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diflunisal vs methotrexate

Side-by-side comparison of diflunisal 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 NSAIDs have been reported to competitively inhibit methotrexate accumulation in rabbit kidney slices. This may indicate that they could enhance the toxicity of methotrexate. Caution should be used when NSAIDs are administered concomitantly with methotrexate.

Recommendation: Be very careful when using these drugs together and make sure your doctor monitors your health and blood work closely.

Drug Class
diflunisal Nonsteroidal Anti-Inflammatory Drug (NSAID)
methotrexate Disease-Modifying Antirheumatic Drug (DMARD)
Type
diflunisal Prescription
methotrexate Prescription
Summary
diflunisal

Diflunisal is a medicine that can help with pain and swelling. It belongs to a class of drugs called NSAIDs.

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.

What It Treats
diflunisal

Diflunisal can help with mild to moderate pain. It can also treat the symptoms of osteoarthritis and rheumatoid arthritis. You should use the lowest dose that works for you, for the shortest time needed.

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.

How It Works
diflunisal

Diflunisal reduces pain and swelling by blocking the production of certain chemicals in your body. These chemicals cause inflammation and pain. By blocking them, diflunisal helps to relieve your symptoms.

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.

Common Side Effects
diflunisal
  • Nausea
  • Vomiting
  • Upset stomach
  • Stomach pain
  • Diarrhea
methotrexate
  • Mouth sores
  • Nausea
  • Abdominal pain
  • Changes in liver tests
FAERS Reports
diflunisal
  • Feeling sick to your stomach 66
  • Feeling very tired 57
  • Discomfort or aching 50
  • Allergic reaction to the medicine 47
  • Pain in your head 45
methotrexate
  • Rheumatoid arthritis 38,053
  • Joint pain 36,283
  • Pain 35,412
  • Tiredness 29,061
  • Feeling sick to your stomach 24,011
Serious Warnings
diflunisal

NSAIDs like diflunisal can increase your risk of heart problems like heart attack and stroke, which can be deadly. This risk is higher if you take it for a long time. You should not take diflunisal if you are having heart bypass surgery. NSAIDs also raise your risk of serious stomach problems like bleeding and ulcers, which can also be deadly. Older adults are at higher risk for these stomach problems.

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.

Pregnancy
diflunisal

Tell your doctor if you are pregnant or plan to become pregnant. Taking diflunisal late in pregnancy may harm your baby. It is not known if diflunisal passes into breast milk, so talk to your doctor before breastfeeding.

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.

Also Compare, Nearby Drugs

How to Read This diflunisal vs methotrexate Comparison

diflunisal 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, diflunisal has 265 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 diflunisal can prevent your kidneys from clearing methotrexate out of your system, which can lead to toxic levels of the drug in your blood. this makes the side effects of methotrexate much more dangerous.. 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 diflunisal 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.