Consumer medicine information

Acetadote

Acetylcysteine

BRAND INFORMATION

Brand name

Acetadote Concentrated Injection

Active ingredient

Acetylcysteine

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Acetadote.

SUMMARY CMI

ACETADOTE®

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why is Acetadote being given?

Acetadote contains the active ingredient acetylcysteine. Acetadote is used to treat an overdose of paracetamol.

For more information, see Section 1. Why is Acetadote being given? in the full CMI.

2. What should I know before Acetadote is given?

Do not use it if you have ever had an allergic reaction to Acetadote or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before Acetadote is given? in the full CMI.

3. What if I am using other medicines?

Some medicines may interfere with Acetadote and affect how it works.

A list of these medicines is in Section 3. What if I am using other medicines? in the full CMI.

4. How is Acetadote given?

  • Acetadote must only be given by a doctor or nurse and your doctor will decide what dose of Acetadote to be given. This depends on your medical condition and whether or not you are taking any other medicines.
  • Acetadote is given by slow injection into a vein.

More instructions can be found in Section 4. How is Acetadote given? in the full CMI.

5. What should I know while using Acetadote?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that Acetadote is being given to you.
  • Tell your doctor or nurse as soon as possible if you do not feel well while you are being given Acetadote.
Driving or using machines
  • Be careful driving or operating machinery after you have been given Acetadote.
Drinking alcohol
  • Tell your doctor if you drink alcohol. Alcohol may affect the use of Acetadote.
Looking after the medicine
  • Acetadote will be stored in the surgery, pharmacy or ward of a hospital. The injection is kept in a cool dry place protected from light where the temperature stays below 25°C.

For more information, see Section 5. What should I know while using Acetadote? in the full CMI.

6. Are there any side effects?

Acetadote side effects include chest pain, bluish discolouration around the mouth, nausea, vomiting and stomach upset, generally feeling unwell or anxious, muscle stiffness, pain and inflammation at the injection site.

Acetadote may cause allergic reactions, symptoms of which include breathing issues, skin problems, dizziness, light-headedness and irregular or fast heartbeat.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

ACETADOTE®

Active ingredient: acetylcysteine

Consumer Medicine Information (CMI)

This leaflet provides important information about using Acetadote. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using Acetadote.

Where to find information in this leaflet:

1. Why is Acetadote being given?
2. What should I know before Acetadote is given?
3. What if I am using other medicines?
4. How is Acetadote given?
5. What should I know while using Acetadote?
6. Are there any side effects?
7. Product details

1. Why is Acetadote being given?

Acetadote contains the active ingredient acetylcysteine. Acetadote is used to treat an overdose of paracetamol.

This medicine belongs to a group of medicines called antidotes.

This medicine works by reacting with the toxic by-products of paracetamol to prevent damage to the liver.

Ask your doctor if you have any questions about why this medicine has been prescribed for you.

Your doctor may have prescribed it for another reason.

There is no evidence that Acetadote is addictive.

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

2. What should I know before Acetadote is given?

Warnings

You should not be given Acetadote if:

  • you are allergic to any medicine containing acetylcysteine, or any of the ingredients listed at the end of this leaflet.
    Always check the ingredients to make sure you can use this medicine.
    Some of the symptoms of an allergic reaction may include:
    - shortness of breath
    - wheezing or difficulty breathing
    - swelling of the face, lips, tongue or other parts of the body
    - rash, itching or hives on the skin
    - redness of the skin
    - dizziness, light-headedness
    - fast heartbeat
  • the solution is discoloured, cloudy, turbid, or a precipitate is present.
    The solution is normally a clear colourless solution but may turn slightly pink or purple once in use. This colour change does not affect the quality of the medicine.
  • when diluted with another solution, it causes the solution to precipitate, become cloudy, turbid, discolour, or particles are visible.
    The doctor or nurse will check to ensure the medicine is not past its expiry date and has not been tampered with.

If you are not sure whether you should be given this medicine, talk to your doctor.

