Hospital Pharmacy Volume 39, Number 3, pp 225237 2004 Wolters Kluwer Health, Inc.

FEATURED ARTICLE

A Guide to Drug Therapy in Patients with Enteral Feeding Tubes: Dosage Form Selection and Administration Methods
M. Christina Beckwith, PharmD,* Sarah S. Feddema, PharmD,* Richard G. Barton, MD, and Caran Graves, RD

Abstract Drug therapy may be complicated in hospitalized patients receiving nutrition via enteral feeding tubes. Dosage form selection and appropriate administration methods are crucial in patients with feeding tubes. Although hospitalized patients receive nutritional support through various routes, oral nutrition is preferred. Enteral or parenteral nutrition may be used if oral intake is inadequate or inadvisable. Patients with functional gastrointestinal tracts usually receive enteral nutrition. Administering oral medications through the enteral feeding tube can lead to complications like tube clogging or decreased drug activity. However, drug therapy need not be compromised in patients receiving enteral nutrition. Careful selection and preparation of dosage forms reduces the complications of medication administration. Flushing the feeding tube and screening for drug incompatibilities decreases the incidence of tube clogging and replacement. Key Words critical care; drug administration; enteral nutrition Hosp Pharm 2004;39:225237

neously, by manual insertion at the bedside, traditional surgical techniques, laparoscopy, endoscopy, or fluoroscopic guidance. Enteral nutrition formulas may be infused into the stomach, duodenum, or jejunum.3,4 Small-Bore Tubes Flexible, small-bore nasoenteric (NE) tubes (ie, Dobhoff, Miller-Frederick) are commonly used for short-term enteral feedings. These tubes can be placed into the stomach or even the duodenum at the bedside, or into the duodenum or jejunum using fluoroscopy or endoscopy. These soft, small lumen tubes may help maintain the competence of the lower esophageal sphincter, providing a physical barrier between the nutrient solution and the bronchial tree.3,4 Tablets, pills, lozenges, and some crushed dosage forms should not be placed in the NE tube because they may clog the tube, necessitating replacement. Only liquid dosage forms should be placed in the NE tube.5,6 The needle catheter jejunostomy (NCJ) is another small-bore tube used for enteral feeding. The NCJ is inserted surgically, has a smaller bore than the NE tube, and clogs easily. Avoid administering drugs by this route whenever possible.4 Because a procedure is needed for insertion, repeated replaceHospital Pharmacy

rug therapy may be complicated in hospitalized patients receiving nutrition via enteral feeding tubes. Although oral nutrition is preferred, patients may require enteral or parenteral nutrition if oral intake is inadequate or inadvisable. Patients with functional gastrointestinal (GI) tracts usually receive enteral nutrition through a feeding tube.1 Some medications may be given through the enteral feeding tube. However, tube obstruction, increased toxicity, or reduced effi-

cacy may occur if an improper administration method is used. In one survey, 74% of hospital staff used at least two incorrect methods to administer drugs via feeding tubes.2 This article describes an approach to dosage form selection and drug administration methods in these patients. Appendix A summarizes medication administration procedures. METHODS OF ENTERAL FEEDING Enteral feeding tubes may be inserted orally, nasally, or percuta-

*Drug Information Service, Department of Surgery, Nutrition Care Services: University of Utah Hospitals and Clinics, Salt Lake City, Utah.

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Table 1. Potential Alternatives to Oral Administration of Medications.9,29,58-61

Route Buccal Some Medications Nicotine lozenge (Commit) Testosterone buccal (Striant) Limitations of Route Inappropriate in patients with mouth injuries, mucosal injury or excoriation, CNS impairment, dry mouth, excessive salivation, nausea, vomiting, reduced intestinal motility, gastric suction, surgical resection, or swallowing difficulties. May cause mucosal irritation. Patient must avoid eating or drinking until medication dissolves completely. Only a few agents available. Inappropriate in patients with upper airway trauma. More expensive than oral treatment. Injections are an invasive procedure. Injections may be painful; patients may be anxious about shots. Drug absorption is slower than with IV administration. Inappropriate in immunosuppressed patients or patients with increased bleeding tendency. Must be given by trained staff. More expensive than oral treatment. Injections are an invasive procedure. Must be given by trained staff. Administration may be embarrassing for patient. Inappropriate in patients with cardiac diseases, immunosuppression, rectal surgery, or increased bleeding tendency. More expensive than oral treatment. Injections are an invasive procedure and may cause local tissue damage. Injections may be painful; patients may be anxious about shots. Drug absorption is slower than with IV or IM administration. Inappropriate in immunosuppressed patients or patients with increased bleeding tendency. Must be given by trained staff. Inappropriate in patients with mouth injuries, mucosal injury or excoriation, CNS impairment, dry mouth, excessive salivation, nausea, vomiting, reduced intestinal motility, gastric suction, surgical resection, or swallowing difficulties. Patient must avoid eating or drinking until medication dissolves completely. Inappropriate in patients with skin irritation, rashes, or open lesions. May cause skin irritation, redness, rashes, pruritus, or allergic contact dermatitis. May leave residue (oil, paste) on the skin or may stain clothing.

Inhalation (inhalers, nebulization) Intramuscular

Albuterol, Nicotine, Zanamivir

Ampicillin/sulbactam, Dicyclomine, Hydroxyzine, Lorazepam, Prednisolone

Intravenous

Dexamethasone, Digoxin, Enalaprilat, Hydromorphone, Methotrexate, Morphine, Phenytoin, Promethazine Acetaminophen, Aspirin, Bisacodyl, Caffeine/ergotamine, Lactulose, Mesalamine, Morphine, Prochlorperazine, Promethazine, Sodium polystyrene sulfonate Fentanyl, Hydromorphone, Morphine

Rectal (enemas, suppositories)

Subcutaneous

Sublingual

Isosorbide, Nitroglyerin

Transdermal (patches, ointment)

Clonidine, Estradiol, Fentanyl, Nicotine, Nitroglycerin

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Table 2. Oral Dosage Forms That Should Not be Crushed13

