250mg & 500mg Tablets
125mg / 5mL & 250mg / 5mL Suspension
DESCRIPTION children corresponds to the pharmacokinetic profile of the suspension in adults.
Claritek (Clarithrom ycin) is a semi-synthetic macrolide antibiotic obtained by Due to its chemical structure (6-O-Methylerythromycin) clarithromycin is quite
substitution of the hydroxyl group in position 6 by a CH3O group in the erythromycin resistant to degradation by stomach acid. After oral administration of 250mg &
lactonic ring. Chemically clarithromycin is 6-O-Methylerythromycin. The molecular 500mg clarithromycin twice daily, peak plasma levels of 1-2 µg/mL & 2.8µg/mL
formula is C38H 69NO13 and the structural formula is: were observed respectively in adu lts. The peak pla sma concentration of
O
pharmacological active 14-hydroxy metabolite was 0.6µg/mL after the administration
of 250m g clarithromycin twice daily. Steady state is attained within 2 days of
H3C CH3 dosing.
OH OCH 3 H3C CH3
H3C N Effect of Food
OH CH3
HO Food slightly delays the absorption of clarithromycin but does not affect the extent
H3C O O CH3 of bioavailability, therefore it may be given without regard to food.
O
H3C Distribution:
O O Clarithromycin penetrates well into different compartments, with an es timated
OCH3
CH3 volume of distribution of 200-400L. Clarithromy cin provides concentrations in
CH3
O some tissues that are several times higher than the circulating level of the active
OH substance. Increased levels have been found in both tonsils and lung tis sue.
CH3
Clarithromycin also penetrates the gastric mucus.
Clarithromycin Clarithromycin is approximately 80% bound to plasma proteins at therapeutic
levels.
QUALITATIVE & QUANTITATIVE COMPOSITION
CLARITEK (Clarithromycin) is available for oral administration as: Metabolism:
Clarithromycin is rapidly and ex tensively metabolised in the liver. Metabolism
1. CLARITEK Tablets 250mg involves mainly N-dealkylation, oxidation and stereospecific hydroxylation at
Each film-coated tablet contains: position C14.
Clarithromycin USP…250mg
Excretion
2. CLARITEK Tablets 500mg Clarit hromycin is excreted in the feces (5-10%) via the bile. At steady state
Each film-coated tablet contains: approximately 20% and 30% of c larithromycin is excreted as unchanged drug
Clarithromycin USP…500mg in urine. 14-hydroxy clarithromycin as well as other metabolites are also excreted
in the urine accounting for 10% to 15% of the dose. The elimination half-life of
3. CLARITEK Granules 125mg/5mL clarithromycin is reportedly about 3 to 4 hours in patients receiving 250mg doses
Each reconstituted 5mL contains: twice daily, and about 5 to 7 hours in those receiving 500mg twice daily. The
Clarithromycin USP…125mg principal metabolite, 14-OH-clarithromycin has an elimination half-life of 5 to 6
hours after a dose of 250mg twice daily and about 7 to 9 hours in those receiving
4. CLARITEK Drops 125mg/5mL 500mg twice daily.
Each reconstituted 5mL contains:
Clarithromycin USP…125mg Special Populations
Renal impairment:
5. CLARITEK Dry Suspension 250mg/5mL The plasma levels, half-life, Cmax and Cmin for both clarithromycin and its 14-OH
Each reconstituted 5mL contains: metabolite were higher and the AUC was larger in subjects with renal impairment.
Clarithromycin USP…250mg
Geriatric:
Elderly patients with severe renal impairment may require dose adjust ment.
CLINICAL PHARMACOLOGY
Mechanism of Action THERAPEUTIC INDICATIONS
Clarithromy cin exerts its anti-bac terial action by binding to the 50s ribosomal CLARITEK (Clari thro mycin) is ind icated for treat ment of infections due to
sub-unit of susceptible bacteria and s uppresses protein synthesis. It is highly susceptible organisms. Such infections include:
potent against a wide variety of aerobic and anaerobic gram-positive and gram- - Lower re spiratory tract in fections (e. g., bronchitis, pneumonia)
negative organisms. - Upper respirator y tract infections (e.g. pha ryngi tis, sinusitis, tonsill itis)
- Acute otitis media in children
Microbiology - Skin and soft tissue infections (e.g., folliculitis, cellulitis, erysipelas, impetigo,
Clarithromy cin has shown to be active against the following microorganisms: abscesses)
- Disseminated or localized mycobacterial infections due to MAC.
Aerobic gram-positive microorganisms - To eradicate Helicobacter pylori in treatment regimens for peptic ulcer disease.