Check with your doctor if you:

  • have allergies to any other medicines, foods, preservatives or dyes.
  • have or have had any of the following medical conditions
    - asthma or difficulty breathing
    - liver disease
    - kidney disease
    - stomach ulcers
  • take any medicines for any other condition

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

Your doctor can discuss with you the risks and benefits involved.

If you have not told your doctor about any of the above, tell them before you are given this medicine.

3. What if I am using other medicines?

Tell your doctor or nurse if you are taking any medicines for any other condition, including any that you get without a prescription from your pharmacy, supermarket or health food shop, naturopath or herbalist.

Some medicines may interfere with Acetadote and affect how it works.

Check with your doctor or nurse if you are not sure about what medicines, vitamins or supplements you are taking and if these affect Acetadote.

Your doctor has more information on medicines to be careful with or avoid while being given this medicine.

4. How is Acetadote given?

How much to be given

  • Acetadote must only be given by a doctor or nurse. Acetadote is given by slow injection into a vein. Your doctor will decide what dose of Acetadote you will receive and how long you will receive it. This depends on your medical condition and other factors, such as your weight.

If too much Acetadote is given

Acetadote must only be given to you by a doctor or nurse and so an overdose is unlikely to occur.

Symptoms of an overdose are the same as side effects but may be more severe.

The symptoms of a side effect are listed under Section 6. Are there any side effects?

If you think too much Acetadote is used, you may need urgent medical attention.

You should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while using Acetadote?

Things you should do

If you are about to be started on any new medicine, remind your doctor and pharmacist that you have been given Acetadote.

Tell any other doctors, dentists, and pharmacists who treat you that you have been given this medicine.

If you are about to have any urine tests, tell your doctor that you are being given this medicine.

It may interfere with the results of some tests.

If you feel light-headed, dizzy or faint when getting out of bed or standing up, get up slowly.

Standing up slowly, especially when you get up from bed or chairs, will help your body get used to the change in position and blood pressure. If this problem continues or gets worse, talk to your doctor.

Call your doctor straight away if you:

  • do not feel well while you are being given Acetadote.
    This medicine helps most people with paracetamol overdose, but it may have unwanted side effects in a few people. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.
  • have any questions you may have.

Remind any doctor, dentist or pharmacist you visit that you are using Acetadote.

Things you should not do

Driving or using machines

Be careful before you drive or use any machines or tools until you know how Acetadote affects you.

Drinking alcohol

Tell your doctor if you drink alcohol. Alcohol may affect the use of Acetadote.

Looking after your medicine

  • Acetadote will be stored in the surgery, pharmacy or ward of a hospital. The injection is kept in a cool dry place protected from light where the temperature stays below 25°C.
  • Acetadote will only be opened when it is time for you to have the injection.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or nurse if you have any further questions about side effects.

Side effects

Side effectsWhat to do
Digestive system:
  • nausea, vomiting and stomach upset
Skin related:
  • redness or swelling of the face or around the eyes
  • itchy rash
Systemic symptoms:
  • generally feeling unwell or anxious
Musculoskeletal symptoms:
  • muscle stiffness
Localized symptoms:
  • pain and inflammation at the injection site
Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
Cardiovascular system:
  • chest pain
  • irregular or fast heartbeat
Symptoms of allergic reactions
Respiratory system:
  • shortness of breath
  • wheezing or difficulty breathing or swallowing
  • coughing
Skin related:
  • bluish discolouration around the mouth
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching or hives on the skin
Nervous system:
  • dizziness, light-headedness
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Tell your doctor or nurse if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Some of these side effects can only be found when your doctor does tests from time to time to check your progress.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor, nurse or pharmacist before you decide to stop taking any of your medicines.

7. Product details

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

What Acetadote contains

Active ingredient
(main ingredient)		acetylcysteine
Other ingredients
(inactive ingredients)		sodium hydroxide
water for injections

Do not take this medicine if you are allergic to any of these ingredients.

