Drug Interaction Report

GENERALLY AVOID: Alcohol may exacerbate the adverse central nervous system effects of psychoactive drugs, including methylphenidate.

GENERALLY AVOID: Consumption of alcohol while taking certain sustained-release formulations of methylphenidate may cause rapid release of the drug, resulting in increased systemic levels of methylphenidate. In vitro studies have been conducted using Metadate CD 60 mg and Ritalin LA 40 mg capsules, as well as Concerta 18 mg tablet. At an alcohol concentration of 40%, an increase in the release rate of methylphenidate was observed in the first hour for Metadate CD and Ritalin LA, resulting in 84% and 98% of the methylphenidate being released, respectively. In contrast, there was no increased release of methylphenidate in the first hour for Concerta. These results are considered to be representative of the other available strengths of the corresponding product.

MANAGEMENT: Patients treated with methylphenidate should be advised to avoid alcohol or medications that contain alcohol.

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.