Drug Interactions between Caplyta and Seroquel

GENERALLY AVOID: Grapefruit juice and/or grapefruit may increase the plasma concentrations of quetiapine. 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. For example, in 12 healthy volunteers, administration of a single 25 mg dose of quetiapine with the potent CYP450 3A4 inhibitor ketoconazole (200 mg once daily for 4 days) increased mean quetiapine peak plasma concentration (Cmax) and systemic exposure (AUC) by 3.4- and 6.2-fold, respectively, and decreased mean oral clearance by 84%. In general, the effects of grapefruit products are concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit (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. High plasma levels of quetiapine may increase the risk and/or severity of serious adverse effects such as extrapyramidal symptoms, tardive dyskinesia, hyperglycemia, dyslipidemia, hyperprolactinemia, orthostatic hypotension, blood pressure increases (in children and adolescents), priapism, QT prolongation, cognitive and motor impairment, dysphagia, heat-related illnesses due to disruption of body temperature regulation, and symptoms of serotonin syndrome (e.g., mental status changes such as irritability, altered consciousness, confusion, hallucination, and coma; autonomic dysfunction such as tachycardia, hyperthermia, diaphoresis, shivering, blood pressure lability, and mydriasis; neuromuscular abnormalities such as hyperreflexia, myoclonus, tremor, rigidity, and ataxia; and gastrointestinal symptoms such as abdominal cramping, nausea, vomiting, and diarrhea).

Food may have varying effects on the absorption of quetiapine from immediate-release versus prolonged-release formulations. In a study examining the effects of food on the bioavailability of quetiapine, a high-fat meal was found to produce statistically significant increases in the quetiapine prolonged release Cmax and AUC of approximately 50% and 20%, respectively. It cannot be excluded that the effect of a high fat meal on the formulation may be larger. In comparison, a light meal had no significant effect on the Cmax or AUC of quetiapine.

Quetiapine may potentiate the cognitive and motor effects of alcohol. The mechanism is likely related to the primary central nervous system effects of quetiapine.

MANAGEMENT: According to the manufacturer, consumption of grapefruit juice should be avoided during treatment with quetiapine. Quetiapine immediate-release tablets may be taken with or without food. It is recommended that quetiapine prolonged release is taken once daily without food or with a light meal. Consumption of alcohol should be limited and used with caution while taking quetiapine.

GENERALLY AVOID: Grapefruit and grapefruit juice may increase the plasma concentrations of lumateperone. 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 but has been reported for other CYP450 3A4 inhibitors. In a drug interaction study, the strong CYP450 3A4 inhibitor itraconazole increased lumateperone peak plasma concentration (Cmax) and systemic exposure (AUC) approximately 3.5- and 4-fold, respectively, while diltiazem (a moderate CYP450 3A4 inhibitor) increased lumateperone Cmax and AUC approximately 2- and 2.5-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.

When administered with a high-fat meal, lumateperone Cmax decreased by 33% while its AUC increased by 9% and its median time to peak plasma concentration (Tmax) was delayed by about 1 hour.

MANAGEMENT: Lumateperone should be administered with food. Coadministration of grapefruit or grapefruit juice with lumateperone should be avoided.

The recommended maximum number of medicines in the 'antipsychotics' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'antipsychotics' category:

• Caplyta (lumateperone)
• Seroquel (quetiapine)

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.