Diflunisal side effects: what 806 FDA adverse event reports show
Drug class
Nonsteroidal Anti-inflammatory Drug
Who reports
806 reports · 60% serious · 66 with death outcome · 70% female
Used for
Carefully consider the potential benefits and risks of diflunisal tablets and other treatment options before deciding to use diflunisal tablets. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS ).
What it is
DESCRIPTION Diflunisal, USP is [1, 1'-Biphenyl]-3-carboxylic acid, 2', 4'-difluoro-4-hydroxy. Its structural formula is: Molecular Formula: C 13 H 8 F 2 O 3 Molecular Weight: 250.20 g/mol Diflunisal, USP is a stable, white, crystalline compound with a melting point of 211° to 213°C.
Boxed warning
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. This risk may occur early in treatment and may increase with duration of use (see WARNINGS and PRECAUTIONS ).
Causality screen of the 13 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.
- Outcome field, not a reaction Death is a report outcome, not a reaction term. It is dominated by the underlying illness; see the seriousness profile and the boxed warning instead.
- 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. 8 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 |
|---|---|---|---|---|---|---|
| Glomerular filtration rate decreased | 12 | 25.8 14.7–45.2ROR 26.1 · χ² 261 / p 5e-59 | 24.7 EB05 14.9 · IC025 +2.7 3/3 methods agree | Lab value / disease marker | serious PRR 18.0 | no trial data cached |
| Blood lactate dehydrogenase increased | 12 | 19.6 11.2–34.3ROR 19.8 · χ² 193 / p 3e-44 | 18.7 EB05 10.8 · IC025 +2.5 3/3 methods agree | Lab value / disease marker | serious PRR 18.5 | no trial data cached |
| Lymphocyte count decreased | 11 | 16.2 9.0–29.1ROR 16.4 · χ² 142 / p 5e-33 | 14.9 EB05 7.8 · IC025 +2.3 3/3 methods agree | Lab value / disease marker | serious PRR 15.7 | no trial data cached |
| Vitreous floaters | 5 | 13.3 5.6–32.0ROR 13.4 · χ² 45 / p 8e-12 | 9.0 EB05 3.3 · IC025 +1.1 3/3 methods agree | Not in label — unassessed | serious n=5 | no trial data cached |
| Anhedonia | 13 | 12.8 7.4–21.9ROR 13.0 · χ² 129 / p 3e-30 | 11.3 EB05 6.3 · IC025 +2.2 3/3 methods agree | Not in label — unassessed | serious PRR 13.7 | no trial data cached |
| Foot deformity | 5 | 11.7 4.9–28.1ROR 11.8 · χ² 39 / p 2e-10 | 7.6 EB05 3.0 · IC025 +1.0 3/3 methods agree | Not in label — unassessed | serious PRR 10.5 | no trial data cached |
| Circulatory collapse | 7 | 10.6 5.1–22.2ROR 10.7 · χ² 52 / p 3e-13 | 7.7 EB05 3.6 · IC025 +1.4 3/3 methods agree | Not in label — unassessed | serious PRR 10.3 | no trial data cached |
| Toxic epidermal necrolysis (severe skin peeling reaction) | 6 | 10.3 4.7–23.0ROR 10.4 · χ² 42 / p 5e-11 | 7.1 EB05 3.1 · IC025 +1.2 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 10.0 | no trial data cached |
| Completed suicide (death by suicide) | 25 | 7.7 5.2–11.4ROR 7.9 · χ² 140 / p 1e-32 | 6.9 EB05 4.9 · IC025 +2.1 3/3 methods agree | Outcome field, not a reaction boxed warning mentions mortality | serious PRR 7.5 · 100% clinician | no trial data cached |
| Osteonecrosis of jaw (jawbone death) | 6 | 6.3 2.8–13.9ROR 6.3 · χ² 22 / p 2e-6 | 4.5 EB05 2.2 · IC025 +0.7 3/3 methods agree | Not in label — unassessed | serious PRR 6.1 | no trial data cached |
| Glycosylated haemoglobin increased | 5 | 5.2 2.2–12.4ROR 5.2 · χ² 13 / p 2e-4 | 3.7 EB05 1.8 · IC025 +0.3 | Lab value / disease marker | serious PRR 9.1 | no trial data cached |
| Injection site pruritus | 9 | 3.5 1.8–6.7ROR 3.5 · χ² 14 / p 1e-4 | 3.1 EB05 1.8 · IC025 +0.5 | Labeled (related wording) related wording | serious PRR 2.7 | no trial data cached |
| Injection site bruising | 10 | 3.3 1.8–6.1ROR 3.3 · χ² 14 / p 1e-4 | 2.9 EB05 1.7 · IC025 +0.5 | Not in label — unassessed | serious PRR 5.8 | no trial data cached |
Trial evidence (ClinicalTrials.gov)
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 |
|---|---|---|---|---|---|---|
