Summary

The interaction between astemizole and erythromycin is considered severe and potentially life-threatening. Erythromycin inhibits the metabolism of astemizole, leading to dangerous accumulation that can cause serious cardiac arrhythmias including torsades de pointes.

Introduction

Astemizole is a long-acting, non-sedating H1 antihistamine that was previously used to treat allergic conditions such as allergic rhinitis and chronic urticaria. Due to serious cardiac safety concerns, astemizole has been withdrawn from most markets worldwide. Erythromycin is a macrolide antibiotic commonly prescribed to treat various bacterial infections including respiratory tract infections, skin infections, and sexually transmitted diseases. It belongs to the CYP3A4 inhibitor class of medications.

Mechanism of Interaction

The interaction occurs through erythromycin's potent inhibition of the cytochrome P450 3A4 (CYP3A4) enzyme system. Astemizole is primarily metabolized by CYP3A4 to its active metabolites. When erythromycin blocks this metabolic pathway, astemizole accumulates to toxic levels in the bloodstream. High concentrations of astemizole can block cardiac potassium channels, particularly the hERG (human ether-a-go-go-related gene) channels, leading to prolongation of the QT interval on electrocardiogram and predisposing patients to potentially fatal ventricular arrhythmias.

Risks and Symptoms

The primary risk of this drug interaction is the development of serious cardiac arrhythmias, particularly torsades de pointes, a potentially fatal form of ventricular tachycardia. Patients may experience symptoms such as dizziness, fainting, palpitations, or sudden cardiac arrest. The risk is dose-dependent and increases with higher concentrations of astemizole. Additional risk factors include female gender, advanced age, electrolyte imbalances (particularly hypokalemia and hypomagnesemia), underlying heart disease, and concurrent use of other QT-prolonging medications. This interaction has been associated with documented cases of sudden cardiac death.

Management and Precautions

Due to the severe nature of this interaction, concurrent use of astemizole and erythromycin should be completely avoided. If antibiotic treatment is necessary in patients taking astemizole, alternative antibiotics that do not inhibit CYP3A4 should be selected, such as azithromycin or certain beta-lactam antibiotics. If erythromycin is essential, astemizole should be discontinued and an alternative antihistamine chosen. Patients should be monitored with electrocardiograms for QT interval prolongation, and electrolyte levels should be corrected before starting either medication. Healthcare providers should counsel patients about the signs and symptoms of cardiac arrhythmias and advise immediate medical attention if these occur.

Erythromycin interactions with food and lifestyle

Erythromycin should be taken on an empty stomach (1 hour before or 2 hours after meals) for optimal absorption, as food can significantly reduce the drug's bioavailability. However, if gastrointestinal upset occurs, it may be taken with food to minimize stomach irritation, though this may reduce effectiveness. Alcohol consumption should be avoided or limited while taking erythromycin, as it may increase the risk of gastrointestinal side effects and potentially reduce the antibiotic's effectiveness. Patients should also avoid taking erythromycin with dairy products or calcium-fortified foods within 2 hours of dosing, as calcium can interfere with absorption.