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Phenytoin-folic acid interaction: a lesson to be learned.
H Seligmann1, I Potasman, B Weller
1Clinical Pharmacology Unit, Bnai Zion Medical Center, Haifa, Israel.
Clinical Neuropharmacology
|October 12, 1999
Summary
Folic acid supplements can lower phenytoin levels, potentially causing seizures. Even low doses may affect drug metabolism, highlighting a critical drug-vitamin interaction for epilepsy patients.
Area of Science:
- Pharmacology
- Nutritional Biochemistry
Background:
- Phenytoin is a widely used antiepileptic drug.
- Folic acid plays a crucial role in various metabolic processes.
Observation:
- A patient on phenytoin developed symptomatic folic acid deficiency.
- Folate supplementation led to decreased serum phenytoin levels and a breakthrough seizure.
Findings:
- Folate supplementation significantly decreased the Km value of phenytoin metabolism.
- This indicates increased affinity of hepatic enzymes for phenytoin, accelerating its metabolism.
- Consequently, serum phenytoin concentration and anticonvulsant effect were reduced.
Implications:
- Highlights a significant drug-vitamin interaction between phenytoin and folic acid.
- Suggests cautious folic acid supplementation in patients on phenytoin therapy.
- Recommends initiating folate supplementation concurrently with phenytoin therapy, possibly at lower doses to prevent metabolic perturbations.