Drug and Dosage Form Acetaminophen: Arthritis Bayer Time Release, Tylenol Extended Relief Acetazolamide: Diamox Sequels Albuterol: Volmax, Proventil Repetabs Aspirin, enteric-coated: various, ASA Enseals, Ascriptin, Bayer Enteric-coated, Bayer Low Adult, Bayer Regular Strength, Easpirin, Ecotrin, ZORprin Benzphetamine: Bontril SR, Prelu-2 Bisacodyl: various, Carters Little Pills, Dulcolax Brompheniramine: Lodrane LD, Respahist Bupropion: Wellbutrin SR, Zyban Carbamazepine: Carbatrol, Tegretol XR Carbidopa/Levodopa: Sinemet CR Carbinoxamine/pseudoephedrine: Carbiset-TR Cefaclor: Cefaclor CR Cefuroxime: Ceftin Charcoal, activated/simethicone: Charcoal Plus Chlorpheniramine: Chlorpheniramine Maleate Time Release, Chlor-Trimeton, Dallergy, Dallergy-JR, Deconamine SR, Extendryl JR, Extendryl S-R, Pannaz Ciprofloxacin: Cipro Dexbrompheniramine: Drixoral various, Disophrol Chronotab Dexchlorpheniramine Dextroamphetamine: Dexedrine Spansule Diclofenac/misoprostol: Arthrotec Diethylpropion Diflunisal: Dolobid Diltiazem: Cardizem CD, Cardizem LA Cardizem SR, Cartia XT, Dilacor XR, Tiazac Dimenhydrinate: Triptone Diosman: Baros Dirithromycin: Dynabac Disopyramide: Norpace CR Divalproex sodium: Depakote ER Divalproex sodium: Depakote Sprinkle, Depakote Enalapril: Lexxel Ergocalciferol: Drisdol (capsule) Ergoloid mesylate: Hydergine LC Ergotamine: Ergomar Reason Sustained-release Sustained-release Sustained-release Enteric-coated

ment of NE/NCJ tubes may increase hospital costs, patient discomfort, and infection risk. Large-Bore Tubes Several types of large-bore tubes may be used for enteral feedings, including nasogastric (NG) and orogastric (OG) tubes (ie, Salem sump), as well as tubes that cross the body wall, such as gastrostomy (G) or jejunostomy (J) tubes.7 These tubes may be placed using open or laparoscopic surgical techniques, endoscopically, or under fluoroscopy. Compared with NE or NCJ tubes, large-bore tubes are less likely to clog. Nasogastric tubes are also stiffer than NE tubes and may be inserted at the bedside. Because tube insertion is relatively easier, tube replacement costs are lower for NG tubes than for NE or NCJ tubes.3,4 Although NG tubes, including the Salem sump, may be used for enteral nutrition, their main purpose is to suction gastric contents in patients with impaired GI tract function (eg, gastric stasis, ileus, bowel obstruction).3,4 These tubes are stiffer than NE tubes and may increase aspiration risk by compromising swallowing and reducing the integrity of the lower esophageal sphincter.3,4 In general, stiff, large-bore NG tubes should not be used as feeding tubes when other options exist. One possible exception may be in the intensive care unit, where patients are often intubated and closely monitored; in such cases, it may be unacceptable to risk transporting patients to place a more traditional feeding tube. Because the primary purpose of an NG tube is to suction gastric contents, it is important to remember that any medications given through the tube may be suctioned

Sustained-release Enteric-coated Sustained-release Sustained-release Sustained-release Sustained-release Sustained-release Sustained-release Taste Enteric-coated Sustained-release

Taste Sustained-release Sustained-release Sustained-release Enteric-coated Sustained-release Irritant Sustained-release

Sustained-release Effervescent Enteric-coated Sustained-release Sustained-release Enteric-coated Sustained-release Liquid-filled capsule Liquid-filled capsule Sublingual product (continued)

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Table 2. Oral Dosage Forms That Should Not be Crushed13

Drug and Dosage Form Erythromycin: E.E.S, E-Mycin, Eryc Ery-tab, Erythromycin base Esomeprazole: Nexium Etodolac: Lodine XL Felodipine: Plendil Ferrous fumarate: Ferro-Sequels Ferrous sulfate: Slow-FE, Slow-FE Folic Ferrous sulfate Fexofenadine: Allegra-D Fiber: Perdiem Fiber Therapy Finasteride: Propecia, Proscar Fluoxetine: Prozac Weekly Ganciclovir: Cytovene Glipizide: Glucotrol XL Guaifenesin: Breonesin, Entex LA, Entex PSE, Guaifed, Guaifed-PD, Guaifenex LA, Guaifenex PSE, Humabid DM, Humabid DM Sprinkle, Humibid LA, Humibid Sprinkle, Muco-Fen-DM, Nasatab LA, PanMist Jr., LA, Profen II, Quibron-T SR, Respa various, Respaire SR, Sudal, Syn-RX, Touro (various) Hyoscyamine: Cystospaz-M, Levbid, Levsinex Timecaps Indomethacin: Indocin SR Isosorbide Dinitrate: Dilatrate-SR, Isosorbide dinitrate sublingual Isosorbide Dinitrate: Imdur, Isosorbide CR, Isotretinoin: Accutane Isradipine: Dynacirc CR Lansoprazole: Prevacid Lithium: Eskalith CR, Lithobid Loratadine: Claritin-D, Claritin-D 24 hour Magnesium chloride: Slow-Mag Mesalamine: Pentasa Mesalamine: Asacol Methylphenidate: Ritalin SR Metoprolol: Toprol XL Morphine: Kadian, MS Contin, Oramorph SR Multiple vitamins: Mi-Cebrin T, Optilets 500 Multiple vitamins: Feocyte, Fumatinic, ICaps Plus, ICaps Time Release Reason Enteric-coated Sustained-release Sustained-release Sustained-release Sustained-release Sustained-release Enteric-coated Sustained-release Wax-coated Teratogenic Delayed-release Irritant Sustained-release Sustained-release

out, preventing absorption.8 Clamping the NG tube for at least 30 minutes after drug administration increases absorption if the GI tract is functioning.6 However, many patients with GI tract dysfunction cannot tolerate long periods of tube clamping.8 MEDICATION ADMINISTRATION PLAN The key to managing medications in enterally fed patients is to focus on prioritizing therapeutic goals. First, temporarily discontinue medications that are not immediately necessary (eg, hormone replacement therapy).9 Second, consider giving medications by an alternate route, such as transdermal, rectal, inhaled, intramuscular, subcutaneous, buccal, sublingual, or intravenous. The appropriateness of each route should be assessed based on the patients clinical status and medication needs (see Table 1). Third, when products are not available in alternate dosage forms, consider using another drug with similar pharmacologic effects. For example, transdermal fentanyl could be used for pain instead of oral morphine. Dosage or frequency adjustments may be necessary when changing administration routes, especially if patients are switched from one agent to another (eg, morphine to fentanyl).9 ENTERAL ADMINISTRATION OF MEDICATIONS Medications may be given via the feeding tube if necessary.9,10 However, clinicians must first evaluate tube type, tube location in the GI tract, site of drug action and absorption, and the effects of food on drug absorption. For example, antacids, bismuth, and sucralfate act locally in the stomach and are not suitable

