METHOTREXATE

85/100 · Critical

Manufactured by Medexus Pharma Inc.

High Safety Concerns with Methotrexate Due to Serious Reactions and Diverse Adverse Events

1,175,376 FDA adverse event reports analyzed

Last updated: 2026-05-12

About METHOTREXATE

METHOTREXATE is a medication tracked in the FDA Adverse Event Reporting System (FAERS), manufactured by Medexus Pharma Inc.. Based on analysis of 1,175,376 FDA adverse event reports, METHOTREXATE has a safety score of 85 out of 100. This score indicates a relatively favorable safety profile, with fewer or less severe adverse events compared to many other tracked medications. The most commonly reported adverse reactions for METHOTREXATE include DRUG INEFFECTIVE, RHEUMATOID ARTHRITIS, ARTHRALGIA, PAIN, OFF LABEL USE. This page provides a comprehensive breakdown of reported side effects, safety signals, patient demographics, and AI-powered safety analysis for METHOTREXATE.

AI Safety Analysis

Methotrexate has a safety concern score of 85 out of 100, placing it in the high concern category based on analysis of FDA adverse event data. The FDA has received approximately 1,175,376 adverse event reports for this medication, which is primarily manufactured by Medexus Pharma Inc..

The most commonly reported adverse events include Drug Ineffective, Rheumatoid Arthritis, Arthralgia. Of classified reports, 74.5% were designated as serious by the FDA, meaning they involved hospitalization, disability, or other significant medical outcomes. Methotrexate has a high rate of serious adverse events, particularly infections and gastrointestinal disorders.

The drug shows a wide range of adverse reactions, indicating potential for diverse side effects. Report volume is substantial, with over 1.1 million reports, highlighting its widespread use and potential risks.

Patients taking Methotrexate should monitor for the commonly reported side effects and contact their healthcare provider if they experience any unusual symptoms. Methotrexate can interact with many drugs, including sulfasalazine, methotrexate, and azathioprine, potentially leading to increased toxicity. Warnings include contraindications with certain conditions and products. This analysis is based on voluntary FDA adverse event reports and should not replace professional medical advice.

Safety Score: 85/100

Methotrexate received a safety concern score of 85/100 (high concern). This is based on a 74.5% serious event ratio across 410,012 classified reports. The score accounts for 1,175,376 total adverse event reports and 100 distinct reaction types. This high score reflects a significant proportion of serious adverse events in the reporting data.

Top Adverse Reactions

DRUG INEFFECTIVE74,947 reports
RHEUMATOID ARTHRITIS38,054 reports
ARTHRALGIA36,283 reports
PAIN35,414 reports
OFF LABEL USE33,470 reports
FATIGUE29,056 reports
NAUSEA24,006 reports
JOINT SWELLING22,292 reports
HEADACHE20,810 reports
RASH19,770 reports
CONDITION AGGRAVATED19,610 reports
DRUG INTOLERANCE19,524 reports
DIARRHOEA18,208 reports
PAIN IN EXTREMITY17,886 reports
PYREXIA16,925 reports
PNEUMONIA16,122 reports
MALAISE15,154 reports
VOMITING15,002 reports
ALOPECIA14,713 reports
TREATMENT FAILURE14,437 reports
DYSPNOEA14,369 reports
NASOPHARYNGITIS14,109 reports
ABDOMINAL DISCOMFORT14,061 reports
INJECTION SITE PAIN14,058 reports
INFECTION13,464 reports
PERIPHERAL SWELLING13,223 reports
ARTHROPATHY13,163 reports
CONTRAINDICATED PRODUCT ADMINISTERED12,941 reports
MUSCULOSKELETAL STIFFNESS12,935 reports
DRUG HYPERSENSITIVITY12,390 reports
SWELLING12,284 reports
SYNOVITIS11,976 reports
HYPERSENSITIVITY11,948 reports
PRURITUS11,163 reports
WEIGHT INCREASED10,870 reports
SINUSITIS10,638 reports
HEPATIC ENZYME INCREASED10,584 reports
HYPERTENSION10,578 reports
COUGH10,506 reports
DIZZINESS10,434 reports
ASTHENIA10,401 reports
SYSTEMIC LUPUS ERYTHEMATOSUS10,400 reports
PSORIASIS10,391 reports
INFUSION RELATED REACTION10,158 reports
WEIGHT DECREASED10,009 reports
THERAPEUTIC PRODUCT EFFECT DECREASED9,869 reports
PSORIATIC ARTHROPATHY9,716 reports
PRODUCT USE IN UNAPPROVED INDICATION9,619 reports
FALL9,374 reports
PRODUCT USE ISSUE9,115 reports
BACK PAIN9,085 reports
ARTHRITIS8,851 reports
PEMPHIGUS8,648 reports
GAIT DISTURBANCE8,493 reports
ABDOMINAL PAIN8,174 reports
HAND DEFORMITY8,159 reports
GLOSSODYNIA8,050 reports
STOMATITIS7,979 reports
MOBILITY DECREASED7,910 reports
WOUND7,560 reports
INTENTIONAL PRODUCT USE ISSUE7,384 reports
OSTEOARTHRITIS7,370 reports
GASTROINTESTINAL DISORDER7,335 reports
LOWER RESPIRATORY TRACT INFECTION7,286 reports
GENERAL PHYSICAL HEALTH DETERIORATION7,257 reports
ABDOMINAL PAIN UPPER7,104 reports
INSOMNIA6,979 reports
C REACTIVE PROTEIN INCREASED6,937 reports
INFLAMMATION6,914 reports
URTICARIA6,830 reports
DISCOMFORT6,786 reports
HYPOAESTHESIA6,694 reports
THERAPEUTIC PRODUCT EFFECT INCOMPLETE6,569 reports
FEBRILE NEUTROPENIA6,513 reports
URINARY TRACT INFECTION6,501 reports
MATERNAL EXPOSURE DURING PREGNANCY6,342 reports
CONFUSIONAL STATE6,258 reports
PERICARDITIS6,255 reports
INJECTION SITE ERYTHEMA6,225 reports
SEPSIS6,149 reports
IMPAIRED HEALING6,049 reports
DECREASED APPETITE5,872 reports
CONTUSION5,862 reports
BLISTER5,855 reports
DEPRESSION5,821 reports
ANAEMIA5,764 reports
CHEST PAIN5,757 reports
PANCYTOPENIA5,739 reports
MUSCULOSKELETAL PAIN5,664 reports
ERYTHEMA5,648 reports
BLOOD PRESSURE INCREASED5,646 reports
ANTI CYCLIC CITRULLINATED PEPTIDE ANTIBODY POSITIVE5,590 reports
NEUTROPENIA5,462 reports
COVID 195,345 reports
LOSS OF PERSONAL INDEPENDENCE IN DAILY ACTIVITIES5,237 reports
INFLUENZA5,175 reports
FIBROMYALGIA5,014 reports
INAPPROPRIATE SCHEDULE OF PRODUCT ADMINISTRATION4,977 reports
DEATH4,957 reports
ANXIETY4,916 reports

