What is the recommended folic acid dose for patients on phenytoin, particularly women of child‑bearing potential?

Folic Acid Dosing for Patients on Phenytoin

For a woman of childbearing potential on phenytoin, prescribe 5000 micrograms (5 mg) of folic acid daily, starting immediately and continuing at least through the first trimester of any pregnancy. 1

Risk Stratification for Women on Phenytoin

• Women with epilepsy taking antiepileptic medications like phenytoin are at increased baseline risk for neural tube defects compared to the general population 1
• Phenytoin therapy decreases serum folate levels in approximately 50% of epileptic patients, further increasing the risk of folate depletion 2
• The American College of Medical Genetics classifies women taking antiepileptic medications as high-risk patients requiring higher-dose supplementation 1

Specific Dosing Algorithm

High-Risk Women (On Phenytoin)

• 5000 micrograms (5 mg) daily is the recommended dose for women on antiepileptic medications 1, 3, 4
• Start supplementation immediately rather than waiting for planned conception, since over 50% of pregnancies are unplanned 1
• Continue the 5 mg dose from at least 3 months before conception through 12 weeks of gestation 1, 3
• After 12 weeks gestation, reduce to 400-1000 micrograms (0.4-1.0 mg) daily for the remainder of pregnancy and 4-6 weeks postpartum 1, 3

Standard-Risk Women (Not Applicable Here)

• Women without risk factors require only 400-800 micrograms (0.4-0.8 mg) daily 5
• This lower dose is insufficient for women on phenytoin 1

Critical Clinical Considerations

Prescription Format

• Prescribe a single 5 mg prescription-strength folic acid tablet rather than multiple over-the-counter multivitamins 1
• This approach avoids excessive intake of other vitamins, particularly vitamin A, which is teratogenic at high doses 1

Vitamin B12 Screening

• Rule out vitamin B12 deficiency before initiating folic acid doses exceeding 1 mg, as high-dose folic acid can mask pernicious anemia while neurologic damage progresses 1, 6
• However, vitamin B12 deficiency is uncommon in young women, affecting fewer than 1% of this population 1

Phenytoin-Folate Interaction

• Folic acid supplementation at 1 mg daily improves phenytoin pharmacokinetics and helps more patients achieve steady-state drug levels 2
• Supplementation prevents the 38% decrease in serum folate levels typically seen with phenytoin therapy 2
• Seizure control must be maintained, so phenytoin should generally be continued despite neural tube defect risk 1

Important Caveats

• Even with adequate 5 mg folic acid supplementation, not all neural tube defects can be prevented due to multifactorial or monogenic etiology 1
• Folic acid supplementation prevents approximately 50-72% of neural tube defect cases 1, 5
• Women taking antiepileptic drugs should undergo perinatal diagnostic ultrasound to rule out neural tube defects, even with supplementary folic acid 1
• Neural tube closure occurs within the first 28 days after conception, making preconception supplementation crucial 1

Why Not Lower Doses?

• The 1000 microgram (1 mg) option is inadequate for women on phenytoin, as this dose is reserved for moderate-risk patients 3
• The 2000 microgram (2 mg) option has no evidence base and is not recommended by any guideline 1, 3
• Only the 5000 microgram (5 mg) dose is specifically recommended for women on antiepileptic medications by the American College of Medical Genetics 1, 3, 4