Sirolimus and Verapamil interaction

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) ].

• Avoid concomitant use with strong CYP3A4/P-gp inducers or strong CYP3A4/P-gp inhibitors that decrease or increase sirolimus concentrations ( 7.4 , 12.3 ).

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.

…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 that could decrease sirolimus concentrations: Carbamazepine, phenobarbital, phenytoin, rifapentine, St.

John's Wort ( Hypericum perforatum ) • Drugs with concentrations that could increase when given with sirolimus: Verapamil 7.5 Cannabidiol The blood levels of sirolimus may increase upon concomitant use with cannabidiol.

Mammalian Target of Rapamycin (mTOR) Inhibitors In a study of 25 healthy volunteers with co-administration of verapamil with sirolimus, whole blood sirolimus C max and AUC were increased 130% and 120%, respectively.

With concomitant use of mTOR inhibitors (e.g., sirolimus, temsirolimus, and everolimus) and verapamil, consider appropriate dose reductions of both medications.