1. NAME OF THE MEDICINAL PRODUCT

Atropine Sulfate Injection 600mcg in 1ml.

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

Each ml contains 600mcg of Atropine Sulfate.

3 PHARMACEUTICAL FORM

Sterile Injection

4.    CLINICAL PARTICULARS

4.1    Therapeutic indications

Atropine Sulfate Injection is used:

•    as a preoperative medication for the reduction of salivary and bronchial secretions.

•    during cardiopulmonary resuscitation to treat sinus bradycardia or asystole.

•    for treatment of symptomatic sinus bradycardia induced by drugs or toxic substances such as pilocarpine, organophosphate pesticides, amanita muscaria mushrooms.

•    for management of bradycardia of acute myocardial infarction.

•    for prevention of cholinergic effects on the heart (e.g. arrhythmias, bradycardia) during surgery.

•    in combination with neostigmine during reversal of effect of nondepolarising muscle relaxants.

4.2    Posology and method of administration

As a preoperative medication Adults:

300-600micrograms IM or SC about one hour before induction of anaesthesia or 300-600micrograms IV immediately before induction.

Children:

Premature infants:    65 micrograms;

children up to 3kg:    100 micrograms;

children 7-9kg:    200 micrograms;

children 12-16kg:    300    micrograms;

children 20-27kg:    400    micrograms;

children 32kg:    500    micrograms;

children 41kg:    600    micrograms;

given IM 30-60 minutes before induction of anaesthesia.

Alternative dosage statement for children over 1 year:

10-20 micrograms/kg 30-60 minutes before induction of anaesthesia.

As an antidote to cholinesterase inhibitors

Adults:

2mg, preferably IV.

Children:

50 micrograms/kg IV or IM.

Repeat dose every 5-10 minutes until signs of atropinisation appear.

As an antidote to organophosphate pesticides and in mushroom poisoning Adults:

2mg IV or IM.

Children:

50 micrograms/kg IV or IM

Repeat dose every 10-30 minutes until muscarinic signs and symptoms subside.

Reversal of effects of non-depolarising muscle relaxants Adults:

0.6 -1.2 mg given IV in conjunction with neostigmine methyl- sulfate.

In cardiopulmonary resuscitation

Adults:

3mg IV once

Children:

20 micrograms/kg IV once In arrhythmias

Bradycardia, particularly if complicated by hypotension,

300 micrograms IV initially, increasing to 1mg if necessary.

4.3    Contraindications

Known hypersensitivity to the drug, closed-angle glaucoma, prostatic enlargement, myasthenia gravis (unless given in conjunction with anticholinesterase), paralytic ileus or pyloric stenosis and severe ulcerative colitis.

4.4    Special warnings and precautions for use

Atropine sulfate should be used with caution in children, the elderly and those with Down’s syndrome. It should be given with caution to patients with diarrhoea, urinary retention or fever, and when the ambient temperature is high. Care is required in patients with acute myocardial infarction as ischaemia and infarction may be exacerbated and in patients with hypertension.

Caution is also required when using the drug in patients with conditions characterised by tachycardia such as thyrotoxicosis, cardiac insufficiency or failure and during cardiac surgery. Paradoxical atrioventricular block or sinus arrest has been reported following administration of atropine in a few patients after heart transplantation. The use of atropine for therapeutic or diagnostic procedures in heart transplant patients should be undertaken with extreme caution, and ECG monitoring and equipment for immediate temporary pacing should be available.

Caution is required when atropine is administered systemically to patients with chronic obstructive pulmonary disease, as a reduction in bronchial secretions may lead to the formation of bronchial plugs.

Antimuscarinics such as atropine may delay gastric emptying, decrease gastric motility and relax the oesophageal sphincter. They should be used with caution in patients whose conditions may be aggravated by these effects e.g. reflux oesophagitis.

4.5    Interactions with other medicinal products and other forms of interaction

The effects of atropine may be enhanced by the concomitant administration of other drugs with antimuscarinic activity including phenothiazines, amantadine, tricyclic antidepressants, MAOI’s, some antihistamines and disopyramide.

Reduced GI motility caused by atropine may affect the absorption of other drugs such as mexilitine and ketoconazole.

Atropine- induced dry mouth may prevent dissolution of sublingual preparations such as the nitrates, reducing their effectiveness.

During anaesthesia, the heart rate responsiveness to IV atropine could be decreased (and not effectively overcome by a large dose of atropine) when the subject is receiving concomitant propofol; it could be due to propofol-induced suppression of the sympathetic nervous system.

4.6 Fertility, pregnancy and lactation

Atropine sulfate crosses the placenta. There is insufficient evidence to establish the safety of atropine in human pregnancy. It should therefore be used during pregnancy only if considered essential by the physician.

