Cyanokit

1 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX I 

 

SUMMARY OF PRODUCT CHARACTERISTICS 



 

2 

1. NAME OF THE MEDICINAL PRODUCT 

 

Cyanokit 2.5 g powder for solution for infusion 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

Each vial contains 2.5 g of hydroxocobalamin.  

After reconstitution with 100 mL of diluent, each mL of the reconstituted solution contains 25 mg of 

hydroxocobalamin.  

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Powder for solution for infusion. 

 

Dark red crystalline powder. 

 

 

4. CLINICAL PARTICULARS 

 

4.1 Therapeutic indications 

 

Treatment of known or suspected cyanide poisoning in all age ranges. 

 

Cyanokit is to be administered together with appropriate decontamination and supportive measures 

(see section 4.4). 

 

4.2 Posology and method of administration 

 

Posology 

 

Initial dose 

Adults: The initial dose of Cyanokit is 5 g (2 x 100 mL). 

 

Paediatric population: In infants to adolescents (0 to 18 years old), the initial dose of Cyanokit is 

70 mg/kg body weight not exceeding 5 g. 

 

Body weight 

in kg 

 

5 

 

10 

 

20 

 

30 

 

40 

 

50 

 

60 

Initial dose  

in g 

in mL 

 

0.35 

14 

 

0.70 

28 

 

1.40 

56 

 

2.10 

84 

 

2.80 

112 

 

3.50 

140 

 

4.20 

168 

 

Subsequent dose 

Depending upon the severity of the poisoning and the clinical response (see section 4.4), a second 

dose may be administered. 

 

Adults: The subsequent dose of Cyanokit is 5 g (2 x 100 mL). 

 

Paediatric population: In infants to adolescents (0 to 18 years old), the subsequent dose of Cyanokit 

is 70 mg/kg body weight not exceeding 5 g. 

 



 

3 

Maximum dose 

 

Adults: The maximum total recommended dose is 10 g. 

 

Paediatric population: In infants to adolescents (0 to 18 years old), the maximum total recommended 

dose is 140 mg/kg not exceeding 10 g. 

 

Renal and hepatic impairment 

 

Although the safety and efficacy of hydroxocobalamin have not been studied in renal and hepatic 

impairments, Cyanokit is administered as emergency therapy in an acute, life-threatening situation 

only and no dose adjustment is required in these patients. 

 

Method of administration 

 

Initial dose of Cyanokit is administered as an intravenous infusion over 15 minutes. 

 

The rate of intravenous infusion for the second dose ranges from 15 minutes (for patients extremely 

unstable) to 2 hours based on patient condition. 

 

For instructions on reconstitution of the medicinal product before administration, see section 6.6. 

 

4.3 Contraindications 

 

None. 

 

4.4 Special warnings and precautions for use 

 

Treatment of cyanide poisoning must include immediate attention to airway patency, adequacy of 

oxygenation and hydration, cardiovascular support, and management of seizures. Consideration must 

be given to decontamination measures based on the route of exposure. 

 

Cyanokit does not substitute oxygen therapy and must not delay the set up of the above measures. 

 

The presence and extent of cyanide poisoning are often initially unknown. There is no widely 

available, rapid, confirmatory cyanide blood test. Treatment decisions must be made on the basis of 

clinical history and/or signs and symptoms of cyanide intoxication.  

 

Cyanide poisoning may result from exposure to smoke from closed space fires, inhalation, ingestion, 

or dermal exposure. Sources of cyanide poisoning include hydrogen cyanide and its salts, cyanogens, 

including cyanogenic plants, aliphatic nitriles, or prolonged exposure to sodium nitroprusside. 

 

Signs and symptoms of cyanide poisoning 

 

Common signs and symptoms of cyanide poisoning include: nausea, vomiting, headache, altered 

mental status (e.g. confusion, disorientation), chest tightness, dyspnoea, tachypnoea or hyperpnoea 

(early), bradypnoea or apnoea (late), hypertension (early) or hypotension (late), cardiovascular 

collapse, seizures or coma, mydriasis, and plasma lactate concentration > 8 mmol/L. 

 

In the setting of multiple casualties such as terrorism or chemical disaster, panic symptoms including 

tachypnoea and vomiting may mimic early cyanide poisoning signs. The presence of altered mental 

status (confusion and disorientation) and/or mydriasis is suggestive of true cyanide poisoning. 

 



 

4 

Smoke inhalation 

 

Not all smoke inhalation victims necessarily will have cyanide poisoning, but may present with burns, 

trauma, and exposure to additional toxic substances aggravating the clinical picture. Before Cyanokit 

is administered, it is recommended to check affected persons for the presence of the following: 

 exposure to fire smoke in an enclosed area 

 soot present around mouth, nose and/or oropharynx 

 altered mental status 

 

In this setting hypotension and/or a plasma lactate concentration ≥ 10 mmol/L (higher than the one 

mentioned under signs and symptoms due to the fact that carbon monoxide contributes to lactic 

acidaemia) are highly suggestive of cyanide poisoning. In the presence of the above signs, treatment 

with Cyanokit must not be delayed to obtain a plasma lactate concentration. 

 

Hypersensitivity reactions 

 

Known hypersensitivity to hydroxocobalamin or vitamin B12 must be taken into benefit-risk 

consideration before administration of Cyanokit, since hypersensitive reactions may occur in patients 

receiving hydroxocobalamin (see section 4.8). 

 

Renal disorders  

Oxalate crystals have been observed in the urine of healthy volunteers given hydroxocobalamin. 

Cases of acute renal failure with acute tubular necrosis, renal impairment and urine calcium oxalate 

crystals present have been reported in patients treated with hydroxocobalamin following known or 

suspected cyanide poisoning. In some situations, hemodialysis  was required to achieve recovery  (see 

section 4.8). 

Therefore, as a precaution, after Cyanokit administration, regular monitoring of renal function 

(including blood urea nitrogen and serum creatinine) should be performed until 7 days after drug 

onset. 

 

Increase in blood pressure 

 

Transient, generally asymptomatic, increase in blood pressure may occur in patients receiving 

hydroxocobalamin. The maximal increase in blood pressure has been observed toward the end of 

infusion (see section 4.8). 

 

Effects on blood cyanide assay 

 

Hydroxocobalamin will lower blood cyanide concentrations. While determination of blood cyanide 

concentration is not required and must not delay treatment with hydroxocobalamin, it may be useful 

for documenting cyanide poisoning. If a cyanide blood level determination is planned, it is 

recommended to draw the blood sample before initiation of treatment with Cyanokit. 

 

Interference with burn assessment 

 

Because of its deep red colour, hydroxocobalamin has the potential to induce a red colouration of the 

skin and therefore may interfere with burn assessment. However, skin lesions, oedema, and pain are 

highly suggestive of burns. 

 



 

5 

Interference with laboratory tests 

 

Because of its deep red colour, hydroxocobalamin has the potential to interfere with determination of 

laboratory parameters (e.g. clinical chemistry, haematology, coagulation, and urine parameters). 

In vitro tests indicate that the extent and duration of the interference is dependant on numerous factors 

such as the dose of hydroxocobalamin, analyte, analyte concentration, methodology, analyser, 

concentrations of cobalamins-(III) including cyanocobalamin and partially the time between sampling 

and measurement. 

 

Based on in vitro studies and pharmacokinetic data obtained in healthy volunteers the following table 

describes interference with laboratory tests that may be observed following a 5 g dose of 

hydroxocobalamin. Interference following a 10 g dose can be expected to last up to an additional 

24 hours. The extent and duration of interference in cyanide-poisoned patients may differ according to 

the severity of intoxication. Results may vary considerably from one analyser to another, therefore, 

caution is required when reporting and interpreting laboratory results. 

 

Observed in vitro interferences of hydroxocobalamin with laboratory tests 

 

Laboratory 

parameter 

No interference 

observed Artificially 

increased* 

Artificially  

decreased* Unpredictable*** 

Duration of 

interference 

after a 5 g dose 

Clinical 

chemistry 

Calcium 

Sodium 

Potassium 

Chloride 

Urea 

Gamma glutamyl 

transferase (GGT) 

Creatinine 

Total and 

conjugate 

bilirubin** 

Triglycerides 

Cholesterol 

Total protein 

Glucose 

Albumin 

Alkaline 

phosphatase 

Alanine 

aminotransferase 

(ALT) 

Amylase 

Phosphate 

Uric acid 

Aspartate 

aminotransferase 

(AST) 

Creatine kinase (CK) 

Creatine kinase 

isoenzym MB 

(CKMB) 

Lactate dehydrogenase 

(LDH) 

24 hours with the 

exception of 

bilirubin (up to 

4 days) 

Haematology Erythrocytes 

Haematocrit 

Mean corpuscular 

volume (MCV) 

Leucocytes 

Lymphocytes 

Monocytes 

Eosinophils 

Neutrophils 

Platelets 

Haemoglobin 

(Hb) 

Mean 

corpuscular 

haemoglobin 

(MCH) 

Mean 

corpuscular 

haemoglobin 

concentration 

(MCHC) 

 

  12-16 hours 

Coagulation    Activated partial 

thromboplastin time 

(aPTT) 

Prothrombin time (PT) 

Quick or INR 

24 hours 

* ≥ 10% interference observed on at least one analyser  

** Artificially decreased using the diazo method 

*** Inconsistent results 

Analysers used: ACL Futura (Instrumentation Laboratory), Axsym/Architect (Abbott), BM Coasys110 

(Boehringer Mannheim), CellDyn 3700 (Abbott), Clinitek 500 (Bayer), Cobas Integra 700, 400 

(Roche), Gen-S Coultronics, Hitachi 917, STA Compact, Vitros 950 (Ortho Diagnostics) 

 

Hydroxocobalamin may interfere with all urine colorimetric parameters. The effects on these tests 

typically last 48 hours after a 5 g dose, but may persist for longer periods. Caution is required in the 

interpretation of urinary colorimetric tests for as long as chromaturia is present. 

 



 

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Interference with haemodialysis 

 

Because of its deep red color, hydroxocobalamin may cause haemodialysis machines to shut down 

due to an erroneous detection of a ‘blood leak’. This should be considered before haemodialysis is 

initiated in patients treated with hydroxocobalamin. 

 

Use with other cyanide antidotes 

 

The safety of administering other cyanide antidotes simultaneously with Cyanokit has not been 

established (see section 6.2). If the decision is made to administer another cyanide antidote with 

Cyanokit, these medicinal products must not be administered concurrently in the same intravenous 

line (see section 6.2). 

