Interaksi Flukonazol dan Sirolimus

Interaction with Strong Inhibitors and Inducers of CYP3A4 and/or P-gp Avoid concomitant use of sirolimus with strong inhibitors of CYP3A4 and/or P-gp (such as ketoconazole, voriconazole, itraconazole, erythromycin, telithromycin, or clarithromycin) or strong inducers of CYP3A4 and/or P-gp (such as rifampin or rifabutin) [ see Drug Interactions (7.2) ].

Strong Inducers and Strong Inhibitors of CYP3A4 and P-gp Avoid concomitant use of sirolimus with strong inducers (e.g., rifampin, rifabutin) and strong inhibitors (e.g., ketoconazole, voriconazole, itraconazole, erythromycin, telithromycin, clarithromycin) of CYP3A4 and P-gp.

• Drugs that could increase sirolimus blood concentrations: Bromocriptine, cimetidine, cisapride, clotrimazole, danazol, diltiazem, fluconazole, letermovir, protease inhibitors (e.g., HIV and hepatitis C that include drugs such as ritonavir, indinavir, boceprevir, and telaprevir), metoclopramide, nicardipine, troleandomycin, verapamil • Drugs and other agents…

Inducers of CYP3A4 and P-gp may decrease sirolimus concentrations whereas inhibitors of CYP3A4 and P-gp may increase sirolimus concentrations.

Use with Cyclosporine Cyclosporine, a substrate and inhibitor of CYP3A4 and P-gp, was demonstrated to increase sirolimus concentrations when co-administered with sirolimus.

(See CLINICAL PHARMACOLOGY: Drug Interaction Studies .) Sirolimus Fluconazole increases plasma concentrations of sirolimus presumably by inhibiting the metabolism of sirolimus via CYP3A4 and P-glycoprotein.

This combination may be used with a dosage adjustment of sirolimus depending on the effect/concentration measurements.