids and immunostimulant drugs. Combinations are, however, more toxic than single drugs.

Precautions and Contraindications

Treatment with cytotoxic drugs should be initiated only after baseline tests of liver and kidney function have been performed and baseline blood counts established. It may be necessary to modify or delay treatment in certain circumstances. The patient should also be monitored regularly during chemotherapy and cytotoxic drugs withheld if there is significant deterioration in bone-marrow, liver or kidney function. Many cytotoxic drugs are teratogenic and should not be 243 NFI-2011

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administered during pregnancy especially in the first trimester. Contraceptive measures are required during therapy and possibly for a period after therapy has ended. Cytotoxic drugs are also contraindicated during lactation. Cytotoxic drugs should be administered with care to avoid undue toxicity to the patient or exposure during handling by the health care provider. All waste, including patients body fluids and excreta (and any material contaminated by them) should be treated as hazardous. Extravasation of intravenously administered cytotoxic drugs can result in severe pain and necrosis of surrounding tissue. If extravasation occurs, aspiration of the drug should first be attempted, then the affected limb is elevated and warm compresses applied to speed and dilute the infusion or it is localized by applying cold compresses until the inflammation subsides; in severe cases, hydrocortisone cream may be applied topically to the site of inflammation. The manufacturers literature should also be consulted for more specific information.

Adverse Effects
Cytotoxic drugs have a considerable potential to damage normal tissue. Specific adverse effects apply, but a number of effects are common to all cytotoxics such as bone-marrow and immunological suppression. Furthermore, the concomitant use of immunosuppressive drugs will enhance susceptibility to infections. Fever associated with neutropenia or immunosuppression requires immediate treatment with antibiotics. Nausea and vomiting: Nausea and vomiting following administration of cytotoxic drugs and abdominal radiotherapy are often distressing and may compromise further treatment. Symptoms may be acute (occurring within 24 h of treatment), delayed (first occurring more than 24 h after treatment), or anticipatory (occurring before subsequent doses). Delayed and anticipatory symptoms are more difficult to control than acute symptoms and require different management. Cytotoxic drugs associated with a low risk of emesis include etoposide, 5- fluorouracil, low-dose methotrexate and the vinca alkaloids; those with an intermediate risk include lowdose cyclophosphamide, doxorubicin and high-dose methotrexate; and the highest risk is with cisplatin, high-dose cyclophosphamide and dacarbazine. For patients at a low risk of emesis, pretreatment with an oral phenothiazine (for example chlorpromazine), continued for up to 24 h after chemotherapy, is often helpful. For patients at a higher risk dexamethasone 6-10 mg by mouth may be added NFI-2011 244

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before chemotherapy. For patients at a high risk of emesis or when other therapies are ineffective, high doses of intravenous metoclopramide may be used.
Note: High doses of metoclopramide are preferably given by continuous intravenous infusion: an initial dose of 2-4 mg/kg is given over 15 to 20 min, followed by a maintenance dose of 3-5 mg/kg over 8 to 12 h; the total dose should not exceed 10 mg/kg in 24 h.

Dexamethasone is the drug of choice for the prevention of delayed symptoms; it is used alone or with metoclopramide. Good symptom control is the best way to prevent anticipatory symptoms and the addition of diazepam to antiemetic therapy is helpful because of its sedative, anxiolytic and amnesic effects. Hyperuricaemia: Hyperuricaemia may complicate treatment of conditions such as non-Hodgkins lymphomas and leukaemia. Renal damage may result from the formation of uric acid crystals. Patients should be adequately hydrated and hyperuricaemia may be managed with allopurinol initiated 24 h before cytotoxic treatment and continued for 7 to 10 days afterwards. Alopecia: Alopecia is common during treatment with cytotoxic drugs. There is no drug treatment, but the condition often reverses spontaneously once treatment has stopped.

Alkylating Drugs:
Alkylating drugs are among the most widely used drugs in cancer chemotherapy. They act by damaging DNA and therefore interfering with cell replication. However, there are two complications. Firstly, they affect gametogenesis and may cause permanent male sterility; in women, the reproductive span may be shortened by the onset of a premature menopause. Secondly, they are associated with a marked increase in the incidence of acute non-lymphocytic leukaemia, in particular when combined with extensive radiation therapy. Cyclophosphamide requires hepatic activation; it can therefore be given orally and is not vesicant when given intravenously. Like all alkylating drugs its major toxic effects are myelosuppression, alopecia, nausea and vomiting. It can also cause haemorrhagic cystitis; an increased fluid intake for 24 to 48 h will help to avoid this complication. Cyclophosphamide is used either as part of treatment or as an adjuvant in NonHodgkins lymphomas, breast cancer, childhood leukaemia and ovarian cancer. It is also used in several palliative regimens. 245 NFI-2011

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Chlorambucil is used to treat chronic lymphocytic leukaemia, Non-Hodgkins lymphomas, Hodgkins disease, ovarian cancer and Waldenstrom (primary) macroglobulinaemia. Adverse effects, apart from bone marrow suppression, are uncommon. However, severe widespread rash can develop and may progress to Stevens-Johnson syndrome or toxic epidermal necrolysis. If a rash occurs, further treatment with chlorambucil is contraindicated. Chlormethine (mustine) forms part of the regimen for treatment of advanced Hodgkins disease and malignant lymphomas. Its toxicity includes myelosuppression, severe nausea and vomiting, alopecia and thrombophlebitis due to vesicant effect.

