neostigmine bromide
Prostigmin

neostigmine methylsulfate
Prostigmin

Available forms
Available by prescription only
Injection: 0.25 mg/ml, 0.5 mg/ml, 1 mg/ml
Tablets: 15 mg

Indications and dosages
 Antidote for nondepolarizing neuromuscular blockers. Adults: 0.5 to 2 mg slow I.V. Repeat, p.r.n. Maximum total dose, 5 mg. Give 0.6 to 1.2 mg atropine sulfate I.V. before antidote dose if patient is bradycardic.
Neonates, infants, and children: 0.04 mg/kg/dose I.V. with atropine sulfate (0.02 mg/kg atropine) with each dose of neostigmine.
 Prevention of postoperative abdominal distention and bladder atony. Adults: 0.25 mg I.M. or S.C. q 4 to 6 hours for 2 to 3 days.
 Treatment of postoperative abdominal distention and bladder atony. Adults: 0.5 to 1 mg S.C. or I.M. If given for urine retention and there’s no response in 1 hour, catheterize patient and repeat dose q 3 hours for five doses after bladder is emptied.
 Diagnosis of myasthenia gravis ◇. Adults: 0.022 mg/kg I.M. Give atropine 0.011 mg/kg I.V. with dose or I.M. 30 minutes before dose. If cholinergic reaction occurs, stop test and give atropine sulfate 0.4 to 0.6 mg I.V. If the results are inconclusive, retest on another day using 0.031 mg/kg I.M. of neostigmine preceded by atropine 0.016 mg/kg I.M.
Children: 0.025 to 0.04 mg/kg I.M. preceded by 0.011 mg/kg S.C. of atropine sulfate.
 Symptomatic control of myasthenia gravis. Adults: 0.5 to 2.5 mg S.C., I.V., or I.M. Oral dose can range from 15 to 375 mg daily (average 150 mg in 24 hours). Subsequent dosages must be individualized, based on response and tolerance of adverse effects. Therapy may be required day and night.
Children: 7.5 to 15 mg P.O. t.i.d. or q.i.d. Or, 0.333 mg/kg or 10 mg/m² P.O. six times daily.
Neonates: 0.1 to 0.2 S.C. or 0.03 mg/kg I.M. q 2 to 4 hours or 1 to 4 mg P.O. q 2 to 3 hours. Gradual dose reduction as symptoms improve.
 Supraventricular tachycardia from tricyclic antidepressant overdose ◇. Children: 0.5 to 1 mg I.V. followed by 0.25 to 0.5 mg q 1 to 3 hours, p.r.n.
 Decrease small bowel transit time during radiography ◇. Adults: 0.5 to 0.75 mg S.C.

Pharmacodynamics
Muscle stimulant action: Neostigmine blocks hydrolysis of acetylcholine by cholinesterase, resulting in acetylcholine accumulation at cholinergic synapses, which leads to increased cholinergic receptor stimulation at the myoneural junction.

Pharmacokinetics
Absorption: Poorly absorbed (1% to 2%) from GI tract after oral administration.
Distribution: About 15% to 25% of dose binds to plasma proteins.
Metabolism: Hydrolyzed by cholinesterases and metabolized by microsomal liver enzymes. Duration of effect varies considerably, depending on patient’s physical and emotional status and on disease severity.
Excretion: About 80% of dose is excreted in urine as unchanged drug and metabolites in the first 24 hours after administration.

Contraindications and precautions
Contraindicated in patients hypersensitive to cholinergics or to bromide and in those with peritonitis or mechanical obstruction of the intestine or urinary tract. Use cautiously in patients with bronchial asthma, bradycardia, seizure disorders, recent coronary occlusion, vagotonia, hyperthyroidism, arrhythmias, and peptic ulcer.

Interactions
Drug-drug. Atropine, corticosteroids, magnesium, procainamide, quinidine: May reverse cholinergic effect of neostigmine on muscle. Observe patient for drug effect.
Cholinergic drugs: May cause additive toxicity. Avoid use together.
Succinylcholine: May prolong respiratory depression. Monitor patient carefully.

Adverse reactions
CNS: dizziness, seizures, headache, muscle weakness, loss of consciousness, drowsiness, syncope.
CV: bradycardia, hypotension, tachycardia, AV block, cardiac arrest, flushing.
EENT: blurred vision, lacrimation, miosis.
GI: nausea, vomiting, diarrhea, abdominal cramps, excessive salivation, flatulence, increased peristalsis.
GU: urinary frequency.
Musculoskeletal: muscle cramps, muscle fasciculations, arthralgia.
Respiratory: bronchospasm, dyspnea, respiratory depression, respiratory arrest, increased secretions.
Skin: rash, urticaria, diaphoresis.
Other: hypersensitivity reactions (anaphylaxis).

Effects on lab test results
None reported.

Overdose and treatment
Signs and symptoms of overdose include headache, nausea, vomiting, diarrhea, blurred vision, miosis, excessive tearing, bronchospasm, increased bronchial secretions, hypotension, incoordination, excessive sweating, muscle weakness, cramps, fasciculations, paralysis, bradycardia or tachycardia, excessive salivation, and restlessness or agitation.
 Discontinue drug immediately. Support respiration; bronchial suctioning may be performed. Atropine may be given to block muscarinic effects of neostigmine, but it won’t counter paralytic effects of drug on skeletal muscle. Avoid atropine overdose because it may lead to bronchial plug formation.

Special considerations
• If muscle weakness is severe, determine if it stems from drug toxicity or from worsening of myasthenia gravis. A test dose of edrophonium I.V. will aggravate drug-induced weakness but will temporarily relieve disease-related weakness.
• Give drug with food or milk to reduce the chance for GI adverse effects.
• To diagnose myasthenia gravis, discontinue all anticholinergics for at least 8 hours before neostigmine administration.
• When giving drug to patient with myasthenia gravis, schedule largest dose before anticipated periods of fatigue. If patient has dysphagia, schedule this dose 30 minutes before each meal.
• Stop all other cholinergic drugs during neostigmine therapy because of risk of additive toxicity.
• When giving neostigmine to prevent abdominal distention and GI distress, inserting a rectal tube may help passage of gas.
• Administering atropine with neostigmine can relieve or eliminate adverse reactions; these symptoms may indicate neostigmine overdose and will be masked by atropine.
• Patients may develop resistance to drug.
 ALERT Don’t confuse neostigmine with etomidate (Amidate) vials. They may look alike.
Breast-feeding patients
• Neostigmine may appear in breast milk, possibly resulting in infant toxicity. Evaluate patient’s clinical status to see if breast-feeding or drug should be discontinued.
Pediatric patients
• Safety and efficacy in children haven’t been fully established.
Geriatric patients
• These patients may be more sensitive to effects of neostigmine. Use cautiously.

Patient education
• Instruct patient to observe and record changes in muscle strength.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use