Consumer medicine information

DBL Acetylcysteine Injection Concentrate

Acetylcysteine

BRAND INFORMATION

Brand name

DBL Acetylcysteine Injection Concentrate

Active ingredient

Acetylcysteine

Schedule

SUMMARY CMI

DBL™ Acetylcysteine Injection Concentrate

Consumer Medicine Information (CMI) summary

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

1. Why am I being treated with DBL Acetylcysteine Injection Concentrate?

DBL Acetylcysteine Injection Concentrate contains the active ingredient acetylcysteine. DBL Acetylcysteine Injection Concentrate is used to treat paracetamol (acetaminophen) poisoning.

For more information, see Section 1. Why am I being treated with DBL Acetylcysteine Injection Concentrate? in the full CMI.

2. What should I know before I am given DBL Acetylcysteine Injection Concentrate?

You should not be given DBL Acetylcysteine Injection Concentrate if you have ever had an allergic reaction to acetylcysteine or any of the ingredients lists at the end of this leaflet.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or breastfeeding. For more information, see Section 2. What should I know before I am given DBL Acetylcysteine Injection Concentrate? in the full CMI.

3. What if I am taking other medicines?

For more information refer to Section 3. What if I am taking other medicines? in the full CMI.

4. How is DBL Acetylcysteine Injection Concentrate given?

Your doctor will decide what dose you will receive. This depends on your condition and other factors, such as your weight. This medicine is given as an infusion (eg. as a ‘drip’) into a vein. It must only be given by a doctor or nurse.

More instructions can be found in Section 4. How is DBL Acetylcysteine Injection Concentrate given? in the full CMI.

5. What should I know while I am being treated with DBL Acetylcysteine Injection Concentrate?

Things you should do	Remind any doctor, pharmacist or dentist you visit in the next few days that you have been given this medicine recently. Ensure you have any tests recommended by your doctor.
Driving or using machines	Avoid driving or using any machines or tools until you know how this medicine affects you, as it may cause dizziness, light-headedness, blurred vision or seizures.
Drinking alcohol	Tell your doctor if you have a history of long-term alcohol use. Be careful when drinking alcohol for the next few days after you have been given this medicine, as it may cause light-headedness or dizziness in some people.

For more information, see Section 5. What should I know while I am being treated with DBL Acetylcysteine Injection Concentrate? in the full CMI.

6. Are there any side effects?

Side effects include: nausea or vomiting, generally feeling unwell, excessive shivering, fever or sweating, pain or swelling in your joints, pain and inflammation at the injection site, blurred vision or any eye pain, flushing or pain in your face, anxiety.

Serious side effects include: allergic reactions including rash, itching, swelling of the face or difficulty breathing; chest pain, fast or irregular heart-beat; dizziness or light-headedness; headache; seizure, jaundice (yellowing of skin and/or eyes); bleeding or bruising more easily than normal; blueish colour to the skin, lips or nails.

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

DBL™ Acetylcysteine Injection Concentrate

Active ingredient(s): Acetylcysteine

Consumer Medicine Information (CMI)

This leaflet provides important information about being treated with DBL Acetylcysteine Injection Concentrate.

You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about treatment with DBL Acetylcysteine Injection Concentrate.

Where to find information in this leaflet:

1. Why am I being treated with DBL Acetylcysteine Injection Concentrate?
2. What should I know before I am given DBL Acetylcysteine Injection Concentrate?
3. What if I am taking other medicines?
4. How is DBL Acetylcysteine Injection Concentrate given?
5. What should I know while I am being treated with DBL Acetylcysteine Injection Concentrate?
6. Are there any side effects?
7. Product details

1. Why am I being treated with DBL Acetylcysteine Injection Concentrate?

DBL Acetylcysteine Injection Concentrate contains the active ingredient acetylcysteine.

DBL Acetylcysteine Injection Concentrate is used to treat paracetamol (acetaminophen) poisoning.

It works by reacting with a toxic metabolite of paracetamol to prevent it damaging the liver.

