Title:Bleeding Complications in a Patient After the Unexpected Interaction
between Valproic Acid and Phenprocoumon
Volume: 19
Issue: 1
Author(s): André Wieringa*, Helle-Brit Fiebrich, Fleur van Gelder, Abraham J. Valkenburg, Jan G. Maring and Elise J. Smolders
Affiliation:
- Department of Clinical Pharmacy, Isala Hospital, Zwolle, The Netherlands
- Department of Clinical Pharmacology,
Isala Hospital, Zwolle, The Netherlands
Keywords:
CYP2C9, drug-drug interaction, INR, coumarin, vitamin K antagonist, CYP inhibitor, valproic acid, phenprocoumon.
Abstract:
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.
