Flumazenil side effects: what 849 FDA adverse event reports show

Flumazenil · 48 reaction terms · 1,041 drug–reaction co-reports · data 2026-09-14

Drug class

Benzodiazepine Antagonist

FDA label (Established Pharmacologic Class)

Who reports

849 reports · 94% serious · 170 with death outcome · 52% female

openFDA FAERS counts, all years, deduplication not applied

Used for

Adult Patients Flumazenil Injection, USP is indicated for the complete or partial reversal of the sedative effects of benzodiazepines in cases where general anesthesia has been induced and/or maintained with benzodiazepines, where sedation has been produced with benzodiazepines for diagnostic and therapeutic procedures, and for the management of benzodiazepine overdose.

FDA label, Indications and Usage

What it is

DESCRIPTION Flumazenil Injection, USP is a benzodiazepine receptor antagonist.

FDA label, Description section

Boxed warning

THE USE OF FLUMAZENIL HAS BEEN ASSOCIATED WITH THE OCCURRENCE OF SEIZURES. THESE ARE MOST FREQUENT IN PATIENTS WHO HAVE BEEN ON BENZODIAZEPINES FOR LONG-TERM SEDATION OR IN OVERDOSE CASES WHERE PATIENTS ARE SHOWING SIGNS OF SERIOUS CYCLIC ANTIDEPRESSANT OVERDOSE. PRACTITIONERS SHOULD INDIVIDUALIZE THE DOSAGE OF FLUMAZENIL AND BE PREPARED TO MANAGE SEIZURES.

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 29 strongest signals

Labeled — boxed warning 6Labeled adverse reaction 3Likely indication confounding 2Reporting / coding artifact 5Not in label — unassessed 13

