Indomethacin side effects: what 13,174 FDA adverse event reports show
Drug class
Nonsteroidal Anti-inflammatory Drug
Who reports
13,174 reports · 79% serious · 1,524 with death outcome · 53% female
Used for
Indomethacin extended-release capsules are indicated for: • Moderate to severe rheumatoid arthritis including acute flares of chronic disease • Moderate to severe ankylosing spondylitis • Moderate to severe osteoarthritis • Acute painful shoulder (burs.
What it is
Indomethacin extended-release capsules are nonsteroidal anti-inflammatory drugs, available as capsules containing 75 mg of indomethacin, administered for oral use.
Boxed warning
RISK OF SERIOUS CARDIOVASCULAR AND GASTROINTESTINAL EVENTS Cardiovascular Thrombotic Events • Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal.
Causality screen of the 40 strongest signals
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.
- 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 flags pairs whose reports are unusually skewed by sex or come mostly from consumers rather than clinicians. 1,136 further terms are in the interactive explorer. Reaction links open the term's cross-drug page.
| Reaction | Reports | PRR 95% CI · ROR · χ²/p | EBGM EB05 · IC025 | Label screen | Serious-only & strata | Trial cross-check |
|---|---|---|---|---|---|---|
| Actinomycotic sepsis | 14 | 1,998.0 907.2–4,400.2ROR 2,000.1 · χ² 11,432 / p <1e-300 | 398.8 EB05 252.5 · IC025 +3.9 3/3 methods agree | Not in label — unassessed | serious n=14 | not reported in cached trials |
| Chronic idiopathic pain syndrome | 21 | 558.8 339.7–919.2ROR 559.6 · χ² 8,216 / p <1e-300 | 299.8 EB05 206.8 · IC025 +4.6 3/3 methods agree | Not in label — unassessed | serious n=21 | not reported in cached trials |
| Amaurosis fugax | 215 | 401.3 345.8–465.7ROR 408.0 · χ² 68,061 / p <1e-300 | 311.0 EB05 277.6 · IC025 +7.3 3/3 methods agree | Not in label — unassessed | serious n=215 · 93% clinician | not reported in cached trials |
| Foetal renal impairment | 15 | 351.5 200.8–615.0ROR 351.9 · χ² 4,001 / p <1e-300 | 210.6 EB05 135.5 · IC025 +3.9 3/3 methods agree | Labeled (related wording) related wording | serious n=15 | not reported in cached trials |
| Diffuse axonal injury | 12 | 330.5 177.4–615.8ROR 330.8 · χ² 2,990 / p <1e-300 | 190.8 EB05 116.3 · IC025 +3.5 3/3 methods agree | Not in label — unassessed | serious n=12 | not reported in cached trials |
| Ductus arteriosus stenosis foetal | 58 | 251.5 190.7–331.7ROR 252.6 · χ² 12,259 / p <1e-300 | 202.5 EB05 162.4 · IC025 +5.8 3/3 methods agree | Labeled (related wording) related wording | serious n=58 · 100% clinician | not reported in cached trials |
| Ductus arteriosus premature closure | 50 | 219.9 163.6–295.4ROR 220.7 · χ² 9,364 / p <1e-300 | 179.8 EB05 141.7 · IC025 +5.6 3/3 methods agree | Labeled (related wording) related wording | serious n=50 · ♀ 0% (drug 53%) · 100% clinician | not reported in cached trials |
