Tramadol and Acetaminophen side effects: what 908 FDA adverse event reports show
Drug class
Not stated in label
Label matched
Tramadol Hydrochloride And Acetaminophen (Tramadol Hydrochloride And Acetaminophen)
Who reports
908 reports · 84% serious · 128 with death outcome · 64% female
Used for
Tramadol hydrochloride and acetaminophen tablets are indicated for the management of acute pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. Limitations of Use Tramadol hydrochloride and acetaminophen tablets are indicated for short-term use of five days or less.
What it is
Tramadol hydrochloride and acetaminophen tablets USP combine two analgesics, tramadol hydrochloride and opioid agonist, and acetaminophen.
Boxed warning
SERIOUS AND LIFE-THREATENING RISKS FROM USE OF TRAMADOL HYDROCHLORIDE and ACETAMINOPHEN Addiction, Abuse, and Misuse Because the use of tramadol hydrochloride and acetaminophen exposes patients and other users to the.
Causality screen of the 31 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.
- 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. 17 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 |
|---|---|---|---|---|---|---|
| Hand deformity | 24 | 42.5 28.6–63.1ROR 43.6 · χ² 930 / p 2e-204 | 41.1 EB05 29.1 · IC025 +3.8 3/3 methods agree | Not in label — unassessed | serious PRR 31.7 · ♀ 100% (drug 64%) · 92% clinician | no trial data cached |
| Helicobacter infection | 15 | 34.1 20.6–56.3ROR 34.6 · χ² 448 / p 8e-100 | 32.7 EB05 21.0 · IC025 +3.2 3/3 methods agree | Not in label — unassessed | serious PRR 24.7 | no trial data cached |
| Pemphigus | 18 | 33.5 21.2–53.0ROR 34.2 · χ² 535 / p 1e-118 | 32.4 EB05 21.7 · IC025 +3.4 3/3 methods agree | Not in label — unassessed | serious PRR 23.1 | no trial data cached |
| Folliculitis | 14 | 31.4 18.6–52.8ROR 31.8 · χ² 381 / p 3e-85 | 30.2 EB05 19.1 · IC025 +3.0 3/3 methods agree | Not in label — unassessed | serious PRR 25.3 | no trial data cached |
| Joint range of motion decreased | 17 | 29.4 18.4–47.2ROR 30.0 · χ² 439 / p 1e-97 | 28.6 EB05 18.9 · IC025 +3.2 3/3 methods agree | Not in label — unassessed | serious PRR 25.8 | no trial data cached |
| Bursitis | 14 | 26.9 16.0–45.2ROR 27.3 · χ² 323 / p 2e-72 | 25.9 EB05 16.3 · IC025 +2.9 3/3 methods agree | Not in label — unassessed | serious PRR 21.7 | no trial data cached |
| Synovitis | 20 | 25.6 16.6–39.6ROR 26.2 · χ² 449 / p 5e-100 | 25.1 EB05 17.1 · IC025 +3.3 3/3 methods agree | Not in label — unassessed | serious PRR 18.4 · 90% clinician | no trial data cached |
| Glossodynia (burning tongue/mouth pain) | 22 | 22.8 15.1–34.4ROR 23.3 · χ² 436 / p 3e-97 | 22.3 EB05 15.5 · IC025 +3.2 3/3 methods agree | Labeled (related wording) related wording | serious PRR 22.6 · ♀ 100% (drug 64%) · 91% clinician | no trial data cached |
| Wound | 21 | 17.5 11.4–26.7ROR 17.9 · χ² 310 / p 1e-69 | 17.1 EB05 11.5 · IC025 +2.9 3/3 methods agree | Not in label — unassessed | serious PRR 14.3 · ♀ 95% (drug 64%) · 90% clinician | no trial data cached |
