Diclofenac and Misoprostol side effects: what 6,640 FDA adverse event reports show
Drug class
Nonsteroidal anti-inflammatory drug
Label matched
Diclofenac (Diclofenac Sodium)
Who reports
6,640 reports · 76% serious · 303 with death outcome · 73% female
Used for
Diclofenac sodium topical solution is indicated for the treatment of the pain of osteoarthritis of the knee(s). Diclofenac sodium topical solution is a nonsteroidal anti-inflammatory drug indicated for the treatment of the pain of osteoarthritis of the knee(s). ( 1 )
What it is
Diclofenac sodium topical solution, USP contains 2% diclofenac sodium USP, a benzeneacetic acid derivative that is a nonsteroidal anti-inflammatory drug, and is available as a clear, colorless to faintly pink or orange solution for topical application.
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.
- 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 flags pairs whose reports are unusually skewed by sex or come mostly from consumers rather than clinicians. 614 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 |
|---|---|---|---|---|---|---|
| Pulmonary mass | 181 | 38.9 33.7–45.0ROR 40.0 · χ² 6,571 / p <1e-300 | 38.3 EB05 33.8 · IC025 +4.9 3/3 methods agree | Not in label — unassessed | serious PRR 31.7 · ♀ 97% (drug 73%) | no trial data cached |
| Red blood cell sedimentation rate increased | 84 | 24.1 19.5–29.8ROR 24.4 · χ² 1,824 / p <1e-300 | 23.8 EB05 19.8 · IC025 +4.0 3/3 methods agree | Lab value / disease marker | serious PRR 19.9 · ♀ 93% (drug 73%) | no trial data cached |
| Rheumatoid arthritis | 684 | 19.2 17.9–20.6ROR 21.3 · χ² 11,787 / p <1e-300 | 19.1 EB05 17.9 · IC025 +4.1 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 17.4 | no trial data cached |
| Ankylosing spondylitis | 70 | 17.1 13.5–21.5ROR 17.2 · χ² 1,037 / p 9e-228 | 16.9 EB05 13.8 · IC025 +3.5 3/3 methods agree | Not in label — unassessed | serious PRR 14.7 | no trial data cached |
| Lower respiratory tract infection | 220 | 15.4 13.5–17.5ROR 15.9 · χ² 2,941 / p <1e-300 | 15.3 EB05 13.7 · IC025 +3.7 3/3 methods agree | Labeled (related wording) related wording | serious PRR 12.2 | no trial data cached |
| Platelet count increased | 63 | 15.3 12.0–19.6ROR 15.4 · χ² 824 / p 1e-181 | 15.1 EB05 12.2 · IC025 +3.4 3/3 methods agree | Lab value / disease marker | serious PRR 15.0 · 95% clinician | no trial data cached |
| Hypercholesterolaemia | 46 | 15.3 11.4–20.4ROR 15.4 · χ² 596 / p 6e-132 | 15.0 EB05 11.6 · IC025 +3.2 3/3 methods agree | Not in label — unassessed | serious PRR 11.8 · ♀ 100% (drug 73%) | no trial data cached |
| Blood pressure systolic increased | 89 | 14.4 11.7–17.7ROR 14.6 · χ² 1,093 / p 5e-240 | 14.3 EB05 11.9 · IC025 +3.4 3/3 methods agree | Lab value / disease marker | serious PRR 11.8 | no trial data cached |
| Secretion discharge | 55 | 14.1 10.8–18.4ROR 14.2 · χ² 655 / p 1e-144 | 13.9 EB05 11.0 · IC025 +3.2 3/3 methods agree | Not in label — unassessed | serious PRR 17.6 · ♀ 95% (drug 73%) · 91% clinician | no trial data cached |
| Arthropathy | 199 | 11.3 9.9–13.0ROR 11.6 · χ² 1,857 / p <1e-300 | 11.2 EB05 9.9 · IC025 +3.2 3/3 methods agree | Not in label — unassessed | serious PRR 10.4 | no trial data cached |
