Tapentadol side effects: what 33,272 FDA adverse event reports show
Drug class
Opioid agonist
Label matched
Tapentadol Hydrochloride (Nucynta Er)
Who reports
33,272 reports · 90% serious · 20,613 with death outcome · 63% female
Used for
NUCYNTA ER (tapentadol) is indicated for the management of: Severe and persistent pain in adults that requires an opioid analgesic and that cannot be adequately treated with alternative options, including immediate-release opioids. Severe and persisten.
What it is
NUCYNTA ER (tapentadol) is an opioid agonist, supplied in extended-release film-coated tablets for oral administration, containing 58.24, 116.48, 174.72, 232.96, and 291.20 mg of tapentadol hydrochloride in each tablet strength, corresponding to 50, 100, 150, 200, and 250 mg of tapentadol free-base, respectively.
Boxed warning
SERIOUS AND LIFE-THREATENING RISKS FROM USE OF NUCYNTA ER WARNING: SERIOUS LIFE-THREATENING RISKS FROM USE OF NUCYNTA ER See FULL PRESCRIBING INFORMATION for complete boxed warning . NUCYNTA ER exposes users to risks of addiction, abuse, and misuse, which can lead to overdose and death.
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.
- 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.
- 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. 1,006 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 |
|---|---|---|---|---|---|---|
| Paroxysmal extreme pain disorder | 18 | 1,596.7 666.9–3,822.5ROR 1,597.5 · χ² 7,596 / p <1e-300 | 303.4 EB05 203.0 · IC025 +4.3 3/3 methods agree | Not in label — unassessed | serious n=18 | not reported in cached trials |
| Polyneuropathy in malignant disease | 18 | 177.4 105.1–299.5ROR 177.5 · χ² 2,320 / p <1e-300 | 120.8 EB05 80.8 · IC025 +4.1 3/3 methods agree | Not in label — unassessed | serious n=18 | not reported in cached trials |
| Confusional arousal | 19 | 85.5 52.9–138.1ROR 85.5 · χ² 1,321 / p 1e-289 | 70.2 EB05 47.5 · IC025 +3.9 3/3 methods agree | Not in label — unassessed | serious n=19 | not reported in cached trials |
| Post procedural hypothyroidism | 20 | 67.1 42.3–106.5ROR 67.2 · χ² 1,117 / p 4e-245 | 57.5 EB05 39.3 · IC025 +3.9 3/3 methods agree | Reporting / coding artifact | serious n=20 | not reported in cached trials |
| Post cholecystectomy syndrome | 26 | 64.1 42.8–95.9ROR 64.1 · χ² 1,406 / p <1e-300 | 55.9 EB05 40.1 · IC025 +4.2 3/3 methods agree | Not in label — unassessed | serious n=26 · ♀ 100% (drug 63%) · 100% clinician | not reported in cached trials |
| Ocular pemphigoid | 10 | 57.5 30.1–109.9ROR 57.5 · χ² 458 / p 8e-102 | 48.2 EB05 28.0 · IC025 +2.9 3/3 methods agree | Not in label — unassessed | serious n=10 | not reported in cached trials |
| Aspartate aminotransferase | 18 | 50.3 31.1–81.4ROR 50.4 · χ² 760 / p 1e-167 | 44.6 EB05 29.8 · IC025 +3.6 3/3 methods agree | Not in label — unassessed | serious n=18 | not reported in cached trials |
| Drug withdrawal syndrome neonatal | 944 | 42.4 39.7–45.3ROR 43.6 · χ² 35,724 / p <1e-300 | 39.7 EB05 37.7 · IC025 +5.2 3/3 methods agree | Labeled (related wording) related wording | serious PRR 25.6 · 98% consumer | not reported in cached trials |
| Granulocyte count increased | 25 | 41.4 27.6–62.0ROR 41.4 · χ² 886 / p 5e-195 | 37.8 EB05 27.0 · IC025 +3.8 3/3 methods agree | Lab value / disease marker | serious n=25 · ♀ 100% (drug 63%) · 100% clinician | not reported in cached trials |
