PARVOLEX

Acetylcysteine should be administered by intravenous infusion preferably using Glucose 5% as the infusion fluid. 9% solution may be used if Glucose 5% is not suitable. Adults The full course of treatment with acetylcysteine comprises 3 consecutive intravenous infusions: First infusion Initial loading dose of 150 mg/kg body weight infused in 200 mL over 1 hour.

Second infusion 50 mg/kg in 500 mL over the next 4 hours. Third infusion 100 mg/kg in 1 litre over the next 16 hours. The patient should therefore receive a total of 300 mg/kg over a 21 hour period. Continued treatment with acetylcysteine (given at the dose and rate as used in the third infusion) may be necessary depending on the clinical evaluation of the individual patient.

A ceiling weight of 110 kg should be used when calculating the dosage for obese patients. Dosage should be calculated using the patient’s actual weight. Adult N-acetylcysteine prescription (each ampoule = 200mg/mL N-acetylcysteine) Please circle appropriate weight, dose and volume.

9% Duration of infusion 60 minutes 4 hours 16 hours Drug dose 150 mg/kg N-acetylcysteine 50 mg/kg N-acetylcysteine 100 mg/kg N-acetylcysteine Patient Weight1 Dose Ampoule volume2 Infusion Rate Dose Ampoule volume2 Infusion Rate Dose Ampoule volume2 Infusion Rate Kg mg mL mL/h mg mL mL/h mg mL mL/h 40-49 6750 34 234 2250 12 128 4500 23 64 50-59 8250 42 242 2750 14 129 5500 28 64 60-69 9750 49 249 3250 17 129 6500 33 65 70-79 11250 57 257 3750 19 130 7500 38 65 80-89 12750 64 264 4250 22 131 8500 43 65 90-99 14250 72 272 4750 24 131 9500 48 66 100-109 15750 79 279 5250 27 132 10500 53 66 >110- Max dose 16500 83 283 5500 28 132 11000 55 66 1 Dose calculations are based on the weight in the middle of each band.

2 Ampoule volume has been rounded up to the nearest whole number.

Children:

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 N-acetylcysteine should be administered by intravenous infusion preferably using Glucose 5% as the infusion fluid.

9% solution may be used if Glucose 5% is not suitable. Doses should be administered using an appropriate infusion pump. The full course of treatment with N-acetylcysteine comprises 3 consecutive intravenous infusions: First infusion Initial loading dose of 150 mg/kg infused over 1 hour (150 mg/kg/h).

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. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard.

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 temporarily 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.

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.

There are no contraindications to the treatment of paracetamol overdose with acetylcysteine.