ATROPINE INJECTION BP MINIJET - summary of medicine characteristics

1 NAME OF THE MEDICINAL PRODUCT

Atropine Injection BP Minijet

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Atropine Sulfate 0.1 mg/ml

3 PHARMACEUTICAL FORM

Sterile aqueous solution for parenteral administration to humans.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Acute myocardial infarction with AV conduction block due to excess vagal tone (Wenkebach Type I, second-degree AV block) and sinus bradycardia, with associated hypotension and increased ventricular irritability.

Atropine can also be used in cardiopulmonary resuscitation for the treatment of sinus bradycardia accompanied by hypotension, hypoperfusion or ectopic arrhythmias.

Parenteral atropine is indicated as an antisialogogue in anaesthetic premedication to prevent or reduce secretions of the respiratory tract.

During anaesthesia, atropine may be used to prevent reflex bradycardia and restore cardiac rate and arterial pressure resulting from increased vagal activity associated with laryngoscopy, tracheal intubation and intra-abdominal manipulation. It may also be administered to block muscarinic effects when neostigmine is used to counteract muscle relaxants such as tubocurarine.

Parenteral atropine is an antidote for cardiovascular collapse following overdose of anticholineste­rases; in the treatment of poisoning from organophosphorous insecticides or from chemical warfare ‚nerve‘ gases and in the treatment of mushroom poisoning.

4.2 Posology and method of administrationAdults, children over 12 and the elderly:

Bradyarrhythmias: intramuscular or intravenous, 300 to 600mcg (0.3 to 0.6mg) every four to six hours to a total dose of 2mg.

In cardiac resuscitation, intravenous 500mcg (0.5mg) repeated at 5 minute intervals until the desired heart rate is achieved. In asystole, 3mg may be given intravenously as a once only single dose. If atropine cannot be administered intravenously during resuscitation, 2–3 times the intravenous dose may be administered via an endotracheal tube.

Premedication before anaesthesia: intramuscular or subcutaneous, 300 to 600mcg (0.3 to 0.6mg) 30–60 minutes before surgery or the same dose intravenously immediately before surgery.

To control muscarinic side effects of neostigmine: intravenous, 600 to 1200mcg (0.6 – 1.2mg).

Anticholinesterase poisoning: intramuscular or intravenous, 1 to 2mg repeated every 5 to 60 minutes until signs and symptoms disappear, up to a maximum of 100mg in the first 24 hours.

The usual intramuscular, intravenous or subcutaneous dose in children is 10mcg/kg (0.01mg/kg), but generally not exceeding 400mcg (0.4mg). If necessary, these doses may be repeated every 4–6 hours.

Cardiac: for advanced cardiac life support: intravenous, 20mcg/kg (0.02mg/kg) with a minimum dose of 10mcg (0.01mg) repeated at 5 minute intervals, to a maximum dose of 100mcg (0.1mg).

Premedication before anaesthesia: intramuscular or subcutaneous; 30–60 minutes before surgery.

Up to 3 kg       -     100mcg (0.1mg)

7 – 9 kg         -     200mcg (0.2mg)

12 – 16 kg       -      300mcg (0.3mg)

Over 20 kg       -      as for adults

To control the muscarinic side effects of neostigmine: intravenous; neonates, infants and children – 20mcg/kg (0.02mg/kg). Maximum dosage 600mcg.

Anticholinesterase poisoning: intramuscular or intravenous, 50mcg/kg (0.05mg/kg) every 10–30 minutes until muscarinic signs and symptoms disappear.

4.3 Contraindications

Contra-indications are not applicable to the use of atropine in life-threatening emergencies (e.g. asystole).

Atropine is contraindicated in patients with known hypersensitivity to the drug, obstruction of the bladder neck e.g. due to prostatic hypertrophy, reflux oesophagitis, closed angle glaucoma, myasthenia gravis (unless used to treat the adverse effects of an anticholinesterase agent), paralytic ileus, severe ulcerative colitis and obstructive disease of the gastrointesti­nal tract.

4.4 Special warnings and precautions for use

Antimuscarinic agents should be used with caution in the elderly and children since these patients may be more susceptible to adverse effects. Atropine should also be used with caution in patients with hyperthyroidism, hepatic or renal disease or hypertension. Use with caution in febrile patients or when ambient temperature is high since antimuscarinics may cause an increase in temperature. 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. Parenterally administered atropine should be used cautiously in patients with chronic pulmonary disease since a reduction in bronchial secretions may lead to formation of bronchial plugs. Antimuscarinics should be used with extreme caution in patients with autonomic neuropathy.

Antimuscarinics decrease gastric motility, relax the lower oesophageal sphincter and may delay gastric emptying; they should therefore be used with caution in patients with gastric ulcer, oesophageal reflux or hiatus hernia associated with reflux oesophagitis, diarrhoea or GI infection.