| Toxicity to various agents | 9,796 | 39.0 38.4–39.7ROR 54.9 · χ² 344,292 / p <1e-300 | 36.8 EB05 36.2 · IC025 +5.2 3/3 methods agree | Not in label — unassessed | serious PRR 24.3 | not reported in cached trials |
| Chronic respiratory disease | 20 | 38.2 24.3–60.0ROR 38.2 · χ² 648 / p 3e-143 | 35.0 EB05 23.9 · IC025 +3.5 3/3 methods agree | Labeled (related wording) related wording | serious n=20 · 100% clinician | not reported in cached trials |
| Blood immunoglobulin a increased | 25 | 30.8 20.6–46.0ROR 30.8 · χ² 659 / p 1e-145 | 28.8 EB05 20.5 · IC025 +3.6 3/3 methods agree | Lab value / disease marker | serious n=25 · ♀ 100% (drug 63%) · 100% clinician | not reported in cached trials |
| Drug dose titration not performed | 78 | 29.9 23.8–37.5ROR 29.9 · χ² 2,049 / p <1e-300 | 28.4 EB05 23.5 · IC025 +4.2 3/3 methods agree | Not in label — unassessed | serious n=28 | not reported in cached trials |
| Degenerative bone disease | 19 | 28.2 17.8–44.7ROR 28.2 · χ² 452 / p 2e-100 | 26.4 EB05 17.8 · IC025 +3.2 3/3 methods agree | Not in label — unassessed | serious n=19 | not reported in cached trials |
| Vitamin b12 increased | 27 | 22.2 15.1–32.6ROR 22.3 · χ² 508 / p 7e-113 | 21.2 EB05 15.3 · IC025 +3.3 3/3 methods agree | Lab value / disease marker | serious n=27 · ♀ 100% (drug 63%) · 100% clinician | not reported in cached trials |
| Electric shock | 28 | 21.5 14.7–31.3ROR 21.5 · χ² 509 / p 5e-113 | 20.5 EB05 14.9 · IC025 +3.3 3/3 methods agree | Not in label — unassessed | serious n=28 · ♀ 100% (drug 63%) · 100% clinician | not reported in cached trials |
| Convulsive threshold lowered | 13 | 21.5 12.4–37.3ROR 21.5 · χ² 226 / p 2e-51 | 20.0 EB05 12.1 · IC025 +2.6 3/3 methods agree | Not in label — unassessed | serious n=13 | not reported in cached trials |
| Glomerular filtration rate increased | 26 | 20.8 14.1–30.7ROR 20.8 · χ² 455 / p 3e-101 | 19.9 EB05 14.2 · IC025 +3.2 3/3 methods agree | Lab value / disease marker | serious n=26 · ♀ 100% (drug 63%) · 100% clinician | not reported in cached trials |
| Drug diversion | 163 | 18.4 15.8–21.5ROR 18.5 · χ² 2,595 / p <1e-300 | 17.9 EB05 15.7 · IC025 +3.8 3/3 methods agree | Reporting / coding artifact | serious n=153 · ♀ 32% (drug 63%) · 76% consumer | not reported in cached trials |
| Dactylitis | 27 | 17.8 12.1–26.1ROR 17.8 · χ² 400 / p 3e-89 | 17.0 EB05 12.2 · IC025 +3.1 3/3 methods agree | Not in label — unassessed | serious n=27 · ♀ 100% (drug 63%) · 100% clinician | not reported in cached trials |
| Overdose | 5,888 | 17.6 17.2–18.0ROR 21.2 · χ² 90,492 / p <1e-300 | 17.1 EB05 16.8 · IC025 +4.1 3/3 methods agree | Reporting / coding artifact | serious PRR 13.8 · 91% consumer | NCT00361504: 1/894 (0.1%) on Tapentadol (serious AE) |
| Allodynia | 29 | 16.7 11.5–24.1ROR 16.7 · χ² 401 / p 2e-89 | 16.0 EB05 11.5 · IC025 +3.1 3/3 methods agree | Labeled adverse reaction exact term | serious n=29 · ♀ 14% (drug 63%) | not reported in cached trials |
| Rheumatoid factor increased | 26 | 15.0 10.2–22.1ROR 15.0 · χ² 318 / p 2e-71 | 14.2 EB05 9.9 · IC025 +2.9 3/3 methods agree | Not in label — unassessed | serious n=25 · ♀ 100% (drug 63%) · 100% clinician | not reported in cached trials |
| Breakthrough pain | 52 | 14.4 10.9–18.9ROR 14.4 · χ² 619 / p 6e-137 | 13.9 EB05 10.9 · IC025 +3.2 3/3 methods agree | Not in label — unassessed | serious n=17 | not reported in cached trials |