| Retinopathy of prematurity | 64 | 209.7 161.7–272.1ROR 210.8 · χ² 11,546 / p <1e-300 | 175.5 EB05 142.3 · IC025 +5.8 3/3 methods agree | Not in label — unassessed | serious n=64 · 100% clinician | not reported in cached trials |
| Herpes zoster infection neurological | 14 | 151.6 87.6–262.3ROR 151.7 · χ² 1,775 / p <1e-300 | 116.7 EB05 73.9 · IC025 +3.7 3/3 methods agree | Not in label — unassessed | serious n=14 | not reported in cached trials |
| Heterophoria | 11 | 129.8 70.2–240.1ROR 129.9 · χ² 1,183 / p 2e-259 | 99.7 EB05 59.4 · IC025 +3.3 3/3 methods agree | Not in label — unassessed | serious n=11 | not reported in cached trials |
| Necrotising enterocolitis neonatal | 28 | 119.1 81.2–174.9ROR 119.4 · χ² 2,939 / p <1e-300 | 103.2 EB05 74.9 · IC025 +4.6 3/3 methods agree | Not in label — unassessed | serious n=28 | not reported in cached trials |
| Intraventricular haemorrhage neonatal | 33 | 115.4 81.1–164.2ROR 115.7 · χ² 3,380 / p <1e-300 | 101.4 EB05 75.5 · IC025 +4.8 3/3 methods agree | Labeled (related wording) related wording | serious n=33 · 100% clinician | not reported in cached trials |
| Periventricular leukomalacia | 18 | 107.4 66.7–173.2ROR 107.6 · χ² 1,678 / p <1e-300 | 91.2 EB05 61.0 · IC025 +4.0 3/3 methods agree | Not in label — unassessed | serious n=18 | not reported in cached trials |
| Synovial disorder | 28 | 104.2 71.1–152.6ROR 104.4 · χ² 2,587 / p <1e-300 | 91.8 EB05 66.6 · IC025 +4.5 3/3 methods agree | Not in label — unassessed | serious n=28 · ♀ 100% (drug 53%) | not reported in cached trials |
| Porphyria acute | 75 | 91.4 72.5–115.3ROR 91.9 · χ² 6,253 / p <1e-300 | 84.6 EB05 69.7 · IC025 +5.4 3/3 methods agree | Not in label — unassessed | serious n=75 · ♀ 100% (drug 53%) · 95% clinician | not reported in cached trials |
| Neck deformity | 22 | 81.8 53.3–125.6ROR 82.0 · χ² 1,594 / p <1e-300 | 73.1 EB05 50.9 · IC025 +4.1 3/3 methods agree | Not in label — unassessed | serious n=22 | not reported in cached trials |
| Bronchopulmonary dysplasia | 38 | 79.1 57.1–109.5ROR 79.3 · χ² 2,716 / p <1e-300 | 72.7 EB05 55.3 · IC025 +4.7 3/3 methods agree | Not in label — unassessed | serious n=38 · 100% clinician | not reported in cached trials |
| Oesophageal spasm | 81 | 73.2 58.6–91.4ROR 73.6 · χ² 5,440 / p <1e-300 | 68.9 EB05 57.2 · IC025 +5.3 3/3 methods agree | Not in label — unassessed | serious n=80 · ♀ 100% (drug 53%) | not reported in cached trials |
| Necrotising colitis | 54 | 70.0 53.3–91.9ROR 70.3 · χ² 3,450 / p <1e-300 | 65.6 EB05 52.2 · IC025 +4.9 3/3 methods agree | Not in label — unassessed | serious n=54 · 100% clinician | not reported in cached trials |
| X-ray abnormal | 75 | 69.8 55.4–87.9ROR 70.2 · χ² 4,804 / p <1e-300 | 65.8 EB05 54.2 · IC025 +5.2 3/3 methods agree | Lab value / disease marker | serious n=75 · ♀ 100% (drug 53%) · 92% clinician | not reported in cached trials |
| Urinary tract disorder | 187 | 69.0 59.7–79.8ROR 70.0 · χ² 11,946 / p <1e-300 | 65.7 EB05 58.2 · IC025 +5.6 3/3 methods agree | Labeled (related wording) related wording | serious n=188 · 95% clinician | NCT02476279: 2/975 (0.2%) on Indomethacin (serious AE) |