This medicine does not contain lactose, sucrose, gluten, tartrazine, alcohol, dyes or preservatives.

What Acetadote looks like

Acetadote is a clear, colourless to purplish solution with a faint odour of hydrogen sulphide in a clear glass vial with a plastic top.

Acetadote is available in 30 mL vials, packaged in a pack of 4 (Aust R 183299).

Who distributes Acetadote

In Australia:

Phebra Pty Ltd
17-19 Orion Road
Lane Cove West, NSW 2066
Australia
Telephone: 1800 720 020

In New Zealand:

AFT Pharmaceuticals Ltd
PO Box 33-203, Auckland.
Telephone: +64 9 4880232

The leaflet was prepared in January 2025.

Phebra and the Phi symbol are registered trademarks of Phebra Pty Ltd.

Published by MIMS April 2025

BRAND INFORMATION

Brand name

Acetadote Concentrated Injection

Active ingredient

Acetylcysteine

Schedule

S4

 

1 Name of Medicine

Acetylcysteine.

2 Qualitative and Quantitative Composition

Acetylcysteine 200 mg per mL (as acetylcysteine). Each 30 mL vial contains 6 g acetylcysteine.
While the concentration of acetylcysteine in Acetadote Concentrated Injection is exactly the same as in other acetylcysteine injectable products, each vial does contain three times the quantity of the active ingredient; that is, 6 g in 30 mL for Acetadote, as compared to 2 g in 10 mL for other acetylcysteine injectable products.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Acetadote Concentrated Injection is a clear, colourless or purplish solution with a faint odour of hydrogen sulfide, sterile, pyrogen free aqueous solution of acetylcysteine (N-acetyl-mercapto-alanine) with a pH of approximately 6.5 to 7.5.
Acetadote Concentrated Injection is intended for intravenous administration, following dilution in 5% glucose solution.

4 Clinical Particulars

4.1 Therapeutic Indications

As an antidote for paracetamol poisoning: Acetadote Concentrated Injection is indicated in the treatment of paracetamol overdose to protect against hepatotoxicity.

4.2 Dose and Method of Administration

To be most effective in protecting against liver damage, therapy with Acetadote should be started within 10 hours of paracetamol ingestion. Although the role of Acetadote therapy in patients presenting later than 15 hours after paracetamol ingestion is not established, it may be considered as a clinical option in high risk patients.

Management of paracetamol overdosage.

It should be noted that, after an ingestion of a potentially fatal dose of paracetamol, the patient may appear relatively well initially and may even continue normal activities for a day or two before the onset of hepatic failure. Hepatic damage is more likely to occur with a lower dosage of paracetamol in patients who have a history of chronic alcohol or enzyme-inducing drug ingestion (e.g. isoniazid, rifampicin, anticonvulsants including carbamazepine, phenytoin, phenobarbitone, primidone, sodium valproate).
Patients are notoriously unreliable as to the amount of paracetamol ingested and the time of ingestion. Hepatic necrosis is preventable if treatment can be instituted within 10 to 12 hours of paracetamol ingestion.

Note.

Liver damage may not be biochemically apparent for 24 to 48 hours after ingestion.
Hepatic necrosis has been seen following ingestion of 6 grams of paracetamol, and death with 15 grams.
A. Patient presenting within 15 hours of ingestion. Give activated charcoal (1 to 2 grams/kg) if it is within 1 hour of paracetamol ingestion, and the patient's conscious state is not impaired.
Plasma paracetamol levels should be obtained no earlier than 4 hours after ingestion of the paracetamol overdose. Concentrations determined prior to this time are not reliable for assessing potential hepatotoxicity. If the time of ingestion is unknown, paracetamol levels should be measured immediately.
Measurements of plasma liver enzymes and bilirubin levels, and coagulation studies, should be performed as soon as possible after admission. Blood urea, electrolytes, glucose and blood gases should be obtained. The laboratory measurements are used to monitor hepatic and renal function and electrolyte balance. An ECG should also be performed.
Plasma paracetamol levels can be used to determine the likelihood of hepatic damage when compared with the nomogram in Figure 1.