Key Safety Signals

  • Serious reactions such as pneumonia and sepsis are common.
  • Gastrointestinal issues like nausea and diarrhea are frequently reported.
  • There are multiple reports of hematological issues, including anemia and pancytopenia.

Patient Demographics

Adverse event reports by sex: Female: 259,708, Male: 107,137, Unknown: 1,344. The most frequently reported age groups are age 60 (6,835 reports), age 59 (6,347 reports), age 63 (6,343 reports). These demographics reflect reporting patterns and may not represent the full patient population.

Report Outcomes

Out of 410,012 classified reports for METHOTREXATE:

  • Serious: 305,513 reports (74.5%) — includes hospitalization, disability, life-threatening events, or death
  • Non-Serious: 104,499 reports (25.5%)
Serious 74.5%Non-Serious 25.5%

The FDA classifies an adverse event as “serious” if it results in death, hospitalization, disability, congenital anomaly, or requires intervention to prevent permanent damage.

Demographics Breakdown

Reports by Sex

Female259,708 (70.5%)
Male107,137 (29.1%)
Unknown1,344 (0.4%)

Reports by Age

Age 606,835 reports
Age 596,347 reports
Age 636,343 reports
Age 616,230 reports
Age 656,164 reports
Age 646,146 reports
Age 626,080 reports
Age 566,055 reports
Age 576,049 reports
Age 586,012 reports
Age 545,777 reports
Age 555,674 reports
Age 675,463 reports
Age 535,323 reports
Age 665,302 reports
Age 435,082 reports
Age 445,065 reports
Age 524,972 reports
Age 684,923 reports
Age 704,700 reports

Demographics reflect voluntary FDA adverse event reporting patterns and may not represent the full patient population.

Drug Interactions & Warnings

Methotrexate can interact with many drugs, including sulfasalazine, methotrexate, and azathioprine, potentially leading to increased toxicity. Warnings include contraindications with certain conditions and products.

What You Should Know

If you are taking Methotrexate, here are important things to know. The most commonly reported side effects include drug ineffective, rheumatoid arthritis, arthralgia, pain, off label use. While many of these may be mild and temporary, you should contact your healthcare provider if any symptoms are severe or persistent. Patients should strictly follow prescribed dosages and schedules to minimize risk. Regular monitoring of blood counts and liver function is essential. If you experience a serious adverse reaction, seek emergency medical attention immediately or call 911. You can report side effects to the FDA's MedWatch program at 1-800-FDA-1088.

Regulatory Context

The FDA closely monitors Methotrexate due to its high risk of serious adverse events, particularly in older adults and those with pre-existing conditions.

Frequently Asked Questions

How many adverse event reports has the FDA received for Methotrexate?

