Summary

Ritonavir significantly increases mometasone levels by inhibiting CYP3A4 metabolism, potentially leading to systemic corticosteroid effects including Cushing's syndrome and adrenal suppression. This interaction requires careful monitoring and possible dose adjustments or alternative therapy selection.

Introduction

Mometasone is a potent synthetic corticosteroid used topically for inflammatory skin conditions, intranasally for allergic rhinitis, and by inhalation for asthma management. It belongs to the class of glucocorticoids and is designed to have minimal systemic absorption when used as directed. Ritonavir is a protease inhibitor primarily used in HIV treatment regimens, often as a pharmacokinetic booster for other antiretroviral medications due to its potent inhibition of cytochrome P450 enzymes, particularly CYP3A4.

Mechanism of Interaction

The interaction between mometasone and ritonavir occurs through ritonavir's potent inhibition of the CYP3A4 enzyme system. Mometasone is extensively metabolized by CYP3A4, and when this pathway is blocked by ritonavir, mometasone clearance is significantly reduced. This leads to increased systemic exposure to mometasone, even when administered topically or by inhalation. The inhibition can increase mometasone plasma concentrations by several-fold, converting what is typically a locally-acting medication into one with significant systemic corticosteroid activity.

Risks and Symptoms

The primary clinical risk of this interaction is the development of systemic corticosteroid effects, including Cushing's syndrome, characterized by weight gain, moon face, buffalo hump, and metabolic disturbances. Patients may experience adrenal suppression, leading to hypothalamic-pituitary-adrenal axis dysfunction. Other significant risks include hyperglycemia, hypertension, osteoporosis, increased infection susceptibility, mood changes, and growth suppression in pediatric patients. The severity of these effects depends on the dose, duration of concurrent use, and individual patient factors.

Management and Precautions

Healthcare providers should consider alternative corticosteroids with less CYP3A4 dependence, such as beclomethasone or prednisolone, when possible. If mometasone must be continued, use the lowest effective dose and monitor closely for signs of systemic corticosteroid effects. Regular monitoring should include blood glucose, blood pressure, bone density assessments, and evaluation for Cushing's syndrome symptoms. Patients should be educated about potential side effects and advised to report any concerning symptoms. Gradual tapering may be necessary when discontinuing mometasone to prevent adrenal insufficiency. Consider consultation with an endocrinologist for complex cases involving adrenal suppression.

Ritonavir interactions with food and lifestyle

Ritonavir should be taken with food to improve absorption and reduce gastrointestinal side effects. Taking ritonavir on an empty stomach may result in decreased drug levels and reduced effectiveness. Alcohol consumption should be avoided or limited while taking ritonavir, as both can cause liver toxicity and the combination may increase the risk of hepatic adverse effects. Patients should also avoid grapefruit juice, as it may affect the metabolism of ritonavir through CYP3A4 inhibition, potentially leading to increased drug levels and toxicity. St. John's wort should be strictly avoided as it significantly reduces ritonavir levels by inducing CYP3A4, which can lead to treatment failure and development of drug resistance.