This medicine is most effective when started within 8 hours of exposure to paracetamol.

2. What should I know before I am given DBL Acetylcysteine Injection Concentrate?

Warnings

You must not be given DBL Acetylcysteine Injection Concentrate if:

you are allergic to acetylcysteine or any of the ingredients listed at the end of this leaflet.
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.
Always check the ingredients to make sure you can use this medicine.

If you are not sure whether you should be given DBL Acetylcysteine Injection Concentrate, talk to your doctor or nurse.

Check with your doctor if you:

have or have had any other medical conditions, especially the following:
- asthma or difficulty breathing
- stomach ulcers
- kidney problems
- liver problems.
have a history of chronic or long-term alcohol use
take any medicines for any other condition, especially the following:
- isoniazid and/or rifampicin (antibiotics often used together for the treatment of tuberculosis (TB))
- anticonvulsants including carbamazepine, phenytoin, phenobarbitone, primidone, sodium valproate.

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

Tell your doctor if you are pregnant or are breast-feeding

If there is a need to consider using this medicine while you are pregnant or breastfeeding, your doctor will discuss with you the benefits and risks of you being given it.

3. What if I am taking other medicines?

Tell your doctor or nurse if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

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

4. How is DBL Acetylcysteine Injection Concentrate given?

How much is given

Your doctor will decide what dose you will receive. This depends on your condition and other factors, such as your weight.

How it is given

DBL Acetylcysteine Injection Concentrate is given as a slow infusion (eg. as a ‘drip’) into a vein. It must only be given by a doctor or nurse.

How many infusions will you need

You will receive two separate infusions, containing different doses, as determined by your doctor. You may also be given treatment for nausea at the same time.

If you experience side effects to DBL Acetylcysteine Injection Concentrate, you may also be given an anti-histamine.

The overall duration of treatment is approximately 20 hours.

Your doctor may do some tests before and during treatment, to make sure the medicine is working and to prevent unwanted side effects.

If you are given too much DBL Acetylcysteine Injection Concentrate

As DBL Acetylcysteine Injection Concentrate is given to you under the supervision of a doctor, it is very unlikely that you will receive too much.

It is important to immediately tell your doctor or nurse if you experience a rash, itching or hives on the skin, swelling of the face, lips, tongue or other parts of the body, shortness of breath, wheezing or trouble breathing.

However, if you think that you have been given too much DBL Acetylcysteine Injection Concentrate and/or if you experience severe side effects, you may need additional urgent medical attention.

You should immediately:

talk to your doctor or nurse.

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

5. What should I know while I am being treated with DBL Acetylcysteine Injection Concentrate?

Things you should do

Remind any doctor, pharmacist or dentist you visit over the next few days that you have been given DBL Acetylcysteine Injection Concentrate recently.

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

Keep all of your doctor's appointments so that your progress can be checked.

Driving or using machines

Be careful before driving or using any machines or tools until you know how DBL Acetylcysteine Injection Concentrate affects you.

As with some other medicines, acetylcysteine may cause dizziness or light-headedness in some people. It may also cause blurred vision or seizures.

Make sure you know how you react to this medicine before you drive a car, operate machinery, or do anything else that could be dangerous.

Drinking alcohol

Be careful when drinking alcohol for a few days after being given this medicine.

This medicine may cause dizziness or light-headedness in some people.

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.

Less serious side effects

Less serious side effects	What to do
nausea or vomiting generally feeling unwell excessive shivering fever or sweating painful or swollen joints pain and inflammation at the injection site blurred vision or any eye pain flushing or pain in your face anxiety	Speak to your doctor or nurse if you have any of these side effects and they worry you.

Serious side effects

Serious side effects

What to do

Symptoms of an allergic reaction, which 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 in the skin.

Other serious side effects, which may include:

headache
chest pain
fast or irregular heart beat
dizziness or light-headedness, feeling faint/fainting
seizure
jaundice (yellowing of skin and/or eyes)
bleeding or bruising more easily than normal
have a bluish colour to the skin, lips or nails

Tell your doctor or nurse straight away if you notice any of these 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.

