Febuxostat side effects: what 16,659 FDA adverse event reports show
Who reports
16,659 reports · 76% serious · 2,179 with death outcome · 32% female
Used for
Febuxostat tablets are xanthine oxidase (XO) inhibitor indicated for the chronic management of hyperuricemia in adult patients with gout who have an inadequate response to a maximally titrated dose of allopurinol, who are intolerant to allopurinol, or for whom treatment with allopurinol is not advisable. Limitations of Use: Febuxostat tablets are not recommended for the treatment of asymptomatic hyperuricemia.
What it is
Febuxostat is a xanthine oxidase inhibitor. The active ingredient in febuxostat tablets is 2-[3-cyano-4-(2-methylpropoxy) phenyl]-4-methylthiazole-5-carboxylic acid, with a molecular weight of 316.38.
Boxed warning
CARDIOVASCULAR DEATH Gout patients with established cardiovascular (CV) disease treated with febuxostat tablets had a higher rate of CV death compared to those treated with allopurinol in a CV outcomes study [see Warnings and Precautions (5.1) ].
Causality screen of the 40 strongest signals
What the badges mean
- Labeled — boxed warning The term (or its clinical synonym) appears in the FDA boxed warning: causality is regulator-recognised and considered serious.
- 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.
- 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. 1,096 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 |
|---|---|---|---|---|---|---|
| Red blood cell sedimentation rate | 129 | 1,074.3 849.2–1,359.3ROR 1,082.7 · χ² 73,569 / p <1e-300 | 530.7 EB05 458.2 · IC025 +7.2 3/3 methods agree | Lab value / disease marker | serious n=129 · ♀ 75% (drug 32%) · 91% clinician | not reported in cached trials |
| Congenital diaphragmatic anomaly | 10 | 477.3 230.2–989.6ROR 477.6 · χ² 3,097 / p <1e-300 | 208.3 EB05 120.9 · IC025 +3.2 3/3 methods agree | Not in label — unassessed | serious n=10 | not reported in cached trials |
| Cytomegalovirus nephritis | 11 | 332.9 171.2–647.6ROR 333.1 · χ² 2,614 / p <1e-300 | 180.8 EB05 107.8 · IC025 +3.4 3/3 methods agree | Not in label — unassessed | serious n=11 | not reported in cached trials |
| Granuloma skin | 145 | 267.4 223.6–319.7ROR 269.7 · χ² 31,439 / p <1e-300 | 214.0 EB05 186.3 · IC025 +6.7 3/3 methods agree | Not in label — unassessed | serious n=145 · ♀ 78% (drug 32%) · 92% clinician | not reported in cached trials |
| Enthesopathy | 247 | 234.0 204.4–267.8ROR 237.5 · χ² 48,016 / p <1e-300 | 194.1 EB05 174.6 · IC025 +6.9 3/3 methods agree | Not in label — unassessed | serious n=247 · ♀ 56% (drug 32%) | not reported in cached trials |
| Splenic necrosis | 13 | 224.1 124.1–404.4ROR 224.2 · χ² 2,260 / p <1e-300 | 148.9 EB05 92.6 · IC025 +3.6 3/3 methods agree | Not in label — unassessed | serious n=13 | not reported in cached trials |
| Polycystic liver disease | 13 | 173.5 97.1–309.9ROR 173.6 · χ² 1,807 / p <1e-300 | 124.9 EB05 77.6 · IC025 +3.6 3/3 methods agree | Not in label — unassessed | serious n=13 | not reported in cached trials |
