Summary

Posaconazole significantly increases fluticasone levels by inhibiting CYP3A4 metabolism, potentially leading to systemic corticosteroid effects including adrenal suppression and Cushing's syndrome. This interaction requires careful monitoring and possible dose adjustments.

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. Posaconazole is a triazole antifungal medication used to prevent and treat serious fungal infections, particularly in immunocompromised patients. It works by inhibiting fungal cell membrane synthesis and is known to be a potent inhibitor of the cytochrome P450 3A4 (CYP3A4) enzyme system.

Mechanism of Interaction

The interaction between fluticasone and posaconazole occurs through competitive inhibition of the CYP3A4 enzyme system. Fluticasone is extensively metabolized by CYP3A4 in the liver, which normally results in rapid clearance and minimal systemic exposure when used topically or by inhalation. Posaconazole is a potent CYP3A4 inhibitor that significantly reduces fluticasone metabolism, leading to increased plasma concentrations and prolonged half-life. This results in enhanced systemic corticosteroid activity, as the normal first-pass metabolism that limits fluticasone's systemic effects is impaired.

Risks and Symptoms

The primary clinical risk of this interaction is the development of systemic corticosteroid effects due to elevated fluticasone levels. Patients may experience Cushing's syndrome symptoms including weight gain, moon face, buffalo hump, purple striae, and muscle weakness. Adrenal suppression is a significant concern, potentially leading to adrenal insufficiency if treatment is discontinued abruptly. Other risks include hyperglycemia, hypertension, osteoporosis, increased infection susceptibility, and growth suppression in pediatric patients. The interaction is particularly concerning with inhaled or intranasal fluticasone, as these routes typically have minimal systemic exposure under normal circumstances.

Management and Precautions

Healthcare providers should exercise caution when co-prescribing these medications and consider alternative treatments when possible. If concurrent use is necessary, patients require close monitoring for signs of corticosteroid excess, including regular assessment of blood pressure, blood glucose, and signs of Cushing's syndrome. Consider reducing fluticasone dose or switching to a corticosteroid with less CYP3A4 dependence, such as beclomethasone. Monitor adrenal function, especially with prolonged concurrent therapy. Educate patients about symptoms of steroid excess and the importance of not discontinuing fluticasone abruptly. Regular follow-up appointments should be scheduled to assess treatment response and monitor for adverse effects. If posaconazole is discontinued, fluticasone levels will return to normal, but this process may take several days to weeks.

Posaconazole interactions with food and lifestyle

Posaconazole should be taken with food or a nutritional supplement to enhance absorption, as food significantly increases bioavailability. The delayed-release tablet formulation should be taken with food, while the oral suspension should be taken with a full meal or liquid nutritional supplement. Avoid taking posaconazole on an empty stomach as this can result in significantly reduced drug levels and potential treatment failure. Patients should also avoid antacids, proton pump inhibitors, and H2-receptor antagonists when possible, as these medications can reduce posaconazole absorption by increasing gastric pH.