Summary

Aprepitant significantly interacts with warfarin by inhibiting CYP2C9 metabolism, leading to increased warfarin levels and enhanced anticoagulant effects. This interaction requires careful monitoring of INR levels and potential warfarin dose adjustments to prevent bleeding complications.

Introduction

Aprepitant (brand name Emend) is a neurokinin-1 (NK1) receptor antagonist primarily used to prevent chemotherapy-induced nausea and vomiting. It belongs to the class of antiemetic medications and is commonly prescribed as part of combination antiemetic regimens for cancer patients. Warfarin is an oral anticoagulant medication belonging to the vitamin K antagonist class, widely used for preventing and treating thromboembolic disorders such as atrial fibrillation, deep vein thrombosis, and pulmonary embolism.

Mechanism of Interaction

The interaction between aprepitant and warfarin occurs through cytochrome P450 enzyme inhibition. Aprepitant is a moderate inhibitor of CYP2C9, the primary enzyme responsible for metabolizing the more potent S-enantiomer of warfarin. When aprepitant inhibits CYP2C9, it reduces warfarin metabolism, leading to increased plasma concentrations of warfarin and prolonged anticoagulant effects. This mechanism can result in elevated International Normalized Ratio (INR) values and increased bleeding risk.

Risks and Symptoms

The primary clinical risk of this interaction is an increased bleeding tendency due to enhanced anticoagulation. Patients may experience prolonged INR values, which can lead to serious bleeding complications including gastrointestinal bleeding, intracranial hemorrhage, or excessive bruising. The interaction is particularly concerning because aprepitant is often used in cancer patients who may already have increased bleeding risks due to thrombocytopenia or other chemotherapy-related effects. The onset of this interaction typically occurs within 2-3 days of starting aprepitant and may persist for several days after discontinuation.

Management and Precautions

Close monitoring of INR levels is essential when aprepitant and warfarin are used concurrently. INR should be checked more frequently than usual, typically within 2-3 days of starting aprepitant and again 7-10 days after completing the aprepitant course. Healthcare providers should consider reducing the warfarin dose by 25-50% when initiating aprepitant therapy, with subsequent dose adjustments based on INR results. Patients should be educated about signs and symptoms of bleeding and advised to report any unusual bruising, bleeding, or other concerning symptoms immediately. Alternative antiemetic options that do not significantly interact with warfarin should be considered when clinically appropriate.

Warfarin interactions with food and lifestyle

Warfarin has significant interactions with vitamin K-rich foods (such as leafy green vegetables like spinach, kale, broccoli, and Brussels sprouts) that can reduce its effectiveness. Patients should maintain consistent vitamin K intake rather than avoiding these foods entirely. Alcohol consumption can increase bleeding risk and should be limited or avoided. Cranberry juice and cranberry products may enhance warfarin's effects and increase bleeding risk. Large amounts of green tea may also interfere with warfarin effectiveness. Patients should avoid major dietary changes and consult their healthcare provider before making significant modifications to their diet or alcohol consumption patterns.