Clarithromycin

FDA Drug Information • Also known as: Clarithromycin

Brand Names: Clarithromycin
Drug Class: Macrolide Antimicrobial [EPC]
Route: ORAL
Dosage Form: TABLET, FILM COATED
Product Type: HUMAN PRESCRIPTION DRUG

Description

11 DESCRIPTION Clarithromycin is a semi-synthetic macrolide antimicrobial for oral use. Chemically, it is 6- 0 ‑ methylerythromycin. The molecular formula is C 38 H 69 NO 13 , and the molecular weight is 747.96. The structural formula is: Clarithromycin is a white to off-white crystalline powder. It is soluble in acetone, slightly soluble in methanol, ethanol, and acetonitrile, and practically insoluble in water. Clarithromycin tablets, USP are intended for oral administration and contain 250 mg or 500 mg of clarithromycin, USP. In addition, each clarithromycin tablet contains the following inactive ingredients: croscarmellose sodium, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polysorbate 80, povidone, talc, and titanium dioxide. chemicalstructure

What Is Clarithromycin Used For?

1 INDICATIONS AND USAGE Clarithromycin is a macrolide antimicrobial indicated for mild to moderate infections caused by designated, susceptible bacteria in the following: Acute Bacterial Exacerbation of Chronic Bronchitis in Adults ( 1.1 ) Acute Maxillary Sinusitis ( 1.2 ) Community-Acquired Pneumonia ( 1.3 ) Pharyngitis/Tonsillitis ( 1.4 ) Uncomplicated Skin and Skin Structure Infections ( 1.5 ) Acute Otitis Media in Pediatric Patients ( 1.6 ) Treatment and Prophylaxis of Disseminated Mycobacterial Infections ( 1.7 ) Helicobacter pylori Infection and Duodenal Ulcer Disease in Adults ( 1.8 ) Limitations of Use To reduce the development of drug-resistant bacteria and maintain the effectiveness of clarithromycin tablets and other antibacterial drugs, clarithromycin tablets should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. ( 1.9 ) 1.1 Acute Bacterial Exacerbation of Chronic Bronchitis Clarithromycin tablets are indicated in adults for the treatment of mild to moderate infections caused by susceptible isolates due to Haemophilus influenzae , Haemophilus parainfluenzae , Moraxella catarrhalis , or Streptococcus pneumoniae [see Indications and Usage ( 1.9 )] . 1.2 Acute Maxillary Sinusitis Clarithromycin tablets are indicated for the treatment of mild to moderate infections caused by susceptible isolates due to Haemophilus influenzae , Moraxella catarrhalis , or Streptococcus pneumoniae [see Indications and Usage ( 1.9 )] . 1.3 Community-Acquired Pneumonia Clarithromycin tablets are indicated [see Indications and Usage ( 1.9 )] for the treatment of mild to moderate infections caused by susceptible isolates due to: Haemophilus influenzae (in adults) Mycoplasma pneumoniae, Streptococcus pneumoniae, Chlamydophila pneumoniae (in adults and pediatric patients) 1.4 Pharyngitis/Tonsillitis Clarithromycin tablets are indicated for the treatment of mild to moderate infections caused by susceptible isolates due to Streptococcus pyogenes as an alternative in individuals who cannot use first line therapy. 1.5 Uncomplicated Skin and Skin Structure Infections Clarithromycin tablets are indicated for the treatment of mild to moderate infections caused by susceptible isolates due to Staphylococcus aureus , or S treptococcus pyogenes . 1.6 Acute Otitis Media Clarithromycin tablets are indicated in pediatric patients for the treatment of mild to moderate infections caused by susceptible isolates due to Haemophilus influenzae , Moraxella catarrhalis , or Streptococcus pneumoniae [see Clinical Studies ( 14.2 )] . 1.7 Treatment and Prophylaxis of Disseminated Mycobacterial Infections Clarithromycin tablets are indicated for the treatment of mild to moderate infections caused by susceptible isolates due to Mycobacterium avium or Myc obacterium intracellulare in patients with advanced HIV infection [see Clinical Studies ( 14.1 )] . 1.8 Helicobacter pylori Infection and Duodenal Ulcer Disease Clarithromycin...