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.

7. Product details

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

What DBL Acetylcysteine Injection Concentrate contains

Active ingredient (main ingredient)	Acetylcysteine
Other ingredients (inactive ingredients)	Sodium hydroxide Disodium edetate Water for injections

DBL Acetylcysteine Injection Concentrate does not contain lactose, sucrose, gluten, tartrazine or any other azo dyes.

You should not be given this medicine if you are allergic to any of these ingredients.

What DBL Acetylcysteine Injection Concentrate looks like

DBL Acetylcysteine Injection Concentrate is a clear, colourless solution.

It is available as follows:

2 g in 10 mL glass ampoules (AUST R 121503)

Who distributes DBL Acetylcysteine Injection Concentrate

Pfizer Australia Pty Ltd
Sydney NSW
Toll Free Number: 1800 675 229
www.pfizermedicalinformation.com.au

This leaflet was prepared in January 2025.

™ Trademark

Published by MIMS February 2025

BRAND INFORMATION

Brand name

DBL Acetylcysteine Injection Concentrate

Active ingredient

Acetylcysteine

Schedule

1 Name of Medicine

Acetylcysteine.

2 Qualitative and Quantitative Composition

Each ampoule contains 200 milligrams/mL of acetylcysteine as well as sodium hydroxide, disodium edetate and water for injections.
DBL Acetylcysteine Injection Concentrate is a clear, colourless, sterile, pyrogen free aqueous solution of acetylcysteine (N-acetyl-mercapto-alanine) with a pH of approximately 7.0. It is soluble in water and alcohol and practically insoluble in chloroform, dichloromethane and ether.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

DBL Acetylcysteine is a concentrated injection for intravenous use.
Acetylcysteine is a white, crystalline powder with a slight acetic odour.

4 Clinical Particulars

4.1 Therapeutic Indications

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

4.2 Dose and Method of Administration

Dosage.

DBL Acetylcysteine Injection Concentrate is infused in two intravenous infusions containing different doses.
Adults (age ≥ 14 years).

Initial infusion.

An initial dose of 200 milligrams/kg (maximum 22 g) of acetylcysteine diluted in 500 mL of 5% glucose or 0.9% sodium chloride and infused intravenously over 4 hours.

Second infusion*.

The initial infusion is followed by a continuous intravenous infusion of 100 milligrams/kg (maximum 11 g) of acetylcysteine in 1000 mL of 5% glucose or 0.9% sodium chloride over 16 hours.
*If the initial serum paracetamol concentration was more than double the nomogram line (see Figure 1) following an acute ingestion of paracetamol, increase acetylcysteine dose to 200 milligrams/kg (maximum 22 g) diluted in 1000 mL of 5% glucose or 0.9% sodium chloride intravenously, over 16 hours.
Children (age < 14 years). Children should be treated with the same doses (milligrams/kg) and regimens as adults. However the volume of intravenous fluid should be modified to take into account age and weight, as fluid overload is a potential danger in children.

Initial infusion.

An initial dose of 200 milligrams/kg (maximum 22 g) of acetylcysteine diluted in 7 mL/kg up to 500 mL of 5% glucose or 0.9% sodium chloride and infused intravenously over 4 hours.

Second infusion*.

The initial infusion is followed by a continuous intravenous infusion of 100 milligrams/kg (maximum 11 g) of acetylcysteine in 14 mL/kg up to 1000 mL of 5% glucose or 0.9% sodium chloride over 16 hours.
*If the initial serum paracetamol concentration was more than double the nomogram line (see Figure 1) following an acute ingestion of paracetamol, increase acetylcysteine dose to 200 milligrams/kg (maximum 22 g) diluted in 14 mL/kg up to 1000 mL of 5% glucose or 0.9% sodium chloride intravenously, over 16 hours.

DBL Acetylcysteine Injection Concentrate intravenous infusion dosage guide.