Staphylococcus aureus - To prevent disseminated Mycobacterium av ium complex (MAC) disease in
Streptococcus pneumoniae patients with advanced HIV infection.
Streptococcus pyogenes - As an alter native treatment to penicillins for prophy laxis of endocar ditis.
Listeria monocytogenes
DOSAGE AND ADMINISTRATION
Aerobic gram-negative microorganisms Adults:
Haemophilus influenzae The usual recommended dosage of CLARITEK (Clarithromycin) is 250mg tablet
Haemophilus parainfluenzae twice daily. In more severe infections the dosage can be increased to 500mg
Moraxella catarrhalis twice daily. The usual duration of therapy is 6 to 14 days.
Neisseria gonorrheae
Legionella spp. (e.g., Legionella pneumophila) Th e following table is a suggested guide for determining dosage:
Mycobacteria
Mycobacterium leprae
Mycobacterium kansasii
Mycobacterium chelonae
Mycobacterium fortuitum
Mycobacterium avium complex [MAC] (consisting of: Mycobacterium avium
Mycobacterium intracellulare)
Helicobacter
Helicobacter pylori
Other microorganisms
Mycoplasma pneumoniae
Chlamydia pneumoniae (TWAR)
Chlamydia trachomatis
Ureaplasma urealytieum
Protozoan Toxoplasma gondii
Pharmacokinetics
Absorption:
Clarithromycin is rapidly and well absorbed from the gastrointestinal tr act but
undergoes extensive first-pass metabolism after oral administration. The absolute
bioav ailabi lity of a 250mg clarith romycin tablet is approx imately 50%. The
bio availab ilit y of the suspension is identi cal to or slightl y higher than the
bioavailability of the table ts. The pharmac okinetic profile of the suspension in
Children: The usual recommended daily dosage of CLARITEK (Clarithromycin) Drug interactions
suspension is 7.5mg/kg B.I.D up to a maximum of 500mg twice daily. The usual Digoxin: Elevated digoxin serum concentrations have been reported in patients
duration of treatment is 5 to 10 days depending on the pathogen involved and receiving clarithromycin and digoxin concomitantly. Monitoring of serum digoxin
the severity of the condition. levels should be considered.
The following table is a suggested guide for determining dosage.
Quinidine/D isopyramide: Concurrent use of clarithrom ycin and quinidine or
disopyramide may cause Torsades de Pointes. Electrocardiogram and serum
levels of these medications should be monitored during clarithromycin therapy.
HMG-CoA Reductase Inhibitors: As with other macrolides, clarithromycin has
been reported to increase concentrations of HMG-CoA reductase inhibitors (e.g.
statins). Rare reports of rhabdomyolysis have been reported in patients taking
these drugs concomitantly.
Zidov udine: Simultaneous oral administration of clarit hromycin tablets and
Dosage for the eradication of H. pylori associated with peptic ulcer disease zidovudine to HIV-infected adult patients may result in decreased steady-state
CLARITEK (Clarithromy cin), usually in a dose of 500mg twice daily, is given zidovudine concentrations. This interaction does not appear to occur in pediatric
with another antibacterial and either a proton pump inhibitor or a histamine H 2- HIV-infected patients taking clarithrom ycin suspension with zidovudine or
receptor antagonist, for 7 to 14 days. dideoxyinosine.
Dosage for Mycobacterial Infections Ritonavir: Concomitant administration of clarithromycin and ritonavir resulted in
Adults: CLARITEK (Clarithromycin) is recommended as the primary agent for a 77% increase in clarithromycin AUC and a 100% decrease in the AUC of 14-
the prophylaxis and treatment of disseminated infection due to Mycobacterium OH clarithromycin. Clarithromycin may be administered without dosage adjustment
avium complex. Clarithromycin should be used in combination with other anti- to patients with normal renal function taking ritonavir. However, for patients with
mycobacterial drugs that have shown in vitro ac tivity against MAC or clinical ren al imp ai rme nt , d os ag e ad ju st me nt s sh ou l d be c on si de re d .
benefit in MAC treatment. The recommended dose for mycobacterial infections
in adults is 500mg b.i.d. OVERDOSAGE:
Overdose of clarit hromycin can cause gastrointes tinal symptoms such as
Children: In children, the recommended dose is 7.5mg/kg b.i.d up to 500mg abdominal pain, vomiting, nausea, and diarrhea. Adverse reactions accompanying
b.i.d. Dosing recommendations for children are in the table above. overdosage s hould be treated by the prom pt elimination of unabsorbed drug
and support ive measures. As with other macrolides , clari thromycin serum
Renal Impaired Patients: concentrations are not expected to be appreciably affected by hemodialysis or
The maximum recommended dosages should be reduced proportionately to peritoneal dialysis.
renal impairment. At creatinine clearance rate of < 30 mL/min, the dosage should
be halved to 250mg daily or in the most severe infections to 250mg twice daily HOW SUPPLIED
for adults and 7.5 mg/kg once a day for children. The duration of treatment Claritek (Clarithromy cin) Tablets 250mg are available in blister pack of 10's.
should not exceed 14 days in these patients. Claritek (Clarithromy cin) Tablets 500mg are available in blister pack of 10's.