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 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.
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.
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. 19 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
Respiratory depression	22	44.4 29.4–67.1ROR 45.5 · χ² 889 / p 1e-195	42.8 EB05 29.8 · IC025 +3.8 3/3 methods agree	Labeled — boxed warning exact term	serious PRR 28.0 · 90% clinician	no trial data cached
Intentional overdose	106	41.1 34.4–49.2ROR 46.9 · χ² 4,116 / p <1e-300	40.8 EB05 34.7 · IC025 +4.8 3/3 methods agree	Reporting / coding artifact	serious PRR 26.2 · 98% clinician	no trial data cached
Depressed level of consciousness	64	40.1 31.7–50.8ROR 43.3 · χ² 2,402 / p <1e-300	39.6 EB05 32.1 · IC025 +4.5 3/3 methods agree	Likely indication confounding shares a disease stem with the indications wording	serious PRR 25.3 · 98% clinician	no trial data cached
Generalised tonic-clonic seizure	26	39.3 26.9–57.4ROR 40.5 · χ² 932 / p 6e-205	38.2 EB05 27.4 · IC025 +3.9 3/3 methods agree	Not in label — unassessed	serious PRR 24.5 · 92% clinician	no trial data cached
Coma	70	36.3 29.0–45.5ROR 39.5 · χ² 2,371 / p <1e-300	35.9 EB05 29.4 · IC025 +4.5 3/3 methods agree	Not in label — unassessed	serious PRR 22.3 · 94% clinician	no trial data cached
Mydriasis	18	34.7 22.0–54.9ROR 35.5 · χ² 556 / p 3e-123	33.6 EB05 22.5 · IC025 +3.4 3/3 methods agree	Labeled — boxed warning exact term	serious PRR 27.6	no trial data cached
Unresponsive to stimuli	33	31.7 22.7–44.3ROR 33.0 · χ² 951 / p 3e-209	31.2 EB05 23.2 · IC025 +3.9 3/3 methods agree	Not in label — unassessed	serious PRR 19.9 · 97% clinician	no trial data cached
Encephalopathy	30	30.3 21.3–43.0ROR 31.4 · χ² 820 / p 1e-180	29.7 EB05 21.8 · IC025 +3.7 3/3 methods agree	Not in label — unassessed	serious PRR 18.7 · 97% clinician	no trial data cached
Sinus tachycardia	17	29.7 18.5–47.5ROR 30.2 · χ² 442 / p 2e-98	28.8 EB05 19.0 · IC025 +3.2 3/3 methods agree	Not in label — unassessed	serious PRR 18.6	no trial data cached
Drug level increased	16	23.9 14.7–38.8ROR 24.3 · χ² 328 / p 1e-73	23.2 EB05 15.1 · IC025 +3.0 3/3 methods agree	Reporting / coding artifact	serious PRR 16.2	no trial data cached
Status epilepticus	10	21.8 11.8–40.5ROR 22.1 · χ² 179 / p 5e-41	20.6 EB05 11.3 · IC025 +2.4 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 13.4	no trial data cached
Ventricular tachycardia	14	20.9 12.4–35.1ROR 21.2 · χ² 245 / p 1e-55	20.2 EB05 12.5 · IC025 +2.7 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 12.9	no trial data cached
Intentional product misuse	61	17.4 13.6–22.1ROR 18.6 · χ² 927 / p 6e-204	17.2 EB05 13.9 · IC025 +3.5 3/3 methods agree	Reporting / coding artifact	serious PRR 24.2 · 97% clinician	no trial data cached
Sedation	18	17.1 10.8–27.0ROR 17.4 · χ² 257 / p 5e-58	16.5 EB05 10.7 · IC025 +2.8 3/3 methods agree	Labeled — boxed warning exact term	serious PRR 14.5	no trial data cached
Hypoxia (low oxygen)	24	16.9 11.4–25.1ROR 17.4 · χ² 344 / p 4e-77	16.6 EB05 11.5 · IC025 +3.0 3/3 methods agree	Labeled — boxed warning exact term	serious PRR 10.6 · ♀ 32% (drug 52%) · 95% clinician	no trial data cached
Serotonin syndrome	13	16.8 9.8–28.8ROR 17.0 · χ² 178 / p 8e-41	15.9 EB05 9.1 · IC025 +2.5 3/3 methods agree	Not in label — unassessed	serious PRR 10.4	no trial data cached
Altered state of consciousness	14	16.1 9.5–27.0ROR 16.3 · χ² 183 / p 6e-42	15.2 EB05 8.9 · IC025 +2.5 3/3 methods agree	Likely indication confounding shares a disease stem with the indications wording	serious PRR 10.0	no trial data cached
Metabolic acidosis	20	15.6 10.1–24.1ROR 16.0 · χ² 259 / p 1e-58	15.1 EB05 9.9 · IC025 +2.8 3/3 methods agree	Not in label — unassessed	serious PRR 9.6 · ♀ 80% (drug 52%)	no trial data cached
Electrocardiogram qt prolonged	21	14.4 9.4–22.0ROR 14.8 · χ² 249 / p 2e-56	13.8 EB05 9.1 · IC025 +2.7 3/3 methods agree	Not in label — unassessed	serious PRR 9.0 · 95% clinician	no trial data cached
Suicide attempt	33	13.4 9.6–18.8ROR 13.9 · χ² 368 / p 3e-82	13.1 EB05 9.5 · IC025 +2.9 3/3 methods agree	Not in label — unassessed	serious PRR 8.3 · 97% clinician	no trial data cached
Multiple organ dysfunction syndrome	15	13.3 8.0–21.9ROR 13.5 · χ² 158 / p 1e-36	12.2 EB05 7.2 · IC025 +2.4 3/3 methods agree	Not in label — unassessed	serious PRR 8.2	no trial data cached
Toxicity to various agents	90	13.3 10.9–16.1ROR 14.7 · χ² 1,015 / p 6e-223	13.1 EB05 11.0 · IC025 +3.3 3/3 methods agree	Not in label — unassessed	serious PRR 8.4 · 98% clinician	no trial data cached
