Package Insert: Information for the User

Cyanokit 5 g Powder for Solution for Infusion

Cyanocobalamin

Read this package insert carefully before using this medicine, as it contains important information for you.

• Keep this package insert, as you may need to read it again.

• If you have any questions, consult your doctor or pharmacist.

• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this package insert. See section 4.

1. How to Use Cyanokit
2. Adverse Effects
3. Storage of Cyanokit
4. Contents of the Package and Additional Information

Cyanokit contains the active ingredient 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 measures for decontamination and supportive therapy.

Cyanide is a highly toxic chemical substance. Cyanide poisoning can be caused by exposure to smoke from domestic or industrial fires, inhalation or ingestion of cyanide, or by contact of cyanide with the skin.

Warnings and precautions

Inform your doctor or another healthcare professional:

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

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

Use of Cyanokit with other medications

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

The detailed information for your doctor or another healthcare professional about the simultaneous administration of Cyanokit with other medications can be found at the end of this prospectus (see “Instructions for use and handling”).

Pregnancy and breastfeeding

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

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

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

Your doctor or a healthcare professional will administer Cyanokit through a vein by infusion. You may need one or two infusions.

The first infusion of Cyanokit 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 you need a second infusion, its duration will be 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.

You may find detailed instructions for your doctor or another healthcare professional on how to prepare the Cyanokit infusion and how to determine the dose at the end of this leaflet (see “Instructions for use and handling”).

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

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

Allergic (hypersensitivity) reaction

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

• 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 side effects may be severe and require immediate attention.

Cardiovascular and blood pressure problems

• Symptoms such as headache or dizziness, which may be due to increased blood pressure. This increase in blood pressure occurs especially at the end of treatment administration and usually resolves after a few hours.

• Irregular heart rhythm.
• Redness of the face (sensation of heat).

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

Respiratory and chest problems

• Presence of fluid in the chest (pleural effusion)
• Difficulty breathing
• Sensation of throat constriction
• Throat dryness
• Chest tightness (in the chest).

Renal and urinary problems

• Renal damage such as acute renal failure and crystals in the urine.
• Red-colored urine.

All patients will show dark red urine, quite pronounced, during the first three days after administration. Urine color may remain for up to 35 days after Cyanokit administration. This coloration has no other consequence on the body.

Gastrointestinal (digestive) problems

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

Eye problems

• Inflammation, irritation, redness.Skin reactions

• Most patients will experience reversible red discoloration of the skin and mucous membranes that may remain for up to 15 days after Cyanokit administration.

• Blisters on the skin (pustular eruptions). These may last several weeks and primarily affect the face and neck.

• Inflammation of the body part where the medication was administered by infusion.

Other side effects

• Anxiety
• Memory problems
• Dizziness
• Headache
• Swelling of the ankles

• Changes in some blood test results related to blood cells (lymphocytes)

• Coloration of the plasma, which may cause an artificial increase or decrease in the concentrations of some laboratory values.

Reporting side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect not listed in this prospectus. You can also report them directly through thenational notification system included in theAppendix V. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the vial, the carton box, and the carton after “CAD”.

Do not store at a temperature above 25°C.

For outpatient use, Cyanokit may be exposed for brief periods to temperature variations of:

• ordinary transportation (15 days exposed to temperatures between 5°C and 40°C)
• desert transportation (4 days exposed to temperatures between 5°C and 60°C) and
• freezing and thawing cycles (15 days exposed to temperatures between -20°C and 40°C).

For the storage conditions of the reconstituted medication, see “Instructions for use and handling”, at the end of this leaflet.

Medicines should not be disposed of through the drains or in the trash. Ask your pharmacist how to dispose of the containers and the medication that you no longer need. This will help protect the environment.

Composition of Cyanokit

• The active ingredient is hydroxocobalamin. The vial contains 5 g of hydroxocobalamin. After reconstitution with 200 mL of the 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 package

Cyanokit powder for solution for infusion is a dark brown crystalline powder, supplied in a closed glass vial with a bromobutyl rubber stopper and an aluminum cap with a plastic cap.