| Congenital aplasia | 12 | 68.8 38.6–122.5ROR 68.8 · χ² 704 / p 2e-155 | 59.9 EB05 36.5 · IC025 +3.2 3/3 methods agree | Not in label — unassessed | serious n=12 | not reported in cached trials |
| Intestinal diaphragm disease | 11 | 65.9 36.1–120.5ROR 66.0 · χ² 614 / p 8e-136 | 57.3 EB05 34.2 · IC025 +3.1 3/3 methods agree | Labeled (related wording) related wording | serious n=11 | not reported in cached trials |
| Oligohydramnios | 115 | 56.5 47.0–68.0ROR 57.0 · χ² 6,003 / p <1e-300 | 54.1 EB05 46.3 · IC025 +5.2 3/3 methods agree | Labeled adverse reaction exact term | serious n=115 · ♀ 100% (drug 53%) · 100% clinician | not reported in cached trials |
| Phonophobia | 15 | 53.8 32.1–89.9ROR 53.8 · χ² 701 / p 1e-154 | 49.0 EB05 31.5 · IC025 +3.4 3/3 methods agree | Not in label — unassessed | serious n=15 | not reported in cached trials |
| Haemorrhagic stroke | 256 | 53.6 47.4–60.6ROR 54.6 · χ² 12,725 / p <1e-300 | 51.6 EB05 46.6 · IC025 +5.4 3/3 methods agree | Not in label — unassessed | serious PRR 37.8 · 91% clinician | not reported in cached trials |
| Episcleritis | 22 | 52.6 34.4–80.4ROR 52.7 · χ² 1,028 / p 9e-226 | 48.9 EB05 34.0 · IC025 +3.9 3/3 methods agree | Not in label — unassessed | serious n=22 | not reported in cached trials |
| Dislocation of vertebra | 70 | 51.7 40.8–65.5ROR 52.0 · χ² 3,320 / p <1e-300 | 49.4 EB05 40.5 · IC025 +4.8 3/3 methods agree | Not in label — unassessed | serious n=70 · ♀ 100% (drug 53%) · 91% clinician | not reported in cached trials |
| Medication overuse headache | 26 | 49.9 33.8–73.7ROR 50.0 · χ² 1,161 / p 1e-254 | 46.8 EB05 33.6 · IC025 +4.0 3/3 methods agree | Labeled (related wording) related wording | serious n=24 · ♀ 100% (drug 53%) · 100% clinician | not reported in cached trials |
| Hydrops foetalis | 18 | 48.2 30.2–77.1ROR 48.3 · χ² 762 / p 4e-168 | 44.8 EB05 29.9 · IC025 +3.6 3/3 methods agree | Not in label — unassessed | serious n=18 | not reported in cached trials |
| Allergic sinusitis | 25 | 47.6 32.0–70.9ROR 47.7 · χ² 1,063 / p 2e-233 | 44.8 EB05 31.9 · IC025 +3.9 3/3 methods agree | Labeled (related wording) related wording | serious n=25 · ♀ 100% (drug 53%) | not reported in cached trials |
| Adjustment disorder with depressed mood | 54 | 43.8 33.4–57.4ROR 44.0 · χ² 2,155 / p <1e-300 | 42.0 EB05 33.4 · IC025 +4.5 3/3 methods agree | Not in label — unassessed | serious n=54 · ♀ 100% (drug 53%) · 91% clinician | not reported in cached trials |
| Focal nodular hyperplasia | 14 | 43.4 25.5–73.8ROR 43.5 · χ² 524 / p 3e-116 | 40.2 EB05 25.4 · IC025 +3.2 3/3 methods agree | Not in label — unassessed | serious n=14 | not reported in cached trials |
| Sepsis neonatal | 21 | 42.6 27.7–65.8ROR 42.7 · χ² 791 / p 2e-174 | 40.2 EB05 27.7 · IC025 +3.7 3/3 methods agree | Not in label — unassessed | serious n=21 | not reported in cached trials |
| Cellulitis staphylococcal | 17 | 42.5 26.3–68.8ROR 42.5 · χ² 631 / p 2e-139 | 39.7 EB05 26.3 · IC025 +3.4 3/3 methods agree | Not in label — unassessed | serious n=17 | not reported in cached trials |
