- Drugs List
- Therapeutic Indications
- Precautions and Warnings
- Pregnancy and Lactation
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Solution for infusion containing acetylcysteine 2 grams per 10ml
Treatment of paracetamol overdosage in patients:
- who have taken a staggered overdose irrespective of plasma paracetamol level. Staggered is defined as an overdose where the paracetamol was ingested over a period of 1 hour or more;
- where there is any doubt over the time of the overdose, irrespective of plasma paracetamol level;
- who present with a timed plasma paracetamol concentration on or above a single treatment line joining points of 100mg/L at 4 hours and 15mg/L at 15 hours nomogram ( https://www.mhra.gov.uk/home/groups/pl-p/documents/drugsafetymessage/con184396.pdf ), regardless of risk factors of hepatotoxicity.
Treatment of meconium ileus in neonates
Treatment of distal intestinal obstructive syndrome in children with cystic fibrosis
Prevention of distal intestinal obstructive syndrome in children with cystic fibrosis
Acetylcysteine is effective at preventing paracetamol-induced hepatotoxicity when administered during the first 8 hours after a paracetamol overdose.
When administered after the first 8 hours, the protective effect diminishes progressively as the overdose-treatment interval increases.
Clinical experience indicates that acetylcysteine can still be of benefit when administered up to 24 hours after paracetamol overdose without any change in its safety profile. It may also be administered up to 24 hours after paracetamol overdose in patients at risk of severe liver damage.
Patients who present 8 to 36 hours after a potentially toxic ingestion should commence treatment with acetylcysteine immediately. If plasma-paracetamol concentrations are not available treatment should not be delayed.
In patients presenting more than 24 hours after a paracetamol overdose, guidance should be sought from the National Poisons Centre.
In accordance with the MHRA guidance detailed weight based dosing for paracetamol poisoning in adults and children is included in each pack of the injection
The full course of treatment comprises three consecutive intravenous infusions:
150mg/kg infused in 200ml over 1 hour.
50mg/kg in 500ml over 4 hours.
100mg/kg in 1000ml over 16 hours.
Total dose: 300mg/kg over 21 hours.
A maximum bodyweight of 110kg should be used when calculating the dosage for obese patients. Dosage should be calculated using the patient's actual weight.
(See Dosage; Adult).
The quantity of intravenous fluid used should be adjusted in accordance with the patient's age and weight, as fluid overload is a potential danger.
Treatment of distal intestinal obstruction syndrome (unlicensed)
By mouth (See Administration).
Children aged 1 month to 2 years: 0.4g to 3g as a single dose.
Children aged 2 to 7 years: 2g to 3g as a single dose.
Children aged 7 to 18 years: 4g to 6g as a single dose.
Prophylaxis of distal intestinal obstruction syndrome (unlicensed)
By mouth (See Administration).
Children aged 1 month to 2 years: 100 to 200mg three times daily.
Children aged 2 to 12 years: 200mg three times daily.
Children aged 12 to 18 years: 200 to 400mg three times daily.
Meconium ileus (unlicensed)
By mouth (See Administration).
200mg to 400mg up to three times a day.
Additional Dosage Information
After a clinical evaluation, the third infusion may be repeated if necessary.
Plasma paracetamol concentration in relation to time after the overdose is commonly used to determine whether a patient is at risk of hepatotoxicity and should, therefore, receive treatment with an antidote such as acetylcysteine.
Most anaphylactoid reactions can be managed by temporally suspending the acetylcysteine infusion, administering appropriate supportive care and restarting at a lower infusion rate. Once an anaphylactoid is under control, the infusion can normally be restarted at an infusion rate of 50mg/kg over 4 hours, followed by the final 16 hour infusion (100mg/kg over 16 hours).
A plasma-paracetamol concentration treatment graph is available from UK National Poisons Information Service (See overdose section).
