Summary

Erlotinib can significantly increase warfarin's anticoagulant effects, leading to elevated INR levels and increased bleeding risk. This interaction requires careful monitoring and potential dose adjustments of warfarin when used concurrently with erlotinib.

Introduction

Erlotinib (Tarceva) is an oral tyrosine kinase inhibitor primarily used to treat non-small cell lung cancer and pancreatic cancer by blocking epidermal growth factor receptor (EGFR) signaling. Warfarin is a widely prescribed oral anticoagulant belonging to the vitamin K antagonist class, commonly used for preventing blood clots in conditions such as atrial fibrillation, deep vein thrombosis, and pulmonary embolism.

Mechanism of Interaction

Erlotinib inhibits cytochrome P450 enzymes, particularly CYP2C9, which is the primary enzyme responsible for metabolizing the more potent S-enantiomer of warfarin. By inhibiting CYP2C9, erlotinib reduces warfarin clearance, leading to increased plasma concentrations of warfarin and enhanced anticoagulant effects. This pharmacokinetic interaction results in prolonged prothrombin time and elevated International Normalized Ratio (INR) values.

Risks and Symptoms

The primary clinical risk of this interaction is significantly increased bleeding potential, including both minor bleeding (bruising, nosebleeds) and major bleeding events (gastrointestinal bleeding, intracranial hemorrhage). Patients may experience a rapid rise in INR levels within days of starting erlotinib, potentially reaching dangerous levels that require immediate medical attention. The interaction can be unpredictable and may vary between patients based on individual metabolic factors and baseline warfarin sensitivity.

Management and Precautions

Close monitoring of INR levels is essential when initiating erlotinib in patients taking warfarin, with more frequent testing recommended during the first few weeks. Consider checking INR within 3-5 days of starting erlotinib and then weekly until stable. Warfarin dose reduction may be necessary, typically by 10-25% initially, with further adjustments based on INR results. Patients should be educated about bleeding signs and symptoms and advised to report any unusual bleeding immediately. Alternative anticoagulation options, such as direct oral anticoagulants (DOACs), may be considered in consultation with oncology and cardiology teams, though these also require careful evaluation for potential interactions.

Erlotinib interactions with food and lifestyle

Erlotinib should be taken on an empty stomach, at least 1 hour before or 2 hours after eating, as food significantly reduces absorption and effectiveness. Grapefruit juice should be avoided as it may increase erlotinib levels and risk of side effects. Smoking tobacco significantly reduces erlotinib effectiveness and patients are strongly advised to quit smoking during treatment. Proton pump inhibitors (PPIs) and H2 receptor antagonists should be avoided or used with caution as they reduce stomach acid needed for proper erlotinib absorption.

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.