Butalbital and Acetaminophen side effects: what 602 FDA adverse event reports show

Butalbital And Acetaminophen · 45 reaction terms · 450 drug–reaction co-reports · data 2026-09-14

Drug class

Barbiturate

FDA label (Established Pharmacologic Class)

Who reports

602 reports · 50% serious · 48 with death outcome · 81% female

openFDA FAERS counts, all years, deduplication not applied

Used for

Butalbital and acetaminophen 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.

FDA label, Indications and Usage

What it is

DESCRIPTION Butalbital and acetaminophen are supplied in tablet form for oral administration. Butalbital (5-allyl-5-isobutylbarbituric acid), a slightly bitter, white, odorless, crystalline powder, is a short to intermediate-acting barbiturate.

FDA label, Description section

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.

FDA label

How to read this page. FAERS is a spontaneous-reporting system: counts are not incidence rates and a signal is not proof of causation. Each reaction below is run through an automated screen — is the term in the FDA label (known), in the indications (the disease being treated), an administrative/coding term, or none of these (unlabeled)? That screen is mechanical text matching, not a causality assessment. The 30 hand-written Bradford Hill assessments are on the causality assessment page. Not medical advice.

Causality screen of the 23 strongest signals

Labeled — boxed warning 1Reporting / coding artifact 2Outcome field, not a reaction 1Not in label — unassessed 19

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.
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. 22 further terms are in the interactive explorer. Reaction links open the term's cross-drug page.

Show: hide coding/lab/outcome terms hide indication terms unlabeled only hide PRR-only

