Consumer medicine information

DBL Acetylcysteine Injection Concentrate

Acetylcysteine

BRAND INFORMATION

Brand name

DBL Acetylcysteine Injection Concentrate

Active ingredient

Acetylcysteine

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using DBL Acetylcysteine Injection Concentrate.

What is in this leaflet

This leaflet answers some common questions about DBL™ Acetylcysteine Injection Concentrate. It does not contain all the available information. It does not take the place of talking to your doctor.

All medicines have risks and benefits. Your doctor has weighed the risks of you being given DBL™ Acetylcysteine Injection Concentrate against the benefits they expect it will have for you.

If you have any concerns about being given this medicine, ask your doctor.

Keep this leaflet with the medicine. You may need to read it again.

What DBL™ Acetylcysteine Injection Concentrate is used for

This medicine is used to treat paracetamol 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 10 hours of exposure to paracetamol.

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.

This medicine is not addictive.

It is available only with a doctor’s prescription.

Before you are given DBL™ Acetylcysteine Injection Concentrate

When you must not be given it

You should not be given DBL™ Acetylcysteine Injection Concentrate if you have an allergy to:

  • Any medicine containing acetylcysteine
  • any of the ingredients listed at the end of this leaflet.

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.

If you are not sure whether you should be given this medicine, talk to 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 of the following medical conditions:

  • asthma or difficulty breathing
  • stomach ulcers
  • kidney problems
  • liver problems.

Tell your doctor if you weigh less than 40 kilograms. Your doctor may have to adjust the amount of acetylcysteine you will receive.

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

If you have not told your doctor about any of the above, tell him/her before you are given DBL™ Acetylcysteine Injection Concentrate.

Taking other medicines

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

DBL™ Acetylcysteine Injection Concentrate may interfere with the results of some urinary dipstick tests.

Your doctor or pharmacist have more information on medicines to avoid while being treated with this medicine.

How DBL™ Acetylcysteine Injection Concentrate is given

How much is given

Your doctor will decide what dose 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 into a vein. The duration of treatment is approximately 20 hours. It must only be given by a doctor or nurse.

If you receive too much (overdose)

As DBL™ Acetylcysteine Injection Concentrate is given to you under the supervision of your doctor, it is very unlikely that you will receive too much. However if you experience severe side effects tell your doctor immediately.

In case of overdose, immediately contact the Poisons Information Centre for advice on management. (In Australia, call 13 11 26; In New Zealand call 0800 764 766).

Symptoms an overdose may include the side effects listed below in the ‘Side Effects’ section but are usually of a more severe nature.

Ask your doctor if you have any concerns.

While you are being given DBL™ Acetylcysteine Injection Concentrate

Things you must do

If you are to be started on any new medicine, remind your doctor and pharmacist that you are being given acetylcysteine.

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

If you are going to have surgery, tell the surgeon or anaesthetist that you are being given this medicine. It may affect other medicines used during surgery.

If you become pregnant while you are being treated with this medicine, tell your doctor immediately.

Keep all of your doctor’s appointments so that your progress can be checked. Your doctor may do some tests from time to time to make sure the medicine is working and to prevent unwanted side effects.

Side effects

Tell your doctor as soon as possible if you do not feel well while you are being given DBL™ Acetylcysteine Injection Concentrate. 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 treatment if you get some of the side effects.

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

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

Tell your doctor, nurse or pharmacist if you notice any of the following and they worry you:

  • nausea or vomiting
  • generally feeling unwell
  • excessive shivering
  • fever or sweating
  • pain in your bones
  • pain and inflammation at the injection site.
  • bleeding or bruising more easily than normal

Tell your doctor, nurse or pharmacist immediately if you notice any of the following:

  • allergic reactions including flushing, rashes, itching, swelling of the face or difficulty breathing.
  • chest pain
  • fast or irregular heart beat
  • dizziness or lightheadedness
  • seizure
  • jaundice
  • blurred vision or any eye pain
  • pain in your face.

Tell your doctor, nurse or pharmacist if you notice anything that is making you feel unwell.

