Consumer medicine information

Atropine Juno Injection BP

Atropine sulfate monohydrate

BRAND INFORMATION

Brand name

Atropine Juno

Active ingredient

Atropine sulfate monohydrate

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Atropine Juno Injection BP.

What is in this leaflet

This leaflet answers some common questions about Atropine Juno Injection. It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have benefits and risks. Your doctor has weighed the risks of you taking Atropine Juno Injection against the benefits this medicine is expected to have for you.

This medicine is likely to be used while you are at the clinic or in hospital. If possible, please read this leaflet carefully before this medicine is given to you. In some cases this leaflet may be given to you after the medicine has been used.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Keep this leaflet. You may need to read it again.

What Atropine Juno Injection is used for

Atropine sulfate monohydrate belongs to a group of medicines called antimuscarinic agents. Atropine Juno Injection is given before anaesthesia to decrease mucus secretions, such as saliva. During anaesthesia and surgery, atropine is used to help keep the heart beat normal. Atropine sulfate monohydrate is also used to block or reverse the adverse effects caused by some medicines and certain type of pesticides.

Atropine Juno Injection may be used for the management of other conditions that are not mentioned above. Your doctor will be able to tell you about the specific condition for which you have been prescribed Atropine Juno Injection.

This medicine is available only with a doctor's prescription.

Before you are given Atropine Juno Injection

When you must not be given it

Do not use Atropine Juno Injection if you have an allergy or have had an unusual reaction to atropine or any of the anticholinergic medicines such as hyoscyamine and belladonna.

Do not use Atropine Juno Injection if you have or have had any medical conditions, especially the following:

  • severe and chronic inflammation of the large intestine and rectum
  • gastrointestinal blockage and/or diseases
  • enlarged prostate
  • urinary tract blockage and/or bladder problems
  • fever, or if you are exposed to very high temperatures
  • glaucoma and/or family history of glaucoma
  • myasthenia gravis (severe muscle weakness)
  • acute bleeding, especially if you have heart problems
  • heart disease
  • high blood pressure due to pregnancy
  • overactive thyroid.

If you are not sure whether any of these apply to you, check with your doctor.

Before you are given it

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you have or have had any medical conditions, especially the following:

  • brain damage and/or mental confusion
  • lung diseases
  • liver and/or kidney diseases
  • hormone problems
  • high blood pressure
  • fast heart beat
  • hiatus hernia
  • heart diseases
  • stomach and intestinal problems
  • gastric ulcer, diarrhoea or gastrointestinal infection.

Tell your doctor if you are pregnant or plan to become pregnant or are breast-feeding. Your doctor can discuss with you the risks and benefits involved.

Taking other medicines

Tell your doctor if you are taking any other medicines, including:

  • all prescription medicines
  • all medicines, vitamins, herbal supplements or natural therapies you buy without a prescription from a pharmacy, supermarket, naturopath or health food shop.

Some medicines and atropine sulfate monohydrate may interfere with each other. These include:

  • medicines to treat irregular heart beat e.g. disopyramide and quinidine
  • blood "thinning" medicines e.g. heparin, warfarin
  • medicines to treat Parkinson's disease
  • metoclopramide, a medicine to treat nausea and vomiting
  • cisapride, a medicine used in certain stomach problems
  • anticholinergic medicines to prevent travel sickness, relieve stomach cramps or spasms
  • antispasmodics
  • bethanechol, a medicine used in bladder function disorders
  • antihistamines
  • medicines to treat depression such as tricyclic antidepressants
  • medicines used to treat certain mental and emotional conditions
  • ketaconazole, a medicine to treat fungal infections
  • narcotic analgesics to treat severe pain
  • medicines used for glaucoma e.g. pilocarpine, carbachol
  • medicines to treat Alzheimer's disease e.g. rivastigmine and donepezil
  • muscle relaxants used during an operation.

If you are to receive Atropine Juno Injection as a premedication, your doctor will advise if you should continue to take your regular medicines.

How Atropine Juno Injection is given

Atropine sulfate monohydrate will be injected by your doctor or nurse under the skin, into the muscle or directly into the blood stream.

