Summary

The combination of methylergonovine and itraconazole represents a significant drug interaction that can lead to serious ergot toxicity. Itraconazole, a potent CYP3A4 inhibitor, can dramatically increase methylergonovine levels, potentially causing life-threatening vasoconstriction and ergotism.

Introduction

Methylergonovine is an ergot alkaloid medication primarily used to prevent and treat postpartum hemorrhage by causing uterine contractions and vasoconstriction. It belongs to the class of ergot derivatives and is commonly administered after childbirth or abortion procedures. Itraconazole is a triazole antifungal medication used to treat various fungal infections, including aspergillosis, blastomycosis, and histoplasmosis. As a potent inhibitor of the cytochrome P450 3A4 (CYP3A4) enzyme system, itraconazole can significantly affect the metabolism of many co-administered medications.

Mechanism of Interaction

The interaction between methylergonovine and itraconazole occurs through inhibition of the CYP3A4 enzyme system. Methylergonovine is primarily metabolized by CYP3A4 enzymes in the liver. When itraconazole is co-administered, it acts as a potent competitive inhibitor of CYP3A4, significantly reducing the clearance of methylergonovine from the body. This inhibition leads to elevated plasma concentrations of methylergonovine, prolonged half-life, and enhanced pharmacological effects. The result is an increased risk of ergot toxicity, characterized by excessive vasoconstriction of peripheral and coronary arteries.

Risks and Symptoms

The primary clinical risk of this interaction is ergot toxicity (ergotism), which can manifest as severe peripheral vasoconstriction leading to ischemia of extremities, coronary artery spasm, hypertension, and potentially life-threatening cardiovascular complications. Patients may experience symptoms including severe headache, nausea, vomiting, numbness or tingling in fingers and toes, muscle pain, and in severe cases, gangrene of extremities. The interaction is considered contraindicated due to the potential for serious adverse outcomes. Even short-term co-administration can result in clinically significant increases in methylergonovine exposure, making this a high-severity drug interaction that requires immediate attention.

Management and Precautions

The co-administration of methylergonovine and itraconazole should be avoided whenever possible. If antifungal treatment is necessary in patients requiring methylergonovine, alternative antifungal agents that do not significantly inhibit CYP3A4, such as fluconazole (at lower doses) or terbinafine, should be considered. If the combination cannot be avoided due to clinical necessity, extreme caution is required with close monitoring for signs of ergot toxicity, including peripheral circulation checks, blood pressure monitoring, and assessment for neurological symptoms. Healthcare providers should educate patients about the signs and symptoms of ergotism and advise immediate medical attention if symptoms occur. The timing of administration should be carefully considered, and the lowest effective doses should be used for the shortest duration possible.

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.