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

After using DBL™ Acetylcysteine Injection Concentrate

Storage

DBL™ Acetylcysteine Injection Concentrate will be stored in the pharmacy or on the ward. The injection is kept in a cool dry place, protected from light, where the temperature stays below 25°C.

Product description

What it looks like

DBL™ Acetylcysteine Injection Concentrate is supplied as a clear, colourless solution. It is supplied in 10 mL glass ampoules, packs of 10.

Ingredients

DBL™ Acetylcysteine Injection Concentrate contains 200 mg/mL of acetylcysteine as the active ingredient.

It also contains:

  • sodium hydroxide
  • disodium edetate
  • water for injections.

This medicine does not contain lactose, sucrose, gluten, tartrazine or any other azo dyes.

Sponsor

Australia Sponsor:

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

DBL™ Acetylcysteine Injection Concentrate is supplied in the following strength:

  • 2g/10mL x 10 amps
    AUST R 121503

Date of leaflet update: May 2019.

Published by MIMS August 2019

BRAND INFORMATION

Brand name

DBL Acetylcysteine Injection Concentrate

Active ingredient

Acetylcysteine

Schedule

S4

 

1 Name of Medicine

Acetylcysteine.

6.7 Physicochemical Properties

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

Chemical structure.


CAS number.

616-91-1.

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.

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.

No data available.

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.

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.

4.3 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 ulceration (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.

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 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 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 DBL Acetylcysteine Injection Concentrate in the elderly has not been established.

Paediatric use.

The safety and effectiveness of DBL Acetylcysteine Injection Concentrate in children has not been established. No paediatric specific adverse effects 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)
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 foetus 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. There are no well controlled studies in pregnant women but experience does not include any positive evidence of adverse effects to the foetus.
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.

4.8 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 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, generalized 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, coughing, stridor.

Gastrointestinal disorders.

Vomiting, nausea.

Hepatobiliary disorders.

Deterioration of liver function.

Skin and subcutaneous tissue disorders.

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

Musculoskeletal and connective tissue disorders.

Arthralgia.

General disorders and administration site conditions.

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

Investigations.

Raised temperature.
Hypokalaemia and 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.

4.2 Dose and Method of Administration

Dosage.

DBL Acetylcysteine Injection Concentrate 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 or 0.9% sodium chloride 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 or 0.9% sodium chloride over the next 4 hours.

Third infusion.

The second infusion is followed by a continuous infusion of 100 milligrams/kg of acetylcysteine in 1000 mL of 5% glucose or 0.9% sodium chloride over the next 16 hours.

DBL Acetylcysteine Injection Concentrate intravenous infusion dosage guide.

DBL Acetylcysteine Injection Concentrate is supplied in ampoules containing 10 mL of 200 mg/mL acetylcysteine for intravenous administration.
Since DBL Acetylcysteine Injection Concentrate does not contain an antimicrobial preservative, use in one patient on one occasion only and discard any residue.
Table 1 is intended as a guide on the volume (mL) of DBL Acetylcysteine Injection Concentrate 200 mg/mL that is required to be added to 5% glucose or 0.9% sodium chloride 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 DBL Acetylcysteine Injection Concentrate 200 mg/mL that should be added to 5% glucose or 0.9% sodium chloride 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.

Method of administration.

To be most effective in protecting against liver damage, therapy with DBL Acetylcysteine Injection Concentrate should be started within 10 hours of paracetamol ingestion. Although the role of DBL Acetylcysteine Injection Concentrate 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 ingested and the time of ingestion. Hepatic necrosis is preventable if treatment can be instituted within 10 to 12 hours of ingestion.

Note.

Liver damage may not be biochemically apparent for 24 to 48 hours after ingestion.
Hepatic necrosis has been seen with 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 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 DBL Acetylcysteine Injection Concentrate.

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. DBL Acetylcysteine Injection Concentrate may be beneficial in patients presenting later than 15 hours after ingestion. The use of DBL Acetylcysteine Injection Concentrate 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.

DBL Acetylcysteine Injection Concentrate should be administered if appropriate (see A and B 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.
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.

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.

4.9 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 (Australia), 0800 764 766 (New Zealand).

7 Medicine Schedule (Poisons Standard)

S4.

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.

Summary Table of Changes