Drug Interactions between apomorphine and cariprazine

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.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of cariprazine. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism of cariprazine by certain compounds present in grapefruit. When cariprazine (0.5 mg/day) was coadministered with the potent CYP450 3A4 inhibitor, ketoconazole (400 mg/day), cariprazine peak plasma concentration (Cmax) and systemic exposure (AUC) increased by approximately 3.5- and 4-fold, respectively, while Cmax and AUC of DDCAR increased by approximately 1.5-fold each. The Cmax and AUC of another active metabolite, desmethyl cariprazine (DCAR), decreased by approximately one-third. The interaction has not been studied with grapefruit juice. 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 cariprazine may increase the risk of adverse effects such as extrapyramidal symptoms, cognitive and motor impairment, hyperglycemia, dyslipidemia, weight gain, orthostatic hypotension, leucopenia, neutropenia, seizures, and dysphagia.

MANAGEMENT: Patients should avoid the consumption of grapefruit and grapefruit juice during treatment with cariprazine.