Summary

Brexpiprazole and verapamil have a moderate drug interaction primarily mediated through CYP3A4 enzyme inhibition. Verapamil can increase brexpiprazole plasma concentrations, potentially leading to enhanced side effects and requiring dose adjustments.

Introduction

Brexpiprazole is an atypical antipsychotic medication approved for treating schizophrenia and as adjunctive therapy for major depressive disorder. It belongs to the quinolinone class and works as a partial agonist at dopamine D2 and serotonin 5-HT1A receptors. Verapamil is a calcium channel blocker primarily used to treat hypertension, angina, and certain cardiac arrhythmias. It belongs to the phenylalkylamine class of calcium channel blockers and also has significant effects on cardiac conduction.

Mechanism of Interaction

The interaction between brexpiprazole and verapamil occurs through cytochrome P450 enzyme inhibition. Verapamil is a moderate inhibitor of CYP3A4, the primary enzyme responsible for brexpiprazole metabolism. When co-administered, verapamil reduces the clearance of brexpiprazole, leading to increased plasma concentrations and prolonged half-life. This pharmacokinetic interaction can result in enhanced therapeutic effects as well as increased risk of adverse reactions associated with brexpiprazole.

Risks and Symptoms

The primary clinical risks include increased brexpiprazole-related side effects such as extrapyramidal symptoms, sedation, weight gain, and metabolic changes. Patients may experience enhanced CNS depression, increased risk of orthostatic hypotension, and potential cardiac effects including QT prolongation. The combination may also increase the risk of tardive dyskinesia and other movement disorders. Additionally, both medications can cause hypotension, which may be additive when used together, potentially leading to symptomatic blood pressure drops.

Management and Precautions

When co-administering brexpiprazole and verapamil, consider reducing the brexpiprazole dose by approximately 50% to account for decreased clearance. Monitor patients closely for signs of brexpiprazole toxicity, including extrapyramidal symptoms, excessive sedation, and cardiovascular effects. Regular blood pressure monitoring is essential due to the additive hypotensive effects. Consider ECG monitoring for QT interval changes, especially in patients with cardiac risk factors. If possible, consider alternative antihypertensive agents with less CYP3A4 inhibition potential. Always consult with a healthcare professional before making any dose adjustments or medication changes.

Brexpiprazole interactions with food and lifestyle

Alcohol: Brexpiprazole may enhance the sedative effects of alcohol. Patients should avoid or limit alcohol consumption while taking brexpiprazole as it can increase drowsiness, dizziness, and impair cognitive and motor functions. This combination may also increase the risk of falls and accidents.

Verapamil interactions with food and lifestyle

Grapefruit and grapefruit juice should be avoided while taking verapamil as they can significantly increase blood levels of the medication, potentially leading to dangerous drops in blood pressure and heart rate. Alcohol consumption should be limited or avoided as it can enhance verapamil's blood pressure-lowering effects and increase the risk of dizziness, fainting, and falls. High-fiber foods or fiber supplements may reduce verapamil absorption when taken at the same time, so it's recommended to separate their administration by at least 2 hours.