Your doctor will decide what dose and how often you will receive Atropine Juno Injection. The dosage you will be given will depend on your condition, what it is being used for and other factors, such as your age, and whether or not other medicines are being given at the same time.

If you are given too much (overdose)

This rarely happens as Atropine Juno Injection is administered under the care of a highly trained doctor.

However, if you are given too much atropine sulfate monohydrate, you may experience some of the effects listed under "Side effects" below.

The signs of overdose are dilation of the pupils, difficulty in swallowing, hot dry skin, flushing and inability to pass urine. Rapid breathing, increased heart rate and hyperactivity may also occur.

Your doctor has information on how to recognise and treat an overdose. Ask your doctor if you have any concerns.

Side Effects

Tell your doctor, nurse or pharmacist as soon as possible if you do not feel well after you have being given atropine sulfate monohydrate.

Like other medicines, atropine sulfate monohydrate can cause some side effects. If they occur, most are likely to be minor or temporary.

However, some may be serious and need medical attention.

Ask your doctor or pharmacist to answer any questions that you may have.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

Tell your doctor if you notice any of the following:

  • blurred vision and/or discomfort in the eyes especially if your eyes are more sensitive to light than normal, dilation of pupils
  • difficulty in urinating
  • constipation
  • fever
  • flushing, dryness of skin
  • skin rash, hives
  • headache, dizziness, drowsiness and/or weakness
  • nervousness, restlessness, confusion, unusual excitement shaking and/or tremor
  • nausea, vomiting
  • fast and/or irregular heart beat
  • loss of taste
  • dryness of the mouth, nose and throat, thirst.

Other side effects not listed above may also occur in some patients. If you notice any other effects, check with your doctor or nurse.

Storage

Atropine Juno Injection will be stored in the pharmacy or on the ward. The injection is kept in a cool dry place, where the temperature stays below 25°C.

Product description

What it looks like

Atropine Juno Injection is a clear, colourless solution in a glass ampoule.

It is available in packs of 10 (600 microgram only.

Ingredients

Atropine Juno Injection contains the active ingredient atropine sulfate monohydrate 600 microgram per mL or 400 microgram per mL, 500 microgram per mL or 1.2 mg per mL. It also contains sodium chloride and Water for Injections.

It does not contain preservatives.

Supplier

Atropine Juno Injection is supplied in Australia by:

Juno Pharmaceuticals Pty Ltd
42 Kelso Street
Cremorne, VIC – 3121,
Australia
www.junopharm.com.au

Date of preparation

This leaflet was prepared in October 2021.

Published by MIMS September 2022

BRAND INFORMATION

Brand name

Atropine Juno

Active ingredient

Atropine sulfate monohydrate

Schedule

S4

 

1 Name of Medicine

Atropine sulfate monohydrate.

2 Qualitative and Quantitative Composition

0.6 mg/mL injection.

A clear, colourless, sterile solution containing 0.6 mg/mL atropine sulphate.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Clear colourless particle free solution.

4 Clinical Particulars

4.1 Therapeutic Indications

Surgery.

Atropine Juno may be given as a pre-anaesthetic medication to inhibit excessive salivary and bronchial secretions and to diminish the risk of vagal inhibition of the heart. The use of Atropine Juno as an antisialagogue is rarely necessary since the introduction of halothane and similar anaesthetics in place of ether anaesthesia.
Atropine Juno may be administered concurrently with anticholinesterase agents (e.g. neostigmine, physostigmine) to block the adverse muscarinic effects when they are used after surgery to terminate curarisation.

Cardiopulmonary resuscitation.

It may be used in the management of patients with sinus bradycardia who have associated hypotension and increased ventricular irritability.

Anticholinesterase poisoning.

Atropine Juno is also used in the treatment of sinus bradycardia induced by organophosphate pesticides, Amanita muscaria mushrooms or other compounds with anticholinesterase activity. A cholinesterase reactivator, e.g. pralidoxime iodide, may be given concurrently.

