Summary

Brexpiprazole and clarithromycin have a clinically significant drug interaction due to clarithromycin's strong inhibition of CYP3A4, which can increase brexpiprazole levels by up to 2-fold. This interaction may lead to enhanced side effects and requires careful monitoring and potential dose adjustments.

Introduction

Brexpiprazole (Rexulti) is an atypical antipsychotic medication 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. Clarithromycin is a macrolide antibiotic commonly prescribed for respiratory tract infections, skin infections, and Helicobacter pylori eradication. It is a potent inhibitor of the cytochrome P450 enzyme CYP3A4, which is responsible for metabolizing many medications including brexpiprazole.

Mechanism of Interaction

The interaction between brexpiprazole and clarithromycin occurs through inhibition of the CYP3A4 enzyme system. Brexpiprazole is primarily metabolized by CYP3A4 and CYP2D6 enzymes, with CYP3A4 playing a major role in its elimination. Clarithromycin is a strong CYP3A4 inhibitor that can significantly reduce the metabolism of brexpiprazole, leading to increased plasma concentrations. This mechanism-based inhibition can result in approximately 2-fold increase in brexpiprazole exposure, potentially lasting several days after clarithromycin discontinuation due to the irreversible nature of the enzyme inhibition.

Risks and Symptoms

The primary clinical risks of this interaction include increased incidence and severity of brexpiprazole-related adverse effects. Patients may experience enhanced central nervous system effects such as sedation, dizziness, confusion, and cognitive impairment. Extrapyramidal symptoms including tremor, rigidity, and tardive dyskinesia risk may be elevated. Metabolic side effects such as weight gain, hyperglycemia, and dyslipidemia could be more pronounced. Additionally, there is an increased risk of QT interval prolongation, which could lead to serious cardiac arrhythmias, particularly in patients with pre-existing cardiac conditions or other risk factors.

Management and Precautions

When concurrent use of brexpiprazole and clarithromycin is necessary, consider reducing the brexpiprazole dose by half during clarithromycin therapy and for several days after discontinuation. Monitor patients closely for increased side effects, particularly neurological and psychiatric symptoms. Assess for signs of extrapyramidal symptoms and metabolic changes. Consider ECG monitoring in patients at risk for QT prolongation. If possible, consider alternative antibiotics that do not significantly inhibit CYP3A4, such as azithromycin or cephalexin, depending on the clinical indication. Healthcare providers should counsel patients about potential increased side effects and advise them to report any new or worsening symptoms promptly.

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.

Clarithromycin interactions with food and lifestyle

Clarithromycin can be taken with or without food. However, taking clarithromycin with food may help reduce stomach upset and gastrointestinal side effects. Grapefruit juice should be avoided as it may increase clarithromycin blood levels and potentially increase the risk of side effects. Alcohol does not have a direct interaction with clarithromycin, but it's generally recommended to limit alcohol consumption while taking antibiotics to support immune system function and recovery.