| Accidental overdose | 712 | 12.5 11.6–13.5ROR 12.8 · χ² 7,388 / p <1e-300 | 12.3 EB05 11.5 · IC025 +3.5 3/3 methods agree | Reporting / coding artifact | serious PRR 12.9 · 93% consumer | not reported in cached trials |
| Drug abuse | 1,552 | 11.9 11.3–12.5ROR 12.4 · χ² 15,250 / p <1e-300 | 11.7 EB05 11.2 · IC025 +3.5 3/3 methods agree | Reporting / coding artifact | serious PRR 7.6 · ♀ 41% (drug 63%) | not reported in cached trials |
| Parasomnia | 13 | 11.9 6.9–20.6ROR 11.9 · χ² 117 / p 2e-27 | 10.2 EB05 5.7 · IC025 +2.1 3/3 methods agree | Not in label — unassessed | serious n=13 | not reported in cached trials |
| Short-bowel syndrome | 12 | 11.8 6.7–20.9ROR 11.8 · χ² 106 / p 3e-25 | 9.9 EB05 5.4 · IC025 +2.0 3/3 methods agree | Not in label — unassessed | serious n=11 | not reported in cached trials |
| Reflexes abnormal | 12 | 11.8 6.6–20.8ROR 11.8 · χ² 106 / p 5e-25 | 9.9 EB05 5.4 · IC025 +2.0 3/3 methods agree | Not in label — unassessed | serious n=12 | not reported in cached trials |
| Drug screen negative | 29 | 10.5 7.3–15.2ROR 10.5 · χ² 236 / p 1e-53 | 9.7 EB05 6.8 · IC025 +2.5 3/3 methods agree | Reporting / coding artifact | – | not reported in cached trials |
| Sepsis neonatal | 13 | 10.3 6.0–17.9ROR 10.3 · χ² 99 / p 1e-23 | 8.6 EB05 5.0 · IC025 +2.0 3/3 methods agree | Not in label — unassessed | serious n=13 | not reported in cached trials |
| Intervertebral discitis | 28 | 9.4 6.5–13.7ROR 9.5 · χ² 200 / p 1e-45 | 8.6 EB05 6.1 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | serious n=28 · ♀ 100% (drug 63%) · 100% clinician | not reported in cached trials |
| Post herpetic neuralgia | 20 | 8.9 5.7–13.8ROR 8.9 · χ² 130 / p 2e-30 | 7.7 EB05 5.1 · IC025 +2.1 3/3 methods agree | Not in label — unassessed | serious n=18 | not reported in cached trials |
| Death | 11,643 | 8.6 8.5–8.8ROR 12.7 · χ² 80,712 / p <1e-300 | 8.5 EB05 8.4 · IC025 +3.1 3/3 methods agree | Outcome field, not a reaction boxed warning mentions mortality | serious PRR 5.5 · 92% consumer | not reported in cached trials |
| Joint noise | 26 | 8.6 5.8–12.6ROR 8.6 · χ² 164 / p 9e-38 | 7.7 EB05 5.4 · IC025 +2.2 3/3 methods agree | Not in label — unassessed | serious n=26 · ♀ 100% (drug 63%) · 100% clinician | not reported in cached trials |
| Serotonin syndrome | 245 | 8.2 7.2–9.3ROR 8.2 · χ² 1,515 / p <1e-300 | 8.0 EB05 7.2 · IC025 +2.8 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 5.2 | not reported in cached trials |
| Complex regional pain syndrome | 19 | 8.1 5.2–12.8ROR 8.1 · χ² 111 / p 4e-26 | 7.0 EB05 4.6 · IC025 +2.0 3/3 methods agree | Not in label — unassessed | serious n=17 | not reported in cached trials |
| Mouth injury | 18 | 7.5 4.7–12.0ROR 7.5 · χ² 94 / p 1e-22 | 6.4 EB05 4.2 · IC025 +1.9 3/3 methods agree | Labeled (related wording) related wording | serious n=18 | not reported in cached trials |
| White blood cells urine positive | 22 | 7.5 4.9–11.4ROR 7.5 · χ² 116 / p 2e-27 | 6.6 EB05 4.5 · IC025 +2.0 3/3 methods agree | Lab value / disease marker | serious n=22 · ♀ 100% (drug 63%) · 100% clinician | not reported in cached trials |
| Therapeutic response increased | 11 | 7.5 4.1–13.6ROR 7.5 · χ² 55 / p 6e-14 | 5.9 EB05 3.5 · IC025 +1.5 3/3 methods agree | Reporting / coding artifact | – | 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 Tapentadol 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).
