Two medicines, side by side
Hydroxychloroquine vs methotrexate
Hydroxychloroquine and methotrexate are both labeled for rheumatoid arthritis. Drugs@FDA records approvals of hydroxychloroquine since 1955 and of methotrexate since 1953. Pharmacies paid $0.149 per hydroxychloroquine 200 mg tablet and $0.158 per methotrexate 2.5 mg tablet (NADAC, October 7, 2026); the strengths differ, so the two prices are not like for like. Methotrexate's other strengths are brand-only: $21.76 per mL (Xatmep 2.5 mg/mL oral solution). In FDA's classes, hydroxychloroquine is an antirheumatic agent and methotrexate a folate analog metabolic inhibitor.
Check it at the source: the hydroxychloroquine FDA label on DailyMed (effective October 8, 2024); the methotrexate FDA label on DailyMed (effective May 27, 2026).
Highlights of the hydroxychloroquine record
Hydroxychloroquine (Plaquenil) · label of October 8, 2024
Used for
From the label: indicationsSOVUNA is an antimalarial and antirheumatic indicated for the: Treatment of uncomplicated malaria due to Plasmodium falciparum, Plasmodium malariae, Plasmodium ovale, and Plasmodium vivax in adult and pediatric patients. (1.1) Prophylaxis of malaria in geographic areas where chloroquine resistance is not reported in adult and pediatric patients. (1.1) Treatment of rheumatoid arthritis in adults. […]
On the market
- Earliest approval on file
- April 18, 1955
- Generic labelers
- 28 labelers
- Pharmacy cost
- $0.149 per tablet
Supply and safety
- Shortage
- A presentation being discontinued
- Recalls
- 2
Highlights of the methotrexate record
Methotrexate (Rasuvo) · label of May 27, 2026
EMBRYO-FETAL TOXICITY, HYPERSENSITIVITY REACTIONS, SEVERE ADVERSE REACTIONS, and RISK OF MEDICATION ERRORS Methotrexate Tablets can cause embryo-fetal toxicity, including fetal death. For non-neoplastic diseases, Methotrexate Tablets is contraindicated in pregnancy. For neoplastic diseases, advise females and males of reproductive potential to use effective contraception [see Contraindications (4), Warnings and Precautions (5.1), Use in Specific Populations (8.1 , 8.3) ].
Used for
From the label: indicationsMethotrexate tablets is a dihydrofolate reductase inhibitor indicated for the: Treatment of adults and pediatric patients with acute lymphoblastic leukemia (ALL) as part of a combination chemotherapy maintenance regimen ( 1.1 ) Treatment of adults with mycosis fungoides ( 1.1 ) Treatment of adults with relapsed or refractory non-Hodgkin lymphoma as part of a metronomic combination regimen ( 1.1 ) Treatment of adults […]
On the market
- Earliest approval on file
- December 7, 1953
- Generic labelers
- 29 labelers
- Pharmacy cost
- $0.158 per tablet
Supply and safety
- Shortage
- In shortage
- Recalls
- 8
Source: FDA drug labels via openFDA (Hydroxychloroquine label of October 8, 2024, Methotrexate label of May 27, 2026); NDC Directory, Drugs@FDA, NADAC, FDA shortages and recalls (October 8, 2026)
How do hydroxychloroquine and methotrexate differ on the record?
In FDA's classes, hydroxychloroquine is an antirheumatic agent and methotrexate a folate analog metabolic inhibitor.
How each works, in its label's words: Hydroxychloroquine, “Malaria Hydroxychloroquine is a 4-aminoquinoline antimalarial [see Microbiology (12.4)] and antirheumatic agent.”; Methotrexate, “Methotrexate inhibits dihydrofolic acid reductase.”
Half-life, in each label's words: Hydroxychloroquine, “Results following a single oral dose of a 200 mg tablet demonstrated a half-life of hydroxychloroquine about 40 days in …”; Methotrexate, “Elimination The elimination half-life of methotrexate is approximately 3 to 10 hours.”
Only the methotrexate label carries a boxed warning.
Generics: hydroxychloroquine since 1994; methotrexate since 1979 (Drugs@FDA).
| Hydroxychloroquine | Methotrexate | |
|---|---|---|
| Labeled for | Rheumatoid arthritis | Rheumatoid arthritis, Psoriasis, Leukemia, lymphoma and myeloma, Breast cancer |
| Pharmacologic class | Antimalarial, Antirheumatic Agent | Folate Analog Metabolic Inhibitor |
| How it works (label) | Malaria Hydroxychloroquine is a 4-aminoquinoline antimalarial [see Microbiology (12.4)] and antirheumatic agent. | Methotrexate inhibits dihydrofolic acid reductase. Dihydrofolates must be reduced to tetrahydrofolates by this enzyme before they can be utilized as carriers of one-carbon groups in the synthesis of purine nucleotides and thymidylate. |
| Half-life (label) | Results following a single oral dose of a 200 mg tablet demonstrated a half-life of hydroxychloroquine about 40 days in whole blood. | Elimination The elimination half-life of methotrexate is approximately 3 to 10 hours. |
| Earliest approval on file (Drugs@FDA) | April 18, 1955 | December 7, 1953 |
| First generic approved | September 30, 1994 | September 5, 1979 |
| Generic labelers (NDC) | 28 labelers | 29 labelers |
| Pharmacy cost (NADAC, each one's most listed form; strengths differ) | $0.149 per tablet (Hydroxychloroquine 200 mg tablet) | $0.158 per tablet (Methotrexate 2.5 mg tablet) |
| 12-month price change | -8% | -4% |
| Boxed warning | No | Yes |
| Shortage now | A presentation being discontinued | In shortage |
| Recalls recorded | 2 | 8 |
| FAERS reports (a report is not proof of cause; counts follow how widely a medicine is used) | 151,392 | 489,791 |
| DEA schedule | none | none |
Source: Drugs@FDA, FDA NDC Directory, CMS NADAC of October 7, 2026, FDA shortages and recalls, FAERS via openFDA (FDA files October 8, 2026)
Do their labels mention each other?
Hydroxychloroquine label, drug interactionsConcomitant use of SOVUNA and methotrexate may increase the incidence of adverse reactions.
Hydroxychloroquine label, drug interactionsConcomitant use of PLAQUENIL and methotrexate may increase the incidence of adverse reactions.
Methotrexate label, drug interactionsCombined use of methotrexate with gold, penicillamine, hydroxychloroquine, sulfasalazine, or cytotoxic agents, has not been studied and may increase the incidence of adverse effects.
Source: FDA drug labels via openFDA
What do the labels say about using others of their kind?
Methotrexate label, drug interactionsOral antibiotics (including neomycin) Antifolate drugs (e.g., dapsone, pemetrexed, pyrimethamine and sulfonamides) Oral or intravenous penicillin or sulfonamide antibiotics Aspirin and other nonsteroidal anti-inflammatory drugs Highly protein-bound drugs (e.g., oral anticoagulants, phenytoin, salicylates, sulfonamides, sulfonylureas, and tetracyclines) Hepatotoxic products Proton pump inhibitors Weak acids (e.g. …
Source: FDA drug labels via openFDA
What next?
- Alternatives to hydroxychloroquine
- every medicine labeled for the same conditions