Drug Interaction Report

MONITOR CLOSELY: Apomorphine may potentiate the hypotensive effects of vasodilators, antihypertensive agents, or agents with hypotensive properties. Apomorphine alone has been associated with orthostatic hypotension, hypotension, syncope, and dose-dependent decreases in systolic and diastolic blood pressure. In clinical studies of the subcutaneous formulation of apomorphine in patients with advanced Parkinson's disease, hypotension (10% vs 4%), myocardial infarction (3% vs. 1%), serious pneumonia (5% vs. 3%), serious falls (9% vs. 3%), and bone and joint injuries (6% vs. 2%) were experienced more commonly in patients receiving concomitant antihypertensive medications or vasodilators (n=94) compared to those not receiving these medications (n=456). Some of these events may be related to the increased incidence of hypotension.

MANAGEMENT: Caution and close monitoring for altered efficacy and safety are recommended if patients receive apomorphine with an antihypertensive agent, vasodilator, or agents with hypotensive properties. Patients should be made aware of the possible side effects (e.g., dizziness, lightheadedness, orthostasis) and be cautioned about driving, operating machinery, or performing other hazardous tasks. They should also be advised to avoid rising abruptly from a sitting or recumbent position and to contact their physician if they experience symptoms of hypotension such as dizziness, lightheadedness, or fainting.

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.