INFORMATION FOR HEALTH PROFESSIONALS
Home | Consumers | Health Professionals | Regulatory | Other | Hot Topics | Search
Home | Consumers | Health Professionals | Regulatory | Other | Hot Topics | Search
Injection solution 2.5 mg/ml: a clear, colourless, particle-free solution containing 2.5 mg/ml NEOSTIGMINE METHYLSULPHATE.
Cholinestrase inhibitor which reversibly inhibits the hydrolysis of acetylcholine thereby potentiating its action.
NEOSTIGMINE is an antcholinesterase agent which inhibits reversibility the hydrolysis of acetycholine by competing with acetylcholine for attachment to acetylcholinesterase. As a result, acetylcholine accumulates at cholinergic synapses and its effects are prolonged and exaggerated.
NEOSTIGMINE is therefore capable of producing a generalised cholinergic response, including meiosis, increased tonus of intestinal and skeletal musculature, constriction of bronchi and ureters, bradycardia and stimulation of salivary and sweat glands. In addition NEOSTIGMINE has a direct cholinomimetic effect on skeletal muscle and to a lesser extent to increase the activity of smooth muscle.
Because of its quaternary ammonium structure, in moderate doses, NEOSTIGMINE does not cross the blood-brain barrier to produce CNS effects. Extremely high doses, however, produce CNS stimulation followed y CNS depression.
Following IV administration the elimation half-life ranges from 47 to 60 minutes and after IM administration 50 to 91 minutes. Approximately 80 % of a single IM dose of NEOSTIGMINE is excreted in the urine in 24 hours, about 50 % as unchanged NEOSTIGMINE and the remainder as metabolites. The major site of uptake is in the liver. It is metabolised partly by the hydrolysis of the ester linkage and partly by microsomal enzymes in the liver.
Reversal of the effects of nondepolarising neuromuscular blocking agents (e.g. tubocurarine, pancuronium, etc.) Prophylaxis and treatment of post-operative urinary retention. Also treatment of myasthenia gravis during acute exacerbations, when the condition is severe or in neonates.
Usually, reversal of neuromuscular blockade with NEOSTIGMINE Injection BP should not be attempted until spontaneous recovery from paralysis is evident. It is recommended that the patient be well ventilated and patent airway maintained until complete recovery of normal respiration is affirmed.
A single dose of NEOSTIGMINE 2 to 3 mg with atropine sulphate 0.6-1.2 mg by slow IV injection over 1 minute. The recommended ratio of atropine to NEOSTIGMINE is 1:2 to 1:3. The maximum recommended dose of NEOSTIGMINE in adults is 5 mg.
The suggested dose in children is 0.05 mg/kg/dose and atropine sulphate 0.02 mg/kg/dose by slow IV injection. Maximum recommended dose of NEOSTIGMINE in children is 2.5 mg.
The NEOSTIGMINE and atropine are often given simultaneously, but in patients with bradycardia, the pulse rate should be increased to about 80 beats/minute with atropine before administering NEOSTIGMINE.
The speed of recovery from neuromuscular blockade is primarily determined by the intensity of the block at the time of antagonism. It is also influenced by other factors including the presence of drugs (eg. anaesthetic drugs, antibiotics and antiarrhythmic drugs) and physiological changes (eg. electrolyte and acid-base imbalance, renal impairment). These factors may prevent successful reversal with NEOSTIGMINE Injection BP or lead to re-curarisation after apparently successful reversal. It is imperative that the patients should not be left unattended until these possibilities have been excluded.
1 mg to 2.5 mg given IM or SC at intervals throughout the day when greater strength may be needed (e.g. mornings and before meals), given a total daily dose of 5 to 20 mg. Duration of action of a single dose is 2 to 4 hours.
0.05-0.25 mg IM every 2-4 hours, half an hour before feeding. Treatment is not usually required beyond 8 weeks of age. Because the condition is usually self limiting the daily dosage should gradually be reduced until the medicine can be withdrawn.
When large doses of NEOSTIGMINE are given to myasthenic patients, atropine sulphate may be required to counteract the muscarinic side effects.
0.25 mg SC or IM before or immediately after the operation, repeated every 4 to 6 hours for 2-3 days.
0.5 mg SC or IM and apply warmth to lower abdomen. After patient has voided continue 0.5 mg SC or IM every 3 hours for at least 5 injections. If there has been no urinary response within one hour of the first dose, the patient should be catheterised.
Mechanical obstruction of intestinal or urinary tract. Known hypersensitivity to NEOSTIGMINE. Peritonitis.
Neostigmine should be used with extreme caution in patients who have undergone recent intestinal or bladder surgery and in patients with bronchial asthma.
Use with caution in patients with cardiac disease and cardiovascular disorders including arrhythmias, bradycardia, recent myocardial infarction or coronary occlusion, and hypotension as well as in patients with, epilepsy, vagotonia, parkinsonism or peptic ulceration, renal impairment, Addison's disease or hyperthyroidism.
With large doses, simultaneous parenteral administration of atropine sulphate may be advisable. Atropine sulphate should always be available along with other anti-shock mediations (adrenaline) in case of hypersensitivity to NEOSTIGMINE.
