Summary

Diltiazem can significantly increase brexpiprazole plasma concentrations through CYP3A4 enzyme inhibition. This interaction may lead to enhanced brexpiprazole effects and increased risk of adverse reactions, requiring careful monitoring and potential dose adjustments.

Introduction

Brexpiprazole is an atypical antipsychotic medication primarily used to treat schizophrenia and as adjunctive therapy for major depressive disorder. It belongs to the quinolinone class of antipsychotics and works as a partial agonist at dopamine D2 and serotonin 5-HT1A receptors. Diltiazem is a calcium channel blocker from the benzothiazepine class, commonly prescribed for hypertension, angina, and certain arrhythmias. It works by blocking calcium channels in cardiac and vascular smooth muscle, leading to vasodilation and reduced cardiac contractility.

Mechanism of Interaction

The interaction between brexpiprazole and diltiazem occurs through cytochrome P450 enzyme inhibition. Brexpiprazole is primarily metabolized by CYP3A4 and CYP2D6 enzymes, with CYP3A4 being the major pathway. Diltiazem is a moderate inhibitor of CYP3A4, which can significantly reduce the metabolism of brexpiprazole. When diltiazem inhibits CYP3A4, it decreases the clearance of brexpiprazole, leading to increased plasma concentrations and prolonged half-life of the antipsychotic medication. This pharmacokinetic interaction can result in enhanced therapeutic effects as well as increased risk of adverse reactions.

Risks and Symptoms

The primary clinical risk of this interaction is increased brexpiprazole exposure, which may lead to enhanced side effects including extrapyramidal symptoms, sedation, weight gain, and metabolic changes. Patients may experience increased drowsiness, dizziness, or motor coordination problems. There is also potential for QT interval prolongation, particularly concerning given that both medications can affect cardiac conduction. The interaction is considered clinically significant and may require dose modifications. Elderly patients and those with hepatic impairment may be at higher risk for adverse effects due to reduced drug clearance capacity.

Management and Precautions

When concurrent use of brexpiprazole and diltiazem is necessary, consider reducing the brexpiprazole dose by approximately 50% and monitor closely for therapeutic response and adverse effects. Regular monitoring should include assessment of extrapyramidal symptoms, sedation levels, vital signs, and ECG monitoring for QT prolongation. Patients should be educated about potential side effects and advised to report any new or worsening symptoms. Alternative calcium channel blockers with less CYP3A4 inhibition potential, such as amlodipine, may be considered if clinically appropriate. Healthcare providers should review the patient's complete medication profile to identify other potential CYP3A4 inhibitors that could compound this interaction.

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.

Diltiazem interactions with food and lifestyle

Grapefruit and grapefruit juice should be avoided while taking diltiazem 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 the blood pressure-lowering effects of diltiazem and increase the risk of dizziness, fainting, and falls. Patients should also be cautious when standing up quickly or engaging in activities requiring alertness, as diltiazem can cause dizziness and lightheadedness, especially when starting treatment or increasing the dose.