Drug interactions
Leucovorin + Phenytoin
Severity: Moderate
Leucovorin and Phenytoin: moderate interaction.
Last updated
For healthcare professionals — reference only. This page is a brief summary, not medical advice and not a substitute for official labeling or clinical judgement. Always verify before prescribing or dispensing.
Summary
Folinic acid may reduce phenytoin levels and anticonvulsant effect, raising the risk of breakthrough seizures. Folate also has been reported to lower phenytoin concentrations.
What this interaction means in plain words
Leucovorin and Phenytoin can affect each other. The combination is often manageable, but it may need a change of dose, a change of timing, or extra checks while both are taken.
Leucovorin belongs to Miscellaneous; Phenytoin belongs to Central Nervous System.
Why it happens
Folate may increase phenytoin metabolism; a pro-convulsant effect has also been proposed.
What to do
Monitor seizure control and phenytoin plasma concentrations during and after leucovorin treatment, adjusting the dose as needed.
What to ask your pharmacist
- Should I take them at different times of day?
- Does the dose of either medicine need to change?
- Is there anything I should avoid, such as alcohol or certain foods, while on both?
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Other interactions of Leucovorin
- Capecitabine + Leucovorin Major
- Fluorouracil + Leucovorin Major
- Glucarpidase + Leucovorin Major
- Leucovorin + Phenobarbitone Moderate
Other interactions of Phenytoin
- Artemether / lumefantrine + Phenytoin Contraindicated
- Bictegravir + Phenytoin Contraindicated
- Cabotegravir + Phenytoin Contraindicated
- Doravirine + Phenytoin Contraindicated
- Elbasvir / grazoprevir + Phenytoin Contraindicated
- Elvitegravir / cobicistat / emtricitabine / tenofovir df + Phenytoin Contraindicated
Frequently asked questions
Can I take Leucovorin with Phenytoin?
MediHelp rates the interaction as moderate. Leucovorin and Phenytoin can affect each other. The combination is often manageable, but it may need a change of dose, a change of timing, or extra checks while both are taken. Folinic acid may reduce phenytoin levels and anticonvulsant effect, raising the risk of breakthrough seizures. Folate also has been reported to lower phenytoin concentrations.
How serious is the interaction between Leucovorin and Phenytoin?
MediHelp rates it moderate, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Monitor seizure control and phenytoin plasma concentrations during and after leucovorin treatment, adjusting the dose as needed.
What other medicines interact with Leucovorin?
MediHelp also lists interactions of Leucovorin with, for example, Capecitabine, Fluorouracil, Glucarpidase. The full list is on the Leucovorin page.
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