DBL Acetylcysteine Injection Concentrate is supplied in ampoules containing 10 mL of 200 milligrams/mL acetylcysteine for intravenous administration.
Since DBL Acetylcysteine Injection Concentrate does not contain an antimicrobial preservative, use each ampoule in one patient on one occasion only and discard any residue.
Tables 1 and 2 are intended as a guide on the dose (g) and volume (mL) of DBL Acetylcysteine Injection Concentrate 200 milligrams/mL that is required to be added to 5% glucose or 0.9% sodium chloride to prepare the initial and second infusion solutions. In order to use these tables, the patient's weight in kilograms should be determined.

Adults (age ≥ 14 years).

For adults (age ≥ 14 years), dosing should be based on actual body weight rounded to the nearest 10 kg, with a ceiling weight of 110 kg.

Children (age < 14 years).

For children (age < 14 years), use actual body weight to calculate dose of acetylcysteine and volume of diluent.

Method of administration.

To be most effective in protecting against liver injury, therapy with DBL Acetylcysteine Injection Concentrate should be started within 8 hours of paracetamol ingestion.

Management of paracetamol overdosage with acetylcysteine.

The paracetamol treatment nomogram is used to decide whether to start or continue acetylcysteine infusion. The dosing depends on the time since paracetamol ingestion, formulation of paracetamol, dose ingested, serum paracetamol concentration (early), and presence of clinical and laboratory features suggesting acute liver injury.
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. Liver injury is more likely to occur with a lower dosage of paracetamol in patients who have a history of chronic alcohol use 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 ingested and the time of ingestion. Hepatic necrosis is preventable if treatment can be instituted within 8 hours of ingestion.

Note.

Liver injury may not be clinically or biochemically apparent for up to 24 hours after ingestion.
Hepatic necrosis has been seen with 6 grams of paracetamol, and death with 15 grams.
The following A-C sections are applicable to both adults and children, for both solid and liquid paracetamol ingestion.

A. Acute ingestion of immediate-release paracetamol.

In patients who present within 8 hours after an overdose, with a serum paracetamol concentration on or over the nomogram line, commence acetylcysteine infusion.*
In patients who present between 8 to 24 hours after an overdose, commence acetylcysteine infusion immediately. Measure serum paracetamol concentration and alanine aminotransferase (ALT). For patients who have serum paracetamol concentration on or over the nomogram line and/or ALT > 50 U/L, continue the rest of the treatment (otherwise no further treatment is required).*
* For patients who have serum paracetamol concentration double the nomogram line, complete acetylcysteine infusion with double dose of the second bag (200 milligrams/kg over 16 hours).
In patients who present more than 24 hours after an overdose, commence acetylcysteine infusion immediately. Measure serum paracetamol concentration and ALT. If serum paracetamol concentration is ≥ 10 milligrams/L (66 micromol/L) and/or ALT > 50 U/L, continue the rest of the treatment (otherwise no further treatment required).
In patients whose time of ingestion is not known, follow the advice above for between 8 to 24 hours after an overdose, commence acetylcysteine immediately. Measure serum paracetamol concentration and ALT.
If the serum paracetamol concentration is ≥ 10 milligrams/L (66 micromol/L) and/or the ALT is > 50 U/L, continue the rest of the treatment (otherwise no further treatment required).
Two hours before the completion of acetylcysteine infusion, ALT measurement should be repeated in all patients. For those with an initial serum paracetamol concentration double the nomogram line, a serum paracetamol concentration should also be repeated. Acetylcysteine treatment should be continued if the serum paracetamol concentration is > 10 milligrams/L (66 micromol/L), or ALT is elevated (> 50 U/L) and increasing (if baseline ALT > 50 U/L).

