Methotrexate side effects: what 418,279 FDA adverse event reports show

Methotrexate · 1,255 reaction terms · 2,216,110 drug–reaction co-reports · data 2026-09-14

Drug class

Folate analog metabolic inhibitor

FDA label, Indications wording

Who reports

418,279 reports · 75% serious · 33,856 with death outcome · 71% female

openFDA FAERS counts, all years, deduplication not applied

Used for

Methotrexate Injection is a folate analog metabolic inhibitor indicated for: • The following neoplastic diseases for the: o Treatment of adult and pediatric patients with acute lymphoblastic leukemia as part of a combination chemotherapy regimen. ( 1.1 ) o Prophylaxis and treatment of adult and pediatric patients with meningeal leukemia. ( 1.2 ) o Treatment of adult and pediatric patients with non-Hodgkin lymphoma.

FDA label, Indications and Usage

What it is

Methotrexate is a member of pteridines, a monocarboxylic acid amide and a dicarboxylic acid. It has a role as an antimetabolite, an antineoplastic agent, an immunosuppressive agent, an antirheumatic drug, a dermatologic drug, an EC 1.5.1.3 (dihydrofolate reductase) inhibitor, an abortifacient and a DNA synthesis...

PubChem CID 126941 (ChEBI)

Boxed warning

EMBRYO-FETAL TOXICITY, HYPERSENSITIVITY REACTIONS, BENZYL ALCOHOL TOXICITY, and OTHER SERIOUS ADVERSE REACTIONS • Methotrexate Injection can cause embryo-fetal toxicity, including fetal death. For non-neoplastic diseases, Methotrexate Injection is contraindicated in pregnancy.

FDA label

How to read this page. FAERS is a spontaneous-reporting system: counts are not incidence rates and a signal is not proof of causation. Each reaction below is run through an automated screen — is the term in the FDA label (known), in the indications (the disease being treated), an administrative/coding term, or none of these (unlabeled)? That screen is mechanical text matching, not a causality assessment. The 30 hand-written Bradford Hill assessments are on the causality assessment page. Not medical advice.

Causality screen of the 40 strongest signals

Labeled adverse reaction 1Labeled (related wording) 4Likely indication confounding 3Reporting / coding artifact 2Lab value / disease marker 12Not in label — unassessed 18

What the badges mean

Labeled adverse reaction The exact term appears in the label's warnings or adverse-reactions sections: a known, expected effect. The FAERS signal confirms the label rather than discovering anything.
Labeled (related wording) The label describes this effect under different wording (e.g. 'neutropenia' for 'neutrophil count decreased'). Treated as known.
Likely indication confounding The term appears in the label's indications: reports probably describe the disease being treated (or its progression), not a drug effect. Classic confounding by indication.
Reporting / coding artifact An administrative, monitoring or exposure term (product issue, off-label use, 'test normal', overdose...). Not a biological reaction; a high PRR here reflects how reports are coded.
Lab value / disease marker A laboratory result, investigation or disease-activity marker (antibody positive, CRP abnormal, swollen joint count) not described in the label. These usually mirror the monitored disease or testing protocol rather than a drug effect; not screened further.
Not in label — unassessed Not found in the label text, not an artifact pattern. This is a genuine candidate for a formal causality assessment (Bradford Hill / WHO-UMC); it has NOT had one here.

Strongest disproportionality signals

Flagged terms (PRR ≥ 2, χ² ≥ 4, n ≥ 10), ranked by PRR; infinite PRRs (no comparator reports) excluded. The EBGM column is a second, shrinkage-based estimate (MGPS) with its 5th percentile EB05 and the BCPNN IC025; a pair flagged by PRR alone is marked PRR-only and should be read as fragile. The strata column recomputes the PRR on serious reports only (and, for the 300 most-reported drugs, adjusted for age band), and flags pairs whose reports are unusually skewed by sex or come mostly from consumers. Each row also shows the PRR against the other drugs of the same FDA class, which removes most confounding by the condition being treated, and a calibrated p-value: on validation, known non-causes average an ROR of about 2, so significance is judged against that empirical null (✓ = p < 0.05 after calibration). 1,215 further terms are in the interactive explorer. Reaction links open the term's cross-drug page.

