Summary

Erythromycin significantly increases fluticasone levels by inhibiting the CYP3A4 enzyme responsible for fluticasone metabolism. This interaction can lead to systemic corticosteroid effects and adrenal suppression, particularly with inhaled or nasal fluticasone formulations.

Introduction

Fluticasone is a synthetic corticosteroid widely used for treating asthma, allergic rhinitis, and inflammatory skin conditions. It's available in inhaled, nasal spray, and topical formulations and works by reducing inflammation in the airways and tissues. Erythromycin is a macrolide antibiotic used to treat various bacterial infections, including respiratory tract infections, skin infections, and as an alternative for patients allergic to penicillin. Both medications are commonly prescribed, making their potential interaction clinically relevant.

Mechanism of Interaction

The interaction between fluticasone and erythromycin occurs through cytochrome P450 3A4 (CYP3A4) enzyme inhibition. Fluticasone is extensively metabolized by CYP3A4 in the liver and intestines, which normally results in rapid clearance and minimal systemic exposure. Erythromycin is a potent CYP3A4 inhibitor that significantly reduces fluticasone metabolism, leading to increased plasma concentrations and prolonged exposure to the corticosteroid. This mechanism is particularly important for inhaled and intranasal fluticasone, where systemic absorption is normally minimal but can become clinically significant when metabolism is impaired.

Risks and Symptoms

The primary risk of this interaction is the development of systemic corticosteroid effects due to elevated fluticasone levels. Patients may experience Cushing's syndrome symptoms, including moon face, weight gain, muscle weakness, and mood changes. Adrenal suppression is a serious concern, potentially leading to adrenal crisis if fluticasone is suddenly discontinued. Other risks include increased susceptibility to infections, delayed wound healing, osteoporosis, hyperglycemia, and hypertension. The risk is highest with inhaled fluticasone propionate and intranasal formulations, where cases of severe systemic effects have been reported. Patients with hepatic impairment or those receiving high doses of fluticasone are at increased risk.

Management and Precautions

When concurrent use is necessary, consider using alternative antibiotics that don't inhibit CYP3A4, such as azithromycin or doxycycline. If erythromycin must be used with fluticasone, reduce the fluticasone dose and duration to the minimum effective amount. Monitor patients closely for signs of systemic corticosteroid effects, including blood glucose levels, blood pressure, and signs of adrenal suppression. Consider switching to a corticosteroid with less CYP3A4 dependence, such as beclomethasone or budesonide. Educate patients about potential symptoms and advise them to report any unusual side effects. For long-term erythromycin therapy, evaluate the need for continued fluticasone use and consider gradual dose reduction under medical supervision to prevent adrenal insufficiency.

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.