InteractionsFor a discussion of drug interactions of macrolide anti-bacterials, see Erythromycin, p.271.Antidiabetics. For reference to hypoglycaemia resulting fromthe addition of clarithromycin to glibenclamide or glipizide, seeAntibacterials, p.462.Antiretroviral drugs. In studies in healthy subjects,1,2 theHIV-protease inhibitor ritonavir inhibited the metabolism ofclarithromycin, increasing plasma concentrations and prolong-ing half-life. The metabolism of ritonavir was not affected signif-icantly. The two drugs may be given together in usual doses tothose with normal renal function but licensed product informa-tion for clarithromycin recommends that its dose should be re-duced in patients with renal impairment receiving ritonavir andit should be noted that this is an extra reduction over and abovethat which may be needed for the renal impairment alone. Dosesof clarithromycin should be reduced by 50% in patients with acreatinine clearance (CC) of 30 to 60 mL/minute and reduced by75% in those with a CC below 30 mL/minute; the daily doseshould not exceed 1 g. It has been suggested that other HIV-pro-tease inhibitors (see also Table of Interactions of Drugs Used inthe Treatment of HIV, p.917) and the NNRTI delavirdine mayhave a similar effect on clarithromycin. Use of efavirenz withclarithromycin has decreased plasma concentration of clarithro-mycin and increased its hydroxy metabolite. The combinationhas been associated with a high incidence of skin rashes. De-creases in the plasma concentration of clarithromycin have alsobeen noted with nevirapine. Decreased concentrations of zidovudine (p.915) have been re-ported in patients also taking clarithromycin and clarithromycinproduct information recommends that doses of the two drugsshould be separated by 1 to 2 hours.1. Ouellet D, et al. Assessment of the pharmacokinetic interactionbetween ritonavir and clarithromycin. Clin Pharmacol Ther1996; 59: 143. 2. Ouellet D, et al. Pharmacokinetic interaction between ritonavirand clarithromycin. Clin Pharmacol Ther 1998; 64: 355–62.Colchicine. For mention of fatal colchicine toxicity associatedwith concomitant use of clarithromycin, see Macrolides, p.557.Disulfiram. For a report of an interaction between clarithromy-cin and disulfiram, see Macrolides, p.2297.Fluoxetine. For a report of delirium following use of clarithro-mycin with fluoxetine, see Antibacterials, p.396.Gastrointestinal drugs. In a study1 in healthy subjects, con-centrations of clarithromycin and its active metabolite were in-creased in gastric tissue and mucus and, to a lesser extent, in plas-ma during use of omeprazole. In addition, use of clarithromycinwith omeprazole resulted in higher and more prolonged plasmaconcentrations of omeprazole. The investigators suggest that thisinteraction could account for the synergistic action observed withthis combination when used for eradication of Helicobacter py-lori. However, licensed product information for clarithromycinstates that no dosage adjustment to either drug is necessary.
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