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.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.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.