Summary
Itraconazole may increase medroxyprogesterone levels by inhibiting CYP3A4 metabolism, potentially leading to enhanced progestogenic effects. This interaction is considered moderate and requires careful monitoring when these medications are used concurrently.
Introduction
Itraconazole is a triazole antifungal medication commonly prescribed for systemic fungal infections, including aspergillosis, blastomycosis, and histoplasmosis. It works by inhibiting fungal cytochrome P450 enzymes, particularly 14α-demethylase. Medroxyprogesterone is a synthetic progestin used in various formulations including contraceptive injections (Depo-Provera), hormone replacement therapy, and treatment of endometrial disorders. Both medications are metabolized through the cytochrome P450 system, creating potential for drug interactions.
Mechanism of Interaction
The interaction between itraconazole and medroxyprogesterone occurs through cytochrome P450 enzyme inhibition, specifically CYP3A4. Itraconazole is a potent inhibitor of CYP3A4, the primary enzyme responsible for metabolizing medroxyprogesterone. When itraconazole inhibits this metabolic pathway, it reduces the clearance of medroxyprogesterone, leading to increased plasma concentrations and prolonged half-life of the progestin. This mechanism can result in enhanced and prolonged progestogenic effects.
Risks and Symptoms
The primary clinical risks of this interaction include enhanced progestogenic side effects such as increased breakthrough bleeding, mood changes, weight gain, and potential thrombotic events. Patients may experience more pronounced hormonal side effects including breast tenderness, headaches, and changes in menstrual patterns. For patients using medroxyprogesterone as contraception, the interaction may theoretically increase contraceptive efficacy but also increase the risk of adverse effects. Long-term exposure to elevated progestin levels may increase risks of mood disorders, metabolic changes, and cardiovascular complications in susceptible individuals.
Management and Precautions
Healthcare providers should monitor patients closely when prescribing itraconazole to those already taking medroxyprogesterone. Consider dose reduction of medroxyprogesterone if clinically appropriate, particularly for non-contraceptive indications. Monitor for signs of enhanced progestogenic effects including mood changes, breakthrough bleeding, breast tenderness, and weight gain. Assess cardiovascular risk factors and monitor blood pressure regularly. For patients on long-term itraconazole therapy, consider alternative antifungal agents with less CYP3A4 inhibition if clinically suitable. Educate patients about potential side effects and advise them to report any concerning symptoms promptly. Regular follow-up appointments should be scheduled to assess treatment response and monitor for adverse effects.
Itraconazole interactions with food and lifestyle
Itraconazole should be taken with food to enhance absorption and bioavailability. The capsule formulation requires an acidic environment for optimal absorption, so it should be taken with a full meal or acidic beverage. Avoid taking itraconazole with antacids, H2 blockers, or proton pump inhibitors as these reduce stomach acid and significantly decrease drug absorption. Grapefruit juice should be avoided as it can increase itraconazole levels and risk of side effects. Alcohol should be used with caution as both itraconazole and alcohol can affect liver function.