 

4.5 Interaction with other medicinal products and other forms of interaction 

 

No interaction studies have been performed. 

 

4.6 Fertility, pregnancy and lactation 

 

Pregnancy 

 

Animal studies have shown teratogenic effects following daily exposure throughout organogenesis 

(see section 5.3). There are no adequate data from the use of hydroxocobalamin in pregnant women 

and the potential risk for humans is unknown.  

However, taken into account: 

- that no more than two injections of hydroxocobalamin are to be administered, 

- the potentially life threatening condition, 

- the lack of alternative treatment, 

hydroxocobalamin may be given to a pregnant woman. 

 

In case of known pregnancy at the time of treatment with Cyanokit or in case that pregnancy becomes 

known after treatment with Cyanokit, health care professionals are requested to promptly report the 

exposure during pregnancy to the Marketing Authorisation Holder and/or Health Authorities and to 

carefully follow-up on the pregnancy and its outcome. 

 

Breast-feeding  

 

Because hydroxocobalamin will be administered in potentially life-threatening situations, breast-

feeding is not a contraindication to its use. In the absence of data in breast-fed infants, breast-feeding 

discontinuation is recommended after receiving Cyanokit. 

 

Fertility 

 

No studies on fertility have been performed (see section 5.3). 

 

4.7 Effects on ability to drive and use machines 

 

Not relevant. 

 



 

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4.8 Undesirable effects 

 

Summary of the safety profile 

 

A total of 347 subjects were exposed to hydroxocobalamin in clinical studies. Of these 347 subjects, 

245 patients had suspected exposure to cyanide at the time of hydroxocobalamin administration. The 

remaining 102 subjects were healthy volunteers who had not been exposed to cyanide at the time of 

hydroxocobalamin administration. 

 

List of adverse reactions 

 

The following adverse reactions have been reported in association with Cyanokit use. However, 

because of the limitations of the available data, it is not possible to apply frequency estimations: 

 

Blood and lymphatic system disorders 

 

Decrease in the percentage of lymphocytes. 

 

Immune system disorders 

 

Allergic reactions including angioneurotic oedema, skin eruption, urticaria and pruritus. 

 

Psychiatric disorders 

 

Restlessness. 

 

Nervous system disorders 

 

Memory impairment; dizziness. 

 

Eye disorders 

 

Swelling, irritation, redness.  

 

Cardiac disorders 

 

Ventricular extrasystoles. An increase in heart rate was observed in cyanide-poisoned patients. 

 

Vascular disorders 

 

Transient increase in blood pressure, usually resolving within several hours; hot flush. A decrease in 

blood pressure was observed in cyanide-poisoned patients. 

 

Respiratory, thoracic and mediastinal disorders 

 

Pleural effusion, dyspnoea, throat tightness, dry throat, chest discomfort. 

 

Gastrointestinal disorders 

 

Abdominal discomfort, dyspepsia, diarrhoea, vomiting, nausea, dysphagia. 

 



 

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Skin and subcutaneous tissue disorders 

 

Reversible red colouration of the skin and mucous membranes : most patients will experience it up to 

15 days after administration of Cyanokit. 

Pustular rashes, which may last for several weeks, affecting mainly the face and the neck. 

 

Renal and urinary disorders 

 

 Acute renal failure with acute tubular necrosis, renal impairment, urine calcium oxalate crystals 

present (see section 4.4). 

 

 Chromaturia : all patients will show a dark red colouration of the urine quite marked during the 

first three days following administration. Urine colouration may last up to 35 days after 

administration of Cyanokit (see section 4.4 ). 

 

General disorders and administration site conditions 

 

Headache; injection site reaction; peripheral oedema. 

 

Investigations 

 

Cyanokit may cause red discolouration of the plasma, which may cause artificial elevation or 

reduction in the levels of certain laboratory parameters (see section 4.4). 

 

Paediatric population 

 

Limited data on children (0 to 18 years old) treated with hydroxocobalamin did not show any 

difference in the safety profile of hydroxocobalamin between adults and children. 

 

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 

listed in Appendix V. 

 

4.9 Overdose 

 

Doses as high as 15 g have been administered without reported specific dose related adverse 

reactions. If overdose occurs, treatment is directed to the management of symptoms. Haemodialysis 

may be effective in such a circumstance, but is only indicated in the event of significant 

hydroxocobalamin-related toxicity. However, hydroxocobalamin because of its deep red colour may 

interfere with the performance of haemodialysis machines (see section 4.4). 

 

 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1 Pharmacodynamic properties 

 

Pharmacotherapeutic group: Antidotes, ATC code: V03AB33 

 



 

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Mechanism of action 

 

The action of hydroxocobalamin in the treatment of cyanide poisoning is based on its ability to tightly 

bind cyanide ions. Each hydroxocobalamin molecule can bind one cyanide ion by substituting the 

hydroxo ligand linked to the trivalent cobalt ion to form cyanocobalamin. Cyanocobalamin is a stable, 

non-toxic compound that is excreted in the urine.  

 

Efficacy 

 

Due to ethical considerations, no controlled human efficacy studies have been performed.  

 

 Animal pharmacology 

 

The effectiveness of hydroxocobalamin was examined in a controlled study in cyanide-poisoned adult 

dogs. Dogs were poisoned by intravenous administration of a lethal dose of potassium cyanide. Dogs 

then received sodium chloride 9 mg/mL, 75 mg/kg or 150 mg/kg hydroxocobalamin, administered 

intravenously over 7.5 minutes. The 75 mg/kg and 150 mg/kg doses are approximately equivalent to 

5 g and 10 g of hydroxocobalamin, respectively, in humans, not only on a body weight basis but also 

on Cmax basis of hydroxocobalamin [total cobalamins-(III), see section 5.2]. 

 

Survival at hour 4 and at day 14 was significantly greater in 75 mg/kg and 150 mg/kg 

hydroxocobalamin dose groups compared with dogs receiving sodium chloride 9 mg/mL alone: 

 

Survival of cyanide-poisoned dogs 

 

Parameter 

Treatment 

Sodium chloride 

9 mg/mL 

(N=17) 

Hydroxocobalamin 

75 mg/kg 

(N=19) 

150 mg/kg 

(N=18) 

Survival at Hour 4, N (%) 7 (41) 18 (95)* 18 (100)* 

Survival at Day 14, N (%) 3 (18) 15 (79)* 18 (100)* 
* p< 0.025 

 

Histopathology revealed brain lesions that were consistent with cyanide-induced hypoxia. The 

incidence of brain lesions was markedly lower in dogs having received 150 mg/kg hydroxocobalamin 

than in dogs having received 75 mg/kg hydroxocobalamin or sodium chloride 9 mg/mL. 

 

The rapid and complete recovery of haemodynamics and subsequently of blood gases, pH, and lactate 

after cyanide poisoning likely contributed to the better outcome of the hydroxocobalamin-treated 

animals. Hydroxocobalamin reduced whole blood cyanide concentrations from about 120 nmol/mL to 

30-40 nmol/mL by the end of the infusion compared with 70 nmol/mL in dogs receiving sodium 

chloride 9 mg/mL alone. 

 

 Cyanide-poisoned patients 

 

A total of 245 patients with suspected or known cyanide-poisoning were included in the clinical 

studies of the efficacy of hydroxocobalamin as an antidote. Of the 213 patients in whom the outcome 

was known the survival was 58%. Of the 89 patients who died, 63 were initially found in cardiac 

arrest, suggesting that many of these patients had almost certainly suffered irreparable brain injury 

prior to administration of hydroxocobalamin. Among 144 patients not in initial cardiac arrest whose 

outcomes were known, 118 (82%) survived. Furthermore, in 34 patients with known cyanide 

concentrations above the lethal threshold (≥ 100 µmol/L), 21 (62%) survived following treatment with 

hydroxocobalamin. 

Administration of hydroxocobalamin was generally associated with a normalisation of blood pressure 

(systolic blood pressure > 90 mmHg) in 17 of 21 patients (81%) who had low blood pressure (systolic 



 

10 

blood pressure > 0 and ≤ 90 mmHg) after exposure to cyanide. Where neurological assessment over 

time was possible, (96 patients of the 171 patients who presented with neurological symptoms prior to 

hydroxocobalamin administration), 51 (53%) patients receiving hydroxocobalamin showed 

improvement or a complete restoration.  

 

 Elderly 

 

Approximately 50 known or suspected cyanide victims aged 65 or older received hydroxocobalamin 

in clinical studies. In general, the effectiveness of hydroxocobalamin in these patients was similar to 

that of younger patients. 

 

 Paediatric population 

 

Documentation on efficacy is available for 54 paediatric patients. The mean age of the paediatric 

patients was about six years and the mean dose of hydroxocobalamin was about 120 mg/kg body 

weight. The survival rate of 41% depended very much on the clinical situation. Out of the 

20 paediatric patients without initial cardiac arrest, 18 (90%) survived, of whom 4 with sequelae. In 

general, the effectiveness of hydroxocobalamin in paediatric patients was similar to that of adults. 

 

5.2 Pharmacokinetic properties 

 

Following intravenous administration of Cyanokit, significant binding to plasma proteins and low 

molecular weight physiological compounds occurs, to form various cobalamin-(III) complexes by 

replacing the hydroxo ligand. The low molecular weight cobalamins-(III) formed including 

hydroxocobalamin are termed free cobalamins-(III); the sum of free and protein-bound cobalamins is 

termed total cobalamins-(III). In order to reflect the exposure to the sum of all derivatives, 

pharmacokinetics of cobalamins-(III) were investigated instead of hydroxocobalamin, requiring the 

concentration unit µg eq/mL (i.e. cobalamin-(III) entity without specific ligand). 

 

Dose-proportional pharmacokinetics were observed following single dose intravenous administration 

of 2.5 to 10 g of Cyanokit in healthy volunteers. Mean free and total cobalamins-(III) Cmax values of 

113 and 579 µg eq/mL, respectively, were determined following a dose of 5 g Cyanokit (the 

recommended initial dose). Similarly, mean free and total cobalamins-(III) Cmax values of 197 and 

995 µg eq/mL, respectively, were determined following the dose of 10 g Cyanokit. The predominant 

mean half-life of free and total cobalamins-(III) was approximately 26 to 31 hours at the 5 and 10 g 

dose level. 

