hydroxychloroquine vs methotrexate
Side-by-side comparison of hydroxychloroquine 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
7.5 Methotrexate Concomitant use of hydroxychloroquine sulfate tablets and methotrexate may increase the incidence of adverse reactions.
Recommendation: Your doctor may need to watch you more closely for any new or worsening symptoms while you are on both drugs.
Plaquenil
Trexall, Otrexup
Hydroxychloroquine is a drug used to treat or prevent malaria, and to treat certain autoimmune diseases. It works by interfering with the immune system and by killing malaria parasites.
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.
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.
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.
Hydroxychloroquine is an antimalarial and antirheumatic drug. It is thought to work by interfering with the immune system's activity. It also stops the growth of malaria parasites in red blood cells.
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.
- • Nausea
- • Vomiting
- • Diarrhea
- • Abdominal pain
- • Fatigue
- • Mouth sores
- • Nausea
- • Abdominal pain
- • Changes in liver tests
- The medicine did not work 20,457
- Using the medicine for a condition it is not approved for 15,128
- Rheumatoid arthritis 12,921
- Pain 10,409
- Joint pain 9,276
- 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 heart problems, including a weakened heart muscle and irregular heartbeats. It can also cause irreversible damage to your retina, so regular eye exams are needed. This medicine can also cause serious skin reactions. If you have psoriasis or porphyria, talk to your doctor before taking this medicine. It can also cause liver and kidney problems.
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.
Tell your doctor if you are pregnant or plan to become pregnant. This drug can cross the placenta, but studies haven't shown a risk of major birth defects. Talk to your doctor about the risks and benefits of taking this medicine while pregnant. Hydroxychloroquine passes into breast milk. Talk to your doctor about breastfeeding 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 hydroxychloroquine vs methotrexate Comparison
hydroxychloroquine 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, hydroxychloroquine has 68,191 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 using these two medications at the same time can make it more likely that you will experience side effects.. 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 hydroxychloroquine 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.