Concomitant use of clarithromycin and drugs metabolized by the cytochrome P-450 (CYP) system may be associated with increased serum concentrations of the latter drugs, and serum concentrations of such concomitantly administered drugs should be monitored closely.
Concomitant use of clarithromycin with cisapride, pimozide, terfenadine, or astemizole, is contraindicated because of QT prolongation and serious cardiovascular effects.
Concurrent use of clarithromycin with ergot alkaloids (ergotamine, dihydroergotamine) is contraindicated due to acute ergot toxicity, vasospasm and ischemia of the extremities and other tissues, including the CNS.
Clarithromycin should be used with caution in patients receiving carbamazepine. A reduction in carbamazepine, dosage and/or monitoring plasma carbamazepine concentrations is advised.
Clarithromycin has been reported to increase serum concentrations of HMG-CoA reductase inhibitor (e.g., lovastatin, simvastatin) via inhibition of metabolism by cytochrome-P450 isoenzymes.
Concomitant use of clarithromycin and rifabutin or rifampicin increases the metabolism of clarithromycin. This leads to decrease serum clarithromycin concentrations >50%.
Concurrent use of clarithromycin with oral anticoagulants may potentiate the effects of the oral anticoagulant, so prothrombin time must be monitored carefully in patients receiving such concomitant therapy.
CNS effects (e.g., somnolence, confusion) have been reported when clarithromycin was used concomitantly with triazolam.
Elevated serum concentrations of digoxin have been reported in patients receiving digoxin and clarithromycin concomitantly, monitoring of digoxin serum concentrations is recommended in such patients.
Clarithromycin has been shown to increase serum theophylline concentrations. Therefore, patients receiving clarithromycin concomitantly with high doses of theophylline or in those with theophylline serum concentrations in the upper therapeutic range should be monitored serum theophylline concentrations. Theophylline dosage should be adjusted if necessary when clarithromycin is added or withdrawn in a patient receiving theophylline.
Concurrent administration with antiretroviral agents: Concomitant use of clarithromycin and atazanavir results in an increased peak plasma concentrations and AUC of both drugs. Clarithromycin dosage should be reduced by 50% in patients receiving atazanavir.
Concomitant use of clarithromycin with delavirdine causes a 100% increase in the AUC of clarithromycin. Concurrent administration with the fixed combination of lopinavir and ritonavir may result in an increased clarithromycin concentrations. In addition, ritonavir has been found to increase peak plasma concentrations and AUC of clarithromycin but decrease those of clarithromycin active metabolite. Modification of the usual dosage of clarithromycin is not necessary in patients with normal renal function. However, the dose should be reduced by 50% in patients with creatinine clearances of 30-60 mL/minute and reduced by 75% in individuals with creatinine clearances less than 30 mL/minute.
Administration of clarithromycin and efavirenz decreases peak plasma concentration and AUC of clarithromycin but increases those of clarithromycin active metabolite. Because rash develops in 46% of individual receiving such concomitant therapy, alternatives to clarithromycin (e.g., azithromycin) and monitoring for macrolide efficacy should be considered.
Concurrent use of clarithromycin with saquinavir may result in increased plasma concentrations of both drugs. Dosage adjustments may not be needed if clarithromycin and saquinavir are used concomitantly for a limited time at the dosage studies (clarithromycin 600 mg twice daily and saquinavir 1.2 g 3 times daily).