| Musculoskeletal pain | 181 | 10.9 9.4–12.5ROR 11.1 · χ² 1,609 / p <1e-300 | 10.7 EB05 9.5 · IC025 +3.2 3/3 methods agree | Labeled (related wording) related wording | serious PRR 12.3 · ♀ 46% (drug 73%) | no trial data cached |
| Fibromyalgia | 81 | 10.6 8.5–13.1ROR 10.7 · χ² 691 / p 2e-152 | 10.3 EB05 8.5 · IC025 +2.9 3/3 methods agree | Not in label — unassessed | serious PRR 10.3 · ♀ 100% (drug 73%) | no trial data cached |
| Neck pain | 185 | 10.5 9.1–12.1ROR 10.7 · χ² 1,575 / p <1e-300 | 10.4 EB05 9.1 · IC025 +3.1 3/3 methods agree | Labeled (related wording) related wording | serious PRR 11.9 | no trial data cached |
| Skin laceration | 35 | 10.3 7.4–14.3ROR 10.3 · χ² 283 / p 9e-64 | 9.7 EB05 7.1 · IC025 +2.6 3/3 methods agree | Not in label — unassessed | serious PRR 10.6 | no trial data cached |
| Joint swelling | 374 | 9.8 8.9–10.9ROR 10.4 · χ² 2,967 / p <1e-300 | 9.8 EB05 8.9 · IC025 +3.1 3/3 methods agree | Not in label — unassessed | serious PRR 12.2 | no trial data cached |
| Infusion related reaction (reaction during infusion) | 203 | 9.7 8.5–11.1ROR 10.0 · χ² 1,582 / p <1e-300 | 9.6 EB05 8.5 · IC025 +3.0 3/3 methods agree | Not in label — unassessed | serious PRR 9.3 | no trial data cached |
| Kidney infection | 59 | 9.5 7.4–12.3ROR 9.6 · χ² 441 / p 3e-98 | 9.2 EB05 7.3 · IC025 +2.7 3/3 methods agree | Not in label — unassessed | serious PRR 8.1 · ♀ 37% (drug 73%) | no trial data cached |
| Synovitis | 54 | 9.5 7.3–12.4ROR 9.5 · χ² 400 / p 3e-89 | 9.1 EB05 7.1 · IC025 +2.7 3/3 methods agree | Not in label — unassessed | serious PRR 7.5 · ♀ 100% (drug 73%) | no trial data cached |
| Oral herpes | 58 | 9.4 7.3–12.2ROR 9.5 · χ² 429 / p 2e-95 | 9.1 EB05 7.2 · IC025 +2.7 3/3 methods agree | Not in label — unassessed | serious PRR 16.5 · ♀ 32% (drug 73%) | no trial data cached |
| Joint stiffness | 78 | 9.4 7.5–11.7ROR 9.5 · χ² 577 / p 8e-128 | 9.1 EB05 7.5 · IC025 +2.8 3/3 methods agree | Not in label — unassessed | serious PRR 12.2 | no trial data cached |
| Staphylococcal infection | 98 | 9.4 7.7–11.4ROR 9.5 · χ² 724 / p 9e-160 | 9.1 EB05 7.7 · IC025 +2.8 3/3 methods agree | Not in label — unassessed | serious PRR 7.8 | no trial data cached |
| Contraindicated product administered | 89 | 9.3 7.6–11.5ROR 9.5 · χ² 654 / p 2e-144 | 9.1 EB05 7.6 · IC025 +2.8 3/3 methods agree | Reporting / coding artifact | serious PRR 8.8 | no trial data cached |
| Intervertebral disc degeneration | 27 | 9.2 6.3–13.4ROR 9.2 · χ² 188 / p 4e-43 | 8.4 EB05 5.9 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | serious PRR 8.0 | no trial data cached |
| Blood pressure fluctuation | 69 | 9.1 7.2–11.5ROR 9.2 · χ² 487 / p 3e-108 | 8.8 EB05 7.1 · IC025 +2.7 3/3 methods agree | Lab value / disease marker | serious PRR 8.7 · 91% clinician | no trial data cached |
| Musculoskeletal stiffness | 247 | 8.9 7.9–10.1ROR 9.2 · χ² 1,732 / p <1e-300 | 8.8 EB05 7.9 · IC025 +2.9 3/3 methods agree | Not in label — unassessed | serious PRR 10.4 | no trial data cached |
| Foot deformity | 31 | 8.8 6.2–12.6ROR 8.9 · χ² 207 / p 2e-47 | 8.1 EB05 5.9 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | serious PRR 7.1 | no trial data cached |
| Blood lactate dehydrogenase increased | 44 | 8.7 6.5–11.7ROR 8.8 · χ² 293 / p 5e-66 | 8.2 EB05 6.3 · IC025 +2.5 3/3 methods agree | Lab value / disease marker | serious PRR 7.1 · ♀ 94% (drug 73%) | no trial data cached |
