methotrexate vs phenytoin

According to this portal's Publishing Organization, this page was last reviewed in August 2026 against our methodology. Figures and extracts on this site, including tables above 1,000 rows when the corpus is that large, are the publisher's responsibility.

Side-by-side comparison of methotrexate and phenytoin. Data from FDA drug databases (Orange Book, NDC Directory, recalls, shortages) covering 20,000+ approved drugs, plus CMS pricing; see our methodology.

minor Known Drug Interaction

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) Proton pump inhibitors Weak acids (e.g., salicylates) Nephrotoxic products Probenecid Nitrous Oxide...

Drug Class
methotrexate Disease-Modifying Antirheumatic Drug (DMARD)
phenytoin Anticonvulsant (Hydantoin)
Type
methotrexate Prescription
phenytoin Prescription
Summary
methotrexate

Methotrexate is a drug that can treat certain cancers, rheumatoid arthritis, psoriasis, and other conditions. It works by slowing the growth of cells in the body.

phenytoin

Phenytoin injection is used to treat certain types of seizures. It can also prevent seizures during or after neurosurgery.

What It Treats
methotrexate

Methotrexate can treat acute lymphoblastic leukemia, a type of cancer, in adults and children. It also treats mycosis fungoides, a skin lymphoma, in adults. Additionally, it treats relapsed or refractory non-Hodgkin lymphoma in adults. For non-cancer conditions, it treats rheumatoid arthritis in adults, polyarticular juvenile idiopathic arthritis (pJIA) in children, and severe psoriasis in adults.

phenytoin

This medicine treats generalized tonic-clonic status epilepticus, a type of prolonged seizure. It also helps prevent and treat seizures that may happen during or after brain surgery. Sometimes, it can be used for a short time instead of the oral form of phenytoin when you cannot take the medicine by mouth.

How It Works
methotrexate

Methotrexate blocks an enzyme called dihydrofolate reductase. This enzyme is needed for cells to grow and multiply. By blocking this enzyme, methotrexate slows down the growth of cells, especially cancer cells and cells that cause inflammation in arthritis and psoriasis.

phenytoin

Phenytoin works by slowing down the signals in the brain that cause seizures. It stabilizes nerve cell membranes, reducing excessive electrical activity. This helps to prevent seizures from starting or spreading.

Common Side Effects
methotrexate
  • Mouth sores
  • Nausea
  • Abdominal pain
  • Changes in liver tests
phenytoin

No common side effects listed.

FAERS Reports
methotrexate
  • Rheumatoid Arthritis 38,053
  • Arthralgia 36,283
  • Pain 35,413
  • Fatigue 29,061
  • Nausea 24,009
phenytoin
  • Drug Interaction 1,547
  • Seizure 1,382
  • Toxicity To Various Agents 1,353
  • Convulsion 1,262
  • Status Epilepticus 791
Serious Warnings
methotrexate

Methotrexate can cause serious harm to an unborn baby, including death. If you are pregnant, you should not take this medicine for non-cancer conditions. If you are taking it for cancer, talk to your doctor about the risks. This medicine can also cause severe allergic reactions and other serious side effects that can be life-threatening. Contact your doctor immediately if you experience any signs of infection, lung problems, or kidney problems.

phenytoin

This medicine can cause serious heart problems if given too quickly. The injection rate should not be faster than 50 mg per minute for adults, and 1 to 3 mg/kg/min (or 50 mg per minute, whichever is slower) for children. Your heart will be monitored closely during and after the injection.

Pregnancy
methotrexate

Methotrexate can cause birth defects or fetal death if taken during pregnancy for non-cancer conditions. If you are pregnant or plan to become pregnant, talk to your doctor. Do not breastfeed while taking methotrexate, as it can pass into breast milk and harm your baby.

phenytoin

Taking phenytoin during pregnancy may increase the risk of birth defects. If you are pregnant or plan to become pregnant, talk to your doctor about the risks and benefits of this medicine.

Also Compare, Nearby Drugs

How to Read This methotrexate vs phenytoin Comparison

methotrexate is classified in the Disease-Modifying Antirheumatic Drug (DMARD) drug class, while phenytoin sits within the Anticonvulsant (Hydantoin) class. Drugs from different classes work through distinct mechanisms, so a head-to-head comparison illustrates trade-offs rather than equivalence. Both drugs are prescription-only, so a licensed provider must authorize use.

Adverse event totals above are pulled from the FDA's Adverse Event Reporting System (FAERS). For these top-ranked reactions alone, methotrexate has 162,819 submissions while phenytoin has 6,335. Those figures reflect cumulative reporting volume, not per-patient risk, so older, widely dispensed drugs typically look worse on count alone. These two drugs have a known minor interaction flagged in FDA labeling, attributed to phenytoin can push methotrexate off the proteins in your blood, which increases the amount of active methotrexate in your system.. Serious warnings, pregnancy guidance, and contraindications can differ even when indications overlap.

A table cannot represent individual circumstances. Data here is sourced from FDA Structured Product Labels (SPL) and FAERS, both of which update as manufacturers and clinicians submit new information. This registry does not provide medical, treatment, substitution, or medication-change directions for methotrexate or phenytoin.

Registry boundary: This comparison displays source-record fields and does not provide individualized medical direction.