Hidonac

N-acetylcysteine.

Each bottle of 25 ml contains: Active ingredient: N-acetylcysteine 5 g.
Excipients/Inactive Ingredients: Sodium Hydroxide, Disodium edetate, Water for injection.

Pharmacotherapeutic classification: Antidote.
Pharmacology: Toxicology: Preclinical safety data: Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity and toxicity to reproduction and development.
High dose treatment in pregnant rats and rabbits revealed no evidence of impaired female fertility or harm to the foetus due to acetylcysteine.
Treatment of male rats for 16 weeks with acetylcysteine at an oral dose considered sufficiently in excess compared to the recommended human dose did not affect the fertility or general reproductive performance of the animals.

Voluntary or accidental paracetamol poisoning.

Acetylcysteine should be administered by intravenous infusion preferably using Glucose 5% as the infusion fluid. Sodium Chloride 0.9% 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 N-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. (See Table 1.)

Click on icon to see table/diagram/image

Children: Children should be treated with the same doses and regimen as adults; however, the quantity of intravenous fluid used must 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. Sodium Chloride 0.9% 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). Given as a 50 mg/mL solution at a rate of 3 mL/kg/h.
Second infusion: Dose: 50 mg/kg infused over 4 hours (12.5 mg/kg/h). Given as a 6.25 mg/mL solution at a rate of 2 mL/kg/h.
Third infusion: Dose: 100 mg/kg infused over 16 hours (6.25 mg/kg/h). Given as a 6.25 mg/mL solution at a rate of 1 mL/kg/h.
Preparation of the solution: Dose 1: Prepare a 50 mg/mL solution. Dilute 10mL of N-acetylcysteine (200 mg/mL) with 30 mL glucose 5% or sodium chloride 0.9% to give a total volume of 40 mL.
Dose 2: Prepare a 6.25 mg/mL solution. Dilute 10 mL of N-acetylcysteine (200 mg/mL) with 310 mL glucose 5% or sodium chloride 0.9% to give a total volume of 320 mL.
Dose 3: Prepare a 6.25 mg/mL solution. Dilute 10 mL of N-acetylcysteine (200 mg/mL) with 310 mL glucose 5% or sodium chloride 0.9% to give a total volume of 320 mL.
Administration: Weigh the child.
Determine the total volume of solution to be infused (infusion fluid + N-acetylcysteine prepared as previously mentioned) into the child from Table 2. A separate volume will be required for each of the three infusion periods.
For example for a child weighing 12 kg, 38mL of solution is required for Dose 1, 100mL for Dose 2 and 200mL for Dose 3.
Infuse intravenously according to the weight of the child (see Table 2).
For example for a child weighing 12 kg, Dose 1 is infused at 38mL/h over 60 minutes, Dose 2 would be infused at 25mL/h and Dose 3 at 13mL/h.
Doses should be administered sequentially with no break between the doses. (See Table 2.)

Click on icon to see table/diagram/image

Symptoms: Overdose of acetylcysteine has been reported to be associated with effects similar to the 'anaphylactoid' reactions noted in Adverse Reactions, but they may be more severe.
Treatment: Overdose treatment is based on immediate discontinuation of the infusion administration and symptomatic treatment and resuscitation. There are no specific antidotal treatments; acetylcysteine is dialyzable.
Paediatric population: The same symptoms and treatment apply to the paediatric population.

Known hypersensitivity to the drug or to other chemically correlated substances.

