HIDONAC ANTIDOTE 200 mg/mL CONCENTRATE FOR PERFUSION SOLUTION

Introduction

Package Leaflet: Information for the User

Hidonac Antidote 200 mg/ml Concentrate for Solution for Infusion

Acetylcysteine

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the Package Leaflet

1. What is Hidonac Antidote and what is it used for
2. What you need to know before you use Hidonac Antidote
3. How to use Hidonac Antidote
4. Possible side effects
5. Storage of Hidonac Antidote
6. Contents of the pack and further information

1. What is Hidonac Antidote and what is it used for

Hidonac Antidote is used in the treatment of paracetamol overdose.

This medicine contains a derivative of cysteine (acetylcysteine) which is used in the synthesis of glutathione. Glutathione eliminates free radicals that can cause tissue damage and are released in inflammatory processes.

In a paracetamol overdose, there is a relative deficiency of glutathione in the liver. Glutathione can bind to the toxic breakdown products of paracetamol. If acetylcysteine is administered in time after a paracetamol overdose, it can prevent liver damage.

2. What you need to know before you use Hidonac Antidote

Before starting treatment, blood samples should be taken to analyze paracetamol levels in your blood.

Warnings and Precautions

Consult your doctor before starting to use this medicine

• if you are asthmatic or have a severe respiratory disease, as this medicine may cause respiratory difficulties (bronchospasm).
• if you have previously suffered an adverse reaction to acetylcysteine.
• if you are pregnant or breastfeeding.
• high doses of acetylcysteine may lead to alterations in blood coagulation, prolonging bleeding.

The possible sulfurous odor (like rotten eggs) of the medicine is characteristic of the active ingredient, but it does not indicate that the medicine is in poor condition.

Children and Adolescents

In children and adolescents, the same precautions and warnings apply.

Interference with Laboratory Tests

• acetylcysteine may interfere with the determination of salicylates.
• acetylcysteine may interfere with the determination of ketones in urine.

Using Hidonac Antidote with Other Medicines

Tell your doctor or pharmacist if you are using or have recently used other medicines, including those obtained without a prescription.

• nitroglycerin, as its effect of decreasing blood pressure (hypotension) may increase, and headache may appear.
• carbamazepine, a medicine used to combat epilepsy attacks, as it may increase the risk of attacks.

Using Hidonac Antidote with Food and Drinks

The intake of food and drinks does not affect the efficacy of the medicine.

Pregnancy, Breastfeeding, and Fertility

Consult your doctor or pharmacist before using any medicine.

There is no information available on the use of the medicine during pregnancy or breastfeeding, so its use is not recommended during these periods.

There is no data available on the effect of acetylcysteine on human fertility. Animal studies do not indicate harmful effects on human fertility at the recommended doses.

Driving and Using Machines

There is no evidence of effects on the ability to drive and use machines.

Hidonac Antidote Contains Sodium

This medicine contains 748 mg of sodium (the main component of table salt) in each 25 ml vial. This is equivalent to 37.4% of the maximum daily sodium intake recommended for an adult.

3. How to Use Hidonac Antidote

Follow exactly the administration instructions of this medicine indicated by your doctor. In case of doubt, consult your doctor or pharmacist again.

This medicine is administered by intravenous infusion under strict medical supervision.

Use in Adults and Adolescents (over 40 kg body weight)

Your doctor will determine the treatment to follow (see detailed information in the section intended for healthcare professionals at the end of this leaflet).

The recommended dose is 300 mg of acetylcysteine per kilogram of body weight, equivalent to 1.5 ml/kg of Hidonac Antidote over 21 hours, according to the following 3-step scheme:

• 150 mg/kg, equivalent to 0.75 ml/kg, slowly intravenously diluted in 200 ml of 5% glucose over 60 minutes.
• 50 mg/kg, equivalent to 0.25 ml/kg, in 500 ml of 5% glucose in slow infusion over 4 hours.
• 100 mg/kg, equivalent to 0.50 ml/kg, in 1000 ml of 5% glucose in slow infusion over 16 hours.

Use in Children

In children, the volume of 5% glucose solution for infusion must be adjusted based on age and body weight to avoid the risk of pulmonary vascular congestion. Your doctor will calculate the amounts to be administered.

To be effective, treatment should be started as soon as possible, usually no later than 8-10 hours after paracetamol overdose; after this time, the protective effect of acetylcysteine decreases progressively and rapidly, and after 15 hours of intoxication, it may not be effective.

The administration of the medicine may be interrupted when blood test results show hematic levels of paracetamol below 200 micrograms/ml.

If You Use More Hidonac Antidote Than You Should

If you have used more Hidonac Antidote than you should, consult your doctor, pharmacist, or call the Toxicology Information Service, phone 91.562.04.20, indicating the medicine and the amount used.

If you have any other questions about the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible Side Effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

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

The following side effects have been reported, although their frequency cannot be established from the available information:

Immune System Disorders: Anaphylactic shock, anaphylactic reaction, anaphylactoid reaction, hypersensitivity.