Reaction	Reports	PRR 95% CI · ROR · χ²/p	EBGM EB05 · IC025	Label screen	Serious-only & strata	Trial cross-check
Helicobacter infection	16	54.7 33.7–88.8ROR 56.2 · χ² 790 / p 3e-174	51.5 EB05 33.6 · IC025 +3.5 3/3 methods agree	Not in label — unassessed	serious PRR 65.9	no trial data cached
Folliculitis	16	54.0 33.3–87.6ROR 55.5 · χ² 780 / p 7e-172	50.9 EB05 33.2 · IC025 +3.5 3/3 methods agree	Not in label — unassessed	serious PRR 72.3	no trial data cached
Sciatica	17	37.4 23.4–59.7ROR 38.4 · χ² 566 / p 2e-125	36.0 EB05 23.8 · IC025 +3.4 3/3 methods agree	Not in label — unassessed	serious PRR 53.8	no trial data cached
Hand deformity	14	37.3 22.2–62.6ROR 38.2 · χ² 459 / p 4e-102	35.6 EB05 22.5 · IC025 +3.1 3/3 methods agree	Not in label — unassessed	serious PRR 46.2	no trial data cached
Wound infection	11	35.3 19.6–63.4ROR 35.9 · χ² 333 / p 1e-74	33.4 EB05 19.9 · IC025 +2.8 3/3 methods agree	Not in label — unassessed	serious PRR 43.1	no trial data cached
Pemphigus	12	33.6 19.2–58.9ROR 34.3 · χ² 348 / p 6e-78	32.1 EB05 19.5 · IC025 +2.9 3/3 methods agree	Not in label — unassessed	serious PRR 38.4	no trial data cached
Synovitis	15	29.0 17.6–47.8ROR 29.7 · χ² 378 / p 2e-84	28.0 EB05 18.0 · IC025 +3.1 3/3 methods agree	Not in label — unassessed	serious PRR 34.6	no trial data cached
Bursitis	10	28.9 15.6–53.4ROR 29.4 · χ² 242 / p 7e-55	27.4 EB05 15.7 · IC025 +2.6 3/3 methods agree	Not in label — unassessed	serious PRR 38.7	no trial data cached
Pericarditis	13	27.2 15.9–46.6ROR 27.8 · χ² 302 / p 5e-68	26.2 EB05 16.2 · IC025 +2.8 3/3 methods agree	Not in label — unassessed	serious PRR 31.2	no trial data cached
Irritable bowel syndrome	16	26.1 16.1–42.3ROR 26.8 · χ² 362 / p 6e-81	25.4 EB05 16.5 · IC025 +3.0 3/3 methods agree	Not in label — unassessed	serious PRR 37.8	no trial data cached
Joint range of motion decreased	10	26.1 14.1–48.2ROR 26.5 · χ² 217 / p 2e-49	24.8 EB05 14.1 · IC025 +2.5 3/3 methods agree	Not in label — unassessed	serious PRR 37.9	no trial data cached
Fibromyalgia	18	25.8 16.4–40.7ROR 26.6 · χ² 405 / p 2e-90	25.2 EB05 16.8 · IC025 +3.2 3/3 methods agree	Not in label — unassessed	serious PRR 32.3	no trial data cached
Glossodynia (burning tongue/mouth pain)	14	21.8 13.0–36.6ROR 22.3 · χ² 258 / p 3e-58	21.1 EB05 13.1 · IC025 +2.8 3/3 methods agree	Labeled — boxed warning synonym match	serious PRR 36.0	no trial data cached
Wound	16	20.1 12.4–32.5ROR 20.6 · χ² 271 / p 3e-61	19.5 EB05 12.5 · IC025 +2.8 3/3 methods agree	Not in label — unassessed	serious PRR 27.2	no trial data cached
Prescribed overdose	11	19.8 11.0–35.6ROR 20.2 · χ² 178 / p 6e-41	18.8 EB05 10.4 · IC025 +2.4 3/3 methods agree	Not in label — unassessed	serious PRR 31.5	no trial data cached
Systemic lupus erythematosus	18	17.7 11.2–28.0ROR 18.2 · χ² 268 / p 2e-60	17.2 EB05 11.2 · IC025 +2.8 3/3 methods agree	Not in label — unassessed	serious PRR 20.7	no trial data cached
Impaired healing	15	15.9 9.7–26.2ROR 16.3 · χ² 195 / p 1e-44	15.1 EB05 9.1 · IC025 +2.6 3/3 methods agree	Reporting / coding artifact	serious PRR 21.9	no trial data cached
Type 2 diabetes mellitus	15	15.5 9.4–25.5ROR 15.8 · χ² 189 / p 2e-43	14.6 EB05 8.7 · IC025 +2.5 3/3 methods agree	Not in label — unassessed	serious PRR 18.6	no trial data cached
Psoriatic arthropathy	17	14.7 9.2–23.5ROR 15.1 · χ² 204 / p 1e-46	14.0 EB05 8.7 · IC025 +2.6 3/3 methods agree	Not in label — unassessed	serious PRR 21.1	no trial data cached
Road traffic accident	17	14.2 8.9–22.6ROR 14.5 · χ² 195 / p 1e-44	13.3 EB05 8.2 · IC025 +2.5 3/3 methods agree	Not in label — unassessed	serious PRR 17.7	no trial data cached
Therapeutic product effect decreased	15	11.8 7.1–19.4ROR 12.1 · χ² 138 / p 5e-32	10.5 EB05 6.2 · IC025 +2.3 3/3 methods agree	Reporting / coding artifact	serious PRR 21.2	no trial data cached
Completed suicide (death by suicide)	12	5.0 2.8–8.7ROR 5.0 · χ² 34 / p 2e-9	4.2 EB05 2.6 · IC025 +1.1 3/3 methods agree	Outcome field, not a reaction boxed warning mentions mortality	serious PRR 5.7	no trial data cached
Injection site bruising	11	4.9 2.7–8.7ROR 4.9 · χ² 30 / p 2e-8	4.1 EB05 2.5 · IC025 +1.0 3/3 methods agree	Not in label — unassessed	serious PRR 15.2	no trial data cached

Trial evidence (ClinicalTrials.gov)

Trial cross-check not yet run for this drug (ClinicalTrials.gov pull covers the 800 most-reported drugs first).