Caution.

Use correct units for paracetamol concentration.

Note.

To convert paracetamol concentrations from micromol/L to microgram/mL, divide by 6.61.
Do not delay acetylcysteine therapy while awaiting the results of plasma assays. Once the results become available, treatment may be discontinued if the initial concentration is below the nomogram reference line.
Do not discontinue acetylcysteine therapy if the initial level is above the reference line and subsequent levels fall below the reference line.
The nomogram is designed to be used for single acute ingestions. It is not helpful in determining the need for acetylcysteine in multiple or chronic ingestions.
The nomogram may not be suitable for use when patients have taken sustained release preparations of paracetamol.
Patients whose plasma paracetamol level is above the solid line are at a high risk of developing hepatotoxicity.
The middle line (25% below the solid line) is included to allow for possible errors in plasma assays and estimated time from ingestion and should be used as a guide to treatment.
Patients who have a history of chronic alcohol abuse or are receiving enzyme-inducing drugs are at greater risk of developing hepatotoxicity and if their plasma paracetamol level is up to 50% below the solid line they may require treatment with Acetadote Concentrated Injection.
B. Patients presenting more than 15 hours after ingestion. Plasma paracetamol, bilirubin and AST levels should be determined on an urgent basis, and a clinical decision made on how to proceed. Acetadote Concentrated Injection may be beneficial in patients presenting later than 15 hours after ingestion. The use of Acetadote Concentrated Injection should therefore be considered in high risk patients who present late, but only after discussion with physicians with substantial experience in the management of patients with paracetamol poisoning.
C. General management. Acetadote Concentrated Injection should be administered if appropriate (see A and B above). Acetadote Concentrated Injection should be diluted in 5% glucose solution, and administered by intravenous infusion. Nausea should be treated.
Daily liver function tests, and measurements of plasma urea, electrolytes, haemoglobin levels, white blood cell counts, platelets and prothrombin time should be made. Patients should be monitored for coagulation disorders, hepatic encephalopathy, renal failure and cardiac toxicity (minor ST changes are common). There is usually a mild metabolic acidosis. Hepatic encephalopathy is likely if bilirubin is above 60 millimoles per litre on days 3 to 5, or if the prothrombin time is prolonged.

Dosage in adults.

Acetadote Concentrated Injection is infused in three intravenous infusions containing different doses. This will give a total dose of 300 milligrams/kg of acetylcysteine infused over 20 hours.

Initial infusion.

An initial dose of 150 milligrams/kg of acetylcysteine diluted in 200 mL of 5% glucose solution and infused over 15 to 60 minutes.

Second infusion.

The initial infusion is followed by a continuous infusion of 50 milligrams/kg of acetylcysteine in 500 mL of 5% glucose solution over the next 4 hours.

Third infusion.

The second infusion is followed by a continuous infusion of 100 milligrams/kg of acetylcysteine in 1,000 mL of 5% glucose solution over the next 16 hours.
To reduce microbiological hazard, use as soon as practicable after dilution. If storage is necessary, hold at 2 to 8°C for not more than 24 hours.

Acetadote Concentrated Injection intravenous infusion dosage guide.

Acetadote Concentrated Injection is supplied in vials containing 30 mL of 200 mg/mL acetylcysteine for intravenous administration. While the concentration of acetylcysteine in Acetadote Concentrated Injection is exactly the same as in other acetylcysteine injectable products, each vial does contain three times the quantity of the active ingredient; that is, 6 g in 30 mL for Acetadote Concentrated Injection, as compared to 2 g in 10 mL for other acetylcysteine injectable products.
Since Acetadote Concentrated Injection does not contain an antimicrobial preservative, use in one patient on one occasion only and discard any residue.

Note.

