Alternatives to methotrexate
Same-class medications cross-checked against FDA data — compare uses, side effects, and safety profiles.
Brand: Trexall, Otrexup
About 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.
Used for: 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.
Disease-Modifying Antirheumatic Drug (DMARD) Alternatives (3)
hydroxychloroquine
RxPlaquenil
This medicine can treat uncomplicated malaria caused by certain parasites. It can also prevent malaria in areas where the parasites are not resistant to the drug. Hydroxychloroquine also treats rheumatoid arthritis, systemic lupus erythematosus, and chronic discoid lupus erythematosus.
leflunomide
RxArava
Leflunomide treats active rheumatoid arthritis in adults. Rheumatoid arthritis is a disease that causes pain, swelling, and stiffness in the joints. This medicine can help reduce these symptoms.
sulfasalazine
RxAzulfidine
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.
Side Effect Comparison
Adverse event reports from the FDA FAERS database. Higher counts may reflect wider use, not necessarily higher risk.
| Side Effect | methotrexate | hydroxychloroquine | leflunomide | sulfasalazine |
|---|---|---|---|---|
| The medicine is not working | 74,948 | — | 36,982 | 29,013 |
| Rheumatoid arthritis | 38,053 | 12,921 | 24,921 | 19,190 |
| Joint pain | 36,283 | 9,276 | 16,943 | 13,161 |
| Pain | 35,412 | 10,409 | 20,055 | 15,658 |
| Using the medicine for a condition it is not approved for | 33,471 | 15,128 | — | — |
| Tiredness | 29,061 | 8,853 | 15,384 | 13,017 |
| Feeling sick to your stomach | 24,011 | 6,584 | — | 8,384 |
| Swollen joints | 22,295 | — | — | — |
"—" means no reports for that reaction. Report counts reflect total FAERS submissions, not prevalence rates.
Why Consider Alternatives?
Cost
Generic alternatives may be significantly cheaper. Ask your pharmacist about generic options in the Disease-Modifying Antirheumatic Drug (DMARD) class.
Side Effects
Different drugs in the same class can have different side effect profiles. If one doesn't work for you, another might.
Availability
Drug shortages happen. Knowing alternatives helps your doctor switch quickly if your usual medication is unavailable.
Frequently Asked Questions
What are the alternatives to methotrexate? ▼
Can I switch from methotrexate to an alternative? ▼
How to Read These Disease-Modifying Antirheumatic Drug (DMARD) Alternatives
methotrexate (marketed as Trexall, Otrexup) sits within the Disease-Modifying Antirheumatic Drug (DMARD) class, and the 3 alternatives above share the same therapeutic classification under FDA labeling. Drugs grouped this way typically work through similar mechanisms, but they are not interchangeable — each has its own pharmacokinetics, dosing schedule, contraindications, and adverse-event profile derived from separate clinical trials. The labeled indication for methotrexate focuses on: Methotrexate can treat acute lymphoblastic leukemia, a type of cancer, in adults and children.
The side-effect comparison above draws on FDA FAERS data, where methotrexate has 334,120 reports across its top 10 reactions, measured against hydroxychloroquine, leflunomide, sulfasalazine. Raw report counts reflect total exposure — a medication prescribed to tens of millions will accumulate more reports than a newer or niche option even when per-patient risk is lower. Dashes in the comparison table mean that reaction was not among the top reported events for that drug, not that it never occurs. Generic availability for methotrexate is well established, and competing products often have substantially different acquisition costs under NADAC.
Switching between medications in the same class is a clinical decision with real consequences — dosing conversions are not one-to-one, interaction profiles differ, and prior treatment response is individual. Shortage status, insurance formulary placement, and out-of-pocket cost all influence which alternative is practical in a given situation. This comparison surfaces public FDA data to help patients and caregivers prepare informed questions; it is for educational purposes only and does not constitute medical advice. Always talk to your prescriber or pharmacist before switching or stopping any medication.
Medical Disclaimer: This information is for educational purposes only and is not a substitute for professional medical advice. Do not stop or change your medication without talking to your doctor or pharmacist.
Read our methodology — how this data is sourced, computed, and verified.