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.

ADJUST DOSING INTERVAL: Food reduces the oral absorption and bioavailability of voriconazole. According to the product labeling, administration of multiple doses of voriconazole with high-fat meals decreased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) by 34% and 24%, respectively, when the drug is administered as a tablet, and by 58% and 37%, respectively, when administered as the oral suspension.

MANAGEMENT: To ensure maximal oral absorption, voriconazole tablets and oral suspension should be taken at least one hour before or after a meal.