The concomitant use of vaginally administered clotrimazole and orally administered tacrolimus (FK-506, immunosuppressive drug) may lead to increased plasma concentrations of tacrolimus. The same happens with the immunosuppressive drug sirolimus. Therefore, patients taking tacrolimus or sirolimus should be closely monitored for overdose symptoms if necessary by determining their plasma concentrations.
Clotrimazole is a moderate inhibitor of the hepatic microsomal isoenzyme CYP3A4, and a weak inhibitor of the CYP2C9 isoenzyme. The 3-10% of the local vaginal dose of clotrimazole is absorbed into the systemic circulation, which may have an effect on the concentrations of drugs metabolised via the CYP3A4 isoenzyme in particular, potentially increasing the plasma concentrations of these drugs when used concomitantly. Since the effect on the CYP2C9 isoenzyme is small, and only a small part of the locally administered clotrimazole is absorbed into the systemic circulation, the effect of clotrimazole on the concentrations of drugs metabolised via the CYP2C9 isoenzyme is modest. Therefore, due to the very low absorption of clotrimazole after vaginal application especially a 500 mg dose, intravaginally applied clotrimazole is unlikely to result in clinically significant drug interactions.