Neostigmine side effects: what 1,147 FDA adverse event reports show

Neostigmine · 54 reaction terms · 940 drug–reaction co-reports · data 2026-09-14

Drug class

Cholinesterase inhibitor

FDA label, Indications wording

Who reports

1,147 reports · 92% serious · 112 with death outcome · 55% female

openFDA FAERS counts, all years, deduplication not applied

Used for

Neostigmine methylsulfate injection is a cholinesterase inhibitor indicated for the reversal of the effects of non-depolarizing neuromuscular blocking agents after surgery. Neostigmine methylsulfate injection, a cholinesterase inhibitor, is indicated for the reversal of the effects of non-depolarizing neuromuscular blocking agents (NMBAs) after surgery (1) .

FDA label, Indications and Usage

What it is

Neostigmine methylsulfate, a cholinesterase inhibitor, is (m-hydroxyphenyl) trimethylammonium methylsulfate dimethylcarbamate.

FDA label, Description section

Boxed warning

None in the current 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 adverse reaction 4Labeled (related wording) 1Reporting / coding artifact 4Lab value / disease marker 1Not in label — unassessed 19

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.
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. 25 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
Serotonin syndrome	80	76.8 62.1–94.9ROR 82.5 · χ² 5,888 / p <1e-300	75.1 EB05 62.3 · IC025 +5.3 3/3 methods agree	Not in label — unassessed	serious PRR 48.1 · 91% clinician	no trial data cached
Ileus	26	38.7 26.5–56.6ROR 39.6 · χ² 916 / p 1e-201	37.7 EB05 27.0 · IC025 +3.8 3/3 methods agree	Not in label — unassessed	serious PRR 24.2 · ♀ 80% (drug 55%)	no trial data cached
Post procedural complication	30	28.5 20.0–40.6ROR 29.3 · χ² 770 / p 1e-169	28.1 EB05 20.6 · IC025 +3.7 3/3 methods agree	Reporting / coding artifact	serious PRR 16.8 · 92% clinician	no trial data cached
Atelectasis	14	26.4 15.7–44.5ROR 26.7 · χ² 317 / p 3e-71	25.5 EB05 16.1 · IC025 +2.9 3/3 methods agree	Not in label — unassessed	serious PRR 16.6	no trial data cached
Muscle rigidity	16	24.5 15.1–39.9ROR 24.8 · χ² 337 / p 1e-75	23.8 EB05 15.5 · IC025 +3.0 3/3 methods agree	Not in label — unassessed	serious PRR 17.2	no trial data cached
Bradycardia (slow heart rate)	71	24.5 19.5–30.6ROR 26.0 · χ² 1,576 / p <1e-300	24.3 EB05 19.9 · IC025 +4.0 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 14.4 · ♀ 31% (drug 55%) · 97% clinician	no trial data cached
Bladder disorder	13	23.9 13.9–41.1ROR 24.2 · χ² 263 / p 2e-59	23.1 EB05 14.1 · IC025 +2.8 3/3 methods agree	Not in label — unassessed	serious n=13	no trial data cached
Tachypnoea	16	21.6 13.3–35.2ROR 21.9 · χ² 294 / p 3e-66	21.0 EB05 13.5 · IC025 +2.9 3/3 methods agree	Not in label — unassessed	serious PRR 13.9	no trial data cached
Metabolic acidosis	37	21.4 15.6–29.4ROR 22.1 · χ² 699 / p 2e-154	21.2 EB05 16.0 · IC025 +3.5 3/3 methods agree	Not in label — unassessed	serious PRR 13.0 · ♀ 17% (drug 55%) · 97% clinician	no trial data cached
Respiratory depression	14	20.9 12.4–35.2ROR 21.1 · χ² 246 / p 1e-55	20.2 EB05 12.5 · IC025 +2.7 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 13.4	no trial data cached
Dystonia	21	19.7 12.9–30.2ROR 20.1 · χ² 355 / p 2e-79	19.3 EB05 13.2 · IC025 +3.0 3/3 methods agree	Not in label — unassessed	serious PRR 13.6 · 100% clinician	no trial data cached
Supraventricular tachycardia	10	19.1 10.3–35.5ROR 19.3 · χ² 154 / p 1e-35	17.9 EB05 9.4 · IC025 +2.3 3/3 methods agree	Not in label — unassessed	serious PRR 12.5	no trial data cached
