Drug Interactions between conivaptan and fosamprenavir

CONTRAINDICATED: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of vasopressin receptor antagonists conivaptan and tolvaptan, both of which are almost exclusively metabolized by the isoenzyme. According to the product labeling, administration of oral conivaptan 10 mg in combination with 200 mg of the potent CYP450 3A4 inhibitor ketoconazole resulted in 4- and 11-fold increases in conivaptan peak plasma concentration (Cmax) and systemic exposure (AUC), respectively, compared to administration alone. Similarly, when a single 30 mg oral dose of tolvaptan was administered to 19 healthy volunteers following pretreatment with ketoconazole 200 mg/day for 3 days, tolvaptan Cmax increased by 3.5-fold and AUC increased by 5.4-fold, although 24-hour urine output increased by just 1.3-fold due to the saturable nature of tolvaptan's effect on urinary excretion rate.

MANAGEMENT: Concomitant use of conivaptan or tolvaptan with potent CYP450 3A4 inhibitors is considered contraindicated. Some authorities recommend avoiding concomitant use of conivaptan or tolvaptan during and for 2 weeks after treatment with itraconazole.