Drug · FAERS side-effect profile with label screen
Pemetrexed side effects: what 21,314 FDA adverse event reports show
Drug class
Folate analog metabolic inhibitor
FDA label, Indications wording
Who reports
21,314 reports · 98% serious · 3,752 with death outcome · 43% female
openFDA FAERS counts, all years, deduplication not applied
Used for
Pemetrexed for injection is a folate analog metabolic inhibitor indicated: • in combination with pembrolizumab and platinum chemotherapy, for the initial treatment of patients with metastatic non-squamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.
FDA label, Indications and Usage
What it is
Pemetrexed for injection, USP is a folate analog metabolic inhibitor. The drug substance, pemetrexed disodium hemipentahydrate, has the chemical name N -[4-[2-(2-amino-4,7-dihydro-4-oxo-1H-pyr.
FDA label, Description section
Boxed warning
None in the current 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 (related wording) 4Likely indication confounding 5Not in label — unassessed 31
What the badges mean
- 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.
- 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 flags pairs whose reports are unusually skewed by sex or come mostly from consumers rather than clinicians. 988 further terms are in the interactive explorer. Reaction links open the term's cross-drug page.
Show:
| Reaction | Reports | PRR 95% CI · ROR · χ²/p | EBGM EB05 · IC025 | Label screen | Serious-only & strata | Trial cross-check |
|---|---|---|---|---|---|---|
| Erosive pustular dermatosis | 19 | 658.0 367.5–1,178.1ROR 658.6 · χ² 7,039 / p <1e-300 | 281.4 EB05 190.4 · IC025 +4.4 3/3 methods agree | Not in label — unassessed | serious n=19 | not reported in cached trials |
| Pseudocellulitis | 68 | 467.7 350.3–624.4ROR 469.2 · χ² 21,049 / p <1e-300 | 290.1 EB05 236.7 · IC025 +6.2 3/3 methods agree | Not in label — unassessed | serious n=66 · ♀ 9% (drug 43%) · 94% clinician | not reported in cached trials |
| Scleroedema | 12 | 253.0 134.0–477.4ROR 253.1 · χ² 2,193 / p <1e-300 | 152.6 EB05 93.0 · IC025 +3.5 3/3 methods agree | Not in label — unassessed | serious n=12 | not reported in cached trials |
| Brain radiation necrosis | 13 | 225.1 123.1–411.5ROR 225.2 · χ² 2,175 / p <1e-300 | 144.6 EB05 89.9 · IC025 +3.6 3/3 methods agree | Not in label — unassessed | serious n=13 | not reported in cached trials |
| Lung adenocarcinoma recurrent | 13 | 157.6 87.7–283.1ROR 157.7 · χ² 1,608 / p <1e-300 | 113.5 EB05 70.6 · IC025 +3.6 3/3 methods agree | Not in label — unassessed | serious n=13 | not reported in cached trials |
| Malignant neoplasm oligoprogression | 22 | 141.3 90.3–220.9ROR 141.4 · χ² 2,554 / p <1e-300 | 111.7 EB05 77.8 · IC025 +4.3 3/3 methods agree | Not in label — unassessed | serious n=22 · 100% clinician | not reported in cached trials |
| Autoimmune lung disease | 14 | 135.8 77.6–237.5ROR 135.8 · χ² 1,527 / p <1e-300 | 102.9 EB05 65.1 · IC025 +3.7 3/3 methods agree | Labeled (related wording) related wording | serious n=14 | not reported in cached trials |
| Egfr gene mutation | 44 | 129.7 94.7–177.6ROR 130.0 · χ² 4,843 / p <1e-300 | 109.2 EB05 84.7 · IC025 +5.2 3/3 methods agree | Not in label — unassessed | serious n=44 · 98% clinician | not reported in cached trials |
