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 )
1.1Acute 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 )] .
1.2Acute 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 )] .
1.3Community-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)
1.4Pharyngitis/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.
1.5Uncomplicated 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 .
1.6Acute 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 )] .
1.7Treatment 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 tablets are given in combination with other drugs in adults as described below to eradicate H. pylori . The eradication of H. pylori has been demonstrated to reduce the risk of duodenal ulcer recurrence [see Clinical Studies ( 14.3 )] . Clarithromycin tablets in combination with amoxicillin and PREVACID (lansoprazole) or PRILOSEC (omeprazole) delayed-release capsules, as triple therapy, are indicated for the treatment of patients with H. pylori infection and duodenal ulcer disease (active or five-year history of duodenal ulcer) to eradicate H. pylori .
Clarithromycin tablets in combination with PRILOSEC (omeprazole) capsules are indicated for the treatment of patients with an active duodenal ulcer associated with H. pylori infection. Regimens which contain clarithromycin tablets as the single antibacterial agent are more likely to be associated with the development of clarithromycin resistance among patients who fail therapy. Clarithromycin-containing regimens should not be used in patients with known or suspected clarithromycin resistant isolates because the efficacy of treatment is reduced in this setting.
1.9Limitations of Use
There is resistance to macrolides in certain bacterial infections caused by Streptococcus pneumoniae and Staphylococcus aureus . Susceptibility testing should be performed when clinically indicated.
1.10Usage
To reduce the development of drug-resistant bacteria and maintain the effectiveness of clarithromycin 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 susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
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 )
4.1Hypersensitivity
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 )] .
4.2Cisapride 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.
4.3Cholestatic Jaundice/Hepatic Dysfunction
Clarithromycin tablets are contraindicated in patients with a history of cholestatic jaundice or hepatic dysfunction associated with prior use of clarithromycin.
4.4Colchicine
Concomitant administration of clarithromycin tablets and colchicine is contraindicated in patients with renal or hepatic impairment.
4.5Lomitapide, 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 Warnings and Precautions ( 5.4 ) and Drug Interactions ( 7 )].
4.6Ergot Alkaloids
Concomitant administration of clarithromycin and ergotamine or dihydroergotamine is contraindicated [see Drug Interactions ( 7 )] .
4.7Contraindications for Co-administered Drugs
For information about contraindications of other drugs indicated in combination with clarithromycin tablets, refer to their full prescribing information (contraindications section).
Warnings and precautions
Severe Acute Hypersensitivity Reactions : Discontinue clarithromycin tablets if occurs ( 5.1 ) QT Prolongation : Avoid clarithromycin tablets in patients with known QT prolongation or receiving drugs known to prolong the QT interval, ventricular arrhythmia ( torsades de pointes ), hypokalemia/hypomagnesemia, significant bradycardia, or taking Class IA or III antiarrhythmics ( 5.2 ) Hepatotoxicity : Discontinue if signs and symptoms of hepatitis occur ( 5.3 ) Serious adverse reactions can occur due to drug interactions of clarithromycin tablets with colchicine, some lipid-lowering agents, some calcium channel blockers, and other drugs ( 5.4 ) Risk of all-cause mortality one year or more after the end of treatment in patients with coronary artery disease.
Balance this potential risk with the treatment benefits when prescribing clarithromycin tablets in these patients ( 5.5 ) Clostridium difficile associated diarrhea (CDAD) : Evaluate if diarrhea occurs ( 5.6 ) Embryo-Fetal Toxicity : Based on animal findings, clarithromycin tablets is not recommended for use in pregnant women except in clinical circumstances where no alternative therapy is appropriate ( 5.7 ) Exacerbation of myasthenia gravis has been reported in patients receiving clarithromycin tablets therapy ( 5.8 )
5.1 Severe Acute Hypersensitivity Reactions In the event of severe acute hypersensitivity reactions, such as anaphylaxis, Stevens-Johnson Syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms (DRESS), Henoch-Schonlein purpura, and acute generalized exanthematous pustulosis, discontinue clarithromycin tablets therapy immediately and institute appropriate treatment.
5.2QT Prolongation
Clarithromycin tablets have been associated with prolongation of the QT interval and infrequent cases of arrhythmia. Cases of torsades de pointes have been spontaneously reported during postmarketing surveillance in patients receiving clarithromycin tablets. Fatalities have been reported. Avoid clarithromycin tablets in the following patients:Avoid clarithromycin tablets in the following patients: patients with known prolongation of the QT interval, ventricular cardiac arrhythmia, including torsades de pointes patients receiving drugs known to prolong the QT interval [see also Contraindications ( 4.2 )]
patients with ongoing proarrhythmic conditions such as uncorrected hypokalemia or hypomagnesemia,clinically significant bradycardia and in patients receiving Class IA (e.g., quinidine, procainamide,disopyramide) or Class III (e.g., dofetilide, amiodarone, sotalol) antiarrhythmic agents. Elderly patients may be more susceptible to drug-associated effects on the QT interval Elderly patients may be more susceptible to drug-associated effects on the QT interval [see Use in Specific Populations ( 8.5 )].
5.3Hepatotoxicity
Hepatic dysfunction, including increased liver enzymes, and hepatocellular and/or cholestatic hepatitis, with or without jaundice, has been reported with clarithromycin. This hepatic dysfunction may be severe and is usually reversible. In some instances, hepatic failure with fatal outcome has been reported and generally has been associated with serious underlying diseases and/or concomitant medications. Symptoms of hepatitis can include anorexia, jaundice, dark urine, pruritus, or tender abdomen.
Discontinue clarithromycin tablets immediately if signs and symptoms of hepatitis occur.
5.4Serious Adverse Reactions Due to Concomitant Use with Other Drugs
Drugs metabolized by CYP3A4: Serious adverse reactions have been reported in patients taking clarithromycin tablets concomitantly with CYP3A4 substrates. These include colchicine toxicity with colchicine; markedly increased transaminases with lomitapide; rhabdomyolysis with simvastatin, lovastatin, and atorvastatin; hypoglycemia and cardiac arrhythmias (e.g., torsades de pointes ) with disopyramide; and hypotension and acute kidney injury with calcium channel blockers metabolized by CYP3A4 (e.g., verapamil, amlodipine, diltiazem, nifedipine).
Most reports of acute kidney injury with calcium channel blockers metabolized by CYP3A4 involved elderly patients 65 years of age or older. Use clarithromycin tablets with caution when administered concurrently with medications that induce the cytochrome CYP3A4 enzyme. The use of clarithromycin with lomitapide, simvastatin, lovastatin, ergotamine, or dihydroergotamine is contraindicated [see Contraindications ( 4.5 , 4.6 ) and Drug Interactions ( 7 )].
Life-threatening and fatal drug interactions have been reported in patients treated with clarithromycin and colchicine. Clarithromycin is a strong CYP3A4 inhibitor and this interaction may occur while using both drugs at their recommended doses. If co-administration of clarithromycin tablets and colchicine is necessary in patients with normal renal and hepatic function, reduce the dose of colchicine. Monitor patients for clinical symptoms of colchicine toxicity.
Concomitant administration of clarithromycin tablets and colchicine is contraindicated in patients with renal or hepatic impairment . Colchicine: Life-threatening and fatal drug interactions have been reported in patients treated with clarithromycin and colchicine. Clarithromycin is a strong CYP3A4 inhibitor and this interaction may occur while using both drugs at their recommended doses. If co-administration of clarithromycin tablets and colchicine is necessary in patients with normal renal and hepatic function, reduce the dose of colchicine.
Monitor patients for clinical symptoms of colchicine toxicity. Concomitant administration of clarithromycin tablets and colchicine is contraindicated in patients with renal or hepatic impairment [see Contraindications ( 4.4 ) and Drug Interactions ( 7 )] . Concomitant use of clarithromycin with lomitapide is contraindicated Lomitapide is metabolized by CYP3A4, and concomitant treatment with clarithromycin increases the plasma concentration of lomitapide, which increases the risk of elevation in transaminases If treatment with clarithromycin cannot be avoided, therapy with lomitapide must be suspended during the course of treatment.
Lomitapide: Concomitant use of clarithromycin with lomitapide is contraindicated [see Contraindications ( 4.5 )]. Lomitapide is metabolized by CYP3A4, and concomitant treatment with clarithromycin increases the plasma concentration of lomitapide, which increases the risk of elevation in transaminases [see Drug Interactions ( 7 )]. If treatment with clarithromycin cannot be avoided, therapy with lomitapide must be suspended during the course of treatment.
Our copy of this section ends here. The full text is in the official label at the FDA. Open Drugs@FDA
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 administration of single doses of clarithromycin and carbamazepine has been shown to result in increased plasma concentrations of carbamazepine. Blood level monitoring of carbamazepine may be considered.
