NEOSTIGMINE METHYL SULPHATE INJECTION INTRAMED 0,5 mg/1 mL; NEOSTIGMINE METHYL SULPHATE INJECTION INTRAMED 2,5 mg/1 mL; NEOSTIGMINE METHYL SULPHATE INJECTION INTRAMED 2,5 mg/mL 5 mL vial

INDICATIONS CONTRA-INDICATIONS DOSAGE SIDE-EFFECTS PREGNANCY OVERDOSE IDENTIFICATION PATIENT INFORMATION

NEOSTIGMINE METHYL SULPHATE INJECTION INTRAMED 0,5 mg/1 mL
NEOSTIGMINE METHYL SULPHATE INJECTION INTRAMED 2,5 mg/1 mL
NEOSTIGMINE METHYL SULPHATE INJECTION INTRAMED 2,5 mg/mL 5 mL vial

SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form):

NEOSTIGMINE METHYL SULPHATE INJECTION INTRAMED 0,5 mg/1 mL
NEOSTIGMINE METHYL SULPHATE INJECTION INTRAMED 2,5 mg/1 mL
NEOSTIGMINE METHYL SULPHATE INJECTION INTRAMED 2,5 mg/mL 5 mL vial

COMPOSITION:
Each 1 mL contains 0,5 mg Neostigmine methyl sulphate
Each 1 mL contains 2,5 mg Neostigmine methyl sulphate
The vials contain 0,45% m/v phenol as preservative

PHARMACOLOGICAL CLASSIFICATION;
A5.3 Cholinomimetics (cholinergics)

PHARMACOLOGICAL ACTION:
Neostigmine is a reversible cholinesterase inhibitor. It is a quaternary ammonium compound and is absorbed poorly after oral administration. Neostigmine is destroyed by plasma esterases. The quaternary alcohol thus formed and the parent compound are excreted in the urine.

INDICATIONS:

–	Atony of the smooth muscle of the gastro-intestinal tract: Paralytic ileus and abdominal distension;
–	Atony of the smooth muscle of the urinary bladder: Post operative dysuria;
–	Myasthenia gravis
–	The 2,5 mg/mL injection: Termination of the effects of competitive neuromuscular blocking agents such as d-tubocurarine and gallamine.

CONTRA-INDICATIONS:
Mechanical intestinal or urinary obstruction. In conjunction with depolarising muscle relaxants, such as suxamethonium. During cyclopropane or halothane anaesthesia, although it may be used after withdrawal of these agents. Patients with diabetes, gangrene or peritonitis. Pregnancy and lactation.

WARNINGS:
When Neostigmine Methylsulphate injection is used for myasthenia gravis; absence of clinical improvement may be indicative of overdosage or underdosage. Overdosage may lead to a cholinergic crisis characterised by muscle weakness affecting respiration. Increase in the severity of the disease may lead to myasthenic crisis also characterised by severe muscle weakness. Differential diagnosis can be aided by the edrophonium chloride test. If 0,1 mL (1 mg) or at most 0,2 mL (2 mg) of edrophonium chloride is given intravenously, a marked improvement indicates myasthenic crisis. Any other response, whether equivocal or exacerbation of symptoms, must be considered to be cholinergic in origin.

DOSAGE AND DIRECTIONS FOR USE:
Childrens dose:
A suggested dose for children is 50 µg per kg body mass.

Paralytic ileus, abdominal distension or dysuria:
0,5 to 1,0 mg subcutaneously or intra-muscularly;

Termination of the effects of neuromuscular blockade:
2 to 3 mg given by slow intravenous injection over a period of 60 seconds. Additional neostigmine may be given until the muscle power is normal but a total of 5 mg should not be exceeded.
Atropine sulphate may be given concomitantly at a dose of 0,6 –1,2 mg to control adverse effects. The recommended ratio of atropine to neostigmine given, varies from 1:2 to 1:3

Myasthenia gravis:
1 to 2,5 mg daily in divided doses subcutaneously or intramuscularly.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Salivation, anorexia, nausea and vomiting. Abdominal cramps and diarrhoea may occur. Muscle cramps, fasciculation and weakness may also occur.
Should be used with caution in elderly patients and in patients with pre-existing cardiac rhythm disturbances. As neostigmine is excreted mainly by the kidneys, caution is advised in cases of impaired renal function.
Should be used with caution in patients with bradycardia, bronchial asthma, recent coronary occlusion, epilepsy, hypotension, Parkinsonism, peptic ulceration or vagotonia. Also to be used with caution in patients with myasthenia gravis to avoid provoking a cholinergic crisis with increased muscular weakness.

INTERACTIONS:
Certain antibiotics such as neomycin, streptomycin and kanamycin have a non-depolarising blocking action which may accentuate neuromuscular block. These agents must be used with care in conjunction with neostigmine in patients with myasthenia gravis.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
Symptoms of overdosage include sweating lachrymation, watery nasal discharge, eructation, involuntary defaecation and urination, flushing, miosis, conjunctival congestion, ciliary spasm, brow ache, nystagmus, restlessness, agitation, fear, excessive dreaming, hallucinations, increased bronchial secretion combined with bronchoconstriction, bradycardia and hypotension, scattered fasciculations and eventually severe weakness and paralysis, convulsions and coma. Paradoxical effects may also occur due to interaction between nicotinic and muscarinic actions. Accordingly there may be tachycardia and hypertension.
Death may follow due to cardiac arrest or central respiratory paralysis and pulmonary oedema. The major symptom of overdosage in myasthenia gravis is increased muscular weakness.

Treatment:
Give atropine sulphate 1 –2 mg intravenously, intramuscularly, or subcutaneously to control the muscarinic effects. This dose may be repeated every 2 – 4 hours as necessary. Further treatment is symptomatic and supportive.

IDENTIFICATION:
Clear colourless solution in amber ampoules or vials

PRESENTATION:
Boxes of 10 ampoules or vials

STORAGE INSTRUCTIONS:
Store below 25°C. Protect from light.
KEEP OUT OF REACH OF CHILDREN

REGISTRATION NUMBER:
C 907 (Act 101/1965) 0,5 mg/mL Injection
W/5.3/260 2,5 mg/mL Injection
W/5.3/403 2,5 mg/mL Injection (5 mL vial)

NAME AND BUSINESS ADDRESS OF APPLICANT:
INTRAMED (Pty) Ltd.
6 Gibaud Road
6001 Port Elizabeth

DATE OF PUBLICATION OF THIS PACKAGE INSERT:

September 1970	12-268/9-92
	KOHLER C&P P.E.