Strong CYP3A4 inhibitors (e.g., ketoconazole) may increase plasma concentrations of sunitinib. Therefore, concomitant use with strong enzyme inhibitors should be avoided or an alternative medication with minimal inhibitory effect should be selected. Co-administration of sunitinib with ketoconazole has been shown to increase combined (sunitinib + active metabolite) Cmax and AUC0-∞ by approximately 49% and 51%, respectively, in healthy volunteers. Other strong CYP3A4 inhibitors such as itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, and voriconazole may also increase sunitinib levels. Grapefruit may similarly elevate plasma concentrations. Dose reduction should be considered if coadministration is necessary. CYP3A4 inducers (e.g., rifampin) may decrease sunitinib plasma concentrations. Rifampin has been shown to reduce combined Cmax and AUC0-∞ by approximately 23% and 46%, respectively. Other inducers such as dexamethasone, phenytoin, carbamazepine, rifabutin, rifapentin, phenobarbital, and St. John’s Wort may also reduce drug levels. St. John’s Wort should be avoided. Dose increase may be required if coadministration with strong inducers is unavoidable.
