Bleeding Complications in a Patient After the Unexpected Interaction between Valproic Acid and Phenprocoumon.
CYP inhibitor
CYP2C9
INR
coumarin
drug-drug interaction
phenprocoumon.
valproic acid
vitamin K antagonist
Journal
Current drug safety
ISSN: 2212-3911
Titre abrégé: Curr Drug Saf
Pays: United Arab Emirates
ID NLM: 101270895
Informations de publication
Date de publication:
2024
2024
Historique:
received:
28
09
2022
revised:
10
01
2023
accepted:
31
01
2023
medline:
28
11
2023
pubmed:
11
3
2023
entrez:
10
3
2023
Statut:
ppublish
Résumé
Phenprocoumon is a vitamin K antagonist that is widely prescribed in Europe and Latin America for the prophylaxis and treatment of thromboembolic events. 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. When prescribing this combination, the prescriber should be warned and advised to intensify INR monitoring if the combination is to be continued.
Sections du résumé
BACKGROUND
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
METHODS
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
CONCLUSIONS
When prescribing this combination, the prescriber should be warned and advised to intensify INR monitoring if the combination is to be continued.
Identifiants
pubmed: 36896908
pii: CDS-EPUB-130102
doi: 10.2174/1574886318666230310104322
doi:
Substances chimiques
Phenprocoumon
Q08SIO485D
Valproic Acid
614OI1Z5WI
Acenocoumarol
I6WP63U32H
Cytochrome P-450 CYP2C9
EC 1.14.13.-
Aryl Hydrocarbon Hydroxylases
EC 1.14.14.1
Anticoagulants
0
Types de publication
Case Reports
Langues
eng
Sous-ensembles de citation
IM
Pagination
142-144Informations de copyright
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