Hydroxocobalamin

Cyanokit®

Antidote

Adult

Hydroxocobalamin

Cyanokit®

Indications

Cyanide poisoning from hydrogen cyanide gas (smoke inhalation), ingestion of cyanide salts, high dose nitroprusside infusions.
May be used alone or in combination with sodium thiosulfate.

Dosage

Initial dose: 5 g IV over 15 minutes.
Depending on severity of poisoning and clinical response, the same dose may be repeated once. The rate of infusion for the second dose may range from 15 minutes to 2 hours as clinically indicated.
Doses up to 20 g have been used in severe poisoning.

Administration

Reconstitution: For a final concentration of 25 mg/mL: reconstitute each 2.5 g vial with 100 mL sodium chloride 0.9% or reconstitute each 5 g vial with 200 mL sodium chloride 0.9%. Use the transfer spike provided. Rock or invert the vial for at least 1 minute to mix. Do not shake.
Infusion: Infuse the reconstituted 5 g dose over 15 minutes. Use administration set provided as it contains the appropriate filter. The provided administration set can be piggybacked into a primary line. Blood pressure monitoring is required.

Compatibility, Stability

Compatible with sodium chloride 0.9% (recommended), dextrose 5% in water and lactated ringer’s.
Do not administer other drugs, especially sodium thiosulfate, in the same line as hydroxocobalamin.
Once reconstituted, the vial is stable for 6 hours at room temperature.
Reconstituted solution should be dark red in colour.
Protect vials from light.

Potential Hazards of Administration

Hypertension (transient; returns to baseline within 4 hours of dose).
Nausea, headache, dizziness.
Red discolouration of the urine (pronounced for 3 days following dose; may last up to 5 weeks).
Erythema of skin or mucous membranes (may last up to 2 weeks), pustular rash mainly affecting the face and neck (usually 7 - 28 days following treatment).
Allergic reactions (including anaphylaxis, chest tightness, edema, urticaria, pruritus, dyspnea, rash.

Miscellaneous

Hydroxocobalamin may interfere with some clinical chemistry assays such as:

- aminotransferases, bilirubin, creatinine, creatine kinase, phosphorus, magnesium, lactate

- Co-oximetry readings such as carboxyhemoglobin, methemoglobin, which may be of significant clinical consequence in the setting of smoke inhalation
Hydroxocobalamin may trigger blood leak alarms on certain hemodialysis machines, likely due to colorimetric interference.

References…

Bailey, B., Blais, R., Gaudreault, P., Gosselin, S., & Laliberte, M. (2009). Antidotes en toxicologie d'urgence (3rd ed.). Quebec, Canada: Centre antipoison du Quebec.

Borron, S. W., Bronstein, A. C., Fernandez, M. C., & et all. (2014). Walter F. G. (Ed.), AHLS advanced hazmat life support, provider manual (4th ed.). Tucson, Arizona: The University of Arizona College of Medicine.

Brunel, C., Widmer, C., Augsburger, M., Dussy, F., & Fracasso, T. (2012). Case report: Antidote treatment for cyanide poisoning with hydroxocobalamin causes bright pink discolouration and chemical-analytical interferences. Forensic Science International, 223, 10-12.

Goldfrank, L. R., Nelson, L. S., Lewin, N. A., Howland, M. A., Hoffman, R. S., (2015). Goldfrank's toxicologic emergencies(Tenth ed.). New York: McGraw Hill.

Hall, A. H., Saiers, J., & Baud, F. (2009). Review article: Which cyanide antidote. Critical Reviews in Toxicology, 39(7), 541-552.

Merck, S. (2012). Cyanokit, hydroxycobalamin package insert. online. Retrieved from http://www.cyanokit.com/prepare.aspx

Micromedex, T. H. A. (2014). Micromedex health care systems. Retrieved from http://www.micromedexsolutions.com

Mintegi, S., Clerigue, N., Tipo, V., Ponticiello, E., Lonati, D., Burillo-Putze, G., & Delvau, N. (2013). Pediatric cyanide poisoning by fire smoke inhalation: A european expert consensus. Pediatric Emergency Care, 29(11), 1234-1240.

Olson, K. R. (2007). Poisoning & drug overdose (Sixth ed.). New York: McGraw Hill.

Phelps SJ, C. C. (2013). Teddy bear, pediatric injectable drugs. Retrieved from http://www.pharmpress.com/product/MC_PED/pediatric-injectable-drugs

Reade, M. C., Davies, S. R., Morley, T. M., & Jacobs, I. C. (2012). Review article: Management of cyanide poisoning. Emergency Medicine Australasia, 24, 225-238.

Shannon, M. W., Borron, S. W., & Burns, M. J. (2007). Haddad and Winchester's clinical management of poisoning and drug overdose (Fourth ed.). Philadelphia: Saunders Elsevier.

Smollin, C. G. (2010). Toxicology: Pearls and pitfalls in the use of antidotes. Emergency Medicine Clinic of North America, 28, 149-161.

Stellpflug, S. J., Gardner, R. L., Leroy, J. M., Ellsworth, H., & Zwank, M. D. (2013). Letter to editor: Hydroxocobalamin hinders hemodialysis. American Journal of Kidney Dialysis, 62, 395.

Stretz, M. J., Bebarta, V. S., Borys, D. J., & Morgan, D. L. (2014). Patterns of cyanide antidote use since regulatory approval of hydroxocobalamin in the United States. American Journal of Therapeutics, 21, 244-249.

Sutter, M. E., Clarke, M. E., Cobb, J., Daubert, G. P., Rathore, V. S., Aston, L. S., . . . Albertson, T. E. (2012). Blood leak alarm interference by hydroxocobalamin is hemodialysis machine dependent. Clinical Toxicology (Philadelphia, Pa.), 50, 892-895.

Thompson, J. P., & Mara, T. C. (2012). Hydroxocobalamin in cyanide poisoning. Clinical Toxicology (Philadelphia, Pa.), 50(10), 875-885.