Convulsion (seizure)	29	12.4 8.6–17.7ROR 12.8 · χ² 292 / p 9e-66	11.8 EB05 8.4 · IC025 +2.8 3/3 methods agree	Labeled — boxed warning exact term	serious PRR 7.8 · ♀ 79% (drug 52%) · 100% clinician	no trial data cached
Bradycardia (slow heart rate)	26	12.1 8.3–17.7ROR 12.4 · χ² 254 / p 2e-57	11.5 EB05 7.9 · IC025 +2.7 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 7.7 · 92% clinician	no trial data cached
Respiratory arrest	13	11.5 6.7–19.8ROR 11.7 · χ² 115 / p 4e-27	10.0 EB05 5.7 · IC025 +2.1 3/3 methods agree	Not in label — unassessed	serious PRR 7.1	no trial data cached
Hyperkalaemia (high potassium)	16	11.3 7.0–18.4ROR 11.5 · χ² 141 / p 1e-32	10.1 EB05 6.1 · IC025 +2.3 3/3 methods agree	Not in label — unassessed	serious PRR 7.1	no trial data cached
Seizure	47	10.1 7.7–13.4ROR 10.7 · χ² 379 / p 1e-84	9.7 EB05 7.5 · IC025 +2.7 3/3 methods agree	Labeled — boxed warning exact term	serious PRR 6.6 · 91% clinician	no trial data cached
Drug dependence	57	8.7 6.7–11.1ROR 9.2 · χ² 381 / p 3e-85	8.3 EB05 6.6 · IC025 +2.6 3/3 methods agree	Reporting / coding artifact	serious PRR 5.3 · 98% clinician	no trial data cached
Drug abuse	15	4.4 2.7–7.3ROR 4.5 · χ² 37 / p 7e-10	3.9 EB05 2.6 · IC025 +1.1 3/3 methods agree	Reporting / coding artifact	serious PRR 2.8	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
Intentional overdose	106	41.1 34.4–49.2ROR 46.9 · χ² 4,116 / p <1e-300	40.8 EB05 34.7 · IC025 +4.8 3/3 methods agree	Reporting / coding artifact	serious PRR 26.2 · 98% clinician	no trial data cached
Toxicity to various agents	90	13.3 10.9–16.1ROR 14.7 · χ² 1,015 / p 6e-223	13.1 EB05 11.0 · IC025 +3.3 3/3 methods agree	Not in label — unassessed	serious PRR 8.4 · 98% clinician	no trial data cached
Coma	70	36.3 29.0–45.5ROR 39.5 · χ² 2,371 / p <1e-300	35.9 EB05 29.4 · IC025 +4.5 3/3 methods agree	Not in label — unassessed	serious PRR 22.3 · 94% clinician	no trial data cached
Depressed level of consciousness	64	40.1 31.7–50.8ROR 43.3 · χ² 2,402 / p <1e-300	39.6 EB05 32.1 · IC025 +4.5 3/3 methods agree	Likely indication confounding shares a disease stem with the indications wording	serious PRR 25.3 · 98% clinician	no trial data cached
Intentional product misuse	61	17.4 13.6–22.1ROR 18.6 · χ² 927 / p 6e-204	17.2 EB05 13.9 · IC025 +3.5 3/3 methods agree	Reporting / coding artifact	serious PRR 24.2 · 97% clinician	no trial data cached
Drug dependence	57	8.7 6.7–11.1ROR 9.2 · χ² 381 / p 3e-85	8.3 EB05 6.6 · IC025 +2.6 3/3 methods agree	Reporting / coding artifact	serious PRR 5.3 · 98% clinician	no trial data cached
Seizure	47	10.1 7.7–13.4ROR 10.7 · χ² 379 / p 1e-84	9.7 EB05 7.5 · IC025 +2.7 3/3 methods agree	Labeled — boxed warning exact term	serious PRR 6.6 · 91% clinician	no trial data cached
Suicide attempt	33	13.4 9.6–18.8ROR 13.9 · χ² 368 / p 3e-82	13.1 EB05 9.5 · IC025 +2.9 3/3 methods agree	Not in label — unassessed	serious PRR 8.3 · 97% clinician	no trial data cached
Unresponsive to stimuli	33	31.7 22.7–44.3ROR 33.0 · χ² 951 / p 3e-209	31.2 EB05 23.2 · IC025 +3.9 3/3 methods agree	Not in label — unassessed	serious PRR 19.9 · 97% clinician	no trial data cached
Encephalopathy	30	30.3 21.3–43.0ROR 31.4 · χ² 820 / p 1e-180	29.7 EB05 21.8 · IC025 +3.7 3/3 methods agree	Not in label — unassessed	serious PRR 18.7 · 97% clinician	no trial data cached
Convulsion (seizure)	29	12.4 8.6–17.7ROR 12.8 · χ² 292 / p 9e-66	11.8 EB05 8.4 · IC025 +2.8 3/3 methods agree	Labeled — boxed warning exact term	serious PRR 7.8 · ♀ 79% (drug 52%) · 100% clinician	no trial data cached
Bradycardia (slow heart rate)	26	12.1 8.3–17.7ROR 12.4 · χ² 254 / p 2e-57	11.5 EB05 7.9 · IC025 +2.7 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 7.7 · 92% clinician	no trial data cached
Generalised tonic-clonic seizure	26	39.3 26.9–57.4ROR 40.5 · χ² 932 / p 6e-205	38.2 EB05 27.4 · IC025 +3.9 3/3 methods agree	Not in label — unassessed	serious PRR 24.5 · 92% clinician	no trial data cached
Hypoxia (low oxygen)	24	16.9 11.4–25.1ROR 17.4 · χ² 344 / p 4e-77	16.6 EB05 11.5 · IC025 +3.0 3/3 methods agree	Labeled — boxed warning exact term	serious PRR 10.6 · ♀ 32% (drug 52%) · 95% clinician	no trial data cached
Respiratory depression	22	44.4 29.4–67.1ROR 45.5 · χ² 889 / p 1e-195	42.8 EB05 29.8 · IC025 +3.8 3/3 methods agree	Labeled — boxed warning exact term	serious PRR 28.0 · 90% clinician	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.

