Methotrexate Sodium side effects: what 483,097 FDA adverse event reports show

Methotrexate Sodium · 1,253 reaction terms · 2,451,188 drug–reaction co-reports · data 2026-09-14

Drug class

Folate analog metabolic inhibitor

FDA label, Indications wording

Who reports

483,097 reports · 73% serious · 37,640 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

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 11Not in label — unassessed 19

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). 1,213 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
Anti-cyclic citrullinated peptide antibody positive	6,113	283.5 264.4–304.0ROR 287.1 · calibrated p 1e-11 ✓	37.3 EB05 36.5 · IC025 +5.2 3/3 methods agree	Lab value / disease marker	serious PRR 29.2 · ♀ 98% (drug 71%) · 92% clinician	no trial arm names this drug
Rheumatoid factor positive	4,842	237.4 220.8–255.4ROR 239.8 · calibrated p 8e-11 ✓	36.4 EB05 35.6 · IC025 +5.1 3/3 methods agree	Lab value / disease marker	serious n=4,835 · ♀ 97% (drug 71%) · 91% clinician	no trial arm names this drug
Swollen joint count increased	2,499	180.2 164.7–197.3ROR 181.2 · calibrated p 1e-9 ✓	34.8 EB05 33.6 · IC025 +5.0 3/3 methods agree	Lab value / disease marker	serious n=2,492 · ♀ 100% (drug 71%) · 94% clinician	no trial arm names this drug
Anti-cyclic citrullinated peptide antibody	527	167.0 138.0–202.1ROR 167.2 · calibrated p 3e-9 ✓	34.2 EB05 31.8 · IC025 +4.9 3/3 methods agree	Lab value / disease marker	serious n=524 · ♀ 100% (drug 71%) · 100% clinician	no trial arm names this drug
Red blood cell sedimentation rate abnormal	1,797	150.3 136.2–166.0ROR 150.9 · calibrated p 5e-9 ✓	33.5 EB05 32.2 · IC025 +5.0 3/3 methods agree	Lab value / disease marker	serious n=1,783	no trial arm names this drug
Pemphigus	9,382	135.9 130.4–141.7ROR 138.6 · calibrated p 9e-9 ✓	32.7 EB05 32.2 · IC025 +5.0 3/3 methods agree	Not in label — unassessed	serious PRR 25.7 · ♀ 100% (drug 71%)	no trial arm names this drug
Synovitis	13,569	133.8 129.3–138.4ROR 137.6 · calibrated p 9e-9 ✓	32.6 EB05 32.2 · IC025 +5.0 3/3 methods agree	Not in label — unassessed	serious PRR 26.3	no trial arm names this drug
Rheumatic fever	3,282	133.3 124.3–142.9ROR 134.2 · calibrated p 1e-8 ✓	32.6 EB05 31.7 · IC025 +5.0 3/3 methods agree	Likely indication confounding shares a disease stem with the indications wording	serious n=3,280 · ♀ 100% (drug 71%) · 94% clinician	no trial arm names this drug
Lupus vulgaris	867	117.7 103.4–134.1ROR 118.0 · calibrated p 4e-8 ✓	31.6 EB05 29.9 · IC025 +4.8 3/3 methods agree	Not in label — unassessed	serious n=867 · ♀ 100% (drug 71%) · 100% clinician	no trial arm names this drug
C-reactive protein abnormal	4,659	117.0 110.7–123.8ROR 118.2 · calibrated p 3e-8 ✓	31.5 EB05 30.8 · IC025 +4.9 3/3 methods agree	Lab value / disease marker	serious n=4,645	no trial arm names this drug
Deep vein thrombosis postoperative	1,372	101.8 92.3–112.2ROR 102.0 · calibrated p 1e-7 ✓	30.3 EB05 29.0 · IC025 +4.8 3/3 methods agree	Not in label — unassessed	serious n=1,372 · ♀ 100% (drug 71%) · 93% clinician	no trial arm names this drug
Duodenal ulcer perforation	5,067	97.3 92.5–102.3ROR 98.3 · calibrated p 1e-7 ✓	29.9 EB05 29.3 · IC025 +4.9 3/3 methods agree	Labeled (related wording) related wording	serious PRR 23.4 · ♀ 100% (drug 71%) · 93% clinician	no trial arm names this drug
