Cyantokit 5 g powder for solution for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Cyanokit 5 g powder for solution for infusion

Hydroxocobalamin

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 questions, ask your doctor or pharmacist.

• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the leaflet:

1. What Cyanokit is and what it is used for

2. What you need to know before you use Cyanokit

3. How to use Cyanokit

4. Possible side effects

5. How to store Cyanokit

6. Contents of the pack and other information

1. What Cyanokit is and what it is used for

Cyanokit contains the active substance hydroxocobalamin.

Cyanokit is an antidote for the treatment of confirmed or suspected cyanide poisoning in all age groups.

Cyanokit should be administered along with appropriate decontamination measures and supportive therapy.

Cyanide is a highly toxic chemical. Cyanide poisoning may result from exposure to smoke in domestic or industrial fires, inhalation or ingestion of cyanide, or skin contact with cyanide.

2. What you need to know before using Cyanokit

Warnings and precautions

Inform your doctor or other healthcare professional:

• If you are allergic to hydroxocobalamin or vitamin B12. They will take this into account before treating you with Cyanokit.

• That you have received treatment with Cyanokit if you need to undergo any of the following procedures:

• blood or urine tests. Cyanokit may alter the results of these tests.

• assessment of burns. Cyanokit may interfere with the assessment because it causes red discoloration of the skin.

• hemodialysis. Cyanokit may cause dialysis machines to shut down until it has been cleared from the blood (at least 5.5 to 6.5 days).

• monitoring of kidney function: Cyanokit may lead to kidney failure and presence of crystals in urine.

Use of Cyanokit with other medicines

Inform your doctor or other healthcare professional if you are taking, have recently taken, or might need to take any other medicines.

Detailed information for your doctor or other healthcare professional regarding concomitant administration of Cyanokit with other medicines can be found at the end of this leaflet (see “Instructions for use and handling”).

Pregnancy and breastfeeding

This medicine is an emergency treatment. It may be administered during pregnancy and breastfeeding.

Inform your doctor as soon as possible if you were pregnant or think you might have been pregnant during treatment with Cyanokit.

Your doctor will advise you to stop breastfeeding after treatment with Cyanokit.

3. How to use Cyanokit

Your doctor or a healthcare professional will administer Cyanokit by intravenous infusion into a vein. You may require one or two infusions.

The first Cyanokit infusion will last 15 minutes. In adults, the initial dose is 5 g. In children, it is 70 mg/kg of body weight, up to a maximum dose of 5 g. If a second infusion is needed, it will last between 15 minutes and 2 hours, depending on the severity of your poisoning. The maximum recommended total dose is 10 g in adults and 140 mg/kg, up to a maximum of 10 g, in children.

Detailed instructions for your doctor or other healthcare professional on how to prepare the Cyanokit infusion and how to determine the dose can be found at the end of this leaflet (see “Instructions for use and handling”).

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

4. Possible adverse effects

Like all medicines, Cyanokit may cause adverse effects, although not everyone experiences them. The following adverse effects may be expected (frequency cannot be estimated from the available data):

Allergy (hypersensitivity)

Inform your doctor immediately if you experience the following symptoms during or after treatment:

• Swelling around the eyes, lips, tongue, throat, or hands.
• Difficulty breathing, hoarseness, or difficulty speaking.
• Redness of the skin, skin rash with irritation (urticaria), or itching.

These adverse effects may be severe and may require immediate medical attention.

Cardiac and blood pressure problems

• Symptoms such as headache or dizziness, which may be due to increased blood pressure. This rise in blood pressure occurs particularly towards the end of treatment administration and usually resolves within a few hours.

• Irregular heartbeat.

• Flushing (redness of the face).

In patients suffering from cyanide poisoning, a decrease in blood pressure and an increase in heart rate have also been observed.

Respiratory and chest problems

• Fluid accumulation in the chest (pleural effusion)
• Difficulty breathing
• Sensation of throat tightness
• Dry throat
• Chest tightness (in the chest).

Renal and urinary problems

• Kidney damage such as acute renal failure and crystals in urine.
• Red discoloration of the urine.

All patients will show dark red discoloration of the urine, which is quite pronounced during the first three days after administration. The discoloration of urine may persist for up to 35 days after administration of Cyanokit. This discoloration has no other consequences for the body.

Gastrointestinal (digestive) problems

• Stomach discomfort
• Indigestion
• Diarrhea
• Nausea
• Vomiting
• Difficulty swallowing.

Ocular problems

• Swelling, irritation, redness. Skin reactions

• Most patients will experience reversible red discoloration of the skin and of the membranes lining body cavities (mucous membranes), which may last up to 15 days after administration of Cyanokit.

• Blister-like skin lesions (pustular eruptions). These may persist for several weeks and mainly affect the face and neck.

• Swelling at the site where the medicine was administered by infusion.

Other adverse effects

• Restlessness

• Memory problems

• Dizziness

• Headache

• Swelling of the ankles

• Changes in the results of certain blood tests related to blood cells (lymphocytes)

• Discoloration of plasma, which may cause artificial increases or decreases in certain laboratory values.

Reporting of adverse effects

If you experience any adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Cyanokit

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

Do not use this medicine after the expiry date stated on the vial, the cardboard box, and the carton after "EXP".

Do not store at temperatures above 25°C.

