4.1. Therapeutic indications

Atropine sulfate 0.5 mg/5 ml, solution for injection in pre-filled syringe is indicated in adults and in paediatric population from birth, but with a body weight superior to 3 kg (see section 4.2).- As a pre-anaesthetic medication to prevent vagal reactions associated with tracheal intubation and surgical manipulation, - To limit the muscarinic effects of neostigmine, when given postsurgically to counteract non-depolarising muscle relaxants- Treatment of hemodynamically compromising bradycardia and/ or atrioventricular block due to excessive vagal tone in emergency situation- Cardiopulmonary resuscitation: to treat symptomatic bradycardia and AV block As antidote following overdosage or poisoning with acetylcholinesterase-inhibitors e.g. anticholinesterases, organophosphorus, carbamates and muscarinic mushrooms

4.2. Posology and method of administration

Atropine sulfate 0.5 mg/5 ml, solution for injection in pre-filled syringe must be administered under medical supervision. Posology:

Pre-anaesthetic medication

Intravenous administration immediately before surgery; if necessary an intramuscular administration 30-60 minutes before surgery is possible. Adults:

0.3 – 0.6 mg IV (3 – 6 ml) Paediatric population:

The usual dose in children is between 0.01-0.02 mg/kg body weight (maximum 0.6 mg per dose), dosage should be adjusted according to the patient's response and tolerance.In combination with neostigmine to limit its muscarinic effects: Adults:

0.6-1.2 mg IV (6 to 12 ml) Paediatric population

0.02 mg/kg IV Treatment of hemodynamically compromising bradycardia, atrioventricular block, cardiopulmonary resuscitation:

Adults:

- Sinus bradycardia: 0.5 mg IV (5ml), every 2-5 minutes until the desired heart rate is achieved.- AV block: 0.5 mg IV (5ml), every 3-5 minutes (maximum 3 mg) Paediatric population

0.02 mg/kg IV in a single dose (maximum dose 0.6 mg). As an antidote to organophosphates (pesticides, nerve gases), to cholinesterase inhibitors and in muscarinic mushroom poisoning:

Intravenous use. Adults:

0.5 - 2 mg atropine sulfate (5 - 20 ml), can be repeated after 5 minutes and subsequently every 10-15 minutes as required, until signs and symptoms disappear (this dose may be exceeded many times). Paediatric population:

0.02 mg atropine sulfate/kg body weight possibly repeated several times until signs and symptoms disappear. Dose adjustments

In general, dosage should be adjusted according to patient's response and tolerance.Dosage to a total maximum dose of 3 mg in adults and 0.6 mg in children is usually increased until adverse effects become intolerable; then a slight reduction in dosage generally yields the maximum dosage tolerated by the patient. Paediatric Population

This medicinal product is not appropriate to deliver a dose of less than 0.5 ml and should therefore not be used in neonates for which the body weight is inferior to 3 kg (see section 4.1).The dosage ranges for the paediatric weight groups as stated below are values for guidance. The usual dose in children is between 0.01-0.02 mg/kg body weight (maximum 0.6 mg per dose), dosage should be adjusted according to the patient's response and tolerance. Body weight (kg) Dose of 0.01 mg/kg body weight

Atropine sulfate 0.5 mg/5 ml Solution for Injection (ml)

Dose of 0.02 mg/kg body weight

Atropine sulfate 0.5 mg/5 ml Solution for Injection (ml)

3 - 5 0.5 ml 0.5-1.0 ml

5-10 0.5-1.0 ml 1.0-2.0 ml

10 - 15 1.0-1.5 ml 2.0-3.0 ml

15 - 20 1.5-2.0 ml 3.0-4.0 ml

20 - 30 2.0-3.0 ml 4.0-6.0 ml

30 - 50 3.0-5.0 ml 6.0 ml

Special populations

Caution is advised for patients with renal or hepatic impairment and in elderly (see section 4.4). Method of administration

Atropine is administered by intravenous injection or intramuscular injection. Other pharmaceutical forms/strengths may be more appropriate in the cases where a dose above 0.5 mg is required.

4.3. Contraindications

- Hypersensitivity to the active substance or to any of the excipients- Closed-angle glaucoma- Risk of urinary retention because of prostatic or urethral disease - Achalasia of the esophagus, paralytic ileus, and toxic megacolonAll these contra-indications are however not relevant in life-threatening emergencies (such as bradyarrhythmia, poisoning).

4.4. Special warnings and precautions for use

Use with caution in case of:- Prostatic enlargement- Renal or hepatic insufficiency- Cardiac insufficiency, arrhythmias, hyperthyroidism- Chronic obstructive pulmonary disease, as a reduction in bronchial secretions may lead to the formation of bronchial plugs- Intestinal atonia in elderly- Pyloric stenosis- Fever, or when ambient temperature is high- In children and elderly, who may be more susceptible to its adverse effects- In reflux oesophagitis, as atropine may delay gastric emptying, decrease gastric motility and relax oesophageal sphincterAtropine should not be given to patients with myasthenia gravis unless given in conjunction with anticholinesterase.Atropine administration should not delay implementation of external pacing for unstable patients, particularly those with high-degree (Mobitz type II second-degree or third-degree) block.Antimuscarinics block vagal inhibition of the SA nodal pacemaker and should thus be used with caution in patients with tachyarrhythmias, congestive heart failure or coronary heart disease.This medicinal product contains sodium. Sodium level is lower than 1 mmol per syringe, i.e. 'without sodium'.

