Does terbinafine interact with Warfarin (Coumadin)?

From the Guidelines

Terbinafine does not have a significant interaction with warfarin, as it does not inhibit the liver enzymes that metabolize warfarin, specifically CYP2C9, to a clinically significant extent. According to the most recent and highest quality study available, 1, the interaction between terbinafine and warfarin is not considered significant. The study focuses on drug interactions affecting oral anticoagulant use and mentions that warfarin's interactions mainly involve moderate to strong inhibitors/inducers of cytochrome P450 (CYP) 2C9. However, terbinafine is not listed as a significant inhibitor of CYP2C9.

Key Points to Consider

• The evidence from 2 suggests that terbinafine's main drug interactions are with rifampicin, which reduces its plasma concentrations, and cimetidine, which increases its plasma concentrations.
• There is no mention of a significant interaction between terbinafine and warfarin in the provided studies, including 1 and 3.
• The study from 1 highlights the importance of monitoring INR levels when certain antibiotics are initiated or discontinued in patients taking warfarin, but terbinafine is not mentioned as a concern.
• The American Heart Association/American College of Cardiology Foundation guide to warfarin therapy, 3, discusses various factors that can affect warfarin's anticoagulant effect, including genetic variability, dietary vitamin K, and other medications, but does not mention terbinafine as a significant interacting drug.

Clinical Implications

• Patients taking terbinafine and warfarin should still be monitored for signs of increased bleeding, such as unusual bruising, nosebleeds, bleeding gums, or blood in urine or stool, as a precautionary measure.
• However, based on the available evidence, it is not necessary to adjust warfarin doses or avoid concomitant use with terbinafine due to a significant drug interaction.
• Alternative antifungal treatments may still be considered if appropriate for the patient's condition, but this decision should be based on the specific clinical context and not solely due to concerns about a terbinafine-warfarin interaction.

From the FDA Drug Label

Altered prothrombin time (prolongation and reduction) in patients concomitantly treated with warfarin has been reported. There have been spontaneous reports of increase or decrease in prothrombin times in patients concomitantly taking oral terbinafine and warfarin, however, a causal relationship between terbinafine tablets and these changes has not been established

Terbinafine Interaction with Warfarin:

• Terbinafine may interact with warfarin, as altered prothrombin times have been reported in patients taking both medications.
• However, a causal relationship between terbinafine and these changes has not been established.
• Key Consideration: Patients taking warfarin and terbinafine concomitantly should be closely monitored for changes in prothrombin times 4.

From the Research

Terbinafine and Warfarin Interaction

• Terbinafine may interact with warfarin, leading to an increased risk of bleeding or reduced anticoagulant effect 5, 6
• The interaction between terbinafine and warfarin is thought to occur through the inhibition of liver enzymes, specifically CYP2C9, which is involved in the metabolism of warfarin 5
• Case reports have described patients experiencing bleeding events or reduced anticoagulation while taking terbinafine and warfarin concomitantly 5, 6

Clinical Implications

• Patients taking warfarin and terbinafine concomitantly should be closely monitored for signs of bleeding or reduced anticoagulation 5, 6
• The risk of bleeding may be increased in patients taking warfarin and terbinafine, particularly in those with other risk factors for bleeding, such as age or concomitant use of other medications that increase bleeding risk 7, 8
• The use of terbinafine in patients taking warfarin should be approached with caution, and alternative treatments should be considered if possible 5, 6

Mechanism of Interaction

• Terbinafine is a potent inhibitor of CYP2D6, but it may also inhibit other liver enzymes, including CYP2C9, which is involved in the metabolism of warfarin 5
• The inhibition of CYP2C9 by terbinafine may lead to increased levels of warfarin, increasing the risk of bleeding 5
• The interaction between terbinafine and warfarin may be influenced by other factors, such as the dose and duration of treatment, as well as the presence of other medications that may interact with warfarin 6, 9