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Published on: March 14, 2014
Failure of Warfarin Anticoagulation Therapy after Administration of Oral Terbinafine
Ivana Štětkářová1, Jitka Čupáková2
1Department of Neurology, Third Faculty of Medicine, Charles University and Faculty Hospital Královské Vinohrady, Prague, Czech Republic. ivana.stetkarova@fnkv.cz.
Insights
Warfarin and terbinafine interaction can reduce warfarin's effectiveness, increasing risks for patients needing anticoagulation. This case highlights the potential dangers of combining these drugs, emphasizing careful monitoring.
Area of Science:
- Pharmacology
- Drug Interactions
- Clinical Case Reports
Background:
- Warfarin is a critical anticoagulant managed via CYP1A2, CYP3A4, and CYP2C9 metabolic pathways.
- Terbinafine, an antifungal, is known to inhibit CYP2D6, with potential for broader enzyme interactions.
Observation:
- An 88-year-old male on warfarin for atrial fibrillation developed dizziness and instability after starting oral terbinafine for onychomycosis.
- INR levels were found to be low, suggesting reduced warfarin efficacy.
- Symptoms emerged approximately two weeks post-terbinafine initiation, aligning with a 10-14 day liver enzyme induction period.
Findings:
- The observed clinical presentation suggests a drug interaction between warfarin and terbinafine.
- Terbinafine may induce liver enzymes (CYP1A2, CYP3A4, CYP2C9), leading to accelerated warfarin metabolism and decreased anticoagulation.
- This interaction resulted in a subtherapeutic International Normalized Ratio (INR).
Implications:
- Combined therapy with warfarin and oral terbinafine, though uncommon, poses significant risks.
- Clinicians must be aware of this potential interaction to prevent adverse events in patients requiring anticoagulation.
- Close INR monitoring is crucial if these medications are co-administered.
Abstract:
Warfarin is widely used anticoagulant drug for a variety of diseases (thromboembolic disease, atrial fibrillation, etc.). It has three most important parallel metabolic pathways, CYP1A2, CYP3A4 and CYP2C9. Terbinafine is a potent CYP2D6 inhibitor. A possible drug interaction could lead to an increased pharmacological effect of the above drugs. Enzyme induction with CYP3A4, CYP2C9, CYP1A2 inducers may have occurred. Case report: We present a case report of an 88-year-old male patient who has been successfully anticoagulated with warfarin due to atrial fibrillation. He was orally administered terbinafine to treat onychomycosis. Two weeks after initiation of this drug the patient experienced dizziness and feelings of instability, for which he was admitted to the neurology department. A low-efficient INR level was found at the baseline, presumably due to warfarin interaction with terbinafine. The induction of liver enzymes lasts 10-14 days, which matches the introduction of the antifungal agent. Conclusion: Combined therapy with warfarin and oral terbinafine is actually rarely prescribed but, if used, their interaction can have serious consequences in many clinical situations for which anticoagulation therapy with warfarin is indicated.
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