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Anticholinesterase — Neuromuscular Blockade Reversal Pregnancy: For use as indicated, animal studies (see section 5.3) are of very limited relevance. Use in human pregnancy has not been systematically evaluated. The 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: Neostigmine Methylsulfate

Neostigmine combined with glycopyrronium is used at the end of anaesthesia to reverse residual non-depolarising neuromuscular blockade, with the antimuscarinic component countering neostigmine's cholinergic side effects.

Adult dose

Dose: Glycopyrronium bromide 0.5 mg/ml and neostigmine metilsulfate 2.5 mg/ml solution for injection (fixed combination; each 1 ml contains glycopyrronium bromide 0.5 mg and neostigmine metilsulfate 2.5 mg), reversal of residual non-depolarising (competitive) neuromuscular block, adults and elderly: 1-2 ml intravenously over 10 to 30 seconds (equivalent to glycopyrronium bromide 0.5 mg with neostigmine metilsulfate 2.5 mg, to glycopyrronium bromide 1 mg with neostigmine metilsulfate 5 mg); alternatively 0.02 ml/kg intravenously over 10 to 30 seconds (equivalent to glycopyrronium bromide 0.01 mg/kg with neostigmine metilsulfate 0.05 mg/kg)
Route: Intravenous injection over a period of 10 to 30 seconds
Frequency: Single injection; the dose may be repeated (total maximum 2 ml) if adequate reversal is not achieved
Max: Total doses in excess of 2 ml are not recommended (2 ml = glycopyrronium bromide 1 mg with neostigmine metilsulfate 5 mg)
The pinned product is GLYCOPYRRONIUM BROMIDE 0.5MG/ML AND NEOSTIGMINE METILSULFATE 2.5MG/ML SOLUTION FOR INJECTION (PL001560116), Martindale Pharmaceuticals Ltd (T/A Martindale Pharma), the fixed-dose combination, so the glycopyrronium and the neostigmine are dosed together as a volume of the one solution. PRODUCT SCOPE: only this fixed-dose combination is covered. Single-agent neostigmine methylsulfate injection, glycopyrronium or atropine given separately, and other neostigmine products have their own SPCs and mg dosing and are NOT covered here. §2 (verbatim): 'Each 1ml of solution contains Glycopyrronium Bromide (Glycopyrrolate) 0.5mg and Neostigmine Metilsulfate 2.5mg.' §4.1 (verbatim): 'Reversal of residual non-depolarising (competitive) Neuromuscular block'. VERBATIM §4.2: 'Posology: Adults and elderly 1-2ml intravenously over a period of 10 to 30 seconds (equivalent to Glycopyrronium Bromide 0.5mg with Neostigmine Metilsulfate 2.5mg to Glycopyrronium Bromide 1mg with Neostigmine Metilsulfate 5mg). Alternatively 0.02ml/kg intravenously over a period of 10 to 30 seconds may be used, (equivalent to Glycopyrronium Bromide 0.01mg/kg with Neostigmine Metilsulfate 0.05mg/kg), dose may be repeated (total maximum 2ml)' 'Paediatric population: 0.02ml/kg intravenously over a period of 10 to 30 seconds (equivalent to Glycopyrronium Bromide 0.01mg/kg with Neostigmine Metilsulfate 0.05mg/kg ). These doses may be repeated if adequate reversal of neuromuscular blockade is not achieved. Total doses in excess of 2ml are not recommended as this dose of Neostigmine may produce depolarising neuromuscular block. Method of administration: For intravenous injection.' CONTRAINDICATED WITH SUXAMETHONIUM (§4.3): 'this product should not be given in conjunction with suxamethonium, as Neostigmine potentiates the depolarising myoneural blocking effects of this agent.' MANAGEMENT OF SEVERE MUSCARINIC EFFECTS (§4.8, verbatim): 'If severe Neostigmine induced muscarinic side effects occur (bradycardia, hypotension, increased or pharyngeal secretions, decreased cardiac conduction rate, bronchospasm or increased gastrointestinal activity etc), these may be treated by the intravenous administration of Glycopyrronium Bromide Injection 200 – 600 micrograms (0.2 – 0.6mg) or atropine 400 – 1200 micrograms (0.4 – 1.2mg).' Sections 4.1 to 4.8 were retrieved without a truncation marker; the MHRA Products listing dates the SPC 2026-05-01.

Paediatric dose

Dose: Paediatric population (as printed in the SPC): 0.02 ml/kg intravenously over a period of 10 to 30 seconds (equivalent to glycopyrronium bromide 0.01 mg/kg with neostigmine metilsulfate 0.05 mg/kg); these doses may be repeated if adequate reversal of neuromuscular blockade is not achieved
Route: Intravenous injection over 10 to 30 seconds
Frequency: Single injection; may be repeated if adequate reversal of neuromuscular blockade is not achieved
Max: Total doses in excess of 2 ml are not recommended
As printed in SPC §4.2 'Paediatric population' for the fixed-dose combination (glycopyrronium bromide 0.5 mg/ml and neostigmine metilsulfate 2.5 mg/ml), not scaled from the adult dose. The SPC prints no age range, minimum age or weight band for the 'Paediatric population' paragraph and gives no neonate-specific dose; none is written here. §4.2 (verbatim): 'Total doses in excess of 2ml are not recommended as this dose of Neostigmine may produce depolarising neuromuscular block.' This is the combination product only; single-agent neostigmine and glycopyrronium dosing is not covered.