Show: hide coding/lab/outcome terms hide indication terms unlabeled only hide PRR-only

Reaction	Reports	PRR 95% CI · ROR · χ²/p	EBGM EB05 · IC025	Label screen	Serious-only & strata	Trial cross-check
Human antichimeric antibody positive	291	320.5 233.5–440.1ROR 320.8 · calibrated p 2e-11 ✓	42.9 EB05 38.9 · IC025 +5.1 3/3 methods agree	Lab value / disease marker	serious n=291 · 100% consumer	no trial arm names this drug
Anti-cyclic citrullinated peptide antibody positive	5,824	237.0 222.7–252.2ROR 240.3 · calibrated p 8e-11 ✓	41.1 EB05 40.2 · IC025 +5.3 3/3 methods agree	Lab value / disease marker	serious PRR 31.7 · ♀ 98% (drug 71%) · 92% clinician	no trial arm names this drug
Rheumatoid factor positive	4,503	183.1 171.8–195.1ROR 185.1 · calibrated p 8e-10 ✓	39.1 EB05 38.2 · IC025 +5.2 3/3 methods agree	Lab value / disease marker	serious n=4,498 · ♀ 98% (drug 71%) · 91% clinician	no trial arm names this drug
Swollen joint count increased	2,402	172.0 157.9–187.3ROR 172.9 · calibrated p 1e-9 ✓	38.6 EB05 37.3 · IC025 +5.2 3/3 methods agree	Lab value / disease marker	serious n=2,393 · ♀ 100% (drug 71%) · 94% clinician	no trial arm names this drug
Anti-cyclic citrullinated peptide antibody	511	167.3 139.4–200.9ROR 167.5 · calibrated p 2e-9 ✓	38.3 EB05 35.6 · IC025 +5.1 3/3 methods agree	Lab value / disease marker	serious n=508 · ♀ 100% (drug 71%) · 100% clinician	no trial arm names this drug
Rheumatic fever	3,138	129.5 121.2–138.5ROR 130.5 · calibrated p 1e-8 ✓	36.0 EB05 34.9 · IC025 +5.1 3/3 methods agree	Likely indication confounding shares a disease stem with the indications wording	serious n=3,136 · ♀ 100% (drug 71%) · 94% clinician	no trial arm names this drug
Pemphigus	8,927	129.4 124.4–134.7ROR 132.2 · calibrated p 1e-8 ✓	36.0 EB05 35.4 · IC025 +5.1 3/3 methods agree	Not in label — unassessed	serious PRR 27.8 · ♀ 100% (drug 71%)	no trial arm names this drug
Red blood cell sedimentation rate abnormal	1,653	124.4 113.6–136.3ROR 124.9 · calibrated p 2e-8 ✓	35.6 EB05 34.2 · IC025 +5.1 3/3 methods agree	Lab value / disease marker	serious n=1,641	no trial arm names this drug
Lupus vulgaris	812	108.4 95.8–122.7ROR 108.6 · calibrated p 7e-8 ✓	34.2 EB05 32.2 · IC025 +5.0 3/3 methods agree	Not in label — unassessed	serious n=812 · ♀ 100% (drug 71%) · 100% clinician	no trial arm names this drug
Synovitis	12,276	107.5 104.1–110.9ROR 110.7 · calibrated p 5e-8 ✓	34.1 EB05 33.6 · IC025 +5.1 3/3 methods agree	Not in label — unassessed	serious PRR 27.3	no trial arm names this drug
Deep vein thrombosis postoperative	1,314	102.4 93.1–112.6ROR 102.7 · calibrated p 1e-7 ✓	33.6 EB05 32.1 · IC025 +5.0 3/3 methods agree	Not in label — unassessed	serious n=1,314 · ♀ 100% (drug 71%) · 94% clinician	no trial arm names this drug
C-reactive protein abnormal	4,291	102.3 97.0–107.8ROR 103.3 · calibrated p 9e-8 ✓	33.6 EB05 32.7 · IC025 +5.0 3/3 methods agree	Lab value / disease marker	serious n=4,279	no trial arm names this drug
