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Drug Reference

neostigmine

anticholinesterase· Brands: ProstigminIMIVPOSC

Mechanism of action
Neostigmine reversibly inhibits acetylcholinesterase, the enzyme that breaks down acetylcholine at cholinergic synapses. This increases the concentration of acetylcholine in the synaptic cleft, prolonging and enhancing cholinergic transmission at both muscarinic and nicotinic receptors. As a quaternary ammonium compound, it does not cross the blood-brain barrier, so it acts peripherally.
Pharmacokinetics
Neostigmine is poorly absorbed orally and is usually given parenterally. After intravenous administration, onset of action is rapid, within minutes, and duration is approximately 20 to 60 minutes, depending on the dose and route. It is metabolised by plasma cholinesterases and hepatic enzymes, and the metabolites and unchanged drug are excreted in the urine. In renal impairment, clearance is reduced and the duration of action is prolonged. It does not cross the blood-brain barrier due to its quaternary structure.
Indications & dosing

Myasthenia gravis

Long-term management. Take with food to reduce gastrointestinal side effects. Dose is individualised.

  • adult · PO: 15 mg every 3-4 hours · Long-term management. Take with food to reduce gastrointestinal side effects. Dose is individualised.

Reversal of non-depolarising neuromuscular blockade

Administer with an antimuscarinic (e.g. glycopyrrolate or atropine) to prevent bradycardia.

  • adult · IV: 0.025–0.07 mg/kg single dose · 25-70 micrograms/kg (typically 2.5-5 mg in a 70 kg adult; maximum single dose 5 mg). Administer with an antimuscarinic (e.g. glycopyrrolate or atropine) to prevent bradycardia.
Contraindications & precautions
  • Hypersensitivity to neostigmine or other anticholinesterases · Cross-sensitivity may occur with other agents in this class.
  • Mechanical intestinal or urinary tract obstruction · Increased peristalsis or bladder contraction may worsen the obstruction.
  • Peritonitis · Risk of exacerbation of bowel perforation or inflammation.
  • Severe bradycardia or heart block · Cholinergic stimulation may cause further slowing of heart rate.
  • Have atropine available to counter muscarinic adverse effects, particularly bradycardia and bronchospasm.
  • Use with caution in patients with asthma or chronic obstructive pulmonary disease, as bronchospasm may be precipitated.
  • Use with caution in patients with bradycardia, recent myocardial infarction, or other cardiac disorders, as these may be worsened.
  • In myasthenia gravis, distinguish between cholinergic crisis (overdosage) and myasthenic crisis (underdosage), as symptoms may overlap.
  • Reduce the dose in patients with renal impairment, as neostigmine is excreted unchanged in urine.
  • Use with caution in patients with epilepsy, as anticholinesterases may lower the seizure threshold.
Adverse effects
  • Bradycardiaserious
  • Increased salivation
  • Sweating
  • Nausea and vomiting
  • Abdominal cramps and diarrhoea
  • Bronchospasmserious
  • Hypotensionserious
  • Muscle fasciculations
  • Respiratory depressionserious
  • Cardiac arrhythmiasserious
Renal & hepatic adjustment
  • eGFR 30–50: No dose change required; use with caution
  • eGFR 10–30: Reduce dose by 50%
  • eGFR 0–10: Reduce dose to 25% of normal; avoid if possible
Monitoring, pregnancy & toxicity
  • Heart rate · During IV administration and in the setting of cholinergic effects
  • Blood pressure · During IV administration
  • Respiratory function · Especially in patients with asthma or chronic lung disease
  • Muscle strength · In myasthenia gravis, to assess response
  • Signs of cholinergic toxicity · Throughout therapy
  • Pregnancy: Use only if potential benefit justifies risk. Animal data inconclusive, human data limited. For myasthenia gravis, specialist consultation advised.
  • Toxicity: Bradycardia, hypotension, and syncope · Stop drug, give IV atropine (0.5–1 mg) repeated as needed, supportive measures
  • Toxicity: Bronchospasm and excessive pulmonary secretions · Stop drug, atropine IV, oxygen, bronchodilators, suction
  • Toxicity: Abdominal cramps, vomiting and diarrhoea · Stop drug, atropine IV, fluid and electrolyte replacement
  • Toxicity: Muscle weakness including respiratory paralysis · Stop drug, atropine IV, ensure airway and ventilator support
Antidotes & reversal
  • Atropine · Excessive muscarinic effects (bradycardia, secretions, bronchospasm): atropine 0.5-1 mg IV.
Clinical notes
Neostigmine is used for the reversal of non-depolarising neuromuscular blockade after surgery, and in the management of myasthenia gravis. It may also be used for the treatment of postoperative ileus or urinary retention. Muscarinic adverse effects include bradycardia, bronchospasm, salivation, diarrhoea, and abdominal cramps. Atropine or glycopyrrolate is often co-administered to prevent these effects. Caution is required in patients with asthma, ischaemic heart disease, bradycardia, or intestinal obstruction. The dose should be reduced in renal impairment. Neostigmine is a reversible inhibitor, so it is less toxic than organophosphates.

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BNF; local formulary