Cyanokit

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. 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 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.

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.

6.

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. 8 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. 4). • Chromaturia : all patients will show a dark red colouration of the urine quite marked during the first three days following administration.

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.

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. 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. 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.