Cimetidine Azithromycin

Macrolides, particularly erythromycin and clarithromycin, inhibit CYP3A4. With erythromycin, the inhibition of CYP3A4 is non-competitive due to irreversible binding with the isoenzyme to form an inactive complex. Thus, unlike the case with inhibitors with a short half-life (e.g. cimetidine), the offset of inhibition is slow since new enzyme must be synthesized to replace the inactive complexes. Azithromycin, clarithromycin and erythromycin can prolong the Q-T interval and must not be co-administered with other Q-T-prolonging drugs. 

A retrospective analysis of 3995 patients treated with azithromycin did not show any pharmacokinetic interactions in patients who were also taking various other drugs, including cimetidine (1,45). 

Foulds G, Hilligoss DM, Henry EB, Gerber N The effects of an antacid or cimetidine on the serum concentrations of azithromycin. /CfiwP armaco/(1991)31,164-7. 

Cimetidine doubled the serum levels of erythromycin in one single-dose study, and a single case report describes reversible deafness, which was attributed to this interaction. No clinically significant interaction appears to occur when cimetidine is given with azithromycin or clarithromycin, or when ranitidine is given with clarithromycin, roxithromycin, or telithromycin. 

The pharmacokinetics of azithromycin were not affected by a single 800-mg dose of cimetidine in one study, and although cimetidine prolongs the absorption of clarithromycin, this is unlikely to be of clinical significance. ... 

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