C-reactive protein	617	92.5 80.3–106.6ROR 92.6 · calibrated p 2e-7 ✓	29.5 EB05 27.6 · IC025 +4.7 3/3 methods agree	Lab value / disease marker	serious n=617 · ♀ 100% (drug 71%) · 100% clinician	no trial arm names this drug
Hand deformity	8,885	92.3 88.9–95.8ROR 94.0 · calibrated p 2e-7 ✓	29.5 EB05 29.0 · IC025 +4.8 3/3 methods agree	Not in label — unassessed	serious PRR 24.7 · ♀ 96% (drug 71%)	no trial arm names this drug
Granuloma skin	539	80.8 69.9–93.4ROR 80.9 · calibrated p 6e-7 ✓	28.2 EB05 26.3 · IC025 +4.6 3/3 methods agree	Not in label — unassessed	serious n=538 · ♀ 100% (drug 71%)	no trial arm names this drug
Epstein barr virus positive mucocutaneous ulcer	324	80.7 67.0–97.2ROR 80.7 · calibrated p 7e-7 ✓	28.2 EB05 25.7 · IC025 +4.6 3/3 methods agree	Not in label — unassessed	serious n=324 · 100% clinician	no trial arm names this drug
Rheumatoid nodule	1,759	74.3 68.8–80.3ROR 74.6 · calibrated p 1e-6 ✓	27.4 EB05 26.3 · IC025 +4.7 3/3 methods agree	Likely indication confounding shares a disease stem with the indications wording	serious n=1,631	no trial arm names this drug
Facet joint syndrome	1,964	71.6 66.5–77.0ROR 71.9 · calibrated p 1e-6 ✓	27.0 EB05 26.0 · IC025 +4.7 3/3 methods agree	Not in label — unassessed	serious n=1,963 · ♀ 100% (drug 71%) · 94% clinician	no trial arm names this drug
Bone erosion	2,084	61.7 57.7–66.0ROR 62.0 · calibrated p 3e-6 ✓	25.5 EB05 24.6 · IC025 +4.6 3/3 methods agree	Labeled (related wording) related wording	serious n=2,061	no trial arm names this drug
X-ray abnormal	1,043	60.7 55.2–66.7ROR 60.8 · calibrated p 4e-6 ✓	25.3 EB05 24.1 · IC025 +4.5 3/3 methods agree	Lab value / disease marker	serious n=1,041 · ♀ 100% (drug 71%) · 91% clinician	no trial arm names this drug
Adjustment disorder with depressed mood	1,109	52.7 48.2–57.5ROR 52.8 · calibrated p 1e-5 ✓	23.9 EB05 22.7 · IC025 +4.5 3/3 methods agree	Not in label — unassessed	serious n=1,108 · ♀ 100% (drug 71%) · 100% clinician	no trial arm names this drug
Dislocation of vertebra	1,211	51.4 47.3–55.9ROR 51.6 · calibrated p 1e-5 ✓	23.6 EB05 22.5 · IC025 +4.5 3/3 methods agree	Not in label — unassessed	serious n=1,209 · ♀ 100% (drug 71%) · 92% clinician	no trial arm names this drug
Body height below normal	343	48.0 41.1–56.0ROR 48.0 · calibrated p 2e-5 ✓	22.9 EB05 20.9 · IC025 +4.3 3/3 methods agree	Reporting / coding artifact	serious n=343 · 100% consumer	no trial arm names this drug
Muscle injury	4,306	47.5 45.4–49.6ROR 47.9 · calibrated p 2e-5 ✓	22.8 EB05 22.2 · IC025 +4.5 3/3 methods agree	Not in label — unassessed	serious PRR 19.3 · ♀ 100% (drug 71%) · 93% clinician	no trial arm names this drug
Helicobacter infection	5,277	46.1 44.4–48.0ROR 46.6 · calibrated p 2e-5 ✓	22.5 EB05 22.0 · IC025 +4.4 3/3 methods agree	Not in label — unassessed	serious PRR 18.5 · ♀ 100% (drug 71%) · 92% clinician	no trial arm names this drug
Lymphoproliferative disorder	1,503	44.9 41.8–48.3ROR 45.1 · calibrated p 3e-5 ✓	22.2 EB05 21.3 · IC025 +4.4 3/3 methods agree	Labeled (related wording) related wording	serious n=1,500 · 100% clinician	no trial arm names this drug
Sleep disorder due to general medical condition, insomnia type	3,191	42.2 40.2–44.3ROR 42.5 · calibrated p 4e-5 ✓	21.5 EB05 20.9 · IC025 +4.4 3/3 methods agree	Not in label — unassessed	serious n=3,174 · ♀ 96% (drug 71%) · 93% clinician	no trial arm names this drug
Enthesopathy	781	42.1 38.1–46.5ROR 42.2 · calibrated p 4e-5 ✓	21.5 EB05 20.2 · IC025 +4.3 3/3 methods agree	Not in label — unassessed	serious n=761	no trial arm names this drug
