Summary

The combination of erythromycin and voriconazole represents a significant drug interaction with increased risk of QT interval prolongation and potentially life-threatening cardiac arrhythmias. Both medications can independently prolong the QT interval, and their concurrent use may have additive effects on cardiac conduction.

Introduction

Erythromycin is a macrolide antibiotic commonly prescribed for respiratory tract infections, skin infections, and as an alternative for patients allergic to penicillin. It works by inhibiting bacterial protein synthesis and is known to have effects on cardiac conduction. Voriconazole is a triazole antifungal medication used to treat serious fungal infections, including invasive aspergillosis and candidemia. Both medications are metabolized through the cytochrome P450 system and have the potential to affect cardiac rhythm through QT interval prolongation.

Mechanism of Interaction

The interaction between erythromycin and voriconazole occurs through multiple mechanisms. Both drugs are known to block cardiac potassium channels (hERG channels), which can lead to QT interval prolongation on electrocardiogram. Additionally, both medications are substrates and inhibitors of the CYP3A4 enzyme system, potentially leading to increased plasma concentrations when used together. Erythromycin can also inhibit voriconazole metabolism, while voriconazole may affect erythromycin clearance, creating a bidirectional pharmacokinetic interaction that compounds the risk of adverse cardiac effects.

Risks and Symptoms

The primary clinical risk of combining erythromycin and voriconazole is the development of QT interval prolongation, which can progress to torsades de pointes, a potentially fatal ventricular arrhythmia. Patients at highest risk include those with pre-existing cardiac conditions, electrolyte imbalances (particularly hypokalemia or hypomagnesemia), elderly patients, and those with hepatic impairment. Additional risk factors include female gender, bradycardia, and concomitant use of other QT-prolonging medications. The interaction is considered clinically significant and may require alternative therapy or intensive cardiac monitoring.

Management and Precautions

Management of this drug interaction requires careful risk-benefit assessment and consideration of alternative therapies when possible. If concurrent use is absolutely necessary, obtain a baseline ECG and monitor QT interval regularly throughout treatment. Correct any electrolyte abnormalities, particularly potassium and magnesium levels, before initiating therapy. Consider dose reduction of one or both medications and monitor for signs of cardiac toxicity. Alternative antibiotics (such as azithromycin with caution, or non-macrolide options) or antifungal agents (such as fluconazole or echinocandins) should be considered when clinically appropriate. Patients should be counseled on symptoms of cardiac arrhythmias and advised to seek immediate medical attention for palpitations, dizziness, or syncope.

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.

Voriconazole interactions with food and lifestyle

Voriconazole should be taken on an empty stomach, at least 1 hour before or 2 hours after meals, as food significantly reduces absorption and bioavailability. High-fat meals can decrease voriconazole absorption by up to 22%. Patients should avoid grapefruit and grapefruit juice during treatment, as these can increase voriconazole blood levels and risk of toxicity. Alcohol consumption should be avoided or limited, as both voriconazole and alcohol are metabolized by the liver and concurrent use may increase the risk of liver toxicity. Patients should also avoid prolonged sun exposure and use adequate sun protection, as voriconazole can cause photosensitivity reactions and increase risk of skin cancer with long-term use.