SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Atropine Sulphate Injection BP 1mg in 5ml

2    QUALITATIVE AND QUANTITATIVE COMPOSITION

Atropine Sulphate BP    0.02% w/v

3    PHARMACEUTICAL FORM

A hypotonic sterile Solution for Injection presented in a glass prefilled syringe

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Reversal of excessive of bradycardia. The administration is given in the algorithm for the emergency treatment of Peri - arrest arrhythmias produced by European Resuscitation Council’s and Resuscitation Council (UK).

4.2 Posology and method of administration

Adults and children over 12 years

Initially 0.5mg by intravenous injection and then increments of 0.5mg to a maximum of 3mg.

Children

Not recommended.

Elderly As for Adults.

4.3 Contraindications

Known Hypersensitivity to Atropine, Closed Angle Glaucoma, Prostatic Enlargement, Paralytic Ileus or Pyloric Stenosis, Myasthenia Gravis, Severe Ulcerative Colitis.

4.4 Special warnings and precautions for use

Atropine Sulphate 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, acute myocardial infarction, hypertension or fever, Gastro-oesophageal reflux disease and when the ambient temperature is high. Chronic lung disease due to the reduction in bronchial secretions which may increase the viscosity of residual secretions. 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.

4.5 Interaction 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, nefopam some antihistamines and disopyramide. Reduced GI motility caused by Atropine may affect the absorption of other drugs such as mexilitine and ketoconazole. Atropine antagonises the gastro-intestinal effects of Metoclopramide. Atropine induced dry mouth may prevent dissolution of sublingual preparations such as the nitrates, reducing their effectiveness.

4.6 Pregnancy and lactation

Atropine Sulphate crosses the placenta. There is insufficient evidence as to drug safety in pregnancy and Lactation.

This product should not be used in pregnancy unless considered essential by the physician. Atropine Sulphate 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 the drug. Atropine Sulphate should only be used in breast feeding if considered essential by the physician.

4.7 Effects on ability to drive and use machines

This may be affected during treatment with Atropine. The time after which the patient can resume such activities must be decided by the physician.

4.8 Undesirable effects

Side effects which are common include, dry mouth with difficulty in swallowing, thirst, dilation of the pupils with loss of accommodation and photophobia, flushing, dryness of skin, bradycardia followed by tachycardia, palpitations and arrhythmias, reduced bronchial secretions, difficulty with micturition, and constipation. Occasionally, nausea, vomiting, giddiness, fever, rashes and confusional states may occur, especially in the elderly.

4.9 Overdose

Symptoms

Overdosage with Atropine Sulphate produces tachycardia, rapid respiration, hyperpyrexia, and CNS stimulation marked by restlessness, confusion, hallucinations, paranoia, incoordination, delirium. In severe overdosage, CNS depression may occur with coma, circulatory and respiratory failure, and death.

Treatment

Treatment of overdosage with atropine sulphate injection consists of symptomatic and supportive therapy, control of delirium. General measures include: reduction of body temperature, administration of fluids orally or intravenously, monitoring of ECG or excitement with diazepam, urinary catheterisation to avoid urinary retention. The use of physostigmine as an antidote to atropine is controversial.

5    PHARMACOLOGICAL PROPERTIES

5.1    Pharmacodynamic properties

Atropine acts as an antimuscarinic and a competitive antagonist of acetylcholine at postganglionic cholinergic nerve endings. The receptors affected are those of exocrine glands, smooth muscle and cardiac muscle and the central nervous system. Atropine does not discriminate between the muscarinic receptor subtypes M1 and M2.

5.2    Pharmacokinetic properties

Absorption

Atropine is well absorbed from the small bowel and not at all from the stomach. Thus the effects of oral dosing are much slower in onset than after parenteral dosing. Atropine is also absorbed by mucous membranes but less readily from the eye and skin, although significant toxicity can sometimes occur through absorption of excessive eye drops. Peak plasma concentrations after intramuscular injection are achieved within 30 minutes. After parenteral injection Atropine disappears rapidly from the circulation and plasma concentrations after the drug is given by intramuscular and intravenous routes are comparable at one hour.

Distribution

Atropine has a volume of distribution of 1-6l/kg. Protein binding is moderate, with approximately 50% of the drug bound in plasma. Its plasma clearance is 8ml/min/kg.

Only traces of atropine are found in breast milk. The drug readily crosses the blood-brain barrier and may cause confusion and delirium postoperatively. It crosses the placenta readily but the foetus is rarely affected by premedication doses.

Elimination

The half life of elimination appears to be between two and five hours. Half of a single parenteral dose appears in the urine within four hours and about 90% within 24 hours with about 30% of the dose excreted as unchanged drug.

Early studies with radioactive atropine had suggested a long half life of 12-36 hours, but recent studies with RIA and RRA have all shown much more rapid elimination with half lives of 4.3 +/-1.7 hours (by RIA) and 3.7 +/-2.3 hours by (RRA).

The differences in the two methods are probably due to the preferential tissue uptake of the 1-isomer (1-hyoscyamine) as the RRA measures only the active l - form while RIA measures both l- and d - isomers.

5.3 Preclinical safety data

The side effect and clinical profile of this active ingredient and product is well known and understood over many years clinical experience. Therefore no further data is provided.

6.1    List of excipients

Water for Injections, Sulphuric Acid, Nitrogen

6.2    Incompatibilities

Atropine Sulphate 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 Sulphate is mixed with methohexital sodium solutions.

6.3 Shelf life

18 Months

6.4    Special precautions for storage

Store below 25°C. Protect from light.

6.5    Nature and contents of container

Sterile aqueous solution for injection in Glass (Type I) 5ml prefilled syringe.

Each syringe is packaged in a lidded blister inside a carton.

No needle is provided with this syringe.

6.6 Special precautions for disposal

Use once and discard any remaining

7    MARKETING AUTHORISATION HOLDER

Aurum Pharmaceuticals Ltd Bampton Road,

Harold Hill,

Romford,

Essex RM3 8UG

MARKETING AUTHORISATION NUMBER(S)

PL 12064/0035

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

13/01/1998 / 16/05/2003

10    DATE OF REVISION OF THE TEXT

15/01/2007