PARVOLEX Solution for infusion Ref.[2452] Active ingredients: Acetylcysteine

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 as it can still be of benefit. It may still be administered after 24 hours in patients at risk of severe liver damage.

Anaphylactoid reactions

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. Nausea, vomiting, flushing, skin rash, pruritus and urticaria are the most common features, but more serious anaphylactoid reactions have been reported where the patient develops angioedema, bronchospasm, respiratory distress, tachycardia and hypotension. In very rare cases these reactions have been fatal. There is some evidence that patients with a history of atopy and asthma may be at increased risk of developing an 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 50 mg/kg over 4 hours, followed by the final 16 hour infusion (100 mg/kg over 16 hours).

Coagulation

Changes in haemostatic parameters have been observed in association with acetylcysteine treatment, some leading to decreased prothrombin time, but most leading to a small increase in prothrombin time. An isolated increase in prothombin time up to 1.3 at the end of a 21 hour course of acetylcysteine without an elevated transaminase activity do not require further monitoring or treatment with acetylcysteine.

Fluid and electrolytes

Use with caution in children, patients requiring fluid restriction or those who weigh less than <40 kg because of the risk of fluid overload which may result in hyponatraemia and seizures which may be life threatening.

Each 10ml of N-acetylcysteine for Infusion contains 322.6mg sodium. To be taken into consideration with patients on a controlled sodium diet.

There are no known interactions.

The safety of acetylcysteine in pregnancy has not been investigated in formal prospective clinical trials. However, clinical experience indicates that use of acetylcysteine in pregnancy for the treatment of paracetamol overdose is effective. Prior to use in pregnancy, the potential risks should be balanced against the potential benefits.

There are no known effects on ability to drive and use machines.

The most common adverse reactions reported with acetylcysteine are nausea, vomiting, flushing and skin rash.

Less commonly, more serious anaphylactoid reactions have been reported that include angioedema, bronchospasm/respiratory distress, hypotension, tachycardia and hypertension.

Adverse reactions to acetylcysteine usually occur between 15 and 60 minutes after the start of infusion and, in many cases, symptoms are relieved by stopping the infusion. An antihistamine drug may be necessary, and occasionally corticosteroids may be required. Once an adverse reaction is under control, the infusion can normally be restarted at the lowest infusion rate (100mg/kg in 1 litre over 16 hours).

Other reported adverse reactions include: injection site reactions, pruritus, cough, chest tightness or pain, puffy eyes, sweating, malaise, raised temperature, vasodilation, blurred vision, bradycardia, facial or eye pain, syncope, acidosis, thrombocytopenia, respiratory or cardiac arrest, stridor, anxiety, extravasation, arthropathy, arthralgia, deterioration of liver function, generalised seizure, cyanosis, lowered blood urea.

Case reports of fatalities with acetylcysteine have been reported very rarely.

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.

If any adverse reactions to acetylcysteine develop, advice should be sought from a National Poisons Centre to ensure that the patient receives adequate treatment of the paracetamol overdose.

Acetylcysteine is not compatible with rubber or metals, particularly iron, copper and nickel. Silicone rubber and plastic are satisfactory for use with Parvolex.

A change in the colour of the solution to light purple has sometimes been noted and is not thought to indicate significant impairment of safety or efficacy.