METHOTREXATE SODIUM

85/100 · Critical

Manufactured by Fresenius Kabi USA, LLC

High Safety Concerns with Methotrexate Sodium: Common and Serious Adverse Reactions

1,310,439 FDA adverse event reports analyzed

Last updated: 2026-05-12

About METHOTREXATE SODIUM

METHOTREXATE SODIUM is a medication tracked in the FDA Adverse Event Reporting System (FAERS), manufactured by Fresenius Kabi USA, LLC. Based on analysis of 1,310,439 FDA adverse event reports, METHOTREXATE SODIUM 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 SODIUM 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 SODIUM.

AI Safety Analysis

Methotrexate Sodium 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 1,310,439 adverse event reports for this medication, which is primarily manufactured by Fresenius Kabi Usa, Llc.

The most commonly reported adverse events include Drug Ineffective, Rheumatoid Arthritis, Arthralgia. Of classified reports, 73.2% were designated as serious by the FDA, meaning they involved hospitalization, disability, or other significant medical outcomes. Methotrexate sodium is associated with a high number of serious adverse reactions, particularly infections and hematological issues.

Common side effects include pain, fatigue, and nausea, which are reported frequently. The drug is often used off-label, indicating potential misuse or unapproved therapeutic applications.

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

Safety Score: 85/100

Methotrexate Sodium received a safety concern score of 85/100 (high concern). This is based on a 73.2% serious event ratio across 473,761 classified reports. The score accounts for 1,310,439 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 INEFFECTIVE91,551 reports
RHEUMATOID ARTHRITIS41,868 reports
ARTHRALGIA39,749 reports
PAIN38,688 reports
OFF LABEL USE38,437 reports
FATIGUE32,132 reports
NAUSEA28,115 reports
JOINT SWELLING24,458 reports
DRUG INTOLERANCE23,987 reports
CONDITION AGGRAVATED23,177 reports
HEADACHE22,744 reports
RASH21,832 reports
DIARRHOEA20,265 reports
PAIN IN EXTREMITY19,574 reports
DRUG HYPERSENSITIVITY19,385 reports
PYREXIA18,367 reports
PNEUMONIA17,710 reports
ALOPECIA16,968 reports
MALAISE16,895 reports
VOMITING16,892 reports
TREATMENT FAILURE16,851 reports
DYSPNOEA15,894 reports
ABDOMINAL DISCOMFORT15,825 reports
NASOPHARYNGITIS15,103 reports
INFECTION14,743 reports
PERIPHERAL SWELLING14,587 reports
MUSCULOSKELETAL STIFFNESS14,481 reports
ARTHROPATHY14,311 reports
INJECTION SITE PAIN14,225 reports
CONTRAINDICATED PRODUCT ADMINISTERED13,977 reports
SWELLING13,309 reports
SYNOVITIS13,268 reports
HYPERSENSITIVITY12,790 reports
PRURITUS12,081 reports
HEPATIC ENZYME INCREASED11,854 reports
WEIGHT INCREASED11,607 reports
COUGH11,589 reports
HYPERTENSION11,559 reports
ASTHENIA11,428 reports
DIZZINESS11,414 reports
PSORIASIS11,259 reports
SINUSITIS11,196 reports
SYSTEMIC LUPUS ERYTHEMATOSUS11,037 reports
WEIGHT DECREASED11,030 reports
INFUSION RELATED REACTION10,671 reports
PSORIATIC ARTHROPATHY10,585 reports
THERAPEUTIC PRODUCT EFFECT DECREASED10,538 reports
PRODUCT USE IN UNAPPROVED INDICATION10,333 reports
FALL10,225 reports
PRODUCT USE ISSUE10,203 reports
BACK PAIN9,923 reports
ARTHRITIS9,854 reports
GAIT DISTURBANCE9,444 reports
ABDOMINAL PAIN9,106 reports
PEMPHIGUS9,099 reports
STOMATITIS8,877 reports
GASTROINTESTINAL DISORDER8,671 reports
HAND DEFORMITY8,627 reports
MOBILITY DECREASED8,578 reports
GLOSSODYNIA8,450 reports
OSTEOARTHRITIS8,102 reports
LOWER RESPIRATORY TRACT INFECTION7,945 reports
WOUND7,909 reports
C REACTIVE PROTEIN INCREASED7,899 reports
GENERAL PHYSICAL HEALTH DETERIORATION7,869 reports
INTENTIONAL PRODUCT USE ISSUE7,822 reports
ABDOMINAL PAIN UPPER7,766 reports
THERAPEUTIC PRODUCT EFFECT INCOMPLETE7,678 reports
INFLAMMATION7,663 reports
INSOMNIA7,637 reports
FEBRILE NEUTROPENIA7,551 reports
URTICARIA7,381 reports
HYPOAESTHESIA7,296 reports
DISCOMFORT7,132 reports
URINARY TRACT INFECTION7,089 reports
SEPSIS6,837 reports
MATERNAL EXPOSURE DURING PREGNANCY6,762 reports
CONFUSIONAL STATE6,711 reports
PANCYTOPENIA6,685 reports
PERICARDITIS6,585 reports
ANAEMIA6,504 reports
DEPRESSION6,489 reports
DECREASED APPETITE6,469 reports
IMPAIRED HEALING6,432 reports
INJECTION SITE ERYTHEMA6,326 reports
CONTUSION6,284 reports
CHEST PAIN6,272 reports
BLISTER6,207 reports
MUSCULOSKELETAL PAIN6,165 reports
BLOOD PRESSURE INCREASED6,132 reports
ERYTHEMA6,115 reports
NEUTROPENIA6,111 reports
LOSS OF PERSONAL INDEPENDENCE IN DAILY ACTIVITIES5,965 reports
ANTI CYCLIC CITRULLINATED PEPTIDE ANTIBODY POSITIVE5,880 reports
COVID 195,875 reports
INFLUENZA5,616 reports
DEATH5,610 reports
INAPPROPRIATE SCHEDULE OF PRODUCT ADMINISTRATION5,453 reports
FIBROMYALGIA5,437 reports
ANXIETY5,382 reports

