Midazolam azithromycin/clarithromycin

Yeates RA, Laufen H, Zimmermann T. Interaction between midazolam and clarithromycin comparison with azithromycin. Int J Clin Pharmacol Ther 1996 34(9) 400-5. 

In an open, randomized, crossover, pharmacokinetic and pharmacodynamic study in 12 healthy volunteers who took clarithromycin 250 mg bd for 5 days, azithromycin 500 mg/day for 3 days, or no pretreatment, followed by a single dose of midazolam (15 mg), clarithromycin increased the AUC of midazolam by over 3.5 times and the mean duration of sleep from 135 to 281 minutes (69). In contrast, there was no change with azithromycin, suggesting that it is much safer for co-administration with midazolam. 

The serum levels and effects of midazolam, triazolam and zopi-clone are markedly increased and prolonged by erythromycin. The same interaction has been seen with clarithromycin, josamy-cin, or troleandomycin but not azithromycin. Alprazolam would be expected to be similarly affected. Other benzodiazepines, and the related hypnotic zaleplon, appear not to interact with the macrolides to a clinically significant extent... 

Azithromycin does not interact with midazolam or triazolam, and the effects of roxithromycin on midazolam and triazolam, and of erythromycin on diazepam, flunitrazepam, nitrazepam, temazepam and zopiclone or clarithromycin on zolpidem appear to be small and unimportant, or the effects negligible, so that no special precautions seem to be necessary. 

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