Does Methotrexate Interact With Phenytoin?

If coadministration cannot be avoided, monitor closely for methotrexate adverse reactions when coadministered with: Oral antibiotics (including neomycin) Antifolate drugs (e.g., dapsone, pemetrexed, pyrimethamine and sulfonamides) Oral or intravenous penicillin or sulfonamide antibiotics Aspirin and other nonsteroidal anti- inflammatory drugs Hepatotoxic products Highly protein-bound drugs (e.g., oral anticoagulants, phenytoin, salicylates, sulfonamides, sulfonylureas, and tetracyclines) Prot…

Severity: Major

Severity basis: drug interactions section (keywords: avoid). Combining Methotrexate (Antimetabolite DMARD) and Phenytoin (Anticonvulsant) is classified as a major interaction.

What to Do

The label advises avoiding this combination or using it only under close medical supervision. Talk to your prescriber or pharmacist before combining them.

From the FDA Label

If coadministration cannot be avoided, monitor closely for methotrexate adverse reactions when coadministered with: Oral antibiotics (including neomycin) Antifolate drugs (e.g., dapsone, pemetrexed, pyrimethamine and sulfonamides) Oral or intravenous penicillin or sulfonamide antibiotics Aspirin and other nonsteroidal anti- inflammatory drugs Hepatotoxic products Highly protein-bound drugs (e.g., oral anticoagulants, phenytoin, salicylates, sulfonamides, sulfonylureas, and tetracyclines) Prot…

Source: FDA structured product labeling (set_id 04a95db9-a124-4b97-bd71-1c37a6b3b0c8).

Methotrexate

Antimetabolite DMARD

Brands: Trexall, Otrexup, Rasuvo

View Methotrexate safety profile

Phenytoin

Anticonvulsant

Brands: Dilantin

View Phenytoin safety profile

Check these against your full medication list in our free Interaction Checker

This information is educational — not medical advice.

This page is provided for general educational purposes and summarizes publicly available data from sources such as the U.S. Food & Drug Administration. It is not a substitute for the judgment of a licensed clinician and should not be used to start, stop, or change any medication. It may be incomplete or out of date, and individual circumstances vary. Always talk with your prescriber or pharmacist about your specific medications and health conditions. If you think you may have a medical emergency, call 911.

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