INTRAMED ATROPINE SULPHATE INJECTION 0,6 mg/mL; INTRAMED ATROPINE SULPHATE INJECTION 1,2 mg/mL

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

INTRAMED ATROPINE SULPHATE INJECTION 0,6 mg/mL
INTRAMED ATROPINE SULPHATE INJECTION 1,2 mg/mL

SCHEDULING STATUS:

0,6 mg/mL –	S1
1,2 mg/mL –	S2

PROPRIETARY NAME
(and dosage form):

INTRAMED ATROPINE SULPHATE INJECTION 0,6 mg/mL
INTRAMED ATROPINE SULPHATE INJECTION 1,2 mg/mL

COMPOSITION:
Atropine sulphate injection contains 0,6 mg (1,2 mg) of Atropine sulphate per mL.

PHARMACOLOGICAL CLASSIFICATION:
A 5.4 Cholinolytics

PHARMACOLOGICAL ACTION:
Atropine sulphate is an antimuscarinic agent. The major action is a competitive or surmountable antagonism to ACh (acetylcholine) and other muscarinic agents, the antagonism can therefore be overcome by increasing sufficiently the concentration of ACh at receptor sites of the effector organ, for example by anticholinesterase agents. The receptors affected are those on peripheral structures that are either stimulated or inhibited by muscarine, that is, exocrine glands and smooth and cardiac muscle. The medicine can block all muscarinic actions of ACh, and other choline esters. Responses to postganglionic cholinergic nerve stimulation may also be inhibited, but less readily than are responses to injected choline esters. The difference may be due to release of ACh by cholinergic nerve terminals so close to receptors that diffusion limits the concentration of antagonist that can be attained in the very narrow synaptic cleft. Atropine-induced parasympathetic block may be preceded by a transient phase of mild stimulation. Atropine has a potent action on heart, intestine and bronchial muscle and has a more prolonged action that scopolamine. It is absorbed rapidly from the gastrointestinal tract. It disappears rapidly from the blood and is distributed through the entire body. Atropine has a half-life of approximately 4 hours; hepatic metabolism accounts for the elimination of about half of a dose, and the remainder is excreted unchanged in the urine.
Traces of atropine are found in various secretions, including breast milk.

INDICATIONS:
Atropine is used for its parasympatholytic effects.

*	Peri-operatively: to counteract the vagal effects that may frequently occur during anaesthesia. Atropine is commonly given with neostigmine to counteract the unwanted muscarinic effects which may accompany reversal of neuromuscular blockade with neostigmine.
*	Atropine is a specific antidote for the cardiovascular collapse that may result from the injudicious administration of a choline ester or an inhibitor of cholinesterase. It is also used to antagonize reflex vagal cardiac slowing. Atropine may be of value in the initial treatment of patients with acute myocardial infarction in whom excessive vagal tone causes sinus or nodal bradycardia.
*	In the treatment of muscarinic toxicity, and in poisoning caused by pesticides that are organophosphate cholinesterase inhibitors; Atropine is a specific antidote for the so-called rapid type of mushroom poisoning due to the cholinomimetic alkaloid muscarine, found in Amanita muscaria and a few other fungi.

CONTRA-INDICATIONS:
Atropine should not be given to patients with closed-angle glaucoma or to patients with a narrow angle between the iris and the cornea, since it may increase the intra-ocular pressure and precipitate in acute attack. It is contraindicated in patients with prostatic enlargement, and in those with paralytic ileus, pyloric stenosis and status asthmaticus. It should not be given to patients with myasthenia gravis unless it is given to reduce adverse muscarinic effects of an anti-cholinesterase agent. Due to the risk of provoking hyperpyrexia atropine should not be given to patients, especially children, when the ambient temperature is high. It should also be used cautiously in patients with fever. Atropine should not be given to patients who are being treated with a monoamine-oxidase inhibitor, or within ten days of the discontinuation of such treatment. Atropine is contraindicated in case of intoxication produced by Amanita muscaria and related species due to the anticholinergic and hallucinogenic properties of a variety of isoxazole derivatives. Caution should be observed in administering this medicine to patients with coronary insufficiency or cardiac failure.

DOSAGE AND DIRECTIONS FOR USE:
Persons with Down's syndrome appear to have an increased susceptibility to the actions of atropine, whereas those with albinism may be resistant.
Premedication: to diminish the risk of vagal inhibition of the heart and to reduce salivary and bronchial secretions.

Adult dose:	IM or SC; 0,3 to 0,6 mg usually in conjunction with 10 to 15 mg of morphine sulphate about an hour before anaesthesia.
	ALTERNATIVELY
	IV; 0,3 to 0,6 mg immediately before induction of anaethesia.
Paediatric dose: SC;		weighing up to 3 kg	:	0,1 mg
		weighing 7 to 9 kg	:	0,2 mg
		weighing 12 to 16 kg	:	0,3 mg
		weighing 20 to 27 kg	:	0,4 mg
		weighing 32 kg	:	0,5 mg
		weighing 41 kg	:	0,6 mg

Post-operatively:

Adult dose:

Slow IV; 0,6 to 1,2 mg in conjunction with neostigmine to reverse the effects of non-depolarising muscle relaxants.

