Drug Interactions between buspirone and Tykerb

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.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of lapatinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

ADJUST DOSING INTERVAL: Food can significantly increase the oral bioavailability of lapatinib. According to the manufacturer, lapatinib peak plasma concentration (Cmax) was approximately 2.5- and 3-fold higher and systemic exposure (AUC) 3- and 4-fold higher when administered with a low fat meal (5% fat; 500 calories) or with a high-fat meal (50% fat; 1000 calories), respectively, compared to fasting. Dividing the daily dose also resulted in an approximately 2-fold higher systemic exposure at steady state compared to the same total dose administered once daily.

MANAGEMENT: Patients treated with lapatinib should preferably avoid the consumption of grapefruit or grapefruit juice. The manufacturer recommends that lapatinib be administered at least one hour before or one hour after a meal. The lapatinib dose is administered once daily and should not be divided.