Drug Interactions between isavuconazonium and Viekira XR

CONTRAINDICATED: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of isavuconazole, which is primarily metabolized by CYP450 3A4 and 3A5 and subsequently by uridine diphosphate glucuronosyltransferases (UGT). When a single dose of isavuconazonium sulfate (equivalent to 200 mg of isavuconazole) was administered to healthy volunteers following multiple dosing of the potent CYP450 3A4 inhibitor ketoconazole (200 mg twice daily for 24 days), isavuconazole peak plasma concentration (Cmax) increased by 9% and systemic exposure (AUC) increased by 422%.

MANAGEMENT: Concomitant use of isavuconazonium sulfate with potent CYP450 3A4 inhibitors is considered contraindicated. Ritonavir given at low dosages as a pharmacokinetic booster may be used with caution, but is contraindicated at high dosages (e.g., 400 mg every 12 hours).

MONITOR: Coadministration with isavuconazonium sulfate (prodrug of isavuconazole) may increase the plasma concentrations of drugs that are substrates of P-glycoprotein (P-gp), such as dabigatran. The proposed mechanism is isavuconazole inhibition of P-gp-mediated efflux of these drugs.

MANAGEMENT: Caution is advised if isavuconazonium sulfate is used concomitantly with drugs that are substrates of P-gp, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring should be considered whenever isavuconazonium sulfate is added to or withdrawn from therapy with these drugs. Patients receiving concomitant dabigatran should be monitored closely for the development of bleeding complications and the dosage of dabigatran adjusted as necessary.

MONITOR: Coadministration with isavuconazonium sulfate (prodrug of isavuconazole) may increase the plasma concentrations of drugs that are substrates of P-glycoprotein (P-gp), such as dabigatran. The proposed mechanism is isavuconazole inhibition of P-gp-mediated efflux of these drugs.

MANAGEMENT: Caution is advised if isavuconazonium sulfate is used concomitantly with drugs that are substrates of P-gp, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring should be considered whenever isavuconazonium sulfate is added to or withdrawn from therapy with these drugs. Patients receiving concomitant dabigatran should be monitored closely for the development of bleeding complications and the dosage of dabigatran adjusted as necessary.