- NCT00487435 — An Open-label Extension Study With Flexible Dosing of Extended-release (ER) Tapentadol (CG5503) to Treat Patie (N=1166, PHASE3; 94 AE terms posted; arms: Tapentadol (CG5503) Extended Release (ER)
- NCT00361504 — A Study to Evaluate Long-Term Safety of Multiple Doses of Tapentadol (CG5503) Prolonged-Release (PR) and Oxyco (N=1123, PHASE3; 92 AE terms posted; arms: Tapentadol (CG5503); Oxycodone)
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 |
|---|---|---|---|---|---|---|
| Death | 11,643 | 8.6 8.5–8.8ROR 12.7 · χ² 80,712 / p <1e-300 | 8.5 EB05 8.4 · IC025 +3.1 3/3 methods agree | Outcome field, not a reaction boxed warning mentions mortality | serious PRR 5.5 · 92% consumer | not reported in cached trials |
| Toxicity to various agents | 9,796 | 39.0 38.4–39.7ROR 54.9 · χ² 344,292 / p <1e-300 | 36.8 EB05 36.2 · IC025 +5.2 3/3 methods agree | Not in label — unassessed | serious PRR 24.3 | not reported in cached trials |
| Overdose | 5,888 | 17.6 17.2–18.0ROR 21.2 · χ² 90,492 / p <1e-300 | 17.1 EB05 16.8 · IC025 +4.1 3/3 methods agree | Reporting / coding artifact | serious PRR 13.8 · 91% consumer | NCT00361504: 1/894 (0.1%) on Tapentadol (serious AE) |
| Drug abuse | 1,552 | 11.9 11.3–12.5ROR 12.4 · χ² 15,250 / p <1e-300 | 11.7 EB05 11.2 · IC025 +3.5 3/3 methods agree | Reporting / coding artifact | serious PRR 7.6 · ♀ 41% (drug 63%) | not reported in cached trials |
| Drug dependence | 1,071 | 4.2 3.9–4.4ROR 4.3 · χ² 2,581 / p <1e-300 | 4.1 EB05 3.9 · IC025 +1.9 3/3 methods agree | Reporting / coding artifact | serious PRR 2.7 · ♀ 40% (drug 63%) | not reported in cached trials |
| Drug ineffective (drug did not work) | 1,024 | 0.5 0.5–0.5ROR 0.5 · χ² 580 / p 2e-128 | 0.5 EB05 0.5 · IC025 -1.1 PRR-only: not supported by EBGM or IC | Reporting / coding artifact | serious PRR 0.4 | not reported in cached trials |
| Drug withdrawal syndrome neonatal | 944 | 42.4 39.7–45.3ROR 43.6 · χ² 35,724 / p <1e-300 | 39.7 EB05 37.7 · IC025 +5.2 3/3 methods agree | Labeled (related wording) related wording | serious PRR 25.6 · 98% consumer | not reported in cached trials |
| Pain | 756 | 0.8 0.7–0.8ROR 0.8 · χ² 51 / p 5e-13 | 0.8 EB05 0.7 · IC025 -0.5 PRR-only: not supported by EBGM or IC | Likely indication confounding term in indications; also in warnings | serious PRR 0.5 | NCT00487435: 1/1,154 (0.1%) on Tapentadol (serious AE) |
| Nausea | 724 | 0.6 0.5–0.6ROR 0.6 · χ² 231 / p 2e-52 | 0.6 EB05 0.5 · IC025 -0.9 PRR-only: not supported by EBGM or IC | Labeled adverse reaction exact term | serious PRR 0.5 | NCT00487435: 1/1,154 (0.1%) on Tapentadol (serious AE) |
| Accidental overdose | 712 | 12.5 11.6–13.5ROR 12.8 · χ² 7,388 / p <1e-300 | 12.3 EB05 11.5 · IC025 +3.5 3/3 methods agree | Reporting / coding artifact | serious PRR 12.9 · 93% consumer | not reported in cached trials |