Increased serum concentrations of carbamazepine were observed in clinical trials with clarithromycin. There have been spontaneous or published reports of CYP3A based interactions of clarithromycin with carbamazepine. Antifungals: Itraconazole Use With Caution Itraconazole: Both clarithromycin and itraconazole are substrates and inhibitors of CYP3A, potentially leading to a bi-directional drug interaction when administered concomitantly (see also Itraconazole under “Drugs That Affect Clarithromycin Tablets” in the table below).
Clarithromycin may increase the plasma concentrations of itraconazole. Patients taking itraconazole and clarithromycin concomitantly should be monitored closely for signs or symptoms of increased or prolonged adverse reactions. Fluconazole No Dose Adjustment Fluconazole: [see Pharmacokinetics ( 12.3 )] Anti-Gout Agents: Colchicine (in patients with renal or hepatic impairment) Contraindicated Colchicine: Colchicine is a substrate for both CYP3A and the efflux transporter, P-glycoprotein (Pgp).
Clarithromycin and other macrolides are known to inhibit CYP3A and Pgp. The dose of colchicine should be reduced when co-administered with clarithromycin in patients with normal renal and hepatic function [see Contraindications ( 4.4 ) and Warnings and Precautions ( 5.4 )] . Colchicine (in patients with normal renal and hepatic function) Use With Caution Antipsychotics: Pimozide Contraindicated Pimozide: [See Contraindications ( 4.2 )] Quetiapine Quetiapine: Quetiapine is a substrate for CYP3A4, which is inhibited by clarithromycin.
Co‑administration with clarithromycin could result in increased quetiapine exposure and possible quetiapine related toxicities. There have been postmarketing reports of somnolence, orthostatic hypotension, altered state of consciousness, neuroleptic malignant syndrome, and QT prolongation during concomitant administration. Refer to quetiapine prescribing information for recommendations on dose reduction if co‑administered with CYP3A4 inhibitors such as clarithromycin.
Antispasmodics: Tolterodine (patients deficient in CYP2D6 activity) Use With Caution Tolterodine: The primary route of metabolism for tolterodine is via CYP2D6. However, in a subset of the population devoid of CYP2D6, the identified pathway of metabolism is via CYP3A. In this population subset, inhibition of CYP3A results in significantly higher serum concentrations of tolterodine. Tolterodine 1 mg twice daily is recommended in patients deficient in CYP2D6 activity (poor metabolizers) when co-administered with clarithromycin.
Antivirals: Atazanavir Use With Caution Atazanavir: Both clarithromycin and atazanavir are substrates and inhibitors of CYP3A, and there is evidence of a bi-directional drug interaction (see Atazanavir under “Drugs That Affect Clarithromycin Tablets” in the table below) [see Pharmacokinetics ( 12.3 )] . Saquinavir (in patients with decreased renal function) Saquinavir: Both clarithromycin and saquinavir are substrates and inhibitors of CYP3A and there is evidence of a bi-directional drug interaction (see Saquinavir under “Drugs That Affect Clarithromycin Tablets” in the table below) [see Pharmacokinetics ( 12.3 )] .
Ritonavir Etravirine Ritonavir, Etravirine: (see Ritonavir and Etravirine under “Drugs That Affect Clarithromycin Tablets” in the table below) [see Pharmacokinetics ( 12.3 )] . Maraviroc Maraviroc: Clarithromycin may result in increases in maraviroc exposures by inhibition of CYP3A metabolism. See maraviroc prescribing information for dose recommendation when given with strong CYP3A inhibitors such as clarithromycin.
Boceprevir (in patients with normal renal function) Didanosine No Dose Adjustment Boceprevir: Both clarithromycin and boceprevir are substrates and inhibitors of CYP3A, potentially leading to a bi-directional drug interaction when co‑administered. No dose adjustments are necessary for patients with normal renal function (see boceprevir prescribing information). Zidovudine Zidovudine: Simultaneous oral administration of clarithromycin immediate-release tablets and zidovudine to HIV-infected adult patients may result in decreased steady-state zidovudine concentrations.
Administration of clarithromycin and zidovudine should be separated by at least two hours [see Pharmacokinetics ( 12.3 )] . The impact of co-administration of clarithromycin extended-release tablets or granules and zidovudine has not been evaluated. Calcium Channel Blockers: Verapamil Use With Caution Verapamil: Hypotension, bradyarrhythmias, and lactic acidosis have been observed in patients receiving concurrent verapamil, [see Warnings and Precautions ( 5.4 )] .
