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methotrexate vs naproxen

Side-by-side comparison of methotrexate and naproxen. 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 naproxen tablets or naproxen sodium tablets and methotrexate, monitor patients for methotrexate toxicity.

Recommendation: Your doctor should monitor you closely for signs of toxicity while you are taking both medications. Report any unusual symptoms like bruising or fatigue to your healthcare provider.

Drug Class
methotrexate Disease-Modifying Antirheumatic Drug (DMARD)
naproxen Nonsteroidal Anti-Inflammatory Drug (NSAID)
Type
methotrexate Prescription
naproxen Over-the-Counter
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.

naproxen

Naproxen is a nonsteroidal anti-inflammatory drug (NSAID). It helps reduce pain, swelling, and stiffness.

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.

naproxen

Naproxen is used to relieve pain and inflammation. You can use it for arthritis, including rheumatoid arthritis and osteoarthritis. It also treats ankylosing spondylitis and juvenile idiopathic arthritis. Naproxen can help with tendonitis, bursitis, gout, menstrual cramps, and general pain.

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.

naproxen

Naproxen works by reducing substances in the body that cause pain and inflammation. It blocks the production of prostaglandins. These substances contribute to the symptoms of pain, swelling, and fever.

Common Side Effects
methotrexate
  • Mouth sores
  • Nausea
  • Abdominal pain
  • Changes in liver tests
naproxen
  • Heartburn
  • Abdominal pain
  • Nausea
  • Constipation
  • Diarrhea
FAERS Reports
methotrexate
  • Rheumatoid arthritis 38,053
  • Joint pain 36,283
  • Pain 35,412
  • Tiredness 29,061
  • Feeling sick to your stomach 24,011
naproxen
  • Pain 8,756
  • Tiredness 7,338
  • Joint pain 7,244
  • Feeling sick to your stomach 7,063
  • Headache 5,717
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.

naproxen

Naproxen may increase your risk of serious heart problems like heart attack or stroke, which can be fatal. This risk may happen early in treatment and increases with longer use. You should not take naproxen if you are having heart bypass surgery. Naproxen can also increase your risk of serious stomach and intestine problems, including bleeding, ulcers, and holes, which can be fatal. These problems can occur without warning. Elderly people are at higher risk.

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.

naproxen

Using naproxen after 20 weeks of pregnancy can cause kidney problems in the unborn baby, leading to low amniotic fluid. Avoid using naproxen at 30 weeks of pregnancy or later because it can cause the baby's heart to close too early. Talk to your doctor if you are pregnant or plan to become pregnant.

Also Compare, Nearby Drugs

How to Read This methotrexate vs naproxen Comparison

methotrexate is classified in the Disease-Modifying Antirheumatic Drug (DMARD) drug class, while naproxen sits within the Nonsteroidal Anti-Inflammatory Drug (NSAID) class. Drugs from different classes work through distinct mechanisms, so a head-to-head comparison illustrates trade-offs rather than equivalence. Both drugs are split between OTC and prescription status, which affects access and supervision.

Adverse event totals above are pulled from the FDA's Adverse Event Reporting System (FAERS). For these top-ranked reactions alone, methotrexate has 162,820 submissions while naproxen has 36,118. 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 naproxen can cause methotrexate to stay in your system longer, which increases the risk of harmful side effects like low blood cell counts or kidney problems.. 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 methotrexate and naproxen - 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.