The colour of Acetadote may turn from essentially colourless to a slight pink or purple once the stopper is punctured. The colour change does not affect the quality of the product.
Table 1 is intended as a guide on the volume (mL) of Acetadote Concentrated Injection 200 mg/mL that is required to be added to 5% glucose solution to prepare the initial, second and third infusion solutions. In order to use this table, the patient's weight in kilograms should be determined. The volume (mL) of Acetadote Concentrated Injection 200 mg/mL that should be added to 5% glucose solution to prepare the initial, second and third infusion solutions is shown in the three columns next to the patient's weight.

Dosage and administration in children.

Children should be treated with the same doses and regimens as adults. However, the quantity of intravenous fluid should be modified to take into account age and weight, as fluid overload is a potential danger.

4.3 Contraindications

Acetadote Concentrated Injection is contraindicated in patients with hypersensitivity or previous anaphylactic reaction to acetylcysteine or any component of the preparation.

4.4 Special Warnings and Precautions for Use

Acetadote Concentrated Injection should be used with caution in patients with asthma or where there is a history of bronchospasm. It should also be used with caution with patients with a past history of oesophageal varices and peptic ulceration (acetylcysteine-induced vomiting may increase the risk of haemorrhage).
Acetylcysteine is not compatible with rubber and some metals, particularly, iron, copper and nickel. Acetadote Concentrated Injection can be used satisfactorily with silicone rubber and plastic.

Patients with body weight less than 40 kg.

For patients weighing less than 40 kg, adjustment of total volume is recommended when administering acetylcysteine, to minimise the risk of hyponatraemia, seizure and death.

Patients on fluid restriction.

For patients on fluid restriction, adjustment of total volume is recommended when administering acetylcysteine, to minimise the risk of hyponatraemia, seizure and death.

Use in hepatic impairment.

Caution should be taken when administering acetylcysteine in patients with hepatic failure, since there is little data relating to the effects of acetylcysteine in impaired hepatic function. The decision to administer acetylcysteine should be passed on a risk/benefit assessment for the individual subject. In the presence of hepatic failure due to paracetamol overdose the degree of existing liver damage and the possible risk associated with the administration of acetylcysteine should be considered.

Use in renal impairment.

Caution should be taken when administering acetylcysteine in patients with renal failure, since there is little data relating to the effects of acetylcysteine in impaired renal function. The decision to administer acetylcysteine should be passed on a risk/benefit assessment for the individual subject.

Use in the elderly.

There are no adequate or well controlled studies in elderly patients. For this reason, the safety and effectiveness of Acetadote Concentrated Injection in the elderly has not been established.

Paediatric use.

While the safety and effectiveness of Acetadote Concentrated Injection in children has not been established, there is some limited clinical data in the use of acetylcysteine injection in children (see Section 5.1 Pharmacodynamic Properties, Clinical trials).
No paediatric specific adverse reactions have been documented.

Effects on laboratory tests.

Acetylcysteine may cause a false-positive reaction with reagent dipstick tests for urinary ketones.

4.5 Interactions with Other Medicines and Other Forms of Interactions

No information is available on the interaction of acetylcysteine with other medicines.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

There was evidence of effects on fertility in male rats given acetylcysteine at doses up to 60% of the maximum clinical dose, on a body surface area basis. No effects were observed at doses 15% the maximum clinical dose, on a body surface area basis.
(Category B2)
There was no evidence of teratogenicity in limited studies in rats and rabbits following administration of acetylcysteine during the period of gestation at doses up to 1.2 times the maximum clinical dose, on a body surface area basis. There are no well controlled studies in pregnant women but experience does not include any positive evidence of adverse effects to the fetus.
Category B2: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed.
Studies in animals are inadequate or may be lacking, but available data show no evidence of an increased occurrence of fetal damage.
 There was no evidence of adverse effects in a limited study in rats following administration of acetylcysteine during late gestation and lactation at 60% of the maximum clinical dose, on a body surface area basis. It is not known whether acetylcysteine and/or its metabolites are excreted in milk. There are no data on the use of acetylcysteine in lactating women and therefore breastfeeding is not recommended during treatment.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