| Scleroderma-like reaction | 17 | 120.3 72.7–199.1ROR 120.4 · χ² 1,685 / p <1e-300 | 95.9 EB05 63.4 · IC025 +3.9 3/3 methods agree | Not in label — unassessed | serious n=17 | not reported in cached trials |
| Lung adenocarcinoma stage iv | 37 | 106.2 75.6–149.0ROR 106.3 · χ² 3,380 / p <1e-300 | 91.4 EB05 69.2 · IC025 +4.9 3/3 methods agree | Not in label — unassessed | serious n=37 · 95% clinician | not reported in cached trials |
| Hyperphosphaturia | 10 | 90.6 47.4–173.3ROR 90.7 · χ² 731 / p 3e-161 | 72.0 EB05 41.8 · IC025 +3.0 3/3 methods agree | Not in label — unassessed | serious n=10 | not reported in cached trials |
| Immune-mediated lung disease | 147 | 90.3 76.3–106.9ROR 91.0 · χ² 11,799 / p <1e-300 | 81.9 EB05 71.4 · IC025 +5.7 3/3 methods agree | Labeled (related wording) related wording | serious n=146 · 98% clinician | not reported in cached trials |
| Tracheal fistula | 13 | 90.0 51.0–158.9ROR 90.1 · χ² 967 / p 1e-212 | 73.9 EB05 45.9 · IC025 +3.4 3/3 methods agree | Not in label — unassessed | serious n=12 | not reported in cached trials |
| Myocarditis-myositis-myasthenia gravis overlap syndrome | 15 | 88.7 52.3–150.5ROR 88.8 · χ² 1,113 / p 3e-244 | 74.0 EB05 47.6 · IC025 +3.6 3/3 methods agree | Not in label — unassessed | serious n=15 | not reported in cached trials |
| Immune-mediated dermatitis | 74 | 84.4 66.6–107.0ROR 84.7 · χ² 5,535 / p <1e-300 | 76.3 EB05 62.8 · IC025 +5.3 3/3 methods agree | Not in label — unassessed | serious n=74 · 92% clinician | not reported in cached trials |
| Non-small cell lung cancer metastatic | 61 | 75.1 57.9–97.4ROR 75.3 · χ² 4,069 / p <1e-300 | 68.3 EB05 55.1 · IC025 +5.1 3/3 methods agree | Likely indication confounding term in indications | serious n=61 · ♀ 63% (drug 43%) · 90% clinician | not reported in cached trials |
| Non-small cell lung cancer | 332 | 74.2 66.5–82.9ROR 75.4 · χ² 22,222 / p <1e-300 | 68.8 EB05 62.8 · IC025 +5.8 3/3 methods agree | Likely indication confounding term in indications | serious n=332 · 95% clinician | not reported in cached trials |
| Malignant transformation | 31 | 73.0 50.7–105.1ROR 73.1 · χ² 1,980 / p <1e-300 | 65.3 EB05 48.2 · IC025 +4.4 3/3 methods agree | Not in label — unassessed | serious n=31 · ♀ 75% (drug 43%) · 100% clinician | not reported in cached trials |
| Immune-mediated neuropathy | 10 | 72.4 38.1–137.6ROR 72.4 · χ² 590 / p 1e-130 | 60.1 EB05 34.9 · IC025 +2.9 3/3 methods agree | Labeled (related wording) related wording | serious n=10 | not reported in cached trials |
| Acquired gene mutation | 86 | 68.5 55.1–85.2ROR 68.8 · χ² 5,282 / p <1e-300 | 63.2 EB05 52.8 · IC025 +5.2 3/3 methods agree | Not in label — unassessed | serious n=86 · ♀ 63% (drug 43%) | not reported in cached trials |
| Non-small cell lung cancer recurrent | 18 | 68.2 42.3–109.9ROR 68.2 · χ² 1,051 / p 6e-231 | 59.9 EB05 40.1 · IC025 +3.8 3/3 methods agree | Likely indication confounding term in indications | serious n=18 | not reported in cached trials |
| Leukaemia cutis | 10 | 67.8 35.7–128.7ROR 67.8 · χ² 554 / p 7e-123 | 56.9 EB05 33.0 · IC025 +2.9 3/3 methods agree | Not in label — unassessed | serious n=10 | not reported in cached trials |
