Summary

The interaction between brexpiprazole and lansoprazole is generally considered minor to moderate, primarily involving potential effects on drug metabolism through cytochrome P450 pathways. While lansoprazole may have minimal impact on brexpiprazole levels, careful monitoring is recommended when initiating or discontinuing either medication.

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. Lansoprazole (Prevacid) 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 hydrogen-potassium ATPase enzyme in gastric parietal cells, reducing stomach acid production.

Mechanism of Interaction

The potential interaction between brexpiprazole and lansoprazole occurs primarily through cytochrome P450 enzyme systems. Brexpiprazole is metabolized mainly by CYP3A4 and CYP2D6 enzymes, while lansoprazole is metabolized by CYP2C19 and CYP3A4. Lansoprazole can act as a weak inhibitor of CYP2C19 and may have minor effects on CYP3A4 activity. However, since brexpiprazole's primary metabolic pathway involves CYP2D6, the direct impact of lansoprazole on brexpiprazole metabolism is typically minimal. The interaction is further complicated by individual genetic variations in enzyme activity, particularly CYP2D6 polymorphisms.

Risks and Symptoms

The clinical significance of the brexpiprazole-lansoprazole interaction is generally low to moderate. Potential risks include slight alterations in brexpiprazole plasma concentrations, which could theoretically affect therapeutic efficacy or increase the risk of side effects. Patients may experience changes in antipsychotic effectiveness or an increased likelihood of adverse reactions such as extrapyramidal symptoms, sedation, or metabolic effects. Additionally, lansoprazole's effect on gastric pH may influence the absorption of other medications, though this is less relevant for brexpiprazole. The risk is higher in patients who are poor metabolizers of CYP2D6 or those taking multiple medications that affect these enzyme systems.

Management and Precautions

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.

Lansoprazole interactions with food and lifestyle

Lansoprazole 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 lansoprazole, 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 lansoprazole is intended to treat.