Drug Interactions between lapatinib and zolpidem

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

ADJUST DOSING INTERVAL: Administration of zolpidem with food may delay the onset of hypnotic effects. In 30 healthy subjects, administration of zolpidem 20 minutes after a meal resulted in decreased mean peak plasma drug concentration (Cmax) and area under the concentration-time curve (AUC) by 25% and 15%, respectively, compared to fasting. The time to reach peak plasma drug concentration (Tmax) was prolonged by 60%, from 1.4 to 2.2 hours.

MANAGEMENT: Patients receiving zolpidem should be advised to avoid the consumption of alcohol. For faster sleep onset, zolpidem should not be administered with or immediately after a meal.

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.