Drug Interaction Report

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease exposure to belumosudil, which is primarily metabolized by the isoenzyme. Concomitant use with the moderate CYP450 3A4 inducer, efavirenz, is predicted to decrease belumosudil peak plasma concentration (Cmax) and systemic exposure (AUC) by 32% and 35%, respectively, in healthy subjects. The interaction has not been studied with other, less potent inducers.

MANAGEMENT: The potential for diminished pharmacologic effects of belumosudil should be considered during coadministration with CYP450 3A4 inducers. Alternative treatments may be required if an interaction is suspected.

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.

MONITOR: Coadministration of two or more sympathomimetic agents may increase the risk of adverse effects such as nervousness, irritability, and increased heart rate. Central nervous system (CNS) stimulants, particularly amphetamines, can potentiate the adrenergic response to vasopressors and other sympathomimetic agents. Additive increases in blood pressure and heart rate may occur due to enhanced peripheral sympathetic activity.

MANAGEMENT: Caution is advised if two or more sympathomimetic agents are coadministered. Pulse and blood pressure should be closely monitored.