Atropina Vitalis

Atropina Vitalis 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.

- 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

Atropina Vitalis sulfate is an antimuscarinic agent used as a cycloplegic and mydriatic. The eye drops are used in the treatment of iritis and uveitis to immobilise the iris and ciliary muscle and to prevent or break down adhesions.

Since it is a powerful cycloplegic it is used in the determination of refraction in children below six years and children with convergent strabismus.

Atropina Vitalis 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 Atropina Vitalis (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 Atropina Vitalis/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.

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.

Special populations

Caution is advised for patients with renal or hepatic impairment and in elderly.

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.

For topical ocular use.

The depth of the angle of the anterior chamber should be assessed before the product is used.

Adults

Elderly

Mydriatics and cycloplegics should only be used with caution in the elderly and others who may have raised intra ocular pressure

Children

- 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 megacolon

All these contra-indications are however not relevant in life-threatening emergencies (such as bradyarrhythmia, poisoning).

The product should not be used in patients with closed angle glaucoma.

It is also contraindicated in patients with narrow angle between the iris and the cornea since it may raise intra-ocular pressure and precipitate an acute attack of closed angle glaucoma.

It should not be used by patients with known hypersensitivity to any component of the preparation.

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 sphincter

Atropine 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'.

It should only be used with caution in patients who may have raised intra ocular pressure.

The product contains benzalkonium chloride solution and soft contact lenses must not be worn during the period of use.

Patients should be warned that antimuscarinic eye drops will temporarily impair vision.

Patients should wash hands after using the eye drops and great care should be taken to avoid getting the product into the mouth.

Due to the risk of provoking hyperpyrexia, Atropina Vitalis should only be used with great caution when the ambient temperature is high or the patient has a fever.

Care is also required in patients with conditions characterised by tachycardia.

Darkly pigmented iris is more resistant to pupillary dilation and caution should be exercised to avoid overdosage.

The eye drops should be discarded 4 weeks after first opening.

During use, care should be taken not to touch the dropper nozzle on to the eyelid or any other surface.

The product is for external use only and should be stored out of the sight and reach of children.

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

May cause transient blurring of vision on instillation. Warn patients not to drive or operate hazardous machinery until vision is clear.

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

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.

Patients may experience photophobia and eyes should be protected from bright light while the pupils are dilated.

Prolonged use of Atropina Vitalis eye drops may lead to local irritation, transient stinging, hyperaemia, oedema and conjunctivitis. An increase in intra-ocular pressure may occur, especially in patients with closed angle glaucoma.

Hypersensitivity to Atropina Vitalis is not uncommon and may appear as a skin rash or conjunctivitis.

Systemic toxicity may be produced by the instillation of the eye drops especially in infants and the elderly. Reported symptoms include severe ataxia, restlessness, excitement and hallucinations.

Other adverse effects may include a dry mouth with difficulty in swallowing and talking, flushing and a dry skin, transient bradycardia followed by tachycardia, palpitations and arrhythmias, reduced bronchial secretions, urinary urgency and retention and constipation.

Side effects that occur occasionally include confusion (particularly in the elderly), nausea, vomiting and giddiness.

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.

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.

Symptoms

Systemic reactions to topical Atropina Vitalis are unlikely at normal doses.), cardiovascular changes (tachycardia, atrial arrhythmias, atrio-ventricular dissociation) and central nervous system effects (confusion, ataxia, restlessness, hallucination, convulsions).

Treatment

Supportive therapy should be given as required.

Pharmacotherapeutic group: Belladonna alkaloids, tertiary amines.

ATC code: A03BA01.

Atropine is an antimuscarinic agent which competitively antagonises acetylcholine at postganglionic nerve endings, thus affecting receptors in 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.

Pharmacotherapeutic group: anticholinergic agents

ATC code: S01FA01

Dilation of the pupil normally occurs within half an hour following local application and lasts for seven days or longer. Paralysis of accommodation in one to three hours with recovery in three to seven days.

Absorption

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 1 hour after intramuscular administration.

Distribution

Plasma levels after intramuscular and intravenous injection are comparable at 1 hour. Atropine is distributed widely throughout the body and crosses the blood brain barrier and the placenta barrier.

Biotransformation

Atropine 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.

Elimination

The elimination half-life is about 2 to 5 hours. Up to 50% of the dose is protein bound.

Paediatric Population

Children, particularly those younger than two years, may be more susceptible to the actions of atropine. The elimination half-life is more than doubled in children less than two years compared to adults.

Elderly

The elimination half-life of atropine is more than doubled in the elderly (>65 years old) compared to adults.

Atropina Vitalis is readily absorbed from the gastro-intestinal tract and mucous membranes, it is also absorbed from the eye.

It is incompletely metabolised in the liver and is excreted in the urine as unchanged drug and metabolites.

Effects in non-clinical studies were observed only at exposures considered sufficiently in excess of the maximum human exposure indicating little relevance to clinical use.

Atropina Vitalis 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.

No additional pre-clinical data of relevance to the prescriber.

This medicinal product must not be mixed with other medicinal products.

None known relevant to topical ocular use.

Instructions for use:

Be careful to strictly respect the protocol for the use of the syringe.

The pre-filled syringe is for single patient only. Discard syringe after use. DO NOT REUSE.

The content of un-opened and un-damaged blister is sterile, and must not be opened until used.

The product should be inspected visually for particles and discoloration prior to administration. Only clear colourless solution free from particles or precipitates should be used.

The product should not be used if the tamper evident seal on syringe (plastic cover to the end cap) is broken.

The external surface of syringe is sterile until blister is opened.

1) Withdraw the pre-filled syringe from the sterile blister.

6) Connect syringe to vascular access device or to needle.

Push the plunger to inject the required volume.

The needle gauge appropriate for use with the syringe are 23 to 20 gauge for IV administration and 23 to 21 gauge for IM administration.

Any unused product or waste material should be disposed of in accordance with local requirements.

None stated.