leflunomide vs methotrexate
Side-by-side comparison of leflunomide and methotrexate Data from FDA drug databases (Orange Book, NDC Directory, recalls, shortages) covering 20,000+ approved drugs, plus CMS pricing; see our methodology.
minor Known Drug Interaction
In patients taking leflunomide, exposure of drugs which are OAT3 substrates (e.g., cefaclor, cimetidine, ciprofloxacin, penicillin G, ketoprofen, furosemide, methotrexate, zidovudine) may be increased. For other substrates of BCRP (e.g., mitoxantrone) and drugs in the OATP family (e.g., methotrexate, rifampin), especially HMG-Co reductase inhibitors (e.g., atorvastatin, nateglinide, pravastatin, repaglinide, and simvastatin), consider reducing the dose of these drugs and monitor patients closely for signs and symptoms of increased exposures to the drugs while patients are taking leflunomide...
Recommendation: Your doctor may need to lower your dose of methotrexate and monitor you closely for side effects.
Arava
Trexall, Otrexup
Leflunomide is a drug that can help reduce the symptoms of rheumatoid arthritis. It works by slowing down the body's immune system.
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.
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.
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.
Leflunomide is a pyrimidine synthesis inhibitor. This means it blocks a certain process in your body. By blocking this process, it can reduce inflammation and slow down the damage to your joints.
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.
- • Diarrhea
- • Respiratory infection
- • Nausea
- • Headache
- • Rash
- • Mouth sores
- • Nausea
- • Abdominal pain
- • Changes in liver tests
- The medicine is not working 36,982
- Rheumatoid arthritis 24,921
- Pain 20,055
- Joint pain 16,943
- Cannot tolerate the medicine 15,586
- 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
This drug can cause serious harm to an unborn baby. If you are pregnant or could become pregnant, you should not take this medicine. This drug can also cause serious liver problems. If you have liver problems, you should not take this medicine. Your doctor will monitor your liver with blood tests.
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.
Do not take leflunomide if you are pregnant. It can cause birth defects. If you are breastfeeding, you should stop while taking this medicine.
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 leflunomide vs methotrexate Comparison
leflunomide is classified in the Disease-Modifying Antirheumatic Drug (DMARD) drug class, while methotrexate 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, leflunomide has 114,487 submissions while methotrexate has 218,167. 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 minor interaction flagged in FDA labeling, attributed to leflunomide blocks the proteins that help remove methotrexate from your body. this can cause methotrexate levels to rise.. 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 leflunomide 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.