Duodenal ulcer perforation	4,847	97.9 93.3–102.8ROR 99.1 · calibrated p 1e-7 ✓	33.1 EB05 32.3 · IC025 +5.0 3/3 methods agree	Labeled (related wording) related wording	serious PRR 25.4 · ♀ 100% (drug 71%) · 94% clinician	no trial arm names this drug
C-reactive protein	587	92.1 80.2–105.7ROR 92.2 · calibrated p 2e-7 ✓	32.4 EB05 30.2 · IC025 +4.8 3/3 methods agree	Lab value / disease marker	serious n=587 · ♀ 100% (drug 71%) · 100% clinician	no trial arm names this drug
Hand deformity	8,415	90.7 87.5–94.0ROR 92.5 · calibrated p 2e-7 ✓	32.2 EB05 31.7 · IC025 +5.0 3/3 methods agree	Not in label — unassessed	serious PRR 26.6 · ♀ 96% (drug 71%)	no trial arm names this drug
Granuloma skin	497	75.0 65.2–86.3ROR 75.1 · calibrated p 1e-6 ✓	30.0 EB05 27.9 · IC025 +4.7 3/3 methods agree	Not in label — unassessed	serious n=496 · ♀ 100% (drug 71%)	no trial arm names this drug
Facet joint syndrome	1,856	71.6 66.7–76.9ROR 71.9 · calibrated p 1e-6 ✓	29.5 EB05 28.4 · IC025 +4.8 3/3 methods agree	Not in label — unassessed	serious n=1,855 · ♀ 100% (drug 71%) · 95% clinician	no trial arm names this drug
Rheumatoid nodule	1,542	61.9 57.4–66.8ROR 62.1 · calibrated p 3e-6 ✓	27.7 EB05 26.6 · IC025 +4.7 3/3 methods agree	Likely indication confounding shares a disease stem with the indications wording	serious n=1,444	no trial arm names this drug
X-ray abnormal	954	57.2 52.1–62.8ROR 57.4 · calibrated p 6e-6 ✓	26.8 EB05 25.4 · IC025 +4.6 3/3 methods agree	Lab value / disease marker	serious n=953 · ♀ 100% (drug 71%) · 91% clinician	no trial arm names this drug
Bone erosion	1,850	54.4 50.9–58.2ROR 54.7 · calibrated p 8e-6 ✓	26.2 EB05 25.2 · IC025 +4.6 3/3 methods agree	Labeled (related wording) related wording	serious n=1,835	no trial arm names this drug
Adjustment disorder with depressed mood	1,044	53.5 49.0–58.4ROR 53.6 · calibrated p 9e-6 ✓	25.9 EB05 24.6 · IC025 +4.6 3/3 methods agree	Not in label — unassessed	serious n=1,043 · ♀ 100% (drug 71%) · 100% clinician	no trial arm names this drug
Dislocation of vertebra	1,127	51.1 47.0–55.6ROR 51.2 · calibrated p 1e-5 ✓	25.4 EB05 24.2 · IC025 +4.6 3/3 methods agree	Not in label — unassessed	serious n=1,125 · ♀ 100% (drug 71%) · 93% clinician	no trial arm names this drug
Muscle injury	4,115	50.0 47.9–52.3ROR 50.5 · calibrated p 1e-5 ✓	25.1 EB05 24.5 · IC025 +4.6 3/3 methods agree	Not in label — unassessed	serious PRR 20.9 · ♀ 100% (drug 71%) · 93% clinician	no trial arm names this drug
Body height below normal	326	50.0 42.8–58.4ROR 50.0 · calibrated p 1e-5 ✓	25.1 EB05 22.9 · IC025 +4.4 3/3 methods agree	Reporting / coding artifact	serious n=326 · ♀ 100% (drug 71%) · 100% consumer	no trial arm names this drug
Helicobacter infection	5,030	48.4 46.6–50.4ROR 49.0 · calibrated p 2e-5 ✓	24.7 EB05 24.2 · IC025 +4.6 3/3 methods agree	Not in label — unassessed	serious PRR 20.1 · ♀ 100% (drug 71%) · 93% clinician	no trial arm names this drug
Sleep disorder due to general medical condition, insomnia type	3,056	44.9 42.7–47.2ROR 45.2 · calibrated p 3e-5 ✓	23.8 EB05 23.1 · IC025 +4.5 3/3 methods agree	Not in label — unassessed	serious n=3,040 · ♀ 96% (drug 71%) · 93% clinician	no trial arm names this drug
