Summary

Erythromycin can significantly increase fexofenadine plasma concentrations by inhibiting P-glycoprotein-mediated efflux transport. This interaction may lead to enhanced antihistamine effects and potential adverse reactions, requiring careful monitoring and possible dose adjustments.

Introduction

Fexofenadine is a second-generation antihistamine commonly used to treat allergic rhinitis and chronic urticaria. It belongs to the H1-receptor antagonist class and is preferred for its non-sedating properties. Erythromycin is a macrolide antibiotic used to treat various bacterial infections, including respiratory tract infections, skin infections, and sexually transmitted diseases. Both medications are frequently prescribed and may be used concurrently in patients with allergies who develop bacterial infections.

Mechanism of Interaction

The interaction between fexofenadine and erythromycin occurs through inhibition of P-glycoprotein (P-gp) transport. Fexofenadine is a substrate of P-glycoprotein, an efflux transporter that limits drug absorption in the intestine and facilitates elimination. Erythromycin acts as a P-glycoprotein inhibitor, reducing the efflux of fexofenadine from intestinal cells and decreasing its elimination. This results in increased bioavailability and elevated plasma concentrations of fexofenadine, potentially leading to enhanced pharmacological effects.

Risks and Symptoms

The primary clinical risk of this interaction is increased fexofenadine exposure, which may lead to enhanced antihistamine effects and potential adverse reactions. While fexofenadine has a wide therapeutic window, elevated levels could result in drowsiness, headache, dizziness, and gastrointestinal disturbances. The interaction is considered moderate in clinical significance, as serious adverse events are uncommon but monitoring is recommended. Patients with renal impairment may be at higher risk due to reduced fexofenadine clearance.

Management and Precautions

Monitor patients for increased antihistamine effects when erythromycin is co-administered with fexofenadine. Consider reducing the fexofenadine dose if excessive sedation or other adverse effects occur. Separate administration times by at least 2 hours when possible to minimize the interaction. Alternative antibiotics that do not significantly inhibit P-glycoprotein, such as azithromycin or clarithromycin, may be considered if clinically appropriate. Patients should be counseled about potential increased drowsiness and advised to avoid activities requiring alertness until the interaction effects are known.

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.