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Bleeding Complications in a Patient After the Unexpected Interaction between Valproic Acid and Phenprocoumon
André Wieringa1,2, Helle-Brit Fiebrich2,3, Fleur van Gelder1
1Department of Clinical Pharmacy, Isala Hospital, Zwolle, The Netherlands.
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.
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