This grade answers one narrow question: how strong is the public evidence and safety record behind this drug, and how clean is its money trail and court record? It is not a verdict on whether the drug is right for you.
WARNING: 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 are 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 )] . Methotrexate tablets are contraindicated in patients with a history of severe hypersensitivity reactions to methotrexate, including anaphylaxis [Contraindications ( 4 ), Warnings and Precautions ( 5.2 )] . Serious adverse reactions, including death, have been reported with methotrexate. Closely monitor for adverse reactions of the bone marrow, gastrointestinal tract, liver, lungs, skin, and kidneys. Withhold or discontinue methotrexate tablets as appropriate [Warnings and Precautions ( 5.3 , 5.4 , 5.5 , 5.6 , 5.7 , 5.8 )] . Methotrexate tablets when inadvertently administered once daily have resulted in death [ Warnings and Precautions ( 5.9 )] . WARNING: EMBRYO-FETAL TOXICITY, HYPERSENSITIVITY REA...
Listed on the WHO Model List of Essential Medicines: a global expert panel judged it among the medicines a health system should always have, on evidence of value, not marketing.
Methotrexate tablets are 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 with rheumatoid arthritis ( 1.2 ) Treatment of pediatric patients with polyarticular juvenile idiopathic arthritis (pJIA) ( 1.3 ) Treatment of adults with severe psoriasis ( 1.4 ) 1.1 Neoplastic Diseases Methotrexate tablets are indicated for the: treatment of adults and pediatric patients with acute lymphoblastic leukemia (ALL) as part of a combination chemotherapy maintenance regimen treatment of adults with mycosis fungoides (cutaneous T-cell lymphoma) as a single agent or as part of a combination chemotherapy regimen treatment of adults with relapsed or refractory non-Hodgkin lymphomas as part of a metronomic combination chemotherapy regimen 1.2 Rheumatoid Arthritis Methotrexate tablets are indicated for the treatment of adults with rheumatoid arthritis. 1.3 Polyar...
Methotrexate tablets are contraindicated in: Pregnant women receiving methotrexate tablets for treatment of non-neoplastic diseases [see Warnings and Precautions ( 5.1 ), and Use in Specific Populations ( 8.1 , 8.3 )] . Patients with a history of a severe hypersensitivity reactions, including anaphylaxis, to methotrexate [see Warnings and Precautions ( 5.2 )] . In pregnancy for non-neoplastic diseases ( 4 ) History of severe hypersensitivity to methotrexate ( 4 )
Serious Infections : Monitor patients for infection during and after treatment with methotrexate tablets. Withhold or discontinue methotrexate tablets for serious infections as appropriate. ( 5.11 ) Neurotoxicity : Monitor patients for neurotoxicity and withhold or discontinue methotrexate tablets as appropriate. ( 5.12 ) Secondary Malignancies : Can occur with methotrexate. ( 5.13 ) Tumor Lysis Syndrome : Institute appropriate prophylactic measures in patients at risk for tumor lysis syndrome prior to initiation of methotrexate tablets. ( 5.14 ) Immunizations and Risk Live Vaccines : Immunizations with live vaccines is not recommended. Follow current vaccination practice guidelines. ( 5.15 ) Infertility : Can cause impairment of fertility, oligospermia, and menstrual dysfunction. ( 5.16 , 8.3 ) 5.1 Embryo-Fetal Toxicity Based on published reports and its mechanism of action, methotrexate tablets can cause fetal harm, including fetal death, when administered to a pregnant woman. Methotrexate tablets are contraindicated for use in pregnant women receiving methotrexate tablets for the treatment of non-malignant diseases. Advise pregnant women with neoplastic diseases of the potential...
