Hydroxocobalamin

CYANOKIT is indicated for the treatment of known or suspected cyanide poisoning.

Cyanide is an extremely toxic poison. In the absence of rapid and adequate treatment, exposure to a high dose of cyanide can result in death within minutes due to the inhibition of cytochrome oxidase resulting in arrest of cellular respiration. Specifically, cyanide binds rapidly with cytochrome a3, a component of the cytochrome c oxidase complex in mitochondria. Inhibition of cytochrome a3 prevents the cell from using oxygen and forces anaerobic metabolism, resulting in lactate production, cellular hypoxia and metabolic acidosis. In massive acute cyanide poisoning, the mechanism of toxicity may involve other enzyme systems as well. Signs and symptoms of acute systemic cyanide poisoning may develop rapidly within minutes, depending on the route and extent of cyanide exposure. The action of CYANOKIT in the treatment of cyanide poisoning is based on its ability to bind cyanide ions.

If clinical suspicion of cyanide poisoning is high, administer CYANOKIT without delay and in conjunction with appropriate airway, ventilatory, and circulatory support, oxygen administration as well as management of seizures. The expert advice of a regional poison control center may be obtained by calling 1-800-222-1222. Dosing: The starting dose of CYANOKIT for adults is 5 g, administered by intravenous infusion over 15 minutes. One 5 g vial is a complete starting dose. Depending upon the severity of the poisoning and the clinical response, a second dose of 5 g may be administered by intravenous infusion for a total dose of 10 g. The rate of infusion for the second 5 g dose may range from 15 minutes (for patients in extremis) to 2 hours based on patient condition. The recommended diluent is 0.9% Sodium Chloride injection. CYANOKIT requires a separate intravenous line for administration.

None None

Risk of Anaphylaxis and Other Hypersensitivity Reactions: Consider alternative therapies, if available, in patients with known anaphylactic reactions to hydroxocobalamin or cyanocobalamin. Risk of Renal Injury: Acute renal failure with acute tubular necrosis, renal impairment and urine calcium oxalate crystals have been reported following CYANOKIT therapy. Monitor renal function for 7 days following CYANOKIT therapy. Risk of Increased Blood Pressure: Substantial increases in blood pressure may occur following CYANOKIT therapy. Monitor blood pressure during treatment.

Serious adverse reactions with hydroxocobalamin include allergic reactions, renal injury, and increases in blood pressure. Most common adverse reactions (>5%) include transient chromaturia, erythema, oxalate crystals in urine, rash, increased blood pressure, nausea, headache, and infusion site reactions.

Formal drug interaction studies have not been conducted with CYANOKIT. Interference with Laboratory Tests Because of its deep red color, hydroxocobalamin has been found to interfere with colorimetric determination of certain laboratory parameters (e.g., clinical chemistry, hematology, coagulation, and urine parameters). Be aware of this when reporting and interpreting laboratory results.

Store at 25°C (77°F), excursions permitted to 15-30°C (59 to 86°F). 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 (41 to 104°F), transport in the desert (4 days submitted to temperatures ranging from 5 to 60°C (41 to 140°F)) and freezing/defrosting cycles (15 days submitted to temperatures ranging from -20 to 40°C (-4 to 104°F)). Do not freeze. Reconstituted solution Store up to 6 hours at a temperature not exceeding 40ºC (104°F).