Key Safety Signals

  • Serious adverse reactions such as pneumonia, sepsis, and death are reported frequently.
  • Hematological issues like anemia, pancytopenia, and neutropenia are common.
  • Infections, including respiratory tract infections and sepsis, are significant safety signals.

Patient Demographics

Adverse event reports by sex: Female: 302,592, Male: 123,885, Unknown: 1,402. The most frequently reported age groups are age 60 (8,254 reports), age 65 (7,845 reports), age 63 (7,842 reports). These demographics reflect reporting patterns and may not represent the full patient population.

Report Outcomes

Out of 473,761 classified reports for METHOTREXATE SODIUM:

  • Serious: 346,680 reports (73.2%) — includes hospitalization, disability, life-threatening events, or death
  • Non-Serious: 127,081 reports (26.8%)
Serious 73.2%Non-Serious 26.8%

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

Female302,592 (70.7%)
Male123,885 (29.0%)
Unknown1,402 (0.3%)

Reports by Age

Age 608,254 reports
Age 657,845 reports
Age 637,842 reports
Age 597,667 reports
Age 617,615 reports
Age 647,528 reports
Age 627,433 reports
Age 587,317 reports
Age 567,284 reports
Age 577,284 reports
Age 546,953 reports
Age 556,849 reports
Age 676,802 reports
Age 666,747 reports
Age 536,387 reports
Age 686,192 reports
Age 525,983 reports
Age 705,905 reports
Age 695,837 reports
Age 435,752 reports

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

Drug Interactions & Warnings

Methotrexate sodium can interact with other drugs, such as sulfasalazine and methotrexate itself, leading to increased toxicity. Warnings include contraindications with certain medications and conditions.

What You Should Know

If you are taking Methotrexate Sodium, 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 be closely monitored for signs of infection, hematological issues, and other serious adverse reactions. Follow prescribed dosing and administration guidelines strictly to minimize the risk of toxicity. 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 sodium 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 Sodium?

The FDA has received approximately 1,310,439 adverse event reports associated with Methotrexate Sodium. 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 Sodium?

The most frequently reported adverse events for Methotrexate Sodium include Drug Ineffective, Rheumatoid Arthritis, Arthralgia, Pain, Off Label Use. By volume, the top reported reactions are: Drug Ineffective (91,551 reports), Rheumatoid Arthritis (41,868 reports), Arthralgia (39,749 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 Sodium.

What percentage of Methotrexate Sodium adverse event reports are serious?

Out of 473,761 classified reports, 346,680 (73.2%) were classified as serious and 127,081 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 Sodium (by sex)?

Adverse event reports for Methotrexate Sodium break down by patient sex as follows: Female: 302,592, Male: 123,885, Unknown: 1,402. 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 Sodium?

The most frequently reported age groups for Methotrexate Sodium adverse events are: age 60: 8,254 reports, age 65: 7,845 reports, age 63: 7,842 reports, age 59: 7,667 reports, age 61: 7,615 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 Sodium?

The primary manufacturer associated with Methotrexate Sodium adverse event reports is Fresenius Kabi Usa, Llc. 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 Sodium?

Beyond the most common reactions, other reported adverse events for Methotrexate Sodium include: Fatigue, Nausea, Joint Swelling, Drug Intolerance, Condition Aggravated. 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 Sodium?

You can report adverse events from Methotrexate Sodium 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 Sodium's safety score and what does it mean?

Methotrexate Sodium 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 sodium is associated with a high number of serious adverse reactions, particularly infections and hematological issues.

What are the key safety signals for Methotrexate Sodium?

Key safety signals identified in Methotrexate Sodium's adverse event data include: Serious adverse reactions such as pneumonia, sepsis, and death are reported frequently.. Hematological issues like anemia, pancytopenia, and neutropenia are common.. Infections, including respiratory tract infections and sepsis, are significant safety signals.. These signals are derived from patterns in FDA reports and should be discussed with a healthcare provider for personalized assessment.

Does Methotrexate Sodium interact with other drugs?

Methotrexate sodium can interact with other drugs, such as sulfasalazine and methotrexate itself, leading to increased toxicity. Warnings include contraindications with certain medications and conditions. Always inform your healthcare provider about all medications, supplements, and over-the-counter drugs you are taking before starting Methotrexate Sodium.

What should patients know before taking Methotrexate Sodium?

Patients should be closely monitored for signs of infection, hematological issues, and other serious adverse reactions. Follow prescribed dosing and administration guidelines strictly to minimize the risk of toxicity.

Are Methotrexate Sodium side effects well-documented?

Methotrexate Sodium has 1,310,439 adverse event reports on file with the FDA. Common side effects include pain, fatigue, and nausea, which are reported frequently. The volume of reports for Methotrexate Sodium reflects both the drug's usage level and the vigilance of the reporting community.

What is the FDA's position on Methotrexate Sodium?

The FDA closely monitors Methotrexate sodium 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 SODIUM 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.