Amlodipine Diltiazem Amlodipine, Diltiazem: [See Warnings and Precautions ( 5.4 )] Nifedipine Nifedipine: Nifedipine is a substrate for CYP3A. Cl
Our copy of this section ends here. The full text is in the official label at the FDA. Open Drugs@FDA
Pregnancy and breastfeeding
8.1Pregnancy 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 of the fetuses. At ≥ 500 mg/kg/day, increases in the incidence of post-implantation loss and cleft palate in the fetuses were observed.
No adverse developmental effects were observed in mice at ≤ 250 mg/kg/day (≤ 1 times MRHD based on body surface area comparison). In pregnant Sprague Dawley rats, clarithromycin was administered during organogenesis (GD 6 to 15) at oral doses of 15, 50, or 150 mg/kg/day. Reductions in body weight and food consumption was observed in dams at 150 mg/kg/day. Increased resorptions and reduced body weight of the fetuses at this dose were considered secondary to maternal toxicity.
Additionally, at 150 mg/kg/day (1 times MRHD based on body surface area comparison), a low incidence of cardiovascular anomalies (complete situs inversus, undivided truncus, IV septal defect) was observed in the fetuses. Clarithromycin did not cause adverse developmental effects in rats at 50 mg/kg/day (0.3 times MRHD based on body surface area comparison). Intravenous dosing of clarithromycin during organogenesis in rats (GD 6 to 15) at 15, 50, or 160 mg/kg/day was associated with maternal toxicity (reduced body weight, body-weight gain, and food consumption) at 160 mg/kg/day but no evidence of adverse developmental effects at any dose (≤ 1 times MRHD based on body surface area comparison).
In pregnant Wistar rat, clarithromycin was administered during organogenesis (GD 7 to 17) at oral doses of 10, 40, or 160 mg/kg/day. Reduced body weight and food consumption were observed in dams at 160 mg/kg/day but there was no evidence of adverse developmental effects at any dose (≤ 1 times MRHD based on body surface area comparison). In pregnant rabbits, clarithromycin administered during organogenesis (GD 6 to 18) at oral doses of 10, 35, or 125 mg/kg/day resulted in reduced maternal food consumption and decreased body weight at the highest dose, with no evidence of any adverse developmental effects at any dose (≤ 2 times MRHD based on body surface area comparison).
Intravenously administered clarithromycin to pregnant rabbits during organogenesis (GD 6 to 18) in rabbits at 20, 40, 80, or 160 mg/kg/day (≥ 0.3 times MRHD based on body surface area comparison) resulted in maternal toxicity and implantation losses at all doses. In pregnant monkeys, clarithromycin was administered (GD 20 to 50) at oral doses of 35 or 70 mg/kg/day. Dose-dependent emesis, poor appetite, fecal changes, and reduced body weight were observed in dams at all doses (≥ 0.5 times MRHD based on body surface area comparison).
Growth retardation in 1 fetus at 70 mg/kg/day was considered secondary to maternal toxicity. There was no evidence of primary drug related adverse developmental effects at any dose tested. In a reproductive toxicology study in rats administered oral clarithromycin late in gestation through lactation (GD 17 to post-natal day 21) at doses of 10, 40, or 160 mg/kg/day (≤ 1 times MRHD based on body surface area comparison), reductions in maternal body weight and food consumption were observed at 160 mg/kg/day.
Reduced body-weight gain observed in offspring at 160 mg/kg/day was considered secondary to maternal toxicity. No adverse developmental effects were observed with clarithromycin at any dose tested.
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.
6.1Clinical 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 (4%) 0/95 SGOT >5 x ULN ULN=Upper Limit of Normal 7/196 (4%) 5/208 (2%) SGPT >5 x ULN 6/217 (3%) 4/232 (2%) Treatment of Mycobacterial Infections The adverse reaction profiles for both the 500 mg and 1000 mg twice a day dose regimens were similar.
In AIDS patients and other immunocompromised patients treated with the higher doses of clarithromycin tablets over long periods of time for mycobacterial infections, it was often difficult to distinguish adverse reactions possibly associated with clarithromycin tablets administration from underlying signs of HIV disease or intercurrent illness. The following analysis summarizes experience during the first 12 weeks of therapy with clarithromycin tablets.
Data are reported separately for trial 1 (randomized, double-blind) and trial 2 (open‑labeled, compassionate use) and also combined. Adverse reactions were reported less frequently in trial 2, which may be due in part to differences in monitoring between the two studies. In adult patients receiving clarithromycin tablets 500 mg twice a day, the most frequently reported adverse reactions, considered possibly or possibly related to study drug, with an incidence of 5% or greater, are listed below ( Table 6 ).
