Divalproex and Warfarin

In the database of official manuals used in the service creation an interaction registered by statistical results of studies was found, which can either lead to negative consequences for the patient health or strengthen a mutual positive effect. A doctor should be consulted to address the issue of joint drug administration.

Using warfarin together with divalproex sodium may cause you to bleed more easily. You may need a dose adjustment based on your prothrombin time or International Normalized Ratio (INR). Call your doctor promptly if you have any unusual bleeding or bruising, vomiting, blood in your urine or stools, headache, dizziness, or weakness. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

MONITOR: Valproic acid may transiently potentiate the hypoprothrombinemic effect of warfarin and other oral anticoagulants. The mechanism is protein binding displacement by valproic acid, resulting in increased plasma concentrations of unbound (active) anticoagulant drug. In an in vitro study, valproic acid increased the unbound fraction of warfarin by up to 33%. The clinical significance of this effect is unknown. The interaction was suspected in one case report, although a causal relationship was not established. Because drug clearance is also increased with higher levels of unbound drug, the pharmacokinetic effect produced by valproic acid is expected to balance out over time, resulting in little or no net effect on anticoagulant pharmacokinetics in the long-term. However, valproic acid appears to cause dose-related thrombocytopenia. This effect should be considered in patients treated concomitantly with oral anticoagulants.

MANAGEMENT: Based on the proposed transient nature of the pharmacokinetic interaction, appropriate monitoring for excessive hypoprothrombinemia is recommended during the first week following the addition of valproic acid to a stabilized regimen of warfarin or other oral anticoagulants. Patients should be advised to promptly report any signs of bleeding to their physician, including pain, swelling, headache, dizziness, weakness, prolonged bleeding from cuts, increased menstrual flow, vaginal bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding or bruising, red or brown urine, or red or black stools.

Divalproex

Generic Name: divalproex sodium

Brand name: Depakote ER, Depakote Sprinkles, Depakote, Depakene, Depacon

Synonyms: Divalproex sodium

What is Divalproex?

Warfarin

Generic Name: warfarin

Brand name: Coumadin, Jantoven

Synonyms: n.a.

What is Warfarin?