Abstract Number: PB2417
Meeting: ISTH 2020 Congress
Background: Antiepileptic drugs (AEDs), as sodium valproate, inducing cytochrome P450 isoenzymes, especially CYP3A4/5, might increase the metabolism of anti-Xa DOACs (rivaroxaban, apixaban, edoxaban) and reduce their anticoagulant effect. Valproate induces also P-gp efflux pump activity reducing the intestinal absorption of DOACs. These interactions may lead to decreased antithrombotic efficacy.
Aims: To measure plasma levels of rivaroxaban and dabigatran on valproat treatment.
Methods: We are reporting a case of a 30-years old man, who had a history of symptomatic post-traumatic epilepsy, manifested by simple partial motor and complex seizures, some of which are generalized secondary. He received a chronic valproate treatment at a stable dose (1000 mg) for three years. During active sports he developed deep ileofemoral vein thrombosis. Thrombophilic screening revealed a Prothrombin 20210 G/A heterozygous mutation. Treatment with 2 x 15 mg rivaroxaban was started for 21 days, followed by 20 mg OD without significant clinical improvement after one month.
Results: Anti-Xa activity was measured twice at peak level (3rd hour) after administration of 20 mg rivaroxaban with values below 10 ng/ml in two consecutive days. Ultrasonography showed no withdrawal of venous thrombosis. Rivaroxaban was replaced with dabigatran 2 x 150 mg/d for 4 days. Again low anticoagulant activity was measured – trought level 40 ng/ml vs median value of 85 ng/ml (52 – 182 ng/ml). We used DTI (Hemoclot, Hyphen) assay for dabigatran and DiXaI (Hyphen) assay for rivaroxaban on Sysmex 2000i. We decided to switch the patient to vitamin K antagonist acenocoumarol and received a good anticoagulant response at a dose of 28 mg/weekly (INR 2.8). There was an improve of the clinical symptoms of edema and swelling in the next 4 weeks.
Conclusions: The pharmacokinetic interaction between valproate and DOACs significantly reduces plasma levels and anticoagulant activity of DOACs (rivaroxaban and dabigatran) and adversely affects antithrombotic efficacy.
To cite this abstract in AMA style:Paskaleva I, Doncheva E, Simeonova R, Ignatova V, Dramov A. Sodium Valproate-induced Drug Interactions with DOAC Anticoagulant Activity: A Case Report [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/sodium-valproate-induced-drug-interactions-with-doac-anticoagulant-activity-a-case-report/. Accessed November 30, 2021.
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