Bleeding Complications in a Patient After the Unexpected Interaction between Valproic Acid and Phenprocoumon

Background: Phenprocoumon is a vitamin K antagonist that is widely prescribed in Europe and Latin America for the prophylaxis and treatment of thromboembolic events. Case Presentation: A 90-year-old female was admitted to our hospital with tonic-clonic seizures, possibly due to dementia syndrome. Valproic acid (VPA) was prescribed for the treatment of seizures. VPA is an inhibitor of cytochrome P450 (CYP) 2C9 enzymes. A pharmacokinetic interaction with phenprocoumon occurred, which is a substrate for CYP2C9 enzymes. The interaction resulted in a strong INR increase and subsequent clinically relevant bleeding in our patient. Valproic acid is not specifically mentioned in the phenprocoumon drug label as a CYP2C9 inhibitor, and in the Dutch medication surveillance database, no medication alert is shown when prescribing this combination, and no interaction with phenprocoumon has been reported so far. Conclusion: When prescribing this combination, the prescriber should be warned and advised to intensify INR monitoring if the combination is to be continued.