Recurrent venous thrombosis under rivaroxaban and carbamazepine for symptomatic epilepsy

BACKGROUND: The direct oral anticoagulant (DOAC) rivaroxaban, an oral Factor Xa inhibitor, is increasingly used as an alternative to vitamin-K-antagonists (VKAs). Absorption and elimination of DOACs are dependent on the permeability glycoprotein (P-gp) efflux transporter protein system, and DOACs are substrates of the hepatic cytochrome P 450 3A4 (CYP3A4) enzymes. Therefore, drug-interactions may occur when DOACs are administered with drugs affecting the activity of P-gp or CYP3A4 systems. Several antiepileptic drugs like carbamazepine are known to affect P-gp and CYP3A4-activity. CASE REPORT: A 55-year-old male was admitted because of pain and swelling of his right leg spontaneously since 2 days. He was under a therapy with 20mg rivaroxaban since 4 months because of an unprovoked venous thrombosis of his right leg. He had a history of poliomyelitis at age 6 months, structural epilepsy due to poly-microgyria with complex partial seizures with secondary generalization since age 6 years, why he was treated with carbamazepine (900mg/d). He reported to be highly adherent to his anticoagulant and antiepileptic medication. Anti-Xa activity was <20ng/ml according to a rivaroxaban calibrated anti-factor Xa assay. Therapy with rivaroxaban was stopped, and low-molecular-weight heparin, followed by phenprocoumon, was started. CONCLUSION: The combination of DOACs with carbamazepine, an inducer of P-gp and CYP3A4-activity, should be avoided since the anticoagulant effect is decreased. There is an urgent need to increase our knowledge and physicians' awareness about the potential of drug-drug interactions of DOACs.