| Gouty tophus | 26 | 164.6 109.4–247.7ROR 164.9 · χ² 3,590 / p <1e-300 | 131.6 EB05 94.4 · IC025 +4.6 3/3 methods agree | Not in label — unassessed | serious n=12 · ♀ 0% (drug 32%) | not reported in cached trials |
| Blood parathyroid hormone decreased | 165 | 156.7 133.3–184.1ROR 158.2 · χ² 22,522 / p <1e-300 | 137.0 EB05 120.4 · IC025 +6.4 3/3 methods agree | Lab value / disease marker | serious n=165 · ♀ 79% (drug 32%) · 91% clinician | not reported in cached trials |
| Tenosynovitis | 249 | 124.6 109.5–141.8ROR 126.5 · χ² 27,633 / p <1e-300 | 112.4 EB05 101.1 · IC025 +6.3 3/3 methods agree | Not in label — unassessed | serious n=249 · ♀ 55% (drug 32%) | not reported in cached trials |
| Osteoma | 13 | 97.2 55.3–170.9ROR 97.3 · χ² 1,060 / p 8e-233 | 80.0 EB05 49.7 · IC025 +3.5 3/3 methods agree | Not in label — unassessed | serious n=13 | not reported in cached trials |
| Panniculitis | 165 | 92.4 79.0–108.2ROR 93.4 · χ² 13,806 / p <1e-300 | 85.3 EB05 74.9 · IC025 +5.8 3/3 methods agree | Not in label — unassessed | serious n=165 · ♀ 80% (drug 32%) · 91% clinician | not reported in cached trials |
| Alanine aminotransferase abnormal | 142 | 91.3 77.1–108.2ROR 92.1 · χ² 11,736 / p <1e-300 | 84.2 EB05 73.2 · IC025 +5.8 3/3 methods agree | Lab value / disease marker | serious n=142 | NCT01101035: 1/3,098 (0.0%) on Febuxostat (serious AE) |
| Splenic cyst | 14 | 89.1 51.8–153.2ROR 89.2 · χ² 1,057 / p 4e-232 | 75.0 EB05 47.5 · IC025 +3.5 3/3 methods agree | Not in label — unassessed | serious n=14 | not reported in cached trials |
| Haemoglobin urine present | 13 | 85.4 48.7–149.7ROR 85.4 · χ² 937 / p 6e-206 | 71.8 EB05 44.7 · IC025 +3.4 3/3 methods agree | Lab value / disease marker | serious n=13 | not reported in cached trials |
| Rheumatoid nodule | 164 | 78.7 67.3–92.1ROR 79.5 · χ² 11,763 / p <1e-300 | 73.5 EB05 64.5 · IC025 +5.7 3/3 methods agree | Not in label — unassessed | serious n=164 · ♀ 80% (drug 32%) · 90% clinician | not reported in cached trials |
| Respiratory tract haemorrhage | 33 | 73.5 51.8–104.4ROR 73.7 · χ² 2,161 / p <1e-300 | 66.9 EB05 49.8 · IC025 +4.5 3/3 methods agree | Not in label — unassessed | serious n=33 · ♀ 0% (drug 32%) · 100% clinician | not reported in cached trials |
| Activated partial thromboplastin time abnormal | 13 | 70.1 40.1–122.6ROR 70.2 · χ² 774 / p 1e-170 | 60.8 EB05 37.8 · IC025 +3.3 3/3 methods agree | Lab value / disease marker | serious n=13 | not reported in cached trials |
| Metastases to soft tissue | 13 | 65.8 37.7–115.0ROR 65.9 · χ² 728 / p 1e-160 | 57.6 EB05 35.8 · IC025 +3.3 3/3 methods agree | Not in label — unassessed | serious n=13 | not reported in cached trials |
| Rheumatoid lung | 46 | 63.1 46.9–84.8ROR 63.2 · χ² 2,616 / p <1e-300 | 58.7 EB05 45.8 · IC025 +4.7 3/3 methods agree | Not in label — unassessed | serious n=46 · ♀ 74% (drug 32%) | not reported in cached trials |
| Blood uric acid decreased | 20 | 53.8 34.4–84.2ROR 53.9 · χ² 944 / p 1e-207 | 49.4 EB05 33.7 · IC025 +3.8 3/3 methods agree | Lab value / disease marker | serious n=12 | not reported in cached trials |
