Summary

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

Introduction

Terbinafine is an oral antifungal medication belonging to the allylamine class, primarily used to treat fungal infections of the skin, hair, and nails, including onychomycosis and dermatophyte infections. Warfarin is an oral anticoagulant from the coumarin class that prevents blood clot formation by inhibiting vitamin K-dependent clotting factors, commonly prescribed for conditions such as atrial fibrillation, deep vein thrombosis, and pulmonary embolism.

Mechanism of Interaction

Terbinafine enhances warfarin's anticoagulant effect through hepatic enzyme inhibition, particularly affecting cytochrome P450 enzymes involved in warfarin metabolism. This inhibition reduces warfarin clearance, leading to increased plasma concentrations of the more potent S-warfarin enantiomer. Additionally, terbinafine may interfere with vitamin K metabolism or synthesis, further potentiating warfarin's anticoagulant activity and resulting in prolonged prothrombin time and elevated INR values.

Risks and Symptoms

The primary clinical risk of this interaction is significantly increased bleeding potential, ranging from minor bruising and nosebleeds to life-threatening hemorrhages including gastrointestinal, intracranial, or retroperitoneal bleeding. Patients may experience prolonged bleeding from minor cuts, excessive menstrual bleeding, or spontaneous bruising. The interaction can develop within days of starting terbinafine and may persist for several weeks after discontinuation due to terbinafine's long half-life and tissue accumulation.

Management and Precautions

Close INR monitoring is essential, with baseline measurement before starting terbinafine and frequent follow-up testing (every 3-7 days initially, then weekly). Warfarin dose reduction of 25-50% may be necessary based on INR results. Patients should be educated about bleeding signs and symptoms, advised to avoid activities with high injury risk, and instructed to seek immediate medical attention for unusual bleeding. Consider alternative antifungal agents with lower interaction potential if clinically appropriate. Upon terbinafine discontinuation, gradual warfarin dose increases may be needed with continued INR monitoring.

Terbinafine interactions with food and lifestyle

Terbinafine should be taken with food to improve absorption and reduce gastrointestinal side effects. Alcohol consumption should be avoided or limited during terbinafine treatment due to the potential for increased risk of liver toxicity, as both terbinafine and alcohol can affect liver function. Patients should also avoid excessive caffeine intake, as terbinafine can reduce caffeine metabolism, potentially leading to increased caffeine effects such as jitteriness, insomnia, and rapid heartbeat.

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.