Cytotoxic Antibiotics:
Bleomycin is used in regimens for the treatment of Hodgkins disease and testicular cancer. It has several antineoplastic drug toxicities; it is known to cause dose-related pneumonitis and fibrosis which can be fatal and is associated with rare acute hypersensitivity reactions. Cutaneous toxicity has also been reported. Doxorubicin is the most widely used anthracycline antibiotic. It is used for acute leukaemias although other anthracyclines are more commonly used in these circumstances. Doxorubicin also plays a palliative role in the treatment of other malignancies. The primary toxic effects are myelosuppression, alopecia, nausea, vomiting and dose-related cardiomyopathy. It is also vesicant and can cause severe skin ulceration on extravasation. Dactinomycin is used to treat paediatric cancers. Its toxicity is similar to that of doxorubicin, but it is not cardiotoxic. Daunorubicin is used in acute leukaemias. Its toxicity is similar to that of doxorubicin.

Antimetabolites and Related Therapy:

Cytarabine is used in the treatment of acute leukaemia; children may tolerate high doses better than adults. Its effects are highly dependent upon the schedule of administration. It causes myelosuppression, mucositis and in high doses, central neurotoxicity. 5-Fluorouracil is primarily used in the adjuvant treatment of colorectal and breast cancer. It is also employed in the palliative treatment of other malignancies. It causes myelosuppression and the palmar-plantar syndrome (erythema and painful desquamation of the hands and feet). When its action is modified by other drugs (such as calcium folinate), its toxicity NFI-2011 246

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profile can change; mucositis and diarrhoea may be significant problems. Central neurotoxicity can also occur. 6-Mercaptopurine is frequently used in the therapy of childhood leukaemia. It can be administered orally and myelosuppression and nausea are the only important toxic effects. Methotrexate is used to treat a variety of malignancies and it plays a major role as an adjuvant for the treatment of breast cancer. Like 5-fluorouracil, methotrexate is myelotoxic, but nausea and vomiting are minimal. It also causes mucositis. Renal impairment reduces methotrexate excretion and can exacerbate toxicity. Calcium folinate is used to counteract the folate-antagonist action of methotrexate and thus speeds recovery from methotrexate-induced mucositis or myelosuppression. Calcium folinate also enhances the effects of 5-fluorouracil when the two are used together for metastatic colorectal cancer.

Vinca Alkaloids and Etoposide:

The vinca alkaloids, vinblastine and vincristine, are primarily used in the treatment of acute leukaemias. Vinblastine is also used for Hodgkins disease and some solid tumours. Vincristine is also used in the management of Non-Hodgkins lymphomas. Both can cause neurotoxicity, but this is more of a problem with vincristine. Myelosuppression is more common with vinblastine. Etoposide is an important component of the treatment of testicular carcinoma and is also used in several regimens for lung cancers and lymphomas. It causes myelosuppression and alopecia and it can cause hypotension during infusion. It does not produce significant nausea and vomiting.

Other Antineoplastic Drugs:

The enzyme asparaginase is an important component in the management of childhood leukaemia, but is not used in any other malignancy. Its toxicity profile is broad and the drug must be carefully administered because of the risk of anaphylaxis. Cisplatin is a platinum compound used in the treatment of ovarian and testicular malignancies. It is also a component of regimens used in non-small cell and small cell lung cancer and plays a palliative role in other malignancies. Cisplatin is myelosuppressive and also produces slight alopecia. However, it causes severe dose-related nausea and vomiting. It is also nephrotoxic and neurotoxic. Nephrotoxicity can be reduced by maintaining high urine output during cisplatin administration and immediately afterwards, but neurotoxicity is often dose-limiting. 247 NFI-2011

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Dacarbazine, thought to act as an alkylating drug, is a component of a regimen for Hodgkins disease. It is also used in the palliative therapy of metastatic malignant melanoma. Its major toxic effects are myelosuppression and intense nausea and vomiting. Levamisole is an anthelminthic with immunostimulating properties; it is used in combination with 5-fluorouracil as adjuvant therapy for colorectal cancer following resection of the tumour. Its major toxic effects are a variety of CNS symptoms, nausea, dermatitis and hypersensitivity reactions. Procarbazine is used in the treatment of advanced Hodgkins disease. Toxic effects include myelosuppression, nausea, vomiting, CNS symptoms and depression. Procarbazine possesses a weak monoamine oxidase inhibitory effect but dietary restriction is not necessary.

Actinomycin D*
Pregnancy Category-C Indications Availability Dose Schedule H Trophoblastic tumours, Wilms tumour, Ewings sarcoma, rhabdomyosarcoma. INJECTION Vial 500 mg. Intravenous injection Adult and child above 6 months- 15 g/kg/ day. Principally used to treat paediatric cancers. Contraindications See notes above and consult literature; hypersensitivity; lactation; infection with children; herpes zoster; pregnancy (Appendix 7c) and lactation. See notes above and consult literature. See notes above and consult literature. Hair loss; nausea; vomiting; mouth sores; diarrhoea.

Precautions Adverse Effects

Note: Irritant to tissues

Alpha Interferon*
Pregnancy Category-C Indications Schedule H Hairy cell leukaemia, AIDS related Kaposis sarcoma in patients above 18 years. Malignant melanoma. VIALS 3, 5 & 6 million IU; 44 g (Interferon B).

