Drug Interactions between buspirone and sirolimus

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of buspirone. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

ADJUST DOSING INTERVAL: In a small, randomized, crossover study, the consumption of large amounts of grapefruit juice (compared to water) was associated with significantly increased plasma buspirone concentrations, slightly prolonged elimination half-lives, and delayed times to reach peak drug concentration. The perceived pharmacodynamic effect of buspirone, as measured by subjective drowsiness and overall subjective drug effect, was also enhanced by grapefruit juice. These alterations may stem from the delay of gastric emptying as well as inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits.

MANAGEMENT: Patients receiving buspirone should be advised to avoid consumption of alcohol. Patients also should preferably avoid the consumption of large amounts of grapefruits and grapefruit juice to prevent any undue fluctuations in plasma drug levels. If this is not possible, the buspirone dose should be taken at least 2 hours before or 8 hours after grapefruit or grapefruit juice. Monitoring for increased CNS depression is recommended.

ADJUST DOSING INTERVAL: Consumption of food can decrease the rate and extent of gastrointestinal absorption of sirolimus. Also, the consumption of grapefruit juice may result in increased sirolimus trough concentrations.

MANAGEMENT: Experts recommend that this drug be taken either at least one hour prior to eating or consistently with or without food to avoid variations in sirolimus blood levels. The manufacturer recommends against using grapefruit juice for dilution of sirolimus doses. Patients should be monitored for clinical and laboratory evidence of altered immunosuppressant effects.