Drug Interactions between amoxicillin / clarithromycin / vonoprazan and belumosudil

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.

Grapefruit juice may delay the gastrointestinal absorption of clarithromycin but does not appear to affect the overall extent of absorption or inhibit the metabolism of clarithromycin. The mechanism of interaction is unknown but may be related to competition for intestinal CYP450 3A4 and/or absorptive sites. In an open-label, randomized, crossover study consisting of 12 healthy subjects, coadministration with grapefruit juice increased the time to reach peak plasma concentration (Tmax) of both clarithromycin and 14-hydroxyclarithromycin (the active metabolite) by 80% and 104%, respectively, compared to water. Other pharmacokinetic parameters were not significantly altered. This interaction is unlikely to be of clinical significance.