danocrine and Bosentan Interactions

Interactions between danocrine(danazol) and Bosentan (bosentan)

danazol and bosentan (Moderate Drug-Drug)

MONITOR: Coadministration with inhibitors of CYP450 2C9 and/or 3A4 may increase the plasma concentrations of bosentan, which is metabolized by these isoenzymes. According to bosentan product labeling, ketoconazole (a potent CYP450 3A4 inhibitor) alone increased the plasma concentrations of bosentan (125 mg orally twice a day) by approximately 2-fold. It is conceivable that concomitant administration of both a CYP450 2C9 inhibitor and a CYP450 3A4 inhibitor may lead to even larger increases in plasma concentrations of bosentan.

MANAGEMENT: The possibility of prolonged and/or increased pharmacologic effects of bosentan, including serious adverse effects such as hepatotoxicity, should also be considered. Patients should be advised to notify their physician if they experience signs and symptoms of hepatotoxicity such as fever, rash, anorexia, nausea, vomiting, fatigue, right upper quadrant pain, dark urine, and jaundice. Concomitant administration of both a potent CYP450 2C9 inhibitor (e.g., fluconazole, amiodarone) and a potent CYP450 3A4 inhibitor (e.g., ketoconazole, itraconazole, ritonavir) is not recommended. Concomitant administration with combination 2C9/3A4 inhibitors (e.g., delavirdine, imatinib, miconazole, voriconazole) should probably be avoided also, if possible.