Clarithromycin drug interactions

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]


List of drug interactions


Theophylline

Carbamazepine

Terfenadine

Omeprazole

Ranitidine bismuth citrate

Zidovudine

Didanosine

Fluconazole

Ritonavir

Oral anticoagulants

Digoxin

Colchicine

Erythromycin

CYP3A based drug interactions


Complete List of Drug Interactions









Theophylline

Clarithromycin use in patients who are receiving theophylline may be associated with an increase of serum theophylline concentrations. Monitoring of serum theophylline concentrations should be considered for patients receiving high doses of theophylline or with baseline concentrations in the upper therapeutic range. In two studies in which theophylline was administered with Clarithromycin (a theophylline sustained-release formulation was dosed at either 6.5 mg/kg or 12 mg/kg together with 250 or 500 mg q12h Clarithromycin), the steady-state levels of Cmax, Cmin, and the area under the serum concentration time curve (AUC) of theophylline increased about 20%. Return to top

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. Return to top

Terfenadine

When Clarithromycin and terfenadine were coadministered, plasma concentrations of the active acid metabolite of terfenadine were threefold higher, on average, than the values observed when terfenadine was administered alone.

The pharmacokinetics of Clarithromycin and the 14-hydroxy-Clarithromycin were not significantly affected by coadministration of terfenadine once Clarithromycin reached steady-state conditions. Concomitant administration of Clarithromycin with terfenadine is contraindicated. Return to top

Omeprazole

Clarithromycin 500 mg every 8 hours was given in combination with omeprazole 40 mg daily to healthy adult subjects. The steady-state plasma concentrations of omeprazole were increased (Cmax, AUC0-24, and T1/2 increases of 30%, 89%, and 34%, respectively), by the concomitant administration of Clarithromycin. The mean 24-hour gastric pH value was 5.2 when omeprazole was administered alone and 5.7 when co-administered with Clarithromycin. Return to top

Ranitidine bismuth citrate

Co-administration of Clarithromycin with ranitidine bismuth citrate resulted in increased plasma ranitidine concentrations (57%), increased plasma bismuth trough concentrations (48%), and increased 14-hydroxy-Clarithromycin plasma concentrations (31%). These effects are clinically insignificant. Return to top

Zidovudine

Simultaneous oral administration of Clarithromycin tablets and zidovudine to HIV-infected adult patients resulted in decreased steady-state zidovudine concentrations. When 500 mg of Clarithromycin were administered twice daily, steady-state zidovudine AUC was reduced by a mean of 12% (n=4). Individual values ranged from a decrease of 34% to an increase of 14%. Based on limited data in 24 patients, when Clarithromycin tablets were administered two to four hours prior to oral zidovudine, the steady-state zidovudine Cmax was increased by approximately 2-fold, whereas the AUC was unaffected. Return to top

Didanosine

Simultaneous administration of Clarithromycin tablets and didanosine to 12 HIV-infected adult patients resulted in no statistically significant change in didanosine pharmacokinetics. Return to top

Fluconazole

Concomitant administration of fluconazole 200 mg daily and Clarithromycin 500 mg twice daily to 21 healthy volunteers led to increases in the mean steady-state Clarithromycin Cmin and AUC of 33% and 18%, respectively. Steady-state concentrations of 14-OH Clarithromycin were not significantly affected by concomitant administration of fluconazole. Return to top

Ritonavir

Concomitant administration of Clarithromycin and ritonavir (n=22) resulted in a 77% increase in Clarithromycin AUC and a 100% decrease in the AUC of 14-OH Clarithromycin. Clarithromycin[ may be administered without dosage adjustment to patients with normal renal function taking ritonavir. However, for patients with renal impairment, the following dosage adjustments should be considered. For patients with CLCR30 to 60 mL/min, the dose of Clarithromycin should be reduced by 50%. For patients with CLCR <30 mL/min, the dose of Clarithromycin should be decreased by 75%. Return to top

Oral anticoagulants

Spontaneous reports in the post-marketing 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. Return to top

Digoxin

Elevated digoxin serum concentrations in patients receiving Clarithromycin and digoxin concomitantly have also been reported in post-marketing surveillance. Some patients have shown clinical signs consistent with digoxin toxicity, including potentially fatal arrhythmias. Serum digoxin concentrations should be carefully monitored while patients are receiving digoxin and Clarithromycin simultaneously. Return to top

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. When Clarithromycin and colchicine are administered together, inhibition of Pgp and/or CYP3A by Clarithromycin may lead to increased exposure to colchicine. Patients should be monitored for clinical symptoms of colchicine toxicity. Return to top

Erythromycin

Erythromycin and Clarithromycin are substrates and inhibitors of the 3A isoform subfamily of the cytochrome P450 enzyme system (CYP3A). Coadministration of erythromycin or Clarithromycin and a drug primarily metabolized by CYP3A may be associated with elevations in drug concentrations that could increase or prolong both the therapeutic and adverse effects of the concomitant drug. Dosage adjustments may be considered, and when possible, serum concentrations of drugs primarily metabolized by CYP3A should be monitored closely in patients concurrently receiving Clarithromycin or erythromycin. Return to top

CYP3A based drug interactions

The following are examples of some clinically significant CYP3A based drug interactions. Interactions with other drugs metabolized by the CYP3A isoform are also possible. Increased serum concentrations of carbamazepine and the active acid metabolite of terfenadine were observed in clinical trials with Clarithromycin.
There have been spontaneous or published reports of CYP3A based interactions of erythromycin and/or Clarithromycin with cyclosporine, carbamazepine, tacrolimus, alfentanil, disopyramide, rifabutin, quinidine, methylprednisolone, cilostazol, and bromocriptine.
Concomitant administration of Clarithromycin with cisapride, pimozide, astemizole, or terfenadine is contraindicated.
In addition, there have been reports of interactions of erythromycin or Clarithromycin with drugs not thought to be metabolized by CYP3A including hexobarbital, phenytoin, and valproate. Return to top

Antiarrhythmics

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. Serum concentrations of these medications should also be monitored. Return to top

Ergotamine/dihydroergotamine

Post-marketing reports indicate that coadministration of Clarithromycin with ergotamine or dihydroergotamine has been associated with acute ergot toxicity characterized by vasospasm and ischemia of the extremities and other tissues including the central nervous system. Concomitant administration of Clarithromycin with ergotamine or dihydroergotamine is contraindicated. Return to top

Triazolobenziodidiazepines/related benzodiazepines

Erythromycin has been reported to decrease the clearance of triazolam and midazolam, and thus, may increase the pharmacologic effect of these benzodiazepines. There have been post-marketing reports of drug interactions and CNS effects (e.g., somnolence and confusion) with the concomitant use of Clarithromycin and triazolam. Return to top

HMG-CoA reductase inhibitors

As with other macrolides, Clarithromycin has been reported to increase concentrations of HMG-CoA reductase inhibitors (e.g., lovastatin and simvastatin). Rare reports of rhabdomyolysis have been reported in patients taking these drugs concomitantly. Return to top

Sildenafil

Erythromycin has been reported to increase the systemic exposure (AUC) of sildenafil. A similar interaction may occur with Clarithromycin; reduction of sildenafil dosage should be considered. (See Viagra package insert.) Return to top

Complete List of Drug Interactions

Major Interactions

Moderate Interactions

Minor Interactions




Adapted from the FDA Package Insert.


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