Drug Interaction Report

MONITOR: Coadministration with gastric acid-reducing agents other than proton pump inhibitors (PPIs) may reduce the oral bioavailability of belumosudil. The mechanism of interaction has not been established. Concomitant use of the PPI rabeprazole decreased belumosudil peak plasma concentration (Cmax) and systemic exposure (AUC) by 87% and 80%, respectively, while coadministration of omeprazole decreased belumosudil Cmax and AUC by 68% and 47%, respectively, in healthy subjects. Data for other gastric acid-reducing agents are not available.

MANAGEMENT: The potential for diminished pharmacologic effects of belumosudil should be considered during coadministration with gastric acid-reducing agents other than PPIs. Other authorities recommend having a dosing interval of at least 12 hours between the latter and belumosudil (GB).

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.