| Immune-mediated gastritis | 12 | 67.7 37.7–121.4ROR 67.7 · χ² 676 / p 3e-149 | 57.8 EB05 35.2 · IC025 +3.2 3/3 methods agree | Not in label — unassessed | serious n=12 | not reported in cached trials |
| Drug resistance mutation | 11 | 65.4 35.5–120.5ROR 65.5 · χ² 595 / p 1e-131 | 55.8 EB05 33.2 · IC025 +3.1 3/3 methods agree | Not in label — unassessed | serious n=11 | not reported in cached trials |
| Immune-mediated arthritis | 22 | 62.2 40.4–95.7ROR 62.3 · χ² 1,188 / p 1e-260 | 55.8 EB05 38.9 · IC025 +4.0 3/3 methods agree | Not in label — unassessed | serious n=22 · ♀ 68% (drug 43%) · 100% clinician | not reported in cached trials |
| Microvascular coronary artery disease | 12 | 59.7 33.3–106.9ROR 59.7 · χ² 598 / p 2e-132 | 51.9 EB05 31.6 · IC025 +3.2 3/3 methods agree | Not in label — unassessed | serious n=12 | not reported in cached trials |
| Autoimmune nephritis | 12 | 57.3 32.0–102.6ROR 57.4 · χ² 575 / p 2e-127 | 50.1 EB05 30.6 · IC025 +3.1 3/3 methods agree | Not in label — unassessed | serious n=12 | not reported in cached trials |
| Non-small cell lung cancer stage iv | 19 | 54.7 34.4–86.8ROR 54.7 · χ² 898 / p 2e-197 | 49.4 EB05 33.4 · IC025 +3.7 3/3 methods agree | Likely indication confounding shares a disease stem with the indications wording | serious n=19 | not reported in cached trials |
| Immune-mediated hypothyroidism | 53 | 51.0 38.7–67.2ROR 51.1 · χ² 2,420 / p <1e-300 | 47.7 EB05 37.9 · IC025 +4.6 3/3 methods agree | Not in label — unassessed | serious n=53 · 92% clinician | not reported in cached trials |
| Immune-mediated nephritis | 22 | 50.2 32.7–77.0ROR 50.2 · χ² 962 / p 1e-211 | 46.0 EB05 32.0 · IC025 +3.8 3/3 methods agree | Not in label — unassessed | serious n=22 | not reported in cached trials |
| Immune-mediated hepatitis | 94 | 49.4 40.2–60.8ROR 49.6 · χ² 4,199 / p <1e-300 | 46.7 EB05 39.3 · IC025 +4.9 3/3 methods agree | Not in label — unassessed | serious n=90 | not reported in cached trials |
| Hypercreatininaemia | 23 | 47.6 31.3–72.3ROR 47.6 · χ² 955 / p 5e-210 | 43.8 EB05 30.8 · IC025 +3.8 3/3 methods agree | Not in label — unassessed | serious n=23 · ♀ 22% (drug 43%) · 91% clinician | not reported in cached trials |
| Tumour pseudoprogression | 50 | 47.4 35.7–63.0ROR 47.6 · χ² 2,123 / p <1e-300 | 44.6 EB05 35.1 · IC025 +4.5 3/3 methods agree | Not in label — unassessed | serious n=50 | not reported in cached trials |
| Dermo-hypodermitis | 27 | 46.9 31.9–69.0ROR 47.0 · χ² 1,114 / p 1e-244 | 43.5 EB05 31.4 · IC025 +4.0 3/3 methods agree | Not in label — unassessed | serious n=27 · ♀ 69% (drug 43%) · 93% clinician | not reported in cached trials |
| Cancer fatigue | 10 | 45.3 24.0–85.4ROR 45.3 · χ² 373 / p 2e-83 | 40.3 EB05 23.4 · IC025 +2.8 3/3 methods agree | Not in label — unassessed | serious n=10 | not reported in cached trials |
| Lung adenocarcinoma | 133 | 45.3 38.1–53.9ROR 45.6 · χ² 5,461 / p <1e-300 | 43.1 EB05 37.3 · IC025 +4.9 3/3 methods agree | Not in label — unassessed | serious n=133 · 91% clinician | not reported in cached trials |
| Immune-mediated enterocolitis | 151 | 44.0 37.4–51.7ROR 44.3 · χ² 6,028 / p <1e-300 | 41.9 EB05 36.6 · IC025 +4.9 3/3 methods agree | Not in label — unassessed | serious n=151 · 92% clinician | not reported in cached trials |