Intravenous administration of acetylcysteine, especially in the large doses needed to treat paracetamol overdose, may result in nausea, vomiting and other gastrointestinal symptoms. Hypersensitivity reactions have been reported following intravenous administration of acetylcysteine. Bronchospasm may occur in conjunction with a generalised anaphylactoid reaction. The symptoms of the anaphylactic-like reaction to acetylcysteine include airway obstruction (bronchospasm), angioedema, dyspnoea, hypotension, shock, tachycardia, urticaria and injection site reaction (including rash). These reactions occur most commonly either during, or at the end of the period of the loading dose infusion, and may be dose related. Since these anaphylactic-like reactions usually occur following the loading dose, careful monitoring is recommended.
There have been rare instances of death associated with the use of intravenous acetylcysteine.
Adverse reactions reported are summarised in Table 2.
Hypokalaemia and electrocardiograph (ECG) changes have been noted in patients with paracetamol poisoning irrespective of the treatment given. Monitoring of plasma potassium concentration is therefore recommended.

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 www.tga.gov.au/reporting-problems.

4.9 Overdose

Symptoms.

Symptoms following overdosage with acetylcysteine have been similar to those of anaphylactoid reactions noted, see Section 4.8 Adverse Effects (Undesirable Effects), but they may be more severe. Hypotension appears to be especially prominent. There is also a theoretical risk of hepatic encephalopathy.

Treatment.

There is no specific treatment. General supportive measures should be carried out.
It has been suggested that generalised reactions to acetylcysteine can be treated with intravenous injection of an antihistamine, and infusion of acetylcysteine should be temporarily stopped but can be restarted at a slower rate without further reaction.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Paracetamol is metabolised in the liver, mainly by conjugation with glucuronide and sulfate. It is also metabolised by cytochrome P450 to form a reactive, potentially toxic metabolite. This metabolite is normally detoxified by conjugation with hepatic glutathione, to form nontoxic derivatives. In paracetamol overdosage, the glucuronide and sulphate conjugation pathways are saturated, so that more of the toxic metabolite is formed. As hepatic glutathione stores are depleted, this toxic metabolite may bind to hepatocyte proteins, leading to liver cell damage and necrosis. Acetylcysteine is a sulfydryl (SH) group donor, and may protect the liver from damage by restoring depleted hepatic-reduced glutathione levels, or by acting as an alternative substrate for conjugation with, and thus detoxification of, the toxic paracetamol metabolite.

Clinical trials.

Observational study - paediatric patients.

An open-label, observational study conducted in the greater Newcastle area, New South Wales, Australia, documented treatment for paediatric patients who presented with a paracetamol overdose during a 16 year period from January 1987 to January 2003. This study was primarily considered a safety study.
Data from 148 paediatric patients, with an age range of 2 months to 15 years (this corresponds to 186 cases) were evaluated. Twenty-three (23) out of 148 paediatric patients were given intravenous acetylcysteine treatment on at least one admission. Of these, 14 paediatric patients in the age group 12 to < 16 years (9.5% of the group), received acetylcysteine within 8 hours of ingesting paracetamol on at least one admission. There was a delay of at least 8 hours for 9 paediatric patients in this age group (6.1% of the group). One other paediatric patient in the age group 2 to < 5 years of age (0.7% of the group), received acetylcysteine with a delay of at least 8 hours on at least one admission.
Of the 23 patients who received intravenous acetylcysteine treatment, 3 patients (13%) experienced an adverse reaction (anaphylactoid reaction, rash and flushing, transient erythema). There were no deaths of paediatric patients. None of the paediatric patients receiving intravenous acetylcysteine developed hepatotoxicity, whilst two patients not receiving intravenous acetylcysteine did develop hepatotoxicity. The number of paediatric patients examined in this study is too small to provide a statistically significant finding for efficacy; however, the results appear to be consistent to those observed in adults.

