Two medicines, side by side
Methotrexate vs sulfasalazine
Methotrexate and sulfasalazine are both labeled for rheumatoid arthritis. Drugs@FDA records approvals of methotrexate since 1953 and of sulfasalazine since 1950. Pharmacies paid $0.158 per methotrexate 2.5 mg tablet and $0.199 per sulfasalazine 500 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, methotrexate is a folate analog metabolic inhibitor and sulfasalazine an aminosalicylate.
Check it at the source: the methotrexate FDA label on DailyMed (effective May 27, 2026); the sulfasalazine FDA label on DailyMed (effective May 29, 2026).
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
Highlights of the sulfasalazine record
Sulfasalazine (Azulfidine) · label of May 29, 2026
Used for
From the label: indicationsAZULFIDINE Tablets are indicated: • in the treatment of mild to moderate ulcerative colitis, and as adjunctive therapy in severe ulcerative colitis; and • for the prolongation of the remission period between acute attacks of ulcerative colitis.
On the market
- Earliest approval on file
- June 20, 1950
- Generic labelers
- 5 labelers
- Pharmacy cost
- $0.199 per tablet
Supply and safety
- Shortage
- No current entry
- Recalls
- 0
Source: FDA drug labels via openFDA (Methotrexate label of May 27, 2026, Sulfasalazine label of May 29, 2026); NDC Directory, Drugs@FDA, NADAC, FDA shortages and recalls (October 8, 2026)
How do methotrexate and sulfasalazine differ on the record?
In FDA's classes, methotrexate is a folate analog metabolic inhibitor and sulfasalazine an aminosalicylate.
Half-life, in each label's words: Methotrexate, “Elimination The elimination half-life of methotrexate is approximately 3 to 10 hours.”; Sulfasalazine, “The observed plasma half-life for intravenous sulfasalazine is 7.6 ± 3.4 hours.”
Only the methotrexate label carries a boxed warning.
Generics: methotrexate since 1979; sulfasalazine since 1973 (Drugs@FDA).
| Methotrexate | Sulfasalazine | |
|---|---|---|
| Labeled for | Rheumatoid arthritis, Psoriasis, Leukemia, lymphoma and myeloma, Breast cancer | Crohn's disease and ulcerative colitis, Rheumatoid arthritis |
| Pharmacologic class | Folate Analog Metabolic Inhibitor | Aminosalicylate |
| How it works (label) | 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. | n/a |
| Half-life (label) | Elimination The elimination half-life of methotrexate is approximately 3 to 10 hours. | The observed plasma half-life for intravenous sulfasalazine is 7.6 ± 3.4 hours. |
| Earliest approval on file (Drugs@FDA) | December 7, 1953 | June 20, 1950 |
| First generic approved | September 5, 1979 | November 12, 1973 |
| Generic labelers (NDC) | 29 labelers | 5 labelers |
| Pharmacy cost (NADAC, each one's most listed form; strengths differ) | $0.158 per tablet (Methotrexate 2.5 mg tablet) | $0.199 per tablet (Sulfasalazine 500 mg tablet) |
| 12-month price change | -4% | +10% |
| Boxed warning | Yes | No |
| Shortage now | In shortage | No current entry |
| Recalls recorded | 8 | 0 |
| FAERS reports (a report is not proof of cause; counts follow how widely a medicine is used) | 489,791 | 77,784 |
| 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)
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 methotrexate
- every medicine labeled for the same conditions