| Gout | 698 | 50.9 47.2–54.8ROR 53.0 · χ² 32,751 / p <1e-300 | 48.8 EB05 45.9 · IC025 +5.4 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 19.0 | NCT01101035: 4/3,098 (0.1%) on Febuxostat (serious AE) |
| Splenic lesion | 14 | 49.8 29.2–84.9ROR 49.8 · χ² 597 / p 3e-132 | 45.2 EB05 28.6 · IC025 +3.3 3/3 methods agree | Not in label — unassessed | serious n=14 | not reported in cached trials |
| C-reactive protein abnormal | 239 | 48.7 42.9–55.4ROR 49.4 · χ² 10,711 / p <1e-300 | 46.8 EB05 42.0 · IC025 +5.2 3/3 methods agree | Lab value / disease marker | serious n=239 · ♀ 57% (drug 32%) | not reported in cached trials |
| Lordosis | 13 | 48.2 27.7–83.8ROR 48.2 · χ² 533 / p 3e-118 | 43.6 EB05 27.1 · IC025 +3.2 3/3 methods agree | Not in label — unassessed | serious n=13 | not reported in cached trials |
| Skin necrosis | 172 | 43.0 36.9–50.0ROR 43.4 · χ² 6,776 / p <1e-300 | 41.4 EB05 36.5 · IC025 +5.0 3/3 methods agree | Not in label — unassessed | serious n=171 · ♀ 78% (drug 32%) · 91% clinician | not reported in cached trials |
| Drug tolerance decreased | 89 | 41.3 33.4–51.0ROR 41.5 · χ² 3,348 / p <1e-300 | 39.7 EB05 33.2 · IC025 +4.7 3/3 methods agree | Not in label — unassessed | serious n=88 · ♀ 87% (drug 32%) | not reported in cached trials |
| Tongue disorder | 229 | 40.8 35.8–46.5ROR 41.4 · χ² 8,575 / p <1e-300 | 39.4 EB05 35.3 · IC025 +5.0 3/3 methods agree | Not in label — unassessed | serious n=228 · ♀ 57% (drug 32%) | not reported in cached trials |
| Dyspnoea paroxysmal nocturnal | 20 | 35.1 22.5–54.7ROR 35.1 · χ² 611 / p 4e-135 | 33.1 EB05 22.7 · IC025 +3.5 3/3 methods agree | Not in label — unassessed | serious n=20 | not reported in cached trials |
| Gouty arthritis | 21 | 34.1 22.1–52.5ROR 34.1 · χ² 624 / p 5e-138 | 32.3 EB05 22.3 · IC025 +3.5 3/3 methods agree | Not in label — unassessed | serious n=20 | NCT01101035: 1/3,098 (0.0%) on Febuxostat (serious AE) |
| Nephrogenic anaemia | 109 | 30.0 24.8–36.3ROR 30.2 · χ² 2,958 / p <1e-300 | 29.2 EB05 24.9 · IC025 +4.4 3/3 methods agree | Not in label — unassessed | serious n=109 · 90% clinician | not reported in cached trials |
| Hyperuricaemia | 89 | 27.9 22.6–34.4ROR 28.0 · χ² 2,231 / p <1e-300 | 27.2 EB05 22.7 · IC025 +4.2 3/3 methods agree | Likely indication confounding shares a disease stem with the indications wording | serious n=85 | not reported in cached trials |
| Prothrombin time abnormal | 15 | 27.9 16.7–46.5ROR 27.9 · χ² 354 / p 3e-79 | 26.4 EB05 17.0 · IC025 +3.0 3/3 methods agree | Lab value / disease marker | serious n=13 | NCT01101035: 1/3,098 (0.0%) on Febuxostat (serious AE) |
| Blood uric acid increased | 124 | 27.6 23.1–33.0ROR 27.8 · χ² 3,088 / p <1e-300 | 27.0 EB05 23.2 · IC025 +4.3 3/3 methods agree | Lab value / disease marker | serious n=71 | not reported in cached trials |
| Hyperparathyroidism secondary | 54 | 27.4 20.9–35.9ROR 27.5 · χ² 1,319 / p 5e-289 | 26.6 EB05 21.2 · IC025 +4.0 3/3 methods agree | Not in label — unassessed | serious n=53 | not reported in cached trials |
| Pneumonia haemophilus | 10 | 26.3 14.1–49.3ROR 26.4 · χ² 215 / p 7e-49 | 24.5 EB05 13.9 · IC025 +2.5 3/3 methods agree | Not in label — unassessed | serious n=10 | not reported in cached trials |
