Summary

Methylergonovine and efavirenz have a significant drug interaction due to efavirenz's inhibition of CYP3A4 metabolism. This interaction can lead to increased methylergonovine levels, potentially causing ergotism and serious cardiovascular complications.

Introduction

Methylergonovine is an ergot alkaloid medication primarily used to prevent and treat postpartum hemorrhage by causing uterine contractions. It belongs to the class of ergot derivatives and is commonly administered after childbirth or abortion. Efavirenz is a non-nucleoside reverse transcriptase inhibitor (NNRTI) used as part of combination antiretroviral therapy for HIV-1 infection. It works by blocking the reverse transcriptase enzyme, preventing HIV replication in infected cells.

Mechanism of Interaction

The interaction between methylergonovine and efavirenz occurs through cytochrome P450 enzyme inhibition. Efavirenz is a moderate inhibitor of CYP3A4, the primary enzyme responsible for metabolizing methylergonovine. When efavirenz inhibits CYP3A4, it reduces the clearance of methylergonovine, leading to increased plasma concentrations and prolonged half-life. This pharmacokinetic interaction can result in enhanced and prolonged ergot effects, potentially reaching toxic levels.

Risks and Symptoms

The primary clinical risk of this interaction is ergotism, a serious condition characterized by severe vasoconstriction and potential tissue necrosis. Patients may experience peripheral ischemia, coronary artery spasm, cerebral vasoconstriction, and hypertensive episodes. Symptoms can include severe headaches, nausea, vomiting, numbness or tingling in extremities, muscle pain, and in severe cases, gangrene of fingers or toes. The interaction is considered clinically significant and may require immediate medical intervention if signs of ergot toxicity develop.

Management and Precautions

Concurrent use of methylergonovine and efavirenz should generally be avoided due to the high risk of serious adverse effects. If methylergonovine is absolutely necessary in a patient taking efavirenz, consider alternative uterotonic agents such as oxytocin or misoprostol. If no alternatives are available, use the lowest effective dose of methylergonovine for the shortest duration possible, with close monitoring for signs of ergotism including peripheral circulation, blood pressure, and neurological symptoms. Patients should be counseled to report any unusual symptoms immediately, and healthcare providers should have protocols in place for rapid intervention if ergot toxicity occurs.