Summary

Lurasidone and verapamil have a significant drug interaction that can lead to dangerously increased lurasidone levels in the blood. This interaction occurs because verapamil strongly inhibits the CYP3A4 enzyme responsible for metabolizing lurasidone, potentially causing severe side effects.

Introduction

Lurasidone (brand name Latuda) is an atypical antipsychotic medication primarily used to treat schizophrenia and bipolar depression. It belongs to the benzisothiazol class of antipsychotics and works by modulating dopamine and serotonin receptors in the brain. Verapamil is a calcium channel blocker commonly prescribed for hypertension, angina, and certain heart rhythm disorders. It works by blocking calcium channels in blood vessels and heart muscle, leading to vasodilation and reduced cardiac workload.

Mechanism of Interaction

The interaction between lurasidone and verapamil occurs through inhibition of the cytochrome P450 3A4 (CYP3A4) enzyme system. Lurasidone is primarily metabolized by CYP3A4 enzymes in the liver and intestines. Verapamil is a strong CYP3A4 inhibitor that significantly reduces the metabolism of lurasidone, leading to substantially increased plasma concentrations of the antipsychotic. This can result in lurasidone levels that are 9-fold higher than normal, dramatically increasing the risk of adverse effects.

Risks and Symptoms

The primary risk of this interaction is severe lurasidone toxicity due to dramatically elevated drug levels. Patients may experience increased extrapyramidal symptoms (muscle stiffness, tremors, involuntary movements), sedation, orthostatic hypotension, and potential cardiac effects including QT prolongation. The interaction is considered contraindicated due to the significant increase in lurasidone exposure, which can lead to serious adverse events including tardive dyskinesia, neuroleptic malignant syndrome, and cardiovascular complications.

Management and Precautions

Concurrent use of lurasidone and verapamil is generally contraindicated and should be avoided. If both medications are clinically necessary, alternative treatments should be considered. For verapamil, alternatives might include other antihypertensive agents that don't significantly inhibit CYP3A4, such as amlodipine or diltiazem (though diltiazem is also a moderate CYP3A4 inhibitor). For lurasidone, alternative antipsychotics with different metabolic pathways may be considered. If no alternatives exist, extreme caution is required with frequent monitoring, potential lurasidone dose reduction, and close observation for signs of toxicity.

Lurasidone interactions with food and lifestyle

Lurasidone should be taken with food (at least 350 calories) to ensure proper absorption and effectiveness. Taking lurasidone on an empty stomach can significantly reduce drug absorption by approximately 50%. Patients should avoid grapefruit and grapefruit juice while taking lurasidone, as grapefruit can increase lurasidone blood levels and potentially increase the risk of side effects. Alcohol should be avoided or limited while taking lurasidone, as it may increase drowsiness, dizziness, and impair judgment and motor skills.

Verapamil interactions with food and lifestyle

Grapefruit and grapefruit juice should be avoided while taking verapamil as they can significantly increase blood levels of the medication, potentially leading to dangerous drops in blood pressure and heart rate. Alcohol consumption should be limited or avoided as it can enhance verapamil's blood pressure-lowering effects and increase the risk of dizziness, fainting, and falls. High-fiber foods or fiber supplements may reduce verapamil absorption when taken at the same time, so it's recommended to separate their administration by at least 2 hours.