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
Systemic lupus erythematosus	18	17.7 11.2–28.0ROR 18.2 · χ² 268 / p 2e-60	17.2 EB05 11.2 · IC025 +2.8 3/3 methods agree	Not in label — unassessed	serious PRR 20.7	no trial data cached
Fibromyalgia	18	25.8 16.4–40.7ROR 26.6 · χ² 405 / p 2e-90	25.2 EB05 16.8 · IC025 +3.2 3/3 methods agree	Not in label — unassessed	serious PRR 32.3	no trial data cached
Road traffic accident	17	14.2 8.9–22.6ROR 14.5 · χ² 195 / p 1e-44	13.3 EB05 8.2 · IC025 +2.5 3/3 methods agree	Not in label — unassessed	serious PRR 17.7	no trial data cached
Psoriatic arthropathy	17	14.7 9.2–23.5ROR 15.1 · χ² 204 / p 1e-46	14.0 EB05 8.7 · IC025 +2.6 3/3 methods agree	Not in label — unassessed	serious PRR 21.1	no trial data cached
Sciatica	17	37.4 23.4–59.7ROR 38.4 · χ² 566 / p 2e-125	36.0 EB05 23.8 · IC025 +3.4 3/3 methods agree	Not in label — unassessed	serious PRR 53.8	no trial data cached
Wound	16	20.1 12.4–32.5ROR 20.6 · χ² 271 / p 3e-61	19.5 EB05 12.5 · IC025 +2.8 3/3 methods agree	Not in label — unassessed	serious PRR 27.2	no trial data cached
Irritable bowel syndrome	16	26.1 16.1–42.3ROR 26.8 · χ² 362 / p 6e-81	25.4 EB05 16.5 · IC025 +3.0 3/3 methods agree	Not in label — unassessed	serious PRR 37.8	no trial data cached
Folliculitis	16	54.0 33.3–87.6ROR 55.5 · χ² 780 / p 7e-172	50.9 EB05 33.2 · IC025 +3.5 3/3 methods agree	Not in label — unassessed	serious PRR 72.3	no trial data cached
Helicobacter infection	16	54.7 33.7–88.8ROR 56.2 · χ² 790 / p 3e-174	51.5 EB05 33.6 · IC025 +3.5 3/3 methods agree	Not in label — unassessed	serious PRR 65.9	no trial data cached
Therapeutic product effect decreased	15	11.8 7.1–19.4ROR 12.1 · χ² 138 / p 5e-32	10.5 EB05 6.2 · IC025 +2.3 3/3 methods agree	Reporting / coding artifact	serious PRR 21.2	no trial data cached
Type 2 diabetes mellitus	15	15.5 9.4–25.5ROR 15.8 · χ² 189 / p 2e-43	14.6 EB05 8.7 · IC025 +2.5 3/3 methods agree	Not in label — unassessed	serious PRR 18.6	no trial data cached
Impaired healing	15	15.9 9.7–26.2ROR 16.3 · χ² 195 / p 1e-44	15.1 EB05 9.1 · IC025 +2.6 3/3 methods agree	Reporting / coding artifact	serious PRR 21.9	no trial data cached
Synovitis	15	29.0 17.6–47.8ROR 29.7 · χ² 378 / p 2e-84	28.0 EB05 18.0 · IC025 +3.1 3/3 methods agree	Not in label — unassessed	serious PRR 34.6	no trial data cached
Glossodynia (burning tongue/mouth pain)	14	21.8 13.0–36.6ROR 22.3 · χ² 258 / p 3e-58	21.1 EB05 13.1 · IC025 +2.8 3/3 methods agree	Labeled — boxed warning synonym match	serious PRR 36.0	no trial data cached
Hand deformity	14	37.3 22.2–62.6ROR 38.2 · χ² 459 / p 4e-102	35.6 EB05 22.5 · IC025 +3.1 3/3 methods agree	Not in label — unassessed	serious PRR 46.2	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.

✓ 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?

In FDA FAERS, the most frequently co-reported reaction terms for Butalbital and Acetaminophen are systemic lupus erythematosus, fibromyalgia, road traffic accident, psoriatic arthropathy, sciatica, wound. 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 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 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 2eb09253-7f59-401e-afbc-70bb9600fedf, effective 20240506; matched on openfda.generic_name.exact:"BUTALBITAL 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, field patient.drug.openfda.generic_name.exact, 45 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.