| Obesity | 12 | 17.4 9.9–30.5ROR 17.6 · χ² 169 / p 5e-39 | 16.4 EB05 9.1 · IC025 +2.4 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 13.9 | no trial data cached |
| Back disorder | 12 | 17.0 9.7–29.8ROR 17.2 · χ² 165 / p 4e-38 | 15.9 EB05 8.9 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | serious PRR 16.8 | no trial data cached |
| Pericarditis | 12 | 16.7 9.5–29.2ROR 16.9 · χ² 161 / p 3e-37 | 15.6 EB05 8.6 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | serious PRR 11.5 | no trial data cached |
| Irritable bowel syndrome | 15 | 16.2 9.8–26.8ROR 16.5 · χ² 200 / p 1e-45 | 15.5 EB05 9.3 · IC025 +2.6 3/3 methods agree | Not in label — unassessed | serious PRR 13.2 | no trial data cached |
| Gait inability | 22 | 15.4 10.2–23.2ROR 15.7 · χ² 282 / p 2e-63 | 14.9 EB05 10.0 · IC025 +2.8 3/3 methods agree | Not in label — unassessed | serious PRR 13.1 | no trial data cached |
| Pulmonary fibrosis | 12 | 14.5 8.3–25.5ROR 14.7 · χ² 138 / p 4e-32 | 13.2 EB05 7.1 · IC025 +2.3 3/3 methods agree | Not in label — unassessed | serious PRR 10.1 | no trial data cached |
| Systemic lupus erythematosus | 22 | 14.4 9.5–21.7ROR 14.7 · χ² 261 / p 5e-59 | 13.8 EB05 9.2 · IC025 +2.8 3/3 methods agree | Not in label — unassessed | serious PRR 10.1 · ♀ 95% (drug 64%) | no trial data cached |
| Fibromyalgia | 14 | 13.3 7.9–22.4ROR 13.5 · χ² 148 / p 3e-34 | 12.1 EB05 7.0 · IC025 +2.3 3/3 methods agree | Not in label — unassessed | serious PRR 12.0 | no trial data cached |
| Lower limb fracture | 10 | 12.1 6.5–22.4ROR 12.2 · χ² 91 / p 7e-22 | 10.1 EB05 5.1 · IC025 +1.9 3/3 methods agree | Not in label — unassessed | serious PRR 9.1 | no trial data cached |
| Altered state of consciousness | 11 | 11.8 6.6–21.2ROR 11.9 · χ² 98 / p 2e-23 | 9.9 EB05 5.3 · IC025 +2.0 3/3 methods agree | Labeled (related wording) related wording | serious PRR 8.2 | no trial data cached |
| Road traffic accident | 20 | 11.1 7.2–17.0ROR 11.3 · χ² 173 / p 8e-40 | 10.1 EB05 6.5 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | serious PRR 8.4 | no trial data cached |
| Type 2 diabetes mellitus | 16 | 11.0 6.7–17.8ROR 11.1 · χ² 135 / p 2e-31 | 9.7 EB05 5.9 · IC025 +2.2 3/3 methods agree | Labeled (related wording) related wording | serious PRR 7.4 | no trial data cached |
| Hepatitis (liver inflammation) | 12 | 10.8 6.2–19.0ROR 11.0 · χ² 98 / p 2e-23 | 9.1 EB05 5.1 · IC025 +2.0 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 7.6 | no trial data cached |
| Lower respiratory tract infection | 21 | 10.7 7.0–16.4ROR 10.9 · χ² 176 / p 2e-40 | 9.8 EB05 6.4 · IC025 +2.4 3/3 methods agree | Labeled (related wording) related wording | serious PRR 7.8 · ♀ 100% (drug 64%) | no trial data cached |
| Arthropathy | 25 | 10.4 7.0–15.3ROR 10.6 · χ² 203 / p 3e-46 | 9.6 EB05 6.6 · IC025 +2.5 3/3 methods agree | Not in label — unassessed | serious PRR 8.7 · ♀ 96% (drug 64%) | no trial data cached |