4.2 Dose and Method of Administration

Atropine Juno may be administered by subcutaneous (SC), intramuscular (IM) or direct intravenous (IV) injection. Atropine Juno contains no antimicrobial agent. It should be used only once in one patient only and any residue discarded. Atropine Juno should not be added to any IV infusion solution.

Surgery.

Adults.

300-600 microgram of atropine sulfate IM or SC, approximately 1 hour before anaesthesia, usually in conjunction with a narcotic. Alternatively, 300-600 microgram atropine sulfate may be given IV immediately prior to induction of anaesthesia.
To reverse the effects of non depolarising muscle relaxants, 600 microgram - 1.2 mg atropine sulfate may be given to adults as a slow IV injection in conjunction with the anticholinesterase agent (e.g. neostigmine methylsulfate) of choice.

Paediatrics.

Suitable premedication doses to be given subcutaneously 30-60 minutes prior to surgery in children are suggested below:
Infants weighing less than 3 kg: 100 microgram.
Children weighing 7 to 9 kg: 200 microgram.
Children weighing 12 to 16 kg: 300 microgram.
Children weighing 20 to 27 kg: 400 microgram.
Children weighing 32 kg: 500 microgram.
Children weighing 41 kg: 600 microgram
To reverse the effects of non depolarising muscle relaxants, atropine 0.02 mg/kg for each 0.04 mg/kg of neostigmine methylsulfate may be given to children as a slow IV injection.

Cardiopulmonary resuscitation.

Adults.

Atropine Juno 0.5-1 mg IV may be repeated every 5 minutes until the desired effect on heart rate or asystole is achieved. IV doses of less than 0.5 mg should usually not be used in adults, since paradoxical slowing of the heart rate may occur. The total dose should not exceed 2 mg.

Paediatrics.

The usual paediatric dose is 0.02 mg/kg with a minimum of 0.1 mg (maximum single dose 0.5 mg) intravenously, which may be repeated at 5 minute intervals until the desired heart rate is achieved. The total dose should not exceed 1 mg in children and 2 mg in adolescents.
When cardiac arrest has occurred, external cardiac massage or other method of resuscitation is required to distribute the drug after intravenous injection.

Treatment of anticholinesterase poisoning.

Adults.

An initial dose of 1-2 mg for mild poisoning, and up to 6 mg for severe poisoning; this is given IV preferably, or IM. Atropine can be given as often as every 5 minutes until secretions are minimal and ventilation is adequate. Treatment should be repeated if muscarinic symptoms reappear. In moderate to severely poisoned adult, atropine is given for at least two days. In severe cases atropine therapy should be withdrawn gradually to avoid abrupt recurrence of symptoms (e.g. pulmonary oedema). Pralidoxime enhances the effect of atropine.

Paediatrics.

0.05 mg/kg intramuscularly or intravenously repeated at 10 to 30 minute intervals until muscarinic signs and symptoms subside. This is to be repeated if these reappear.

4.3 Contraindications

Known hypersensitivity to atropine or other anticholinergic agents.
Obstructive disease of the gastrointestinal tract (e.g. pyloroduodenal stenosis, achalasia), cardiospasm, paralytic ileus or intestinal atony.
Reflux oesophagitis.
Severe ulcerative colitis or megacolon complicating ulcerative colitis.
Prostatic enlargement.
Acute angle-closure glaucoma.
Unstable cardiovascular status in acute haemorrhage.
Tachycardia secondary to cardiac insufficiency or thyrotoxicosis.
Toxaemia of pregnancy.
Obstructive uropathy (e.g. bladder neck obstruction caused by prostatic hypertrophy).
Myasthenia gravis (unless used to treat the adverse effects of an anticholinesterase agent).
Due to risk of provoking hyperpyrexia due to reduced sweating, atropine should not be given to febrile patients, or when the ambient temperature is high.