Sustained-release Sustained-release Sublingual product Sustained-release Irritant Sustained-release Sustained-release Sustained-release Sustained-release Sustained-release Sustained-release Enteric-coated Sustained-release Sustained-release Sustained-release Enteric-coated Sustained-release (continued)

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Table 2. Oral Dosage Forms That Should Not be Crushed13

Drug and Dosage Form Mycophenolate: Cellcept Naproxen: Naprelan Niacin: Slo-Niacin Nicardipine: Cardene SR Nicotinic acid: Nicotinic acid extended-release Nifedipine: Adalat CC, Procardia XL Nifedipine: Procardia Nisoldipine: Sular Nitroglycerin: Nitroglyn, Nitro-Time Nitroglycerin: Nitrostat Omeprazole: Prilosec Orphenadrine citrate: Norflex Oxybutynin: Ditropan XL Oxycodone: Oxycontin Pancreatic enzymes: Creon 10, Creon 20, Pancrease, Pancrease MT, Ultrase, Ultrase MT Pantoprazole: Protonix Papaverine: Papaverine Sustained Action, Pentoxyfylline: Trental Phendimetrazine Piroxicam: Feldene Potassium citrate: Urocit K Potassium supplements: K-Dur, Klor-Con/EF, Klotrix, K-Tab, Micro K Potassium supplements: K-Lyte, K-Lyte CL, K-Lyte DS Procainamide: Procanbid, Procainamide hydrochloride SR, Pronestyl SR Propranolol: Betachron, Inderal LA Pseudoephedrine: Disophrol Chronotab, Sudafed 12 hour Pyridostigmine: Mestinon Timespan Quinidine gluconate: Various Rabeprazole: Aciphex Riboflavin: Iberet 500 Sodium Valproate: Depakote ER Sulfasalazine: Azulfidine EN-tabs Tamsulosin: Flomax Theophylline derivatives: Choledyl SA, Slo-bid Gyrocaps, Theo-24, Theochron, Uniphyl Venlafaxine: Effexor XR Verapamil: Calan SR, Covera HS, Verelan Reason Teratogenic Sustained-release Sustained-release Sustained-release Sustained-release Sustained-release Delays absorption Sustained-release Sustained-release Sublingual product Delayed-release Sustained-release Sustained-release Sustained-release Enteric-coated Sustained-release Sustained-release Sustained-release Sustained-release Irritant Wax-coated Sustained-release Effervescent product

Sustained-release Sustained-release Sustained-release Sustained-release Sustained-release Sustained-release Sustained-release Sustained-release Enteric-coated Sustained-release Sustained-release Sustained-release Sustained-release

for administration via intestinal feeding tubes.9,10 Bioavailability may increase with intrajejunal administration of drugs with extensive first-pass metabolism, such as opioids, tricyclics, beta blockers, or nitrates. Buccal and sublingual dosage forms may be ineffective when given enterally. For drugs that require administration on an empty stomach, stop enteral feeding for 30 minutes before and after dosing if the tube is placed in the stomach.9,10 The use of liquid dosage forms is preferred whenever possible. Liquid preparations for oral or IV use may be substituted for solid dosage forms.3,6,7 Many tablets may be crushed to a fine powder, mixed to a slurry in water, and given through large-bore feeding tubes. The contents of most capsules may be administered in the same manner.3 Regardless of which dosage form is used, the feeding tube should be flushed with at least 30 mL of water before and after administration to clear any residual medication.3,6,7 In general, medications should not be added to the enteral formula, both to reduce the risk of microbial contamination and to avoid drugnutrient incompatibilities.11,12 Many oral products should not be crushed (see Table 2). Sustained-release, enteric-coated, or microencapsulated products should neither be crushed nor given through feeding tubes as intact tablets or capsules.13 Crushing destroys the sustained-release properties of sustained-release tablets and microencapsulated drugs, resulting in erratic blood levels. Enteric coatings do not crush well but break into small chunks that bond together when moist, clogging the tube.13 Because aerosolized particles

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may be harmful to hospital staff, avoid crushing drugs with teratogenic, carcinogenic, or cytotoxic properties, such as antineoplastics, hormones, and prostaglandin analogs. Cross-contamination from the tablet crushing device is also possible; avoid crushing medications that commonly cause allergic reactions.9,10 The pellets inside some microencapsulated products may be poured down the large-bore enteral feeding tube after being removed from the capsule, provided that the pellets are not crushed. Medications that may be given in this manner include diltiazem (Cardizem CD, Cardizem SR), ferrous gluconate (Fergon), nizatidine (Axid), pancreatic enzymes (Creon, Pancrease, Pancrease MT), theophylline (many generic brands), and verapamil (Verelan).6,13 Cromolyn (Gastrocrom) capsules may be administered by opening the capsule and dissolving the contents in water before pouring the mixture down the feeding tube. Liquid contents of soft gelatin capsules (acetazolamide, nifedipine) may be aspirated from the capsule and given via the feeding tube as immediate-release dosage forms, provided that the capsule contents are completely removed.6,13 Proton-Pump Inhibitors The proton pump inhibitors (PPIs) present a special dilemma. Because the active drugs are acidlabile and undergo gastric degradation, the products are formulated to reduce the amount of drug lost to hydrolysis. Omeprazole (Prilosec), lansoprazole (Prevacid), and esomeprazole (Nexium) are formulated as delayed-release capsules containing enteric-coated drug granules.1417 Gastric acid dis-

