Butalbital and Acetaminophen and Caffeine side effects: what 1,766 FDA adverse event reports show
Drug class
Barbiturate, Central Nervous System Stimulant, Methylxanthine
Label matched
Butalbital, Acetaminophen And Caffeine (Butalbital, Acetaminophen And Caffeine)
Who reports
1,766 reports · 64% serious · 284 with death outcome · 83% female
Used for
Butalbital, acetaminophen and caffeine tablets are indicated for the relief of the symptom complex of tension (or muscle contraction) headache. Evidence supporting the efficacy and safety of this combination product in the treatment of multiple recurrent headaches is unavailable. Caution in this regard is required because butalbital is habit-forming and potentially abusable.
What it is
DESCRIPTION Butalbital, Acetaminophen and Caffeine Tablets, USP are supplied in tablet form for oral administration.
Boxed warning
Hepatotoxicity Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death. Most of the cases of liver injury are associated with the use of acetaminophen at doses that exceed 4000 milligrams per day, and often involve more than one acetaminophen-containing product.
Causality screen of the 24 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.
- 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. 70 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 |
|---|---|---|---|---|---|---|
| Infusion site pain | 25 | 23.3 15.8–34.3ROR 23.6 · χ² 510 / p 3e-113 | 22.9 EB05 16.2 · IC025 +3.3 3/3 methods agree | Labeled (related wording) related wording | serious n=11 · 76% consumer | no trial data cached |
| Completed suicide (death by suicide) | 153 | 21.6 18.6–25.1ROR 23.6 · χ² 2,992 / p <1e-300 | 21.5 EB05 18.8 · IC025 +4.1 3/3 methods agree | Outcome field, not a reaction boxed warning mentions mortality | serious PRR 19.5 · 99% clinician | no trial data cached |
| Hepatotoxicity (liver damage) | 25 | 13.4 9.1–19.8ROR 13.6 · χ² 274 / p 6e-62 | 12.9 EB05 8.8 · IC025 +2.8 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 12.4 · ♀ 62% (drug 83%) · 100% clinician | no trial data cached |
| Metabolic acidosis | 35 | 13.1 9.5–18.2ROR 13.4 · χ² 380 / p 6e-85 | 12.8 EB05 9.4 · IC025 +2.9 3/3 methods agree | Not in label — unassessed | serious PRR 11.9 · 97% clinician | no trial data cached |
| Migraine | 101 | 12.6 10.5–15.3ROR 13.3 · χ² 1,075 / p 6e-236 | 12.5 EB05 10.6 · IC025 +3.2 3/3 methods agree | Not in label — unassessed | serious PRR 14.9 | no trial data cached |
| Respiratory depression | 13 | 12.6 7.3–21.6ROR 12.7 · χ² 127 / p 8e-30 | 11.1 EB05 6.2 · IC025 +2.2 3/3 methods agree | Labeled (related wording) related wording | serious PRR 11.7 | no trial data cached |
| Dermatitis contact | 12 | 12.5 7.1–22.1ROR 12.6 · χ² 116 / p 2e-27 | 10.9 EB05 5.9 · IC025 +2.1 3/3 methods agree | Not in label — unassessed | serious n=7 | no trial data cached |
| Coagulopathy | 17 | 12.1 7.6–19.5ROR 12.3 · χ² 163 / p 1e-37 | 11.1 EB05 6.8 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | serious PRR 11.5 | no trial data cached |
| Poisoning | 11 | 10.3 5.7–18.7ROR 10.4 · χ² 84 / p 3e-20 | 8.4 EB05 4.6 · IC025 +1.9 3/3 methods agree | Not in label — unassessed | serious PRR 9.5 | no trial data cached |
| Toxicity to various agents | 137 | 9.7 8.2–11.4ROR 10.4 · χ² 1,066 / p 3e-234 | 9.5 EB05 8.2 · IC025 +2.9 3/3 methods agree | Not in label — unassessed | serious PRR 9.0 · 96% clinician | no trial data cached |
| Fibromyalgia | 18 | 8.8 5.6–13.9ROR 8.9 · χ² 117 / p 2e-27 | 7.6 EB05 4.9 · IC025 +2.1 3/3 methods agree | Not in label — unassessed | serious PRR 8.7 | no trial data cached |
| Product use complaint | 11 | 8.4 4.7–15.2ROR 8.5 · χ² 65 / p 4e-16 | 6.7 EB05 3.8 · IC025 +1.6 3/3 methods agree | Reporting / coding artifact | serious n=8 | no trial data cached |
| Depressed level of consciousness | 24 | 7.2 4.8–10.7ROR 7.3 · χ² 122 / p 9e-29 | 6.5 EB05 4.5 · IC025 +2.0 3/3 methods agree | Not in label — unassessed | serious PRR 6.7 · 96% clinician | no trial data cached |
| Cardio-respiratory arrest | 24 | 6.8 4.5–10.1ROR 6.8 · χ² 112 / p 1e-26 | 6.1 EB05 4.3 · IC025 +1.9 3/3 methods agree | Not in label — unassessed | serious PRR 6.1 · 100% clinician | no trial data cached |
| Ear infection | 15 | 6.7 4.1–11.1ROR 6.8 · χ² 67 / p 1e-16 | 5.7 EB05 3.6 · IC025 +1.6 3/3 methods agree | Not in label — unassessed | serious PRR 9.6 | no trial data cached |
| Respiratory arrest | 15 | 6.4 3.9–10.6ROR 6.4 · χ² 63 / p 1e-15 | 5.4 EB05 3.5 · IC025 +1.6 3/3 methods agree | Not in label — unassessed | serious PRR 5.8 | no trial data cached |
| Coma | 23 | 5.7 3.8–8.6ROR 5.8 · χ² 85 / p 1e-20 | 5.2 EB05 3.6 · IC025 +1.7 3/3 methods agree | Not in label — unassessed | serious PRR 5.2 · 96% clinician | no trial data cached |
| Hepatitis (liver inflammation) | 11 | 5.1 2.8–9.2ROR 5.1 · χ² 32 / p 7e-9 | 4.3 EB05 2.6 · IC025 +1.1 3/3 methods agree | Not in label — unassessed | serious PRR 4.7 | no trial data cached |
| Anhedonia | 10 | 4.5 2.4–8.3ROR 4.5 · χ² 24 / p 6e-7 | 3.8 EB05 2.2 · IC025 +0.9 3/3 methods agree | Not in label — unassessed | serious PRR 4.5 | no trial data cached |
| Device dislocation | 13 | 3.6 2.1–6.1ROR 3.6 · χ² 21 / p 2e-6 | 3.2 EB05 2.0 · IC025 +0.8 3/3 methods agree | Reporting / coding artifact | serious PRR 3.6 | no trial data cached |
| Overdose | 59 | 3.2 2.5–4.2ROR 3.3 · χ² 90 / p 1e-21 | 3.2 EB05 2.5 · IC025 +1.2 3/3 methods agree | Reporting / coding artifact | serious PRR 3.4 | no trial data cached |
| Suicide attempt | 16 | 3.1 1.9–5.1ROR 3.1 · χ² 21 / p 2e-6 | 2.9 EB05 1.9 · IC025 +0.7 | Not in label — unassessed | serious PRR 2.8 | no trial data cached |
| Emotional distress | 25 | 2.4 1.7–3.6ROR 2.5 · χ² 20 / p 4e-6 | 2.4 EB05 1.7 · IC025 +0.6 | Not in label — unassessed | serious PRR 2.5 | no trial data cached |
| Product substitution issue | 11 | 2.3 1.3–4.1ROR 2.3 · χ² 7 / p 0.005 | 2.2 EB05 1.3 · IC025 +0.1 | Reporting / coding artifact | serious PRR 0.8 | 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) | 153 | 21.6 18.6–25.1ROR 23.6 · χ² 2,992 / p <1e-300 | 21.5 EB05 18.8 · IC025 +4.1 3/3 methods agree | Outcome field, not a reaction boxed warning mentions mortality | serious PRR 19.5 · 99% clinician | no trial data cached |
| Toxicity to various agents | 137 | 9.7 8.2–11.4ROR 10.4 · χ² 1,066 / p 3e-234 | 9.5 EB05 8.2 · IC025 +2.9 3/3 methods agree | Not in label — unassessed | serious PRR 9.0 · 96% clinician | no trial data cached |
| Migraine | 101 | 12.6 10.5–15.3ROR 13.3 · χ² 1,075 / p 6e-236 | 12.5 EB05 10.6 · IC025 +3.2 3/3 methods agree | Not in label — unassessed | serious PRR 14.9 | no trial data cached |
| Overdose | 59 | 3.2 2.5–4.2ROR 3.3 · χ² 90 / p 1e-21 | 3.2 EB05 2.5 · IC025 +1.2 3/3 methods agree | Reporting / coding artifact | serious PRR 3.4 | no trial data cached |
| Metabolic acidosis | 35 | 13.1 9.5–18.2ROR 13.4 · χ² 380 / p 6e-85 | 12.8 EB05 9.4 · IC025 +2.9 3/3 methods agree | Not in label — unassessed | serious PRR 11.9 · 97% clinician | no trial data cached |
| Emotional distress | 25 | 2.4 1.7–3.6ROR 2.5 · χ² 20 / p 4e-6 | 2.4 EB05 1.7 · IC025 +0.6 | Not in label — unassessed | serious PRR 2.5 | no trial data cached |
| Hepatotoxicity (liver damage) | 25 | 13.4 9.1–19.8ROR 13.6 · χ² 274 / p 6e-62 | 12.9 EB05 8.8 · IC025 +2.8 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 12.4 · ♀ 62% (drug 83%) · 100% clinician | no trial data cached |
| Infusion site pain | 25 | 23.3 15.8–34.3ROR 23.6 · χ² 510 / p 3e-113 | 22.9 EB05 16.2 · IC025 +3.3 3/3 methods agree | Labeled (related wording) related wording | serious n=11 · 76% consumer | no trial data cached |
| Cardio-respiratory arrest | 24 | 6.8 4.5–10.1ROR 6.8 · χ² 112 / p 1e-26 | 6.1 EB05 4.3 · IC025 +1.9 3/3 methods agree | Not in label — unassessed | serious PRR 6.1 · 100% clinician | no trial data cached |
| Depressed level of consciousness | 24 | 7.2 4.8–10.7ROR 7.3 · χ² 122 / p 9e-29 | 6.5 EB05 4.5 · IC025 +2.0 3/3 methods agree | Not in label — unassessed | serious PRR 6.7 · 96% clinician | no trial data cached |
| Coma | 23 | 5.7 3.8–8.6ROR 5.8 · χ² 85 / p 1e-20 | 5.2 EB05 3.6 · IC025 +1.7 3/3 methods agree | Not in label — unassessed | serious PRR 5.2 · 96% clinician | no trial data cached |
| Fibromyalgia | 18 | 8.8 5.6–13.9ROR 8.9 · χ² 117 / p 2e-27 | 7.6 EB05 4.9 · IC025 +2.1 3/3 methods agree | Not in label — unassessed | serious PRR 8.7 | no trial data cached |
| Coagulopathy | 17 | 12.1 7.6–19.5ROR 12.3 · χ² 163 / p 1e-37 | 11.1 EB05 6.8 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | serious PRR 11.5 | no trial data cached |
| Suicide attempt | 16 | 3.1 1.9–5.1ROR 3.1 · χ² 21 / p 2e-6 | 2.9 EB05 1.9 · IC025 +0.7 | Not in label — unassessed | serious PRR 2.8 | no trial data cached |
| Respiratory arrest | 15 | 6.4 3.9–10.6ROR 6.4 · χ² 63 / p 1e-15 | 5.4 EB05 3.5 · IC025 +1.6 3/3 methods agree | Not in label — unassessed | serious PRR 5.8 | 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.
- Metabolic acidosis — n=35, PRR 13.1
- Migraine — n=101, PRR 12.6
- Toxicity to various agents — n=137, PRR 9.7
- Depressed level of consciousness — n=24, PRR 7.2
- Cardio-respiratory arrest — n=24, PRR 6.8
- Coma — n=23, PRR 5.7
- Emotional distress — n=25, PRR 2.4
✓ A hand-written Bradford Hill causality assessment exists for this drug: Acetaminophen (paracetamol) ↔ Liver injury / hepatotoxicity.
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 Butalbital and Acetaminophen and Caffeine?
In FDA FAERS, the most frequently co-reported reaction terms for Butalbital and Acetaminophen and Caffeine are toxicity to various agents, migraine, metabolic acidosis, emotional distress, hepatotoxicity, infusion site pain. 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 Butalbital and Acetaminophen and Caffeine have an FDA boxed warning?
Yes. The current FDA label carries a boxed warning: Hepatotoxicity Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death. Most of the cases of liver injury are associated with the use of acetaminophen at doses that exceed 4000 milligrams per day, and often involve more than one acetaminophen-containing product.
Do FAERS signals prove that Butalbital and Acetaminophen and Caffeine 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 21a148d1-b242-4414-82b2-cb78387d7d0f, effective 20250325; matched on
openfda.generic_name.exact:"BUTALBITAL, ACETAMINOPHEN AND CAFFEINE") - 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, 94 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.