| Swelling | 255 | 8.6 7.7–9.8ROR 9.0 · χ² 1,720 / p <1e-300 | 8.5 EB05 7.7 · IC025 +2.9 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 10.1 | no trial data cached |
| Osteoarthritis | 115 | 8.6 7.2–10.3ROR 8.7 · χ² 761 / p 7e-168 | 8.4 EB05 7.1 · IC025 +2.7 3/3 methods agree | Likely indication confounding term in indications; also in warnings | serious PRR 6.9 | no trial data cached |
| Drug hypersensitivity | 521 | 8.5 7.8–9.2ROR 9.1 · χ² 3,460 / p <1e-300 | 8.4 EB05 7.8 · IC025 +2.9 3/3 methods agree | Labeled (related wording) related wording | serious PRR 11.1 | no trial data cached |
| Disease recurrence | 128 | 8.5 7.2–10.1ROR 8.6 · χ² 838 / p 1e-184 | 8.3 EB05 7.1 · IC025 +2.7 3/3 methods agree | Reporting / coding artifact | serious PRR 12.7 · ♀ 96% (drug 73%) | no trial data cached |
| Musculoskeletal discomfort | 46 | 8.5 6.3–11.3ROR 8.5 · χ² 295 / p 2e-66 | 8.0 EB05 6.2 · IC025 +2.5 3/3 methods agree | Not in label — unassessed | serious PRR 10.3 | no trial data cached |
| Pelvic pain | 48 | 8.4 6.3–11.1ROR 8.4 · χ² 303 / p 4e-68 | 7.9 EB05 6.1 · IC025 +2.5 3/3 methods agree | Not in label — unassessed | serious PRR 10.5 · ♀ 25% (drug 73%) | no trial data cached |
| Drug intolerance | 252 | 8.3 7.3–9.4ROR 8.6 · χ² 1,611 / p <1e-300 | 8.2 EB05 7.4 · IC025 +2.8 3/3 methods agree | Reporting / coding artifact | serious PRR 9.7 · ♀ 95% (drug 73%) | no trial data cached |
| Arthritis | 206 | 8.3 7.2–9.5ROR 8.5 · χ² 1,312 / p 1e-287 | 8.2 EB05 7.3 · IC025 +2.8 3/3 methods agree | Likely indication confounding term in indications; also in warnings | serious PRR 7.7 | no trial data cached |
| Pain in jaw | 74 | 8.3 6.6–10.4ROR 8.3 · χ² 465 / p 2e-103 | 8.0 EB05 6.5 · IC025 +2.6 3/3 methods agree | Likely indication confounding term in indications; also in warnings | serious PRR 10.2 · ♀ 96% (drug 73%) | no trial data cached |
| Body temperature decreased | 25 | 8.0 5.4–11.8ROR 8.0 · χ² 145 / p 1e-33 | 7.2 EB05 5.0 · IC025 +2.1 3/3 methods agree | Lab value / disease marker | serious PRR 6.5 | no trial data cached |
| Uveitis | 34 | 8.0 5.7–11.1ROR 8.0 · χ² 200 / p 1e-45 | 7.4 EB05 5.4 · IC025 +2.3 3/3 methods agree | Not in label — unassessed | serious PRR 6.3 · ♀ 100% (drug 73%) | no trial data cached |
| Spinal disorder | 23 | 7.7 5.1–11.5ROR 7.7 · χ² 127 / p 1e-29 | 6.8 EB05 4.7 · IC025 +2.0 3/3 methods agree | Not in label — unassessed | serious PRR 6.2 | no trial data cached |
| Tenderness | 25 | 7.6 5.1–11.2ROR 7.6 · χ² 136 / p 1e-31 | 6.8 EB05 4.8 · IC025 +2.1 3/3 methods agree | Labeled adverse reaction exact term | serious n=25 · ♀ 46% (drug 73%) | 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 |
|---|---|---|---|---|---|---|
| Drug ineffective (drug did not work) | 1,207 | 2.9 2.8–3.0ROR 3.3 · χ² 1,597 / p <1e-300 | 2.9 EB05 2.8 · IC025 +1.4 3/3 methods agree | Reporting / coding artifact | serious PRR 5.3 | no trial data cached |
| Pain | 902 | 4.6 4.4–4.9ROR 5.2 · χ² 2,643 / p <1e-300 | 4.6 EB05 4.4 · IC025 +2.1 3/3 methods agree | Likely indication confounding term in indications; also in warnings | serious PRR 4.8 | no trial data cached |
| Arthralgia (joint pain) | 779 | 5.9 5.6–6.4ROR 6.6 · χ² 3,260 / p <1e-300 | 5.9 EB05 5.6 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | serious PRR 7.5 | no trial data cached |
