Acetylcysteine

Indication (SPC §4.4): paracetamol overdose. Intravenous N-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 the overdose. Efficacy diminishes between 10 and 24 hours but it should still be administered up to 24 hours, and may still be administered after 24 hours in patients at risk of severe liver damage. Dosage should be calculated using the patient's actual weight (ceiling weight 110 kg in obesity). Doses are administered sequentially with no break between doses, using an appropriate infusion pump. Anaphylactoid reactions: these occur particularly with the initial loading dose; most can be managed by temporarily suspending the infusion, giving appropriate supportive care and restarting at a lower infusion rate — once controlled, the infusion can normally be restarted at 50 mg/kg over 4 hours followed by the final 100 mg/kg over 16 hours. Fluid and electrolytes: use with caution in children, in patients requiring fluid restriction and in those weighing less than 40 kg because of the risk of fluid overload, which may result in hyponatraemia and seizures; each 10 mL contains 322.6 mg sodium. Coagulation: an isolated rise in prothrombin time up to 1.3 at the end of a 21 hour course without elevated transaminase activity does not require further monitoring or further treatment. Monitoring of plasma potassium is recommended (hypokalaemia and ECG changes occur in paracetamol poisoning irrespective of treatment). Source: UK SPC for Acetylcysteine 200 mg/mL Injection (eMC product 3447).

SPC §4.2 states: 'Children should be treated with the same doses and regimen as adults; however, the quantity of intravenous fluid used should be modified to take into account age and weight, as fluid overload is a potential danger.' The total course is 300 mg/kg over 21 hours (150 + 50 + 100 mg/kg). Preparation per SPC: dose 1 as a 50 mg/mL solution (dilute each 10 mL ampoule of 200 mg/mL with 30 mL glucose 5% or sodium chloride 0.9% to a total of 40 mL); doses 2 and 3 as a 6.25 mg/mL solution (dilute each 10 mL ampoule with 310 mL to a total of 320 mL). SPC worked example: for a child weighing 12 kg, 38 mL of solution is required for Dose 1 (infused at 38 mL/h over 60 minutes), 100 mL for Dose 2 (25 mL/h) and 200 mL for Dose 3 (13 mL/h). Caution: risk of fluid overload, hyponatraemia and seizures in children and in patients weighing less than 40 kg. Verify paediatric dosing and dilution against a children's formulary before administration.