Major Interaction between Warfarin and Na Valproate: A Case Report
Abstract: Warfarin is the most commonly used oral anticoagulant drug in clinical practice with extreme inter and intra-individual variation in pharmacokinetic properties.
Na Valproate, a broad spectrum anticonvulsant agent, is best known for its enzyme inhibition properties and also displacement of protein binding sites. Interaction between Warfarin and psychotropic drugs including Valproate are important and perhaps under recognized. In this report, we present a 48 year old female patient with chief complaints of abdominal pain, tea-color urine, blurred vision and headache. She had been suffering from “migraine headache” for 15 years that was relatively well controlled with Na Valproate 200mg twice daily. She was experienced a deep vein thrombosis (DVT) following oral contraceptive. For management of DVT, she was received Warfarin 5mg/day which was increased to 7.5 mg /day after 2 weeks. Three days after this increment of dose, her Prothrombin Time (PT) rose to 35.3 seconds (three times of normal value) and evidences of bleeding including hematuria and hematemesis were observed. Based on the history and laboratory findings, “Warfarin toxicity” was the first impression and she was treated with fresh frozen plasma and vitamin K with a well recovery. This experience emphasizes the clinical significant interaction between Warfarin and Na Valproate, which may take place even with the usual doses of each agent.
Holbrook AM, Pereira JA, Labiris R, et al. Systematic overview of Warfarin and its drug and food interactions. Arch Intern Med 2005; 165(10): 1095- 106.
Yin T, Miyata T. Warfarin dose and the pharmacogenomics of CYP2C9 and VKORC1- rationale and perspectives. Thromb Res 2007;120(1): 1-10.
Vanscoy GJ, McAuley JW. Exaggerated Warfarin sensitivity: a case report. Vet Hum Toxicol 1991; 33(3):270-1.
Strandell J, Wahlin S. Pharmacodynamic and pharmacokinetic drug interactions reported to VigiBase, the WHO global individual case safety report database. Eur J Clin Pharmacol 2011;67(6):633-41.
Kutt H. Interactions between anticonvulsants and other commonly prescribed drugs. Epilepsia 1984; 25 Suppl 2:S118-31.
Yoon HW, Giraldo EA, Wijdicks EF.Valproic acid and Warfarin: an underrecognized drug interaction. Neurocrit Care 2011; 15(1):182-5.
Panjehshahin MR, Bowmer CJ, Yates MS. Effect of valproic acid, its unsaturated metabolites and some structurally related fatty acids on the binding of Warfarin and dansylsarcosine to human albumin. Biochem Pharmacol 1991;41(8):1227-33.
Guthrie SK, Stoysich AM, Bader G, Hilleman DE. Hypothesized interaction between valproic acid and Warfarin. J Clin Psychopharmacol 1995; 15(2):138-9.
Nadkarni A, Oldham MA, Howard M, Berenbaum I. Drug-drug interactions between Warfarin and psychotropics: updated review of the literature. Pharmacotherapy 2012;32(10):932-42.
Nadkarni A, Oldham M, Howard M, Lazar HL, Berenbaum I. Detrimental effects of divalproex on Warfarin therapy following mechanical valve replacement. J Card Surg 2011; 26(5):492-4.
Takahashi H, Echizen H. Pharmacogenetics of Warfarin elimination and its clinical implications. Clin Pharmacokinet 2001; 40(8):587-603.
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.