Seronegative arthritis	555	42.0 37.3–47.2ROR 42.0 · calibrated p 4e-5 ✓	21.4 EB05 20.0 · IC025 +4.3 3/3 methods agree	Likely indication confounding shares a disease stem with the indications wording	serious n=549 · ♀ 100% (drug 71%) · 100% clinician	no trial arm names this drug
Folliculitis	5,035	40.8 39.3–42.4ROR 41.2 · calibrated p 4e-5 ✓	21.2 EB05 20.7 · IC025 +4.4 3/3 methods agree	Not in label — unassessed	serious PRR 19.3 · ♀ 98% (drug 71%) · 94% clinician	no trial arm names this drug
Dactylitis	468	39.1 34.4–44.3ROR 39.1 · calibrated p 6e-5 ✓	20.7 EB05 19.1 · IC025 +4.2 3/3 methods agree	Not in label — unassessed	serious n=448	no trial arm names this drug
Retinitis	790	38.5 35.0–42.4ROR 38.6 · calibrated p 7e-5 ✓	20.5 EB05 19.3 · IC025 +4.2 3/3 methods agree	Not in label — unassessed	serious n=789 · ♀ 100% (drug 71%) · 100% clinician	no trial arm names this drug
Contraindicated product administered	14,237	38.3 37.5–39.2ROR 39.5 · calibrated p 6e-5 ✓	20.5 EB05 20.2 · IC025 +4.3 3/3 methods agree	Reporting / coding artifact	age-adj. PRR 28.6 · serious PRR 19.0 · ♀ 91% (drug 71%)	no trial arm names this drug
Rheumatoid lung	451	37.7 33.2–42.9ROR 37.8 · calibrated p 8e-5 ✓	20.3 EB05 18.8 · IC025 +4.2 3/3 methods agree	Labeled (related wording) related wording	serious n=439	no trial arm names this drug
Drug clearance decreased	570	35.4 31.7–39.6ROR 35.5 · calibrated p 1e-4 ✓	19.6 EB05 18.3 · IC025 +4.1 3/3 methods agree	Lab value / disease marker	serious n=556 · ♀ 39% (drug 71%) · 100% clinician	no trial arm names this drug
Joint destruction	684	33.3 30.1–36.8ROR 33.3 · calibrated p 2e-4 ✓	19.0 EB05 17.8 · IC025 +4.1 3/3 methods agree	Not in label — unassessed	serious n=661 · ♀ 100% (drug 71%)	no trial arm names this drug
Pericarditis	6,863	30.0 29.0–30.9ROR 30.4 · calibrated p 2e-4 ✓	17.9 EB05 17.5 · IC025 +4.1 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 14.1 · ♀ 96% (drug 71%) · 92% clinician	no trial arm names this drug
Peripheral venous disease	1,635	29.6 27.8–31.6ROR 29.7 · calibrated p 3e-4 ✓	17.8 EB05 17.0 · IC025 +4.1 3/3 methods agree	Not in label — unassessed	serious n=1,624 · ♀ 100% (drug 71%) · 93% clinician	no trial arm names this drug
Blood parathyroid hormone decreased	609	29.5 26.6–32.7ROR 29.6 · calibrated p 3e-4 ✓	17.7 EB05 16.6 · IC025 +4.0 3/3 methods agree	Lab value / disease marker	serious n=608 · ♀ 100% (drug 71%)	no trial arm names this drug
Blood pressure diastolic abnormal	1,029	28.5 26.4–30.9ROR 28.6 · calibrated p 3e-4 ✓	17.4 EB05 16.5 · IC025 +4.0 3/3 methods agree	Lab value / disease marker	serious n=1,004 · 91% 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	9,522	4.74.6–4.8	signal
Liver injury	26,816	4.14.1–4.2	signal
Opportunistic infection	11,853	4.04.0–4.1	signal
Serious infection	48,273	2.82.8–2.9	signal
Neutropenia / agranulocytosis	15,014	2.72.7–2.8	signal
Tendon disorder	2,298	2.72.6–2.8	signal
Thrombocytopenia	8,027	1.61.6–1.6	raised
Pancreatitis	2,767	1.51.5–1.6	raised
Anaemia	10,207	1.51.5–1.5	raised
Fall / fracture	11,952	1.41.4–1.4	raised
Kidney injury	13,280	1.31.2–1.3	raised
Osteonecrosis	1,635	1.21.2–1.3	raised
Hyperglycaemia / diabetes	9,723	1.21.2–1.3	raised
Malignancy	10,588	1.21.2–1.2	raised
Venous thromboembolism	6,059	1.21.2–1.3	raised
Depression	7,698	1.21.2–1.2	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)	92,614	3.2 3.2–3.2ROR 3.7 · calibrated p 0.431	3.1 EB05 3.0 · IC025 +1.6 3/3 methods agree	Reporting / coding artifact	age-adj. PRR 3.5 · serious PRR 4.9	no trial arm names this drug