Availability

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Dose

Adult- Hairy cell leukaemia induction: 3 million IU daily for 16 to 24 weeks. Maintenance 3 million IU three times a week. Treatment for 6 months approx. Kaposis Sarcoma: 36 million IU for 10 to 12 weeks, maintenance 36 million IU three times a week. Child- Not recommended for children. Consult product literature; avoid injections containing benzyl alcohol in neonates; pregnancy (Appendix 7c); lactation. Consult product literature; leukaemia; renal impairment. hairy cell

Contraindications

Precautions Adverse Effects

Anorexia, nausea, influenza-like symptoms and lethargy. Ocular side-effects and depression (including suicidal behaviour) have also been reported. Myelosuppression may occur, particularly affecting granulocyte counts. Cardiovascular problems (hypotension, hypertension and arrhythmias), nephrotoxicity and hepatotoxicity have been reported. Hypertriglyceridaemia, monitoring of lipid concentration is recommended. Hypersensitivity reactions, thyroid abnormalities, hyperglycaemia, alopecia, psoriasiform rash, confusion, coma and seizures (usually with high doses in the elderly), leucopenia; thrombocytopenia; mucosities; pancreatitis. Store protected from light at or below -20C.

Storage

Bleomycin*
Pregnancy Category-D Indications Schedule H, G Adjunct to surgery and radiotherapy in palliative treatment of Hodgkins and non-Hodgkins lymphomas; reticulum cell sarcoma and lymphoma; carcinomas of the head, neck, larynx, cervix, penis, skin, vulva, testicles including embryonal cell carcinoma, choriocarcinoma and teratoma; malignant effusions. INJECTION 15 and 30 mg/vial. Intramuscular and subcutaneous injection 30 mg twice a week, dose can also vary from 15 mg daily to 15 mg weekly; total 300 to 400 mg. Small cell cancer; 0.25 to 0.5 mg/kg body weight once or twice a week. Contraindications Precautions See notes above and literature; preexisting lung disease; pregnancy (Appendix 7c) and lactation (Appendix 7b). See notes above and consult literature; renal impairment; interactions (Appendix 6c).

Availability Dose

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Adverse Effects Storage

See notes above and consult literature. Dermatitis; nephrotoxicity; hepatotoxicity. Store protected from light in a sealed container.

Note: Irritant to tissues

Busulphan*
Pregnancy Category-D Indications Availability Dose Schedule G Chronic granulocytic leukaemia, chronic myelogenous leukaemia, polycythaemia vera, myelofibrosis, thrombocythaemia. TABLET 2 mg. Oral Chronic myeloid leukaemia, induction of remission: 60 g/kg body weight daily (max 4 mg) maintenance dose 0.5 to 2 mg daily. Contraindications Pregnancy (Appendix 7c); bone marrow suppression; chronic lymphocytic leukaemia; lactation. Monitor cardiac function; pregnancy; lactation previous radiation therapy; avoid in porphyria, hepatic impairment; interactions (Appendix 6c). Hepatotoxicity (including hepatic venoocclusive disease, hyperbilirubinaemia, jaundice and fibrosis); cardiac tamponade at high doses in thalassaemic patients; pneumonia; skin hyperpigmentation; hyperuraecemia; pulmonary fibrosis. Store protected from light.

Precautions

Adverse Effects

Storage

Chlorambucil*
Pregnancy Category-D Indications Schedule G Chronic lymphocytic leukaemia; some nonHodgkins lymphomas; Hodgkins disease, ovarian cancer and Waldenstrom (primary) macroglobulinaemia. TABLETS 2 and 5 mg. Oral

Availabilty: Dose

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Adult- Chronic lymphocytic leukaemia: initially 150 g/kg body weight daily until leucocyte count sufficiently reduced. Maintenance (started 4 weeks after first course) 100 g/kg body weight. Waldarstroms macroglobulinaemia: 6 to 12 mg daily until leucopenia occurs, then reduce to 2 to 8 mg daily. Child- Not recommended. Contraindications See notes above and consult literature; hypersensitivity; porphyria; pregnancy (Appendix 7c) and lactation (Appendix 7b). See notes above and consult literature; renal impairment; hepatic impairment (Appendix 7a). See notes above and consult literature. Hepatotoxicity; peripheral neuropathy; cystitis; seizures; pulmonary fibrosis. Store protected from light.

Precautions

Adverse Effects

Storage

Cisplatin*
Pregnancy Category-D Indications Schedule H Metastatic testicular tumours, metastatic ovarian tumours, advanced bladder carcinoma and other solid tumours. INJECTION 10 ml (10 mg) and 50 ml (50 mg) vials. Intravenous injection (use syringes devoid of aluminium component) Ovarian tumor: 50 mg/m2 of body surface area once every three weeks. Bladder cancer: 50 to 70 mg/m2 once every 3 to 4 weeks. Testicular tumor: 20 mg/m2 for 5 days every 3 weeks for 3 courses. Contraindications See notes above and consult literature; hypersensitivity; renal impairment (Appendix 7d); pregnancy (Appendix 7c) and lactation (Appendix 7b). See notes above and consult literature; hyperuraemia; hypomagnesaemia; hypocalcaemia; interactions (Appendix 6c). See notes above and consult literature. Tinnitus; neuropathy.

Availability Dose

Precautions

Adverse Effects

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Storage

Store protected from light.

Cyclophosphamide*
Pregnancy Category-D Indications Schedule G Malignant lymphomas including NonHodgkins lymphomas, lymphocytic lymphoma, Burkitts lymphoma; multiple myeloma; leukaemias, mycosis fungoides; neuroblastoma; adenocarcinoma of the ovary; retinoblastoma; breast cancer. TABLET 50 mg; INJECTION 15 ml (200 mg), 30 ml (500 mg) and 50 ml (1g) vials; dry powder to be reconstituted before administration. Intravenous injection Malignancy: 40 to 50 mg/kg body weight in divided doses over 2 to 5 days. Alternatively 10 to 15 mg/kg body weight every 7 to 10 days or 3 to 5 mg/kg body weight twice a week. Oral 1 to 5 mg/kg body weight. Minimal change nephrotic syndrome: 2.5 to 3 mg/kg body weight. Contraindications See notes above and consult literature; bladder haemorrhage; thrombocytopenia; severe bone marrow depression; pregnancy (Appendix 7c) and lactation (Appendix 7b). See notes above and consult literature; renal impairment (Appendix 7d) and hepatic impairment (Appendix 7a); interactions (Appendix 6c). See notes above and consult literature. Haemorrhagic cystitis; colitis; cardiac toxicity; anorexia; thrombocytopenia; dermatitis. Injection: Store in refrigerator (2 to 8C). Avoid long exposure to temperature above 30C. The solution should be used immediately after preparation as it deteriorates on storage. Tablet: Store at a temperature not exceeding 30C.

