Folic Acid - Phenobarbital, Phenytoin Interaction

Interaction Details

Phenobarbital, Phenytoin is classified as belonging to the following category: Phenobarbital (Luminal)

Folic acid might have antagonistic effects on phenobarbital and increase the risk for seizures.
Folic acid can have direct convulsant activity in some people, reversing the effects of phenobarbital and worsening seizure control. Monitor closely for increased seizure activity.

Interaction Rating

Likelihood of Occurrence

Interaction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.

References

• Froscher W, Maier V, Laage M, et al. Folate deficiency, anticonvulsant drugs, and psychiatric morbidity. Clin Neuropharmacol 1995;18:165-82.
• Reynolds EH. Neurological aspects of folate and vitamin B12 metabolism. Clin Haematol 1976;5:661-96.
• Reynolds EH. Folate metabolism and anticonvulsant therapy. Proc R Soc Med 1974;67:68.

Interaction Details

Phenobarbital, Phenytoin is classified as belonging to the following category: Phenytoin (Dilantin)

Folic acid might reduce serum levels of phenytoin in some patients.
Folic acid may be a cofactor in phenytoin metabolism. Folic acid, in doses of 1 mg daily or more, can reduce serum levels of phenytoin in some patients. Increases in seizure frequency have been reported. If folic acid supplements are added to established phenytoin therapy, monitor serum phenytoin levels closely. If phenytoin and folic acid are started at the same time and continued together, adverse changes in phenytoin pharmacokinetics are avoided. Note that phenytoin also reduces serum folate levels.

Interaction Rating

Likelihood of Occurrence

Interaction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.

References

• Lewis DP, Van Dyke DC, Willhite LA, et al. Phenytoin-folic acid interaction. Ann Pharmacother 1995;29:726-35.
• Berg MJ, Stumbo PJ, Chenard CA, et al. Folic acid improves phenytoin pharmacokinetics. J Am Diet Assoc 1995;95:352-6.
• Berg MJ, Fincham RW, Ebert BE, et al. Phenytoin pharmacokinetics: Before and after folic acid administration. Epilepsia 1992;33:712-20.
• Shafer RB, Nuttall FQ. Calcium and folic acid absorption in patients taking anticonvulsant drugs. J Clin Endocrinol Metab 1975;41:1125-9.
• Segal S, Kaminski S. Drug-nutrient interactions. American Druggist 1996 Jul;42-8.
• Lambie DG, Johnson RH. Drugs and folate metabolism. Drugs 1985;30:145-55.

Folic Acid - More Interactions

Folic Acid interacts with 40 drugs

Interaction Rating Key

These severity listings are for informational use only. Never start, stop or otherwise change your therapy before speaking with your provider.