Cardiac Disorders: Tachycardia, bradycardia.

Respiratory, Thoracic, and Mediastinal Disorders: Bronchospasm, dyspnea, stridor, cough.

Gastrointestinal Disorders: Vomiting, nausea.

Skin and Subcutaneous Tissue Disorders: Angioedema, urticaria, flushing, rash, pruritus.

General Disorders and Administration Site Conditions: Facial edema, discomfort.

Investigations: Decreased blood pressure, increased prothrombin time.

In very rare cases, the appearance of severe skin reactions such as Stevens-Johnson syndrome and Lyell syndrome has been described in temporal connection with the administration of acetylcysteine. In most cases, at least one other suspect drug could also be identified to trigger the mucocutaneous syndrome. If any new changes in the skin or mucous membranes occur, the administration of acetylcysteine should be immediately interrupted. The specialist doctor will determine the treatment to follow.

In some cases, a decrease in blood coagulation (decrease in platelet aggregation) has been described.

Reporting of Side Effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if it is possible side effects not listed in this leaflet. You can also report them directly through the Spanish Medicines Monitoring System for Human Use: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Hidonac Antidote

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton after the abbreviation EXP. The expiry date refers to the last day of the month shown.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the Pack and Further Information

Composition of Hidonac Antidote

The active substance is acetylcysteine. Each 25 ml vial contains 5 g of acetylcysteine.

The other ingredients are: disodium edetate, sodium hydroxide (E524) (for pH adjustment), and water for injections.

Appearance of the Product and Contents of the Pack

Appearance: transparent glass vials containing 25 ml of clear and colorless solution, and equipped with a rubber stopper and an aluminum seal.

Each pack contains 1 vial.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Zambon S.A.U.

Maresme, 5. Pol. Can Bernades-Subirà

08130 Sta. Perpètua de Mogoda (Barcelona)

Manufacturer

Alfasigma S.p.A.

Via Enrico Fermi, 1

65020 Alanno (PE) Italy

Date of Last Revision of this Leaflet: October 2019

Detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/.

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This information is intended only for healthcare professionals:

Acetylcysteine is administered by intravenous infusion, preferably using 5% glucose as the infusion solution, although it is possible to use 0.9% sodium chloride if 5% glucose is not advisable.

The infusion should be performed slowly to reduce the risk of side effects.

Posology

The dose should be calculated using the patient's actual weight to determine the total volume of solution.

For more information, consult the medicine's technical data sheet, which includes dosage tables for both adults and children, detailing by weight ranges, doses, volumes to be infused, and infusion rates.

Adults and Adolescents (> 40 kg body weight)

The complete treatment cycle with acetylcysteine includes 3 consecutive intravenous infusions:

First infusion: Initial dose of 150 mg/kg body weight in 200 ml of solution over 1 hour.

Second infusion: 50 mg/kg body weight in 500 ml over the next 4 hours.

Third infusion: 100 mg/kg body weight in 1 liter over the next 16 hours.

Therefore, the patient should receive a total of 300 mg/kg body weight over a period of 21 hours.

Children

Children should be treated with the same doses and regimen as adults. However, the volume of solution to be infused should be modified taking into account the patient's age and body weight due to the possible risk of pulmonary vascular congestion.

The complete treatment cycle with acetylcysteine includes 3 consecutive intravenous infusions:

First infusion:

Initial dose of 150 mg/kg body weight in infusion over 1 hour (150 mg/kg/h), administered as a 50 mg/ml solution at a rate of 3 ml/kg/h.

Second infusion:

Dose: 50 mg/kg body weight in infusion over 4 hours (12.5 mg/kg/h), administered as a 6.25 mg/ml solution at a rate of 2 ml/kg/h.

Third infusion:

Dose: 100 mg/kg body weight in infusion over 16 hours (6.25 mg/kg/h), administered as a 6.25 mg/ml solution at a rate of 1 mg/kg/h.

Preparation of the Solution

1st dose

Prepare a 50 mg/ml solution. Dilute 10 ml of acetylcysteine (200 mg/ml) with 30 ml of 5% glucose or 0.9% sodium chloride to obtain a total volume of 40 ml.

2nd dose

Prepare a 6.25 mg/ml solution. Dilute 10 ml of acetylcysteine (200 mg/ml) with 310 ml of 5% glucose or 0.9% sodium chloride to obtain a total volume of 320 ml.

3rd dose

Prepare a 6.25 mg/ml solution. Dilute 10 ml of acetylcysteine (200 mg/ml) with 310 ml of 5% glucose or 0.9% sodium chloride to obtain a total volume of 320 ml.

• Incompatibilities:

It is not recommended to administer acetylcysteine together with other medicines, particularly it should not be mixed with medicines for treating infections (antibiotics), due to the possible inactivation of the antibiotic (mainly beta-lactam antibiotics).