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mefenamic acid vs methotrexate

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

moderate Known Drug Interaction

Methotrexate Clinical Impact: Concomitant use of NSAIDs and methotrexate may increase the risk for methotrexate toxicity (e.g., neutropenia, thrombocytopenia, renal dysfunction). Intervention: During concomitant use of mefenamic acid and methotrexate, monitor patients for methotrexate toxicity.

Recommendation: Your doctor should monitor you for signs of toxicity, such as kidney issues or changes in your blood cell counts.

Drug Class
mefenamic acid Nonsteroidal Anti-Inflammatory Drug (NSAID)
methotrexate Disease-Modifying Antirheumatic Drug (DMARD)
Type
mefenamic acid Prescription
methotrexate Prescription
Summary
mefenamic acid

Mefenamic acid is a medicine used to treat mild to moderate pain and menstrual cramps. It is a type of nonsteroidal anti-inflammatory drug (NSAID).

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.

What It Treats
mefenamic acid

Mefenamic acid is used to relieve mild to moderate pain in people 14 years and older. It should not be used for more than 7 days. It is also used to treat menstrual cramps.

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.

How It Works
mefenamic acid

Mefenamic acid reduces pain and inflammation in the body. It does this by blocking substances in the body that cause pain and swelling. This medicine helps to reduce pain and discomfort.

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.

Common Side Effects
mefenamic acid
  • Abdominal pain
  • Constipation
  • Diarrhea
  • Upset stomach
  • Gas
methotrexate
  • Mouth sores
  • Nausea
  • Abdominal pain
  • Changes in liver tests
FAERS Reports
mefenamic acid
  • Feeling sick to your stomach 296
  • Feeling tired 253
  • Head pain 227
  • General pain 202
  • Feeling lightheaded 177
methotrexate
  • Rheumatoid arthritis 38,053
  • Joint pain 36,283
  • Pain 35,412
  • Tiredness 29,061
  • Feeling sick to your stomach 24,011
Serious Warnings
mefenamic acid

Mefenamic acid may increase the risk of serious heart problems, including heart attack and stroke, which can be fatal. This risk may occur early in treatment and may increase with longer use. You should not take this medicine if you are having heart bypass surgery. Mefenamic acid can also increase the risk of serious stomach and intestinal problems, including bleeding, ulcers, and holes, which can be fatal. These problems can occur without warning. The elderly and those with a history of stomach ulcers or bleeding are at higher risk.

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.

Pregnancy
mefenamic acid

Tell your doctor if you are pregnant or plan to become pregnant. Mefenamic acid may harm your unborn baby. It is not known if mefenamic acid passes into breast milk. Talk to your doctor before breastfeeding.

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.

Also Compare, Nearby Drugs

How to Read This mefenamic acid vs methotrexate Comparison

mefenamic acid is classified in the Nonsteroidal Anti-Inflammatory Drug (NSAID) drug class, while methotrexate sits within the Disease-Modifying Antirheumatic Drug (DMARD) 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, mefenamic acid has 1,155 submissions while methotrexate has 162,820. 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 moderate interaction flagged in FDA labeling, attributed to this pain medicine can prevent your body from clearing out methotrexate, which can lead to toxic levels in your system.. Serious warnings, pregnancy guidance, and contraindications can differ even when indications overlap.

A table cannot substitute for clinical judgment. Effectiveness, tolerability, drug-drug interactions with your other medications, kidney and liver function, pregnancy status, insurance formulary, and price all feed into a decision that only a licensed prescriber can make responsibly. Data here is sourced from FDA Structured Product Labels (SPL) and FAERS, both of which update as manufacturers and clinicians submit new information. This page is for educational purposes only, is not medical advice, and should not be used to self-switch between mefenamic acid and methotrexate - always consult your physician or pharmacist first.

Important: This comparison is for informational purposes only. Drug effects vary between individuals. Always consult your doctor or pharmacist for personalized medical advice.