Drug General Information (ID: DDIOM07DUN)
Drug Name			Valproic acid		Drug Info		Anisindione		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Anticonvulsants				Anticoagulants
Structure

Mechanism of Valproic acid-Anisindione Interaction (Severity Level: Moderate)
Competitive binding of plasma proteins Click to Show/Hide Mechanism Graph
Drug Name		Valproic acid				Anisindione
Mechanism		Competition for plasma protein binding sites				Competition for plasma protein binding sites
Key Mechanism Factor 1
		Factor Name		Plasma protein binding
		Factor Description		Plasma protein binding refers to the degree of binding of a drug to proteins in the blood, and the lower the degree of binding, the more efficiently the drug can cross cell membranes or diffuse. Plasma protein binding alters the distribution and therapeutic characteristics of the drugs.
Mechanism Description		Increased plasma concentration of Anisindione and Valproic acid due to competitive binding of plasma proteins

Recommended Action
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.

References
1	Guthrie SK, Stoysich AM, Bader G, Hilleman DE "Hypothesized interaction between valproic acid and warfarin." J Clin Psychopharmacol 15 (1995): 138-9. [PMID: 7782487]
2	Product Information. Depakene (valproic acid). Abbott Pharmaceutical, Abbott Park, IL.