Summary

Ketoconazole can significantly increase mometasone levels in the body by inhibiting its metabolism, potentially leading to enhanced corticosteroid effects and increased risk of systemic side effects. This interaction is particularly important when mometasone is used in higher doses or over large body surface areas.

Introduction

Mometasone is a potent synthetic corticosteroid available in various formulations including topical creams, nasal sprays, and inhalation products, primarily used to treat inflammatory conditions such as eczema, allergic rhinitis, and asthma. Ketoconazole is a broad-spectrum antifungal medication belonging to the azole class, commonly prescribed for fungal infections of the skin, nails, and systemic mycoses. Both medications are frequently prescribed and may be used concurrently in patients with multiple conditions.

Mechanism of Interaction

The interaction between mometasone and ketoconazole occurs through the inhibition of the cytochrome P450 3A4 (CYP3A4) enzyme system. Ketoconazole is a potent CYP3A4 inhibitor that significantly reduces the hepatic metabolism of mometasone. This inhibition leads to increased plasma concentrations and prolonged half-life of mometasone, resulting in enhanced and prolonged corticosteroid activity. The interaction is dose-dependent and can occur with both systemic and topical formulations of mometasone, particularly when applied to large surface areas or under occlusive conditions.

Risks and Symptoms

The primary clinical risks include increased systemic corticosteroid effects such as adrenal suppression, Cushing's syndrome, hyperglycemia, hypertension, and increased susceptibility to infections. Patients may experience mood changes, sleep disturbances, and delayed wound healing. Long-term exposure to elevated mometasone levels can lead to bone density loss, growth suppression in children, and skin thinning. The risk is particularly elevated in patients using high-potency mometasone formulations, those with compromised skin barriers, or when applied to large body surface areas. Elderly patients and those with hepatic impairment may be at higher risk for significant interactions.

Management and Precautions

Healthcare providers should carefully monitor patients receiving both medications for signs of systemic corticosteroid effects. Consider reducing mometasone dose or frequency when ketoconazole is initiated, and monitor for symptoms of adrenal suppression, hyperglycemia, and hypertension. Regular assessment of HPA axis function may be warranted in long-term users. Patients should be educated about potential side effects and advised to report unusual symptoms. Alternative antifungal agents with less CYP3A4 inhibition potential may be considered when appropriate. If concurrent use is necessary, use the lowest effective dose of mometasone for the shortest duration possible, and consider more frequent clinical monitoring.

Ketoconazole interactions with food and lifestyle

Ketoconazole requires an acidic environment for optimal absorption. Take ketoconazole with food or an acidic beverage to enhance absorption. Avoid taking ketoconazole with antacids, H2 blockers, or proton pump inhibitors as these medications reduce stomach acid and significantly decrease ketoconazole absorption. If antacids must be used, take them at least 2 hours after ketoconazole. Alcohol should be avoided during ketoconazole treatment as both ketoconazole and alcohol can cause liver toxicity, and concurrent use may increase the risk of hepatotoxicity. Grapefruit juice may increase ketoconazole blood levels and should be avoided to prevent increased risk of side effects.