Cardiac arrest (heart stopping)	72	15.9 12.7–19.9ROR 16.9 · χ² 993 / p 2e-218	15.8 EB05 12.9 · IC025 +3.5 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 9.6 · 96% clinician	no trial data cached
Pulmonary oedema	36	14.7 10.7–20.3ROR 15.1 · χ² 446 / p 2e-99	14.4 EB05 10.7 · IC025 +3.1 3/3 methods agree	Not in label — unassessed	serious PRR 9.0 · 94% clinician	no trial data cached
Unresponsive to stimuli	20	14.2 9.2–22.0ROR 14.5 · χ² 233 / p 7e-53	13.6 EB05 8.8 · IC025 +2.7 3/3 methods agree	Not in label — unassessed	serious PRR 9.0	no trial data cached
Sinus tachycardia	11	14.2 7.9–25.6ROR 14.3 · χ² 122 / p 1e-28	12.6 EB05 6.6 · IC025 +2.1 3/3 methods agree	Not in label — unassessed	serious PRR 9.0	no trial data cached
Bronchospasm (airway tightening)	11	14.1 7.8–25.3ROR 14.2 · χ² 121 / p 2e-28	12.5 EB05 6.5 · IC025 +2.1 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 8.8	no trial data cached
White blood cell count increased	29	13.8 9.6–19.7ROR 14.1 · χ² 331 / p 2e-74	13.4 EB05 9.5 · IC025 +2.9 3/3 methods agree	Lab value / disease marker	serious PRR 10.3	no trial data cached
Premature delivery	11	12.6 7.0–22.7ROR 12.7 · χ² 106 / p 4e-25	10.8 EB05 5.7 · IC025 +2.0 3/3 methods agree	Not in label — unassessed	serious PRR 6.6	no trial data cached
Multi-organ failure	12	12.5 7.1–22.0ROR 12.6 · χ² 116 / p 3e-27	10.9 EB05 5.9 · IC025 +2.1 3/3 methods agree	Not in label — unassessed	serious PRR 7.8	no trial data cached
Toxic epidermal necrolysis (severe skin peeling reaction)	10	12.1 6.5–22.5ROR 12.2 · χ² 91 / p 6e-22	10.1 EB05 5.1 · IC025 +1.9 3/3 methods agree	Not in label — unassessed	serious PRR 7.6	no trial data cached
Hyperkalaemia (high potassium)	21	11.0 7.2–16.8ROR 11.2 · χ² 181 / p 1e-41	10.1 EB05 6.6 · IC025 +2.4 3/3 methods agree	Not in label — unassessed	serious PRR 7.0 · ♀ 24% (drug 55%)	no trial data cached
Drug interaction	92	10.6 8.7–12.9ROR 11.4 · χ² 796 / p 2e-175	10.4 EB05 8.7 · IC025 +3.0 3/3 methods agree	Reporting / coding artifact	serious PRR 7.4 · 94% clinician	no trial data cached
Anaphylactic reaction (severe allergic reaction)	27	9.0 6.2–13.1ROR 9.2 · χ² 184 / p 3e-42	8.2 EB05 5.8 · IC025 +2.3 3/3 methods agree	Labeled (related wording) related wording	serious PRR 5.7 · ♀ 79% (drug 55%) · 96% clinician	no trial data cached
Dementia	13	8.5 5.0–14.7ROR 8.6 · χ² 79 / p 3e-19	7.0 EB05 4.2 · IC025 +1.8 3/3 methods agree	Not in label — unassessed	serious PRR 5.7	no trial data cached
Rhabdomyolysis (muscle breakdown)	19	8.3 5.3–13.0ROR 8.5 · χ² 116 / p 3e-27	7.3 EB05 4.8 · IC025 +2.0 3/3 methods agree	Not in label — unassessed	serious PRR 5.2	no trial data cached
Stevens-johnson syndrome (severe blistering skin reaction)	10	8.2 4.4–15.2ROR 8.3 · χ² 56 / p 3e-14	6.4 EB05 3.6 · IC025 +1.5 3/3 methods agree	Not in label — unassessed	serious PRR 5.2	no trial data cached
Exposure during pregnancy	24	7.1 4.8–10.5ROR 7.2 · χ² 119 / p 5e-28	6.3 EB05 4.4 · IC025 +2.0 3/3 methods agree	Reporting / coding artifact	serious PRR 3.9 · ♀ 100% (drug 55%) · 100% clinician	no trial data cached
Foetal exposure during pregnancy	14	3.2 1.9–5.3ROR 3.2 · χ² 19 / p 8e-6	2.9 EB05 1.9 · IC025 +0.6	Reporting / coding artifact	serious PRR 2.0	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
Drug interaction	92	10.6 8.7–12.9ROR 11.4 · χ² 796 / p 2e-175	10.4 EB05 8.7 · IC025 +3.0 3/3 methods agree	Reporting / coding artifact	serious PRR 7.4 · 94% clinician	no trial data cached
Serotonin syndrome	80	76.8 62.1–94.9ROR 82.5 · χ² 5,888 / p <1e-300	75.1 EB05 62.3 · IC025 +5.3 3/3 methods agree	Not in label — unassessed	serious PRR 48.1 · 91% clinician	no trial data cached
Cardiac arrest (heart stopping)	72	15.9 12.7–19.9ROR 16.9 · χ² 993 / p 2e-218	15.8 EB05 12.9 · IC025 +3.5 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 9.6 · 96% clinician	no trial data cached
Bradycardia (slow heart rate)	71	24.5 19.5–30.6ROR 26.0 · χ² 1,576 / p <1e-300	24.3 EB05 19.9 · IC025 +4.0 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 14.4 · ♀ 31% (drug 55%) · 97% clinician	no trial data cached
Metabolic acidosis	37	21.4 15.6–29.4ROR 22.1 · χ² 699 / p 2e-154	21.2 EB05 16.0 · IC025 +3.5 3/3 methods agree	Not in label — unassessed	serious PRR 13.0 · ♀ 17% (drug 55%) · 97% clinician	no trial data cached
Pulmonary oedema	36	14.7 10.7–20.3ROR 15.1 · χ² 446 / p 2e-99	14.4 EB05 10.7 · IC025 +3.1 3/3 methods agree	Not in label — unassessed	serious PRR 9.0 · 94% clinician	no trial data cached
Post procedural complication	30	28.5 20.0–40.6ROR 29.3 · χ² 770 / p 1e-169	28.1 EB05 20.6 · IC025 +3.7 3/3 methods agree	Reporting / coding artifact	serious PRR 16.8 · 92% clinician	no trial data cached
White blood cell count increased	29	13.8 9.6–19.7ROR 14.1 · χ² 331 / p 2e-74	13.4 EB05 9.5 · IC025 +2.9 3/3 methods agree	Lab value / disease marker	serious PRR 10.3	no trial data cached
Anaphylactic reaction (severe allergic reaction)	27	9.0 6.2–13.1ROR 9.2 · χ² 184 / p 3e-42	8.2 EB05 5.8 · IC025 +2.3 3/3 methods agree	Labeled (related wording) related wording	serious PRR 5.7 · ♀ 79% (drug 55%) · 96% clinician	no trial data cached
Ileus	26	38.7 26.5–56.6ROR 39.6 · χ² 916 / p 1e-201	37.7 EB05 27.0 · IC025 +3.8 3/3 methods agree	Not in label — unassessed	serious PRR 24.2 · ♀ 80% (drug 55%)	no trial data cached
Exposure during pregnancy	24	7.1 4.8–10.5ROR 7.2 · χ² 119 / p 5e-28	6.3 EB05 4.4 · IC025 +2.0 3/3 methods agree	Reporting / coding artifact	serious PRR 3.9 · ♀ 100% (drug 55%) · 100% clinician	no trial data cached
Hyperkalaemia (high potassium)	21	11.0 7.2–16.8ROR 11.2 · χ² 181 / p 1e-41	10.1 EB05 6.6 · IC025 +2.4 3/3 methods agree	Not in label — unassessed	serious PRR 7.0 · ♀ 24% (drug 55%)	no trial data cached
Dystonia	21	19.7 12.9–30.2ROR 20.1 · χ² 355 / p 2e-79	19.3 EB05 13.2 · IC025 +3.0 3/3 methods agree	Not in label — unassessed	serious PRR 13.6 · 100% clinician	no trial data cached
Unresponsive to stimuli	20	14.2 9.2–22.0ROR 14.5 · χ² 233 / p 7e-53	13.6 EB05 8.8 · IC025 +2.7 3/3 methods agree	Not in label — unassessed	serious PRR 9.0	no trial data cached
Rhabdomyolysis (muscle breakdown)	19	8.3 5.3–13.0ROR 8.5 · χ² 116 / p 3e-27	7.3 EB05 4.8 · IC025 +2.0 3/3 methods agree	Not in label — unassessed	serious PRR 5.2	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.

Serotonin syndrome — n=80, PRR 76.8
Ileus — n=26, PRR 38.7
Metabolic acidosis — n=37, PRR 21.4
Dystonia — n=21, PRR 19.7
Pulmonary oedema — n=36, PRR 14.7
Unresponsive to stimuli — n=20, PRR 14.2
Hyperkalaemia — n=21, PRR 11.0

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 Neostigmine?

In FDA FAERS, the most frequently co-reported reaction terms for Neostigmine are serotonin syndrome, cardiac arrest, bradycardia, metabolic acidosis, pulmonary oedema, white blood cell count increased. 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 Neostigmine have an FDA boxed warning?

No. The FDA label retrieved for Neostigmine has no boxed warning; see the label's Warnings and Precautions for the recognised risks.

Do FAERS signals prove that Neostigmine 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 81243f47-bd25-bd02-518a-087badcca755, effective 20210202; matched on openfda.generic_name.exact:"NEOSTIGMINE")
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, 54 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.