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Antacids: 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 20mg at steady-state resulted in no pharmacokinetic interaction and no significant changes in the QT interval.
Didanosine (Dideoxyinosine): Coadministration of 1200mg/day azithromycin with 400mg/day didanosine in 6 HIV-positive subjects did not appear to affect the steady-state pharmacokinetics of didanosine as compared with placebo.
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 1000mg doses and multiple 1200mg or 600mg 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. The clinical significance of this finding is unclear, but it may be of benefit to patients. 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 (10mg daily) and azithromycin (500mg 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: In a pharmacokinetic study investigating the effects of a single dose of cimetidine, given 2 hours before azithromycin, on the pharmacokinetics of azithromycin, no alteration of azithromycin pharmacokinetics was seen.
Coumarin-Type Oral Anticoagulants: There have been reports of potentiated anticoagulation subsequent to coadministration of azithromycin and coumarin-type oral anticoagulants. Although a causal relationship has not been established, consideration should be given to the frequency of monitoring prothrombin time when azithromycin is used in patients receiving coumarin-type oral anticoagulants.
Cyclosporin: Caution should be exercised before considering concurrent administration of cyclosporin and azithromycin. If coadminstration of these drugs is necessary, cyclosporin levels should be monitored and the dose adjusted accordingly.
Efavirenz: Coadministration of a 600mg single dose of azithromycin and 400mg efavirenz daily for 7 days did not result in any clinically significant pharmacokinetic interactions.
Fluconazole: Coadministration of a single dose of 1200mg azithromycin did not alter the pharmacokinetics of a single dose of 800mg fluconazole. Total exposure and half-life of azithromycin were unchanged by the coadministration of fluconazole, however a clinically insignificant decrease in Cmax (18%) of azithromycin was observed.
Indinavir: Coadministration of a single dose of 1200mg 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 500mg/day for 3 days did not cause clinically significant changes in the pharmacokinetics and pharmacodynamics of a single 15mg dose of midazolam.
Nelfinavir: Coadministration of azithromycin (1200mg) and nelfinavir at steady state (750mg three times daily) resulted in increased azithromycin concentrations. No clinically significant adverse effects were observed and no dose adjustment is required.
Rifabutin: Coadministration of azithromycin and rifabutin did not affect the serum concentrations of either drug. Neutropenia was observed in subjects receiving concomitant treatment of azithromycin and rifabutin. Although neutropenia has been associated with the use of rifabutin, a causal relationship to combination with azithromycin has not been established.
Sildenafil: There was 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: Pharmacokinetic studies have reported no evidence of an interaction between azithromycin and 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 a clinically significant pharmacokinetic interaction when azithromycin and theophylline are co-administered to healthy volunteers.
Triazolam: Coadministration of azithromycin with 0.125mg triazolam had no significant effect on any of the pharmacokinetic variables for triazolam compared to triazolam and placebo.
Trimethoprim/sulfamethoxazole: Coadministration of trimethoprim / sulfamethoxazole DS (160mg/800mg) for 7 days with azithromycin 1200mg on Day 7 had no significant effect on peak concentrations, total exposure or urinary excretion of either trimethoprim or sulfamethoxazole. Azithromycin serum concentrations were similar to those seen in other studies.