| Urinary sediment present | 13 | 26.0 15.0–45.1ROR 26.0 · χ² 282 / p 1e-63 | 24.6 EB05 15.2 · IC025 +2.8 3/3 methods agree | Lab value / disease marker | serious n=13 | not reported in cached trials |
| Tonsil cancer | 16 | 25.3 15.4–41.5ROR 25.3 · χ² 342 / p 9e-77 | 24.1 EB05 15.7 · IC025 +3.0 3/3 methods agree | Not in label — unassessed | serious n=16 | not reported in cached trials |
| Cerebral artery thrombosis | 10 | 24.8 13.3–46.4ROR 24.8 · χ² 201 / p 5e-46 | 23.1 EB05 13.0 · IC025 +2.5 3/3 methods agree | Not in label — unassessed | serious n=10 | not reported in cached trials |
| Orthostatic intolerance | 13 | 23.3 13.5–40.4ROR 23.4 · χ² 251 / p 6e-57 | 22.1 EB05 13.5 · IC025 +2.7 3/3 methods agree | Not in label — unassessed | serious n=13 | 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 Febuxostat 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 (4 of 40 signal terms matched).
- NCT01101035 — Cardiovascular Safety of Febuxostat and Allopurinol in Participants With Gout and Cardiovascular Comorbidities (N=6198, PHASE3; 857 AE terms posted; arms: Febuxostat; Allopurinol)
- NCT00430248 — Efficacy and Safety of Oral Febuxostat in Participants With Gout (N=2269, PHASE3; 59 AE terms posted; arms: Febuxostat 40 mg QD; Febuxostat 80 mg QD; Allopurinol 200 mg or 300 mg QD)
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 |
|---|---|---|---|---|---|---|
| Diarrhoea (diarrhea) | 881 | 1.7 1.6–1.8ROR 1.8 · χ² 276 / p 3e-62 | 1.7 EB05 1.6 · IC025 +0.7 | Labeled adverse reaction exact term | serious PRR 1.7 | NCT01101035: 3/3,098 (0.1%) on Febuxostat (serious AE) |
| Acute kidney injury (sudden kidney damage) | 857 | 7.1 6.7–7.6ROR 7.4 · χ² 4,506 / p <1e-300 | 7.1 EB05 6.7 · IC025 +2.7 3/3 methods agree | Labeled (related wording) related wording | serious PRR 5.4 · 92% clinician | NCT01101035: 139/3,098 (4.5%) on Febuxostat (serious AE) |
| Nausea | 856 | 1.4 1.3–1.5ROR 1.4 · χ² 87 / p 6e-21 | 1.4 EB05 1.3 · IC025 +0.3 | Labeled adverse reaction exact term | serious PRR 1.5 | NCT01101035: 2/3,098 (0.1%) on Febuxostat (serious AE) |
| Rash | 799 | 2.3 2.2–2.5ROR 2.4 · χ² 611 / p 3e-135 | 2.3 EB05 2.2 · IC025 +1.1 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 2.3 | NCT01101035: 2/3,092 (0.1%) on Febuxostat (serious AE) |
| Off label use (used outside approved label) | 752 | 1.1 1.0–1.2ROR 1.1 · χ² 6 / p 0.008 | 1.1 EB05 1.0 · IC025 +0.0 | Reporting / coding artifact | serious PRR 1.3 | not reported in cached trials |
| Drug ineffective (drug did not work) | 701 | 0.7 0.6–0.7ROR 0.7 · χ² 121 / p 2e-28 | 0.7 EB05 0.6 · IC025 -0.7 PRR-only: not supported by EBGM or IC | Reporting / coding artifact | serious PRR 1.0 | not reported in cached trials |
| Gout | 698 | 50.9 47.2–54.8ROR 53.0 · χ² 32,751 / p <1e-300 | 48.8 EB05 45.9 · IC025 +5.4 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 19.0 | NCT01101035: 4/3,098 (0.1%) on Febuxostat (serious AE) |