Dose adjustments

Renal

No numerical renal dose adjustment is printed. §4.4: administer with caution to patients with renal impairment.

Hepatic

No hepatic dose adjustment or hepatic information is printed in the SPC.

Dose independently re-sourced from UK Summary of Product Characteristics (SPC) via MHRA Products — clinician-reviewed. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

  • Hypersensitivity to glycopyrronium bromide or neostigmine metilsulfate or to any of the excipients listed in section 6.1 (§4.3)
  • Mechanical obstruction of the gastrointestinal or urinary tracts (§4.3)
  • Concomitant use with suxamethonium, as neostigmine potentiates the depolarising myoneural blocking effects of this agent (§4.3)
  • Anticholinesterase-antimuscarinic combinations such as neostigmine plus glycopyrronium should be avoided in patients with a prolonged QT interval (§4.3)

Side effects

  • Glycopyrronium bromide component: dry mouth, difficulty in micturition, cardiac dysrhythmias, disturbances of visual accommodation and inhibition of sweating (§4.8)
  • Neostigmine component: nausea, vomiting, increased salivation, diarrhoea, abdominal cramps (more marked with higher doses) (§4.8)
  • Signs of overdosage: bronchoconstriction, increased bronchial secretions, lacrimation, excessive sweating, involuntary defecation and micturition, miosis, nystagmus, bradycardia, photophobia, heart block, arrhythmias, hypotension, agitation, excessive dreaming, and weakness eventually leading to fasciculation and paralysis (§4.8)
  • Hypersensitivity, angioedema and anaphylactic reaction; frequency not known (§4.8)
  • Total doses in excess of 2 ml: the neostigmine dose may produce depolarising neuromuscular block (§4.2)

Interactions

  • Suxamethonium: neostigmine enhances its effects; this product should not be given in conjunction with suxamethonium (§4.5, §4.3)
  • Non-depolarising muscle relaxants: neostigmine antagonises their effects (§4.5)
  • Aminoglycosides: effects of neostigmine are antagonised (§4.5)
  • Clindamycin: effects of neostigmine are antagonised (§4.5)
  • Lithium: effects of neostigmine are antagonised (§4.5)
  • Polymyxins: effects of neostigmine are antagonised (§4.5)
  • Procainamide and quinidine: effects of neostigmine are antagonised; propafenone: effects of neostigmine possibly antagonised (§4.5)
  • Propranolol: effects of neostigmine are antagonised (§4.5)
  • Chloroquine and hydroxychloroquine: effects of neostigmine may be diminished because of their potential to increase symptoms of myasthenia gravis (§4.5)
  • Antimuscarinics: effects of parasympathomimetics are antagonised; many drugs have antimuscarinic effects, and concomitant use of two or more such drugs can increase side-effects such as dry mouth, urine retention and constipation, and can lead to confusion in the elderly (§4.5)

Monitoring

  • Administer with caution to patients with bronchospasm (extreme caution), bradycardia, arrhythmias, recent myocardial infarction, epilepsy, hypotension, parkinsonism, vagotonia, peptic ulceration, hyperthyroidism, renal impairment or glaucoma (§4.4)
  • Administration of anticholinesterase agents to patients with intestinal anastomoses may produce rupture of the anastomosis or leakage of intestinal contents (§4.4)
  • Use with caution in coronary artery disease, congestive heart failure, cardiac dysrhythmias, hypertension or thyrotoxicosis, although the combination has less impact on the cardiovascular system than atropine with neostigmine (§4.4)
  • In patients with myasthenia gravis, quaternary ammonium compounds in large dose have been shown to block nicotinic muscle end plate receptors; this must be evaluated prior to administration (§4.4)
  • Use cautiously in pyrexial patients because of inhibition of sweating (§4.4)
  • Reversal of residual non-depolarising neuromuscular block; repeat dosing only if adequate reversal is not achieved, keeping the total within 2 ml (§4.2)

Clinical monograph

How it works

Neostigmine inhibits acetylcholinesterase, raising acetylcholine at the neuromuscular junction to overcome competitive blockade, while glycopyrronium blocks muscarinic receptors to prevent bradycardia and excess secretions.

Prescribing in practice

  • Give only once spontaneous neuromuscular recovery has begun (some twitch response present) — administering neostigmine in deep or complete block can deepen weakness and precipitate post-operative residual curarisation.
  • The fixed antimuscarinic pairing limits muscarinic effects (bradycardia, bronchospasm, salivation), but watch for tachyarrhythmia from glycopyrronium and have atropine available.
  • Use with caution in asthma, peptic ulcer disease and bradyarrhythmias, and note it does not reverse aminosteroid block as predictably or rapidly as a selective binding agent in deep blockade.

Monitoring

Confirm adequacy of reversal with quantitative neuromuscular monitoring (train-of-four) alongside heart rate, respiratory effort and airway secretions before extubation.

Counselling the patient

  • This medicine is given by the anaesthetist to wake up your muscles after the operation.
  • Report any persistent weakness, double vision or difficulty breathing after surgery.

Evidence & guidelines

Anticholinesterase reversal with a co-administered antimuscarinic is a long-standing, guideline-recognised anaesthetic technique.

Reference: AAGBI Guidelines on Neuromuscular Blockade Monitoring; Blobner et al. (sugammadex vs neostigmine); Miller's Anaesthesia; 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).

Related

Curated clinical cross-links plus same-class fallbacks.

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