Summary

Methylergonovine and delavirdine have a potentially serious drug interaction due to delavirdine's inhibition of CYP3A4 enzymes, which can lead to increased methylergonovine levels and risk of ergotism. This combination is generally contraindicated and requires careful clinical consideration.

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 uterotonic agents and is metabolized primarily through the CYP3A4 enzyme system. Delavirdine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) used in the treatment of HIV-1 infection. As a potent inhibitor of the CYP3A4 enzyme system, delavirdine can significantly affect the metabolism of drugs that are CYP3A4 substrates, including methylergonovine.

Mechanism of Interaction

The interaction between methylergonovine and delavirdine occurs through competitive inhibition of the CYP3A4 enzyme system. Delavirdine acts as a potent CYP3A4 inhibitor, significantly reducing the hepatic metabolism of methylergonovine. This inhibition leads to increased plasma concentrations and prolonged half-life of methylergonovine, potentially resulting in enhanced pharmacological effects. The reduced clearance of methylergonovine can lead to accumulation of the drug in the system, increasing the risk of dose-dependent adverse effects including vasoconstriction and ergotism.

Risks and Symptoms

The primary clinical risk of this interaction is the development of ergotism, a serious condition characterized by severe vasoconstriction, peripheral ischemia, and potential tissue necrosis. Patients may experience symptoms including severe headache, nausea, vomiting, numbness and tingling in extremities, muscle pain, and in severe cases, gangrene of fingers and toes. The interaction can also lead to dangerous elevations in blood pressure, coronary artery spasm, and cerebrovascular events. Due to the narrow therapeutic window of ergot alkaloids and the potent inhibitory effects of delavirdine on CYP3A4, even standard doses of methylergonovine may result in toxic levels when co-administered with delavirdine.

Management and Precautions

The concurrent use of methylergonovine and delavirdine is generally contraindicated due to the high risk of serious adverse events. If methylergonovine therapy is absolutely necessary in a patient taking delavirdine, alternative uterotonic agents such as oxytocin or carboprost should be strongly considered. If no alternatives are available, extreme caution must be exercised with significantly reduced methylergonovine doses, close monitoring for signs of ergotism, and frequent assessment of peripheral circulation. Healthcare providers should monitor for symptoms of vasoconstriction, check peripheral pulses, and assess for signs of ischemia. Patients should be educated about the signs and symptoms of ergotism and advised to seek immediate medical attention if they occur. The interaction may persist for several days after discontinuation of delavirdine due to its long half-life and irreversible enzyme inhibition.