Sibutramine Ketoconazole

Ketoconazole modestly increases steady-state levels of sibutramine and its active metabolites. The UK manufacturers recommend caution when sibutramine is used with itraconazole or ketoconazole. 

Twelve obese patients were given sibutramine hydrochloride monohydrate 20 mg daily for 14 days, with ketoconazole 200 mg twice daily for the last 7 days. Ketoconazole caused moderate increases in the serum levels of sibutramine and its two metabolites (AUC and maximum serum level increases of 58% and 36%, respectively, for metabolites Ml, and 20% and 19%, respectively, for M2, probably through inhibition of the cytochrome P450 isoenzyme CYP3A4). Small increases in heart rates were seen (2.5 bpm at 4 hours and 1.4 bpm at 8 hours), while ECO parameters were unchanged. Sibutramine alone can cause an increase in heart rate, and a rate increase of 10 bpm is an indication to withdraw the drug. There-... 

Hinson JL, Leone MB, Kisiki MJ, Moult JT, Trammel A and Faulkner RD. Steady-state interaction study of sibutramine (Meridia) and ketoconazole in uncomplicated obese subjects. PharmRes 996) 13 (9 Suppl), S116. 

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