 

The mean total amount of cobalamins-(III) excreted in urine during the collection period of 72 hours 

was approximately 60% of a 5 g dose and approximately 50% of a 10 g dose of Cyanokit. Overall, the 

total urinary excretion was calculated to be at least 60 to 70% of the administered dose. The majority 

of the urinary excretion occurred during the first 24 hours, but red coloured urine was observed for up 

to 35 days following the intravenous infusion. 

 

When normalized for body weight, male and female subjects revealed no major differences in plasma 

and urinary pharmacokinetic parameters of free and total cobalamins-(III) following the 

administration of 5 g or 10 g Cyanokit. 

 

In cyanide-poisoned patients, hydroxocobalamin is expected to bind cyanide to form cyanocobalamin, 

which is excreted in the urine. The pharmacokinetics of total cobalamins-(III) in this population may 

be affected by the body's cyanide load, since cyanocobalamin was reported to exhibit a 2-3 times 

lower half-life than total cobalamins-(III) in healthy volunteers. 

 



 

11 

5.3 Preclinical safety data 

 

In anaesthetised rabbits, hydroxocobalamin exerted haemodynamic effects (increased mean arterial 

blood pressure and total peripheral resistance, decreased cardiac output) related to its nitric oxide-

scavenging property. 

 

No special hazard for humans was identified based on conventional studies of single and repeated 

dose toxicity and genotoxicity. The liver and kidney were found to be the major target organs. 

However findings were only seen at exposure levels considered being higher than the maximum 

human exposure, indicating limited relevance to clinical use. In particular, liver fibrosis was observed 

in dogs after administration of hydroxocobalamin for 4 weeks at 300 mg/kg. The relevance of this 

finding to humans is unlikely since it was not reported in short-term studies conducted with 

hydroxocobalamin. 

 

Developmental toxicity, including teratogenicity, was observed in rats and rabbits at dose levels of 

150 mg/kg and higher administered daily throughout organogenesis. The dose of 150 mg/kg 

approximately corresponds to the maximum recommended human dose. 

 

No data are available on male and female fertility as well as on peri- and postnatal development. 

Hydroxocobalamin has not been evaluated for carcinogenic potential. 

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 

 

Hydrochloric acid (for pH-adjustment) 

 

6.2 Incompatibilities 

 

This medicinal product must not be mixed with other medicinal products except those mentioned in 

section 6.6. 

 

Physical incompatibility (particle formation) was observed with the mixture of hydroxocobalamin 

reconstituted solution and the following medicinal products: diazepam, dobutamine, dopamine, 

fentanyl, nitroglycerin, pentobarbital, phenytoin sodium, propofol and thiopental.  

 

Chemical incompatibility was observed with the mixture of hydroxocobalamin reconstituted solution 

and the following medicinal products: epinephrine, lidocaine hydrochloride, adenosine, atropine, 

midazolam, ketamin, succinylcholine chloride, amiodarone hydrochloride, sodium bicarbonate, 

sodium thiosulfate, sodium nitrite, and has been reported with ascorbic acid.  

Consequently, these and other medicinal products must not be administered simultaneously through 

the same intravenous line as hydroxocobalamin. 

 

Simultaneous administration of hydroxocobalamin and blood products (whole blood, packed red cells, 

platelet concentrate and fresh frozen plasma) through the same intravenous line is not recommended.  

 

6.3 Shelf life 

 

3 years. 

 

For the purpose of ambulatory use, Cyanokit may be exposed during short periods to the temperature 

variations of usual transport (15 days submitted to temperatures ranging from 5°C to 40°C), transport 

in the desert (4 days submitted to temperatures ranging from 5°C to 60°C) and freezing/defrosting 

cycles (15 days submitted to temperatures ranging from -20°C to 40°C). If these temporary conditions 

have been exceeded, the product should be discarded. 



 

12 

 

Chemical and physical in-use 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 medicinal product should be used immediately. If not used 

immediately, in-use storage times and conditions prior to use are the responsibility of the user and 

would normally not be longer than 6 hours at 2°C to 8ºC. 

 

6.4 Special precautions for storage 

 

Do not store above 25°C. 

 

For storage conditions after reconstitution of the medicinal product, see section 6.3. 

 

6.5 Nature and contents of container 

 

Type II colourless 250 mL glass vial closed with bromobutyl rubber stopper and an aluminium cap 

with a plastic lid.  

Each pack contains two vials (each vial packed in one cardboard box), two sterile transfer devices, 

one sterile intravenous infusion set and one sterile short catheter for administration to children. 

 

6.6 Special precautions for disposal and other handling 

 

No special requirements for disposal. 

 

Each vial is to be reconstituted with 100 mL of diluent using the supplied sterile transfer device.  

Sodium chloride 9 mg/mL (0.9%) solution for injection is the recommended diluent. Only when 

sodium chloride 9 mg/mL (0.9%) solution for injection is not available, Lactated Ringer solution or 

glucose 50 mg/mL (5%) solution for injection can also be used.  

 

The Cyanokit vial is to be rocked or inverted for at least 30 seconds to mix the solution. It must not be 

shaken as shaking the vial may cause foam and therefore may make checking reconstitution less easy. 

Because the reconstituted solution is a dark red solution, some insoluble particles may not be seen. 

The intravenous infusion set provided in the kit must then be used as it includes an appropriate filter 

and is to be primed with the reconstituted solution. Repeat this procedure if necessary with the second 

vial. 

 

 

7. MARKETING AUTHORISATION HOLDER 

 

SERB S.A. 

Avenue Louise 480  

1050 Brussels 

Belgium 

 

 

8. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/07/420/001 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

 

Date of first authorisation: 23 November 2007 

Date of latest renewal: 20 July 2012 

 

 



 

13 

10. DATE OF REVISION OF THE TEXT 

 

MM/YYYY 

 

 

Detailed information on this medicinal product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu. 



 

14 

1. NAME OF THE MEDICINAL PRODUCT 

 

Cyanokit 5 g powder for solution for infusion 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

The vial contains 5 g of hydroxocobalamin.  

After reconstitution with 200 mL of diluent, each mL of the reconstituted solution contains 25 mg of 

hydroxocobalamin.  

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Powder for solution for infusion. 

 

Dark red crystalline powder. 

 

 

4. CLINICAL PARTICULARS 

 

4.1 Therapeutic indications 

 

Treatment of known or suspected cyanide poisoning in all age ranges. 

 

Cyanokit is to be administered together with appropriate decontamination and supportive measures 

(see section 4.4). 

 

4.2 Posology and method of administration 

 

Posology 

 

Initial dose 

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

 

Paediatric population: In infants to adolescents (0 to 18 years old), the initial dose of Cyanokit is 

70 mg/kg body weight not exceeding 5 g. 

 

Body weight 

in kg 

 

5 

 

10 

 

20 

 

30 

 

40 

 

50 

 

60 

Initial dose  

in g 

in mL 

 

0.35 

14 

 

0.70 

28 

 

1.40 

56 

 

2.10 

84 

 

2.80 

112 

 

3.50 

140 

 

4.20 

168 

 

Subsequent dose 

Depending upon the severity of the poisoning and the clinical response (see section 4.4), a second 

dose may be administered. 

 

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

 

Paediatric population: In infants to adolescents (0 to 18 years old), the subsequent dose of Cyanokit 

is 70 mg/kg body weight not exceeding 5 g. 

 



 

15 

Maximum dose 

 

Adults: The maximum total recommended dose is 10 g. 

 

Paediatric population: In infants to adolescents (0 to 18 years old), the maximum total recommended 

dose is 140 mg/kg not exceeding 10 g. 

 

Renal and hepatic impairment 

 

Although the safety and efficacy of hydroxocobalamin have not been studied in renal and hepatic 

impairments, Cyanokit is administered as emergency therapy in an acute, life-threatening situation 

only and no dose adjustment is required in these patients. 

 

Method of administration 

 

Initial dose of Cyanokit is administered as an intravenous infusion over 15 minutes. 

 

The rate of intravenous infusion for the second dose ranges from 15 minutes (for patients extremely 

unstable) to 2 hours based on patient condition. 

 

For instructions on reconstitution of the medicinal product before administration, see section 6.6. 

 

4.3 Contraindications 

 

None. 

 

4.4 Special warnings and precautions for use 

 

Treatment of cyanide poisoning must include immediate attention to airway patency, adequacy of 

oxygenation and hydration, cardiovascular support, and management of seizures. Consideration must 

be given to decontamination measures based on the route of exposure. 

 

Cyanokit does not substitute oxygen therapy and must not delay the set up of the above measures. 

 

The presence and extent of cyanide poisoning are often initially unknown. There is no widely 

available, rapid, confirmatory cyanide blood test. Treatment decisions must be made on the basis of 

clinical history and/or signs and symptoms of cyanide intoxication.  

 

Cyanide poisoning may result from exposure to smoke from closed space fires, inhalation, ingestion, 

or dermal exposure. Sources of cyanide poisoning include hydrogen cyanide and its salts, cyanogens, 

including cyanogenic plants, aliphatic nitriles, or prolonged exposure to sodium nitroprusside. 

 

Signs and symptoms of cyanide poisoning 

 

Common signs and symptoms of cyanide poisoning include: nausea, vomiting, headache, altered 

mental status (e.g. confusion, disorientation), chest tightness, dyspnoea, tachypnoea or hyperpnoea 

(early), bradypnoea or apnoea (late), hypertension (early) or hypotension (late), cardiovascular 

collapse, seizures or coma, mydriasis, and plasma lactate concentration > 8 mmol/L. 

 

In the setting of multiple casualties such as terrorism or chemical disaster, panic symptoms including 

tachypnoea and vomiting may mimic early cyanide poisoning signs. The presence of altered mental 

status (confusion and disorientation) and/or mydriasis is suggestive of true cyanide poisoning. 

 



 

16 

Smoke inhalation 

 

Not all smoke inhalation victims necessarily will have cyanide poisoning, but may present with burns, 

trauma, and exposure to additional toxic substances aggravating the clinical picture. Before Cyanokit 

is administered, it is recommended to check affected persons for the presence of the following: 

 exposure to fire smoke in an enclosed area 

 soot present around mouth, nose and/or oropharynx 

 altered mental status 

 

In this setting hypotension and/or a plasma lactate concentration ≥ 10 mmol/L (higher than the one 

mentioned under signs and symptoms due to the fact that carbon monoxide contributes to lactic 

acidaemia) are highly suggestive of cyanide poisoning. In the presence of the above signs, treatment 

with Cyanokit must not be delayed to obtain a plasma lactate concentration. 