B. Acute ingestion of modified-release (MR) paracetamol.

In patients who ingested MR paracetamol dose of < 10 grams and < 200 milligrams/kg, measure 2 serum paracetamol concentrations at least 4 hours post-ingestion and 4 hours apart. If either serum paracetamol concentration is over the nomogram treatment line, commence acetylcysteine infusion.*
In patients who ingested MR paracetamol dose of ≥ 10 grams or ≥ 200 milligrams/kg (whichever is less) and present more than 4 hours post-ingestion, commence acetylcysteine infusion immediately.
If dose ingested is ≥ 30 grams or ≥ 500 milligrams/kg (whichever is less), complete acetylcysteine infusion with double dose of the second bag (200 milligrams/kg over 16 hours).
If dose ingested is not ≥ 30 grams or not ≥ 500 milligrams/kg, measure 2 serum paracetamol concentrations at least 4 hours post-ingestion and 4 hours apart, and if either serum paracetamol concentration is more than double the nomogram treatment line, acetylcysteine treatment should be continued.*
* For patients with either of the two serum paracetamol concentration more than double the nomogram line, complete acetylcysteine infusion with double dose of the second bag (200 milligrams/kg over 16 hours).
Measure serum paracetamol concentration and ALT for all patients before ceasing acetylcysteine infusion. Acetylcysteine treatment should be continued if serum paracetamol concentration is > 10 milligrams/L (66 micromol/L), or ALT is elevated (> 50 U/L) and increasing (if baseline ALT > 50 U/L).

C. Repeated supratherapeutic ingestion (RSTI) of paracetamol.

Patients who ingest excessive paracetamol for a therapeutic purpose (e.g. pain, viral infection) or ingest therapeutic doses of paracetamol and have symptoms of acute liver injury (e.g. abdominal pain, nausea and vomiting) are managed as RSTI. If the ingestion is deliberate/intentional they should be managed as per acute intentional ingestion.
In patients who ingested paracetamol dose of ≥ 10 grams or ≥ 200 milligrams/kg (whichever is less) over a single 24 hour period, and have an ALT ≥ 50 U/L or serum paracetamol concentration ≥ 20 milligrams/L (132 micromol/L), commence acetylcysteine infusion.
In patients who ingested paracetamol dose of ≥ 12 grams or ≥ 300 milligrams/kg (whichever is less) over a single 48 hour period, and have an ALT ≥ 50 U/L or serum paracetamol concentration ≥ 20 milligrams/L (132 micromol/L), commence acetylcysteine infusion.
In patients who ingested a daily therapeutic dose per day for more than 48 hours in those who also have abdominal pain or nausea or vomiting, and have an ALT ≥ 50 U/L or serum paracetamol concentration ≥ 20 milligrams/L (132 micromol/L), commence acetylcysteine infusion.
Repeat serum paracetamol concentration and ALT, 8 hours after the previous concentration sampling. If ALT ≥ 50 U/L or serum paracetamol concentration ≥ 10 milligrams/L (66 micromol/L), continue acetylcysteine infusion and check ALT at 12 hourly intervals.

D. Paediatric (< 6 years) liquid paracetamol ingestion.

In children less than 6 years of age, where ingestion of greater than 200 milligrams/kg of liquid paracetamol is suspected, a serum paracetamol concentration should be measured at least 2 hours post-ingestion. If the 2-hour post-ingestion serum paracetamol concentration is greater than 150 milligrams/L (1000 micromol/L), this should be repeated 4 hours post-ingestion and acetylcysteine commenced if this is ≥ 150 milligrams/L (1000 micromol/L). Further, for those children who present later than 4 hours post-ingestion or in children older than 6 years of age, treatment is as per the adult acute paracetamol exposure guideline.

E. General management.

DBL Acetylcysteine Injection Concentrate should be administered if appropriate (see above). DBL Acetylcysteine Injection Concentrate should be diluted in 5% glucose or 0.9% sodium chloride solution, and administered by intravenous infusion. Nausea should be treated.
Measurements of plasma hepatic enzymes and blood bilirubin, and coagulation tests, should be performed as soon as possible after admission.
Daily liver function tests, and measurements of blood urea, blood electrolytes, blood glucose, blood gases, haemoglobin, white blood cell counts, platelets and prothrombin time should be conducted. An electrocardiogram (ECG) should also be performed. Patients should be monitored for coagulopathy, hepatic encephalopathy, renal failure and cardiotoxicity (minor ST changes are common). There is usually a metabolic acidosis. Hepatic encephalopathy is likely if bilirubin is above 60 millimoles/L on days 3 to 5, or if the prothrombin time is prolonged.
If ongoing acetylcysteine treatment is required, continue at the rate of the second infusion (e.g. 100 milligrams/kg over 16 hours). Higher ongoing infusion rates (e.g. 200 milligrams/kg over 16 hours) may be required for massive paracetamol ingestions and a clinical toxicologist should be consulted.

