Drug Interactions between fluconazole and ruxolitinib

ADJUST DOSE: Coadministration of fluconazole with ruxolitinib may significantly increase the plasma concentrations of ruxolitinib and the risk of cytopenias. The proposed mechanism is decreased clearance due to fluconazole-mediated inhibition of CYP450 3A4 and 2C9, the isoenzymes responsible for the metabolic clearance of ruxolitinib. Following concomitant administration of fluconazole at doses of 100 mg to 400 mg daily, the AUC of ruxolitinib is predicted to increase by approximately 100% to 300%, respectively.

MANAGEMENT: Coadministration of ruxolitinib with fluconazole doses greater than 200 mg per day should be avoided except in patients with acute graft versus host disease (GVHD). For patients with myelofibrosis (MF) coadministered fluconazole 200 mg per day or less, ruxolitinib should be started at 10 mg twice a day when the platelet count is at least 100 X 10(9)/L or greater and 5 mg once a day when the platelet counts is at least 50 X 10(9)/L. and less than 100 x 10(9)/L. The recommended starting dose for patients with Polycythemia vera (PV) coadministered fluconazole 200 mg per day or less is ruxolitinib 5 mg twice a day. For patients with MF or PV who are stabilized on ruxolitinib 10 mg twice a day or greater and starting fluconazole (at a dose of 200 mg per day or less), the ruxolitinib dose should be reduced by 50% (rounded up to the closest available tablet strength). For patients with MF or PV stabilized on ruxolitinib 5 mg twice a day and starting fluconazole (at a dose of 200 mg per day or less), the ruxolitinib dose should be reduced to 5 mg once a day. For patients with MF or PV stabilized on ruxolitinib 5 mg once a day, avoid starting fluconazole or interrupt ruxolitinib therapy for the duration of fluconazole use. Additional dosage modifications should be made with careful monitoring of safety and efficacy.