 

Renal disorders 

 

Oxalate crystals have been observed in the urine of healthy volunteers given hydroxocobalamin. 

Cases of acute renal failure with acute tubular necrosis, renal impairment and urine calcium oxalate 

crystals present have been reported in patients treated with hydroxocobalamin following known or 

suspected cyanide poisoning. In some situations, hemodialysis was required to achieve recovery  (see 

section 4.8). 

Therefore, as a precaution, after Cyanokit administration, regular monitoring of renal function 

(including blood urea nitrogen and serum creatinine)  should be performed until 7 days after drug 

onset. 

 

Hypersensitivity reactions 

 

Known hypersensitivity to hydroxocobalamin or vitamin B12 must be taken into benefit-risk 

consideration before administration of Cyanokit, since hypersensitive reactions may occur in patients 

receiving hydroxocobalamin (see section 4.8). 

 

Increase in blood pressure 

 

Transient, generally asymptomatic, increase in blood pressure may occur in patients receiving 

hydroxocobalamin. The maximal increase in blood pressure has been observed toward the end of 

infusion (see section 4.8). 

 

Effects on blood cyanide assay 

 

Hydroxocobalamin will lower blood cyanide concentrations. While determination of blood cyanide 

concentration is not required and must not delay treatment with hydroxocobalamin, it may be useful 

for documenting cyanide poisoning. If a cyanide blood level determination is planned, it is 

recommended to draw the blood sample before initiation of treatment with Cyanokit. 

 

Interference with burn assessment 

 

Because of its deep red colour, hydroxocobalamin has the potential to induce a red colouration of the 

skin and therefore may interfere with burn assessment. However, skin lesions, oedema, and pain are 

highly suggestive of burns. 

 



 

17 

Interference with laboratory tests 

 

Because of its deep red colour, hydroxocobalamin has the potential to interfere with determination of 

laboratory parameters (e.g. clinical chemistry, haematology, coagulation, and urine parameters). 

In vitro tests indicate that the extent and duration of the interference is dependant on numerous factors 

such as the dose of hydroxocobalamin, analyte, analyte concentration, methodology, analyser, 

concentrations of cobalamins-(III) including cyanocobalamin and partially the time between sampling 

and measurement. 

 

Based on in vitro studies and pharmacokinetic data obtained in healthy volunteers the following table 

describes interference with laboratory tests that may be observed following a 5 g dose of 

hydroxocobalamin. Interference following a 10 g dose can be expected to last up to an additional 

24 hours. The extent and duration of interference in cyanide-poisoned patients may differ according to 

the severity of intoxication. Results may vary considerably from one analyser to another, therefore, 

caution is required when reporting and interpreting laboratory results. 

 

Observed in vitro interferences of hydroxocobalamin with laboratory tests 

 

Laboratory 

parameter 

No interference 

observed Artificially 

increased* 

Artificially  

decreased* Unpredictable*** 

Duration of 

interference 

after a 5 g dose 

Clinical 

chemistry 

Calcium 

Sodium 

Potassium 

Chloride 

Urea 

Gamma glutamyl 

transferase (GGT) 

Creatinine 

Total and 

conjugate 

bilirubin** 

Triglycerides 

Cholesterol 

Total protein 

Glucose 

Albumin 

Alkaline 

phosphatase 

Alanine 

aminotransferase 

(ALT) 

Amylase 

Phosphate 

Uric acid 

Aspartate 

aminotransferase 

(AST) 

Creatine kinase (CK) 

Creatine kinase 

isoenzym MB 

(CKMB) 

Lactate dehydrogenase 

(LDH) 

24 hours with the 

exception of 

bilirubin (up to 

4 days) 

Haematology Erythrocytes 

Haematocrit 

Mean corpuscular 

volume (MCV) 

Leucocytes 

Lymphocytes 

Monocytes 

Eosinophils 

Neutrophils 

Platelets 

Haemoglobin 

(Hb) 

Mean 

corpuscular 

haemoglobin 

(MCH) 

Mean 

corpuscular 

haemoglobin 

concentration 

(MCHC) 

 

  12-16 hours 

Coagulation    Activated partial 

thromboplastin time 

(aPTT) 

Prothrombin time (PT) 

Quick or INR 

24 hours 

* ≥ 10% interference observed on at least one analyser  

** Artificially decreased using the diazo method 

*** Inconsistent results 

Analysers used: ACL Futura (Instrumentation Laboratory), Axsym/Architect (Abbott), BM Coasys110 

(Boehringer Mannheim), CellDyn 3700 (Abbott), Clinitek 500 (Bayer), Cobas Integra 700, 400 

(Roche), Gen-S Coultronics, Hitachi 917, STA Compact, Vitros 950 (Ortho Diagnostics) 

 

Hydroxocobalamin may interfere with all urine colorimetric parameters. The effects on these tests 

typically last 48 hours after a 5 g dose, but may persist for longer periods. Caution is required in the 

interpretation of urinary colorimetric tests for as long as chromaturia is present. 

 



 

18 

Interference with haemodialysis 

 

Because of its deep red color, hydroxocobalamin may cause haemodialysis machines to shut down 

due to an erroneous detection of a ‘blood leak’. This should be considered before haemodialysis is 

initiated in patients treated with hydroxocobalamin. 

 

Use with other cyanide antidotes 

 

The safety of administering other cyanide antidotes simultaneously with Cyanokit has not been 

established (see section 6.2). If the decision is made to administer another cyanide antidote with 

Cyanokit, these medicinal products must not be administered concurrently in the same intravenous 

line (see section 6.2). 

 

4.5 Interaction with other medicinal products and other forms of interaction 

 

No interaction studies have been performed. 

 

4.6 Fertility, pregnancy and lactation 

 

Pregnancy 

 

Animal studies have shown teratogenic effects following daily exposure throughout organogenesis 

(see section 5.3). There are no adequate data from the use of hydroxocobalamin in pregnant women 

and the potential risk for humans is unknown.  

However, taken into account: 

- that no more than two injections of hydroxocobalamin are to be administered, 

- the potentially life threatening condition, 

- the lack of alternative treatment, 

hydroxocobalamin may be given to a pregnant woman. 

 

In case of known pregnancy at the time of treatment with Cyanokit or in case that pregnancy becomes 

known after treatment with Cyanokit, health care professionals are requested to promptly report the 

exposure during pregnancy to the Marketing Authorisation Holder and/or Health Authorities and to 

carefully follow-up on the pregnancy and its outcome. 

 

Breast-feeding  

 

Because hydroxocobalamin will be administered in potentially life-threatening situations, breast-

feeding is not a contraindication to its use. In the absence of data in breast-fed infants, breast-feeding 

discontinuation is recommended after receiving Cyanokit. 

 

Fertility 

 

No studies on fertility have been performed (see section 5.3). 

 

4.7 Effects on ability to drive and use machines 

 

Not relevant. 

 



 

19 

4.8 Undesirable effects 

 

Summary of the safety profile 

 

A total of 347 subjects were exposed to hydroxocobalamin in clinical studies. Of these 347 subjects, 

245 patients had suspected exposure to cyanide at the time of hydroxocobalamin administration. The 

remaining 102 subjects were healthy volunteers who had not been exposed to cyanide at the time of 

hydroxocobalamin administration. 

 

List of adverse reactions 

 

The following adverse reactions have been reported in association with Cyanokit use. However, 

because of the limitations of the available data, it is not possible to apply frequency estimations: 

 

Blood and lymphatic system disorders 

 

Decrease in the percentage of lymphocytes. 

 

Immune system disorders 

 

Allergic reactions including angioneurotic oedema, skin eruption, urticaria and pruritus. 

 

Psychiatric disorders 

 

Restlessness. 

 

Nervous system disorders 

 

Memory impairment; dizziness. 

 

Eye disorders 

 

Swelling, irritation, redness.  

 

Cardiac disorders 

 

Ventricular extrasystoles. An increase in heart rate was observed in cyanide-poisoned patients. 

 

Vascular disorders 

 

Transient increase in blood pressure, usually resolving within several hours; hot flush. A decrease in 

blood pressure was observed in cyanide-poisoned patients. 

 

Respiratory, thoracic and mediastinal disorders 

 

Pleural effusion, dyspnoea, throat tightness, dry throat, chest discomfort. 

 

Gastrointestinal disorders 

 

Abdominal discomfort, dyspepsia, diarrhoea, vomiting, nausea, dysphagia. 

 



 

20 

Skin and subcutaneous tissue disorders 

 

Reversible red colouration of the skin and mucous membranes: most patients will experience it up to 

15 days after administration of Cyanokit. 

Pustular rashes, which may last for several weeks, affecting mainly the face and the neck. 

 

Renal and urinary disorders 

 

 Acute renal failure with acute tubular necrosis, renal impairment, urine calcium oxalate crystals 

present (see section 4.4). 

 

 Chromaturia: all patients will show a dark red colouration of the urine quite marked during the first 

three days following administration. Urine colouration may last up to 35 days after administration of 

Cyanokit (see section 4.4).   

 

General disorders and administration site conditions 

 

Headache; injection site reaction; peripheral oedema. 

 

Investigations 

 

Cyanokit may cause red discolouration of the plasma, which may cause artificial elevation or 

reduction in the levels of certain laboratory parameters (see section 4.4). 

 

Paediatric population 

 

Limited data on children (0 to 18 years old) treated with hydroxocobalamin did not show any 

difference in the safety profile of hydroxocobalamin between adults and children. 

 

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 

listed in Appendix V. 

 

4.9 Overdose 

 

Doses as high as 15 g have been administered without reported specific dose related adverse 

reactions. If overdose occurs, treatment is directed to the management of symptoms. Haemodialysis 

may be effective in such a circumstance, but is only indicated in the event of significant 

hydroxocobalamin-related toxicity. However, hydroxocobalamin because of its deep red colour may 

interfere with the performance of haemodialysis machines (see section 4.4). 

 

 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1 Pharmacodynamic properties 

 

Pharmacotherapeutic group: Antidotes, ATC code: V03AB33 

 



 

21 

Mechanism of action 

 

The action of hydroxocobalamin in the treatment of cyanide poisoning is based on its ability to tightly 

bind cyanide ions. Each hydroxocobalamin molecule can bind one cyanide ion by substituting the 

hydroxo ligand linked to the trivalent cobalt ion to form cyanocobalamin. Cyanocobalamin is a stable, 

non-toxic compound that is excreted in the urine.  