4.3 Contraindications

DBL Acetylcysteine Injection Concentrate 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

DBL Acetylcysteine Injection Concentrate should be used with caution in 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 ulcer (acetylcysteine induced vomiting may increase the risk of haemorrhage).
Acetylcysteine is not compatible with rubber and some metals, particularly, iron, copper and nickel. DBL Acetylcysteine Injection Concentrate 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 (see Section 4.2 Dose and Method of Administration).

Patients on fluid intake restriction.

For patients on fluid intake 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 abnormal hepatic function. The decision to administer should be based on a risk/benefit assessment for the individual subject.
In the presence of hepatic failure due to paracetamol overdose, the degree of existing liver injury 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 renal impairment. The decision to administer should be based 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 DBL Acetylcysteine Injection Concentrate in the elderly has not been established.

Paediatric use.

The safety and effectiveness of DBL Acetylcysteine Injection Concentrate in children have 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 effects have been documented.
Use of DBL Acetylcysteine Injection Concentrate in paediatric patients is based on clinical practice (see Section 4.2 Dose and Method of Administration).

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)
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.
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.
Studies in animals are inadequate or may be lacking, but available data show no evidence of an increased occurrence of fetal damage. There are no well controlled studies in pregnant women but experience does not include any positive evidence of adverse effects to the fetus.
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 has 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 in fact 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.
The following adverse effects have been reported.

Blood and lymphatic system disorders.

Thrombocytopenia.

Immune system disorders.

Anaphylactoid reaction.

Metabolism and nutrition disorders.

Acidosis.

Psychiatric disorders.

Anxiety.

Nervous system disorders.

Syncope, seizure.

Eye disorders.

Blurred vision, eye pain.

Cardiac disorders.

Cyanosis, tachycardia, bradycardia, cardiac arrest, extrasystoles.

Vascular disorders.

Flushing, hypotension, hypertension, vasodilation.

Respiratory, thoracic and mediastinal disorders.

Dyspnoea, respiratory arrest, bronchospasm, cough, stridor.

Gastrointestinal disorders.

Vomiting, nausea.

Hepatobiliary disorders.

Hepatic function abnormal.

Skin and subcutaneous tissue disorders.

Angioedema, urticaria, rash (erythematous and maculopapular), hyperhidrosis, oedema periorbital.

Musculoskeletal and connective tissue disorders.

Arthralgia.

General disorders and administration site conditions.

Malaise, chills, injection site reaction, chest pain, facial pain, face oedema.

Investigations.

Body temperature increased.
Hypokalaemia and ECG changes have been noted in patients with paracetamol poisoning irrespective of the treatment given. Monitoring of blood 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 (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 13 11 26.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Paracetamol is metabolised in the liver, mainly by conjugation with glucuronide and sulphate. 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 non-toxic 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 sulphydryl (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, 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, multi-centre 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.

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

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

Disodium edetate, sodium hydroxide, water for injections.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

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

DBL Acetylcysteine Injection Concentrate should be stored below 25°C. Protect from light.

6.5 Nature and Contents of Container

DBL Acetylcysteine Injection Concentrate is supplied in ampoules of 10 mL (acetylcysteine 200 mg/mL) for intravenous administration. It is available in packs 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

Chemical structure.

The chemical name of acetylcysteine is (2R)-2-(acetylamino)-3-sulphanylpropanoic acid.
Molecular formula: C₅H₉NO₃S.
Molecular weight: 163.2.

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