Drug Interactions between conivaptan and panobinostat

ADJUST DOSE: Coadministration with potent inhibitors of CYP450 3A4 may increase the plasma concentrations of panobinostat, which is partially metabolized by the isoenzyme. In 14 patients with advanced or metastatic solid tumors, administration of a single 20 mg dose of panobinostat on day 4 of multiple once daily dosing of 400 mg ketoconazole, a potent CYP450 3A4 inhibitor, resulted in 1.6- and 1.8-fold increases in mean panobinostat peak plasma concentration (Cmax) and systemic exposure (AUC), respectively, compared to administration of panobinostat alone. Ketoconazole caused a greater than 2-fold increase in Cmax and AUC of panobinostat in a limited number of patients. QTc prolongation >30 ms over baseline occurred in 5 patients during concomitant administration, compared to 4 patients during panobinostat alone and 3 patients during ketoconazole alone. Other ECG abnormalities occurred in 6 patients during concomitant administration and 3 patients during either panobinostat or ketoconazole alone. No significant alteration in time to maximum concentration (Tmax) or half-life of panobinostat was observed.

MANAGEMENT: For the treatment of multiple myeloma in combination with bortezomib and dexamethasone, the dose of panobinostat should be reduced to 10 mg when coadministered with potent CYP450 3A4 inhibitors.