The following clinically significant adverse reactions are described elsewhere in the labeling: Hypersensitivity Reactions [see Warnings and Precautions ( 5.2 )] Myelosuppression [see Warnings and Precautions ( 5.3 )] Gastrointestinal Toxicity [see Warnings and Precautions ( 5.4 )] Hepatotoxicity [see Warnings and Precautions ( 5.5 )] Pulmonary Toxicity [see Warnings and Precautions ( 5.6 )] Dermatologic Reactions [see Warnings and Precautions ( 5.7 )] Renal Toxicity [see Warnings and Precautions ( 5.8 )] Serious Infections [see Warnings and Precautions ( 5.11 )] Neurotoxicity [see Warnings and Precautions ( 5.12 )] Secondary Malignancies [see Warnings and Precautions ( 5.13 )] Tumor Lysis Syndrome [see Warnings and Precautions ( 5.14 )] Increased Risk of Adverse Reactions Due to Third-Space Accumulation [see Warnings and Precautions ( 5.17 )] Common adverse reactions include ulcerative stomatitis, leukopenia, nausea, abdominal distress. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Teva at 1-888-838-2872 or FDA at 1-800-FDA-1088 www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials and other studies are conducted under widely varying conditions, adv...
Boxed Warning 05/2026
Source: FDA SPL label for Methotrexate (A-S Medication Solutions), effective 20260827. Full label on DailyMed.
These are counts of reports people filed, not rates of harm. Anyone can file one, and nobody checks whether the drug was the cause. Millions of doses are taken for every report sent, so the useful part is how this drug compares with the average across all drugs.
| 2019 | 2020 | 2021 | 2022 | 2023 | 2024 | 2025 | 2026 |
|---|---|---|---|---|---|---|---|
| 46,776 | 50,109 | 33,164 | 35,529 | 32,913 | 28,316 | 24,019 | 9,095 |
25,173 reports blaming this drug for every million Medicare prescriptions filled, which is 9.1× the typical drug on this site. (60,960 reports in 2024–2026, against 2,421,601 Medicare fills in one year. This is the one number here that accounts for how many people take the drug.)
Source: the FDA's Adverse Event Reporting System (FAERS). Reports are voluntary and unverified. Drugs that are prescribed a lot, in the news, or in lawsuits attract more reports, so the percentages are compared with the whole database to correct for that partly, not fully.
| Date | Class | Firm | Reason |
|---|---|---|---|
| 09/2023 | Class III | West-Ward Columbus Inc | Failed Tablet/Capsule Specifications: Tablets were observed to have an unsmooth surface with two tablets demonstrating illegible tablet identification and scoring. |
| 03/2021 | Class II | Cardinal Health Inc. | CGMP Deviations: Intermittent exposure to temperature excursion during storage. |
| 06/2012 | Class II | Hospira Inc. | The affected lots of Carboplatin Injection, Cytarabine Injection, Methotrexate Injection, USP, and Paclitaxel Injection are being recalled due to visible particles embedded in the glass located at the neck of the vial. There may be the pot |
Class I = reasonable probability of serious harm. Class II = temporary or reversible harm. Class III = unlikely to harm. Most generic recalls are manufacturing or labeling defects for one lot, not a verdict on the molecule.
Counts measure how much evidence exists and how transparent it is, not how big the benefit is. For that, ask your prescriber: if 100 people like me took this, how many would get better because of it, and how many would be harmed? (Doctors call these the "number needed to treat" and "number needed to harm.") It differs by condition and is the number drug ads leave out. Sources: PubMed, ClinicalTrials.gov.
In 2024, drug companies reported $1,373 in payments to US physicians and hospitals tied to this drug across 61 transactions (Jylamvo $741, Xatmep $632).
No pending federal MDL names this drug or its brands.
Not named in any federal pharmaceutical settlement of $100M or more on record.
Sources: CMS Open Payments (Sunshine Act); Judicial Panel on Multidistrict Litigation pending docket list; DOJ settlements as tabulated on Wikipedia with links to the primary record. State-court and individual suits are not included.
| Product | Fills | $/fill |
|---|---|---|
| Methotrexate | 2,414,242 | $24 |
| Trexall | 7,121 | $326 |
| Xatmep | 238 | $1,036 |
Same ATC pharmacological class, graded ones first, best grade at the top. Being in the same class does not make them interchangeable for your condition; it makes them worth asking about.