 

Efficacy 

 

Due to ethical considerations, no controlled human efficacy studies have been performed.  

 

 Animal pharmacology 

 

The effectiveness of hydroxocobalamin was examined in a controlled study in cyanide-poisoned adult 

dogs. Dogs were poisoned by intravenous administration of a lethal dose of potassium cyanide. Dogs 

then received sodium chloride 9 mg/mL, 75 mg/kg or 150 mg/kg hydroxocobalamin, administered 

intravenously over 7.5 minutes. The 75 mg/kg and 150 mg/kg doses are approximately equivalent to 

5 g and 10 g of hydroxocobalamin, respectively, in humans, not only on a body weight basis but also 

on Cmax basis of hydroxocobalamin [total cobalamins-(III), see section 5.2]. 

 

Survival at hour 4 and at day 14 was significantly greater in 75 mg/kg and 150 mg/kg 

hydroxocobalamin dose groups compared with dogs receiving sodium chloride 9 mg/mL alone: 

 

Survival of cyanide-poisoned dogs 

 

Parameter 

Treatment 

Sodium chloride 

9 mg/mL 

(N=17) 

Hydroxocobalamin 

75 mg/kg 

(N=19) 

150 mg/kg 

(N=18) 

Survival at Hour 4, N (%) 7 (41) 18 (95)* 18 (100)* 

Survival at Day 14, N (%) 3 (18) 15 (79)* 18 (100)* 
* p< 0.025 

 

Histopathology revealed brain lesions that were consistent with cyanide-induced hypoxia. The 

incidence of brain lesions was markedly lower in dogs having received 150 mg/kg hydroxocobalamin 

than in dogs having received 75 mg/kg hydroxocobalamin or sodium chloride 9 mg/mL. 

 

The rapid and complete recovery of haemodynamics and subsequently of blood gases, pH, and lactate 

after cyanide poisoning likely contributed to the better outcome of the hydroxocobalamin-treated 

animals. Hydroxocobalamin reduced whole blood cyanide concentrations from about 120 nmol/mL to 

30-40 nmol/mL by the end of the infusion compared with 70 nmol/mL in dogs receiving sodium 

chloride 9 mg/mL alone. 

 

 Cyanide-poisoned patients 

 

A total of 245 patients with suspected or known cyanide-poisoning were included in the clinical 

studies of the efficacy of hydroxocobalamin as an antidote. Of the 213 patients in whom the outcome 

was known the survival was 58%. Of the 89 patients who died, 63 were initially found in cardiac 

arrest, suggesting that many of these patients had almost certainly suffered irreparable brain injury 

prior to administration of hydroxocobalamin. Among 144 patients not in initial cardiac arrest whose 

outcomes were known, 118 (82%) survived. Furthermore, in 34 patients with known cyanide 

concentrations above the lethal threshold (≥ 100 µmol/L), 21 (62%) survived following treatment with 

hydroxocobalamin. 

Administration of hydroxocobalamin was generally associated with a normalisation of blood pressure 

(systolic blood pressure > 90 mmHg) in 17 of 21 patients (81%) who had low blood pressure (systolic 



 

22 

blood pressure > 0 and ≤ 90 mmHg) after exposure to cyanide. Where neurological assessment over 

time was possible, (96 patients of the 171 patients who presented with neurological symptoms prior to 

hydroxocobalamin administration), 51 (53%) patients receiving hydroxocobalamin showed 

improvement or a complete restoration.  

 

 Elderly 

 

Approximately 50 known or suspected cyanide victims aged 65 or older received hydroxocobalamin 

in clinical studies. In general, the effectiveness of hydroxocobalamin in these patients was similar to 

that of younger patients. 

 

 Paediatric population 

 

Documentation on efficacy is available for 54 paediatric patients. The mean age of the paediatric 

patients was about six years and the mean dose of hydroxocobalamin was about 120 mg/kg body 

weight. The survival rate of 41% depended very much on the clinical situation. Out of the 

20 paediatric patients without initial cardiac arrest, 18 (90%) survived, of whom 4 with sequelae. In 

general, the effectiveness of hydroxocobalamin in paediatric patients was similar to that of adults. 

 

5.2 Pharmacokinetic properties 

 

Following intravenous administration of Cyanokit, significant binding to plasma proteins and low 

molecular weight physiological compounds occurs, to form various cobalamin-(III) complexes by 

replacing the hydroxo ligand. The low molecular weight cobalamins-(III) formed including 

hydroxocobalamin are termed free cobalamins-(III); the sum of free and protein-bound cobalamins is 

termed total cobalamins-(III). In order to reflect the exposure to the sum of all derivatives, 

pharmacokinetics of cobalamins-(III) were investigated instead of hydroxocobalamin, requiring the 

concentration unit µg eq/mL (i.e. cobalamin-(III) entity without specific ligand). 

 

Dose-proportional pharmacokinetics were observed following single dose intravenous administration 

of 2.5 to 10 g of Cyanokit in healthy volunteers. Mean free and total cobalamins-(III) Cmax values of 

113 and 579 µg eq/mL, respectively, were determined following a dose of 5 g Cyanokit (the 

recommended initial dose). Similarly, mean free and total cobalamins-(III) Cmax values of 197 and 

995 µg eq/mL, respectively, were determined following the dose of 10 g Cyanokit. The predominant 

mean half-life of free and total cobalamins-(III) was approximately 26 to 31 hours at the 5 and 10 g 

dose level. 

 

The mean total amount of cobalamins-(III) excreted in urine during the collection period of 72 hours 

was approximately 60% of a 5 g dose and approximately 50% of a 10 g dose of Cyanokit. Overall, the 

total urinary excretion was calculated to be at least 60 to 70% of the administered dose. The majority 

of the urinary excretion occurred during the first 24 hours, but red coloured urine was observed for up 

to 35 days following the intravenous infusion. 

 

When normalized for body weight, male and female subjects revealed no major differences in plasma 

and urinary pharmacokinetic parameters of free and total cobalamins-(III) following the 

administration of 5 g or 10 g Cyanokit. 

 

In cyanide-poisoned patients, hydroxocobalamin is expected to bind cyanide to form cyanocobalamin, 

which is excreted in the urine. The pharmacokinetics of total cobalamins-(III) in this population may 

be affected by the body's cyanide load, since cyanocobalamin was reported to exhibit a 2-3 times 

lower half-life than total cobalamins-(III) in healthy volunteers. 

 



 

23 

5.3 Preclinical safety data 

 

In anaesthetised rabbits, hydroxocobalamin exerted haemodynamic effects (increased mean arterial 

blood pressure and total peripheral resistance, decreased cardiac output) related to its nitric oxide-

scavenging property. 

 

No special hazard for humans was identified based on conventional studies of single and repeated 

dose toxicity and genotoxicity. The liver and kidney were found to be the major target organs. 

However findings were only seen at exposure levels considered being higher than the maximum 

human exposure, indicating limited relevance to clinical use. In particular, liver fibrosis was observed 

in dogs after administration of hydroxocobalamin for 4 weeks at 300 mg/kg. The relevance of this 

finding to humans is unlikely since it was not reported in short-term studies conducted with 

hydroxocobalamin. 

 

Developmental toxicity, including teratogenicity, was observed in rats and rabbits at dose levels of 

150 mg/kg and higher administered daily throughout organogenesis. The dose of 150 mg/kg 

approximately corresponds to the maximum recommended human dose. 

 

No data are available on male and female fertility as well as on peri- and postnatal development. 

Hydroxocobalamin has not been evaluated for carcinogenic potential. 

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 

 

Hydrochloric acid (for pH-adjustment) 

 

6.2 Incompatibilities 

 

This medicinal product must not be mixed with other medicinal products except those mentioned in 

section 6.6. 

 

Physical incompatibility (particle formation) was observed with the mixture of hydroxocobalamin 

reconstituted solution and the following medicinal products: diazepam, dobutamine, dopamine, 

fentanyl, nitroglycerin, pentobarbital, phenytoin sodium, propofol and thiopental.  

 

Chemical incompatibility was observed with the mixture of hydroxocobalamin reconstituted solution 

and the following medicinal products: epinephrine, lidocaine hydrochloride, adenosine, atropine, 

midazolam, ketamin, succinylcholine chloride, amiodarone hydrochloride, sodium bicarbonate, 

sodium thiosulfate, sodium nitrite, and has been reported with ascorbic acid.  

Consequently, these and other medicinal products must not be administered simultaneously through 

the same intravenous line as hydroxocobalamin. 

 

Simultaneous administration of hydroxocobalamin and blood products (whole blood, packed red cells, 

platelet concentrate and fresh frozen plasma) through the same intravenous line is not recommended.  

 

6.3 Shelf life 

 

3 years. 

 

For the purpose of ambulatory use, Cyanokit may be exposed during short periods to the temperature 

variations of usual transport (15 days submitted to temperatures ranging from 5°C to 40°C), transport 

in the desert (4 days submitted to temperatures ranging from 5°C to 60°C) and freezing/defrosting 

cycles (15 days submitted to temperatures ranging from -20°C to 40°C). If these temporary conditions 

have been exceeded, the product should be discarded. 



 

24 

 

Chemical and physical in-use 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 medicinal product should be used immediately. If not used 

immediately, in-use storage times and conditions prior to use are the responsibility of the user and 

would normally not be longer than 6 hours at 2°C to 8ºC. 

 

6.4 Special precautions for storage 

 

Do not store above 25°C. 

 

For storage conditions after reconstitution of the medicinal product, see section 6.3. 

 

6.5 Nature and contents of container 

 

Type I colourless 250 mL glass vial closed with bromobutyl rubber stopper and an aluminium cap 

with a plastic lid.  

Each pack contains one vial packed in one cardboard box, one sterile transfer device, one sterile 

intravenous infusion set and one sterile short catheter for administration to children. 

 

6.6 Special precautions for disposal and other handling 

 

No special requirements for disposal. 

 

The vial is to be reconstituted with 200 mL of diluent using the supplied sterile transfer device. 

Sodium chloride 9 mg/mL (0.9%) solution for injection is the recommended diluent. Only when 

sodium chloride 9 mg/mL (0.9%) solution for injection is not available, Lactated Ringer solution or 

glucose 50 mg/mL (5%) solution for injection can also be used.  