| Epilepsy | 13 | 9.9 5.7–16.9ROR 10.0 · χ² 95 / p 1e-22 | 8.2 EB05 4.8 · IC025 +2.0 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 6.8 | no trial data cached |
| Interstitial lung disease | 18 | 8.6 5.5–13.6ROR 8.8 · χ² 114 / p 7e-27 | 7.5 EB05 4.9 · IC025 +2.0 3/3 methods agree | Not in label — unassessed | serious PRR 6.0 | no trial data cached |
| Psoriatic arthropathy | 13 | 7.5 4.4–12.8ROR 7.6 · χ² 67 / p 2e-16 | 6.2 EB05 3.8 · IC025 +1.7 3/3 methods agree | Not in label — unassessed | serious PRR 6.5 | no trial data cached |
| Intentional overdose | 19 | 6.9 4.4–10.8ROR 7.0 · χ² 90 / p 1e-21 | 6.0 EB05 4.0 · IC025 +1.8 3/3 methods agree | Reporting / coding artifact | serious PRR 4.9 | no trial data cached |
| Rheumatoid arthritis | 28 | 5.7 4.0–8.2ROR 5.9 · χ² 105 / p 6e-25 | 5.3 EB05 3.8 · IC025 +1.8 3/3 methods agree | Not in label — unassessed | serious PRR 4.8 · ♀ 96% (drug 64%) | no trial data cached |
| Completed suicide (death by suicide) | 17 | 4.7 2.9–7.5ROR 4.7 · χ² 46 / p 7e-12 | 4.2 EB05 2.8 · IC025 +1.3 3/3 methods agree | Outcome field, not a reaction boxed warning mentions mortality | serious PRR 3.2 | no trial data cached |
| Suicide attempt | 12 | 4.6 2.6–8.0ROR 4.6 · χ² 30 / p 2e-8 | 3.9 EB05 2.4 · IC025 +1.0 3/3 methods agree | Labeled (related wording) related wording | serious PRR 3.1 | 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 |
|---|---|---|---|---|---|---|
| Rheumatoid arthritis | 28 | 5.7 4.0–8.2ROR 5.9 · χ² 105 / p 6e-25 | 5.3 EB05 3.8 · IC025 +1.8 3/3 methods agree | Not in label — unassessed | serious PRR 4.8 · ♀ 96% (drug 64%) | no trial data cached |
| Arthropathy | 25 | 10.4 7.0–15.3ROR 10.6 · χ² 203 / p 3e-46 | 9.6 EB05 6.6 · IC025 +2.5 3/3 methods agree | Not in label — unassessed | serious PRR 8.7 · ♀ 96% (drug 64%) | no trial data cached |
| Hand deformity | 24 | 42.5 28.6–63.1ROR 43.6 · χ² 930 / p 2e-204 | 41.1 EB05 29.1 · IC025 +3.8 3/3 methods agree | Not in label — unassessed | serious PRR 31.7 · ♀ 100% (drug 64%) · 92% clinician | no trial data cached |
| Systemic lupus erythematosus | 22 | 14.4 9.5–21.7ROR 14.7 · χ² 261 / p 5e-59 | 13.8 EB05 9.2 · IC025 +2.8 3/3 methods agree | Not in label — unassessed | serious PRR 10.1 · ♀ 95% (drug 64%) | no trial data cached |
| Gait inability | 22 | 15.4 10.2–23.2ROR 15.7 · χ² 282 / p 2e-63 | 14.9 EB05 10.0 · IC025 +2.8 3/3 methods agree | Not in label — unassessed | serious PRR 13.1 | no trial data cached |
| Glossodynia (burning tongue/mouth pain) | 22 | 22.8 15.1–34.4ROR 23.3 · χ² 436 / p 3e-97 | 22.3 EB05 15.5 · IC025 +3.2 3/3 methods agree | Labeled (related wording) related wording | serious PRR 22.6 · ♀ 100% (drug 64%) · 91% clinician | no trial data cached |
| Lower respiratory tract infection | 21 | 10.7 7.0–16.4ROR 10.9 · χ² 176 / p 2e-40 | 9.8 EB05 6.4 · IC025 +2.4 3/3 methods agree | Labeled (related wording) related wording | serious PRR 7.8 · ♀ 100% (drug 64%) | no trial data cached |