Seronegative arthritis	523	43.3 38.5–48.8ROR 43.4 · calibrated p 3e-5 ✓	23.3 EB05 21.7 · IC025 +4.4 3/3 methods agree	Likely indication confounding shares a disease stem with the indications wording	serious n=517 · ♀ 100% (drug 71%) · 100% clinician	no trial arm names this drug
Folliculitis	4,788	42.9 41.3–44.6ROR 43.4 · calibrated p 3e-5 ✓	23.2 EB05 22.7 · IC025 +4.5 3/3 methods agree	Not in label — unassessed	serious PRR 20.9 · ♀ 98% (drug 71%) · 94% clinician	no trial arm names this drug
Retinitis	739	39.4 35.8–43.4ROR 39.5 · calibrated p 6e-5 ✓	22.2 EB05 20.9 · IC025 +4.3 3/3 methods agree	Not in label — unassessed	serious n=738 · ♀ 100% (drug 71%) · 100% clinician	no trial arm names this drug
Contraindicated product administered	13,196	38.6 37.7–39.5ROR 39.8 · calibrated p 5e-5 ✓	21.9 EB05 21.6 · IC025 +4.4 3/3 methods agree	Reporting / coding artifact	age-adj. PRR 29.1 · serious PRR 20.2 · ♀ 91% (drug 71%)	no trial arm names this drug
Enthesopathy	684	38.0 34.4–42.0ROR 38.0 · calibrated p 7e-5 ✓	21.7 EB05 20.4 · IC025 +4.3 3/3 methods agree	Not in label — unassessed	serious n=671	no trial arm names this drug
Rheumatoid lung	407	36.3 31.9–41.2ROR 36.3 · calibrated p 1e-4 ✓	21.2 EB05 19.5 · IC025 +4.2 3/3 methods agree	Labeled (related wording) related wording	serious n=399	no trial arm names this drug
Dactylitis	404	34.7 30.5–39.4ROR 34.7 · calibrated p 1e-4 ✓	20.6 EB05 19.0 · IC025 +4.2 3/3 methods agree	Not in label — unassessed	serious n=388	no trial arm names this drug
Pericarditis	6,527	31.9 30.9–32.9ROR 32.4 · calibrated p 2e-4 ✓	19.6 EB05 19.2 · IC025 +4.3 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 15.2 · ♀ 96% (drug 71%) · 92% clinician	no trial arm names this drug
Peripheral venous disease	1,553	31.5 29.6–33.6ROR 31.6 · calibrated p 2e-4 ✓	19.5 EB05 18.7 · IC025 +4.2 3/3 methods agree	Not in label — unassessed	serious n=1,542 · ♀ 100% (drug 71%) · 93% clinician	no trial arm names this drug
Blood pressure diastolic abnormal	979	30.5 28.1–33.0ROR 30.5 · calibrated p 2e-4 ✓	19.1 EB05 18.1 · IC025 +4.1 3/3 methods agree	Lab value / disease marker	serious n=954 · 90% clinician	no trial arm names this drug
Blood parathyroid hormone decreased	562	29.9 26.9–33.2ROR 30.0 · calibrated p 3e-4 ✓	18.9 EB05 17.6 · IC025 +4.1 3/3 methods agree	Lab value / disease marker	serious n=561 · ♀ 100% (drug 71%)	no trial arm names this drug
Joint destruction	589	29.9 27.0–33.1ROR 29.9 · calibrated p 3e-4 ✓	18.9 EB05 17.6 · IC025 +4.1 3/3 methods agree	Not in label — unassessed	serious n=565 · ♀ 100% (drug 71%)	no trial arm names this drug
Blood pressure systolic abnormal	932	29.6 27.3–32.1ROR 29.7 · calibrated p 3e-4 ✓	18.7 EB05 17.8 · IC025 +4.1 3/3 methods agree	Lab value / disease marker	serious n=906 · 91% clinician	no trial arm names this drug
Glossodynia (burning tongue/mouth pain)	8,347	29.5 28.7–30.3ROR 30.1 · calibrated p 3e-4 ✓	18.7 EB05 18.4 · IC025 +4.2 3/3 methods agree	Labeled (related wording) related wording	serious PRR 20.7 · ♀ 100% (drug 71%) · 90% clinician	no trial arm names this drug

