Drug Interaction Report

Coadministration with remdesivir may increase the plasma concentrations of drugs metabolized via CYP450 3A4, but many sources indicate that clinically significant interactions are unlikely. The proposed mechanism is inhibition of CYP450 3A4 by remdesivir. Two drug interaction studies were conducted using the sensitive CYP450 3A4 substrate, midazolam. In the first study, healthy volunteers (n=19) received a single dose of remdesivir (200 mg) and a single dose of midazolam (2.5 mg), which resulted in midazolam's maximum concentration (Cmax) and systemic exposure (AUC) increasing by 29% and 20%, respectively. In the second study, healthy volunteers (n=14) received remdesivir (200 mg once, followed by 100 mg daily) for a total of 10 doses and a single dose of midazolam (2.5 mg) administered with the last dose of remdesivir. Midazolam's Cmax and AUC increased by 45% and 30%, respectively. Both studies indicated that remdesivir is a weak in vivo inhibitor of CYP450 3A4; however, some authorities consider these findings to be clinically insignificant.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of suvorexant. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills. In addition, alcohol may increase the risk of cognitive and complex behavioral changes associated with the use of hypnotics including suvorexant, such as amnesia, anxiety, hallucinations, sleep-driving, and other neuropsychiatric symptoms.

ADJUST DOSE: Grapefruit juice may significantly increase the plasma concentrations of suvorexant. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit.

ADJUST DOSING INTERVAL: Administration with or soon after a meal may delay the gastrointestinal absorption of suvorexant. According to the product labeling, administration of suvorexant with a high-fat meal resulted in no meaningful change in peak plasma concentration (Cmax) or systemic exposure (AUC), but a delay in Tmax of approximately 1.5 hours.

MANAGEMENT: Concomitant use of suvorexant with alcohol should be avoided. Patients should be advised not to use suvorexant if they had alcohol that evening or before bed. Grapefruit juice should preferably be avoided; otherwise, the recommended dose of suvorexant is 5 mg when used with grapefruit juice and should not exceed 10 mg. Suvorexant may be taken with or without food; however, for faster sleep onset, suvorexant should not be administered with or soon after a meal.