For outpatient use, Cyanokit may be exposed for short periods to temperature variations during:

• normal transport (15 days at temperatures between 5°C and 40°C),
• desert transport (4 days at temperatures between 5°C and 60°C), and
• freeze-thaw cycles (15 days at temperatures between -20°C and 40°C).

For storage conditions of the reconstituted medicine, see "Instructions for use and handling" at the end of this leaflet.

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

6. Contents of the pack and other information

Composition of Cyanokit

• The active substance is hydroxocobalamin. The vial contains 5 g of hydroxocobalamin. After reconstitution with 200 mL of solvent, each mL of the reconstituted solution contains 25 mg of hydroxocobalamin.

• The other component is hydrochloric acid (for pH adjustment).

Appearance of the product and contents of the pack

Cyanokit powder for solution for infusion is a dark red crystalline powder supplied in a glass vial closed with a bromobutyl rubber stopper and an aluminium seal with a plastic cap.

Each pack contains one vial packed in a cardboard box, a sterile transfer device, a sterile intravenous infusion set, and a sterile short catheter for administration in children.

Marketing Authorisation Holder

SERB S.A.
Avenue Louise 480
1050 Brussels
Belgium

Manufacturer

Merck Santé s.a.s. / SEMOY
2, rue du Pressoir Vert
45400 Semoy
France

Or

SERB S.A.
Avenue Louise 480
1050 Brussels
Belgium

Or

SERB
40 avenue George V
75008 Paris
France

Date of the most recent revision of this leaflet: MM/YYYY

Other sources of information

Detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu.

This information is intended for healthcare professionals only:

Instructions for use and handling

Treatment of cyanide poisoning must include immediate medical care, ensuring airway patency, adequate oxygenation and hydration, cardiovascular support, and management of seizures. Decontamination measures should be considered depending on the route of exposure.

Cyanokit does not replace oxygen therapy and should not delay the implementation of the above measures. The presence and severity of cyanide poisoning are often initially unknown. There is no widely available, rapid test to confirm cyanide levels in blood. However, if blood cyanide concentration measurement is planned, it is recommended to collect the blood sample before starting treatment with Cyanokit. Therapeutic decisions should be based on clinical history and/or the presence of signs and symptoms of cyanide poisoning. If there is clinical suspicion of cyanide poisoning, prompt administration of Cyanokit is strongly recommended.

Preparation of Cyanokit

The vial must be reconstituted with 200 mL of solvent, using the sterile transfer device provided. The recommended solvent is sodium chloride 9 mg/mL (0.9%) for injection. Only if sodium chloride 9 mg/mL (0.9%) for injection is not available, lactated Ringer's solution or glucose 50 mg/mL (5%) for injection may also be used.

The Cyanokit vial should be gently rotated or inverted for at least one minute to mix the solution. It must not be shaken, as this may cause foaming and thus make it difficult to assess complete reconstitution. Since the reconstituted solution is dark red, insoluble particles may not be visible. For this reason, the intravenous infusion set provided in the kit, which includes an appropriate filter, must be used and should be primed with the reconstituted solution.

Dosage

Initial dose

Adults: The initial dose of Cyanokit is 5 g (200 mL, full volume of the reconstituted solution).

Paediatric population: From infants to adolescents (0 to 18 years of age), the initial dose of Cyanokit is 70 mg/kg body weight, not exceeding 5 g.

Subsequent Dose

Depending on the severity of poisoning and the clinical response, a second dose may be administered.

Adults: The subsequent dose of Cyanokit is 5 g (200 mL, full volume of the reconstituted solution).

Pediatric population: From infants to adolescents (0 to 18 years of age), the subsequent dose of Cyanokit is 70 mg/kg body weight, not exceeding 5 g.

Maximum Dose

Adults: The maximum recommended total dose is 10 g.

Pediatric population: From infants to adolescents (0 to 18 years of age), the maximum recommended total dose is 140 mg/kg, not exceeding 10 g.

Renal or Hepatic Impairment

Dose adjustment is not required in these patients.

Route of Administration

The initial dose of Cyanokit should be administered by intravenous infusion over 15 minutes.

The intravenous infusion rate for the second dose ranges from 15 minutes (for highly unstable patients) to 2 hours, depending on the patient's condition.

Concomitant Administration of Cyanokit and Other Products

Cyanokit must not be mixed with other diluents except sodium chloride solution 9 mg/mL (0.9%), Ringer's lactate solution, or glucose 50 mg/mL (5%) in injectable solution.

Physical and chemical incompatibilities have been observed with several commonly used resuscitation drugs; therefore, these or any other medications must not be administered simultaneously through the same intravenous line as hydroxocobalamin.

If blood products (blood, red blood cell concentrate, platelet concentrate, and fresh frozen plasma) and hydroxocobalamin are to be administered simultaneously, the use of separate intravenous lines (preferably in contralateral limbs) is recommended.

Combination with another cyanide antidote: Chemical incompatibility has been observed with sodium thiosulfate and sodium nitrite. If another cyanide antidote is to be administered together with Cyanokit, these medications must not be given at the same time through the same intravenous line.

Stability of the Reconstituted Solution During Use

Chemical and physical stability of the reconstituted solution with sodium chloride 9 mg/mL (0.9%) has been demonstrated for 6 hours at temperatures between 2°C and 40°C.

From a microbiological standpoint, the medicinal product should be used immediately. If not used immediately, the storage time and conditions prior to use are the responsibility of the user and should normally not exceed 6 hours at a temperature of 2°C to 8°C.