| Immune-mediated renal disorder | 16 | 41.9 25.4–69.2ROR 42.0 · χ² 574 / p 3e-127 | 38.5 EB05 25.2 · IC025 +3.4 3/3 methods agree | Labeled (related wording) related wording | serious n=16 | not reported in cached trials |
| Pleural mesothelioma malignant | 12 | 41.9 23.5–74.6ROR 41.9 · χ² 420 / p 1e-93 | 38.0 EB05 23.1 · IC025 +3.0 3/3 methods agree | Likely indication confounding term in indications | serious n=12 | not reported in cached trials |
| Tumour associated fever | 16 | 40.9 24.8–67.5ROR 41.0 · χ² 560 / p 3e-124 | 37.7 EB05 24.6 · IC025 +3.3 3/3 methods agree | Not in label — unassessed | serious n=16 | not reported in cached trials |
Trial evidence (ClinicalTrials.gov)
✓ Trial adverse-event data found on ClinicalTrials.gov
Largest completed trials with posted results that list Pemetrexed as a study intervention. The right-hand column of the signal table shows whether each FAERS term was also recorded in these trials, with a real denominator (0 of 40 signal terms matched).
- NCT01107626 — Bevacizumab or Pemetrexed Disodium Alone or In Combination After Induction Therapy in Treating Patients With A (N=1516, PHASE3; 204 AE terms posted; arms: Arm I (Induction Therapy - Carboplatin, ; Arm A (Maintenance Therapy - Bevacizumab; Arm B (Maintenance Therapy - Pemetrexed); Arm C (Maintenance Therapy - Bevacizumab)
Caveats: trial populations, doses and follow-up differ from the reporting population; AE terms are sponsor-coded and matched here by wording; absence from a trial list means the term was not reported above the sponsor's frequency threshold, not that it cannot occur.
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 |
|---|---|---|---|---|---|---|
| Malignant neoplasm progression | 1,689 | 16.6 15.8–17.4ROR 17.9 · χ² 24,401 / p <1e-300 | 16.3 EB05 15.7 · IC025 +3.9 3/3 methods agree | Reporting / coding artifact | serious PRR 9.8 | not reported in cached trials |
| Anaemia (low red blood cells) | 1,278 | 6.6 6.3–7.0ROR 7.0 · χ² 6,113 / p <1e-300 | 6.6 EB05 6.3 · IC025 +2.6 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 4.2 · 91% clinician | NCT01107626: 19/286 (6.6%) on Pemetrexed (serious AE) |
| Disease progression | 1,119 | 9.4 8.9–10.0ROR 9.9 · χ² 8,374 / p <1e-300 | 9.3 EB05 8.9 · IC025 +3.1 3/3 methods agree | Reporting / coding artifact | serious PRR 6.2 · 97% clinician | not reported in cached trials |
| Off label use (used outside approved label) | 1,096 | 1.2 1.2–1.3ROR 1.3 · χ² 54 / p 1e-13 | 1.2 EB05 1.2 · IC025 +0.2 | Reporting / coding artifact | serious PRR 1.3 | not reported in cached trials |
| Neutropenia (low neutrophils (infection-fighting cells)) | 1,027 | 7.5 7.1–8.0ROR 7.8 · χ² 5,778 / p <1e-300 | 7.4 EB05 7.1 · IC025 +2.8 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 4.5 · 91% clinician | NCT01107626: 4/286 (1.4%) on Pemetrexed (serious AE) |
| Nausea | 1,016 | 1.3 1.2–1.3ROR 1.3 · χ² 59 / p 7e-15 | 1.3 EB05 1.2 · IC025 +0.2 | Labeled adverse reaction exact term | serious PRR 1.4 | NCT01107626: 7/286 (2.4%) on Pemetrexed (serious AE) |
| Diarrhoea (diarrhea) | 993 | 1.5 1.4–1.6ROR 1.5 · χ² 181 / p 1e-41 | 1.5 EB05 1.4 · IC025 +0.5 | Labeled adverse reaction exact term | serious PRR 1.6 | NCT01107626: 5/286 (1.7%) on Pemetrexed (serious AE) |
