Summary

Clarithromycin significantly increases fluticasone exposure by inhibiting CYP3A4 metabolism, potentially leading to systemic corticosteroid effects including adrenal suppression. This interaction is considered clinically significant and requires careful monitoring or alternative therapy selection.

Introduction

Fluticasone is a synthetic corticosteroid commonly used as an inhaled medication for asthma and allergic rhinitis, and as a topical treatment for inflammatory skin conditions. It belongs to the glucocorticoid class and works by reducing inflammation in the airways and tissues. Clarithromycin is a macrolide antibiotic used to treat various bacterial infections including respiratory tract infections, skin infections, and Helicobacter pylori eradication. Both medications are frequently prescribed, making their potential interaction clinically relevant.

Mechanism of Interaction

The interaction occurs through clarithromycin's potent inhibition of the cytochrome P450 3A4 (CYP3A4) enzyme system. Fluticasone is extensively metabolized by CYP3A4 in the liver, with this pathway being the primary route of elimination. When clarithromycin inhibits CYP3A4, it significantly reduces fluticasone clearance, leading to increased systemic exposure to the corticosteroid. This can result in plasma fluticasone concentrations that are several times higher than normal, potentially causing systemic corticosteroid effects despite the medication being administered locally (inhaled or topical).

Risks and Symptoms

The primary risk of this interaction is the development of systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression. Patients may experience symptoms such as weight gain, moon face, purple striae, muscle weakness, mood changes, and increased susceptibility to infections. Adrenal suppression can be particularly dangerous as it may lead to adrenal crisis if steroids are suddenly discontinued. Additional risks include hyperglycemia, hypertension, osteoporosis, and growth suppression in children. The interaction is most significant with inhaled and intranasal fluticasone formulations, as topical applications typically have lower systemic absorption.

Management and Precautions

Healthcare providers should avoid concurrent use of clarithromycin with fluticasone when possible, especially for prolonged treatment courses. If co-administration is necessary, consider using alternative antibiotics such as azithromycin or doxycycline that do not significantly inhibit CYP3A4. If the combination cannot be avoided, use the lowest effective dose of fluticasone for the shortest duration possible, and monitor patients closely for signs of systemic corticosteroid effects. Regular monitoring should include assessment of adrenal function, blood glucose levels, blood pressure, and growth parameters in children. Patients should be educated about the signs and symptoms of steroid excess and advised to seek medical attention if these occur.

Clarithromycin interactions with food and lifestyle

Clarithromycin can be taken with or without food. However, taking clarithromycin with food may help reduce stomach upset and gastrointestinal side effects. Grapefruit juice should be avoided as it may increase clarithromycin blood levels and potentially increase the risk of side effects. Alcohol does not have a direct interaction with clarithromycin, but it's generally recommended to limit alcohol consumption while taking antibiotics to support immune system function and recovery.