Drug Interactions between belumosudil and st. john's wort

GENERALLY AVOID: An isolated case report suggests that foods containing large amounts of tyramine may precipitate a hypertensive crisis in patients treated with St. John's wort. The mechanism of interaction is unknown, as St. John's wort is not thought to possess monoamine oxidase (MAO) inhibiting activity at concentrations achieved in vivo. The case patient was a 41-year-old man who had been taking St. John's wort for seven days prior to presentation at the emergency room with confusion and disorientation. The patient recalled last eating aged cheese and having a glass of red wine approximately 10 hours prior to admission. No other cause of delirium or hypertension could be identified. In addition, alcohol may potentiate some of the pharmacologic effects of St. John's wort. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Until further information is available, patients treated with St. John's wort should consider avoiding consumption of protein foods in which aging or breakdown of protein is used to increase flavor. These foods include cheese (particularly strong, aged or processed cheeses), sour cream, wine (particularly red wine), champagne, beer, pickled herring, anchovies, caviar, shrimp paste, liver (particularly chicken liver), dry sausage, figs, raisins, bananas, avocados, chocolate, soy sauce, bean curd, yogurt, papaya products, meat tenderizers, fava beans, protein extracts, and dietary supplements. Caffeine may also precipitate hypertensive crisis so its intake should be minimized as well. Patients should also be advised to avoid or limit consumption of alcohol.

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.