| Pancytopenia (all blood cells low) | 959 | 17.2 16.2–18.3ROR 18.0 · χ² 14,409 / p <1e-300 | 16.9 EB05 16.0 · IC025 +4.0 3/3 methods agree | Labeled (related wording) related wording | serious PRR 10.0 · 93% clinician | not reported in cached trials |
| Drug ineffective (drug did not work) | 958 | 0.7 0.7–0.8ROR 0.7 · χ² 115 / p 4e-27 | 0.7 EB05 0.7 · IC025 -0.6 PRR-only: not supported by EBGM or IC | Reporting / coding artifact | serious PRR 1.2 · 94% clinician | not reported in cached trials |
| Thrombocytopenia (low platelets) | 958 | 8.5 8.0–9.1ROR 8.9 · χ² 6,326 / p <1e-300 | 8.4 EB05 8.0 · IC025 +3.0 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 5.1 · 92% clinician | not reported in cached trials |
| Acute kidney injury (sudden kidney damage) | 808 | 5.2 4.9–5.6ROR 5.4 · χ² 2,774 / p <1e-300 | 5.2 EB05 4.9 · IC025 +2.3 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 3.1 · 93% clinician | not reported in cached trials |
| Vomiting | 786 | 1.7 1.5–1.8ROR 1.7 · χ² 205 / p 9e-47 | 1.6 EB05 1.6 · IC025 +0.6 | Labeled adverse reaction exact term | serious PRR 1.4 | NCT01107626: 6/286 (2.1%) on Pemetrexed (serious AE) |
| Pneumonia (lung infection) | 777 | 2.4 2.2–2.5ROR 2.4 · χ² 621 / p 3e-137 | 2.4 EB05 2.2 · IC025 +1.1 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 1.4 · 91% clinician | not reported in cached trials |
| Death | 768 | 0.9 0.8–0.9ROR 0.9 · χ² 14 / p 1e-4 | 0.9 EB05 0.8 · IC025 -0.3 PRR-only: not supported by EBGM or IC | Outcome field, not a reaction | serious PRR 0.5 | NCT01107626: 1/286 (0.3%) on Pemetrexed (serious AE) |
| Febrile neutropenia | 756 | 11.3 10.6–12.2ROR 11.7 · χ² 7,064 / p <1e-300 | 11.2 EB05 10.6 · IC025 +3.4 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 6.6 · 93% clinician | NCT01107626: 4/286 (1.4%) on Pemetrexed (serious AE) |
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.
- Pseudocellulitis — n=68, PRR 467.7
- Malignant neoplasm oligoprogression — n=22, PRR 141.3
- Egfr gene mutation — n=44, PRR 129.7
- Lung adenocarcinoma stage iv — n=37, PRR 106.2
- Immune-mediated dermatitis — n=74, PRR 84.4
- Malignant transformation — n=31, PRR 73.0
- Acquired gene mutation — n=86, PRR 68.5
- Immune-mediated arthritis — n=22, PRR 62.2
- Immune-mediated hypothyroidism — n=53, PRR 51.0
- Immune-mediated nephritis — n=22, PRR 50.2
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 Pemetrexed?
In FDA FAERS, the most frequently co-reported reaction terms for Pemetrexed are anaemia, neutropenia, nausea, diarrhoea, pancytopenia, thrombocytopenia. 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 Pemetrexed have an FDA boxed warning?
No. The FDA label retrieved for Pemetrexed has no boxed warning; see the label's Warnings and Precautions for the recognised risks.
Do FAERS signals prove that Pemetrexed 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 737ead51-f73c-414f-b68f-d3affc27a225, effective 20230727; matched on
openfda.generic_name.exact:"PEMETREXED") - 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, fieldpatient.drug.openfda.generic_name.exact, 1,028 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
PEMETREXED, results-bearing studies sorted by enrollment)
Page generated 2026-10-08. 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.