Drug interactions
Methotrexate + Phenytoin
Severity: Moderate
Methotrexate 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
Phenytoin may increase methotrexate toxicity. Phenytoin levels can also fall, risking seizure control, and both drugs have antifolate effects.
What this interaction means in plain words
Methotrexate 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.
Methotrexate belongs to Oncology; Phenytoin belongs to Central Nervous System.
Why it happens
Displacement of methotrexate from plasma proteins plus additive antifolate effects; methotrexate may also alter phenytoin levels.
What to do
Monitor blood counts and methotrexate toxicity. Check phenytoin levels and adjust 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 Methotrexate
- Acitretin + Methotrexate Contraindicated
- Adenovirus types 4 and 7 live + Methotrexate Contraindicated
- Influenza virus vaccine quadrivalent intranasal + Methotrexate Contraindicated
- Ketorolac + Methotrexate Contraindicated
- Measles mumps and rubella vaccine live + Methotrexate Contraindicated
- Measles mumps and rubella vaccine + Methotrexate Contraindicated
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 Methotrexate with Phenytoin?
MediHelp rates the interaction as moderate. Methotrexate 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. Phenytoin may increase methotrexate toxicity. Phenytoin levels can also fall, risking seizure control, and both drugs have antifolate effects.
How serious is the interaction between Methotrexate 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 blood counts and methotrexate toxicity. Check phenytoin levels and adjust the dose as needed.
What other medicines interact with Methotrexate?
MediHelp also lists interactions of Methotrexate with, for example, Acitretin, Adenovirus types 4 and 7 live, Influenza virus vaccine quadrivalent intranasal. The full list is on the Methotrexate page.
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