This information is generalized and not intended as specific medical advice. Consult your healthcare professional before taking or discontinuing any drug or commencing any course of treatment.
Moderate. These medicines may cause some risk when taken together. Contact your healthcare professional (e.g. doctor or pharmacist) for more information.
How the interaction occurs:
When warfarin is taken with valproic acid, divalproex or valproate, your body may process your warfarin more slowly.
What might happen:
Your warfarin level may increase, leading to elevated prothrombin (PT or INR) laboratory tests. If the INR or prothrombin time is too high you have an increased chance for bleeding episodes such bleeding from your gums, nosebleeds, unusual bruising, or dark stools.
What you should do about this interaction:
Let your healthcare professionals (e.g. doctor or pharmacist) know that you are taking these medicines together. You may need to have your INR or PT tests checked more often, especially when you first start taking valproic acid or if your dose changes. If you have any signs of bleeding, such as bleeding from your gums, nosebleeds, unusual bruising, or dark stools, contact your doctor right away.Your healthcare professionals may already be aware of this interaction and may be monitoring you for it. Do not start, stop, or change the dosage of any medicine before checking with them first.
1.Coumadin (warfarin sodium) US prescribing information. Bristol-Myers Squibb Company January 22, 2010.
2.Gunes A, Bilir E, Zengil H, Babaoglu MO, Bozkurt A, Yasar U. Inhibitory effect of valproic acid on cytochrome P450 2C9 activity in epilepsy patients. Basic Clin Pharmacol Toxicol 2007 Jun;100(6):383-6.
3.Wen X, Wang JS, Kivisto KT, Neuvonen PJ, Backman JT. In vitro evaluation of valproic acid as an inhibitor of human cytochrome P450 isoforms: preferential inhibition of cytochrome P450 2C9 (CYP2C9). Br J Clin Pharmacol 2001 Nov;52(5):547-53.
4.Anderson Gail D. Chapter 42: Pharmacokinetics and Drug Interactions. In: Wyllie's Treatment of Epilepsy: Principles and Practice, 5th Ed. 2011.
5.Depakote (divalproex sodium) US prescribing information. AbbVie Inc. June, 2013.
6.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 Apr 15;41(8):1227-33.
7.Yoon HW, Giraldo EA, Wijdicks EF. Valproic acid and warfarin: an underrecognized drug interaction. Neurocrit Care 2011 Aug;15(1):182-5.
8.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 Sep;26(5):492-4.