| Dyspnoea (shortness of breath) | 640 | 1.4 1.3–1.5ROR 1.4 · χ² 83 / p 5e-20 | 1.4 EB05 1.3 · IC025 +0.4 | Labeled adverse reaction exact term | serious PRR 1.3 | NCT01101035: 22/3,098 (0.7%) on Febuxostat (serious AE) |
| Fatigue (tiredness) | 619 | 1.0 0.9–1.1ROR 1.0 · χ² 0 / p 0.480 | 1.0 EB05 0.9 · IC025 -0.1 PRR-only: not supported by EBGM or IC | Labeled adverse reaction exact term | serious PRR 1.1 | NCT01101035: 2/3,098 (0.1%) on Febuxostat (serious AE) |
| Headache | 591 | 1.2 1.1–1.3ROR 1.2 · χ² 18 / p 1e-5 | 1.2 EB05 1.1 · IC025 +0.1 | Labeled adverse reaction exact term | serious PRR 1.5 | NCT01101035: 2/3,092 (0.1%) on Febuxostat (serious AE) |
| Anaemia (low red blood cells) | 588 | 3.9 3.6–4.2ROR 4.0 · χ² 1,265 / p 2e-277 | 3.9 EB05 3.6 · IC025 +1.8 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 3.1 | NCT01101035: 1/3,098 (0.0%) on Febuxostat (serious AE) |
| Pneumonia (lung infection) | 557 | 2.2 2.0–2.4ROR 2.2 · χ² 355 / p 1e-79 | 2.2 EB05 2.0 · IC025 +1.0 3/3 methods agree | Labeled (related wording) related wording | serious PRR 1.7 | NCT01101035: 1/3,098 (0.0%) on Febuxostat (serious AE) |
| Pyrexia (fever) | 556 | 2.0 1.9–2.2ROR 2.1 · χ² 291 / p 2e-65 | 2.0 EB05 1.9 · IC025 +0.9 | Not in label — unassessed | serious PRR 1.8 | NCT01101035: 3/3,098 (0.1%) on Febuxostat (serious AE) |
| Death | 524 | 0.8 0.7–0.8ROR 0.8 · χ² 39 / p 2e-10 | 0.8 EB05 0.7 · IC025 -0.5 PRR-only: not supported by EBGM or IC | Outcome field, not a reaction boxed warning mentions mortality | serious PRR 0.6 | NCT01101035: 1/3,092 (0.0%) on Febuxostat (serious AE) |
| Renal impairment | 518 | 7.8 7.2–8.5ROR 8.1 · χ² 3,074 / p <1e-300 | 7.8 EB05 7.2 · IC025 +2.8 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 5.9 | NCT01101035: 7/3,098 (0.2%) on Febuxostat (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.
- Granuloma skin — n=145, PRR 267.4
- Enthesopathy — n=247, PRR 234.0
- Gouty tophus — n=26, PRR 164.6
- Tenosynovitis — n=249, PRR 124.6
- Panniculitis — n=165, PRR 92.4
- Rheumatoid nodule — n=164, PRR 78.7
- Respiratory tract haemorrhage — n=33, PRR 73.5
- Rheumatoid lung — n=46, PRR 63.1
- Skin necrosis — n=172, PRR 43.0
- Drug tolerance decreased — n=89, PRR 41.3
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 Febuxostat?
In FDA FAERS, the most frequently co-reported reaction terms for Febuxostat are diarrhoea, acute kidney injury, nausea, rash, gout, dyspnoea. 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 Febuxostat have an FDA boxed warning?
Yes. The current FDA label carries a boxed warning: CARDIOVASCULAR DEATH Gout patients with established cardiovascular (CV) disease treated with febuxostat tablets had a higher rate of CV death compared to those treated with allopurinol in a CV outcomes study [see Warnings and Precautions (5.1) ].
Do FAERS signals prove that Febuxostat 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 14f80ad5-37cc-4672-9caa-2dd2f469af0a, effective 20240130; matched on
openfda.generic_name.exact:"FEBUXOSTAT") - 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, 1,136 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
FEBUXOSTAT, 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.