Availability

Dose

Precautions

Adverse Effects

Storage

Cytosine Arabinoside (Cytarabine)*

Pregnancy Category-D Indications Schedule H Acute lymphoblastic leukaemia; chronic myeloid leukaemia; meningeal leukaemia; erythroleukaemia; Non-Hodgkins lymphomas; lymphosarcoma.

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Availability Dose

INJECTION vials 1 ml (100 mg), 5 ml (500 mg) and 10 ml (1g). Intravenous injection Adult- 100 mg/m2 body surface area every 12 h for seven days. Child- 100 mg/m2 body surface area twice daily by rapid injection or 100 mg/m2 body surface area daily by contiuous infusion given by 5 to 10 days.

Contraindications

See notes above and consult literature; hypersensitivity; pregnancy (Appendix 7c) and lactation (Appendix 7b). See notes above and consult literature; uric acid level monitoring recommended; hepatic impairment (Appendix 7a). See notes above and consult literature; g.i.t. disturbances. Store protected from light.

Precautions

Adverse Effects Storage

Doxorubicin*
Pregnancy Category-D Indications Schedule H, G Soft tissue and bone sarcomas, acute leukemia, malignant lymphoma, Hodgkin's disease, non-Hodgkin's disease, breast carcinoma, small-cell carcinoma of lungs, AIDSrelated Kaposis sarcoma, multiple myeloma, gastro-intestinal tract carcinoma, bladder cancer, ovarian carcinoma, acute myeloblastic leukemia, thyroid carcinoma, neuroblastoma. INJECTION 10 & 50 mg lyophilized powder/vial, 2 mg/ml solution LIPOSOMAL injection 10 ml vial (2 mg/ml). Intravenous 50-75 mg/m2 body surface area by slow i.v injection every 3 weeks. AIDS-related Kaposi's sarcoma: Adult: As pegylated liposome: 20 mg/m2 body surface area infused over 1 hr once every 3 weeks. Ovarian carcinoma: Adult: As pegylated liposome: 50 mg/m2 BSA infused over 1 hr once every 4 weeks. Contraindications Known hypersensitivity, cardiac disease, pregnancy (Appendix 7c), lactation, neonates.

Availability

Dose

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Precautions

Avoid extravasation, monitor ECG changes, arrhythmias, blood counts, hypotension or congestive heart failure, hepatic impairment, interactions (Appendix 6c). Liposomal and non-liposomal preparations are not interchangeable. Infusion reactions, cardiotoxicity, bone marrow suppression, liver impairment, nausea and vomiting, reversible alopecia, stomatitis, conjunctivitis, keratitis, mucositis, discolouration of body fluids, local skin reactions and tissue damage, secondary leukemias. Store protected from light, in well closed containers at temperature between (1530C); Store intact vials of solution under refrigeration at 2-8C. Use the solution prepared using the liquid stated on the label immediately after preparation but, in any case, within the period recommended by the manufacturer when prepared and stored strictly in accordance with the instructions of the manufacturer. Liposomal formulations: Refrigerate at 2-8C. Do not freeze.

Adverse Effects

Storage

Etoposide*
Pregnancy Category-D Indications Refractory leukaemia; cancer. testicular malignant Schedule H tumours; acute lymphoma; lung

Availability Dose

CAPSULES 25, 50 and 100 mg; INJECTION vial 100 mg/5 ml. Intramuscular injection Adult- Initially 50 to 100 mg/m2 body surface area daily by infusing over 30 to 60 min. Thereafter, no injection for 3 to 4 weeks is given. Small cell lung cancer: 350 mg/m2 daily. Oral Adult- 100 to 200 mg/m2 body surface area from day 1 to 5 taken on empty stomach, thereafter no treatment for 3 to 4 weeks.

Contraindications

See notes above and consult literature; hypersensitivity; severe liver dysfunction; pregnancy (Appendix 7c) and lactation (Appendix 7b). See notes above and consult literature; hepatic impairment (Appendix 7a); interactions (Appendix 6c); renal impairment (Appendix 7d).

Precautions

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Adverse Effects

See notes above and consult literature. Alopecia; gastrointestinal disturbances; thrombophlebitis; neuritis. Store protected from moisture at a temperature not exceeding 30C. Capsules should not be stored in refrigerator.

Storage

Note: Irritant to tissues

5-Fluorouracil* (Refer Page No. 361)

Pregnancy Category-D Indications Schedule H Carcinomas of the colorectum, breast, stomach, pancreas, cervix, prostate, ovary and endometrium; liver tumours; head and neck tumours; actinic keratosis. INJECTION 5 and 10 ml ampoule (50 mg/ml). TABLETS 50 mg. Intravenous injection Initially 12 mg/kg body weight once a day for 4 days, max. daily dose 800 mg. If tolerated well without toxicity 6 mg/kg body weight can be given on 6th, 8th, 10th and 12th day. Discontinue on 12th day. Maintenance dose 10 to 15 mg/kg body weight every week (max dose 1g/week). Contraindications See notes above and consult literature; bone marrow depression; pregnancy (Appendix 7c) and lactation (Appendix 7b). See notes above and consult literature; lactation; pelvic irradiation; renal impairment; hepatic impairment (Appendix 7a); interactions (Appendix 6c). See notes above and consult literature. Cardiac toxicity; tachycardia; dermatitis; diarrhoea. Store protected from light in single dose container at a temperature not exceeding 30C. The injection should not be allowed to freeze.