solves the delayed-release capsule during transit of the dosage form. The enteric-coated granules are delivered to the small intestine, the base-labile coating dissolves, and drug is absorbed.1417 Pantoprazole (Protonix) and rabeprazole (Aciphex) are formulated as entericcoated, delayed-release tablets; the coating dissolves in the stomach and drug is absorbed in the intestine.18,19 Several studies have evaluated methods for giving omeprazole and lansoprazole through enteral tubes.2022 Crushing the entericcoated granules results in tube clogging from the enteric coating.1416 Instead the granules should be mixed with an appropriate diluent, such as apple or orange juice, to ensure that maximal amounts of drug reach the duodenum. To accomplish this, different methods must be used depending on the type of feeding tube in place and its location in the GI tract (see Appendix A).2024 In patients with a large-bore NG or G tube (18 French or larger), mix the intact granules with acidic fruit juice, pour the mixture down the tube, then flush with additional juice. The fruit juice protects the base-labile granules until they reach the small intestine, ensuring maximal drug delivery. Suitable juices include apple, cranberry, grape, orange, pineapple, prune, tomato, and V-8 juice.1416,2024 In patients with an intestinal feeding tube, give oral PPI suspensions. Oral suspensions of lansoprazole 3 mg/mL or omeprazole 2 mg/mL may be prepared by dissolving the unencapsulated, intact granules in sodium bicarbonate 8.4% solution.1416,2024 Because the intact granules dissolve incompletely in acidic fruit juice, oral suspensions may also be used in

patients with small-bore G tubes (less than 18 French), although the amount of drug absorbed may be reduced. For maximal effectiveness, give oral PPI suspensions into the intestine and intact granules into the stomach.20,21,25 Lansoprazole is also available as a packet of granules that are mixed with water before administration to form a suspension.26 However, this product is not appropriate for administration via enteral tubes. The formulation contains xanthan gum, an ingredient that increases the suspensions viscosity and causes it to expand within the feeding tube, increasing the risk of tube blockage.27 There is no information about administering esomeprazole (Nexium), pantoprazole (Protonix), or rabeprazole (Aciphex) via feeding tubes. Because esomeprazole is formulated similarly to omeprazole and lansoprazole, it may be reasonable to give esomeprazole either as intact granules or an oral suspension.17 Because pantoprazole and rabeprazole are enteric-coated tablets and cannot be split, chewed, or crushed, these medications cannot be administered via feeding tubes.18,19 Laxatives Bulk-forming laxatives, such as methylcellulose or psyllium (Metamucil), should not be given via feeding tubes.6,15 These products form a semisolid mass that may occlude the feeding tube when mixed with less than 250 mL fluid. Even when mixed properly, the resultant viscous solutions may block feeding tubes. In one study, clogging occurred in 33% of patients given psyllium via the enteral feeding tube, necessitating tube replacement.11 Similarly, cholestyramine (Questran), a bile acid sequestrant, may clog small-

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Table 3. Osmolality (mOsm/kg) of Some Liquid Medications30,31*

Commercially Available Product Acetaminophen elixir, 65 mg/mL Acetaminophen/codeine elixir Amantadine HCl solution, 10 mg/mL Aminophylline liquid, 21 mg/mL Amoxicillin suspension, 25 mg/mL Amoxicillin suspension, 50 mg/mL Ampicillin suspension, 50 mg/mL Belladonna alkaloids elixir Cephalexin suspension, 50 mg/mL Cimetidine solution, 60 mg/mL Co-trimoxazole suspension Dexamethasone intensol solution, 1 mg/mL Digoxin elixir, 50 mcg/mL Diphenhydramine HCl elixir, 2.5 mg/mL Diphenoxylate/atropine suspension Docusate sodium syrup, 3.3 mg/mL Erythromycin ethyl succinate suspension, 40 mg/mL Ferrous sulfate liquid, 60 mg/mL Furosemide solution, 10 mg/mL Haloperidol concentrate, 2 mg/mL Hydroxyzine HCl syrup, 2 mg/mL Kaolin-pectin suspension Lactulose syrup, 0.67 g/mL Lithium citrate syrup, 1.6 mEq/mL Magnesium citrate solution Milk of magnesia suspension Multivitamin liquid Nystatin suspension, 100,000 units/mL Phenytoin sodium suspension, 25 mg/mL Promethazine HCl syrup, 1.25 mg/mL Pyrantel pamoate suspension, 50 mg/mL Pyridostigmine bromide syrup, 12 mg/mL Sodium citrate liquid Sodium phosphate liquid, 0.5 g/mL Theophylline solution, 5.33 mg/mL Thiabendazole suspension, 100 mg/mL Average Osmolality 5400 4700 3900 450 1541 2250 2250 1050 1950 5550 2200 3100 1350 850 8800 3900 1750 4700 2050 500 4450 900 3600 6850 1000 1250 5700 3300 1500 3500 4350 3800 2050 7250 700 2150

bore feeding tubes.9 Consider using a fiber-containing enteral nutrition formula (eg, Jevity, Pediasure with fiber, or Promote with fiber) in patients who require additional dietary fiber for laxative effects.28 CONSIDERATIONS WITH LIQUID MEDICATIONS Liquid dosage forms are preferable if medication must be given via the enteral feeding tube. The medication dosage or frequency may need adjustment when switching from solid to liquid preparations.9 For example, phenytoin capsules are extended-release products and may be given once daily; phenytoin suspension is an immediate-release product and must be dosed 2 to 4 times daily. Extended-release diltiazem tablets may be given once daily, but immediate-release diltiazem tablets must be given 4 times daily.29 In some cases, the feeding rate or schedule must be adjusted to maintain adequate nutrition, especially if enteral feedings are interrupted several times daily for medication administration.5,9 Many commercial liquids have osmolalities well over 1000 mOsm/kg (see Table 3).5,30 The osmolality of GI secretions ranges from 100 to 400 mOsm/kg. Diarrhea, cramping, abdominal distention, and vomiting may occur after administration of hyperosmolar products through the feeding tube.3,5 These effects may be reduced by diluting medication with 10 to 30 mL of sterile water before administration.5,11,12 The osmolality of the resulting mixture may be calculated using the formula: Osmolality of diluted mixture = (Osmolality of drug x Volume of drug)/Total volume of mixture.31 Sterile water contains no solute and does not contribute to the