4.4 Special Warnings and Precautions for Use

Atropine should be used with caution in all patients, and especially in patients over 40 years old as they may be more susceptible to adverse effects. Atropine should be administered with extreme care in patients with any severe heart disease, hypertension, mild or moderate ulcerative colitis, ileus, chronic pulmonary disease, hyperthyroidism, autonomic neuropathy, hepatic or renal disease or prostatic hypertrophy, oesophageal reflux or hiatus hernia, gastric ulcer, diarrhoea or gastrointestinal infection.
Elderly patients may react with excitement, agitation, drowsiness or confusion to even small doses of atropine. Changes in dosage should be gradual.
Atropine should be used with caution in elderly patients since they may be more susceptible to its adverse effects. Atropine may cause mental confusion, especially in elderly or brain damaged patients. Elderly patients may react with excitement, agitation, drowsiness or confusion to even small doses of Atropine. Changes in dosage should be gradual.
Memory may become severely impaired in elderly patients, especially those who already have memory problems, with the continued use of anticholinergics since these drugs block the actions of acetylcholine, which is responsible for many functions of the brain, including memory functions.

Glaucoma.

Conventional parenteral doses of atropine may precipitate acute glaucoma in susceptible individuals.

Myasthenia gravis.

Atropine should be used with extreme caution in patients with myasthenia gravis and should generally only be given to reduce adverse muscarinic effects of an anticholinesterase (see Section 4.3 Contraindications).

Cardiovascular status.

In conditions characterised by tachycardia, such as cardiac insufficiency or failure, extreme caution must be exercised (see Section 4.3 Contraindications). Care is also required in cardiac surgery, in patients with acute myocardial infarction or ischaemia as atropine may worsen the symptoms, and in patients with hypertension.
Patients with known cardiac problems have developed angina following administration of atropine.
Atropine has been associated with the development of arrhythmias in adult and paediatric patients. Accelerated heart rate and intraventricular conduction delays have been associated with the development of ventricular fibrillation.

Gastrointestinal.

Since atropine decreases gastrointestinal motility, it should be used with caution in patients with gastric ulcer, oesophageal reflux, known or suspected gastrointestinal infections, e.g. Clostridium difficile associated diarrhoea and colitis (antibiotic associated pseudomembranous colitis), incomplete intestinal obstruction or ulcerative colitis. Atropine should also be used with caution in patients with diarrhoea, since diarrhoea may be an early symptom of incomplete intestinal obstruction, especially in patients with ileostomy or colostomy.

Down's syndrome and albinism.

Persons with Down's syndrome appear to have an increased susceptibility to some of the actions of atropine, whereas those with albinism may have a reduced susceptibility.

Use in the elderly.

Atropine should be used with caution in debilitated patients. These patients, especially those with chronic pulmonary disease, may be susceptible to the formation of bronchial mucous plugs due to decreased bronchial secretions.

Paediatric use.

Atropine should be used with caution in infants and small children as they may be more susceptible to its adverse effects. Children are particularly at risk of rapid increase in body temperature in hot weather, due to reduced sweating. It should be used with caution in children with Down's syndrome, spastic paralysis or brain damage as they may be hypersensitive to the effects of atropine.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Potentiating effects.

Antimuscarinic effects.

The effect of atropine may be enhanced by concomitant administration of other drugs with antimuscarinic properties, such as:
amantadine;
some antihistamines, including cyproheptadine, promethazine;
butyrophenones e.g. haloperidol;
phenothiazines e.g. chlorpromazine, fluphenazine, prochlorperazine, thioridazine, trifluoperazine;
tricyclic antidepressants e.g. amitriptyline, desipramine, doxepin, imipramine, nortriptyline;
belladonna;
procainamide;
antispasmodics;
antiparkinsonian drugs;
antiarrhythmics with anticholinergic activity (e.g. disopyramide, quinidine).
Patients should be advised to report occurrence of gastrointestinal problems promptly since paralytic ileus may occur with concurrent therapy.

MAOIs.

Inhibition of drug metabolizing enzymes by MAOIs may possibly enhance the effects of atropine.

Opioid (narcotic) analgesics.

Concurrent use with anticholinergics may result in increased risk of severe constipation, which may lead to paralytic ileus and/or urinary retention.

Urinary alkalizers.

Urinary excretion of atropine may be delayed by alkalization of the urine, thus potentiating its effects.

Absorption.

The absorption of other medicines may be affected by the reduction in gastric motility caused by atropine.

