Summary

The interaction between ziprasidone and lansoprazole is primarily of moderate clinical significance due to potential QT interval prolongation. While lansoprazole may slightly increase ziprasidone plasma levels through CYP2C19 inhibition, the main concern is the additive risk of cardiac arrhythmias when these medications are used together.

Introduction

Ziprasidone is an atypical antipsychotic medication primarily used to treat schizophrenia and bipolar disorder. It belongs to the benzisothiazole class and works by blocking dopamine D2 and serotonin 5-HT2A receptors. Lansoprazole 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 ziprasidone and lansoprazole occurs through multiple mechanisms. Lansoprazole is a moderate inhibitor of CYP2C19, an enzyme involved in ziprasidone metabolism, which may lead to slightly increased ziprasidone plasma concentrations. More importantly, both medications have the potential to prolong the QT interval on electrocardiogram. Ziprasidone blocks cardiac potassium channels (hERG channels), while lansoprazole can cause hypomagnesemia, which indirectly affects cardiac repolarization and may contribute to QT prolongation.

Risks and Symptoms

The primary clinical risk of combining ziprasidone and lansoprazole is an increased potential for QT interval prolongation and subsequent cardiac arrhythmias, including torsades de pointes. This risk is particularly elevated in patients with pre-existing cardiac conditions, electrolyte imbalances (especially hypokalemia or hypomagnesemia), or those taking other QT-prolonging medications. The metabolic interaction may result in slightly elevated ziprasidone levels, potentially increasing the risk of extrapyramidal side effects or other ziprasidone-related adverse events, though this effect is generally considered mild to moderate.

Management and Precautions

When ziprasidone and lansoprazole are used concurrently, obtain a baseline ECG and monitor for QT prolongation, especially during treatment initiation or dose changes. Regular monitoring of serum electrolytes, particularly magnesium and potassium levels, is recommended. Consider alternative acid suppression therapy if clinically appropriate, such as H2 receptor antagonists, which have less potential for drug interactions. If continuation of both medications is necessary, use the lowest effective doses and maintain close clinical monitoring. Patients should be educated about symptoms of cardiac arrhythmias and advised to seek immediate medical attention if they experience palpitations, dizziness, or syncope.

Ziprasidone interactions with food and lifestyle

Ziprasidone should be taken with food to optimize absorption and bioavailability. Taking ziprasidone on an empty stomach can reduce absorption by approximately 50%. Patients should be advised to take ziprasidone with meals or within 2 hours of eating. Alcohol should be avoided or used with extreme caution while taking ziprasidone, as both substances can cause sedation and may increase the risk of falls, impaired judgment, and respiratory depression. The combination may also worsen side effects such as dizziness and drowsiness.

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.