Drug Interactions between darunavir and tofacitinib

ADJUST DOSE: Coadministration with one or more medications that may result in both moderate inhibition of CYP450 3A4 and potent inhibition of CYP450 2C19 may significantly increase the plasma concentrations of tofacitinib, which is primarily metabolized by the former isoenzyme with minor contribution from the latter. In study subjects, administration with the moderate CYP450 3A4 and potent CYP450 2C19 inhibitor fluconazole increased tofacitinib peak plasma concentration (Cmax) and systemic exposure (AUC) by approximately 27% and 79%, respectively, compared to administration of tofacitinib alone. Side effects including lymphopenia, neutropenia, anemia, serious infections, and hyperlipidemia may be increased.

MANAGEMENT: The dosage of tofacitinib should be reduced by 50% when used concomitantly with one or more medications that may result in both moderate inhibition of CYP450 3A4 and potent inhibition of CYP450 2C19. For example, the dose for patients receiving 10 mg twice daily should be reduced to 5 mg twice daily and the dose for patients receiving 5 mg twice daily should be reduced to 5 mg once daily. For patients receiving 11 mg once daily of the extended-release formulation, the dose should be reduced to 5 mg once daily of the immediate-release formulation. The dose for patients receiving 3.2 mg twice daily should be reduced to 3.2 mg once daily and the dose for patients receiving 4 mg twice daily should be reduced to 4 mg once daily. Moderate inhibitors of CYP450 3A4 include amiodarone, aprepitant, ciprofloxacin, crizotinib, darunavir, dalfopristin-quinupristin, diltiazem, dronedarone, erythromycin, fluconazole, fusidic acid, grapefruit juice, imatinib, isavuconazonium, netupitant, and verapamil. Potent inhibitors of CYP450 2C19 include fluconazole, fluvoxamine, esomeprazole, lansoprazole, and omeprazole. Inhibitors of CYP450 2C19 alone are unlikely to substantially alter the pharmacokinetics of tofacitinib.

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