Drug Interaction Report

ADJUST DOSE: Coadministration with potent inducers of CYP450 3A4 may decrease systemic exposure to belumosudil, which is primarily metabolized by the isoenzyme. Concomitant use with the potent CYP450 3A4 inducer, rifampin, decreased belumosudil peak plasma concentration (Cmax) and systemic exposure (AUC) by 59% and 72%, respectively, in healthy subjects. Reduced efficacy of belumosudil may occur.

MANAGEMENT: When coadministered with potent CYP450 3A4 inducers, the dose of belumosudil should be increased to 200 mg twice daily.

ADJUST DOSING INTERVAL: Administration with food increases the oral bioavailability of belumosudil. The mechanism has not been described. Administration of belumosudil (200 mg single oral dose) in healthy subjects, with a fatty and calorie-rich meal (approximately half of the calories were contained in the fat) increased the mean belumosudil peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) by 120% and 100%, respectively, compared to administration under fasting conditions. The time to reach peak concentration (Tmax) was delayed by 30 minutes. Administration of oral belumosudil 200 mg once daily with food in patients with chronic graft-versus-host disease (chronic GVHD) lead to steady-state concentrations of the drug with an accumulation ration of 1.4.

MANAGEMENT: To ensure maximal oral absorption, belumosudil should be administered with a meal, every day at the same time.