| Fatigue (tiredness) | 448 | 0.4 0.3–0.4ROR 0.4 · χ² 519 / p 4e-115 | 0.4 EB05 0.3 · IC025 -1.6 PRR-only: not supported by EBGM or IC | Labeled adverse reaction exact term | serious PRR 0.3 | NCT00487435: 77/1,154 (6.7%) on Tapentadol |
| Headache | 412 | 0.4 0.4–0.5ROR 0.4 · χ² 351 / p 1e-78 | 0.4 EB05 0.4 · IC025 -1.4 PRR-only: not supported by EBGM or IC | Labeled adverse reaction exact term | serious PRR 0.4 | NCT00487435: 151/1,154 (13.1%) on Tapentadol |
| Dizziness | 411 | 0.5 0.5–0.6ROR 0.5 · χ² 186 / p 1e-42 | 0.5 EB05 0.5 · IC025 -1.1 PRR-only: not supported by EBGM or IC | Labeled adverse reaction exact term | serious PRR 0.4 | NCT00487435: 98/1,154 (8.5%) on Tapentadol |
| Intentional product misuse | 400 | 2.9 2.6–3.2ROR 2.9 · χ² 500 / p 6e-111 | 2.9 EB05 2.7 · IC025 +1.4 3/3 methods agree | Reporting / coding artifact | serious PRR 4.0 | not reported in cached trials |
| Somnolence (drowsiness) | 398 | 1.2 1.1–1.4ROR 1.3 · χ² 20 / p 5e-6 | 1.2 EB05 1.1 · IC025 +0.2 | Labeled — boxed warning synonym match | serious PRR 1.1 | NCT00487435: 61/1,154 (5.3%) on Tapentadol |
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.
- Post cholecystectomy syndrome — n=26, PRR 64.1
- Toxicity to various agents — n=9,796, PRR 39.0
- Drug dose titration not performed — n=78, PRR 29.9
- Electric shock — n=28, PRR 21.5
- Dactylitis — n=27, PRR 17.8
- Rheumatoid factor increased — n=26, PRR 15.0
- Breakthrough pain — n=52, PRR 14.4
- Intervertebral discitis — n=28, PRR 9.4
- Post herpetic neuralgia — n=20, PRR 8.9
- Joint noise — n=26, PRR 8.6
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 Tapentadol?
In FDA FAERS, the most frequently co-reported reaction terms for Tapentadol are toxicity to various agents, drug withdrawal syndrome neonatal, pain, nausea, fatigue, headache. 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 Tapentadol have an FDA boxed warning?
Yes. The current FDA label carries a boxed warning: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF NUCYNTA ER WARNING: SERIOUS LIFE-THREATENING RISKS FROM USE OF NUCYNTA ER See FULL PRESCRIBING INFORMATION for complete boxed warning . NUCYNTA ER exposes users to risks of addiction, abuse, and misuse, which can lead to overdose and death.
Do FAERS signals prove that Tapentadol 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 c3d04d70-0155-4147-9ce4-a3b1fad4b373, effective 20251230; matched on
openfda.generic_name.exact:"TAPENTADOL HYDROCHLORIDE") - 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, 1,046 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
TAPENTADOL, 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.