Summary

Brexpiprazole and erythromycin have a clinically significant drug interaction due to erythromycin's inhibition of CYP3A4, which can increase brexpiprazole plasma concentrations. This interaction may lead to enhanced side effects and requires careful monitoring and potential dose adjustments.

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 as a partial agonist at dopamine D2 and serotonin 5-HT1A receptors. Erythromycin is a macrolide antibiotic commonly prescribed for bacterial infections, including respiratory tract infections, skin infections, and certain sexually transmitted infections. Both medications are metabolized through the cytochrome P450 system, which creates the potential for drug interactions.

Mechanism of Interaction

The interaction between brexpiprazole and erythromycin occurs through cytochrome P450 enzyme inhibition. Brexpiprazole is primarily metabolized by CYP3A4 and CYP2D6 enzymes. Erythromycin is a moderate inhibitor of CYP3A4, which can significantly reduce the metabolism of brexpiprazole. When erythromycin inhibits CYP3A4, it decreases 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 of this interaction include increased brexpiprazole-related side effects such as sedation, dizziness, extrapyramidal symptoms, and metabolic changes including weight gain and glucose elevation. Both medications can potentially prolong the QT interval, creating an additive risk for cardiac arrhythmias when used together. Patients may experience enhanced central nervous system depression, increased risk of falls, and worsening of movement disorders. The interaction is particularly concerning in elderly patients, those with cardiac conditions, or patients taking other QT-prolonging medications. Increased brexpiprazole exposure may also lead to hyperprolactinemia and associated endocrine effects.

Management and Precautions

When concurrent use of brexpiprazole and erythromycin is necessary, consider reducing the brexpiprazole dose by 50% and monitor patients closely for increased side effects. Obtain baseline and periodic ECGs to monitor for QT prolongation, especially in patients with cardiac risk factors. Monitor for signs of extrapyramidal symptoms, sedation, and metabolic changes. Consider alternative antibiotics that do not significantly inhibit CYP3A4, such as azithromycin or cephalexin, when clinically appropriate. If erythromycin must be used, use the shortest effective duration and lowest effective dose. Educate patients about potential side effects and advise them to report any new or worsening symptoms. Regular monitoring of vital signs, mental status, and laboratory parameters may be warranted during concurrent therapy.

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.

Erythromycin interactions with food and lifestyle

Erythromycin should be taken on an empty stomach (1 hour before or 2 hours after meals) for optimal absorption, as food can significantly reduce the drug's bioavailability. However, if gastrointestinal upset occurs, it may be taken with food to minimize stomach irritation, though this may reduce effectiveness. Alcohol consumption should be avoided or limited while taking erythromycin, as it may increase the risk of gastrointestinal side effects and potentially reduce the antibiotic's effectiveness. Patients should also avoid taking erythromycin with dairy products or calcium-fortified foods within 2 hours of dosing, as calcium can interfere with absorption.