Drug Interactions between apomorphine and eplerenone

GENERALLY AVOID: Coadministration with grapefruit juice may increase the plasma concentrations of eplerenone. The primary mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. Inhibition of hepatic CYP450 3A4 may also contribute. In drug interaction studies, administration of a single 100 mg dose of eplerenone in combination with grapefruit juice resulted in a 25% increase in eplerenone systemic exposure (AUC). High blood levels of eplerenone can increase the risk of side effects including hyperkalemia. 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.

MANAGEMENT: It may be advisable for patients to avoid the consumption of grapefruit, grapefruit juice, or supplements that contain grapefruit during treatment with eplerenone.

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.