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What the label lists and what reports show

Methotrexate side effects

Methotrexate's FDA label: “The most common adverse reactions of methotrexate that exceeded the rate of placebo in 12- to 18-week double-blind studies in patients (n=128) with rheumatoid arthritis are listed below.” FAERS holds 489,791 reports naming it through July 30, 2026; the reaction reported most often, leaving out the conditions it is used for, product-use terms and outcomes, is arthralgia (40,827 reports).

  • Generic listed
  • In shortage
  • Boxed warning

Check it at the source: the methotrexate FDA label on DailyMed (effective May 27, 2026, Accord Healthcare Inc.); the FDA FAERS public dashboard.

What does the patient leaflet say about side effects?

From the patient leaflet: What are the possible side effects of Methotrexate?

Methotrexate can cause serious side effects that may be severe and lead to death including: See What is the most important information I should know about Methotrexate? Serious infections. People who take Methotrexate have an increased risk of developing infections that can be life-threatening or cause death. These infections may include: bacterial, fungal, or viral infections, including Pneumocystis jiroveci pneumonia, invasive fungal infections, hepatitis B infection that comes back (reactivation), turberculosis infection that may be new or reactivation, and Herpes zoster or cytomegalovirus (CMV) that spreads throughout the body (disseminated). Tell your healthcare provider right away if you develop a new fever or if you have any symptoms of infection during treatment with Methotrexate. Brain and spinal cord (nervous system) problems. […]

Source: FDA drug label, Accord Healthcare Inc., effective May 27, 2026 (SPL set 874c7f43-a3be-4236-89cc-24c44e3c5813), via openFDA; the full label on DailyMed

What does the label list?

From the label: adverse reactions

The most common adverse reactions of methotrexate that exceeded the rate of placebo in 12- to 18-week double-blind studies in patients (n=128) with rheumatoid arthritis are listed below.

From the label: adverse reactions, continued

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 Accord Healthcare Inc. at 1-866-941-7875 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. …

Source: FDA drug label, Accord Healthcare Inc., effective May 27, 2026 (SPL set 874c7f43-a3be-4236-89cc-24c44e3c5813), via openFDA; the full label on DailyMed

What do FAERS reports show?

489,791 reports list methotrexate among the medicines taken, each a report of something that happened, not proof the medicine caused it; 37,720 are coded as a death and 133,303 as a hospital stay. Counts follow how widely a medicine is used and watched, and they are not a measure of how risky it is. Of the 20 reactions below, 11 are named by the same term (in US spelling) in the label's adverse reactions, warnings or patient leaflet; a reaction the label does not name may still be there under another word, and a report does not show that the medicine caused it.

Reports received each year

The 25 most reported reactions

  • Drug Ineffective (a use or a product term, not a reaction)93,149
  • Rheumatoid Arthritis (a use or a product term, not a reaction)42,800
  • Arthralgia (named in the label)40,827
  • Off Label Use (a use or a product term, not a reaction)40,061
  • Pain39,719
  • Fatigue (named in the label)33,049
  • Nausea (named in the label)28,999
  • Joint Swelling25,029
  • Drug Intolerance24,402
  • Condition Aggravated (a use or a product term, not a reaction)23,854
  • Headache (named in the label)23,433
  • Rash (named in the label)22,473
  • Diarrhoea (named in the label)20,865
  • Pain In Extremity20,089
  • Drug Hypersensitivity19,663
  • Pyrexia18,946
  • Pneumonia (named in the label)18,285
  • Malaise (named in the label)17,517
  • Vomiting (named in the label)17,470
  • Alopecia (named in the label)17,463
  • Treatment Failure (a use or a product term, not a reaction)17,176
  • Dyspnoea16,359
  • Abdominal Discomfort16,222
  • Nasopharyngitis15,599
  • Infection (named in the label)15,226

Source: FDA Adverse Event Reporting System (FAERS) via openFDA, reports through July 30, 2026; reactions as MedDRA preferred terms

What next?

Methotrexate: the full record
label, generics, price, shortages, recalls
Side effects hub
the most reported medicines and reactions