Note: These preparations require dilution with 10 to 30 mL sterile water prior to administration via the feeding tube. *Adapted with permission from Dickerson RN, Melnick G30

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mixtures osmolality.32 Inactive ingredients or excipients in liquid products may also cause side effects when given enterally. Ingredient-related diarrhea may occur in up to 50% of patients.33 Many sweeteners, including mannitol, lactose, saccharin, and sucrose, may cause or worsen diarrhea. However, the excipient most likely to cause GI problems is sorbitol.5,11,34 A poorly absorbed polyalcohol sugar, sorbitol is used therapeutically as a laxative in doses of 7.5 to 30 g.15 It is added to many liquid products to sweeten solutions, improve solution stability, and to provide a vehicle for medication.5,34 Sorbitol frequently causes gas and bloating at total daily doses of 10 g, while cramping and diarrhea occur with 20 g/day.34 Table 4 lists the sorbitol content of various medications. The list is not comprehensive, because sorbitol content varies by manufacturer and by drug concentration. While many preparations contain only small amounts, sorbitols effects are cumulative, based on the total daily dose. Patients receiving multiple drugs containing sorbitol are more likely to experience adverse reactions. Minimize risk by avoiding sorbitol-containing agents whenever possible.11,12,34 Sudden-onset diarrhea due to sorbitol or hyperosmolar medications is not a reason to discontinue tube feeding, but may suggest the need for changes in medications or administration routes.11,12,34 DRUG INTERACTIONS AND INCOMPATIBILITY Some medications may not be administered with enteral formulas because they form precipitates that may clog the feeding tube and reduce drug absorption (see Table 5). Syrups and other acidic medica-

tions (pH less than 4) may clump when mixed with enteral feeding formulas. In most cases, these interactions may be avoided by stopping the enteral feeding for 1 to 2 hours before and 2 hours after drug administration.9,10,35,36 To avoid compromising nutritional status, minimize the amount of time that feeding is interrupted by using once daily or twice daily dosage regimens.9,10 Nutrient intake is reduced 12.5% to 17% with once daily dosing and 25% to 33% with twice daily dosing, unless the feeding rate is increased. Phenytoin Phenytoin absorption decreases dramatically when given with enteral nutrition, reducing serum levels by 50% to 75%.5,37 The clinical effect of this interaction may be decreased by interrupting tube feeding for 2 hours before and after each dose, in addition to flushing the tube before and after each phenytoin dose.5,9 Maintain adequate nutrition by placing the patient on a twice daily phenytoin regimen and gradually increasing the feeding rate to account for the lost time. Monitor serum levels closely, especially once the patient begins oral intake. Warfarin Warfarins effects may decrease in patients receiving enteral feeding, due to reduced absorption and vitamin K antagonism. Warfarin absorption may be decreased by drug binding to components of the enteral feeding solution. Vitamin K is found in most enteral formulas and directly blocks warfarins effects when given in doses of 140 to 500 mcg/day, a level that may be reached in patients receiving large volumes of tube feeds.5,3841 Monitor prothrombin time carefully in patients requiring anti-

coagulation. Consider increasing the warfarin dose or using alternate anticoagulants (heparin, lowmolecular weight heparin). When the patient is switched from enteral feeding to oral or parenteral feeding, it may be necessary to reduce the warfarin dosage. Fluoroquinolones The pharmacokinetics of some fluoroquinolone antibiotics [ie, ciprofloxacin (Cipro), levofloxacin (Levaquin), ofloxacin (Floxin)] may change erratically when given via NG tubes or J tubes in patients receiving enteral feeds.4247 Peak concentrations decrease and the time to peak increases, changes that may alter antimicrobial efficacy and adversely affect patient outcomes.4246 The bioavailability of ciprofloxacin varies from 31% to 82% when given via the NG tube in patients receiving continuous enteral feeding. Although there is wide variability among patients, peak concentrations and overall drug exposure tend to be lower with administration via NG tubes.47 The mechanism for these changes is not well-understood, although it may be caused by fluoroquinolone binding of divalent cations in the enteral feeding formula.42-45,48 To reduce the interaction, fluoroquinolones should not be given within 2 hours before or 4 hours after enteral formulas. Although studies have only evaluated three agents (ciprofloxacin, levofloxacin, ofloxacin), the interaction is likely a class effect of all fluoroquinolones, including gatifloxacin (Tequin), due to their similar chemical structures and drug interaction profiles.15,49 To ensure efficacy, avoid giving fluoroquinolones via enteral feeding tubes or concomitantly with enteral formulas. Instead, adminis-

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Table 4. Sorbitol Content of Selected Oral Liquid Medications34,49*

Generic Name (Trade Name, Manufacturer(s)) Acetaminophen (Tylenol) Aluminum hydroxide gel (Roxane) Aluminum hydroxide/magnesium carbonate (Gaviscon) Aluminum hydroxide/magnesium hydroxide (Maalox) Aluminum hydroxide/magnesium hydroxide (Maalox TC) Amantadine HCl (Symmetrel) Aminocaproic acid (Amicar) Carbamazepine (Tegretol) Charcoal, activated (Actidose w/Sorbitol) Chlorpromazine HCl (Roxane) Cimetidine (Tagamet) Diphenoxylate HCL/atropine sulfate (G.D. Searle) Ferrous sulfate (FerInSol) Furosemide (Roxane) Furosemide (Roxane) Ibuprofen (Whitehall) Indomethacin (Indocin) Lithium citrate (Roxane) Morphine sulfate (Roxane) Oxybutynin (Ditropan) Perphenazine Phenobarbital (Rugby) Potassium chloride (UDL) Pseudoephedrine (Rugby) Pseudoephedrine/triprolidine Pyridostigmine HBr (Mestinon) Ranitidine (Zantac) Sodium polystyrene sulfonate (Roxane) Sulfamethoxazole/trimethoprim (Biocraft) Tetracycline HCl (Sumycin) Theophylline (Roxane) Thioridazine (Pharm Assoc) Valproate sodium (Depakene) Vitamin E (Aquasol)
*Adapted with permission from Lutomski DM et al34 Lithium citrate 8 mEq is equivalent to lithium carbonate 300 mg

