Drug Interactions between nefazodone and sunitinib

GENERALLY AVOID: Coadministration with potent inhibitors of CYP450 3A4 may increase the plasma concentrations of sunitinib and its pharmacologically active metabolite, both of which are substrates of the isoenzyme. In healthy volunteers, concurrent administration of a single dose of sunitinib with the potent CYP450 3A4 inhibitor, ketoconazole, resulted in a 49% and 51% increase in the combined (i.e., sunitinib plus its primary active metabolite) peak plasma concentration (Cmax) and systemic exposure (AUC) values, respectively, compared to administration of sunitinib alone. Because sunitinib is associated with concentration-dependent prolongation of the QT interval, increased levels may potentiate the risk of ventricular arrhythmias such as torsade de pointes and sudden death.

MANAGEMENT: Alternative agents with no or minimal CYP450 3A4-inhibiting activity are recommended in patients treated with sunitinib. Some authorities recommend avoiding concomitant use of sunitinib during and for 2 weeks after treatment with itraconazole. A dose reduction for sunitinib to a minimum of 37.5 mg daily for gastrointestinal stromal tumor (GIST) and metastatic renal cell carcinoma (mRCC) or 25 mg daily for pancreatic neuroendocrine tumors (pNET) should be considered if it must be coadministered with potent CYP450 3A4 inhibitors such as itraconazole, ketoconazole, voriconazole, nefazodone, delavirdine, protease inhibitors, and ketolide and certain macrolide antibiotics.