methotrexate vs sulfasalazine
Side-by-side comparison of methotrexate and sulfasalazine Data from FDA drug databases (Orange Book, NDC Directory, recalls, shortages) covering 20,000+ approved drugs, plus CMS pricing; see our methodology.
Trexall, Otrexup
Azulfidine
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.
Sulfasalazine is a drug that reduces inflammation in the body. It is used to treat ulcerative colitis.
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.
Sulfasalazine treats ulcerative colitis, a condition that causes inflammation and sores in the lining of the large intestine. It can help with mild to moderate ulcerative colitis. It can also be used with other treatments for severe ulcerative colitis. This medicine can also help keep ulcerative colitis from coming back.
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.
Sulfasalazine is an anti-inflammatory drug. It works by reducing inflammation in the colon. The exact way it does this is not fully known.
- • Mouth sores
- • Nausea
- • Abdominal pain
- • Changes in liver tests
- • Loss of appetite
- • Headache
- • Nausea
- • Vomiting
- • Stomach upset
- The medicine is not working 74,948
- Rheumatoid arthritis 38,053
- Joint pain 36,283
- Pain 35,412
- Using the medicine for a condition it is not approved for 33,471
- The medicine is not working 29,013
- Rheumatoid arthritis 19,190
- Pain 15,658
- Cannot tolerate the medicine 13,521
- Joint pain 13,161
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.
You should not take this medicine if you have a blockage in your intestines or urinary tract. You should not take this medicine if you have porphyria, as it could cause an attack. You should not take this medicine if you are allergic to sulfasalazine, its ingredients, sulfonamides, or salicylates.
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.
Tell your doctor if you are pregnant or plan to become pregnant. It is not known if Sulfasalazine will harm your unborn baby. Talk to your doctor about the risks and benefits of taking this medicine while breastfeeding.
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How to Read This methotrexate vs sulfasalazine Comparison
methotrexate is classified in the Disease-Modifying Antirheumatic Drug (DMARD) drug class, while sulfasalazine sits within the Disease-Modifying Antirheumatic Drug (DMARD) class. Because both drugs share the same classification, they are often considered interchangeable in theory — but clinical outcomes rarely track that cleanly. 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 218,167 submissions while sulfasalazine has 90,543. Those figures reflect cumulative reporting volume — not per-patient risk — so older, widely dispensed drugs typically look worse on count alone. No direct interaction between these two drugs is listed in our FDA-derived dataset, though co-prescription still warrants pharmacist review. 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 sulfasalazine — 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.