Acetylcysteine should be given by intravenous route under strict medical supervision. The undesirable effects following acetylcysteine intravenous perfusion are more likely to appear if the drug is administered too quickly or in an excessive amount. It is therefore recommended to strictly follow the indications reported under Dosage & Administration.
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. In very rare cases these reactions have been fatal.
Anaphylactoid/hypersensitivity reactions to acetylcysteine usually occur between 15 and 60 minutes after the start of the infusion and, in many cases, symptoms are relieved by stopping the infusion. An antihistamine drug may be necessary, and occasionally corticosteroids may be required.
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).
Bronchial asthma: There is some evidence that patients with a history of atopy and asthma may be at increased risk of developing an anaphylactoid reaction.
Patients suffering from bronchial asthma must be closely monitored during therapy. Should bronchospasm occur, acetylcysteine must be stopped immediately and appropriate treatment must be initiated.
Fluid and electrolytes: Caution should be used for administration of antidotal doses in patients with body weight less than 40 kilograms because of the possible risk of fluid overload with subsequent hyponatremia, seizures, and death. It is therefore recommended to strictly follow the indications reported under Dosage & Administration.
Coagulation: Acetylcysteine administration at antidotal dosages may prolong prothrombin time (decrease in prothrombin index, increase in INR).
Information on excipients: This medicinal product contains 748 mg sodium (main component of cooking/table salt) in each vial (32.5 mmol), equivalent to 37.4 % of the WHO recommended maximum daily intake of 2 g sodium for an adult.
A mild smell of sulphur does not indicate an alteration of the product but pertains to the specific nature of the active ingredient.
Effects on ability to drive and use machines: Acetylcysteine has no known influence on the ability to drive and use machines.
Use in children and adolescents: The same warnings and precautions reported for adults apply to children and adolescents.

Pregnancy: There are limited clinical data from the use of acetylcysteine in pregnant women.
Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see Pharmacology: Toxicology: Preclinical safety data under Actions).
Prior to use in pregnancy, the potential risks should be balanced against the potential benefits.
Breast feeding: There is no information available on excretion in breast milk.
A risk to the suckling child cannot be excluded.
A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from HIDONAC 5g/25ml therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.
Fertility: No data is available on the effect of acetylcysteine on human fertility. Animal studies do not indicate harmful effects with respect to fertility for humans at the recommended doses (see Pharmacology: Toxicology: Preclinical safety data under Actions).

Summary of safety profile: Adverse reactions to acetylcysteine are mainly anaphylactoid, hypersensitivity in nature; urticaria, rash, pruritus, and dyspnoea are the most frequent features.
More serious anaphylactoid / hypersensitivity reactions have been reported where the patient develops angioedema, bronchospasm, tachycardia and hypotension.
Case reports of fatalities with intravenous acetylcysteine as antidote for paracetamol overdose have been reported very rarely.
Tabulated list of adverse reactions: The following adverse reactions were reported during post-marketing experience; their frequency is not known (cannot be estimated from the available data). (See Table 3.)

Click on icon to see table/diagram/image

Description of selected adverse reactions: In very rare cases, the occurrence of severe skin reactions such as Stevens-Johnson syndrome and Lyell's syndrome has been reported in temporal connection with the administration of acetylcysteine.
In most cases at least one co-suspect drug more probably involved in triggering the reported mucocutaneous syndrome could be identified.
Because of this, medical advice should be sought straight away if any new changes to the skin or mucous membranes occur, and acetylcysteine should be stopped immediately.
A decrease in platelet aggregation in the presence of N-acetylcysteine has been confirmed by various investigations. The clinical significance has not yet been established.
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. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system.

Drug-Drug interactions: Concurrent administration of nitroglycerin and acetylcysteine has been shown to cause significant hypotension and enhance temporal artery dilation. If concurrent nitroglycerin and acetylcysteine therapy is necessary, patients should be monitored for hypotension, which can be severe, and warned of the possibility of headaches.
Reports of an inactivation of antibiotics resulting from acetylcysteine so far only relate to in-vitro tests in which the relevant substances were mixed directly. Therefore, dissolution of acetylcysteine formulations concomitantly with other drugs is not recommended.
Paediatric population: Interaction studies have only been performed in adults.
Drug-Lab modifications: Acetylcysteine may cause interference with colorimetric assay method for salicylate measurement. Acetylcysteine may interfere with urine ketone test.

Shelf-life and Storage Conditions: 3 years in the original packaging and properly stored.
24 hours, at room temperature, as solution for phleboclysis.

Antidotes & Detoxifying Agents

V03AB23 - acetylcysteine ; Belongs to the class of antidotes. Used to neutralize paracetamol overdose.

P₁S₁S₃