Interactions between rifampin and Sirolimus (sirolimus)
rifampin and sirolimus (Major Drug-Drug)
GENERALLY AVOID: Coadministration with rifamycins, particularly rifampin, may significantly decrease the plasma concentrations and pharmacologic effects of sirolimus. The mechanism probably involves reduced absorption as well as accelerated clearance of sirolimus due to induction of both intestinal P-glycoprotein drug efflux pumps and hepatic/intestinal CYP450 3A4 isoenzymes by rifamycins. In a study of 14 healthy volunteers, rifampin (600 mg daily for 14 days) increased the oral clearance of sirolimus (20 mg single dose) by 5.5-fold, representing mean decreases in peak blood concentration (Cmax) and area under the concentration-time curve (AUC) of 71% and 82%, respectively. This interaction is likely to occur with other rifamycins but to a lesser extent. In vitro and in vivo enzyme studies have suggested rifapentine induction potential to be less than that of rifampin but greater than that of rifabutin.
MANAGEMENT: Given the risk of organ rejection associated with inadequate immunosuppressant levels, the use of sirolimus with rifampin or other rifamycins is not recommended. Alternative therapeutic agents with less enzyme induction potential should be considered.
