indomethacin vs methotrexate
Side-by-side comparison of indomethacin 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 indomethacin capsules and methotrexate, monitor patients for methotrexate toxicity.
Recommendation: Your doctor should monitor you closely for signs of drug toxicity while you are using both medications.
Indocin
Trexall, Otrexup
Indomethacin is a drug that reduces pain and swelling. It belongs to a class of drugs called NSAIDs.
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.
Indomethacin treats moderate to severe rheumatoid arthritis, ankylosing spondylitis, and osteoarthritis. It can also help with acute painful shoulder (bursitis or tendinitis) and gouty arthritis. This medicine reduces pain and swelling in your joints.
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.
Indomethacin works by blocking substances in the body that cause pain and inflammation. These substances are called prostaglandins. By blocking them, indomethacin helps to reduce swelling, pain, and stiffness.
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.
- • Headache
- • Dizziness
- • Upset stomach
- • Nausea
- • Mouth sores
- • Nausea
- • Abdominal pain
- • Changes in liver tests
- Feeling tired 1,102
- Joint pain 1,002
- Head pain 990
- Aches or soreness 921
- Feeling sick to your stomach 907
- Rheumatoid arthritis 38,053
- Joint pain 36,283
- Pain 35,412
- Tiredness 29,061
- Feeling sick to your stomach 24,011
Indomethacin may increase your risk of serious heart problems like heart attack or stroke, which can be fatal. This risk may occur early in treatment and may increase with longer use. You should not take this medicine before or after heart bypass surgery (CABG). Indomethacin can also increase your risk of serious stomach and intestine problems like bleeding, ulcers, and holes, which can be fatal. These problems can happen without warning. Elderly patients and those with a history of ulcers or GI bleeding are at higher risk.
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.
Using indomethacin during the later stages of pregnancy may harm your unborn baby. Limit use between 20 and 30 weeks of pregnancy, and avoid use after 30 weeks. Talk to your doctor if you are pregnant or plan to become pregnant.
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.
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How to Read This indomethacin vs methotrexate Comparison
indomethacin 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, indomethacin has 4,922 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 indomethacin can cause methotrexate to build up to dangerous levels in your body, which may harm your kidneys or blood cells.. 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 indomethacin 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.