Dosage and Administration

2 DOSAGE AND ADMINISTRATION Adults : clarithromycin tablets 250 mg or 500 mg every 12 hours for 7 to 14 days ( 2.2 ) H. pylori eradication (in combination with lansoprazole/amoxicillin, omeprazole/amoxicillin, or omeprazole): clarithromycin tablets 500 mg every 8 or 12 hours for 10 to 14 days. See full prescribing information (FPI) for additional information. ( 2.3 ) Pediatric Patients : clarithromycin 15 mg/kg/day divided every 12 hours for 10 days ( 2.4 ) Mycobacterial Infections : clarithromycin tablets 500 mg every 12 hours; clarithromycin tablets 7.5 mg/kg up to 500 mg every 12 hours in pediatric patients ( 2.5 ) Reduce dose in moderate renal impairment with concomitant atazanavir or ritonavir-containing regimens and in severe renal impairment ( 2.6 ) 2.1 Important Administration Instructions Clarithromycin tablets may be given with or without food. 2.2 Adult Dosage The recommended dosages of clarithromycin tablets for the treatment of mild to moderate infections in adults are listed in Table 1 . Table 1. Adult Dosage Guidelines Infection Clarithromycin Tablets Dosage (every 12 hours) Duration (days) Acute bacterial exacerbation of chronic bronchitis 250 to 500 mg 7 † -14 Acute maxillary sinusitis 500 mg 14 Community-acquired pneumonia 250 mg 7 ǂ -14 Pharyngitis/Tonsillitis 250 mg 10 Uncomplicated skin and skin structure infections 250 mg 7-14 Treatment and prophylaxis of disseminated Mycobacterium avium disease [see Dosage and Administration ( 2.5 )] 500 mg § - H.pylori eradication to reduce the risk of duodenal ulcer recurrence with amoxicillin and omeprazole or lansoprazole [see Dosage and Administration ( 2.3 )] 500 mg 10-14 H.pylori eradication to reduce the risk of duodenal ulcer recurrence with omeprazole [see Dosage and Administration ( 2.3 )] 500 mg every 8 hours 14 * For M. catarrhalis and S. pneumoniae use 250 mg. For H. influenzae and H. parainfluenzae , use 500 mg. † For H parainfluenzae , the duration of therapy is 7 days. ǂ For H. influenzae , the duration of therapy is 7 days. § Clarithromycin therapy should continue if clinical response is observed. Clarithromycin can be discontinued when the patient is considered at low risk of disseminated infection. 2.3 Combination Dosing Regimens for H. pylori Infection Triple therapy: clarithromycin/lansoprazole/amoxicillin The recommended adult dosage is 500 mg clarithromycin tablets, 30 mg lansoprazole, and 1 gram amoxicillin, all given every 12 hours for 10 or 14 days [see Indications and Usage ( 1.8 ) and Clinical Studies ( 14.3 )] . Triple therapy: clarithromycin/omeprazole/amoxicillin The recommended adult dosage is 500 mg clarithromycin tablets, 20 mg omeprazole, and 1 gram amoxicillin; all given every 12 hours for 10 days. In patients with an ulcer present at the time of initiation of therapy, an additional 18 days of omeprazole 20 mg once daily is recommended for ulcer healing and symptom relief [see Indications and Usage ( 1.8 ) and Clinical Studies ( 14.3 )] . Dual therapy:...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following serious adverse reactions are described below and elsewhere in the labeling: Acute Hypersensitivity Reactions [see Warnings and Precautions ( 5.1 )] QT Prolongation [see Warnings and Precautions ( 5.2 )] Hepatotoxicity [see Warnings and Precautions ( 5.3 )] Serious Adverse Reactions Due to Concomitant Use with Other Drugs [see Warnings and Precautions ( 5.4 )] Clostridium difficile Associated Diarrhea [see Warnings and Precautions ( 5.6 )] Exacerbation of Myasthenia Gravis [see Warnings and Precautions ( 5.8 )] Most frequent adverse reactions for both adult and pediatric populations in clinical trials: abdominal pain, diarrhea, nausea, vomiting, dysgeusia ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Sandoz Inc. at 1-800-525-8747 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. Based on pooled data across all indications, the most frequent adverse reactions for both adult and pediatric populations observed in clinical trials are abdominal pain, diarrhea, nausea, vomiting and dysgeusia. Also reported were dyspepsia, liver function test abnormal, anaphylactic reaction, candidiasis, headache, insomnia, and rash. The subsequent subsections list the most common adverse reactions for prophylaxis and treatment of mycobacterial infections and duodenal ulcer associated with H. pylori infection. In general, these profiles are consistent with the pooled data described above. Prophylaxis of Mycobacterial Infections In AIDS patients treated with clarithromycin over long periods of time for prophylaxis against M. avium , it was often difficult to distinguish adverse reactions possibly associated with clarithromycin administration from underlying HIV disease or intercurrent illness. Median duration of treatment was 10.6 months for the clarithromycin group and 8.2 months for the placebo group. Table 4. Incidence Rates (%) of Selected Adverse Reactions Includes those events possibly or probably related to study drug and excludes concurrent conditions in Immunocompromised Adult Patients Receiving Prophylaxis Against M. avium Complex Body System 2% or greater Adverse Reaction Incidence Rates for either treatment group Adverse Reaction Clarithromycin (n=339) % Placebo (n=339) % Body as a Whole Abdominal pain 5% 4% Headache 3% 1% Digestive Diarrhea 8% 4% Dyspepsia 4% 3% Flatulence 2% 1% Nausea 11% 7% Vomiting 6% 3% Skin & Appendages Rash 3% 4% Special Senses Taste Perversion 8% Significant higher incidence compared to the placebo-treated group 0.3% Discontinuation due to adverse reactions occurred in 18% of patients receiving clarithromycin compared to 17% of patients receiving placebo in this trial. Primary reasons for discontinuation in clarithromycin tablets treated patients include headache, nausea, vomiting, depression, and taste perversion. Changes in Laboratory Values Selected laboratory adverse experiences that were reported during therapy in greater than 2 % of adult patients treated with clarithromycin tablets in a randomized double-blind clinical trial involving 682 patients are presented in Table 5 . In immunocompromised patients receiving prophylaxis against M. avium , evaluations of laboratory values were made by analyzing those values outside the seriously abnormal value (i.e., the extreme high or low limit) for the specified test. Table 5. Percentage of Patients Includes only patients with baseline values within the normal range or borderline high (hematology variables) and within normal range or borderline low (chemistry variables) Exceeding Extreme Laboratory Values in Patients Receiving Prophylaxis Against M. avium Complex Clarithromycin 500 mg twice a day Placebo WBC Count <1 x 10 9 /L 2/103...

