Drug side effects
methotrexate Side Effects
The reactions most often reported to the FDA for methotrexate (also sold as Trexall, Otrexup), with demographics, serious outcomes, and reporting trends.
Data updated 2026-05-15
- 410,053
- FAERS reports
Data from the FDA Adverse Event Reporting System (FAERS), 1999 to 2025. A FAERS report records a temporal association, not proof of cause. See our methodology for how figures are compiled and de-duplicated.
The most commonly reported side effects of methotrexate come from 410,053 reports to the FDA, broken down here by frequency, patient demographics, and serious outcomes.
This page analyzes 410,053 reports to the FDA Adverse Event Reporting System (FAERS) for methotrexate (Trexall): the reactions reported most often, who reported them, serious outcomes such as hospitalization, and year-over-year trends. A FAERS report does not prove the drug caused the effect, and report volume tracks how widely a drug is used, not how likely an effect is for any one person. Educational information, not medical advice.
Total Reports
410,053
Reports Mentioning Death
32,502
7.9% of reports — not proof the medicine caused the death
Hospitalizations
115,535
28.2% of reports
Top Indication
Rheumatoid Arthritis
Most Reported Adverse Reactions
Who Reports Side Effects
Gender Distribution
Age Distribution
Reporting Trend by Year
Reactions in Death Reports
Top reactions reported in 32,502 reports where death was an outcome. These are voluntarily reported and do not establish causation.
| Reaction | Reports |
|---|---|
| DEATH | 4,939 |
| PNEUMONIA | 3,509 |
| SEPSIS | 2,515 |
| GENERAL PHYSICAL HEALTH DETERIORATION | 2,444 |
| PYREXIA | 2,393 |
| DIARRHOEA | 2,379 |
| RHEUMATOID ARTHRITIS | 2,344 |
| INFECTION | 2,338 |
| VOMITING | 2,324 |
| RASH | 2,272 |
| FATIGUE | 2,247 |
| PAIN | 2,244 |
| HYPERTENSION | 2,159 |
| CONDITION AGGRAVATED | 2,094 |
| SYSTEMIC LUPUS ERYTHEMATOSUS | 2,084 |
| DYSPNOEA | 2,077 |
| TYPE 2 DIABETES MELLITUS | 2,044 |
Reactions in Hospitalization Reports
Top reactions in 115,535 reports where hospitalization was an outcome.
| Reaction | Reports |
|---|---|
| ARTHRALGIA | 9,790 |
| PAIN | 9,473 |
| PYREXIA | 9,136 |
| RHEUMATOID ARTHRITIS | 9,082 |
| PNEUMONIA | 8,949 |
| FATIGUE | 8,109 |
| NAUSEA | 8,009 |
| VOMITING | 7,344 |
| DIARRHOEA | 7,185 |
| HEADACHE | 6,745 |
| DYSPNOEA | 6,592 |
| CONDITION AGGRAVATED | 6,490 |
| RASH | 6,108 |
| MALAISE | 5,986 |
| JOINT SWELLING | 5,837 |
| INFECTION | 5,269 |
| PAIN IN EXTREMITY | 5,218 |
| FALL | 5,211 |
Nearby, Related Medications
What the FAERS Data Reveals About methotrexate Side Effects
The FDA Adverse Event Reporting System (FAERS) contains 410,053 voluntary reports linked to methotrexate and its brand equivalents (Trexall, Otrexup), spanning 1999 through 2025. Of those, 32,502 (7.9%) listed death as an outcome and 115,535 (28.2%) involved hospitalization. The most common indication reported alongside adverse events was Rheumatoid Arthritis.
Demographic breakdowns help contextualize who is being exposed to the drug. Of reports with known sex, 71% were female and 29% male; age distribution skews toward 45-64, with 105,081 reports in that bracket. The single most reported reaction is rheumatoid arthritis with 38,053 submissions, followed by arthralgia and pain.
How to read these numbers
FAERS is a signal-detection tool, not a scorecard. Reports are voluntary, and a single case may list multiple suspect drugs, so numbers above should not be read as incidence rates or per-patient risk. Widely prescribed drugs naturally accumulate more reports than niche therapies even when individual risk is low. These aggregates are useful for spotting patterns that merit further pharmacovigilance, not for choosing between medications. This page is for educational reference only and is not medical advice, speak with a licensed clinician about any side-effect concerns.
Drugs With a Similar FAERS Report Volume
Other medications with a total FDA adverse-event report count closest to methotrexate's 410,053.
Read our methodology - how this data is sourced, computed, and verified.