Antacids: In a pharmacokinetic study investigating the effects of simultaneous administration of antacid with azithromycin, no effect on overall bioavailability was seen although peak serum concentrations were reduced by approximately 25%. In patients receiving both oral azithromycin and antacids, the drugs should not be taken simultaneously.
Cetirizine: Coadministration of a 5-day regimen of azithromycin with cetirizine 20 mg at steady-state resulted in no pharmacokinetic interaction and no significant charges in the QT interval.
Digoxin: Some of the macrolide antibiotics have been reported to impair the microbial metabolism of digoxin in the gut in some patients. In patients receiving concomitant azithromycin, a related azalide antibiotic, and digoxin the possibility of raised digoxin levels should be borne in mind.
Zidovudine: Single 1000 mg doses and multiple 1200 mg or 600 mg doses of azithromycin had little effect on the plasma pharmacokinetics or urinary excretion of zidovudine or its glucuronide metabolite. However, administration of azithromycin increased the concentrations of phosphorylated zidovudine, the clinically active metabolite, in peripheral blood mononuclear cells.
Azithromycin does not interact significantly with the hepatic cytochrome P450 system. It is not believed to undergo the pharmacokinetic drug interactions as seen with erythromycin and other macrolides. Hepatic cytochrome P450 induction or inactivation via cytochrome-metabolite complex does not occur with azithromycin.
Ergot: Due to the theoretical possibility of ergotism, the concurrent use of azithromycin with ergot derivatives is not recommended.
Pharmacokinetic studies have been conducted between azithromycin and the following drugs known to undergo significant cytochrome P450 mediated metabolism.
Atorvastatin: Coadministration of atorvastatin (10 mg daily) and azithromycin (500 mg daily) did not alter the plasma concentrations of atorvastatin.
Carbamazepine: No significant effect was observed on the plasma levels of carbamazepine or its active metabolite in patients receiving concomitant azithromycin.
Cimetidine: Single dose of cimetidine, given 2 hours before azithromycin, on the pharmacokinetic of azithromycin, no alteration of azithromycin pharmacokinetics was seen.
Coumarin-Type Oral Anticoagulants: Azithromycin did not alter the anticoagulant effect of a single 15 mg dose of warfarin. Although a causal relationship has not been established, consideration should be given to the monitoring prothrombin time when azithromycin is used in patients receiving coumarin-type oral anticoagulants.
Cyclosporin: A 500 mg/day oral dose of azithromycin for 3 days and were then administered a single 10 mg/kg oral dose of cyclosporin, the resulting cyclosporin Cmax and AUC0-5 were found to be significantly elevated. Consequently, caution should be exercised before considering concurrent administration of these drugs. If coadministration of these drugs is necessary, cyclosporin levels should be monitored and the dose adjusted accordingly.
Fluconazole: Coadministration of a single dose of 1200 mg azithromycin did not alter the pharmacokinetics of a single dose of 800 mg fluconazole. Total exposure and half-life of azithromycin were unchanged by the coadministration of fluconazole.
Indinavir: Coadministration of a single dose of 1200 mg azithromycin had no statistically significant effect on the pharmacokinetics of indinavir administered as 800 mg three times daily for 5 days.
Methylprednisolone: Azithromycin had no significant effect on the pharmacokinetics of methylprednisolone.
Midazolam: Coadministration of azithromycin 500 mg/day for 3 days did not cause clinically significant changes in the pharmacokinetics and pharmacodynamics of a single 15 mg dose of midazolam.
Nelfinavir: Coadministration of azithromycin (1200 mg) and nelfinavir at steady state (750 mg three times daily) resulted in increased azithromycin concentrations.
Rifabutin: Coadministration of azithromycin and rifabutin did not affect the serum concentrations of either drug. Neutropenia is seen when taken with rifabutin. Although neutropenia has been associated with the use of rifabutin, a causal relationship to combination with azithromycin has not been established.
Sildenafil: No evidence of an effect of azithromycin (500mg daily for 3 days) on the AUC and Cmax, of sildenafil or its major circulating metabolite.
Terfenadine: There have been rare cases reported where the possibility of such an interaction could not be entirely excluded; however, there was no specific evidence that such an interaction had occurred.
Theophylline: There is no evidence of an interaction when azithromycin and theophylline are co-administered.
Trimethoprim/ Sulfamethoxazole: Coadministration of trimethoprim/sulfamethoxazole had no significant effect on peak concentrations, total exposure or urinary excretion of either trimethoprim or sulfamethoxazole.