Strength (per mL) 32 mg 135 mg 6.3 mg A/23.9 mg M 45 mg A/40 mg M 120 mg A/60 mg M 10 mg 0.25 g 20 mg 0.208 g 100 mg 60 mg 0.5 mg D/0.005 mg A 125 mg 8 mg 10 mg 20 mg 5 mg 1.6 mEq 2 mg 1 mg 3.2 mg 4 mg 1.33 mEq 6 mg 6 mg P/0.25 mg T 12 mg 15 mg 250 mg 40 mg S/8 mg T 25 mg 5.33 mg 30 mg 50 mg 50 IU

Sorbitol (% w/v) < 20 10.5 7.3 4.5 15 72 18.2 17 40 3.5 46.1 21 30.9 28 30 10 <1 54 14 26 20 12.8 17.5 5 49 14 10 23.5 10 23 45.5 21 15 20

Average Adult Dose (per day) 1.3 3.9 g 15 180 mL 15 180 mL 15 180 mL 15 180 mL 200 mg 13 15 g 400 1200 mg 110 260 g 40 300 mg 800 mg 5 20 mg D 975 mg 20 80 mg 20 80 mg 1.2 3.2 g 75 150 mg 900 1800 mg 40 120 mg 10 15 mg 12 24 mg 30 120 mg 16 100 mEq 240 360 mg 240 360 mg P 600 mg 150 300 mg 15 60 g 1600 mg S 12g 150 600 mg 200 800 mg 14g 200 400 IU

Sorbitol Dose (g/day) < 8 24 1.6 18.9 1.1 13.1 0.7 8.1 2.2 27 14.4 9.5 10.9 3.4 10.2 211.0 499.2 0.01 0.1 6.1 2.1 8.4 2.4 1.2 4.0 13 6.0 16.0 0.2 0.5 8.1 16.2 1.7 5 2.6 3.9 0.8 1.5 1 3.8 2.1 13.1 14 21 19.6 29.4 7 12 14.1 56.4 4 9.2 18.4 12.8 51.2 1.4 5.6 3 12 0.8 1.6

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Table 5. Drug/Formula Incompatibilities.9-11,35,36,45,47,62

Aluminum hydroxide Aluminum hydroxide magnesium hydroxide Brompheniramine/phenylephrine elixir Calcium glubionate 1.8 g/5 mL (Calcionate) Chlorpromazine 100 mg/mL Ferrous sulfate 220 mg/5 mL Fluoroquinolones: ciprofloxacin (Cipro), gatifloxacin (Tequin), levofloxacin (Levaquin) ofloxacin (Floxin) Guaifenesin 20 mg/mL (Robitussin) Lithium citrate 8 mEq/5 mL* Medium chain triglyceride oil (MCT Oil) Metoclopramide 1 mg/mL (Roxane) Opium tincture, camphorated, 0.04% elixir (Paregoric) Potassium chloride 10% liquid Potassium chloride 20% liquid Pseudoephedrine 6 mg/mL (Rugby) Sodium biphosphate 480 mg/mL (Fleets Phospho-soda) Sucralfate (Carafate) Thioridazine 30 mg/mL; 100 mg/mL Zinc sulfate capsules
*Lithium citrate 8 mEq is equivalent to lithium carbonate 300 mg

tablet and the contents of one Viokase or Cotazym capsule. Both products contain lipase 8000 units, amylase 30,000 units, and protease 30,000 units.31,49,55 Cranberry juice and carbonated colas have been used in the past to restore the patency of occluded tubes.2,9,53,54 However, these liquids are acidic and may actually contribute to tube occlusion by denaturating proteins in the enteral formulas.9,57 SUMMARY Drug therapy need not be compromised in patients receiving enteral nutrition. Careful selection and preparation of dosage forms reduces the complications of drug administration. Properly flushing the feeding tube and screening for incompatibilities lowers the risk of tube clogging and the need for replacement. REFERENCES
1. Rollins CJ. Adult enteral nutrition. In: Koda-Kimble MA et al, eds. Applied Therapeutics: The Clinical Use of Drugs. 6th ed. Vancouver: Applied Therapeutics; 1995, 34.128. 2. Belknap DC, et al. Administration of medications through enteral feeding catheters. Am J Crit Care. 1997;6(5):38292. 3. Silberman H. Parenteral and Enteral Nutrition. 2nd ed. Norwalk, CT: Appleton & Lange; 1989, 11758. 4. Rombeau JL, Caldwell MD, eds. In: Clinical Nutrition: Enteral and Tube Feeding. 2nd ed. Philadelphia, PA: WB Saunders; 1990. 5. Estoup M. Approaches and limitations of medication delivery in patients with enteral feeding tubes. Crit Care Nurse. 1994;14:6872,79. 6. Gora ML, et al. Considerations of drug therapy in patients receiving enteral nutrition. Nutr Clin Pract. 1989; 4:10510. 7. Klein S, Fleming CR. Enteral and parenteral nutrition. In: Sleisenger MG, et

ter the drugs parenterally in patients who cannot take oral medications. If a fluoroquinolone must be given via the feeding tube, crush the tablets and mix in 20 to 60 mL sterile water immediately before giving.4247,50 Adjust the feeding rate to compensate for the lost time.5,9,10 Ciprofloxacin suspension should never be given via the feeding tube, since its thick consistency may clog the tube. In addition, the oil-based suspension does not mix with aqueous solutions and cannot be easily flushed with water.51,52 CLOGGED FEEDING TUBES Medications cause occlusion in approximately 15% of patients with enteral feeding tubes.2,9 Sever-

al mechanisms for managing clogged feeding tubes are outlined in Appendix B. Before removing the tube, attempt to clear the obstruction with warm water and gentle pressure.11,5355 If the feeding tube remains clogged, flush the tube with carbonated water, Clog Zapper, or alkalinized enzyme solution.11,55,56 Clog Zapper is a commercial product containing papain, amylase, and cellulase that may be used for occlusions caused by enteral formulas. Because Clog Zapper has not been evaluated for drug-related occlusions,56 alkalinized enzyme solution should be used in these cases. To prepare the solution, crush one sodium bicarbonate 324 mg