Availability Dose

Precautions

Adverse Effects

Storage

Folinic Acid*
Pregnancy Category-A Indications High-dose methotrexate therapy (folate rescue); inadvertent overdose of methotrexate; with 5-fluorouracil in the palliative treatment of advanced colorectal cancer.

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Availability Dose

INJECTION 3 mg/ml. Prevention of methotrexate induced adverse reactions; started 24 h after treatment with methotrexate by intravenous infusion or by intravenous injection. 15 mg repeat every 6 h for 48 to 72 h. Intrathecal injection. Avoid simultaneous administration of methotrexate; not indicated for pernicious anaemia or other megaloblastic anaemias due to vitamin B12 deficiency; pregnancy (Appendix 7c) and lactation; interactions (Appendix 6c). Hypersensitivity reactions; rarely, pyrexia after parenteral use; wheezing; swelling of facial features.

Contraindications Precautions

Adverse Effects

Gemcitabine*
Pregnancy Category-D Indications Availability Dose Adenocarcinoma of pancreas. INJECTION Vial 200 mg and 1g (dry powder to be reconstituted before administration). 1g/m2 body surface area for over 30 min once a week for up to 7 weeks, if not tolerated reduce or withhold. After one week rest administer by infusion once weekly for three weeks, withhold for 4th week before repeating. Pregnancy (Appendix 7c); concurrent radial radiotherapy; hypersensitivity; lactation. Gemcitabine is not recommended for patients who can have potentially curative surgery. There is insufficient evidence about its use for second-line treatment of pancreatic adenocarcinoma, hepatic impairment; renal impairment, interactions (Appendix 6c). Nausea, vomiting, oral mucositis, hyperuricaemia, bone marrow suppression, alopecia, thromboembolism, flu like syndrome; edema; thrombocyathemia; somnolence; hematuria; dyspnoea; loss of appetite. Store in a sterile, airtight, tamperproof container. Schedule H

Contraindications Precautions

Adverse Effects

Storage

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Imatinib*
Pregnancy Category-D Indications Chronic myeloid leukaemia, Philadelphia chromosome positive acute lymphoblastic leukaemia, Gastrointestinal stromal tumor. CAPSULES 100 and 400 mg. 400-600 mg/day. Hypersensitivity. Interactions (Appendix 6c); pregnancy (Appendix 7c). Acute-nausea and vomiting; chronic fluid retention with ankle and periorbital edema, diarrhoea, myalgias, congestive heart failure.

Availability Dose Contraindications Precautions Adverse Effects

L- Asparaginase*
Pregnancy Category-C Indications Availability Dose Acute lymphoblastic leukaemia. INJECTION 5,000, 6,000 and 10,000 IU (for reconstitution before administration). Intramuscular, intravenous or subcutaneous injection Exclusively in acute lymphoblastic leukaemia. Careful monitoring is required. Urine is tested for glucose because of risk of hyperglycaemia. Contraindications See notes above and consult literature; pregnancy (Appendix 7c) and lactation (Appendix 7b). See notes above and consult literature. See notes above and consult literature. Schedule G

Precautions Adverse Effects

Melphalan*
Pregnancy Category-D Indications Schedule H Breast carcinoma, multiple myeloma, advanced ovarian carcinoma, malignant melanoma, polycythaemia vera. TABLETS 2 and 5 mg; INJECTION 50 mg/vial. Oral

Availability Dose

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Adult- Multiple myeloma: usual dose 6 mg/ day. Maintenance dose 2 mg/day. Alternatively 10 mg daily for 7 days (total dose 70 mg), repeat if required after blood counts particularly neutrophils and platelets. Ovarian carcinoma: 0.2 mg/kg body weight daily for 5 days, repeat after 4 to 5 weeks. Child- 0.15 mg/kg body weight daily for 7 days. Maintenance dose is 0.05 mg/kg body weight daily when platelet count is rising. Intravenous injection For Injection: 16 mg/m2. Contraindications Precautions Adverse Effects Pregnancy (Appendix 7c); hypersensitivity; myelosuppression; lactation. Hepatic impairment; renal impairment; interactions (Appendix 6d). Nausea, vomiting, oral mucositis, hyperuricaemia, bone marrow suppression, alopecia, thromboembolism, leucopenia; menstrual irregularities; haemolytic anaemia. Store protected from light and moisture at a cool place.

Storage

6-Mercaptopurine*
Pregnancy Category-D Indications Availability Dose Schedule G Acute leukaemias; Chronic granulocytic leukaemia; choreocarcinoma. INJECTION 2 ml ampoule (200 mg/2 ml) TABLET 50 mg. Oral Leukaemia in children (maintenance): 2.5 mg/ kg body weight in continuation with other drugs daily. Contraindications See notes above and consult literature; hypersensitivity; pregnancy (Appendix 7c) and lactation (Appendix 7b). See notes above and consult literature; monitor blood count; uric acid levels; renal impairment and hepatic impairment (Appendix 7a); interactions (Appendix 6c). See notes above and consult literature. Hepatotoxicity; anorexia; nausea; hyperuricaemia; ulcers.

