Two medicines, side by side
Azathioprine vs methotrexate
Azathioprine and methotrexate are both labeled for rheumatoid arthritis. Drugs@FDA records approvals of azathioprine since 1968 and of methotrexate since 1953. Pharmacies paid $0.124 per azathioprine 50 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, azathioprine is a purine antimetabolite and methotrexate a folate analog metabolic inhibitor.
Check it at the source: the azathioprine FDA label on DailyMed (effective November 8, 2025); the methotrexate FDA label on DailyMed (effective May 27, 2026).
Highlights of the azathioprine record
Azathioprine (Imuran) · label of November 8, 2025
MALIGNANCY Chronic immunosuppression with IMURAN, a purine antimetabolite increases risk of malignancy in humans. Reports of malignancy include post-transplant lymphoma and hepatosplenic T-cell lymphoma (HSTCL) in patients with inflammatory bowel disease. Physicians using this drug should be very familiar with this risk as well as with the mutagenic potential to both men and women and with possible hematologic toxicities. Physicians should inform patients of the risk of malignancy with IMURAN.
Used for
From the label: indicationsIMURAN is indicated as an adjunct for the prevention of rejection in renal homotransplantation. It is also indicated for the management of active rheumatoid arthritis to reduce signs and symptoms. Renal Homotransplantation: IMURAN is indicated as an adjunct for the prevention of rejection in renal homotransplantation. […]
On the market
- Earliest approval on file
- March 20, 1968
- Generic labelers
- 17 labelers
- Pharmacy cost
- $0.124 per tablet
Supply and safety
- Shortage
- No current entry
- Recalls
- 1
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 (Azathioprine label of November 8, 2025, Methotrexate label of May 27, 2026); NDC Directory, Drugs@FDA, NADAC, FDA shortages and recalls (October 8, 2026)
How do azathioprine and methotrexate differ on the record?
In FDA's classes, azathioprine is a purine antimetabolite and methotrexate a folate analog metabolic inhibitor.
Half-life, in each label's words: Azathioprine, “Maximum serum radioactivity occurs at 1 to 2 hours after oral 35 S-azathioprine and decays with a half-life of 5 hours.”; Methotrexate, “Elimination The elimination half-life of methotrexate is approximately 3 to 10 hours.”
Both labels carry a boxed warning; the records quote them.
Generics: azathioprine since 1995; methotrexate since 1979 (Drugs@FDA).
| Azathioprine | Methotrexate | |
|---|---|---|
| Labeled for | Organ transplant rejection, Rheumatoid arthritis | Rheumatoid arthritis, Psoriasis, Leukemia, lymphoma and myeloma, Breast cancer |
| Pharmacologic class | Purine Antimetabolite | Folate Analog Metabolic Inhibitor |
| How it works (label) | n/a | 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) | Maximum serum radioactivity occurs at 1 to 2 hours after oral 35 S-azathioprine and decays with a half-life of 5 hours. | Elimination The elimination half-life of methotrexate is approximately 3 to 10 hours. |
| Earliest approval on file (Drugs@FDA) | March 20, 1968 | December 7, 1953 |
| First generic approved | March 31, 1995 | September 5, 1979 |
| Generic labelers (NDC) | 17 labelers | 29 labelers |
| Pharmacy cost (NADAC, each one's most listed form; strengths differ) | $0.124 per tablet (Azathioprine 50 mg tablet) | $0.158 per tablet (Methotrexate 2.5 mg tablet) |
| 12-month price change | -10% | -4% |
| Boxed warning | Yes | Yes |
| Shortage now | No current entry | In shortage |
| Recalls recorded | 1 | 8 |
| FAERS reports (a report is not proof of cause; counts follow how widely a medicine is used) | 89,586 | 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)
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 azathioprine
- every medicine labeled for the same conditions