Summary

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

Introduction

Gefitinib (Iressa) is an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor primarily used to treat non-small cell lung cancer (NSCLC) with specific EGFR mutations. 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 used in cancer patients, making this interaction clinically relevant.

Mechanism of Interaction

The interaction between gefitinib and warfarin occurs through multiple potential mechanisms. Gefitinib may inhibit cytochrome P450 enzymes, particularly CYP2C9, which is responsible for warfarin metabolism. This inhibition can lead to increased warfarin plasma concentrations and enhanced anticoagulant effects. Additionally, gefitinib may affect vitamin K metabolism or interfere with clotting factor synthesis, further potentiating warfarin's anticoagulant activity.

Risks and Symptoms

The primary risk of this interaction is an increased bleeding tendency, which can range from minor bruising to life-threatening hemorrhage. Patients may experience prolonged International Normalized Ratio (INR) values, indicating enhanced anticoagulation. Clinical manifestations may include gastrointestinal bleeding, intracranial hemorrhage, excessive bruising, prolonged bleeding from cuts, or unusual bleeding from mucous membranes. Cancer patients may be at particularly high risk due to their underlying condition and potential for thrombocytopenia.

Management and Precautions

When gefitinib and warfarin are used together, frequent INR monitoring is essential, especially during the first few weeks of concurrent therapy. INR should be checked more frequently than usual (potentially every 2-3 days initially, then weekly once stable). Warfarin dosage may need to be reduced based on INR results. Patients should be educated about bleeding signs and symptoms and advised to report any unusual bleeding immediately. Consider alternative anticoagulation strategies if the interaction proves difficult to manage. Healthcare providers should maintain close communication between oncology and anticoagulation management teams.

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.