| Occipital neuralgia | 14 | 40.6 23.9–69.0ROR 40.7 · χ² 490 / p 9e-109 | 37.8 EB05 23.9 · IC025 +3.2 3/3 methods agree | Not in label — unassessed | serious n=14 | not reported in cached trials |
| Bradycardia foetal | 20 | 39.8 25.6–62.1ROR 39.9 · χ² 701 / p 8e-155 | 37.6 EB05 25.7 · IC025 +3.6 3/3 methods agree | Not in label — unassessed | serious n=20 | not reported in cached trials |
| Nephrogenic anaemia | 113 | 39.4 32.7–47.5ROR 39.7 · χ² 4,090 / p <1e-300 | 38.2 EB05 32.7 · IC025 +4.7 3/3 methods agree | Not in label — unassessed | serious n=113 | not reported in cached trials |
| Facet joint syndrome | 76 | 39.3 31.3–49.3ROR 39.5 · χ² 2,730 / p <1e-300 | 38.0 EB05 31.4 · IC025 +4.6 3/3 methods agree | Not in label — unassessed | serious n=76 · ♀ 92% (drug 53%) | not reported in cached trials |
| Retrograde amnesia | 12 | 39.2 22.1–69.4ROR 39.2 · χ² 399 / p 5e-89 | 36.2 EB05 22.1 · IC025 +3.0 3/3 methods agree | Not in label — unassessed | serious n=12 | 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 Indomethacin 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 (1 of 40 signal terms matched).
- NCT02002650 — Rectal Indomethacin to Prevent Post-ERCP Pancreatitis (N=2600, NA; 7 AE terms posted; arms: Pre-ERCP Group; Post-ERCP Group)
- NCT02476279 — Stent vs. Indomethacin for Preventing Post-ERCP Pancreatitis (N=1950, PHASE3; 225 AE terms posted; arms: Indomethacin Alone; Indomethacin+Pancreatic Stent)
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 |
|---|---|---|---|---|---|---|
| Drug ineffective (drug did not work) | 1,410 | 1.7 1.6–1.8ROR 1.8 · χ² 438 / p 2e-97 | 1.7 EB05 1.6 · IC025 +0.7 | Reporting / coding artifact | serious PRR 2.8 | not reported in cached trials |
| Fatigue (tiredness) | 1,141 | 2.3 2.2–2.5ROR 2.5 · χ² 907 / p 2e-199 | 2.3 EB05 2.2 · IC025 +1.1 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 2.8 | not reported in cached trials |
| Headache | 1,044 | 2.7 2.5–2.8ROR 2.8 · χ² 1,108 / p 2e-243 | 2.7 EB05 2.5 · IC025 +1.3 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 3.5 · ♀ 77% (drug 53%) | NCT02476279: 2/975 (0.2%) on Indomethacin (serious AE) |
| Arthralgia (joint pain) | 1,030 | 4.0 3.7–4.2ROR 4.2 · χ² 2,320 / p <1e-300 | 4.0 EB05 3.8 · IC025 +1.9 3/3 methods agree | Not in label — unassessed | serious PRR 4.8 | NCT02476279: 1/975 (0.1%) on Indomethacin (serious AE) |
| Off label use (used outside approved label) | 1,003 | 1.8 1.7–2.0ROR 1.9 · χ² 400 / p 2e-89 | 1.8 EB05 1.7 · IC025 +0.8 | Reporting / coding artifact | serious PRR 2.2 · ♀ 76% (drug 53%) | not reported in cached trials |
| Pain | 939 | 2.4 2.3–2.6ROR 2.5 · χ² 813 / p 5e-179 | 2.4 EB05 2.3 · IC025 +1.2 3/3 methods agree | Likely indication confounding term in indications; also in warnings | serious PRR 2.5 | NCT02476279: 166/975 (17.0%) on Indomethacin (serious AE) |
| Nausea | 936 | 1.9 1.8–2.0ROR 2.0 · χ² 406 / p 1e-90 | 1.9 EB05 1.8 · IC025 +0.8 | Labeled adverse reaction exact term | serious PRR 2.2 | NCT02476279: 9/975 (0.9%) on Indomethacin (serious AE) |