Each package contains a vial packaged in a cardboard box, a sterile transfer device, a sterile intravenous infusion set, and a short sterile catheter for administration to children.

Marketing Authorization Holder

SERB S.A.

Avenue Louise 480

1050 Brussels

Belgium

Responsible for manufacturing

Merck Santé s.a.s. / SEMOY

2, rue du Pressoir Vert

45400 Semoy

France

O

SERB S.A.

Avenue Louise 480

1050 Brussels

Belgium

O

SERB

40 avenue George V

75008 Paris

France

Last review date of this leaflet: MM/AAAA.

Other sources of information

The detailed information on this medicine is available on the website of the European Medicines Agency: http://www.ema.europa.eu.

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This information is intended only for doctors or healthcare professionals:

Instructions for use and handling

The treatment of cyanide poisoning should include immediate medical attention, ensuring airway patency, adequate oxygenation and hydration, cardiovascular care, and treatment of seizures. Consideration should be given to decontamination measures based on the route of exposure.

Cyanokit does not replace oxygen therapy and should not delay the establishment of the above measures. Frequently, the presence and magnitude of cyanide poisoning are initially unknown. There is no widely available and rapid test to confirm the presence of cyanide in the blood. However, if blood cyanide concentration is planned to be determined, it is recommended to draw the blood sample before initiating treatment with Cyanokit. Therapeutic decisions should be made based on clinical history, and/or the presence of signs and symptoms of cyanide poisoning. If there is a clinical suspicion of cyanide poisoning, it is strongly recommended to administer Cyanokit without delay.

Preparation of Cyanokit

The vial must be reconstitutedwith 200 mL of solvent, using the sterile transfer device provided. The recommended solvent issodium chloride 9 mg/mL (0.9%) in injectable solutioninjectable solution. If sodium chloride 9 mg/mL (0.9%) in injectable solution is not available, it mayalso be used lactate Ringer solution or glucose 50 mg/mL (5%) in injectable solution.

The Cyanokit vial must be shaken or inverted for at least one minute to mix the solution. It should not be agitated, as this may lead to foam formation, and thus, make it difficult to check the reconstitution. Since the reconstituted solution is a dark brown solution, it is possible that some insoluble particles may not be visible. Therefore, the intravenous infusion set provided in the kit, which contains a suitable filter, should be used to administer the reconstituted solution.

Dosage

Initial dose

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

Pediatric population:From neonates to adolescents (0 to 18 years), the initial dose of Cyanokit is70 mg/kg of body weight, not exceeding 5 g.

Subsequent dose

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

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

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

Maximum dose

Adults:The maximum recommended total dose is 10 g.

Pediatric population:From neonates to adolescents (0 to 18 years), the maximum recommended total doseis 140 mg/kg, not exceeding 10 g.

Renal or hepatic impairment

No dose adjustment is required in these patients.

Administration route

The initial dose of Cyanokit is 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.

Simultaneous administration of Cyanokit and other products

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

As physical and chemical incompatibilities have been observed with several frequently used medications in resuscitation, neither of these nor any other medication should be administered simultaneously in the same intravenous route as hydroxocobalamin.

If blood products (blood, erythrocyte concentrate, platelet concentrate, and frozen plasma) and hydroxocobalamin are to be administered simultaneously, it is recommended to use separate intravenous routes (preferably in contralateral extremities).

Combination with another cyanide antidote:chemical incompatibility was observed with sodium thiosulfate and sodium nitrite. If another cyanide antidote is to be administered with Cyanokit, these medications should not be administered simultaneously in the same intravenous route.

Stability during use of the reconstituted solution

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

From a microbiological point of view, the medicine should be used immediately. If not used immediately, the storage time and previous conditions are the responsibility of the user, and usually should not exceed 6 hours, at a temperature of 2°C to 8°C.