Anticholinesterase + antimuscarinic Pregnancy: §4.6: use in human pregnancy has not been systematically evaluated; use of neostigmine in pregnant patients with myasthenia gravis has revealed no untoward effect of the drug on the course of pregnancy. Breast-feeding: may reach breast milk but in amounts probably too small to be harmful.

Neostigmine with glycopyrronium

Brand names: Robinul-Neostigmine

A fixed combination of the anticholinesterase neostigmine with the antimuscarinic glycopyrronium, given intravenously to reverse residual non-depolarising neuromuscular blockade at the end of anaesthesia.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: 1–2 ml of the 0.5 mg/2.5 mg per ml solution (equivalent to glycopyrronium bromide 0.5 mg with neostigmine metilsulfate 2.5 mg, up to glycopyrronium bromide 1 mg with neostigmine metilsulfate 5 mg)

Route: Intravenous injection over a period of 10 to 30 seconds

Frequency: Single dose for reversal of neuromuscular blockade; may be repeated if adequate reversal is not achieved

Max: Total doses in excess of 2 ml are not recommended, as this dose of neostigmine may produce depolarising neuromuscular block

eMC §4.2 (Glycopyrronium Bromide and Neostigmine Metilsulfate 0.5 mg/2.5 mg per ml Solution for Injection). Adults and elderly: 1–2 ml intravenously over 10 to 30 seconds. ALTERNATIVELY 0.02 ml/kg intravenously over 10 to 30 seconds may be used (equivalent to glycopyrronium bromide 0.01 mg/kg with neostigmine metilsulfate 0.05 mg/kg); the dose may be repeated, total maximum 2 ml. All doses are VOLUMES OF THE FIXED-COMBINATION SOLUTION (ml), not milligrams of a single agent. Must not be given in conjunction with suxamethonium (§4.3). §4.8: if severe neostigmine-induced muscarinic side effects occur (bradycardia, hypotension, increased secretions, decreased cardiac conduction rate, bronchospasm or increased gastrointestinal activity), these may be treated by intravenous glycopyrronium bromide injection 200–600 micrograms (0.2–0.6 mg) or atropine 400–1200 micrograms (0.4–1.2 mg).

Paediatric dose

Dose: 0.02 ml/kg

Route: Intravenous injection over a period of 10 to 30 seconds

Frequency: May be repeated if adequate reversal of neuromuscular blockade is not achieved

Max: Total doses in excess of 2 ml are not recommended, as this dose of neostigmine may produce depolarising neuromuscular block

eMC §4.2 paediatric population: 0.02 ml/kg intravenously over 10 to 30 seconds. UNIT IS ml/kg OF THE 0.5 mg/2.5 mg PER ml COMBINATION SOLUTION — NOT mg/kg. The SPC states this is equivalent to glycopyrronium bromide 0.01 mg/kg with neostigmine metilsulfate 0.05 mg/kg. Verify against a children's formulary before use.

Dose auto-extracted from UK Summary of Product Characteristics (SPC) via the eMC; US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Paediatric weight-based calculator

Patient weight (kg)

Verify in a children's formulary

Contraindications

Hypersensitivity to glycopyrronium bromide or neostigmine metilsulfate, or to any of the excipients
Mechanical obstruction of the gastrointestinal or urinary tracts
Concurrent administration with suxamethonium — neostigmine potentiates its depolarising myoneural blocking effects
Anticholinesterase-antimuscarinic combinations should be avoided in patients with a prolonged QT interval

Side effects

Dry mouth, difficulty in micturition, disturbances of visual accommodation and inhibition of sweating (glycopyrronium component)
Nausea, vomiting, increased salivation, diarrhoea, abdominal cramps — more marked with higher doses (neostigmine component)
Cardiac dysrhythmias, bradycardia, heart block, hypotension
Bronchoconstriction, increased bronchial secretions, lacrimation, excessive sweating, miosis (signs of overdosage)
Hypersensitivity, angioedema and anaphylactic reaction (frequency not known)

Interactions

Suxamethonium — neostigmine enhances its effects (also a contraindication)
Non-depolarising muscle relaxants — neostigmine antagonises their effects
Aminoglycosides, clindamycin, polymyxins — antagonise the effects of neostigmine
Procainamide, propafenone, propranolol, quinidine, lithium — antagonise (or possibly antagonise) the effects of neostigmine
Chloroquine and hydroxychloroquine — effects of neostigmine may be diminished (potential to increase symptoms of myasthenia gravis)
Antimuscarinics — antagonise the effects of parasympathomimetics; concomitant use of two or more antimuscarinic drugs increases dry mouth, urinary retention, constipation and confusion in the elderly

Clinical monograph

How it works

Neostigmine inhibits acetylcholinesterase, raising acetylcholine at the neuromuscular junction to overcome competitive non-depolarising block, while glycopyrronium is co-administered to block the muscarinic effects of that excess acetylcholine, chiefly bradycardia and excess secretions.

Prescribing in practice

Reversal should only be attempted once spontaneous recovery from blockade has begun; giving neostigmine in deep block is ineffective and excess anticholinesterase can paradoxically cause weakness, so neuromuscular monitoring is essential.
The glycopyrronium component causes tachycardia, dry mouth and may precipitate urinary retention, and is cautioned in glaucoma and obstructive uropathy.
Neostigmine can provoke bronchospasm, bradycardia and increased secretions, so use with care in asthma and bradyarrhythmias and ensure resuscitation facilities are available.

Monitoring

Monitor neuromuscular recovery with a nerve stimulator together with heart rate and rhythm during and after reversal.

Counselling the patient

This combination is given at the end of an operation to reverse the muscle-relaxant drugs so normal breathing and strength return.
A dry mouth and a faster heartbeat for a short time are expected from the glycopyrronium part.
The team monitors muscle recovery closely to ensure the relaxant has fully worn off.

Evidence & guidelines

Combining neostigmine with an antimuscarinic to counter its muscarinic effects is long-established anaesthetic practice; quantitative neuromuscular monitoring to confirm adequate reversal is recommended by the Association of Anaesthetists.

Reference: AAGBI; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

Calculators