| Wound | 21 | 17.5 11.4–26.7ROR 17.9 · χ² 310 / p 1e-69 | 17.1 EB05 11.5 · IC025 +2.9 3/3 methods agree | Not in label — unassessed | serious PRR 14.3 · ♀ 95% (drug 64%) · 90% clinician | no trial data cached |
| Road traffic accident | 20 | 11.1 7.2–17.0ROR 11.3 · χ² 173 / p 8e-40 | 10.1 EB05 6.5 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | serious PRR 8.4 | no trial data cached |
| Synovitis | 20 | 25.6 16.6–39.6ROR 26.2 · χ² 449 / p 5e-100 | 25.1 EB05 17.1 · IC025 +3.3 3/3 methods agree | Not in label — unassessed | serious PRR 18.4 · 90% clinician | no trial data cached |
| Intentional overdose | 19 | 6.9 4.4–10.8ROR 7.0 · χ² 90 / p 1e-21 | 6.0 EB05 4.0 · IC025 +1.8 3/3 methods agree | Reporting / coding artifact | serious PRR 4.9 | no trial data cached |
| Interstitial lung disease | 18 | 8.6 5.5–13.6ROR 8.8 · χ² 114 / p 7e-27 | 7.5 EB05 4.9 · IC025 +2.0 3/3 methods agree | Not in label — unassessed | serious PRR 6.0 | no trial data cached |
| Pemphigus | 18 | 33.5 21.2–53.0ROR 34.2 · χ² 535 / p 1e-118 | 32.4 EB05 21.7 · IC025 +3.4 3/3 methods agree | Not in label — unassessed | serious PRR 23.1 | no trial data cached |
| Completed suicide (death by suicide) | 17 | 4.7 2.9–7.5ROR 4.7 · χ² 46 / p 7e-12 | 4.2 EB05 2.8 · IC025 +1.3 3/3 methods agree | Outcome field, not a reaction boxed warning mentions mortality | serious PRR 3.2 | no trial data cached |
| Joint range of motion decreased | 17 | 29.4 18.4–47.2ROR 30.0 · χ² 439 / p 1e-97 | 28.6 EB05 18.9 · IC025 +3.2 3/3 methods agree | Not in label — unassessed | serious PRR 25.8 | 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.
- Hand deformity — n=24, PRR 42.5
- Synovitis — n=20, PRR 25.6
- Wound — n=21, PRR 17.5
- Gait inability — n=22, PRR 15.4
- Systemic lupus erythematosus — n=22, PRR 14.4
- Road traffic accident — n=20, PRR 11.1
- Arthropathy — n=25, PRR 10.4
- Rheumatoid arthritis — n=28, PRR 5.7
✓ A hand-written Bradford Hill causality assessment exists for this drug: Tramadol ↔ Seizures.
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 Tramadol and Acetaminophen?
In FDA FAERS, the most frequently co-reported reaction terms for Tramadol and Acetaminophen are rheumatoid arthritis, arthropathy, hand deformity, systemic lupus erythematosus, gait inability, glossodynia. 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 Tramadol and Acetaminophen have an FDA boxed warning?
Yes. The current FDA label carries a boxed warning: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF TRAMADOL HYDROCHLORIDE and ACETAMINOPHEN Addiction, Abuse, and Misuse Because the use of tramadol hydrochloride and acetaminophen exposes patients and other users to the.
Do FAERS signals prove that Tramadol and Acetaminophen 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 6c2894df-eeeb-4b22-ab32-8ce1601bfdfa, effective 20251117; matched on
openfda.generic_name.exact:"TRAMADOL HYDROCHLORIDE AND ACETAMINOPHEN") - 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, 48 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.