Ketoconazole.

Anticholinergics may increase gastrointestinal pH, possibly resulting in a marked reduction in ketoconazole absorption during concurrent use. If concomitant therapy is necessary, atropine should be given at least two hours after oral ketoconazole.

Antagonist interactions.

Atropine antagonises the actions of a number of compounds, including:
synthetic choline esters e.g. bethanecol, carbachol;
anticholinesterase drugs e.g. physostigmine, neostigmine, pyridostigmine;
cholinomimetic alkaloids e.g. pilocarpine;
parasympathomimetics (each may counteract the effect of the other).

Cisapride and metoclopramide.

Concurrent use with anticholinergics may antagonize the effects of cisapride and metoclopramide on gastrointestinal motility.

Haloperidol.

Antipsychotic effectiveness of haloperidol may be decreased in schizophrenic patients.

Cholinesterase inhibitors.

In view of the pharmacodynamic effects of atropine, atropine may interfere with the activity of cholinesterase inhibitors such as rivastigmine, donepezil.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Studies have not been done in either animals or humans to evaluate the potential to impair fertility.
(Category A)
Although atropine has been taken by a large number of pregnant women and women of childbearing age without an increase in the frequency of malformations or other direct or indirect harmful effects on the foetus being observed, the safety of atropine in pregnancy has not been positively established. As with all other drugs, caution must be exercised in the use of atropine in pregnant women and women of child-bearing age.
Atropine crosses the placental barrier and may cause tachycardia in the foetus.
 Small amounts of atropine have been found in human breast milk, therefore atropine should only be administered to breast-feeding mothers if absolutely necessary. Atropine may cause antimuscarinic effects in the infant. Atropine may inhibit lactation.

4.7 Effects on Ability to Drive and Use Machines

Systemic administration of antimuscarinics may cause drowsiness, blurred vision, dizziness and other effects that may impair a patient's ability to perform tasks requiring mental alertness and/or visual acuity (such as driving or operating machinery).

4.8 Adverse Effects (Undesirable Effects)

Most side effects are directly related to the antimuscarinic actions of atropine. Adverse effects following single or repeated doses are most often the result of excessive dosage.

Cardiovascular.

Transient bradycardia followed by tachycardia with palpitations and arrhythmia. Atropine blocks vagal impulses with consequent increase in heart rate with possible atrial arrhythmias, atrioventricular dissociation, multiple ventricular ectopics and angina.
The development of angina in patients with known cardiac problems has been reported. Hypertensive crises and atrioventricular block have also been reported.

Central nervous system.

Dryness of the mouth with difficulty in swallowing or talking, thirst. These are due to the reduction of salivary, bronchial and sweat secretions and are dose related. Active and passive functions of the Eustachian tube may be affected.
Tremor, fatigue, drowsiness, ataxia, mental confusion and/or excitement, dizziness, loss of taste, headache, nervousness, weakness, nausea, vomiting, insomnia, psychotic reactions, sedation and seizures. Anhidrosis also may occur and produce heat intolerance in patients living in a hot environment. The inhibition of sweat secretions may also result in hyperthermia.

Gastrointestinal.

Constipation; due to inhibition of parasympathetic control of the gastrointestinal tract. Paralytic ileus. Nausea, vomiting, retrosternal pain due to increased gastric reflux, bloated feeling.

Genitourinary.

Urinary difficulty and retention due to inhibition of parasympathetic control of the bladder.

Ocular.

Visual changes, including blurred vision. Dilatation of the pupils (mydriasis) with loss of accommodation (cycloplegia) and photophobia can occur with increasing doses of atropine. Increased ocular tension.

Dermatological.

Flushing and dryness of the skin. Hypersensitivity reactions may manifest as conjuncitivitis or skin rash which, in some instances, progresses to exfoliation and various dermal manifestations.

Other.

More common: Redness or other signs of irritation at the injection site.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration 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 at http://www.tga.gov.au/reporting-problems.

4.9 Overdose

Symptoms.