Atropine sulfate is excreted in breast milk, and infants of nursing mothers may exhibit some effects of the drug. Infants are usually very sensitive to the effects of anticholinergic drugs. Atropine should therefore only be used during breast feeding if considered essential.

4.7    Effects on ability to drive and use machines

Atropine sulfate may cause drowsiness or blurred vision and patients should be advised accordingly.

4.8    Undesirable effects

The most commonly reported adverse events are due to the action of atropine on muscarinic and, at high doses, nicotinic receptors. These effects are dose-related and usually reversible when therapy is discontinued.

Immune system disorders:

Anaphylaxis.

Nervous system/Psychiatric disorders:

Dizziness, confusional states, especially in the elderly. At higher doses hallucinations, restlessness, delirium.

Eye disorders:

Dilatation of the pupils with loss of accommodation and photophobia, raised intraocular pressure.

Cardiac disorders:

Transient bradycardia followed by tachycardia, palpitations, arrhythmias.

There have been reports of paradoxical atrioventricular block, especially after heart transplantation (see section 4.4 Special warnings and precautions for use).

Vascular disorders:

Flushing.

Respiratory disorders:

Reduced bronchial secretion may result in the formation of thick bronchial plugs which are difficult to eject from the respiratory tract (see section 4.4 Special warnings and precautions for use).

Gastrointestinal disorders:

Dry mouth with difficulty in swallowing, nausea, vomiting, constipation. Inhibition of gastric secretion, retrosternal pain due to gastric reflux.

Skin & subcutaneous tissue disorders:

Dry skin, urticaria, rashes, skin exfoliation.

Renal & urinary disorders:

Difficulty with micturition.

General disorders:

Thirst, fever.

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 the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

4.9 Overdose Symptoms

Flushing and dryness of the skin, dilated pupils, dry mouth and tongue, tachycardia, rapid respiration, hyperpyrexia, hypertension, nausea, vomiting. A rash may appear on the face or upper trunk. Symptoms of CNS stimulation include restlessness, confusion, hallucinations, paranoid and psychotic reactions, incoordination, delirium and occasionally convulsions. In severe overdose, 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 central nervous system depression should be considered. Hypoxia and acidosis should be corrected. Antiarrhythmic drugs are not recommended if dysrhythmias occur.

5    PHARMACOLOGICAL PROPERTIES

5.1    Pharmacodynamic properties

Atropine is an antimuscarinic agent which competitively antagonises acetylcholine at postganglionic nerve endings, thus affecting receptors if the exocrine glands, smooth muscle, cardiac muscle and the central nervous system.

Peripheral effects include decreased production of saliva, sweat, nasal, lachrymal and gastric secretions, decreased intestinal motility and inhibition of micturition.

Atropine increases sinus rate and sinoatrial and AV conduction. Usually heart rate is increased, but there may be an initial bradycardia.

Atropine inhibits secretions throughout the respiratory tract and relaxes bronchial smooth muscle producing bronchodilation.

5.2    Pharmacokinetic properties

Following intravenous administration, the peak increase in heart rate occurs within 2 to 4 minutes. Peak plasma concentrations of atropine after intramuscular administration are reached within 30 minutes, although peak effects on the heart, sweating and salivation may occur nearer one hour after intramuscular administration.

Plasma levels after intramuscular and intravenous injection are comparable at one hour. Atropine is distributed widely throughout the body and crosses the blood brain barrier. The elimination half-life is about 2 to 5 hours. Up to 50% of the dose is protein bound. It disappears rapidly from the circulation.

It is incompletely metabolised in the liver and is excreted in the urine as unchanged drug and metabolites. About 50% of the dose is excreted within 4 hours and 90% in 24 hours.

5.3    Preclinical safety data

No further information other than that which is included in the Summary of product characteristics.

6.1    List of excipients

Water for Injections Ph. Eur.

Sulfuric acid 1N (for pH adjustment)

6.2    Incompatibilities

Atropine sulfate injection is reported to be physically incompatible with bromides, iodides, alkalis, noradrenaline bitartrate, metaraminol bitartrate and sodium bicarbonate. A haze or precipitate may form within 15 minutes when atropine sulfate is mixed with methohexital sodium solutions.

6.3    Shelf life

36 months

6.3    Special precautions for storage

Protect from light. Store at less than 25 ^oC.

6.5    Nature and contents of container

Type I clear glass ampoule, 1ml

Packed in cardboard cartons to contain 10 ampoules x 1ml

6.4    Special precautions for disposal and other handling

Use as directed by the physician.

7    MARKETING AUTHORISATION HOLDER

hameln pharmaceuticals limited

Gloucester

UK

8    MARKETING AUTHORISATION NUMBER(S)

PL 01502/0016R

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

24/08/2008

10    DATE OF REVISION OF THE TEXT

05/05/2015