Summary

Methylergonovine and indinavir have a significant drug interaction due to indinavir's potent inhibition of CYP3A4, which can lead to increased methylergonovine levels and risk of ergot toxicity. This combination is generally contraindicated due to the potential for serious cardiovascular and peripheral vascular 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 metabolized primarily through the CYP3A4 enzyme system. Indinavir is a protease inhibitor antiretroviral medication used in the treatment of HIV infection. As a potent CYP3A4 inhibitor, indinavir can significantly affect the metabolism of drugs that are substrates of this enzyme system, including ergot alkaloids like methylergonovine.

Mechanism of Interaction

The interaction between methylergonovine and indinavir occurs through cytochrome P450 3A4 (CYP3A4) enzyme inhibition. Indinavir is a potent inhibitor of CYP3A4, the primary enzyme responsible for metabolizing methylergonovine. When indinavir inhibits CYP3A4, it significantly reduces the clearance of methylergonovine, leading to elevated plasma concentrations of the ergot alkaloid. This pharmacokinetic interaction can result in prolonged and intensified ergot effects, as the normal metabolic pathway for methylergonovine elimination is impaired.

Risks and Symptoms

The primary risk of combining methylergonovine with indinavir is ergot toxicity, which can manifest as severe vasoconstriction affecting both peripheral and coronary circulation. Clinical manifestations may include peripheral ischemia, gangrene of fingers and toes, coronary artery spasm leading to myocardial infarction, and severe hypertension. Additional risks include cerebral ischemia, renal artery spasm, and potential for life-threatening cardiovascular events. The interaction is considered clinically significant and potentially life-threatening, warranting strict avoidance of concurrent use.

Management and Precautions

The combination of methylergonovine and indinavir is contraindicated and should be avoided. If ergot alkaloid therapy is necessary in a patient taking indinavir, alternative uterotonic agents such as oxytocin or carboprost should be considered. Healthcare providers should review all medications before prescribing methylergonovine to HIV-positive patients. If inadvertent co-administration occurs, immediate discontinuation of methylergonovine is recommended, with close monitoring for signs of ergot toxicity including peripheral circulation, blood pressure, and cardiac function. Emergency medical intervention may be required if ergot toxicity develops.

Indinavir interactions with food and lifestyle

Indinavir should be taken on an empty stomach, at least 1 hour before or 2 hours after meals, for optimal absorption. However, if gastrointestinal upset occurs, it may be taken with a light meal that is low in fat, calories, and protein. High-fat meals can significantly reduce indinavir absorption and effectiveness. Patients should maintain adequate hydration by drinking at least 1.5 liters (approximately 6 glasses) of water daily to prevent kidney stone formation, a known side effect of indinavir. Grapefruit juice should be avoided as it may increase indinavir blood levels and potentially increase the risk of side effects. St. John's wort should be strictly avoided as it can significantly reduce indinavir blood levels and lead to treatment failure and potential development of drug resistance.