Summary

Rifampin significantly reduces brexpiprazole plasma concentrations through CYP3A4 enzyme induction, potentially leading to decreased therapeutic efficacy. This interaction requires careful monitoring and possible dose adjustments to maintain optimal treatment outcomes.

Introduction

Brexpiprazole (Rexulti) 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 through partial agonism at dopamine D2 and serotonin 5-HT1A receptors. Rifampin is a potent antibiotic belonging to the rifamycin class, commonly used to treat tuberculosis, mycobacterial infections, and certain bacterial infections. It is well-known for its strong enzyme-inducing properties, particularly affecting cytochrome P450 enzymes.

Mechanism of Interaction

The interaction between brexpiprazole and rifampin occurs through hepatic enzyme induction. Rifampin is a potent inducer of cytochrome P450 3A4 (CYP3A4), the primary enzyme responsible for brexpiprazole metabolism. When rifampin is co-administered, it significantly increases CYP3A4 activity, leading to enhanced metabolism and clearance of brexpiprazole. This results in substantially reduced plasma concentrations of brexpiprazole, potentially decreasing its therapeutic effectiveness. The induction effect typically develops over several days to weeks of rifampin treatment and may persist for weeks after rifampin discontinuation.

Risks and Symptoms

The primary clinical risk of this interaction is reduced therapeutic efficacy of brexpiprazole due to significantly decreased plasma concentrations. Patients may experience worsening of psychiatric symptoms, including increased psychotic symptoms in schizophrenia patients or inadequate response in major depressive disorder treatment. Studies suggest that rifampin can reduce brexpiprazole exposure by approximately 50-70%, which may lead to treatment failure or relapse of underlying psychiatric conditions. This interaction is considered clinically significant and requires proactive management to prevent therapeutic failure.

Management and Precautions

When co-administration is necessary, consider doubling the brexpiprazole dose during rifampin treatment, as recommended by prescribing information. Monitor patients closely for signs of reduced psychiatric symptom control or treatment efficacy. Assess the need for continued rifampin therapy and explore alternative antibiotics with less enzyme-inducing potential when clinically appropriate. After rifampin discontinuation, gradually reduce brexpiprazole dose back to the original level over 1-2 weeks to prevent potential adverse effects from increased drug exposure. Regular psychiatric assessments and symptom monitoring are essential throughout the treatment period. Healthcare providers should verify current prescribing guidelines and consult with specialists when managing this complex 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.

Rifampin interactions with food and lifestyle

Rifampin should be taken on an empty stomach, at least 1 hour before or 2 hours after meals, as food can significantly reduce its absorption and effectiveness. Alcohol consumption should be avoided or limited while taking rifampin, as both rifampin and alcohol can cause liver toxicity, and the combination may increase the risk of hepatotoxicity. Patients should be counseled to take rifampin consistently either with or without food (preferably without) to maintain consistent blood levels.