Dose and Administration ^{3, 4, 5, 6, 7}

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.

Indications

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

Contraindications ⁵

1. Mechanical obstruction of intestinal or urinary tract
2. Peritonitis

Precautions ⁵

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

Drug Interactions ⁵

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

Clinical Pharmacology ^3,4

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

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

Special Considerations

1. Overdosage may cause cholingeric crisis.  Keep atropine available to counteract muscarinic effect.
2. 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.
3. Hypersensitivity reactions reversible with atropine 20 micrograms/kg/ IV.
4. Drug therapy for transient neonatal myasthenia gravis is rarely required beyond 8 weeks of age.
5. 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).