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Drug dosage identifier

Neostigmine methylsulphate

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Dose and administration

  1. Myasthenia gravis

      Route Dose
    Test Dose: IM  150 microgram/kg
    Always have Atropine 20 micrograms/kg available to control undue salivation. 

    Alternatively, Edrophonium may be given (20 micrograms/kg IV followed, after 30 seconds,
    by 80 micrograms/kg IV if no adverse effect [watch for bradycardia or arrhythmia])
     Maintenance:  IM or SC  150 micrograms/kg every 6 to 8 hours.

    Higher doses (300 micrograms/kg Q4H may be necessary)
    PO  An oral dose of Neostigmine bromide 10-20 times the IM maintenance dose of
    Neostigmine methylsulphate every 3 hours.

    Other longer acting preparations (e.g. pyridostigmine) may be preferable.
  2. Reversal of non-depolarising neuromuscular blocking agents (e.g. pancuronium)
    Usually reversed with atropine 20 micrograms/kg IV followed by one (or occasionally 2) 40 microgram/kg/dose of neostigmine.


  • Diagnosis and management of transient neonatal and persistent (congenital) myasthenia gravis.
  • Reversal of the effects of neuromuscular blocking agents.


  • Mechanical obstruction of intestinal or urinary tract
  • Peritonitis


  1. Cardiac disease
  2. Seizures
  3. Hypotension
  4. Peptic ulceration
  5. Hyperthyroidism
  6. Asthma

Drug interactions

  1. Corticosteroids: decrease in anticholinesterase effect of neostigmine. Conversely, the anticholinesterase effect may be increased after stopping corticosteroids.
  2. Atropine: reversal of muscarinic effect of neostigmine.
  3. Aminoglycoside: neostigmine may reverse the neuromuscular blockade induced by aminoglycoside antibiotics.
  4. Depolarising muscle relaxants (eg. suxamethonium): prolongation of blockade.

Clinical pharmacology

Neostigmine prolongs and intensifies the physiological activity of acetylcholine by anticholinesterase activity which is reversible. It is poorly absorbed from the gastrointestinal tract, and CNS penetration is poor. Neostigmine causes vasodilation, increased smooth muscle activity, lacrimation, salivation and increased voluntary muscle tone. It is the preferred agent over edrephonium for the management of neonatal myasthenia gravis, owing to its more prolonged effect (2 to 4 hours), however does have a slower onset of action (20 - 30 minutes).

Possible adverse effects

  • Gastrointestinal disturbances (vomiting, abdominal cramps, increased peristalsis).
  • Respiratory depression and/or arrest.
  • Cardiac arrhythmias (especially bradycardia), hypotension, cardiac arrest.
  • Muscle cramps, paralysis, general weakness.
  • Rash.
  • Convulsion, restlessness, coma.

Special considerations

  • Overdosage may cause cholingeric crisis. Keep atropine available to counteract muscarinic effect.
  • Management of neostigmine overdose and/or toxicity: stop neostigmine, supportive therapy (ventilation, volume expansion etc.), control convulsions, consider administration of atropine 20 micrograms/kg IV.
  • Hypersensitivity reactions reversible with atropine 20 micrograms/kg/ IV.
  • Drug therapy for transient neonatal myasthenia gravis is rarely required beyond 8 weeks of age.
  • Reversal of the effects of neuromuscular blocking agents may be incomplete. Postoperative neonates may demonstrate hypoventilation despite partial reversal of neuromuscular blockade. These infants require close observation and monitoring. (Note: many anaesthetists do not attempt to reverse neuromuscular blockade produced during general anaesthesia).

Management of Neostigmine administration


  • Clear colourless 2.5 mg/ml (=2500mcg/ml). pH 4.5 - 6.5.
  • No proprietary oral preparation available. Refer to Pharmacy.


  • Test doses are charted on the stat page of the prescription chart in micrograms/dose.
  • Treatment doses are charted on the drug prescription chart in micrograms/dose.


Oral, IM, SC:  Administer at least 30 minutes before feeds.

Observation and documentation

  • Monitor for signs of adverse effects and cholinergic crisis.
  • Ensure atropine is available (reverses effects of neostigmine).
  • Nurse on cardiorespiratory monitor and assess respiratory function closely.
  • Ensure resuscitation equipment is available.


  • Unopened store at room temperature below 30°C.

Selected references

  1. Fisher DM, Cronnelly R, Miller RD, Sharma M. The neuromuscular pharmacology of neostigmine in infants and children. Anaesthesiology 1983; 59:220.
  2. Goudsouzian NG, Crone RK, Todres ID. Recovery from pancuronium blockade in the neonatal intensive care unit. Br J Anaesth 1981; 53:1303.
  3. Parfitt K (Editor) Martindale: The Extra Pharmacopoeia. (32nd ed). Royal Pharmaceutical Society; 1999: London
  4. Northern Neonatal Network. Neonatal Formulary 3. London: BMJ Books,2000
  5. Neostigmine Data Sheet. Auckland: Astra Zeneca, 1999
  6. Paediatric Formulary. (5th ed.) Guy's, St. Thomas' and Lewisham Hospitals.
  7. Paediatric Pharmacopoeia (12th ed.)Royal Childrens Hospital, Melbourne

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Document Control

  • Date last published: 31 October 2001
  • Document type: Drug Dosage Guideline
  • Services responsible: ADHB Pharmacy, Neonatology
  • Editor: Sarah Bellhouse
  • Review frequency: 2 years