Rheumatoid arthritis	42,466	25.7 25.4–26.0ROR 28.1 · calibrated p 4e-4 ✓	16.3 EB05 16.2 · IC025 +4.0 3/3 methods agree	Likely indication confounding term in indications; also in warnings	age-adj. PRR 21.1 · serious PRR 14.4	no trial arm names this drug
Arthralgia (joint pain)	40,408	4.6 4.5–4.6ROR 4.9 · calibrated p 0.244	4.2 EB05 4.2 · IC025 +2.1 3/3 methods agree	Labeled adverse reaction exact term	age-adj. PRR 4.1 · serious PRR 4.9	no trial arm names this drug
Off label use (used outside approved label)	39,859	2.0 2.0–2.1ROR 2.1 · calibrated p 0.984	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
Pain	39,309	2.9 2.9–2.9ROR 3.1 · calibrated p 0.606	2.8 EB05 2.7 · IC025 +1.5 3/3 methods agree	Labeled adverse reaction exact term	age-adj. PRR 2.9 · serious PRR 2.9	no trial arm names this drug
Fatigue (tiredness)	32,750	1.9 1.8–1.9ROR 1.9 · calibrated p 0.905	1.8 EB05 1.8 · IC025 +0.9	Labeled adverse reaction exact term	age-adj. PRR 1.7 · serious PRR 2.2	no trial arm names this drug
Nausea	28,656	1.6 1.6–1.6ROR 1.6 · calibrated p 0.729	1.6 EB05 1.6 · IC025 +0.6	Labeled adverse reaction exact term	age-adj. PRR 1.5 · serious PRR 1.9	no trial arm names this drug
Joint swelling	24,834	11.0 10.9–11.2ROR 11.6 · calibrated p 0.019 ✓	8.9 EB05 8.9 · IC025 +3.1 3/3 methods agree	Not in label — unassessed	age-adj. PRR 9.4 · serious PRR 10.7	no trial arm names this drug
Drug intolerance	24,385	14.4 14.2–14.7ROR 15.2 · calibrated p 0.007 ✓	11.0 EB05 10.9 · IC025 +3.4 3/3 methods agree	Reporting / coding artifact	age-adj. PRR 15.8 · serious PRR 12.4	no trial arm names this drug
Condition aggravated	23,715	3.6 3.6–3.7ROR 3.8 · calibrated p 0.427	3.4 EB05 3.4 · IC025 +1.7 3/3 methods agree	Reporting / coding artifact	age-adj. PRR 3.3 · serious PRR 3.7	no trial arm names this drug
Headache	23,243	1.6 1.6–1.7ROR 1.7 · calibrated p 0.749	1.6 EB05 1.6 · IC025 +0.7	Labeled adverse reaction exact term	age-adj. PRR 1.5 · serious PRR 2.1	no trial arm names this drug
Rash	22,362	2.3 2.3–2.3ROR 2.4 · calibrated p 0.870	2.2 EB05 2.2 · IC025 +1.1 3/3 methods agree	Labeled adverse reaction exact term	age-adj. PRR 2.0 · serious PRR 3.3	no trial arm names this drug
Diarrhoea (diarrhea)	20,703	1.4 1.4–1.4ROR 1.4 · calibrated p 0.594	1.4 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	19,877	3.1 3.0–3.1ROR 3.2 · calibrated p 0.579	2.9 EB05 2.9 · IC025 +1.5 3/3 methods agree	Not in label — unassessed	age-adj. PRR 2.8 · serious PRR 3.2	no trial arm names this drug
Drug hypersensitivity	19,622	4.8 4.7–4.8ROR 4.9 · calibrated p 0.242	4.4 EB05 4.3 · IC025 +2.1 3/3 methods agree	Labeled (related wording) related wording	age-adj. PRR 5.2 · serious PRR 6.0	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=9,382, PRR 135.9
Synovitis — n=13,569, PRR 133.8
Lupus vulgaris — n=867, PRR 117.7
Deep vein thrombosis postoperative — n=1,372, PRR 101.8
Hand deformity — n=8,885, PRR 92.3
Granuloma skin — n=539, PRR 80.8
Epstein barr virus positive mucocutaneous ulcer — n=324, PRR 80.7
Facet joint syndrome — n=1,964, PRR 71.6
Adjustment disorder with depressed mood — n=1,109, PRR 52.7
Dislocation of vertebra — n=1,211, PRR 51.4

✓ 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: 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")
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, 1,253 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.