Drug Interactions between apomorphine and Dayvigo

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of lemborexant, which is primarily metabolized by CYP450 3A4. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice but has been reported for other CYP450 3A4 inhibitors. When coadministered with itraconazole, a potent CYP450 3A4 inhibitor, lemborexant peak plasma concentration (Cmax) and systemic exposure (AUC) increased approximately 1.4-fold and 3.8-fold, respectively. When coadministered with fluconazole, a moderate CYP450 3A4 inhibitor, lemborexant Cmax and AUC increased approximately 1.6-fold and 4.2-fold, respectively. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Increased exposure to lemborexant may increase the risk of adverse reactions such as central nervous system (CNS) depression, sleep paralysis, hallucinations, complex sleep behaviors, worsening of depression or suicidal ideation, nightmares, palpitations, or headache.

After administration of a high-fat, high-calorie meal (approximately 1000 calories with 500 to 600 calories from fat), lemborexant Cmax decreased by 23%, AUC increased by 18%, and the time to maximum concentration (Tmax) was delayed by 2 hours.

MANAGEMENT: The manufacturer makes no recommendation regarding administration with food; however, the time to sleep onset may be delayed if taken with or soon after a meal. Patients should avoid consumption of grapefruit, grapefruit juice, or supplements that contain grapefruit during treatment with lemborexant.

GENERALLY AVOID: Alcohol and apomorphine may have additive hypotensive and sedative effects. Coadministration of 0.6 or 0.3 g/kg of ethanol with apomorphine in healthy subjects resulted in greater decreases in blood pressure compared to apomorphine alone. The mean largest decrease (the mean of each subject's largest drop in blood pressure measured within 6 hours after apomorphine administration) in standing systolic and diastolic blood pressure was 6.7 and 8.4 mmHg, respectively, with apomorphine alone. When coadministered with 0.6 g/kg of ethanol (equivalent to approximately 3 standardized alcohol-containing beverages), the mean largest decrease in standing systolic and diastolic blood pressure was 11.3 and 12.6 mmHg, respectively (standing systolic and diastolic blood pressure decreased by as much as 61 and 51 mmHg, respectively, in this group). When coadministered with 0.3 g/kg of ethanol, the mean largest decrease in standing systolic and diastolic blood pressure was 8.4 and 7.1 mmHg, respectively.

MANAGEMENT: Patients should be advised to avoid consumption of alcohol during apomorphine treatment.