There have been cases where severe bradycardia due to hyperkalaemia could not be resolved with atropine.

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 anticholinergic activity e.g. tricyclic antidepressants, antispasmodics, antiparkinsonian drugs, some antihistamines, phenothiazines, disopyramide and quinidine. By delaying gastric emptying, atropine may alter the absorption of other drugs.

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 concomitantly propofol; it could be due to propofol-induced suppression of the sympathetic nervous system.

An extreme caution should be observed when dobutamine-atropine stress echocardiography or the concomitant administration of a catecholamine with atropine has to be performed in patients who seem already extremely stressed or are in an underlying hyperadrenergic state (risk of Tako-tsubo syndrome).

4.6 Fertility, pregnancy and lactation

Atropine crosses the placenta. Studies in humans have not been done and only limited information is available from animal studies. Intravenous administration of atropine during pregnancy or at term may cause tachycardia in the foetus. Atropine should only be administered to pregnant women if the benefits outweigh the risks to the foetus. Trace amounts of atropine appear in the breast milk and may cause antimuscarinic effects in the infant; lactation may be inhibited.

4.7 Effects on ability to drive and use machines

Not applicable; this preparation is intended for use only in emergencies.

4.8 Undesirable effects

Adverse effects are dose-related and usually reversible when therapy is discontinued. In relatively small doses, atropine reduces salivary, bronchial and sweat secretions; dry mouth and anhidrosis may develop, these effects being intensified as the dosage is increased. Reduced bronchial secretion may cause dehydration of residual secretion and consequent formation of thick bronchial plugs that are difficult to eject from the respiratory tract.

Larger doses dilate the pupil and inhibit accommodation of the eye, and block vagal impulses with consequent increase in heart rate with possible atrial arrhythmias, A-V dissociation and multiple ventricular ectopics; parasympathetic control of the urinary bladder and gastrointestinal tract is inhibited, causing urinary retention and constipation. Further increase in dosage inhibits gastric secretion. Anaphylaxis, urticaria and rash occasionally progressing to exfoliation may develop in some patients. Other effects include hallucinations, increased ocular tension, loss of taste, headache, nervousness, drowsiness, weakness, dizziness, flushing, insomnia, nausea, vomiting and bloated feeling. Mental confusion and/or excitement may occur especially in the elderly.

There have been cases where severe bradycardia due to hyperkalaemia could not be resolved with atropine.

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: marked dryness of the mouth accompanied by a burning sensation, difficulty in swallowing, pronounced photophobia, flushing and dryness of the skin, raised body temperature, rash, nausea, vomiting, tachycardia and hypertension. Restlessness, tremor, confusion, excitement, hallucinations and delirium may result from CNS stimulation; this is followed by increasing drowsiness, stupor and general central depression terminating in death from circulatory and respiratory failure.

Treatment: In severe cases, physostigmine, 1 to 4mg, should be administered intravenously, intramuscularly or subcutaneously, the dose may be repeated if necessary since it is rapidly eliminated from the body. Diazepam may be administered for sedation of the delirious patient but the risk of central depression occurring late in the course of atropine poisoning contraindicates large doses of sedative. An adequate airway should be maintained and respiratory failure may be treated with oxygen and carbon dioxide inhalation. Fever is reduced by the application of cold packs or sponging with tepid water. Adequate fluid intake is important. Urethral catheterisation may be necessary. If photophobia is present or likely, the patient should be nursed in a darkened room.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

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

Peripheral effects include tachycardia, decreased production of saliva, sweat, bronchial, 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 bronchodilatation.

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.

Atropine is metabolised in the liver by oxidation and conjugation to give inactive metabolites.

About 50% of the dose is excreted within 4 hours and 90% in 24 hours in the urine, about 30 to 50% as unchanged drug.

5.3 Preclinical safety data

Not applicable since atropine has been used in clinical practice for many years and its effects in man are well known.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Sodium Citrate Dihydrate

Citric Acid Monohydrate Sodium Chloride

Water for Injection

6.2 Incompatibilities

None known

6.3 Shelf life

36 months

6.4 Special precautions for storage

Store below 25°C. Protect from light.

6.5 Nature and contents of container

The solution is contained in a USP type I glass vial with an elastomeric closure which meets all the relevant USP specifications. The product is available either as 5, 10 or 30ml.

6.6 Special precautions for disposal

The container is specially designed for use with the IMS Minijet injector.

7 MARKETING AUTHORISATION HOLDER

International Medication Systems (UK) Ltd

21 St Thomas Street

Bristol

United Kingdom

BS1 6JS

8 MARKETING AUTHORISATION NUMBER(S)

PL 03265/0013R