title: Leflunomide and warfarin interaction: case report and review of the literature.
abstract: A 61-year-old Caucasian woman receiving long-term anticoagulation with warfarin for recurrent thromboembolism and atrial fibrillation was found to have an elevated international normalized ratio (INR) after she started leflunomide therapy for rheumatoid arthritis. Her INR had been stable for 4 months before this event. The patient required an overall decrease of 22% in her weekly warfarin dose to maintain a therapeutic INR within the goal range of 2.0-3.0 after adding leflunomide therapy. A comprehensive PubMed/MEDLINE search was conducted to identify literature addressing the potential interaction between warfarin and leflunomide. Evidence describing the interaction and its potential mechanism was limited to one published case report and to in vitro data, respectively. Our case report provides additional support that such an interaction exists and that it was at least partly responsible for the subsequent increase in the patient's INR. Therefore, continued evaluation and documentation of this potential drug interaction is imperative. To reduce the risk of adverse effects related to excessive anticoagulation with the start of leflunomide in patients taking warfarin, clinicians should increase their frequency of INR monitoring and adjust the warfarin dosage accordingly to maintain therapeutic anticoagulation.
authors.affiliation: Department of Pharmacy: Clinical and Administrative Sciences, College of Pharmacy, University of Oklahoma, Oklahoma City, Oklahoma 73117, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Chonlahan
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Halloran
authors.forename: Amy
authors.initials: A
authors.lastname: Hammonds
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D001281:Atrial Fibrillation / Q000188:drug therapy; D001777:Blood Coagulation / Q000187:drug effects; D004347:Drug Interactions; D005260:Female; D006801:Humans; D019934:International Normalized Ratio; D007555:Isoxazoles / Q000009:adverse effects / Q000627:therapeutic use*; D000077339:Leflunomide; D008875:Middle Aged; D013923:Thromboembolism / Q000188:drug therapy; D014859:Warfarin / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000925:Anticoagulants; D007555:Isoxazoles; D014859:Warfarin; D000077339:Leflunomide