Methotrexate
According to the FDA label: Methotrexate tablets are a diydrofolate 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…
478,278 adverse event reports submitted to the FDA (1999–2026)
Top Reported Adverse Events
The most frequently reported events in association with Methotrexate in the FAERS database. These are events reported by patients taking this medication, not necessarily caused by it. A single report may include multiple events.
Show these terms with plain-language definitions
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Drug Ineffective 92,090 reports
A report that the medication did not work as expected for the person taking it. This is a reporting category, not a sign the drug is defective. It simply means someone felt it was not helping their condition.
Full definition in the glossary →Rheumatoid Arthritis 42,118 reports
An autoimmune condition where the immune system attacks the joints, causing pain and swelling. It often appears in reports because it is a condition being treated, not always a reaction.
Full definition in the glossary →Arthralgia 40,040 reports
Off Label Use 39,186 reports
Using a medication for a condition or in a way that the FDA has not officially approved. This is common and often legal, and a report of it does not mean something went wrong. Doctors sometimes prescribe drugs off label based on their judgment.
Full definition in the glossary →Pain 38,993 reports
A general report of physical discomfort, used when no more specific location is given.
Full definition in the glossary →Fatigue 32,423 reports
Extreme tiredness or lack of energy that does not improve with rest.
Full definition in the glossary → See all drugs reporting this event →Nausea 28,353 reports
The feeling of sickness in your stomach that often comes before vomiting.
Full definition in the glossary → See all drugs reporting this event →Joint Swelling 24,638 reports
Swelling in or around a joint.
Full definition in the glossary →Drug Intolerance 24,176 reports
A report that the person could not tolerate a medication, often due to uncomfortable effects.
Full definition in the glossary →Condition Aggravated 23,416 reports
A report that the person's existing health condition got worse. This describes a worsening of something the person already had, not necessarily a new problem caused by the drug.
Full definition in the glossary →Headache 22,995 reports
Pain in the head or upper neck.
Full definition in the glossary → See all drugs reporting this event →Rash 22,082 reports
An area of irritated, red, or bumpy skin.
Full definition in the glossary → See all drugs reporting this event →Diarrhoea 20,470 reports
Loose or watery bowel movements, often frequent. Also spelled diarrhea in American English.
Full definition in the glossary → See all drugs reporting this event →Pain in Extremity 19,719 reports
Pain in an arm or leg.
Full definition in the glossary →Drug Hypersensitivity 19,485 reports
An allergic-type reaction to a medication.
Full definition in the glossary →
Ranked by frequency of reports, not severity. The most-reported event is not necessarily the most dangerous or the most common in patients taking this drug.
Who Is Reporting
Demographics of patients in FAERS reports that included this information. Not all reports include patient demographics.
By Sex
View reporter sex data as a table
| Sex | Reports |
|---|---|
| Female | 304,931 |
| Male | 125,311 |
| Unknown | 1,402 |
By Age Group
View age group data as a table
| Age group | Reports |
|---|---|
| 0-17 | 31,756 |
| 18-34 | 25,671 |
| 35-49 | 55,934 |
| 50-64 | 106,201 |
| 65-74 | 59,681 |
| 75+ | 30,217 |
This shows who filed reports, reflecting who takes this drug and who tends to report, not who is at greatest risk.
Reported Outcomes
Outcomes recorded in FAERS reports that included Methotrexate. A single report may involve multiple reactions, each with a different outcome. These categories are defined by FDA reporting guidelines, not by PillSignal.
View outcome data as a table
| Outcome | Reports |
|---|---|
| Other Serious | 263,097 |
| Hospitalization | 130,833 |
| Non-Serious | 127,550 |
| Death | 36,884 |
| Life-Threatening | 24,618 |
| Disability | 17,549 |
Serious outcomes are far more likely to be reported than mild ones, so this overstates how often outcomes are serious. A recorded death does not mean the drug caused it.
Report Volume Over Time
Number of FAERS reports received per quarter for Methotrexate. Changes in volume may reflect shifts in prescribing rates, media attention, or reporting behavior, not changes in the medication's safety profile.
View report trend as a table
| Year | Reports |
|---|---|
| 1999 | 3 |
| 2002 | 1 |
| 2003 | 5 |
| 2004 | 5,891 |
| 2005 | 5,584 |
| 2006 | 5,148 |
| 2007 | 8,029 |
| 2008 | 9,258 |
| 2009 | 9,417 |
| 2010 | 9,833 |
| 2011 | 10,986 |
| 2012 | 15,622 |
| 2013 | 17,734 |
| 2014 | 17,445 |
| 2015 | 21,277 |
| 2016 | 25,470 |
| 2017 | 32,185 |
| 2018 | 43,783 |
| 2019 | 40,976 |
| 2020 | 46,023 |
| 2021 | 30,924 |
| 2022 | 34,802 |
| 2023 | 32,366 |
| 2024 | 27,819 |
| 2025 | 23,502 |
| 2026 (partial) | 4,195 |
The steep increase around 2004 reflects the FDA's move to electronic submission, not a change in this drug's safety. Trends track reporting volume, not risk.
Medications commonly reported with Methotrexate
In FDA adverse event reports that mention Methotrexate, these medications appeared most often in the same report.
- Adalimumab (117,517 reports)
- Etanercept (115,824 reports)
- Folic Acid (107,095 reports)
- Prednisone (94,527 reports)
- Leflunomide (59,415 reports)
This reflects co-occurrence in submitted reports, not evidence of drug interaction or combined risk. People often report several medications taken for the same condition or for unrelated reasons. Talk to a doctor or pharmacist about your specific medications.
Related Drugs
Other medications with similar adverse event profiles in FDA FAERS reports.
Data Source
This data is sourced from the FDA's Adverse Event Monitoring System (AEMS), formerly FAERS, via the OpenFDA API. PillSignal is not affiliated with the FDA.
View this data on the FDA website →Data last updated: June 2026