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Valproic acid and warfarin: an underrecognized drug interaction
Hyue W Yoon1, Elias A Giraldo, Eelco F M Wijdicks
1Pharmacy Services, Mayo Clinic, Rochester, MN 55905, USA.
Neurocritical Care
|April 23, 2011
Summary
Valproic acid can dangerously increase warfarin levels by displacing it from protein binding sites, leading to a rapid INR increase. This interaction is crucial for managing patients on both medications, especially in neurocritical care.
Area of Science:
- Neuroscience
- Pharmacology
- Critical Care Medicine
Background:
- Drug interactions involving antiepileptic drugs and warfarin are common in neurocritical care.
- Many antiepileptic drugs affect warfarin metabolism via enzyme induction or inhibition.
- Valproic acid's potential to displace warfarin from protein binding sites is a less recognized but significant interaction.
Observation:
- A 71-year-old female patient with glioblastoma and refractory seizures was on warfarin for deep venous thrombosis.
- Following levetiracetam treatment for seizures, intravenous valproic acid was administered.
- This led to a rapid and significant increase in the patient's international normalized ratio (INR) to 7.6.
Findings:
- The administration of valproic acid, an acidic drug, resulted in a sharp rise in INR.
- Brain MRI revealed a hemorrhagic tumor but no new major bleeding events.
- The observed INR elevation is attributed to valproic acid's displacement of warfarin from protein binding sites.
Implications:
- Clinicians should be aware of valproic acid's protein binding displacement effect on warfarin.
- Careful INR monitoring is essential when initiating valproic acid in patients receiving warfarin.
- This interaction highlights the importance of understanding drug-drug interactions in neurocritical care settings.
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