Generalised tonic-clonic seizure — n=26, PRR 39.3
Coma — n=70, PRR 36.3
Unresponsive to stimuli — n=33, PRR 31.7
Encephalopathy — n=30, PRR 30.3
Metabolic acidosis — n=20, PRR 15.6
Electrocardiogram qt prolonged — n=21, PRR 14.4
Suicide attempt — n=33, PRR 13.4
Toxicity to various agents — n=90, PRR 13.3

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 Flumazenil?

In FDA FAERS, the most frequently co-reported reaction terms for Flumazenil are toxicity to various agents, coma, depressed level of consciousness, seizure, suicide attempt, unresponsive to stimuli. 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 Flumazenil have an FDA boxed warning?

Yes. The current FDA label carries a boxed warning: THE USE OF FLUMAZENIL HAS BEEN ASSOCIATED WITH THE OCCURRENCE OF SEIZURES. THESE ARE MOST FREQUENT IN PATIENTS WHO HAVE BEEN ON BENZODIAZEPINES FOR LONG-TERM SEDATION OR IN OVERDOSE CASES WHERE PATIENTS ARE SHOWING SIGNS OF SERIOUS CYCLIC ANTIDEPRESSANT OVERDOSE. PRACTITIONERS SHOULD INDIVIDUALIZE THE DOSAGE OF FLUMAZENIL AND BE PREPARED TO MANAGE SEIZURES.

Do FAERS signals prove that Flumazenil 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 2190e8d0-d7ca-4f53-b243-0d2c31979aa8, effective 20240614; matched on openfda.generic_name.exact:"FLUMAZENIL")
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, 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.