Acute overdosage of atropine produces both peripheral and central signs and symptoms characterised by dilated pupils, difficulty swallowing, hot dry skin, vasodilation and urinary retention. A rash may appear on the face or upper trunk. Tachycardia and hypertension with arrhythmias, anxiety, delirium, hallucinations, hyperactivity convulsions, marked dryness of the mouth, photophobia, raised body temperature, leucocytosis, nausea, vomiting and restlessness also occur. In severe overdosage, CNS depression, circulatory collapse and hypotension may be followed by coma, skeletal muscle paralysis and death from respiratory and circulatory failure.
In addition to tachycardia, cardiac manifestations may include ECG abnormalities (e.g. ventricular arrhythmias, extrasystoles resulting from enhanced re-entrant excitation secondary to reduced conduction velocity). Widening of the QRS complex, prolongation of the QT interval and ST segment depression may also be seen.
There is considerable variation in susceptibility to atropine; recovery has occurred even after 1 g, whereas deaths have been reported from doses of 100 mg or less for adults and 10 mg in children.

Treatment.

Symptomatic treatment should be instigated to ensure an adequate airway is maintained, fluids are replaced and body temperature is lowered using cold packs and tepid sponging. Artificial respiration with oxygen may be necessary and urinary catheterization may be required. Hypoxia and acidosis should be corrected and sodium bicarbonate may be given even if acidosis is not present. If photophobia occurs, the patient may be kept in a dark room.
Diazepam may be given to control marked excitement and convulsions however the risk of central depression occurring late in the course of atropine poisoning contraindicates large doses of sedative; phenothiazines should not be given since they may exacerbate antimuscarinic effects.
Antiarrhythmics are not recommended if arrhythmias develop.
The use of physostigmine as an antidote for atropine poisoning is controversial due to the potential for physostigmine to produce severe adverse effects, e.g. seizures, asystole. The use of physostigmine should be reserved for treatment of patients with extreme delirium or agitation, patients with repetitive seizures, patients with severe sinus tachycardia or supraventricular tachycardia or unresponsive extreme hyperthermia in patients who fail to respond to alternative therapy. Physostigmine should not be used to treat cardiac conduction defects or ventricular tachyarrhythmias. IV propranolol may be useful for treatment of supraventricular tachyarrhythmias unresponsive to physostigmine or where physostigmine is contraindicated. Physostigmine should be used with caution in the presence of asthma, gangrene, cardiovascular disease or mechanical obstruction of the gastrointestinal or genitourinary tract. Physostigmine should be used in these circumstances only if a life-threatening emergency occurs.
Dialysis is not effective in atropine overdose.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Atropine (dl-hyoscyamine) is often classified as an anticholinergic drug but is more accurately described as an antimuscarinic agent since it inhibits the muscarinic actions of acetylcholine, possessing both central and peripheral activity.
Atropine has activity both on structures innervated by postganglionic cholinergic nerves, and on smooth muscles which respond to endogenous acetylcholine but are not so innervated. As with other antimuscarinic agents, the major action of atropine is a competitive or surmountable antagonism which can be overcome by increasing the concentration of acetylcholine at receptor sites of the effector organ (e.g. by using anticholinesterase agents which inhibit the enzymatic destruction of acetylcholine). The receptors antagonised by atropine in therapeutic doses are primarily the peripheral structures that are stimulated or inhibited by muscarine (i.e. exocrine glands and smooth and cardiac muscle). Responses to postganglionic cholinergic nerve solution also may be inhibited by atropine but this occurs less readily than with responses to injected (exogenous) choline esters.
Atropine-induced parasympathetic inhibition may be preceded by a transient phase of stimulation, especially on the heart where small doses first slow the rate before characteristic tachycardia develops due to paralysis of vagal control. Atropine exerts a more potent and prolonged effect on the heart, intestine and bronchial muscle than hyoscine, but its action on the iris, ciliary body and certain secretory glands is weaker than that of hyoscine. Unlike the latter, atropine in therapeutic doses does not depress the central nervous system but may stimulate the medulla and higher cerebral centres. Although mild vagal excitation occurs, the increased respiratory rate and (sometimes) increased depth of respiration produced by atropine are more probably the result of bronchiolar dilatation. Accordingly, atropine is an unreliable respiratory stimulant and large or repeated doses may depress respiration.
Adequate doses of atropine abolish various types of reflex vagal cardiac slowing or asystole. The drug also prevents or abolishes bradycardia or asystole produced by injection of choline esters, anticholinesterase agents or other parasympathetic drugs, and cardiac arrest produced by stimulation of the vagus.
Atropine sulfate injection in therapeutic doses counteracts the peripheral dilatation and abrupt decrease in blood pressure produced by choline esters. However, when given by itself, atropine does not exert a striking or uniform effect on blood vessels or blood pressure. Systemic doses slightly raise systolic and lower diastolic pressures and can produce significant postural hypotension. Such doses also slightly increase cardiac output and decrease central venous pressure. Occasionally, therapeutic doses dilate the cutaneous blood vessels, particularly in the "blush" area (atropine flush), and may cause atropine "fever" due to suppression of sweat gland activity in infants and small children.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Atropine is well absorbed following IM administration. Peak plasma levels are observed within 30 minutes of injection, accompanied by an increase in heart rate which reaches a maximum at 15 to 50 minutes. The duration of effect on the heart rate is reported to be up to 5 hours. The effect on salivation is delayed, with a peak effect occurring approximately 100 minutes after the injection and persisting for up to 4 hours.