 

The Cyanokit vial is to be rocked or inverted for at least 1 minute to mix the solution. It must not be 

shaken as shaking the vial may cause foam and therefore may make checking reconstitution less easy. 

Because the reconstituted solution is a dark red solution, some insoluble particles may not be seen. 

The intravenous infusion set provided in the kit must then be used as it includes an appropriate filter 

and is to be primed with the reconstituted solution.  

 

 

7. MARKETING AUTHORISATION HOLDER 

 

SERB S.A. 

Avenue Louise 480  

1050 Brussels 

Belgium 

 

 

8. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/07/420/002 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

 

Date of first authorisation: 23 November 2007 

Date of latest renewal: 20 July 2012 

 

 

10. DATE OF REVISION OF THE TEXT 



 

25 

 

MM/YYYY 

 

 

Detailed information on this medicinal product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu. 



 

26 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX II 

 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH 

RELEASE 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 

 

C OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 

PRODUCT 

 

 



 

27 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 

 

Name and address of the manufacturer(s) responsible for batch release 

 

Merck Santé S.A.S. 

Centre de Production de Semoy 

2, rue du Pressoir Vert 

F-45400 Semoy 

France 

 

Or  

 

SERB S.A. 

Avenue Louise 480  

1050 Brussels 

Belgium 

 

Or  

 

SERB 

40 avenue George V 

75008 Paris 

France 

 

The printed package leaflet of the medicinal product must state the name and address of the 

manufacturer responsible for the release of the concerned batch. 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 

Medicinal product subject to medical prescription. 

 

 

C. OTHER CONDITIONS OR REQUIREMENTS OF THE MARKETING 

AUTHORISATION 

 

 Periodic Safety Update Reports (PSUR) 

 

The marketing authorisation holder shall submit periodic safety update reports for this product in 

accordance with the requirements set out in the list of Union reference dates (EURD list) ) provided 

for under Article 107c(7) of Directive 2001/83/EC and published on the European medicines web-

portal. 

 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 

 

 Risk Management Plan (RMP) 

 

The MAH shall perform the required pharmacovigilance activities and interventions detailed in 

the agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed 

subsequent updates of the RMP. 

 

An updated RMP should be submitted: 

 At the request of the European Medicines Agency; 



 

28 

 Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 

an important (pharmacovigilance or risk minimisation) milestone being reached. 

 

If the dates for submission of a PSUR and the update of a RMP coincide, they can be submitted at the 

same time. 



 

29 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 



 

30 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING 



 

31 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Cyanokit 2.5 g powder for solution for infusion 

Hydroxocobalamin 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each vial contains 2.5 g of hydroxocobalamin. After reconstitution with 100 mL of diluent, each mL 

of the reconstituted solution contains 25 mg of hydroxocobalamin. 

 

 

3. LIST OF EXCIPIENTS 

 

Excipient: Hydrochloric acid (for pH adjustment). 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Powder for solution for infusion 

Two vials 

Two transfer devices. 

One intravenous infusion set. 

One short catheter for administration to children. 

 

This kit does not contain diluent. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Intravenous use 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

Read the leaflet for storage conditions in ambulatory use 

 



 

32 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 25°C. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

SERB S.A. 

Avenue Louise 480  

1050 Brussels 

Belgium 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/07/420/001 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Justification for not including Braille accepted 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: {number} 

SN: {number} 

NN: {number} 

 



 

33 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARDBOARD BOX 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Cyanokit 2.5 g powder for solution for infusion 

Hydroxocobalamin  

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each vial contains 2.5 g of hydroxocobalamin. After reconstitution with 100 mL of diluent, each mL 

of the reconstituted solution contains 25 mg of hydroxocobalamin. 

 

 

3. LIST OF EXCIPIENTS 

 

Excipient: Hydrochloric acid (for pH adjustment). 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Powder for solution for infusion 

One vial 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Intravenous use 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 25°C. 

 

 



 

34 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

SERB S.A. 

Avenue Louise 480  

1050 Brussels 

Belgium 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/07/420/001 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Justification for not including Braille accepted 



 

35 

 

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 

 

VIAL 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Cyanokit 2.5 g powder for solution for infusion 

Hydroxocobalamin  

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each vial contains 2.5 g of hydroxocobalamin. After reconstitution with 100 mL of diluent, each mL 

of the reconstituted solution contains 25 mg of hydroxocobalamin. 

 

 

3. LIST OF EXCIPIENTS 

 

Excipient: Hydrochloric acid (for pH adjustment). 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Powder for solution for infusion containing 2.5 g of hydroxocobalamin. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Intravenous use 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 25°C. 

 

 



 

36 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

SERB S.A. 

Avenue Louise 480  

1050 Brussels 

Belgium 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/07/420/001 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Justification for not including Braille accepted 

 



 

37 

 

 

 

MEDICAL OR HEALTH CARE PROFESSIONALS EDUCATIONAL STICKER 

 

 

 

“To be attached to the patient’s medical record: 

Cyanokit has been administered to this patient.  

Cyanokit may interfere with burn assessment (red coloration of the skin) and laboratory tests and may 

lead to shut down of haemodialysis machines (see SmPC).” 



 

38 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Cyanokit 5 g powder for solution for infusion 

Hydroxocobalamin 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

The vial contains 5 g of hydroxocobalamin. After reconstitution with 200 mL of diluent, each mL of 

the reconstituted solution contains 25 mg of hydroxocobalamin. 

 

 

3. LIST OF EXCIPIENTS 

 

Excipient: Hydrochloric acid (for pH adjustment). 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Powder for solution for infusion 

One vial 

One transfer device. 

One intravenous infusion set. 

One short catheter for administration to children. 

 

This kit does not contain diluent. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Intravenous use 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

Read the leaflet for storage conditions in ambulatory use 

 



 

39 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 25°C. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

SERB S.A. 

Avenue Louise 480  

1050 Brussels 

Belgium 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/07/420/002 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Justification for not including Braille accepted 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: {number} 

SN: {number} 

NN: {number} 

 



 

40 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARDBOARD BOX 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Cyanokit 5 g powder for solution for infusion 

Hydroxocobalamin  

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

The vial contains 5 g of hydroxocobalamin. After reconstitution with 200 mL of diluent, each mL of 

the reconstituted solution contains 25 mg of hydroxocobalamin. 

 

 

3. LIST OF EXCIPIENTS 

 

Excipient: Hydrochloric acid (for pH adjustment). 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Powder for solution for infusion 

One vial 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Intravenous use 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 25°C. 

 

 



 

41 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

SERB S.A. 

Avenue Louise 480  

1050 Brussels 

Belgium 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/07/420/002 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Justification for not including Braille accepted 



 

42 

 

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 

 

VIAL 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Cyanokit 5 g powder for solution for infusion 

Hydroxocobalamin  

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

The vial contains 5 g of hydroxocobalamin. After reconstitution with 200 mL of diluent, each mL of 

the reconstituted solution contains 25 mg of hydroxocobalamin. 

 

 

3. LIST OF EXCIPIENTS 

 

Excipient: Hydrochloric acid (for pH adjustment). 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Powder for solution for infusion containing 5 g of hydroxocobalamin. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Intravenous use 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 25°C. 

 

 



 

43 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

SERB S.A. 

Avenue Louise 480  

1050 Brussels 

Belgium 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/07/420/002 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Justification for not including Braille accepted 

 



 

44 

 

 

 

MEDICAL OR HEALTH CARE PROFESSIONALS EDUCATIONAL STICKER 

 

 

 

“To be attached to the patient’s medical record: 

Cyanokit has been administered to this patient.  

Cyanokit may interfere with burn assessment (red coloration of the skin) and laboratory tests and may 

lead to shut down of haemodialysis machines (see SmPC).” 



 

45 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

B. PACKAGE LEAFLET 



 

46 

Package leaflet: Information for the user 

 

Cyanokit 2.5 g powder for solution for infusion 

hydroxocobalamin 

 

Read all of this leaflet carefully before 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 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. 

 

 

What is in this leaflet: 

1. What Cyanokit is and what it is used for 

2. What you need to know before Cyanokit is used 

3. How Cyanokit is used 

4. Possible side effects 

5. How Cyanokit is stored 

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 known or suspected cyanide poisoning in all age ranges.  

Cyanokit is to be administered together with appropriate decontamination and supportive measures. 

 

Cyanide is a highly poisonous chemical. Cyanide poisoning may be caused by exposure to smoke 

from household and industrial fires, breathing or swallowing cyanide, or contact with cyanide on skin.  

 

 

2. What you need to know before Cyanokit is used 

 

Warnings and precautions 

 

Tell your doctor or other health care professional  

 if you are allergic to hydroxocobalamin or vitamin B12. They will have to take it into account 

before treating you with Cyanokit. 

 that you have been treated with Cyanokit if you need to have the following: 

- any blood or urine tests. Cyanokit may modify the results of these tests. 

- burn assessement. Cyanokit may interfere with the assessment as it causes red coloration of 

the skin. 

- haemodialysis. Cyanokit may lead to shut down of haemodialysis machines until it is 

eliminated from the blood (at least 5.5 to 6.5 days). 

monitoring of renal function: Cyanokit may lead to kidney failure and urine crystals. 

 

Other medicines and Cyanokit 

 

Tell your doctor or other health care professional if you are taking, have recently taken or might take 

any other medicines. 

 

Detailed information for your doctor or other health care professional regarding simultaneous 

administration of Cyanokit with other medicines can be found at the end of this package leaflet (see 

'Handling instructions'). 



 

47 

 

Pregnancy and breast-feeding 

 

This medicine is an emergency treatment. It can be administered during pregnancy and breast-feeding. 

Tell your doctor as soon as possible if you were pregnant or think you may have been pregnant during 

treatment with Cyanokit. 

Your doctor will recommend you to stop breast-feeding after treatment with Cyanokit. 

 

 

3. How Cyanokit is used  

 

Your doctor or health care professional will give you Cyanokit by infusion into a vein. You may need 

one or two infusions. 

 

You will have the first infusion of Cyanokit over 15 minutes. For adults, the initial dose is 5 g. For 

children, it is 70 mg/kg body weight, up to a maximum dose of 5 g. If you need a second infusion, you 

will have it over 15 minutes to 2 hours. It depends on how serious the poisoning is. The maximum 

total recommended dose is 10 g for adults, and 140 mg/kg in children up to a maximum of 10 g. 

