Drug Interaction Report

GENERALLY AVOID: Coadministration with a dual CYP450 2C9/3A4 inhibitor, such as fluconazole, miconazole, or voriconazole, may increase the plasma concentrations of bosentan, which is metabolized by these isoenzymes. When bosentan 125 mg orally twice a day was administered with the potent CYP450 3A4 inhibitor ketoconazole, bosentan plasma concentrations increased by approximately 2-fold. Concomitant administration with a dual CYP450 2C9/3A4 inhibitor, such as fluconazole, miconazole, or voriconazole may lead to even larger increases in plasma concentrations of bosentan.

MANAGEMENT: Concomitant use of bosentan with a dual CYP450 2C9/3A4 inhibitor, such as fluconazole, miconazole, or voriconazole, is not recommended. If coadministration is necessary, the possibility of prolonged and/or increased pharmacologic effects of bosentan, including serious adverse effects such as hepatotoxicity, should be considered. Patients should be advised to notify their healthcare provider if they experience signs and symptoms of hepatotoxicity such as fever, rash, anorexia, nausea, vomiting, fatigue, right upper quadrant pain, dark urine, and jaundice.