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al, eds. Gastrointestinal Disease: Pathophysiology Diagnosis Management. 5th ed. Philadelphia, PA: WB Saunders; 1993, 206296. 8. Schuffler MD, Sinanan MN. Intestinal obstruction and pseudo-obstruction. In: Sleisenger MH, et al, eds. Gastrointestinal Disease: Pathophysiology Diagnosis Management. 5th ed. Philadelphia: WB Saunders; 1993, 898916. 9. Thomson FC, et al. Managing drug therapy in patients receiving enteral and parenteral nutrition. Hosp Pharmacist. 2000;7:15564. 10. Gilbar PJ. A guide to enteral drug administration in palliative care. J Pain Symptom Manage. 1999;17:197207. 11. Rombeau JL, Caldwell MD, eds. Clinical Nutrition: Enteral and Tube Feeding. 3rd ed. Philadelphia, PA: WB Saunders; 1997. 12. Janson DD, Chessman KH. Enteral nutrition. In: DiPiro JT et al, eds. Pharmacotherapy: A Pathophysiologic Approach. 5th ed. New York, NY: McGraw-Hill; 2002, 2495517. 13. Mitchell JF. Oral dosage forms that should not be crushed or chewed. Hosp Pharm. 2002; 37:21314. 14. Personal communication. Whitehouse Station, NJ: Merck; 1994. 15. AHFS Drug Information 2002. Bethesda, MD: American Society of Health-System Pharmacists; 2002. 16. Personal communication. Lake Forest, IL: TAP Pharmaceuticals; 1996. 17. Nexium (esomeprazole) [package insert]. Wilmington, DE: AstraZeneca; 2001. 18. Aciphex (rabeprazole sodium) delayed-release tablets package insert. Teaneck, NJ: Eisai Pharmaceuticals; 2000. 19. Protonix (pantoprazole sodium) delayed-release tablets [package insert]. Philadelphia, PA: Wyeth; 2001. 20. Sharma VK, et al. Oral pharmacokinetics of omeprazole and lansoprazole after single and repeated doses as intact capsules or as suspensions in sodium bicarbonate. Aliment Pharmacol Ther. 2000;14:88792. 21. Song JC, et al. A prospective study of

simplified omeprazole suspension for the prophylaxis of stress-related mucosal damage. Am J Health Syst Pharm. 2001;58:68994. 22. Sharma VK, et al. Simplified lansoprazole suspensiona liquid formulation of lansoprazoleeffectively suppresses intragastric acidity when administered through a gastrostomy. Am J Gastroenterol. 1999;94:18137. 23. Zimmermann A, et al. Alternative methods of proton-pump inhibitor administration. Consult Pharm. 1997;12:9908. 24. Phillips JO, et al. A prospective study of simplified omeprazole suspension for the prophylaxis of stress-related mucosal damage. Crit Care Med. 1996;24:1793800. 25. Omeprazole nasogastric administration (Drug Consult). In: Hutchison TA, Shahan DR, eds. Drugdex System. Greenwood Village, CO: Micromedex. (Edition expires September 30, 2002). 26. Prevacid (lansoprazole) delayedrelease capsules and Prevacid (lansoprazole) for delayed-release oral suspension [package insert]. Lake Forest, IL: TAP Pharmaceuticals; 2002. 27. Safety briefs. ISMP Medication Safety Alert! 2002;7(12):12. 28. Product reference guide. Deerfield, IL: Nestle Clinical Nutrition; 2001. 29. Hutchison TA, Shahan DR, eds. Drugdex System. Greenwood Village, CO: Micromedex (Edition expires September 30, 2002). 30. Dickerson RN, Melnik G. Osmolality of oral drug solutions & suspensions. Am J Hosp Pharm. 1988;45:83234. 31. Jew RK, et al. Osmolality of commonly used medications and formulas in the neonatal intensive care unit. Nutr Clin Pract. 1997;12:15863. 32. Sterile water for injection. In: USP24/NF 19 The United States Pharmacopeia/The National Formulary. Rockville, MD: United States Pharmacopeial Convention; 1999, 1753. 33. Klang MG. Medicating tube-fed patients. Nursing. 1996;26:18. 34. Lutomski DM, et al. Sorbitol content of selected oral liquids. Ann Pharmacother. 1993;27:26974.

35. Burns PE, et al. Physical compatibility of enteral formulas with various common medications. J Am Diet Assoc. 1988;88:10946. 36. Cutie AJ, et al. Compatibility of enteral products with commonly employed drug additives. JPEN J Parenter Enter Nutr. 1983;7:18691. 37. Bauer LA. Interference of oral phenytoin absorption by continuous nasogastric feedings. Neurol. 1982:32:5702. 38. Kutsop JJ. Update on vitamin K1 content of enteral products [letter]. Am J Hosp Pharm. 1984;41:1762. 39. Landau J, Moulds RFW. Warfarin resistance caused by vitamin K in intestinal feeds [letter]. Med J Aust. 1982;2634. 40. Watson AJM, et al. Enteral feeds may antagonise warfarin. BMJ. 1984;288: 557. 41. Parr MD, et al. Effect of enteral nutrition on warfarin therapy [letter]. Clin Pharm. 1982;1:2746. 42. Healy DP, et al. Ciprofloxacin absorption is impaired in patients given enteral feedings orally and via gastrostomy and jejunostomy tubes. Antimicrob Agents Chemother. 1996;40:610. 43. de Marie S, et al. Bioavailability of ciprofloxacin after multiple enteral and intravenous doses in ICU patients with severe gram-negative intra-abdominal infections. Intensive Care Med. 1998;24:3436. 44. Wright DH, et al. Decreased in vitro fluoroquinolone concentrations after admixture with an enteral feeding formulation. JPEN J Parenter Enter Nutr. 2000;24:428. 45. Cohn SM, et al. Enteric absorption of ciprofloxacin during tube feeding in the critically ill. J Antimicrob Chemother. 1996;38:8716. 46. Mueller BA, et al. Effect of enteral feeding with Ensure on oral bioavailabilities of ofloxacin and ciprofloxacin. Antimicrob Agents Chemother. 1994;38:21015. 47. Mimoz O, et al. Pharmacokinetics and absolute bioavailability of ciprofloxacin administered through a nasogastric tube with continuous enteral feeding to critically ill patients. Intensive

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Appendix A: Approach to Medication Administration in Patients with Feeding Tubes.3,5-7,9,11,12,14,15,17,22-24,42-46,49