Safety study.

A randomised, open label, multicentre clinical study was conducted in Australia to compare the rates of anaphylactoid reactions between two rates of infusion for the intravenous acetylcysteine loading dose. One hundred and nine subjects were randomised to a 15-minute infusion rate and 71 subjects were randomised to a 60-minute infusion rate. The loading dose was 150 mg/kg, followed by a maintenance dose of 50 mg/kg over 4 hours and then 100 mg/kg over 16 hours. Of the 180 patients examined in this study, 27% were male and 73% were female. Ages ranged from 15 to 83 years, with the mean age being 29.9 years (+ 13.0).
Within the first 2 hours following intravenous acetylcysteine administration, 17% of all patients developed an anaphylactoid reaction (18% in the 15-minute treatment group; 14% in the 60-minute treatment group) (see Section 4.4 Special Warnings and Precautions for Use). A subgroup of 58 subjects (33 in the 15-minute treatment group; 25 in the 60-minute treatment group) was treated within 8 hours of paracetamol ingestion. No hepatotoxicity occurred within this subgroup; however, with 95% confidence, the true hepatotoxicity rates could range from 0% to 9% for the 15-minute treatment group and from 0% to 12% for the 60-minute treatment group.

5.2 Pharmacokinetic Properties

Distribution.

The parent compound and metabolites may be present in the plasma either free or protein bound.

Metabolism.

Acetylcysteine is the N-acetyl derivative of the naturally occurring amino acid, L-cysteine, and is deacetylated in the liver to cysteine, or oxidised to other metabolites such as N-acetylcystine or N,N-diacetylcystine.

Excretion.

Renal clearance accounts for about 30% of total body clearance. Following intravenous administration, mean terminal half lives have been calculated to be 1.95 and 5.58 hours respectively for reduced and total acetylcysteine.

5.3 Preclinical Safety Data

Genotoxicity.

No evidence of mutagenicity was obtained in limited gene mutation assays with acetylcysteine. The potential for acetylcysteine to cause chromosomal damage has not been investigated.

Carcinogenicity.

Carcinogenicity assays have not been performed with acetylcysteine. In rats, no evidence of carcinogenicity was reported following 18 months of daily dietary administration of acetylcysteine at 60% of the maximum clinical dose, on a body surface area basis.

6 Pharmaceutical Particulars

6.1 List of Excipients

Sodium hydroxide, water for injections.

6.2 Incompatibilities

Acetylcysteine is not compatible with rubber and some metals, particularly, iron, copper and nickel. Acetadote Concentrated Injection can be used satisfactorily with silicone rubber and plastic.

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)1. The expiry date can be found on the packaging. Once diluted according to directions (see Section 4.2 Dose and Method of Administration), start using within 24 hours. Until the usage the dilution should be stored at 2 to 8°C.
1 AUST R 183299.

6.4 Special Precautions for Storage

Store the unopened vial below 25°C. Protect from light.
To reduce microbiological hazard, use as soon as practicable after dilution. If storage is necessary, hold at 2 to 8°C for not more than 24 hours.

6.5 Nature and Contents of Container

Acetadote Concentrated Injection is supplied in a 30 mL vial containing 6 g of acetylcysteine (acetylcysteine 200 mg/mL) for intravenous administration. It is available in packs of 4 vials.
Phebra product code - INJ159.

6.6 Special Precautions for Disposal

Product is for single use in one patient only. Discard any residue.
In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Acetylcysteine is a white, crystalline powder with a slight acetic odour. It is soluble in water and alcohol and practically insoluble in chloroform, dichloromethane and ether.
Chemical name: (2R)-2-(acetylamino)-3-sulfanylpropanoic acid.
Molecular formula: C5H9NO3S.
Molecular weight: 163.2.

Chemical structure.


CAS number.

616-91-1.

7 Medicine Schedule (Poisons Standard)

Schedule 4 - Prescription Only Medicine.

Summary Table of Changes