NEOSTIGMINE may prolong the depolarising neuromuscular blocking action of depolarising muscle relaxants such as suxamethonium and prolonged apnoea may result (see INTERACTIONS).
NEOSTIGMINE should not be given whilst anaesthesia with cyclopropane and halothane continues but may be used after withdrawal of these agents.
As the severity of myasthenia gravis can fluctuate considerably, care is required to avoid cholinergic crisis due to overdosage with NEOSTIGMINE (see OVERDOSE).
Caution should be exercised when used on the post-surgical patient as respiratory problems caused by post-operative pain or sedation may be potentiated/aggravated.
Category B2
The maternal need for NEOSTIGMINE may be absolute in the context of myasthenia gravis. Cholinergic effects in the neonate are rare.
The safety of NEOSTIGMINE in pregnancy has not been established with respect to possible adverse effects on foetal development. Anticholinesterase agents may cause uterine irritability and induce premature labour when given IV to pregnant women near term. Therefore NEOSTIGMINE should not be used in pregnant women or those likely to become pregnant unless the expected benefits outweigh any potential risk.
Evidence indicates that only negligible amounts of NEOSTIGMINE enter the breast milk, nevertheless the possibility of adverse effects on the breast-feeding infant should be considered.
Adverse reactions generally associated with NEOSTIGMINE overdosage are:
Cardiac arrhythmias (especially bradycardia), hypotension, cardiac arrest, syncope.
Headache, dizziness, convulsions, loss of consciousness, coma, drowsiness, restlessness, ataxia, slurred speech, agitation and fear.
Nausea, vomiting, diarrhoea, flatulence, abdominal cramps, increased peristalsis and involuntary defaecation.
Involuntary urination or desire to urinate.
Muscle cramps, fasciculation, general weakness and paralysis.
Increased oral, pharyngeal and bronchial secretion, dyspnoea, bronchospasm, respiratory depression, respiratory failure, tight chest and wheezing.
Allergic reactions including anaphylaxis.
Rash and urticaria
Increased sweating and salivation, miosis, vision changes, nystagmus and lacrimation.
Corticosteroids may decrease the anticholinesterase effects of NEOSTIGMINE. Conversely anticholinesterase effects may increase after stopping corticosteroids.
NEOSTIGMINE may prolong the Phase 1 block of depolarising muscle relaxants such as suxamethonium. Prolonged respiratory depression with extended periods of apnoea may occur.
Atropine reverses the muscarinic effects of NEOSTIGMINE. This interaction is used to counteract the muscarinic symptoms of NEOSTIGMINE toxicity, however masking the signs of overdosage can lead to inadvertent induction of cholinergic crisis with the use of atropine.
Anticholinesterase agents can be effective in reversing neuromuscular block induced by aminoglycoside antibiotics. Aminoglycoside antibiotics, local and some general anaesthetics, antiarrhythmic agents and other drugs that interfere with neuromuscular transmission should be used cautiously, if at all, in patients with myasthenia gravis. The dose of NEOSTIGMINE may need to be increased accordingly.
Quinine, chloroquinine, hydroxychloroquine and lithium may reduce the effectiveness of treatment with NEOSTIGMINE.
Overdosage with NEOSTIGMINE can cause cholinergic crisis, which is characterised by increasing muscle weakness. Myasthenic crisis is due to an increase in severity of the disease and may be difficult to distinguish from cholinergic crisis on a symptomatic basis. Cholinergic crisis can lead to respiratory paralysis, which may result in death, while myasthenic crisis is extreme muscle weakness. The differentiation between the two crises is extremely important as treatment is different for each. The two types of crises can be differentiated by the use of edrophonium and clinical judgement.
Signs of overdosage due to muscarinic effects may include abdominal cramps, increased peristalsis, diarrhoea, nausea and vomiting, increased bronchial secretion, salivation, diaphoresis and miosis. Nicotinic effects consist of muscular cramps, fasciculations and general weakness. Bradycardia and hypotension may also occur.
The treatment of cholinergic crisis requires the discontinuation of all cholinergic medication. The immediate use of atropine is also recommended, muscarinic effects are controlled with IV atropine sulfate (1 to 2 mg) followed by IM atropine sulfate every 2 to 4 hours. Assistance of ventilation may be required if respiration is severely depressed.
18 months <25°c
Protect from light
Prescription Medicine.
2.5 mg/mL: 10 x 1 mL Polyamp® Duo Fit®.
NEOSTIGMINE Injection BP is a clear, colourless sterile solution of NEOSTIGMINE methylsulphate with sodium chloride, monobasic sodium phosphate, dibasic sodium phosphate and Water for Injections BP at pH 4.5 to 6.5.
The presentations of NEOSTIGMINE Injection BP solution contain no antimicrobial agents. They are intended for single use only and any solution remaining from an opened container should be discarded.
AstraZeneca Limited
303 Manukau Rd
Epsom
PO Box 1301
Auckland.
Ph: (09) 623 6300
30 October 2003
TGA Approved: 12/9/96 (date of safety related changes 18 June 2003).