Antacid: Giving Azithromycin with antacid containing aluminum or magnesium salts can reduce the rate, but not the extent, of its absorption; Azithromycin should be given at least 1 hour before or 2 hours after the antacid.
Fluconazole: Co-administration of a single dose of 1.2 g Azithromycin did not alter the pharmacokinetics of a single dose of 800 mg fluconazole, however, a clinically insignificant decrease in Cmax (18%) of Azithromycin was observed.
Nelfinavir: Co-administration of Azithromycin (1.2 g) and nelfinavir at steady state (750 mg three times daily) resulted in increased Azithromycin concentrations. No clinically significant adverse effects were observed and no dose adjustment is required.
Rifabutin: Co-administration 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.
Terfenadine: Pharmacokinetics studies have reported no evidence of an interaction between Azithromycin and terfenadine. There have been rare cases reported where possibility of such an interaction could not be entirely excluded; however there was no specific evidence that such interaction had occurred.
Cimetidine: In a pharmacokinetics study investigating the effects of single dose of cimetidine, given 2 hours before Azithromycin, on the pharmacokinetics of Azithromycin, no alteration of Azithromycin pharmacokinetics was seen.
Ergotamine derivatives: Due to the theoretical possibility of ergotism, the concurrent use of Azithromycin with ergot derivatives is not recommended.
Digoxin: It is known that some macrolide antibiotics limit the metabolism of digoxin (in the gut). In patients treated concomitantly with Azithromycin and digoxin, the possibility of increased digoxin levels should be borne in mind, and digoxin levels monitored.
Coumarin-type Oral Anticoagulants: In a pharmacokinetics interaction study, Azithromycin did not alter the anticoagulant effect of a single 15 mg dose of warfarin administered to healthy volunteers. There have been reports receive in the post-marketing period of potentiated anticoagulation subsequent to co-administration of Azithromycin and coumarin-type oral anticoagulant.
Cyclosporine: In a pharmacokinetics study with healthy volunteers that were administered a 500 mg/day oral dose Azithromycin for 3 days and were then administered a single 10 mg/kg oral dose of cyclosporine, the resulting cyclosporine Cmax and AUC0-5 were found to be significant elevated. Consequently, caution should be exercised before considering concurrent administration of these drugs. Cyclosporine levels should be monitored and the dose adjusted accordingly.
Theophylline: There is no evidence of a clinically significant pharmacokinetics interaction when Azithromycin and theophylline are co-administered to healthy volunteers. As interactions of other macrolides with theophylline have been reported, alertness to signs that indicate a rise in theophylline levels is advised.
Trimethoprim/Sulfamethoxazole: Co-administration of trimethoprim/sulfamethoxazole (160 mg/800 mg) for 7 days with Azithromycin 1.2 g 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.
Zidovudine: Single 1 g dose and multiple 1.2 g or 600 mg dose of Azithromycin had little effect on the plasma pharmacokinetics or urinary excretion of zidovudine or its glucuronide metabolite. However, co-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 pharmacokinetics drug interactions as seen with erythromycin and other macrolides. Hepatic cytochrome P450 induction or inactivation via cytochrome-metabolite complex does not occur with Azithromycin.
Astemizole, Alfentanil: There are no known data on interactions with astemizole or alfentanil. Caution is advised in the co-administration of these macrolides with Azithromycin because the known enhancing effect of these medicines when used concurrently with the macrolide antibiotic erythromycin.
Atorvastatin: Co-administration of atorvastatin (10 mg daily) and Azithromycin (500 mg daily) did not alter the plasma concentrations of Atorvastatin (bases on a HMG CoA-reductase inhibition assay).
Carbamazepine: In a pharmacokinetic interaction study in healthy volunteers, no significant effect was observed on the plasma levels of carbamazepine or its active metabolite in patients receiving concomitant Azithromycin.
Cisapride: Cisapride is metabolized in the liver by the enzyme CYP 3A4. Because macrolides inhibit this enzyme, concomitant administration of cisapride may cause the increase of QT interval prolongation, ventricular arrhythmias and torsades de pointes.
Cetirizine: In healthy volunteers, co-administration of a 5-day regimen of Azithromycin with cetirizine 20 mg at steady-state resulted in no pharmacokinetic interaction and no significant changes in the QT interval.
Didanosine (Dideoxyinosine): Co-administration of 1.2 g/day Azithromycin with 400 mg/day didanosine in 6 HIV positive subject did not appear to affect the steady-state pharmacokinetics of didanosine as compared with placebo.
Efavirenz: Co-administration of a 600-mg single dose of Azithromycin and 400 mg efavirenz daily for 7 did not shown any clinically significant pharmacokinetic interactions.