Clinical concept groups

MedDRA splits one clinical problem across several terms (e.g. "neutropenia", "neutrophil count decreased", "agranulocytosis"), which dilutes term-level signals. These rows count reports with any term in a concept group (an exact union, not a sum), compared with all other drugs. Groups are hand-built and listed in the methods.

Concept	Reports	PRR 95% CI	Reading
Interstitial lung disease	8,196	4.64.5–4.7	signal
Opportunistic infection	10,748	4.24.1–4.3	signal
Liver injury	23,353	4.14.1–4.2	signal
Serious infection	43,968	3.02.9–3.0	signal
Tendon disorder	2,099	2.92.7–3.0	signal
Neutropenia / agranulocytosis	13,056	2.72.7–2.8	signal
Thrombocytopenia	7,120	1.61.6–1.7	raised
Pancreatitis	2,523	1.61.5–1.7	raised
Anaemia	9,022	1.51.5–1.6	raised
Fall / fracture	10,937	1.51.4–1.5	raised
Hyperglycaemia / diabetes	9,038	1.31.3–1.3	raised
Kidney injury	11,684	1.31.3–1.3	raised
Venous thromboembolism	5,517	1.31.3–1.3	raised
Osteonecrosis	1,448	1.31.2–1.3	raised
Malignancy	9,414	1.31.2–1.3	raised
Depression	6,907	1.21.2–1.3	raised

Trial evidence (ClinicalTrials.gov)

ClinicalTrials.gov returned results-bearing trials mentioning Methotrexate only as a background or rescue medication (NCT01190930, NCT02883049); no trial listing it as the tested intervention was cached, so no trial cross-check is shown.

Most frequently reported reactions

By raw co-report count, regardless of disproportionality. Common terms here are often the illness itself or generic outcomes.