Drug Interactions

7 DRUG INTERACTIONS Co-administration of clarithromycin tablets is known to inhibit CYP3A, and a drug primarily metabolized by CYP3A may be associated with elevations in drug concentrations that could increase or prolong both therapeutic and adverse effects of the concomitant drug. Clarithromycin tablets should be used with caution in patients receiving treatment with other drugs known to be CYP3A enzyme substrates, especially if the CYP3A substrate has a narrow safety margin (e.g., carbamazepine) and/or the substrate is extensively metabolized by this enzyme. Adjust dosage when appropriate and monitor serum concentrations of drugs primarily metabolized by CYP3A closely in patients concurrently receiving clarithromycin. Table 8. Clinically Significant Drug Interactions with Clarithromycin Tablets Drugs That Are Affected By Clarithromycin Tablets Drug(s) with Pharmacokinetics Affected by Clarithromycin Tablets Recommendation Comments Antiarrhythmics: Disopyramide Quinidine Dofetilide Amiodarone Sotalol Procainamide Not Recommended Disopyramide, Quinidine: There have been postmarketing reports of torsades de pointes occurring with concurrent use of clarithromycin and quinidine or disopyramide. Electrocardiograms should be monitored for QTc prolongation during coadministration of clarithromycin with these drugs [see Warnings and Precautions ( 5.2 )] . Serum concentrations of these medications should also be monitored. There have been spontaneous or published reports of CYP3A based interactions of clarithromycin with disopyramide and quinidine. There have been postmarketing reports of hypoglycemia with the concomitant administration of clarithromycin and disopyramide. Therefore, blood glucose levels should be monitored during concomitant administration of clarithromycin and disopyramide. Digoxin Use With Caution Digoxin: Digoxin is a substrate for P-glycoprotein (Pgp) and clarithromycin is known to inhibit Pgp. When clarithromycin and digoxin are co‑administered, inhibition of Pgp by clarithromycin may lead to increased exposure of digoxin. Elevated digoxin serum concentrations in patients receiving clarithromycin and digoxin concomitantly have been reported in postmarketing surveillance. Some patients have shown clinical signs consistent with digoxin toxicity, including potentially fatal arrhythmias. Monitoring of serum digoxin concentrations should be considered, especially for patients with digoxin concentrations in the upper therapeutic range. Oral Anticoagulants: Warfarin Use With Caution Oral anticoagulants: Spontaneous reports in the postmarketing period suggest that concomitant administration of clarithromycin and oral anticoagulants may potentiate the effects of the oral anticoagulants. Prothrombin times should be carefully monitored while patients are receiving clarithromycin and oral anticoagulants simultaneously [see Warnings and Precautions ( 5.4 )] . Antiepileptics: Carbamazepine Use With Caution Carbamazepine: Concomitant...