Precautions

Adverse Effects

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Storage

Store protected from light and moisture.

Methotrexate* (Refer Page No. 385)

Pregnancy Category-X Indications Schedule H Carcinoma of the breast, head and neck and lung; trophoblastic tumours; acute lymphoblastic leukaemia, meningeal leukaemia; non-Hodgkins lymphomas; advanced cases of mycosis fungoides; non-metastatic osteosarcoma; severe rheumatoid arthritis. TABLETS 2.5, 5, 7.5, 10 and 15 mg; INJECTION 2, 5, 15 and 50 ml/vial; ampoule (5 mg/ml and 25 mg/ml); VIALS 5, 25, 100 mg/ml; GEL 1% w/w. Oral Choriocarcinoma: 15 to 30 mg daily for 5 days repeat 3 to5 full courses after 1 week. Intramuscular route 15 to 30 mg daily for 5 days, repeat 3 to5 courses after 1 week. Leukaemia, maintenance after remission: 30 mg/m2 body surface area (max upto 15 mg twice a week). Contraindications See notes above and consult literature; severe renal and hepatic impairment; alcohol liver disease; severe leucopenia; thrombocytopenia; pregnancy (Appendix 7c) and lactation (Appendix 7b). See notes above and consult literature; bone marrow depression; renal and hepatic impairment (Appendix 7a); interactions (Appendix 6a, 6c, 6d). See notes above and consult literature. CNS toxicity; stomatitis; hepatobiliary disorder; fatigue. Store protected from light and moisture.

Availability

Dose

Precautions

Adverse Effects

Storage

Mitomycin*
Pregnancy Category-D Indications Adrenocarcinoma, lymphosarcoma and seminoma, superficial bladder cancer (adjuvant therapy).

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Availability Dose

INJECTIONS vial 2 and 10 mg (dry powder to be reconstituted before administration). Intravenous injection Adult- 6 to 10 mg twice a week, alternatively 0.5 mg/kg body weight daily for 5 days, repeat after 2 weeks.

Contraindications

Pregnancy (Appendix 7c); bone marrow depression; severe anaemia; thrombocytopenia; lactation. It causes delayed bone-marrow toxicity and therefore it is usually administered at 6-weekly intervals. Caution in handling because it is irritant to tissues, thrombocytopenia; necrosis; leucopenia. Prolonged use may result in permanent bone-marrow damage. It may also cause lung fibrosis and renal damage; dyspnea. Store protected from light.

Precautions

Adverse Effects

Storage

Note: Irritant to tissues

Paclitaxel*
Pregnancy Category-D Indications Availability Schedule H Metastatic ovarian and breast cancer. INJECTION vial 30, 100, 200, 260 and 300 mg (dry powder to be reconstituted before administration). Intravenous infusion Adult- 175 mg/m2 body surface area over 3 h, repeat every 3 weeks. Antihistamines, corticosteroids or H2 antagonist may be required during treatment. Child- Not recommended. Contraindications Hypersensitivity; severe hepatic impairment; lactation; pregnancy (Appendix 7c).

Dose

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Adverse Effects

Myelosuppression, peripheral neuropathy and cardiac conduction defects with arrhythmias (which are nearly always asymptomatic); alopecia, muscle pain; nausea and vomiting is mild to moderate, hypersensitivity reactions; myalgia; arthralgia. Store protected from light at a temperature not exceeding 25C.

Storage

Procarbazine*
Pregnancy Category-D Indications Availability Dose Schedule H Part of MOPP regimen in Hodgkins and NonHodgkins lymphomas. TABLETS 50 mg. Oral 50 mg daily to start with initially, increased to 250 to 300 mg individual doses. Maintenance (on remission): 50 to 100 mg daily to cumulative total of at least 6g. Contraindications See notes above and consult literature; hypersensitivity; pregnancy (Appendix 7c) and lactation (Appendix 7b). See notes above and consult literature; ulceration; haemorrhage; leucopenia: renal and hepatic impairment (Appendix 7a); interactions (Appendix 6a). See notes above and consult literature; leucopenia; anaemia; thrombocytopenia; hypotension; retinal haemorrhage.

Precautions

Adverse Effects

Tamoxifen* (Refer Page No. 472) Thalidomide

Pregnancy Category-X Indications Availability Schedule H Multiple myeloma, erythema nodosum leprosum CAPSULES 50 and 100 mg.

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Dose

Multiple myeloma Adult: The dose is 200 mg administered orally once daily with water, preferably at bedtime and at least 1-hour after the evening meal. Thalidomide is administered in combination with dexamethasone in 28-day treatment cycles. Dexamethasone is 40 mg daily administered orally on days 1-4, 9-12, and 17-20 every 28 days. Erythema nodosum leprosum (ENL) Adult: For cutaneous ENL, thalidomide dosing should be initiated at 100 to 300 mg/day, administered once daily with water, preferably at bedtime and at least 1 hour after the evening meal. Not for monotherapy if moderate or severe neuritis present. Max: 400 mg/day. Patients < 50 kg: Initially, 100 mg daily. Dosing with thalidomide should continue until signs and symptoms of active reaction have subsided, usually a period of at least 2 weeks. Patients may then be tapered off medication in 50 mg decrements every 2 to 4 weeks. Patients who have a history of requiring prolonged maintenance treatment to prevent the recurrence of cutaneous ENL or who flare during tapering, should be maintained on the minimum dose necessary to control the reaction. Tapering off medication should be attempted every 3 to 6 months, in decrements of 50 mg every 2 to 4 weeks. Hypersensitivity, pregnancy (Appendix 7C) and lactation, interactions (Appendix 6c).

