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Folic acid in large amounts may contact the antiepileptic effect of phenobarbital, phenytoin, and primidone, and increase the frequency of seizures in susceptible children.
Preliminary animal and human studies have shown that small quantities of systemically administered leucovorin enter the CSF primarily as 5-methyltetrahydrofolate and, in humans, remain 1 to 3 orders of magnitude lower than the usual methotrexate concentration following intrathecal administration. However, high doses of leucovorin may reduce the efficacy of intrathecally administered methotrexate. Leucovorin may enhance the toxicity of 5-fluorouracil.