For intravenous infusion
Acetylcysteine should be infused with a recommended infusion fluid - see Compatibilities
Meconium ileus in neonates, treatment and prevention of distal intestinal obstruction in children
The solution for infusion should be diluted to a concentration of 50mg/ml and given orally. To mask the bitter taste, consider adding juice or a soft drink to the solution.
The following infusion fluids may be used:
Glucose 5% infusion (preferred)
Sodium chloride 0.9% infusion
Precautions and Warnings
Intravenous acetylcysteine, given within 24 hours of ingestion of a potentially hepatotoxic overdose of paracetamol, is indicated to prevent or reduce the severity of liver damage. It is most effective when administered within 8 to 10 hours of a paracetamol overdose. Although the efficacy of acetylcysteine diminishes between 10 and 24 hours post-overdose, it should be administered up to 24 hours in patients at risk of severe liver damage.
Anaphylactoid hypersensitivity reactions occur with acetylcysteine, particularly with the initial loading dose. The patient should be carefully observed during this period for signs of an anaphylactoid reaction.
There is some evidence that patients with a history of atopy and asthma may be at increased risk of developing and anaphylactoid reaction.
Most anaphylactoid reactions can be managed by temporally suspending the acetylcysteine infusion, administering appropriate supportive care and restarting at a lower infusion rate. Once an anaphylactoid reaction is under control, the infusion can normally be restarted at an infusion rate of 50mg/kg over 4 hours, followed by the final 16 hour infusion (100 mg/kg over 16 hours).
Acetylcysteine should be administered with caution in patients with asthma or a history of bronchospasm.
Patients taking drugs that induce liver enzymes, such as some anticonvulsant drugs (e.g. phenytoin, phenobarbitone, primidone and carbamazepine) and rifampicin, and patients who routinely consume alcohol above recommended levels are considered to be at risk of hepatotoxicity from paracetamol poisoning at lower plasma paracetamol concentrations than other patients.
Patients who are suffering with malnutrition may have depleted glutathione reserves. Such patients should be treated as for chronic alcohol consumers or patients taking anticonvulsant drugs. This may also apply in patients who have not eaten for a few days.
Changes to haemostatic parameters have been observed while treatment with acetylcysteine is ongoing. Increased and decreased prothrombin time has been observed, therefore changes in haemostatic parameters may not indicate liver failure.
Risk of fluid overload in children who require fluid restriction or weigh <40kg which may result in hyponatraemia, seizure or death.
Blood samples taken less than 4 hours after the paracetamol overdose do not give reliable estimates of serum paracetamol concentration.
Use with caution in patients with a history of peptic ulceration.
Monitor potassium concentration as hypokalaemia and ECG changes are symptomatic of paracetamol poisoning irrespective of treatment.
Each 10ml of acetylcysteine for infusion contains 322.6mg sodium. This is to be taken into consideration with patients on a controlled sodium diet.
Pregnancy and Lactation
Clinical experience indicates that acetylcysteine is effective in treating paracetamol overdose in pregnant patients.
The safety of the use of acetylcysteine in pregnancy has not been investigated. Prior to use in pregnancy the potential risks should be balanced against the benefits. Briggs (2011) and Schaefer (2007) both state that overdose in pregnant women should be managed in the same way as in non pregnant patients. Acetylcysteine therapy has been found to be protective to both mother and foetus in paracetamol overdose.
The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
There is limited information available.
The low molecular weight (about 163) indicates that excretion into the breast milk is to be expected. IV acetylcysteine has been administered to preterm neonates for therapeutic indications at doses above those that would be expected to be obtained form breast milk, without toxicity (Briggs 2011).
Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1
Effects on Ability to Drive and Operate Machinery
There are no known effects on the ability to drive or operate machinery.
Injection site reactions
Respiratory distress syndrome
Rise in body temperature
Lowered blood urea
Prothrombin time increased
Prothrombin time decreased
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Shelf Life and Storage
Store below 25 degrees C.
Last Full Review Date: September 2012
Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.
Summary of Product Characteristics: Parvolex Injection. UCB Pharma Ltd. Revised August 2012.
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 16 August 2017
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Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
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