Arrhythmias:
Adult dose:IV; 0,4 to 1 mg and repeated as needed to a total dose of 2 mg.Bradycardia or asystole due to overdosage with parasympathomimetic agents: 1 to 2 mg SC, IM or IV.

Anticholinesterase/Organophosphate poisoning: Atropine Sulphate should be given in adequate doses. Following an initial injection of 2 to 4 mg, given intravenously if possible, otherwise intramuscularly, 2 mg should be given every 5 to 10 minutes until muscarinic symptoms disappear, if they reappear, or until signs of atropine toxicity appear. More than 200 mg may be required on the first day. A mild degree of atropine block should then be maintained for up to 48 hours or as long as symptoms are evident.

Intoxication by cholinergic agonists: Should serious toxic reactions to these drugs arise, 0,5 to 1,0 mg atropine sulphate should be given sub-cutaneously or intravenously.

Intoxication by cholinomimetics: Treatment consists of the parenteral administration of atropine and adequate measures to support the respiration and the circulation and to counteract pulmonary edema.

Mushroom poisoning:
Treatment with 1 - 2 mg atropine given intramuscularly every 30 minutes effectively blocks the muscarine intoxication symptoms.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
With larger doses, the pupil dilates, accommodation of the eyes is inhibited and vagal effects on the heart are blocked so that the heart rate is increased.
Larger doses inhibit the parasympathetic control of the urinary bladder and gastrointestinal tract thus inhibiting micturition and decreasing the tone and motility of the gut. Larger doses also cause progressively increasing tachycardia by blocking vagal effects on the S.A. pace-maker. Tolerance occurs to a limited extent. Habituation and addiction do not occur although vomiting, malaise, sweating and salivation have been recorded in patients with parkinsonism upon sudden withdrawal of the large doses required for therapeutic benefit. In the treatment of parkinsonism, increases in dosage and transfer to other forms of treatment should be gradual and antimuscarinic agents should not be withdrawn abruptly. Minor reactions may be controlled by reducing the dose until tolerance has developed. Atropine may cause mental confusion, especially in the elderly. Reduced bronchial secretion caused by systemic administration of atropine may be associated with the formation of mucous plugs.

Atropine should be used with caution in children and in geriatric patients, who may be more susceptible to its adverse effects. In patients with ulcerative colitis its use may lead to ileus or megacolon, and its effects on the lower oesophageal sphincter may exacerbate reflux. It is generally advisable to be cautious in giving atropine to any patient with diarrhoea. Atropine and other antimuscarinic agents should be used with caution in conditions characterised by tachycardia such as thyrotoxicosis, cardiac insufficiency or failure, and in cardiac surgery, where it may further accelerate the heart-rate. Care is required in patients with acute myocardial infarction as ischaemia and infarction may be made worse. Atropine should be given with care to patients with hypertension.

The effects of atropine and other antimuscarinic agents may be enhanced by the concomitant administration of other agents with antimuscarinic properties, such as amantadine, some antihistamines, butyrophenones and phenothiazines, and tricyclic antidepressants. The reduction in gastric motility caused by atropine may affect the absorption of other medicine. Additive anticholinergic adverse effects may also occur with antipsychotics, quinidine and disopyramide. The degree of absorption of digoxin may be increased.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
Delirium or toxic psychoses can occur after overdosage. Also, hallucinatory effects. Symptoms develop promptly. Vision becomes blurred and photophobia is prominent. The skin is hot, dry and flushed. A rash may appear, especially over the face, neck and upper part of the trunk; desquamation may follow. The body temperature rises and the pulse is weak and very rapid. Palpitation is prominent, and the blood pressure may be elevated. Urinary urgency and difficulty in micturition are sometimes noted. Restlessness and confusion, giddiness and muscular inco-ordination occur.
Treatment:
If marked excitement is present and more specific treatment is not available, diazepam is most suitable for sedation and for control of convulsions. Large doses should be avoided because the central depressant action may coincide with the depression occurring late in atropine poisoning. Artificial respiration with oxygen may be necessary.

IDENTIFICATION:
Atropine Sulphate Injection is a clear colourless solution filled into amber type 1 glass ampoules.

PRESENTATION:
10 x 1 mL ampoules.

STORAGE INSTRUCTIONS:
Store below 25°C. Protect from light.
Keep out of reach of children.

REGISTRATION NUMBER:
Intramed Atropine Sulphate Injection 0,6 mg/mL : J/5.4/400
Intramed Atropine Sulphate Injection 1,2 mg/mL : J/5.4/401

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

DATE OF PUBLICATION OF THIS PACKAGE INSERT:

April 1995	12-072/5-95
	Tradepak PE