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Folic acid antagonists (e.g., methotrexate, trimetrexate, pyrimethamine, trimethoprim): Folinic Acid may reduce or nullify the effect of these antagonists.
5-FU: Concurrent use of Folinic Acid may increase therapeutic and toxic effects (especially on the GI tract) of 5-FU; however, these medications may be used together for therapeutic advantage.
Anticonvulsants: In epileptic patients treated with phenobarbital, phenytoin, primidone, and succinimides, Folinic Acid may increase the frequency of seizures due to a decrease of plasma concentrations of the anticonvulsants.
Direct or indirect DNA synthesis inhibitors: These cytotoxic medications (e.g., hydroxycarbamine, cytarabine, mercaptopurine, thioguanine) may lead to macrocytosis, which should not be treated with folinic acid.
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