 

Detailed instructions for your doctor or other health care professional on how to prepare the Cyanokit 

infusion and how to determine the dose can be found at the end of this package leaflet (see 'Handling 

instructions'). 

 

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

 

 

4. Possible side effects 

 

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

following side effects may be expected (frequency cannot be estimated from the available data):  

 

Allergy (hypersensitivity) 

 

Tell your doctor immediately if you have the following symptoms during or after this treatment: 

 swelling around the eyes, lips, tongue, throat or hands 

 breathing difficulties, hoarseness, difficulty in speaking 

 skin redness, nettle rash (urticaria) or itching. 

Such side effects may be serious and need immediate attention. 

 

Heart and blood pressure problems 

 

 symptoms such as headache or dizziness, as they may be due to a rise in blood pressure. This 

rise in blood pressure especially occurs at the end of having this treatment and usually settles 

down within several hours 

 irregular heart beat 

 redness of the face (flush). 

A decrease in blood pressure and a faster heart beat have also been observed in patients who have 

cyanide poisoning. 

 

Breathing and chest problems 

 

 fluid in the chest (pleural effusion) 

 breathing difficulties 

 a feeling of tightness in the throat  

 dry throat 



 

48 

 chest pressure. 

 

Renal and urinary problems 

 

 kidney injuries such as acute kidney impairment and urine crystals.  

 red colouration of the urine. 

All patients will show a dark red colouration of the urine quite marked during the first three days  

following administration. Urine colouration may last up to 35 days after administration 

of Cyanokit. This red colouration has no other consequences on your body. 

 

Gastrointestinal (digestive) problems 

 

 discomfort in your stomach 

 indigestion 

 diarrhoea 

 feeling sick (nausea) 

 being sick (vomiting) 

 difficulty in swallowing. 

 

Eye problems 

 

 swelling, irritation, redness. 

 

Skin reactions 

 

 most patients will experience a reversible red colouration of the skin and membranes lining 

body cavities (mucous membranes) that may last up to 15 days after administration of Cyanokit. 

 blister-like lesions on the skin (pustular rashes). These may last for several weeks, and affect 

mainly the face and the neck. 

 inflammation in the part of the body where the medicine was infused. 

 

Other side effects 

 

 restlessness 

 problems with memory 

 dizziness 

 headache 

 swelling of ankles 

 changes in the results of blood tests for certain white blood cells (lymphocytes) 

 coloured plasma, which may cause artificial elevation or reduction in the levels of certain 

laboratory parameters. 

 

Reporting of side effects 

 

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 

not listed in this leaflet. You can also report side effects directly via the national reporting system 

listed in Appendix V. By reporting side effects you can help provide more information on the safety 

of this medicine. 

 

 

5. How Cyanokit is stored  

 

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

 



 

49 

Do not use this medicine after the expiry date which is stated on the vial, the cardboard box and the 

carton after EXP. 

 

Do not store above 25°C. 

 

For the purpose of ambulatory use, Cyanokit may be exposed during short periods to the temperature 

variations of 

 usual transport (15 days submitted to temperatures ranging from 5 to 40°C) 

 transport in the desert (4 days submitted to temperatures ranging from 5 to 60°C) and 

 freezing/defrosting cycles (15 days submitted to temperatures ranging from -20 to 40°C). 

 

For storage conditions of the reconstituted medicine, see 'Handling instructions' at the end of this 

package leaflet. 

 

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 

throw away medicines no longer used. These measures will help protect the environment. 

 

 

6. Contents of the pack and other information 

 

What Cyanokit contains 

 

 The active substance is hydroxocobalamin. Each vial contains 2.5 g of hydroxocobalamin. 

After reconstitution with 100 mL of diluent, each mL of the reconstituted solution contains 

25 mg of hydroxocobalamin. 

 The other ingredient is hydrochloric acid (for pH adjustment). 

 

What Cyanokit looks like and contents of the pack 

 

Cyanokit powder for solution for infusion is a dark red crystalline powder supplied in a glass vial 

closed with bromobutyl rubber stopper and an aluminium cap with a plastic lid. 

 

Each pack contains two vials (each vial packed in one cardboard box), two sterile transfer devices, 

one sterile intravenous infusion set and one sterile short catheter for administration to 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 



 

50 

 

Or  

 

SERB 

40 avenue George V 

75008 Paris 

France 

 

 

This leaflet was last revised in MM/YYYY. 

 

Other sources of information 

 

Detailed information on this medicine is available on the European Medicines Agency web site: 

http://www.ema.europa.eu. 

-------------------------------------------------------------------------------------------------------------------------- 

 

The following information is intended for medical or healthcare professionals only: 

 

Handling instructions 

 

Treatment of cyanide poisoning must include immediate attention to airway patency, adequacy 

of oxygenation and hydration, cardiovascular support, and management of seizures. 

Consideration must be given to decontamination measures based on the route of exposure. 

 

Cyanokit does not substitute oxygen therapy and must not delay the set up of the above 

measures. 

 

The presence and extent of cyanide poisoning are often initially unknown. There is no widely 

available, rapid, confirmatory cyanide blood test. However, if a cyanide blood level 

determination is planned, it is recommended to draw the blood sample before initiation of 

treatment with Cyanokit. Treatment decisions must be made on the basis of clinical history 

and/or signs and symptoms of cyanide intoxication. If there is clinical suspicion of cyanide 

poisoning, it is strongly recommended that Cyanokit be administered without delay. 

 

Preparation of Cyanokit 

 

Each vial is to be reconstituted with 100 mL of diluent using the supplied sterile transfer device. 

Sodium chloride 9 mg/mL (0.9%) solution for injection is the recommended diluent. Only when 

sodium chloride 9 mg/mL (0.9%) solution for injection is not available, Lactated Ringer solution or 

glucose 50 mg/mL (5%) solution for injection can also be used.  

 

The Cyanokit vial is to be rocked or inverted for at least 30 seconds to mix the solution. It must not be 

shaken as shaking the vial may cause foam and therefore may make checking reconstitution less easy. 

Because the reconstituted solution is a dark red solution, some insoluble particles may not be seen. 

The intravenous infusion set provided in the kit must then be used as it includes an appropriate filter 

and is to be primed with the reconstituted solution.  Repeat this procedure if necessary with the 

second vial. 

 

Posology 

 

Initial dose 

Adults: The initial dose of Cyanokit is 5 g (2 x 100 mL). 

 



 

51 

Paediatric population: In infants to adolescents (0 to 18 years old), the initial dose of Cyanokit is 

70 mg/kg body weight not exceeding 5 g. 

 

Body weight 

in kg 

 

5 

 

10 

 

20 

 

30 

 

40 

 

50 

 

60 

Initial dose  

in g 

in mL 

 

0.35 

14 

 

0.70 

28 

 

1.40 

56 

 

2.10 

84 

 

2.80 

112 

 

3.50 

140 

 

4.20 

168 

 

Subsequent dose 

Depending upon the severity of the poisoning and the clinical response, a second dose may be 

administered  

 

Adults: The subsequent dose of Cyanokit is 5 g (2 x 100 mL). 

 

Paediatric population: In infants to adolescents (0 to 18 years old), the subsequent dose of Cyanokit 

is 70 mg/kg body weight not exceeding 5 g. 

 

Maximum dose 

 

Adults: The maximum total recommended dose is 10 g. 

 

Paediatric population: In infants to adolescents (0 to 18 years old), the maximum total recommended 

dose is 140 mg/kg not exceeding 10 g. 

 

Renal and hepatic impairment 

 

No dose adjustment is required in these patients. 

 

Method of administration 

 

Initial dose of Cyanokit is administered as an intravenous infusion over 15 minutes. 

 

The rate of intravenous infusion for the second dose ranges from 15 minutes (for patients extremely 

unstable) to 2 hours based on patient condition. 

 

Simultaneous administration of Cyanokit and other products 

 

Cyanokit must not be mixed with diluents other than sodium chloride 9 mg/mL (0.9%) solution for 

injection or Lactated Ringer solution or glucose 50 mg/mL (5%) solution for injection. 

 

As physical and chemical incompatibilities were observed with a number of selected medicinal 

products that are frequently used in resuscitation efforts, these and other medicinal products must not 

be administered simultaneously in the same intravenous line as hydroxocobalamin. 

 

If blood products (whole blood, packed red cells, platelet concentrate and fresh frozen plasma) and 

hydroxocobalamin are administered simultaneously, use of separate intravenous lines (preferably on 

contralateral extremities) is recommended. 

 

Combination with another cyanide antidote: Chemical incompatibility was observed with sodium 

thiosulfate and sodium nitrite. If the decision is made to administer another cyanide antidote with 

Cyanokit, these medicinal products must not be administered concurrently in the same intravenous 

line. 

 



 

52 

In-use stability of the reconstituted solution 

 

Chemical and physical in-use 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 to 40°C.  

From a microbiological point of view, the medicinal product should be used immediately. If not used 

immediately, in-use storage times and conditions prior to use are the responsibility of the user and 

would normally not be longer than 6 hours at 2°C to 8°C. 



 

53 

Package leaflet: Information for the user 

 

Cyanokit 5 g powder for solution for infusion 

hydroxocobalamin 

 

Read all of this leaflet carefully before 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 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. 

 

 

What is in this leaflet: 

1. What Cyanokit is and what it is used for 

2. What you need to know before Cyanokit is used 

3. How Cyanokit is used 

4. Possible side effects 

5. How Cyanokit is stored 

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 known or suspected cyanide poisoning in all age ranges.  

Cyanokit is to be administered together with appropriate decontamination and supportive measures. 

 

Cyanide is a highly poisonous chemical. Cyanide poisoning may be caused by exposure to smoke 

from household and industrial fires, breathing or swallowing cyanide, or contact with cyanide on skin.  

 

 

2. What you need to know before Cyanokit is used 

 

Warnings and precautions 

 

Tell your doctor or other health care professional  

 if you are allergic to hydroxocobalamin or vitamin B12. They will have to take it into account 

before treating you with Cyanokit. 

 that you have been treated with Cyanokit if you need to have the following: 

- any blood or urine tests. Cyanokit may modify the results of these tests. 

- burn assessement. Cyanokit may interfere with the assessment as it causes red coloration of 

the skin. 

- haemodialysis. Cyanokit may lead to shut down of haemodialysis machines until it is 

eliminated from the blood (at least 5.5 to 6.5 days). 

- monitoring of renal function: Cyanokit may lead to kidney failure and urine crystals. 

 

Other medicines and Cyanokit 

 

Tell your doctor or other health care professional if you are taking, have recently taken or might take 

any other medicines. 

 

Detailed information for your doctor or other health care professional regarding simultaneous 

administration of Cyanokit with other medicines can be found at the end of this package leaflet (see 

'Handling instructions'). 



 

54 

 

Pregnancy and breast-feeding 

 

This medicine is an emergency treatment. It can be administered during pregnancy and breast-feeding. 

Tell your doctor as soon as possible if you were pregnant or think you may have been pregnant during 

treatment with Cyanokit. 

Your doctor will recommend you to stop breast-feeding after treatment with Cyanokit. 

 

 

3. How Cyanokit is used  

 

Your doctor or health care professional will give you Cyanokit by infusion into a vein. You may need 

one or two infusions. 

 

You will have the first infusion of Cyanokit over 15 minutes. For adults, the initial dose is 5 g. For 

children, it is 70 mg/kg body weight, up to a maximum dose of 5 g. If you need a second infusion, you 

will have it over 15 minutes to 2 hours. It depends on how serious the poisoning is. The maximum 

total recommended dose is 10 g for adults, and 140 mg/kg in children up to a maximum of 10 g. 

 

Detailed instructions for your doctor or other health care professional on how to prepare the Cyanokit 

infusion and how to determine the dose can be found at the end of this package leaflet (see 'Handling 

instructions'). 

 

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

 

 

4. Possible side effects 

 

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

following side effects may be expected (frequency cannot be estimated from the available data):  

 

Allergy (hypersensitivity) 

 

Tell your doctor immediately if you have the following symptoms during or after this treatment: 

 swelling around the eyes, lips, tongue, throat or hands 

 breathing difficulties, hoarseness, difficulty in speaking 

 skin redness, nettle rash (urticaria) or itching. 

Such side effects may be serious and need immediate attention. 

 

Heart and blood pressure problems 

 

 symptoms such as headache or dizziness, as they may be due to a rise in blood pressure. This 

rise in blood pressure especially occurs at the end of having this treatment and usually settles 

down within several hours 

 irregular heart beat 

 redness of the face (flush). 

A decrease in blood pressure and a faster heart beat have also been observed in patients who have 

cyanide poisoning. 

 

Breathing and chest problems 

 

 fluid in the chest (pleural effusion) 

 breathing difficulties 

 a feeling of tightness in the throat  

 dry throat 



 

55 

 chest pressure. 

 

Renal and urinary problems 

 

 kidney injuries such as acute kidney impairment and urine crystals.  

 red colouration of the urine. 

All patients will show a dark red colouration of the urine quite marked during the first three days  

following administration. Urine colouration may last up to 35 days after administration 

of Cyanokit. This red colouration has no other consequences on your body. 

 

Gastrointestinal (digestive) problems 

 

 discomfort in your stomach 

 indigestion 

 diarrhoea 

 feeling sick (nausea) 

 being sick (vomiting) 

 difficulty in swallowing. 

 

Eye problems 

 

 swelling, irritation, redness. 

 

Skin reactions 

 

 most patients will experience a reversible red colouration of the skin and membranes lining 

body cavities (mucous membranes) that may last up to 15 days after administration of Cyanokit. 

 blister-like lesions on the skin (pustular rashes). These may last for several weeks, and affect 

mainly the face and the neck. 

 inflammation in the part of the body where the medicine was infused. 

 

Skin reactions 

 

 blister-like lesions on the skin (pustular rashes). These may last for several weeks, and affect 

mainly the face and the neck. 

 inflammation in the part of the body where the medicine was infused. 

 

Other side effects 

 

 restlessness 

 problems with memory 

 dizziness 

 headache 

 swelling of ankles 

 changes in the results of blood tests for certain white blood cells (lymphocytes) 

 coloured plasma, which may cause artificial elevation or reduction in the levels of certain 

laboratory parameters. 

 

Reporting of side effects 

 

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 

not listed in this leaflet. You can also report side effects directly via the national reporting system 

listed in Appendix V. By reporting side effects you can help provide more information on the safety 

of this medicine. 



 

56 

5. How Cyanokit is stored  

 

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 vial, the cardboard box and the 

carton after EXP. 

 

Do not store above 25°C. 

 

For the purpose of ambulatory use, Cyanokit may be exposed during short periods to the temperature 

variations of 

 usual transport (15 days submitted to temperatures ranging from 5 to 40°C) 

 transport in the desert (4 days submitted to temperatures ranging from 5 to 60°C) and 

 freezing/defrosting cycles (15 days submitted to temperatures ranging from -20 to 40°C). 

 

For storage conditions of the reconstituted medicine, see 'Handling instructions' at the end of this 

package leaflet. 

 

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 

throw away medicines no longer used. These measures will help protect the environment. 

 

 

6. Contents of the pack and other information 

 

What Cyanokit contains 

 

 The active substance is hydroxocobalamin. The vial contains 5 g of hydroxocobalamin. After 

reconstitution with 200 mL of diluent, each mL of the reconstituted solution contains 25 mg of 

hydroxocobalamin. 

 The other ingredient is hydrochloric acid (for pH adjustment). 

 

What Cyanokit looks like and contents of the pack 

 

Cyanokit powder for solution for infusion is a dark red crystalline powder supplied in a glass vial 

closed with bromobutyl rubber stopper and an aluminium cap with a plastic lid. 

 

Each pack contains one vial packed in one cardboard box, one sterile transfer device, one sterile 

intravenous infusion set and one sterile short catheter for administration to 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  

 



 

57 

SERB S.A. 

Avenue Louise 480  

1050 Brussels 

Belgium 

 

Or  

 

SERB 

40 avenue George V 

75008 Paris 

France 

 

This leaflet was last revised in MM/YYYY. 

 

Other sources of information 

 

Detailed information on this medicine is available on the European Medicines Agency web site: 

http://www.ema.europa.eu. 

-------------------------------------------------------------------------------------------------------------------------- 

 

The following information is intended for medical or healthcare professionals only: 

 

Handling instructions 

 

Treatment of cyanide poisoning must include immediate attention to airway patency, adequacy 

of oxygenation and hydration, cardiovascular support, and management of seizures. 

Consideration must be given to decontamination measures based on the route of exposure. 

 

Cyanokit does not substitute oxygen therapy and must not delay the set up of the above 

measures. 

 

The presence and extent of cyanide poisoning are often initially unknown. There is no widely 

available, rapid, confirmatory cyanide blood test. However, if a cyanide blood level 

determination is planned, it is recommended to draw the blood sample before initiation of 

treatment with Cyanokit. Treatment decisions must be made on the basis of clinical history 

and/or signs and symptoms of cyanide intoxication. If there is clinical suspicion of cyanide 

poisoning, it is strongly recommended that Cyanokit be administered without delay. 

 

Preparation of Cyanokit 

 

The vial is to be reconstituted with 200 mL of diluent using the supplied sterile transfer device. 

Sodium chloride 9 mg/mL (0.9%) solution for injection is the recommended diluent. Only when 

sodium chloride 9 mg/mL (0.9%) solution for injection is not available, Lactated Ringer solution or 

glucose 50 mg/mL (5%) solution for injection can also be used.  

 

The Cyanokit vial is to be rocked or inverted for at least 1 minute to mix the solution. It must not be 

shaken as shaking the vial may cause foam and therefore may make checking reconstitution less easy. 

Because the reconstituted solution is a dark red solution, some insoluble particles may not be seen. 

The intravenous infusion set provided in the kit must then be used as it includes an appropriate filter 

and is to be primed with the reconstituted solution.  

 

Posology 

 

Initial dose 

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



 

58 

 

Paediatric population: In infants to adolescents (0 to 18 years old), the initial dose of Cyanokit is 

70 mg/kg body weight not exceeding 5 g. 

 

Body weight 

in kg 

 

5 

 

10 

 

20 

 

30 

 

40 

 

50 

 

60 

Initial dose  

in g 

in mL 

 

0.35 

14 

 

0.70 

28 

 

1.40 

56 

 

2.10 

84 

 

2.80 

112 

 

3.50 

140 

 

4.20 

168 

 

Subsequent dose 

Depending upon 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 reconstituted solution). 

 

Paediatric population: In infants to adolescents (0 to 18 years old), the subsequent dose of Cyanokit 

is 70 mg/kg body weight not exceeding 5 g. 

 

Maximum dose 

 

Adults: The maximum total recommended dose is 10 g. 

 

Paediatric population: In infants to adolescents (0 to 18 years old), the maximum total recommended 

dose is 140 mg/kg not exceeding 10 g. 

 

Renal and hepatic impairment 

 

No dose adjustment is required in these patients. 

 

Method of administration 

 

Initial dose of Cyanokit is administered as an intravenous infusion over 15 minutes. 

 

The rate of intravenous infusion for the second dose ranges from 15 minutes (for patients extremely 

unstable) to 2 hours based on patient condition. 

 

Simultaneous administration of Cyanokit and other products 

 

Cyanokit must not be mixed with diluents other than sodium chloride 9 mg/mL (0.9%) solution for 

injection or Lactated Ringer solution or glucose 50 mg/mL (5%) solution for injection. 

 

As physical and chemical incompatibilities were observed with a number of selected medicinal 

products that are frequently used in resuscitation efforts, these and other medicinal products must not 

be administered simultaneously in the same intravenous line as hydroxocobalamin. 

 

If blood products (whole blood, packed red cells, platelet concentrate and fresh frozen plasma) and 

hydroxocobalamin are administered simultaneously, use of separate intravenous lines (preferably on 

contralateral extremities) is recommended. 

 

Combination with another cyanide antidote: Chemical incompatibility was observed with sodium 

thiosulfate and sodium nitrite. If the decision is made to administer another cyanide antidote with 

Cyanokit, these medicinal products must not be administered concurrently in the same intravenous 

line. 

 



 

59 

In-use stability of the reconstituted solution 

 

Chemical and physical in-use 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 to 40°C.  

From a microbiological point of view, the medicinal product should be used immediately. If not used 

immediately, in-use storage times and conditions prior to use are the responsibility of the user and 

would normally not be longer than 6 hours at 2°C to 8°C. 

 


	SUMMARY OF PRODUCT CHARACTERISTICS
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	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS OR REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
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