Summary

Lurasidone and diltiazem have a significant drug interaction due to diltiazem's inhibition of CYP3A4, which can substantially increase lurasidone blood levels. This interaction may lead to enhanced side effects and requires careful monitoring or dose adjustments when used together.

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. Diltiazem is a calcium channel blocker commonly prescribed for hypertension, angina, and certain heart rhythm disorders. It works by relaxing blood vessels and reducing the heart's workload by blocking calcium channels in cardiac and vascular smooth muscle.

Mechanism of Interaction

The interaction between lurasidone and diltiazem occurs through the cytochrome P450 enzyme system, specifically CYP3A4. Lurasidone is primarily metabolized by CYP3A4 enzymes in the liver. Diltiazem is a moderate inhibitor of CYP3A4, which means it can significantly reduce the metabolism of lurasidone. When diltiazem inhibits CYP3A4, lurasidone clearance is decreased, leading to increased plasma concentrations and prolonged elimination half-life of lurasidone. This pharmacokinetic interaction can result in lurasidone levels that are 2-3 times higher than normal.

Risks and Symptoms

The primary risk of this interaction is an increased likelihood of lurasidone-related adverse effects due to elevated drug concentrations. Patients may experience enhanced central nervous system effects including excessive sedation, dizziness, confusion, and increased risk of extrapyramidal symptoms such as tremor, rigidity, and tardive dyskinesia. Cardiovascular risks may include prolonged QT interval, orthostatic hypotension, and increased risk of arrhythmias. Metabolic side effects such as weight gain, hyperglycemia, and dyslipidemia may also be more pronounced. The interaction is considered clinically significant and requires careful management to prevent toxicity.

Management and Precautions

When lurasidone and diltiazem must be used together, several management strategies should be implemented. The lurasidone dose should typically be reduced by 50% when co-administered with moderate CYP3A4 inhibitors like diltiazem. Close monitoring for signs of lurasidone toxicity is essential, including regular assessment of neurological symptoms, vital signs, and ECG monitoring for QT prolongation. Patients should be educated about potential side effects and advised to report any new or worsening symptoms immediately. Consider alternative medications when possible - for diltiazem, alternatives might include amlodipine or other calcium channel blockers that don't significantly inhibit CYP3A4. Regular follow-up appointments should be scheduled to assess therapeutic response and monitor for adverse effects. Healthcare providers should always consult current prescribing information and consider individual patient factors when managing this interaction.

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.

Diltiazem interactions with food and lifestyle

Grapefruit and grapefruit juice should be avoided while taking diltiazem 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 the blood pressure-lowering effects of diltiazem and increase the risk of dizziness, fainting, and falls. Patients should also be cautious when standing up quickly or engaging in activities requiring alertness, as diltiazem can cause dizziness and lightheadedness, especially when starting treatment or increasing the dose.