Distribution.

Following intravenous administration serum levels of atropine drop rapidly within the first ten minutes and then decrease more gradually. One hour after either IM or IV injection atropine levels are very similar.
Atropine is well distributed throughout the body, crossing both the blood-brain and placental barriers, and distributing into the milk in small quantities. It has a large apparent volume of distribution (2-4 L/kg).
Atropine shows a high inter-individual variability in serum protein binding, ranging from 22.5% ± 20.6% (children); 14% ± 9.1% (age 16 to 58); 22.2% ± 16.7% (age 65 to 75).

Metabolism and excretion.

Atropine is metabolised by the liver and excreted mainly in the urine. About 30 to 50% of a dose is excreted in urine unchanged, the rest as metabolites. Atropine has a plasma half life of approximately 4 hours in adults, with a longer half-life of approximately 6.5 hours in children.

5.3 Preclinical Safety Data

Genotoxicity.

Studies have not been undertaken in either animals or humans to evaluate the mutagenic potential of atropine.

Carcinogenicity.

Studies have not been undertaken in either animals or humans to evaluate the carcinogenic potential of atropine.

6 Pharmaceutical Particulars

6.1 List of Excipients

Sodium chloride, sulphuric acid/sodium hydroxide, water for injections.

6.2 Incompatibilities

Atropine has been reported to be incompatible with alkaline solutions and solutions containing the following: adrenaline hydrochloride, amylobarbitone sodium, ampicillin sodium, chloramphenicol sodium succinate, chlortetracycline hydrochloride, cimetidine, heparin sodium, hydroxybenzoate preservatives, metaraminol bitartrate, methicillin sodium, methohexitone sodium, nitrofurantoin sodium, novobiocin sodium, oxacillin sodium, pentobarbitone sodium, sodium bicarbonate, sulphadiazine sodium, sulphafurazole diethanolamine, tetracycline hydrochloride, thiopentone sodium, vitamin B complex and ascorbic acid, warfarin sodium. This list is not exhaustive.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C. Protect from light.

6.5 Nature and Contents of Container

1 mL ampoule clear glass (Type 1):600 microgram/mL pack of 10 ampoules.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Atropine sulfate monohydrate is bis[(1R,3r,5S)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl (2RS)-3-hydroxy-2-phenylpropanoate] sulphate monohydrate. It is a white, crystalline powder or colourless crystals, very soluble in water, freely soluble in alcohol and practically insoluble in ether.

Chemical structure.


CAS number.

5908-99-6.
Molecular weight: 694.8.
Molecular formula: (C17H23NO3)2.H2SO4, H2O.

7 Medicine Schedule (Poisons Standard)

Schedule 4 Prescription Medicine Only.

Summary Table of Changes