| Diarrhoea (diarrhea) | 897 | 2.2 2.1–2.4ROR 2.3 · χ² 620 / p 5e-137 | 2.2 EB05 2.1 · IC025 +1.0 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 2.5 | NCT02476279: 2/975 (0.2%) on Indomethacin (serious AE) |
| Dizziness | 889 | 2.8 2.7–3.0ROR 3.0 · χ² 1,086 / p 2e-238 | 2.8 EB05 2.7 · IC025 +1.4 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 3.2 | not reported in cached trials |
| Dyspnoea (shortness of breath) | 765 | 2.2 2.0–2.3ROR 2.2 · χ² 485 / p 1e-107 | 2.2 EB05 2.0 · IC025 +1.0 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 2.0 | NCT02476279: 2/975 (0.2%) on Indomethacin (serious AE) |
| Vomiting | 759 | 2.6 2.4–2.8ROR 2.7 · χ² 748 / p 5e-165 | 2.6 EB05 2.4 · IC025 +1.2 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 2.5 | NCT02476279: 1/975 (0.1%) on Indomethacin (serious AE) |
| Asthenia (weakness) | 656 | 2.8 2.6–3.0ROR 2.9 · χ² 758 / p 3e-167 | 2.8 EB05 2.6 · IC025 +1.3 3/3 methods agree | Not in label — unassessed | serious PRR 2.7 | NCT02476279: 1/975 (0.1%) on Indomethacin (serious AE) |
| Pyrexia (fever) | 626 | 2.9 2.7–3.1ROR 3.0 · χ² 779 / p 1e-171 | 2.9 EB05 2.7 · IC025 +1.4 3/3 methods agree | Labeled (related wording) related wording | serious PRR 2.5 | NCT02476279: 6/975 (0.6%) on Indomethacin (serious AE) |
| Pruritus (itching) | 619 | 2.6 2.4–2.8ROR 2.7 · χ² 623 / p 7e-138 | 2.6 EB05 2.4 · IC025 +1.2 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 4.2 · ♀ 77% (drug 53%) | NCT02476279: 1/975 (0.1%) on Indomethacin (serious AE) |
| Malaise (feeling unwell) | 614 | 2.2 2.1–2.4ROR 2.3 · χ² 421 / p 6e-94 | 2.2 EB05 2.1 · IC025 +1.0 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 2.5 | not reported in cached trials |
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.
- Chronic idiopathic pain syndrome — n=21, PRR 558.8
- Amaurosis fugax — n=215, PRR 401.3
- Retinopathy of prematurity — n=64, PRR 209.7
- Necrotising enterocolitis neonatal — n=28, PRR 119.1
- Synovial disorder — n=28, PRR 104.2
- Porphyria acute — n=75, PRR 91.4
- Neck deformity — n=22, PRR 81.8
- Bronchopulmonary dysplasia — n=38, PRR 79.1
- Oesophageal spasm — n=81, PRR 73.2
- Necrotising colitis — n=54, PRR 70.0
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 Indomethacin?
In FDA FAERS, the most frequently co-reported reaction terms for Indomethacin are fatigue, headache, arthralgia, pain, nausea, diarrhoea. 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 Indomethacin have an FDA boxed warning?
Yes. The current FDA label carries a boxed warning: RISK OF SERIOUS CARDIOVASCULAR AND GASTROINTESTINAL EVENTS Cardiovascular Thrombotic Events • Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal.
Do FAERS signals prove that Indomethacin 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 12821a3a-b5f2-4415-84c9-0a30a4725f1e, effective 20260817; matched on
openfda.generic_name.exact:"INDOMETHACIN") - 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, 1,176 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
INDOMETHACIN, 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.