Summary

Abiraterone may increase warfarin's anticoagulant effects, potentially leading to increased bleeding risk. This interaction requires careful monitoring of INR levels and possible warfarin dose adjustments when used concurrently.

Introduction

Abiraterone acetate is an androgen biosynthesis inhibitor primarily used to treat metastatic castration-resistant prostate cancer. It works by blocking CYP17A1, an enzyme crucial for androgen production. Warfarin is a vitamin K antagonist anticoagulant commonly prescribed to prevent blood clots in conditions such as atrial fibrillation, deep vein thrombosis, and pulmonary embolism. Both medications are frequently prescribed in older male patients, making their potential interaction clinically relevant.

Mechanism of Interaction

The interaction between abiraterone and warfarin likely occurs through multiple mechanisms. Abiraterone may inhibit cytochrome P450 enzymes, particularly CYP2C9, which is responsible for warfarin metabolism. This inhibition can lead to decreased warfarin clearance and increased plasma concentrations of the more potent S-warfarin enantiomer. Additionally, abiraterone's effects on hepatic function and protein synthesis may alter warfarin's pharmacokinetics and pharmacodynamics, potentially enhancing its anticoagulant effects.

Risks and Symptoms

The primary clinical risk of this interaction is an increased risk of bleeding complications, ranging from minor bruising to life-threatening hemorrhages. Patients may experience prolonged International Normalized Ratio (INR) values, indicating enhanced anticoagulation beyond the therapeutic range. This can manifest as gastrointestinal bleeding, intracranial hemorrhage, or excessive bleeding from minor injuries. The risk is particularly concerning in elderly patients who may already have multiple bleeding risk factors and comorbidities.

Management and Precautions

When abiraterone and warfarin are used concurrently, implement frequent INR monitoring, especially during the first few weeks of combination therapy. Check INR levels more frequently than usual (potentially weekly initially, then bi-weekly) and adjust warfarin dosing as needed to maintain therapeutic range. Educate patients about bleeding signs and symptoms, including unusual bruising, prolonged bleeding from cuts, blood in urine or stool, and severe headaches. Consider alternative anticoagulation strategies if bleeding risk becomes unacceptable. Coordinate care between oncology and anticoagulation management teams to ensure optimal monitoring and dose adjustments.

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.