Approximately 8% of the patients who received 500 mg twice a day and 12% of the patients who received 1000 mg twice a day discontinued therapy due to drug related adverse reactions during the first 12 weeks of therapy; adverse reactions leading to discontinuation in at least 2 patients included nausea, vomiting, abdominal pain, diarrhea, rash, and asthenia. Table 6. Selected Treatment-Related Includes those events possibly or probably related to study drug and excludes concurrent conditions Adverse Reaction Incidence Rates (%) in Immunocompromised Adult Patients During the First 12 Weeks of Therapy with 500 mg Twice a Day Clarithromycin Tablets Dose Adverse Reaction Trial 1 (n=53) Trial 2 (n=255) Combined (n=308) Abdominal Pain 8 2 3 Diarrhea 9 2 3 Flatulence 8 0 1 Headache 8 0 2 Nausea 28 9 12 Rash 9 2 3 Taste Perversion 19 0 4 Vomiting 25 4 8 A limited number of pediatric AIDS patients have been treated with clarithromycin suspension for mycobacterial infections.
The most frequently reported adverse reactions excluding those due to the patient’s concurrent conditions were consistent with those observed in adult patients. Changes in Laboratory Values In the first 12 weeks of starting on clarithromycin tablets 500 mg twice a day, 3% of patients has SGOT increases and 2% of patients has SGPT increases > 5 times the upper limit of normal in trial 2 (469 enrolled adult patients) while trial 1 (154 enrolled patients) had no elevation of transaminases.
This includes only patients with baseline values within the normal range or borderline low. Duodenal ulcer associated with H. pylori Infection In clinical trials using combination therapy with clarithromycin plus omeprazole and amoxicillin, no adverse reactions specific to the combination of these drugs have been observed. Adverse reactions that have occurred have been limited to those that have been previously reported with clarithromycin, omeprazole or amoxicillin.
The adverse reaction profiles are shown below ( Table 7 ) for four randomized double-blind clinical trials in which patients received the combination of clarithromycin tablets 500 mg three times a day, and omeprazole 40 mg daily for 14 days, followed by omeprazole 20 mg once a day, (three studies) or 40 mg once a day (one study) for an additional 14 days. Of the 346 patients who received the combination, 3.5% of patients discontinued drug due to adverse reactions.
Table 7. Adverse Reactions with an Incidence of 3% or Greater Adverse Reaction Clarithromycin + Omeprazole (n=346) % of Patients Omeprazole (n=355) % of Patients Clarithromycin (n=166) % of Patients Only two of four studies Taste Perversion 15 1 16 Nausea 5 1 3 Headache 5 6 9 Diarrhea 4 3 7 Vomiting 4 <1 1 Abdominal Pain 3 2 1 Infection 3 4 2 Changes in Laboratory Va
Our copy of this section ends here. The full text is in the official label at the FDA. Open Drugs@FDA
Composition
Active ingredients
CLARITHROMYCIN 500MG
Strengths and forms
The FDA lists each strength of a product separately; these pages share one label.
Prognia shows this product information for reference and learning. It is not treatment advice and can lag behind the official text. Always check the current product information and local protocols before prescribing.
Concomitant use of clarithromycin tablets with lovastatin or simvastatin is contraindicated as these statins are extensively metabolized by CYP3A4, and concomitant treatment with clarithromycin increases their plasma concentration, which increases the risk of myopathy, including rhabdomyolysis. Cases of rhabdomyolysis have been reported in patients taking clarithromycin concomitantly with these statins. If treatment with clarithromycin tablets cannot be avoided, therapy with lovastatin or simvastatin must be suspended during the course of treatment.
HMG-CoA Reductase Inhibitors (statins): Concomitant use of clarithromycin tablets with lovastatin or simvastatin is contraindicated [see Contraindications ( 4.5 )] as these statins are extensively metabolized by CYP3A4, and concomitant treatment with clarithromycin increases their plasma concentration, which increases the risk of myopathy, including rhabdomyolysis. Cases of rhabdomyolysis have been reported in patients taking clarithromycin concomitantly with these statins.
If treatment with clarithromycin tablets cannot be avoided, therapy with lovastatin or simvastatin must be suspended during the course of treatment. Exercise caution when prescribing clarithromycin tablets with atorvastatin or pravastatin. In situations where the concomitant use of clarithromycin tablets wi