Contraindications

4 CONTRAINDICATIONS Hypersensitivity to clarithromycin or any macrolide drug ( 4.1 ) Cisapride and pimozide ( 4.2 ) History of cholestatic jaundice/hepatic dysfunction with use of clarithromycin ( 4.3 ) Colchicine in renal or hepatic impairment ( 4.4 ) Lomitapide, lovastatin, and simvastatin ( 4.5 ) Ergot alkaloids (ergotamine or dihydroergotamine) ( 4.6 ) Lurasidone ( 4.7 ) 4.1 Hypersensitivity Clarithromycin tablets are contraindicated in patients with a known hypersensitivity to clarithromycin, erythromycin, or any of the macrolide antibacterial drugs [see Warnings and Precautions ( 5.1 )] . 4.2 Cisapride and Pimozide Concomitant administration of clarithromycin tablets with cisapride and pimozide is contraindicated [see Drug Interactions ( 7 )] . There have been postmarketing reports of drug interactions when clarithromycin is co‑administered with cisapride or pimozide, resulting in cardiac arrhythmias (QT prolongation, ventricular tachycardia, ventricular fibrillation, and torsades de pointes ) most likely due to inhibition of metabolism of these drugs by clarithromycin tablets. Fatalities have been reported. 4.3 Cholestatic Jaundice/Hepatic Dysfunction Clarithromycin tablets are contraindicated in patients with a history of cholestatic jaundice or hepatic dysfunction associated with prior use of clarithromycin. 4.4 Colchicine Concomitant administration of clarithromycin tablets and colchicine is contraindicated in patients with renal or hepatic impairment. 4.5 Lomitapide, Lovastatin, and Simvastatin Concomitant administration of clarithromycin tablets with lomitapide is contraindicated due to potential for markedly increased transaminases [see Warnings and Precautions ( 5.4 ) and Drug Interactions ( 7 )]. Concomitant administration of clarithromycin tablets with HMG-CoA reductase inhibitors (statins) that are extensively metabolized by CYP3A4 (lovastatin or simvastatin) is contraindicated, due to the increased risk of myopathy, including rhabdomyolysis [see...

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary Based on findings from animal studies, clarithromycin tablets are not recommended for use in pregnant women except in clinical circumstances where no alternative therapy is appropriate. If pregnancy occurs while taking clarithromycin tablets, the patient should be apprised of the potential hazard to the fetus [see Warnings and Precautions ( 5.7 )]. Limited data from a small number of published human studies with clarithromycin tablets use during pregnancy are insufficient to inform drug-associated risks of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies, administration of oral clarithromycin to pregnant mice, rats, rabbits, and monkeys during the period of organogenesis produced malformations in rats (cardiovascular anomalies) and mice (cleft palate) at clinically relevant doses based on body surface area comparison. Fetal effects in mice, rats, and monkeys (e.g., reduced fetal survival, body weight, body weight gain) and implantation losses in rabbits were generally considered to be secondary to maternal toxicity (see Data). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data Animal reproduction studies were conducted in mice, rats, rabbits, and monkeys with oral and intravenously administered clarithromycin. In pregnant mice, clarithromycin was administered during organogenesis (gestation day [GD] 6 to 15) at oral doses of 15, 60, 250, 500, or 1000 mg/kg/day. Reduced body weight observed in dams at 1000 mg/kg/day (3 times the maximum recommended human dose [MRHD] based on body surface area comparison) resulted in reduced survival and body weight...

Overdosage

10 OVERDOSAGE Overdosage of clarithromycin tablets can cause gastrointestinal symptoms such as abdominal pain, vomiting, nausea, and diarrhea. Treat adverse reactions accompanying overdosage by the prompt elimination of unabsorbed drug and supportive measures. As with other macrolides, clarithromycin serum concentrations are not expected to be appreciably affected by hemodialysis or peritoneal dialysis.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING Clarithromycin tablets, USP 500 mg are white, oval-shaped, film-coated tablets, debossed GG C9 on one side and plain on the reverse side, and are supplied as follows: NDC 43063-530-14 in bottles of 14 tablets NDC 43063-530-20 in bottles of 20 tablets Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Dispense in a tight container as described in the USP. Protect from light.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.