Claritek (Clarithromycin) Granules 125mg/5mL are available in 50mL.
Direction for reconstituition Claritek (Clarithromycin) Drops 125mg/5mL are available in 25mL.
Fill previously boiled and cooled water up to the mark on the bottle and shake Claritek (Clarithromycin) Dry Suspension 250mg/5m L are available in 70mL.
well. After mixing, do not refrigerate. Keep tightly closed after use.
STORAGE
o
CONTRAINDICATIONS Store below 30 C.
- Clarithromycin is contraindicated in patients with known hypersensitivity to Protect from sunlight & moisture.
the active substance, other macrolide antibiotics or to any of the excipients. The reconstituted suspension can be used for up to 14 days , when stored at
- Concomitant administration of clari thromycin with any of the follow ing room temperature.
medicines is contraindicated: astemizole, cisapride, pimozide and terfenadine.
- Concomitant administration of Clarithromycin with ergot derivatives is The expiration date refers to the product correctly stored at the required conditions.
contraindicated.
ADVERSE REACTIONS Keep out of reach of children.
The foll owing side effec ts were repor ted with the use of Clarithromycin:
Common: Oral monilia, headache, smell alteration, nausea, diarrhea, vomiting, To be sold on prescription of a registered med ical practitioner only.
abdominal pain, dyspepsia, stomatitis, glossitis, reversible tooth and tongue
discol ora tion, a nd taste pe rversion, i. e. meta llic or bit ter t aste.
Uncommon: Decreased leucocyte levels, allergic reactions ranging from urticaria
and mild skin eruptions to anaphylax is, hepatic dysfunction which is usually
transient and reversible, hepatit is and cholestasis with or without jaundic e, Please read the contents carefully before use.
arthralgia and myalgia. This package insert is continually updated from time to time.
Rare: Tinnitus
Very Rare: Thromboc ytopenia, anxiety, insomnia, hallucinatio ns, psychosis,
disorientation, depersonalisation, bad dreams and confusion, dizziness, vertigo,
paraesthesia, convulsions, Reversible hearing loss, QT prolongation, ventricular
tachycardia and Torsades de Pointes, pancreatitis, pseudomembranous colitis
in range of severity from mild to life threatening, fatal hepatic failure in patients
with pre-existing liver disease or taking other hepatotoxic medicinal products,
Stevens-Johnson syndrome, toxic epidermal necrolysis, interstitial nephritis and
renal failure.
PRECAUTIONS
- Caution should be taken in adminis tering Clarithrom ycin to patients with
impaired hepatic function.
- Caution should also be paid to the possibility of cross-resistances between
Clarithromycin and other macrolide drugs, as well as lincomycin and
clindamycin.
- Pseudomembranous colitis has been reported with the use of broad-spectrum
antibiotics. Therefore, it is important to consider its diagnosis in patients who
develo p severe diarrhea during or after therapy with Clarithromycin.
- Prolonged or r epeated use of Clarit hromycin may result in s uperinfections
with insusceptible organisms. In case of superinfection, Clarithromycin therapy
should be stopped.
- Clarithromycin should be used with caution whenever indicated for use in
patients receiving treatment with an inducer of CYP3A4.
- Clarithromycin in combination with ranitidine bismuth citrate therapy should
not be used in patients with a history of acute porphyria.
- Clarithromycin, is an inhibitor of the metabolising enzyme CYP3A4 should
not be used concomitantly with different CYP3A4 substrates unless plasma
levels, therapeu tic effect or adverse events of the CYP3A4 substrate are
closely monitored.
Pregnancy:
There are no adequ ate or well-controlled studies in pregn ant women.
Clarithromy cin should be used during pregnancy only if the potential benefi t
justifies the potential risk to the fetus.
Nursing Mothers:
Clarithromycin and its active metabolite are excreted in breast milk. Therefore,
diarrhea and fungus infection of the mucous membranes could occur in the
breast-fed infant, so that nursing might have to be discontinued. The possibility
of sensitisation should be born in mind. The benefit of treatment of the mother
should be weighed against the potential risk for the infant.
L02-200007164