Reaction	Reports	PRR 95% CI · ROR · χ²/p	EBGM EB05 · IC025	Label screen	Serious-only & strata	Trial cross-check
Drug ineffective (drug did not work)	75,965	3.0 3.0–3.0ROR 3.5 · calibrated p 0.496	2.9 EB05 2.9 · IC025 +1.5 3/3 methods agree	Reporting / coding artifact	age-adj. PRR 3.1 · serious PRR 4.9	no trial arm names this drug
Rheumatoid arthritis	38,633	25.7 25.4–26.0ROR 28.2 · calibrated p 4e-4 ✓	17.1 EB05 17.0 · IC025 +4.1 3/3 methods agree	Likely indication confounding term in indications; also in warnings	age-adj. PRR 21.3 · serious PRR 14.7	no trial arm names this drug
Arthralgia (joint pain)	36,920	4.8 4.8–4.9ROR 5.2 · calibrated p 0.216	4.5 EB05 4.4 · IC025 +2.1 3/3 methods agree	Labeled adverse reaction exact term	age-adj. PRR 4.4 · serious PRR 5.1	no trial arm names this drug
Pain	36,017	3.1 3.0–3.1ROR 3.3 · calibrated p 0.550	2.9 EB05 2.9 · IC025 +1.5 3/3 methods agree	Labeled adverse reaction exact term	age-adj. PRR 3.1 · serious PRR 3.0	no trial arm names this drug
Off label use (used outside approved label)	34,769	2.1 2.0–2.1ROR 2.1 · calibrated p 0.979	2.0 EB05 2.0 · IC025 +1.0	Reporting / coding artifact	age-adj. PRR 1.9 · serious PRR 2.7	no trial arm names this drug
Fatigue (tiredness)	29,644	1.9 1.9–2.0ROR 2.0 · calibrated p 0.956	1.9 EB05 1.9 · IC025 +0.9	Labeled adverse reaction exact term	age-adj. PRR 1.8 · serious PRR 2.3	no trial arm names this drug
Nausea	24,479	1.6 1.6–1.6ROR 1.6 · calibrated p 0.712	1.6 EB05 1.5 · IC025 +0.6	Labeled adverse reaction exact term	age-adj. PRR 1.4 · serious PRR 1.8	no trial arm names this drug
Joint swelling	22,670	11.4 11.3–11.6ROR 12.0 · calibrated p 0.017 ✓	9.4 EB05 9.3 · IC025 +3.2 3/3 methods agree	Not in label — unassessed	age-adj. PRR 10.0 · serious PRR 11.1	no trial arm names this drug
Headache	21,283	1.7 1.7–1.8ROR 1.8 · calibrated p 0.811	1.7 EB05 1.7 · IC025 +0.7	Labeled adverse reaction exact term	age-adj. PRR 1.6 · serious PRR 2.1	no trial arm names this drug
Rash	20,259	2.4 2.4–2.4ROR 2.5 · calibrated p 0.821	2.3 EB05 2.3 · IC025 +1.2 3/3 methods agree	Labeled adverse reaction exact term	age-adj. PRR 2.1 · serious PRR 3.5	no trial arm names this drug
Condition aggravated	20,123	3.5 3.5–3.6ROR 3.6 · calibrated p 0.452	3.3 EB05 3.3 · IC025 +1.7 3/3 methods agree	Reporting / coding artifact	age-adj. PRR 3.2 · serious PRR 3.6	no trial arm names this drug
Drug intolerance	19,912	12.9 12.7–13.1ROR 13.4 · calibrated p 0.011 ✓	10.4 EB05 10.2 · IC025 +3.4 3/3 methods agree	Reporting / coding artifact	age-adj. PRR 13.3 · serious PRR 12.2	no trial arm names this drug
Diarrhoea (diarrhea)	18,616	1.5 1.4–1.5ROR 1.5 · calibrated p 0.632	1.5 EB05 1.4 · IC025 +0.5	Labeled adverse reaction exact term	age-adj. PRR 1.4 · serious PRR 1.7	no trial arm names this drug
Pain in extremity	18,174	3.2 3.2–3.3ROR 3.3 · calibrated p 0.529	3.1 EB05 3.0 · IC025 +1.6 3/3 methods agree	Not in label — unassessed	age-adj. PRR 3.1 · serious PRR 3.3	no trial arm names this drug
Pyrexia (fever)	17,378	2.6 2.6–2.6ROR 2.7 · calibrated p 0.745	2.5 EB05 2.5 · IC025 +1.3 3/3 methods agree	Labeled (related wording) related wording	age-adj. PRR 2.2 · serious PRR 2.2	no trial arm names this drug

Unlabeled candidate signals

These flagged terms were not found in the FDA label text and do not match an artifact pattern. They are the pairs that would merit a structured assessment (temporality, dose-response, biological plausibility, consistency across databases, trial or cohort evidence). The screen has not done that; string-matching misses label wording, and a strong PRR can still be stimulated reporting, co-medication, or the disease itself.