Oral

Contraindications

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Precautions

During the period of treatment both males and females should take adequate means of contraception before, during and after (atleast 4 weeks) the therapy, therapy to be stopped immediately if pregnancy occurs, no blood or sperm donation during therapy, signs and symptoms of hypersensitivity include the occurrence of erythematous macular rash, possibly associated with fever, tachycardia, and hypotension, and if severe, may necessitate interruption of therapy, Serious dermatologic reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis, seizures, impairment of mental and/or physical abilities required for the performance of hazardous tasks such as driving a car or operating complex machinery, potentiation of somnolence caused by alcohol, peripheral neuropathy, thromboembolism reported. Teratogenicity, Drowsiness/somnolence, peripheral neuropathy, constipation, dizziness, bradycardia, orthostatic hypotension, hypersensitivity, and neutropenia. Store protected from moisture, at a temperature not exceeding 30C.

Adverse Effects

Storage

Vinblastine*
Pregnancy Category-D Indications Schedule H Disseminated Hodgkins and Non-Hodgkins lymphomas; advanced testicular carcinoma, breast carcinoma; palliative treatment of Kaposis sarcoma; trophoblastic tumours; Letterer-Siwe disease; Histolytic lymphoma. VIAL 10 ml (1 mg/ml). Intravenous injection only 3.7 mg/m2 body surface surface area in single dose. Increase on weekly intervals depending on WBC count (max 18.5 mg/m2 body area). Contraindications See notes above and consult literature; hypersensitivity; severe granulocytopenia; lactation (Appendix 7b). Intrathecal injection is contraindicated.

Availability Dose

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Precautions

See notes above and consult literature; neurotoxicity; ischaemic heart disease; hepatic impairment (Appendix 7a); interactions (Appendix 6c); pregnancy (Appendix 7c). See notes above and consult literature. Stomatitis; lucopenia; constipation; bone pain. Store in sealed container in a deep freezer (below -18C).

Adverse Effects

Storage

Note: Irritant to tissues

Vincristine*
Pregnancy Category-D Indications Schedule H Acute lymphoblastic leukaemia; neuroblastoma, Wilms tumour, Hodgkins and NonHodgkins lymphomas; rhabdomyosarcoma, Ewings sarcoma; mycosis fungoides. INJECTION 1 mg/ml. Intravenous route Adult- 1.4 mg/m2 body surface area per week. Contraindications See notes above and consult literature; lactation (Appendix 7b). Intrathecal injection is contraindicated. Precautions See notes above and consult literature; uric acid neuropathy; branchospasm; hepatic impairment (Appendix 7a); pregnancy (Appendix 7c). See notes above and consult literature. Store in sealed container in a deep freezer (below-18C).

Availability Dose

Adverse Effects Storage

Note: Irritant to tissues

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11.2 Immunosuppressives
Note: WHo advises that this class of drugs is for use only when adequate resources and specialist care are available. Specific expertise, diagnostic precision, individualization of dosage or special equipment are required for their proper use

Immunosuppressive drugs are used in organ transplant recipients to suppress rejection; they are also used as second-line drugs in chronic inflammatory conditions. Treatment should only be initiated by a specialist. Careful monitoring of blood counts is required in patients receiving immunosuppressive drugs and the dose should be adjusted to prevent bonemarrow toxicity. Immunosuppressed patients are particularly prone to atypical infections. Azathioprine is the most widely used drug in transplant recipients. It is useful when corticosteroid therapy alone has proven inadequate or for other conditions when a reduction in the dose of concurrently administered corticosteroids is required. It is metabolized to 6-mercaptopurine and, as with mercaptopurine, doses need to be reduced when given with allopurinol. The predominant toxic effect is myelosuppression, although hepatic toxicity also occurs. Cyclosporine is a potent immunosuppressant which is virtually free of myelotoxic effects, but is markedly nephrotoxic. It is particularly useful for the prevention of graft rejection and for the prophylaxis of graft-versus-host disease. The dose is adjusted according to plasma-cyclosporine concentrations and renal function. Dose-related increases in serum creatinine and blood urea nitrogen (BUN) during the first few weeks may necessitate dose reduction. Corticosteroids such as prednisolone have significant immunosuppressant activity and can also be used to prevent rejection of organ transplants.

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Azathioprine* (Refer Page No. 382 and 434)

Pregnancy Category-D Indications Schedule H To prevent rejection in transplant recipients; rheumatoid arthritis; inflammatory bowel disease; Multiple sclerosis; autoimmune hepatitis; atopic dermatitis (AD). TABLETS 25 and 50 mg. Oral Adult and child over 3 months-Renal transplantation: initially 5 mg/kg body weight daily. Maintenance 2 to 2.5 mg/kg daily. Atopic dermatitis (AD): 1 to 3 mg/ kg/day once daily. Contraindications Precautions Hypersensitivity to azathioprine and mercaptopurine; lactation (Appendix 7b). Monitor for toxicity throughout treatment; full blood counts necessary every week (or more frequently with higher doses and in renal or hepatic impairment) for first 4 weeks of treatment and at least every 3 months thereafter; reduce dose in elderly; renal impairment; liver disease (Appendix 7a); interactions (Appendix 6c, 6d); lactation (Appendix 7b); pregnancy (Appendix 7c). Patients should be warned to report immediately any signs or symptoms of bone marrow suppression, for example unexplained bruising or bleeding, infection. Adverse Effects Hypersensitivity reactions including malaise, dizziness, vomiting, fever, muscular pains, arthralgia; rash; hypotension or interstitial nephritis call for immediate withdrawal; haematological toxicity includes leukopenia and thrombocytopenia (reversible upon withdrawal); liver impairment, cholestatic jaundice; hair loss; increased susceptibility to infections and colitis in patients also receiving corticosteroids; nausea; rarely, pancreatitis, pneumonitis, hepatic venoocclusive disease; microcystosis.