Evaluate necessity of each medication; temporarily discontinue if possible. Consider giving medication by an alternate route: Buccal Intramuscular Intravenous Transdermal Nebulized Rectal Subcutaneous Sublingual Administration through feeding tube: Assess drug absorption site, site of action, duration of action, incompatibilities, and effects of food on drug absorption. Select medication dosage form (listed in order of preference*). Only liquid dosage forms should be given via small-bore enteral feeding tubes. Oral liquid. Dilute with 10 to 30 mL sterile water or enteral formula if hyperosmolar. Oral immediate-release tablet. Crush to fine powder and mix with 15 to 30 mL water to form slurry. Oral immediate-release capsule. Crush capsule contents to fine powder and mix with 10 to 30 mL water to form a slurry. Oral soft gelatin capsule. Aspirate liquid contents and mix with 10 to 30 mL water. IV liquid preparation. If drug requires administration on an empty stomach and the tube empties into the stomach, stop enteral feeds for 30 minutes before and after administration. Adjust enteral feeding rate to maintain adequate nutrition. Flush feeding tube with 30 mL sterile water prior to administration. Give each medication separately via the feeding tube and flush with 30 mL sterile water between medications. Flush feeding tube with 30 mL sterile water to clear residual medication. Special situations Cardizem CD, Cardizem SR, Fergon, Respbid oral capsules: Open capsule and pour intact pellets down large bore enteral feeding tube. Flush feeding tube with 30 mL water before and after administration. Gastrocrom oral capsules: Open capsule, dissolve contents in water, pour down feeding tube. Flush feeding tube with 30 mL water before and after administration. Fluoroquinolones (ciprofloxacin, gatifloxacin, levofloxacin): Give IV whenever possible. However, if absolutely necessary to give enterally via large bore feeding tube, crush tablets and mix with 20 to 30 mL water immediately prior to administration. Stop enteral feeding for at least 2 hours before and 4 hours after administration. Phenytoin: Switch patient to twice daily administration of phenytoin suspension. Stop enteral feeding for at least 2 hours before and 2 hours after administration. Proton-pump inhibitors, delayed-release capsules (lansoprazole, omeprazole): Gastric or nasogastric feeding tube, large bore (18 French or larger): Immediately before administration, open capsule and gently mix intact granules with acidic fruit juice. Discontinue enteral feeding temporarily and pour mixture down feeding tube. After administration, flush feeding tube with additional acidic fruit juice and clamp the feeding tube for at least 1 hour. May use apple, cranberry, grape, orange, pineapple, prune, tomato, or V-8 juice. Intestinal feeding tube or small bore gastric feeding tube (smaller than 18 French): Give simplified oral suspension (lansoprazole 3 mg/mL or omeprazole 2 mg/mL). Prior to administration, shake suspension well and temporarily discontinue enteral feeding formula. Pour suspension down feeding tube. After administration, flush the feeding tube with 5 to 10 mL water and clamp the feeding tube for at least 1 hour.
*According to cost, ease of use, and risk of adverse effects

Care Med. 1998;24:104751. 48. Cipro (ciprofloxacin) and enteral nutrition [written communication]. West Haven, CT: Bayer; 2001. 49. Drug Facts and Comparisons. St. Louis, MO: Facts & Comparisons; 2002. 50. Crushing tables/enteral feeds Levaquin (levofloxacin) [written communi-

cation]. Raritan, NJ: Ortho-McNeil; 2001. 51. Cipro (ciprofloxacin) [package insert]. West Haven, CT: Bayer; 2000. 52. Cipro (ciprofloxacin) oral suspension [written communication]. West Haven, CT: Bayer; 2002. 53. Marcuard SP, et al. Clearing obstructed feeding tubes. JPEN J Par-

enter Enter Nutr. 1989;13:813. 54. Bommarito AA, et al. A new approach to the management of obstructed enteral feeding tubes. Nutr Clin Pract. 1989;4:1114. 55. Bailey K. Management of phytobezoars and clogged feeding tubes. Pharmacy Newsletter. (Thomas Jefferson University Hospital) 1994;12:13.

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Appendix B: Approach to Clogged Feeding Tubes11,5356

1. Withdraw any enteral solution remaining in tube. 2. Attempt to remove obstruction, using the following methods in the order given. Warm water: Inject 5 mL warm water into tube and clamp for 5 minutes. Unclamp tube, apply gentle pressure, and attempt suction. If tube is unclogged, flush with water until clear. If still obstructed, try carbonated water or alkalinized enzyme. Carbonated water: Inject carbonated water into tube and clamp for 1 hour. Then, unclamp tube, apply gentle pressure, and attempt suction. If tube is unclogged, flush with water until clear. If still obstructed, try alkalinized enzyme method. Clog Zapper enzyme solution (for formula-related occlusions): Fill enclosed syringe to 10 mL mark with 7.1 mL water, cap syringe, and shake until powder dissolves completely. Inject 2 to 5 mL of mixture into tube and clamp for 30 to 60 minutes. Flush with water until clear. Refrigerate remaining solution and use within 24 hours. Alkalinized enzyme solution (for medication-related occlusions): Crush one sodium bicarbonate 324 mg tablet. Mix powder with contents of one Cotazym or Viokase capsule and 5 mL sterile water. Inject mixture into tube and clamp for 5 minutes. Flush with water until clear. 3. Replace feeding tube, only if there is an inadequate response to steps 1 and 2.

56. Clog Zapper information. Wheeling, IL: Corpak Medsystems; 2002. 57. Guenter P. Administering medications via feeding tubes: What consultant pharmacists need to know. Consult Pharm. 1999;14:414, 478. 58. Mosbys GenRx. 11th ed. St. Louis, MO: Mosby Incorporated; 2001.

59. Medication administration. In: DeLaune SC et al, eds. Fundamentals of Nursing: Standards and Practice. 2nd ed. Clifton Park, NJ: Delmar/Thomson Learning; 2002, 673740. 60. Administering medications. In: Potter PA, et al, eds. Basic Nursing: A Critical Thinking Approach. 4th ed. St. Louis, MO: Mosby; 1999:596670.

61. Beckwith MC, Tyler LS, eds. Cancer Chemotherapy Manual. St. Louis, MO: Facts and Comparisons; 2001. 62. Engle KK, Hannawa TE. Techniques for administering oral medications to critical care patients receiving continuous enteral nutrition. Am J Health Syst Pharm. 1999;56:14414.

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