The FDA has received approximately 1,175,376 adverse event reports associated with Methotrexate. These reports come from healthcare professionals, consumers, and manufacturers through the FDA Adverse Event Reporting System (FAERS). Note that the number of reports does not directly indicate the frequency of side effects, as adverse events are voluntarily reported and may be underrepresented.

What are the most commonly reported side effects of Methotrexate?

The most frequently reported adverse events for Methotrexate include Drug Ineffective, Rheumatoid Arthritis, Arthralgia, Pain, Off Label Use. By volume, the top reported reactions are: Drug Ineffective (74,947 reports), Rheumatoid Arthritis (38,054 reports), Arthralgia (36,283 reports). These figures reflect FDA adverse event reports and may not represent the true incidence rate of these side effects in all patients taking Methotrexate.

What percentage of Methotrexate adverse event reports are serious?

Out of 410,012 classified reports, 305,513 (74.5%) were classified as serious and 104,499 as non-serious. The FDA classifies an event as "serious" if it results in death, hospitalization, disability, or other medically significant outcomes. A higher serious-event ratio warrants closer attention but does not necessarily mean the drug is unsafe.

Who reports adverse events for Methotrexate (by sex)?

Adverse event reports for Methotrexate break down by patient sex as follows: Female: 259,708, Male: 107,137, Unknown: 1,344. This distribution reflects reporting patterns rather than actual risk differences between groups. Reporting rates can be influenced by prescribing patterns, disease demographics, and reporting behavior.

What age groups report the most side effects for Methotrexate?

The most frequently reported age groups for Methotrexate adverse events are: age 60: 6,835 reports, age 59: 6,347 reports, age 63: 6,343 reports, age 61: 6,230 reports, age 65: 6,164 reports. Age-related reporting patterns can reflect both the demographics of the patient population and potential age-related susceptibility to certain side effects.

Who manufactures Methotrexate?

The primary manufacturer associated with Methotrexate adverse event reports is Medexus Pharma Inc.. Multiple manufacturers may produce generic versions of this drug. The manufacturer listed reflects the most frequently reported brand in FDA adverse event data.

What other side effects have been reported for Methotrexate?

Beyond the most common reactions, other reported adverse events for Methotrexate include: Fatigue, Nausea, Joint Swelling, Headache, Rash. Less common side effects can still be clinically significant. Patients should report any unusual symptoms to their healthcare provider.

How do I report a side effect from Methotrexate?

You can report adverse events from Methotrexate to the FDA through their MedWatch program at www.fda.gov/medwatch, by calling 1-800-FDA-1088, or by completing Form FDA 3500. Healthcare professionals, consumers, and manufacturers can all submit reports. Reporting helps the FDA monitor drug safety after approval.

What is Methotrexate's safety score and what does it mean?

Methotrexate has a safety concern score of 85 out of 100 (high concern). This score is calculated from the ratio of serious to non-serious adverse events, the diversity of reported reactions, and the overall volume of reports relative to usage. Methotrexate has a high rate of serious adverse events, particularly infections and gastrointestinal disorders.

What are the key safety signals for Methotrexate?

Key safety signals identified in Methotrexate's adverse event data include: Serious reactions such as pneumonia and sepsis are common.. Gastrointestinal issues like nausea and diarrhea are frequently reported.. There are multiple reports of hematological issues, including anemia and pancytopenia.. These signals are derived from patterns in FDA reports and should be discussed with a healthcare provider for personalized assessment.

Does Methotrexate interact with other drugs?

Methotrexate can interact with many drugs, including sulfasalazine, methotrexate, and azathioprine, potentially leading to increased toxicity. Warnings include contraindications with certain conditions and products. Always inform your healthcare provider about all medications, supplements, and over-the-counter drugs you are taking before starting Methotrexate.

What should patients know before taking Methotrexate?

Patients should strictly follow prescribed dosages and schedules to minimize risk. Regular monitoring of blood counts and liver function is essential.

Are Methotrexate side effects well-documented?

Methotrexate has 1,175,376 adverse event reports on file with the FDA. The drug shows a wide range of adverse reactions, indicating potential for diverse side effects. The volume of reports for Methotrexate reflects both the drug's usage level and the vigilance of the reporting community.

What is the FDA's position on Methotrexate?

The FDA closely monitors Methotrexate due to its high risk of serious adverse events, particularly in older adults and those with pre-existing conditions. For the most current regulatory information, check the FDA's drug labeling database or consult your pharmacist.

Related Drugs

Drugs related to METHOTREXATE based on therapeutic use, drug class, or shared indications:

SulfasalazineAzathioprineCyclosporineAllopurinolLeflunomide
Important Disclaimer: This content is generated by AI analysis of FDA adverse event reports and is provided for informational purposes only. It is not medical advice. Adverse event reports submitted to the FDA do not prove that a medication caused the reported side effect. Always consult your healthcare provider before starting, stopping, or changing any medication. If you experience a serious side effect, contact your doctor or call 911 immediately.