Availability Dose

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Storage

Store protected from light.

Cyclosporine* (Refer Page No. 434)

Pregnancy Category-C Indications Schedule H Rejection in kidney, liver, heart or bonemarrow transplantation; graft-versushost disease; in severe recalcitrant atopic dermatitis. CAPSULES 10, 25, 50 and 100 mg; INFUSION 50 and 100 ml (100 mg/ml); INJECTION 1 and 5 ml ampoule (250 mg/ml). Oral and intravenous infusion Adult and child over 3 months- Initially 5 mg/ kg b.i.d. for 2 weeks; can be reduced to 1.5 to 3 mg/kg/day according to patients response. If no response after 2 weeks, increase dose 7 mg/kg/day. Organ transplant: 10 to 15 mg/kg body weight 2 to 4 h before transplantation, followed by 10 to 15 mg/kg body weight for 1 to 2 weeks post operatively. Decrease thereafter gradually to 2 to 6 mg/kg body weight for maintenance (adjust according to blood cyclosporine concentration and renal function), if required 1/3rd corresponding oral dose can be administered by intravenous infusion over 2 to 6 h. Intravenous infusion Bone marrow transplantation; 3 to 5 mg/kg body weight by intravenous infusion over 2 to 4 h from day before transplantation. Contraindications Patients affected by psoriasis.

Availability

Dose

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Precautions

Monitor kidney function (dose dependent increase in serum creatinine and urea during first few weeks may necessitate dose reduction, exclude rejection if kidney transplant), monitor liver function (adjust dosage according to bilirubin and liver enzymes, also refer Appendix 7a); monitor blood pressure (discontinue if hypertension cannot be controlled by antihypertensives); monitor serum potassium, particularly if marked renal impairment (risk of hyperkalaemia); monitor serum magnesium; hyperuricaemia; measure blood lipids before and during treatment; avoid in porphyria; vaccination ineffective; monitor serum creatinine levels; patients affected with psoriasis; lactation (Appendix 7b); interactions (Appendix 6b, 6c); pregnancy (Appendix 7c). Dose-related and reversible increases in serum creatinine and urea unrelated to tissue rejection; burning sensation in hands and feet during initial therapy; electrolyte disturbances including hyperkalaemia, hypomagnesaemia; hepatic dysfunction; hyperuricaemia; hypercholesterolaemia; hyperglycaemia, hypertension (especially in heart transplant patients); increased incidence of malignancies and lymphoproliferative disorders; increased susceptibility to infections due to immunosuppression; gastrointestinal disturbances; gingival hyperplasia; hirsutism; fatigue; allergic reactions; thrombocytopenia (sometimes with haemolytic uraemic syndrome), also mild anaemia; tremors; convulsions, neuropathy; dysmenorrhoea or amenorrhoea; pancreatitis, myopathy or muscle weakness; cramps, gout, oedema; headache; gingival hypertrophy; renal dysfunction; hypertrichosis; paresthesia; renal toxicity; gastrointestinal symptoms. Store in a well closed container below 25C.

Adverse Effects

Storage

Tacrolimus
Pregnancy Category-C Indications Prophylaxis of organ rejection in patients receiving allogeneic liver, kidney, or heart transplants. Tacrolimus ointment is indicated for atopic dermatitis and psoriasis.

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Availability

TABLETS 0.5, 1, 2 and 5 mg CAPSULES 0.5, 1, 2 and 5 mg OINTMENTS 0.03%, 0.1 %, 0.3% w/w INJECTIONS 5 mg/ml. Starting dose for injection- 0.03 to 0.05 mg/ kg/day as a continuous infusion. Oral Adult- Initial-0.15 to 0.2 mg/kg/day for kidney transplants, 0.1 to 0.15 mg/kg/day for liver transplants. Child- 0.15 to 0.2 mg/kg/day for liver transplant patients in two divided doses 12 hours apart.

Dose

Contraindications Precautions

Hypersensitivity to tacrolimus. Monitoring of blood trough serum concentrations for preventation of organ rejection and to reduce drug related toxicity, pregnancy (Appendix 7c); interactions (Appendix 6c, 6d). Nephrotoxicity; neurotoxicity; hyperglycemia, hypertension, hyperkalemia, and gastrointestinal disturbances. Store protected from light.

Adverse Effects

Storage

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12.
12.1 12.2

Antiseptics and Disinfectants

Antiseptics Disinfectants

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12. Antiseptics and Disinfectants

12.1 Antiseptics
An antiseptic destroys or inhibits growth of micro-organisms on living tissues without causing injurious effects when applied to surfaces of the body or to exposed tissues. Some antiseptics are applied to the unbroken skin or mucous membranes, to burns and to open wounds to prevent sepsis by removing or excluding microbes from these areas. Iodine has been modified for use as an antiseptic. The iodophore, povidoneiodine, is effective against bacteria, fungi, viruses, protozoa, cysts and spores and significantly reduces surgical wound infections. The solution of povidone iodine releases iodine on contact with the skin. Chlorhexidine has a wide spectrum of bactericidal and bacteriostatic activity and is effective against both Gram-positive and Gram-negative bacteria although it is less effective against some species of Pseudomonas and Proteus and relatively inactive against mycobacteria. It is not active against bacterial spores. Chlorhexidine is incompatible with soaps and other anionic materials, such as bicarbonates, chlorides, and phosphates, forming salts of low solubility which may precipitate out of solution