Login Register Cart 0
Generic placeholder image

Current Drug Safety

Editor-in-Chief

ISSN (Print): 1574-8863
ISSN (Online): 2212-3911

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Case Report

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

Author(s): André Wieringa*, Helle-Brit Fiebrich, Fleur van Gelder, Abraham J. Valkenburg, Jan G. Maring and Elise J. Smolders

Volume 19, Issue 1, 2024

Published on: 10 April, 2023

Page: [142 - 144] Pages: 3

DOI: 10.2174/1574886318666230310104322

Price: $65

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.

« Previous Next »
[1]
Palareti G, Cosmi B. Bleeding with anticoagulation therapy - who is at risk, and how best to identify such patients. Thromb Haemost 2009; 102(2): 268-78.
[PMID: 19652877]
[2]
Johannessen SI, Landmark CJ. Antiepileptic drug interactions - principles and clinical implications. Curr Neuropharmacol 2010; 8(3): 254-67.
[http://dx.doi.org/10.2174/157015910792246254] [PMID: 21358975]
[3]
Sanofi-Aventis NBV. Summary of product characteristics: Depakin 500 mg. Available from: https://www.geneesmiddeleninformatiebank.nl/smpc/h11775_smpc.pdf [Accessed on: April 13, 2022].
[4]
Flockhart DA, Thacker D, McDonald C, Desta Z. The flockhart cytochrome P450 drug-drug interaction table. Division of Clinical Pharmacology, Indiana University School of Medicine. 2021.
[http://dx.doi.org/10.1097/00004714-199504000-00010] [PMID: 7782487]
[5]
Zhou C, Sui Y, Zhao W, et al. The critical interaction between valproate sodium and warfarin: Case report and review. BMC Pharmacol Toxicol 2018; 19(1): 60.
[http://dx.doi.org/10.1186/s40360-018-0251-0] [PMID: 30285858]
[6]
Yoon HW, Giraldo EA, Wijdicks EFM. Valproic acid and warfarin: An underrecognized drug interaction. Neurocrit Care 2011; 15(1): 182-5.
[http://dx.doi.org/10.1007/s12028-011-9544-5] [PMID: 21512888]
[7]
Sandoz BV. Summary of product characteristics: Phenprocoumon. Available from: https://www.geneesmiddeleninformatiebank.nl/smpc/h21068_smpc.pdf [Accessed on: April 13, 2022].
[8]
Perucca E, Hebdige S, Frigo GM, Gatti G, Lecchini S, Crema A. Interaction between phenytoin and valproic acid: Plasma protein binding and metabolic effects. Clin Pharmacol Ther 1980; 28(6): 779-89.
[http://dx.doi.org/10.1038/clpt.1980.235] [PMID: 6777108]
[9]
Horn JR, Hansten PD, Chan LN. Proposal for a new tool to evaluate drug interaction cases. Ann Pharmacother 2007; 41(4): 674-80.
[http://dx.doi.org/10.1345/aph.1H423] [PMID: 17389673]
[10]
Federation of Dutch Thrombosis Services. Available from: https://www.fnt.nl/kwaliteit/VKA-interacties [Accessed on: April 13, 2022].
[11]
Drug Interactions Flockhart Table. Available from: https://www.druginteractions.medicine.iu.edu/MainTable.aspx [Accessed on: April 13, 2022].

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy