Section 07 · Monograph

Neostigmine

Reviewed Nov 2026FDA label

BloxiverzAChE inhibitor

Indications

Reversal of the effects of nondepolarizing neuromuscular blocking agents after surgery (current FDA-approved indication for neostigmine methylsulfate injection, e.g., Bloxiverz)FDA-labeled

Diagnosis and symptomatic treatment of myasthenia gravis (off-label; IM/SC neostigmine remains used clinically, particularly when oral pyridostigmine is not feasible, e.g., perioperatively or in myasthenic crisis)Off-label
Treatment of postoperative abdominal distension and acute colonic pseudo-obstruction (Ogilvie syndrome) via slow IV infusion under cardiac monitoringOff-label
Nonobstructive urinary retention (postoperative atony of the bladder)Off-label

Reversible competitive inhibitor of acetylcholinesterase; increases acetylcholine concentration at the neuromuscular junction and other cholinergic synapses
In neuromuscular blockade reversal, elevated synaptic ACh competes with residual nondepolarizing blocking agent for nicotinic receptor binding
In MG, increased synaptic ACh compensates for antibody-mediated reduction of functional postsynaptic AChRs
More pronounced muscarinic effects than pyridostigmine at equivalent neuromuscular effect, and a shorter duration of action

Reversal of neuromuscular blockade (adult, IV): 0.03 mg/kg when spontaneous recovery has reached first twitch >10% of baseline; 0.07 mg/kg for more profound block; maximum total dose 0.07 mg/kg or 5 mg, whichever is less
An anticholinergic (atropine or glycopyrrolate) must be administered prior to or concomitantly with neostigmine to mitigate muscarinic effects
Historical MG diagnostic test dose: 1.5 mg IM (adults), with atropine available, observing for objective improvement in strength within ~20-30 minutes
Historical MG treatment dosing (IM/SC): 0.5-2 mg every 1-3 hours as needed, individualized to symptoms

Potentiates and prolongs the effect of depolarizing neuromuscular blockers (e.g., succinylcholine)
Directly antagonizes nondepolarizing neuromuscular blocking agents (its therapeutic mechanism when used for reversal)
Additive cholinergic toxicity with other cholinesterase inhibitors
Beta-blockers and other bradycardic agents increase risk of significant bradycardia/arrhythmia
Aminoglycosides and clindamycin may antagonize neostigmine's effect and worsen weakness
Magnesium sulfate antagonizes neuromuscular transmission and can counteract neostigmine's effect

Bradycardia (most common), which can progress to significant AV block or asystole if unmitigated
Nausea and vomiting
Increased salivation and bronchial/airway secretions; bronchospasm
Hypotension; rarely cardiac arrhythmias or cardiac arrest
Anaphylaxis/angioedema (postmarketing reports)
Miosis, abdominal cramping, diarrhea
Cholinergic crisis with overdosage

Peripheral nerve stimulator with train-of-four monitoring required before and after dosing when used for reversal of neuromuscular blockade
Continuous cardiac (ECG) and heart rate monitoring for bradycardia/arrhythmia
Blood pressure monitoring
Respiratory status — rate, depth, oxygen saturation, and adequacy of ventilation before extubation
In MG use, clinical strength assessment and vigilance for cholinergic crisis versus myasthenic crisis

Published human data have not identified a drug-associated increased risk of major birth defects
Animal reproduction studies at doses up to approximately 0.2x the maximum recommended human dose showed no adverse developmental effects
Data are insufficient to determine whether neostigmine is present in human milk or its effects on the breastfed infant
Quaternary ammonium structure limits placental and mammary transfer relative to tertiary-amine drugs, but formal data are limited