Possible Interaction: Phenytoin and Folate

“Abstract Oral administration of phenytoin (diphenylhydantoin, ' Dilantin ', ' Epanutin ') impaired intestinal absorption of conjugated folate in some healthy volunteers but did not significantly affect the absorption of free folate.”

“It has been suggested that pH changes in the gut associated with PHT ingestion may be responsible for decreased folate uptake either by direct inhibition of folate transport into the intestinal mucosa or by inhibition of folate conjugase activity.”

“Conclusions: Our meta-analysis indicates that PHT monotherapy is associated with the increase in the serum homocysteine levels and decreased levels of folate and vitamin B12, and hyperhomocysteinaemia may contribute to the acceleration of the atherosclerotic process.”

“ Phenytoin reduces folate levels and may be responsible for the development of a macrocytic anemia.”

“The … between folate … phenytoin metabolism, however, is a dual and interdependent one and the addition of folic acid to a stable anticonvulsant regimen predictably lowers serum phenytoin ….1 We report a case of recurrent seizures in a patient after the addition of folic acid for treatment of macrocytic anemia.”

“ Folate supplementation of 5 mg/d was followed by a decrease of serum phenytoin concentration to a subtherapeutic level with a breakthrough seizure.”

“ Folate is hypothesized to be a cofactor in phenytoin metabolism and may be responsible for the “pseudo-steady-state,” which is a concentration where phenytoin appears to be at steady-state, but in reality, is not.”

“ Phenytoin and folic acid therapy initiated concomitantly prevents decreased folate and phenytoin obtains steady-state concentrations sooner.”

“The data indicate that the effects of phenytoin sodium on the proliferation of HL60 cells may have been slightly mediated via a reduced uptake of folate and possibly also of vitamin B12.”

“They also suggest that one of the mechanisms underlying some of the undesirable effects of long-term therapy with phenytoin may be a drug-related impairment of both folate and vitamin B12 uptake by certain cells, including haemopoietic and neural cells.”

“A significant inverse correlation was observed between serum levels of folates and phenytoin , which suggests a direct toxic effect of the drug.”

“The nutrient-drug interaction between folate and phenytoin is a two-way interaction.”

“The other 2, both taking phenytoin and 1 a heavy alcohol using, had persistent macrocytosis despite folate administration.”