Pemphigus — n=8,927, PRR 129.4
Lupus vulgaris — n=812, PRR 108.4
Synovitis — n=12,276, PRR 107.5
Deep vein thrombosis postoperative — n=1,314, PRR 102.4
Hand deformity — n=8,415, PRR 90.7
Granuloma skin — n=497, PRR 75.0
Facet joint syndrome — n=1,856, PRR 71.6
Adjustment disorder with depressed mood — n=1,044, PRR 53.5
Dislocation of vertebra — n=1,127, PRR 51.1
Muscle injury — n=4,115, PRR 50.0

✓ A hand-written Bradford Hill causality assessment exists for this drug: Methotrexate ↔ Hepatotoxicity.

Want to assess one of these properly? The runbook describes the Bradford Hill / trial-evidence workflow used on the assessment page, and handoff_top1000_signals.csv lists the strongest unassessed pairs across all drugs.

Common questions

What are the most reported side effects of Methotrexate?

In FDA FAERS, the most frequently co-reported reaction terms for Methotrexate are rheumatoid arthritis, arthralgia, pain, fatigue, nausea, joint swelling. These are report counts, not rates: FAERS has no denominator, reporting is voluntary and uneven, and a term can be reported because of the illness being treated rather than the drug.

Does Methotrexate have an FDA boxed warning?

Yes. The current FDA label carries a boxed warning: EMBRYO-FETAL TOXICITY, HYPERSENSITIVITY REACTIONS, BENZYL ALCOHOL TOXICITY, and OTHER SERIOUS ADVERSE REACTIONS • Methotrexate Injection can cause embryo-fetal toxicity, including fetal death. For non-neoplastic diseases, Methotrexate Injection is contraindicated in pregnancy.

Do FAERS signals prove that Methotrexate causes these side effects?

No. A disproportionality signal (PRR, ROR) means a reaction is reported more often with this drug than with others in the database. That can reflect a real effect, but also the disease being treated, stimulated reporting after news or litigation, co-medications, or how reports are coded. Causality needs temporality, dose-response, biological plausibility, consistency across data sources and, ideally, trial or cohort evidence. This page screens each term against the FDA label and ClinicalTrials.gov results; it does not establish causation.

Sources & methods

FDA label via openFDA (set ID 0e30eaef-5a09-4104-8a11-c32933eadeab, effective 20250822; matched on openfda.generic_name.exact:"METHOTREXATE" AND openfda.product_type:"HUMAN PRESCRIPTION DRUG")
PubChem CID 126941 description (ChEBI)
Bayesian shrinkage measures computed offline over all 1,317,300 cached pairs: BCPNN information component (IC, with Norén closed-form IC025) and MGPS empirical-Bayes geometric mean (EBGM, EB05) with a two-component gamma prior fitted by maximum marginal likelihood (α₁=0.57, β₁=0.02, α₂=1.42, β₂=0.70, w=0.17); unstratified
FAERS pair statistics from the OpenPV build of 2026-09-14 (openFDA count= aggregation, field patient.drug.openfda.generic_name.exact, 1,255 reaction terms, min 3 co-reports); PRR/ROR with 95% CI, chi-square with Yates correction
Serious-only and stratified counts (serious:1, patient.patientsex, primarysource.qualification) from openFDA count queries; serious-only PRR uses the drug serious report total and the term global serious total (N_serious=11,882,979); strata shown only when n ≥ 20
Seriousness and sex counts from openFDA count=serious, patient.patientsex, seriousnessdeath
ClinicalTrials.gov API v2 (query METHOTREXATE, results-bearing studies sorted by enrollment)

Page generated 2026-10-14. Label and PubChem text are retrieved automatically and may lag the current label; always check the current prescribing information. OpenPV is a beta research tool of the Open Source Medicine Foundation.