Summary

Brexpiprazole and omeprazole have a moderate drug interaction primarily through CYP2D6 enzyme inhibition. Omeprazole can potentially increase brexpiprazole plasma concentrations, requiring careful monitoring and possible 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. Omeprazole (Prilosec) is a proton pump inhibitor (PPI) commonly prescribed for gastroesophageal reflux disease (GERD), peptic ulcers, and other acid-related disorders. It works by irreversibly blocking the H+/K+-ATPase enzyme in gastric parietal cells, reducing stomach acid production.

Mechanism of Interaction

The interaction between brexpiprazole and omeprazole occurs through cytochrome P450 enzyme inhibition. Brexpiprazole is primarily metabolized by CYP3A4 and CYP2D6 enzymes. Omeprazole is a known inhibitor of CYP2D6, particularly at higher doses or with prolonged use. When omeprazole inhibits CYP2D6, it can reduce the metabolism of brexpiprazole, potentially leading to increased plasma concentrations of the antipsychotic. This interaction is more clinically significant in patients who are extensive metabolizers of CYP2D6, as they rely more heavily on this pathway for brexpiprazole clearance.

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 movement disorders. The risk is generally considered moderate, as brexpiprazole has a relatively wide therapeutic window. However, elderly patients or those with hepatic impairment may be at higher risk for adverse effects. The interaction may also affect the efficacy profile, potentially leading to over-sedation or increased risk of falls, particularly in vulnerable populations.

Management and Precautions

When co-prescribing brexpiprazole and omeprazole, healthcare providers should monitor patients closely for increased brexpiprazole-related side effects, especially during the first few weeks of concurrent therapy. Consider starting with a lower brexpiprazole dose or reducing the current dose if omeprazole is added to existing brexpiprazole therapy. Regular assessment for extrapyramidal symptoms, sedation, and metabolic parameters is recommended. Alternative acid-suppressing medications with less CYP2D6 inhibition potential, such as pantoprazole or rabeprazole, may be considered if clinically appropriate. Patient education about potential side effects and the importance of reporting new or worsening symptoms is essential for safe concurrent use.

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.

Omeprazole interactions with food and lifestyle

Omeprazole should be taken on an empty stomach, preferably 30-60 minutes before meals, as food can significantly reduce its absorption and effectiveness. Alcohol consumption should be limited or avoided while taking omeprazole, as alcohol can increase stomach acid production and counteract the medication's acid-reducing effects. Additionally, alcohol may worsen gastroesophageal reflux disease (GERD) symptoms that omeprazole is treating. Smoking should be avoided or discontinued, as tobacco use increases stomach acid production and can reduce the effectiveness of omeprazole therapy. Patients should also be aware that omeprazole may interact with certain dietary supplements, particularly those containing magnesium, as long-term use of omeprazole can lead to magnesium deficiency.