4.5. Interaction with other medicinal products and other forms of interaction

Combinations to be taken into account

Other drugs with anticholinergic activity, such as tricyclic antidepressants, some H1-antihistamines, antiparkinsonian drugs, disopyramide, mequitazine, phenothiazines, neuroleptic drugs, atropinic antispasmodics, clozapine and quinidine, because of the risk of potentialisation of atropinic adverse effects (urinary retention, constipation, dry mouth).

4.6. Fertility, pregnancy and lactation

Pregnancy

Data on a limited number of exposed pregnancies indicate no adverse effects of atropine on pregnancy or on the health of the fetus/new-born child.Animal studies did not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3).Studies of the pharmacokinetics of atropine in mother and fetus in late pregnancy indicated that atropine rapidly crosses the placental barrier. Intravenous administration of atropine during pregnancy or at term may cause tachycardia in the fetus and the mother. Atropine should not be used during pregnancy unless clearly necessary. Breast-feeding

Small amounts of atropine may pass into human breast milk. Infants have an increased sensitivity to the anticholinergic effects of atropine. Atropine may inhibit the production of milk, particularly upon repeated use. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from treatment taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman. If it is decided during treatment to continue breastfeeding, the child should be monitored for anticholinergic effects. Fertility

There are no data on effects of this atropine sulfate on fertility in humans. Atropine sulfate reduced fertility in male rats, presumably as a consequence of an inhibitory effect on the transport of sperm and semen during the process of emission.

4.7. Effects on ability to drive and use machines

Atropine may cause confusion or blurred vision and patients should be advised of it.

4.8. Undesirable effects

The pattern of adverse effects seen with atropine can mostly be related to their pharmacological actions at muscarinic and, at high doses, nicotinic receptors. Adverse effects are dose-related and usually reversible when therapy is discontinued. The most common effects occurring with relatively small doses are visual disturbances, reduced bronchial secretion, dry mouth, constipation, reflux, flushing, difficulty in micturition and dryness of the skin. Transient bradycardia may develop followed by tachycardia, with palpitations and arrhythmias. The evaluation of adverse reactions is based on the following definition of frequency: Very Common: ≥ 1/10; Common: ≥ 1/100 to <1/10; Uncommon: ≥ 1/1,000 to <1/100; Rare: ≥ 1/10,000 to <1/1,000; Very rare: <1/10,000; Not known: cannot be estimated from the available data Frequency Very Common (≥ 1/10) Common (≥ 1/100 to <1/10) Uncommon (≥ 1/1,000 to <1/100) Rare (≥ 1/10,000 to <1/1,000) Very Rare (<1/10,000) Not known (cannot be estimated from the available data)

System Organ Class

Immune system disorders Allergic reactions Anaphylaxis

Nervous system disorders Excitement, incoordination, mental confusion, and/or hallucinations (especially with higher dosages), hyperthermia Psychotic reactions Seizure, drowsiness Headache, restlessness, ataxia, insomnia

Eye disorders Visual disturbances (mydriasis, inhibition of accommodation, blurred vision, photophobia)

Cardiac disorders Tachycardia (arrhythmias, transient exacerbation of bradycardia) Atrial arrhythmias, ventricular fibrillation, angina, hypertensive crisis

Vascular disorders Flushing

Respiratory, thoracic and mediastinal disorders Reduced bronchial secretion

Gastrointestinal disorders Dryness of the mouth (difficulty in swallowing and talking, thirst), parasympathetic inhibition of gastrointestinal tract (constipation and reflux), inhibition of gastric secretion, loss of taste, nausea, vomiting, bloated feeling

Skin and subcutaneous tissue disorders Anhidrosis, urticaria, rash

Renal and urinary disorders Inhibition of the parasympathetic control of the urinary bladder, urinary retention

Paediatric population

Infants, children and children with spastic paralysis or brain damage may be more susceptible to antimuscarinic effects. Special populations

Atropine may cause excitement, incoordination, confusion and/or hallucinations especially in the elderly. An epidemiological study similarly reported lower cognitive performance in elderly patients receiving antimuscarinics.Patients with Down syndrome may be more susceptible to antimuscarinic effects. Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via: United Kingdom

Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard.

4.9. Overdose

Symptoms: Flushing and dryness of the skin, dilated pupils with photophobia, dry mouth and tongue accompanied by a burning sensation, difficulty in swallowing, tachycardia, rapid respiration, hyperpyrexia, nausea, vomiting, hypertension, rash and excitement. Symptoms of CNS stimulation include restlessness, confusion, hallucinations, paranoid and psychotic reactions, incoordination, delirium and occasionally convulsions. In severe overdose, drowsiness, stupor and CNS depression may occur with coma, circulatory and respiratory failure and death. Treatment:

Treatment should be supportive. An adequate airway should be maintained. Diazepam may be administered to control excitement and convulsions but the risk of CNS depression should be considered.