| Completed suicide (death by suicide) | 25 | 7.7 5.2–11.4ROR 7.9 · χ² 140 / p 1e-32 | 6.9 EB05 4.9 · IC025 +2.1 3/3 methods agree | Outcome field, not a reaction boxed warning mentions mortality | serious PRR 7.5 · 100% clinician | no trial data cached |
| Anhedonia | 13 | 12.8 7.4–21.9ROR 13.0 · χ² 129 / p 3e-30 | 11.3 EB05 6.3 · IC025 +2.2 3/3 methods agree | Not in label — unassessed | serious PRR 13.7 | no trial data cached |
| Blood lactate dehydrogenase increased | 12 | 19.6 11.2–34.3ROR 19.8 · χ² 193 / p 3e-44 | 18.7 EB05 10.8 · IC025 +2.5 3/3 methods agree | Lab value / disease marker | serious PRR 18.5 | no trial data cached |
| Glomerular filtration rate decreased | 12 | 25.8 14.7–45.2ROR 26.1 · χ² 261 / p 5e-59 | 24.7 EB05 14.9 · IC025 +2.7 3/3 methods agree | Lab value / disease marker | serious PRR 18.0 | no trial data cached |
| Lymphocyte count decreased | 11 | 16.2 9.0–29.1ROR 16.4 · χ² 142 / p 5e-33 | 14.9 EB05 7.8 · IC025 +2.3 3/3 methods agree | Lab value / disease marker | serious PRR 15.7 | no trial data cached |
| Injection site bruising | 10 | 3.3 1.8–6.1ROR 3.3 · χ² 14 / p 1e-4 | 2.9 EB05 1.7 · IC025 +0.5 | Not in label — unassessed | serious PRR 5.8 | no trial data cached |
| Injection site pruritus | 9 | 3.5 1.8–6.7ROR 3.5 · χ² 14 / p 1e-4 | 3.1 EB05 1.8 · IC025 +0.5 | Labeled (related wording) related wording | serious PRR 2.7 | no trial data cached |
| Circulatory collapse | 7 | 10.6 5.1–22.2ROR 10.7 · χ² 52 / p 3e-13 | 7.7 EB05 3.6 · IC025 +1.4 3/3 methods agree | Not in label — unassessed | serious PRR 10.3 | no trial data cached |
| Osteonecrosis of jaw (jawbone death) | 6 | 6.3 2.8–13.9ROR 6.3 · χ² 22 / p 2e-6 | 4.5 EB05 2.2 · IC025 +0.7 3/3 methods agree | Not in label — unassessed | serious PRR 6.1 | no trial data cached |
| Toxic epidermal necrolysis (severe skin peeling reaction) | 6 | 10.3 4.7–23.0ROR 10.4 · χ² 42 / p 5e-11 | 7.1 EB05 3.1 · IC025 +1.2 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 10.0 | no trial data cached |
| Glycosylated haemoglobin increased | 5 | 5.2 2.2–12.4ROR 5.2 · χ² 13 / p 2e-4 | 3.7 EB05 1.8 · IC025 +0.3 | Lab value / disease marker | serious PRR 9.1 | no trial data cached |
| Foot deformity | 5 | 11.7 4.9–28.1ROR 11.8 · χ² 39 / p 2e-10 | 7.6 EB05 3.0 · IC025 +1.0 3/3 methods agree | Not in label — unassessed | serious PRR 10.5 | no trial data cached |
| Vitreous floaters | 5 | 13.3 5.6–32.0ROR 13.4 · χ² 45 / p 8e-12 | 9.0 EB05 3.3 · IC025 +1.1 3/3 methods agree | Not in label — unassessed | serious n=5 | no trial data cached |
| Serotonin syndrome | 4 | 5.4 2.0–14.4ROR 5.5 · χ² 10 / p 6e-4 | 3.6 EB05 1.6 · IC025 +0.1 | Not in label — unassessed | serious PRR 5.3 | no trial data cached |
| Tardive dyskinesia (persistent involuntary movements) | 3 | 2.7 0.9–8.5ROR 2.7 · χ² 2 / p 0.090 | 2.2 EB05 0.9 · IC025 -0.9 PRR-only: not supported by EBGM or IC | Not in label — unassessed | serious PRR 2.1 | no trial data cached |
Unlabeled candidate signals
Every screened signal with n ≥ 20 was either labeled, an indication term, or an artifact pattern — no unlabeled candidate stood out in the top signals.
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 Diflunisal?
In FDA FAERS, the most frequently co-reported reaction terms for Diflunisal are anhedonia, blood lactate dehydrogenase increased, glomerular filtration rate decreased, lymphocyte count decreased, injection site bruising, injection site pruritus. 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 Diflunisal have an FDA boxed warning?
Yes. The current FDA label carries a boxed warning: 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. This risk may occur early in treatment and may increase with duration of use (see WARNINGS and PRECAUTIONS ).
Do FAERS signals prove that Diflunisal 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 666f89b4-fd81-420a-a390-eb1cd4014f61, effective 20260804; matched on
openfda.generic_name.exact:"DIFLUNISAL") - 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, 21 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
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.