| Rheumatoid arthritis | 684 | 19.2 17.9–20.6ROR 21.3 · χ² 11,787 / p <1e-300 | 19.1 EB05 17.9 · IC025 +4.1 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 17.4 | no trial data cached |
| Nausea | 633 | 2.5 2.4–2.7ROR 2.7 · χ² 610 / p 6e-135 | 2.5 EB05 2.4 · IC025 +1.2 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 3.1 | no trial data cached |
| Fatigue (tiredness) | 556 | 2.3 2.1–2.4ROR 2.4 · χ² 405 / p 2e-90 | 2.3 EB05 2.1 · IC025 +1.0 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 3.0 | no trial data cached |
| Drug hypersensitivity | 521 | 8.5 7.8–9.2ROR 9.1 · χ² 3,460 / p <1e-300 | 8.4 EB05 7.8 · IC025 +2.9 3/3 methods agree | Labeled (related wording) related wording | serious PRR 11.1 | no trial data cached |
| Diarrhoea (diarrhea) | 519 | 2.6 2.3–2.8ROR 2.7 · χ² 503 / p 1e-111 | 2.5 EB05 2.4 · IC025 +1.2 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 2.9 | no trial data cached |
| Malaise (feeling unwell) | 449 | 3.2 3.0–3.5ROR 3.4 · χ² 703 / p 4e-155 | 3.2 EB05 3.0 · IC025 +1.5 3/3 methods agree | Not in label — unassessed | serious PRR 3.6 | no trial data cached |
| Headache | 413 | 2.1 1.9–2.3ROR 2.2 · χ² 239 / p 3e-54 | 2.1 EB05 1.9 · IC025 +0.9 | Labeled adverse reaction exact term | serious PRR 2.9 | no trial data cached |
| Dizziness | 411 | 2.6 2.4–2.9ROR 2.7 · χ² 416 / p 1e-92 | 2.6 EB05 2.4 · IC025 +1.2 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 3.1 | no trial data cached |
| Pain in extremity | 384 | 4.1 3.7–4.5ROR 4.3 · χ² 914 / p 5e-201 | 4.1 EB05 3.8 · IC025 +1.9 3/3 methods agree | Not in label — unassessed | serious PRR 4.9 | no trial data cached |
| Joint swelling | 374 | 9.8 8.9–10.9ROR 10.4 · χ² 2,967 / p <1e-300 | 9.8 EB05 8.9 · IC025 +3.1 3/3 methods agree | Not in label — unassessed | serious PRR 12.2 | no trial data cached |
| Back pain | 359 | 4.9 4.4–5.4ROR 5.1 · χ² 1,116 / p 6e-245 | 4.8 EB05 4.4 · IC025 +2.1 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 5.8 | no trial data cached |
| Dyspnoea (shortness of breath) | 333 | 1.9 1.7–2.1ROR 1.9 · χ² 135 / p 1e-31 | 1.9 EB05 1.7 · IC025 +0.7 | Labeled adverse reaction exact term | serious PRR 1.8 | no trial data cached |
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.
- Pulmonary mass — n=181, PRR 38.9
- Ankylosing spondylitis — n=70, PRR 17.1
- Hypercholesterolaemia — n=46, PRR 15.3
- Secretion discharge — n=55, PRR 14.1
- Arthropathy — n=199, PRR 11.3
- Fibromyalgia — n=81, PRR 10.6
- Skin laceration — n=35, PRR 10.3
- Joint swelling — n=374, PRR 9.8
- Infusion related reaction — n=203, PRR 9.7
- Kidney infection — n=59, PRR 9.5
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 Diclofenac and Misoprostol?
In FDA FAERS, the most frequently co-reported reaction terms for Diclofenac and Misoprostol are pain, arthralgia, rheumatoid arthritis, nausea, fatigue, drug hypersensitivity. 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 Diclofenac and Misoprostol 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 Diclofenac and Misoprostol 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 45321aec-368d-4ca4-a0c5-2ce56fae74b2, effective 20250529; matched on
openfda.generic_name.exact:"DICLOFENAC") - 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, 654 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.