Summary

Dofetilide and cimetidine have a significant drug interaction that can lead to dangerous increases in dofetilide blood levels. This interaction is considered contraindicated due to the high risk of life-threatening cardiac arrhythmias and QT prolongation.

Introduction

Dofetilide is a Class III antiarrhythmic medication primarily used to treat atrial fibrillation and atrial flutter by blocking potassium channels in the heart. Cimetidine is an H2 receptor antagonist commonly used to reduce stomach acid production for treating peptic ulcers, gastroesophageal reflux disease (GERD), and other acid-related conditions. Both medications are metabolized through different pathways, but their interaction occurs at the level of renal elimination.

Mechanism of Interaction

The interaction between dofetilide and cimetidine occurs through inhibition of renal tubular secretion. Cimetidine blocks the organic cation transport system in the kidneys, specifically inhibiting the renal elimination of dofetilide. Since dofetilide is primarily eliminated unchanged through the kidneys via active tubular secretion, cimetidine significantly reduces its clearance, leading to increased plasma concentrations and prolonged half-life of dofetilide.

Risks and Symptoms

The primary risk of this interaction is a significant increase in dofetilide plasma levels, which can lead to severe cardiac complications including torsades de pointes, a potentially fatal form of ventricular tachycardia. Elevated dofetilide levels increase the risk of QT interval prolongation, which can progress to life-threatening arrhythmias. Studies have shown that cimetidine can increase dofetilide exposure by up to 58%, making this interaction clinically significant and potentially dangerous for patients.

Management and Precautions

This drug combination is contraindicated and should be avoided entirely. If a patient requires both cardiac rhythm management and acid suppression therapy, alternative H2 receptor antagonists such as ranitidine, famotidine, or nizatidine should be considered, as they do not significantly affect dofetilide elimination. Proton pump inhibitors (PPIs) are also safe alternatives for acid suppression. Healthcare providers should thoroughly review all medications before initiating dofetilide therapy and ensure patients understand the importance of avoiding cimetidine during treatment.

Dofetilide interactions with food and lifestyle

Dofetilide should be taken consistently with regard to meals - either always with food or always without food. Grapefruit juice should be avoided as it may increase dofetilide blood levels and risk of dangerous heart rhythm abnormalities. Alcohol should be used with caution as it may worsen heart rhythm problems. Patients should maintain consistent potassium and magnesium levels through diet, as low levels of these electrolytes can increase the risk of serious arrhythmias with dofetilide.

Cimetidine interactions with food and lifestyle

Cimetidine should be taken with food or immediately after meals to reduce stomach upset and improve absorption. Alcohol consumption should be limited or avoided while taking cimetidine, as both substances can affect liver metabolism and may increase the risk of side effects. Smoking may reduce the effectiveness of cimetidine in treating ulcers and should be avoided or minimized during treatment. Caffeine intake should be moderated as cimetidine can increase caffeine levels in the blood, potentially leading to increased caffeine-related side effects such as jitteriness or insomnia.