Canadian antidote guide

Hydroxocobalamin

• Cyanokit™

• Acute poisoning by cyanide salts, acetonitrile, propionitrile, amygdalin, or by hydrocyanic acid (hydrogen cyanide) with significant signs of toxicity:
  • Coma
  • Bradypnea
  • Hypotension
  • Severe metabolic acidosis with lactatemia greater than 8 mmol/L.
• Severe toxicity associated with the IV administration of sodium nitroprusside.
  • Tachycardia
  • Tachypnea
  • Altered state of consciousness
  • Metabolic acidosis

• Red colouring of the skin up to 15 days after administration.
• Dark red biological fluids, especially the first 3 days after administration (may last up to 35 days).
• A rash, possibly pustular, which can occur 7 to 25 days after administration.
• Mild increase in blood pressure.
• Acute kidney injury related to oxalate nephropathy is reported with the use of hydroxocobalamin in patient with smoke inhalation.

• Vital signs
• WARNING:
  • Interference with certain laboratory analyses using colorimetry (creatinine, bilirubin, etc.) may last 24 to 72h. In addition, blood samples can be falsely interpreted as hemolyzed.
  • Alteration (lower) of carboxyhemoglobin has also been reported.

• Improved state of consciousness, correction of hypotension and metabolic acidosis.

Intravenous Route (IV)

• Direct IV
  • Not recommended.
• IV infusion over 15 min.
  • Infuse each IV dose, at a final concentration of 0.025 g/ml (25 mg/ml), over 15 minutes.
  • The IV infusion set supplied with the kit must be used, as it contains an appropriate filter and is to be primed with the reconstituted solution.However, it is not compatible with some pumps; if this is the case, it would need to be administered by gravity.

Subcutaneous Route (SC)

• Not applicable.

Intramuscular Route (IM)

• Not applicable.

Intraosseous Route (IO)

• Possible alternative to IV route.

Reconstitution

5 g Vial

• Each vial must be reconstituted with 200 ml of NS using the sterile transfer device provided.
  • For pediatric population, we specifically advise NOT to use the sterile transfer device provided in the cyanokit for the reconstitution process. Instead, we suggest accurately measuring 200 mL of NS using 4 syringes of 60 ML and injecting this precise volume (200mL) into the hydroxocobalamin vial. This ensures an accurate final concentration of 25 mg/mL.
  • Only if NS not available, D5W or LR can also be used as diluents.
• Rock the vial up and down at least 60 seconds to thoroughly mix the solution.
  • Do not shake the vial, as this could cause the formation of foam which would compromise the control of the reconstitution. Since the reconstituted formula is dark red, a few insoluble particles may not be visible.
• Each vial reconstituted with 200 ml of diluent gives a final concentration of 0.025 g/ml (25 mg/ml).
• Video describing the reconstitution and the preparation of a 5g vial of hydroxocobalamin for further administration to an adult patient: https://youtu.be/lYg2dS5D4SQ

Compatibility

Partial list only. Consult the pharmacist on duty at your health care facility.

• Compatible solutions NS, D5W, LR.
• Y-site compatibility: No data available.
• Y-site incompatibility: Ascorbic acid, diazepam, dobutamine, dopamine, fentanyl, sodium nitrite, nitroglycerin, pentobarbital, propofol, thiopental, sodium thiosulfate.

Stability

• The content of the diluted vial will be stable for 6 hours after reconstitution.

• Cyanokit, 5 g/vial, pd. Inj. IV, 1 vial per kit, Methapharm, DIN 02375370, 
•  

• At least 10 g.

Anseeuw, Kurt, Nicolas Delvau, Guillermo Burillo-Putze, Fabio De Iaco, Götz Geldner, Peter Holmström, Yves Lambert, and Marc Sabbe. 2013. “Cyanide Poisoning by Fire Smoke Inhalation: A European Expert Consensus.” European Journal of Emergency Medicine: Official Journal of the European Society for Emergency Medicine 20 (1):2–9.



Bebarta, Vikhyat S. 2016. “Cyanide Binding Antidotes: Dicobalt Edetate and Hydroxocobalamin.” In Critical Care Toxicology, edited by Jeffrey Brent, Keith Burkhart, Paul Dargan, Benjamin Hatten, Bruno Megarbane, and Robert Palmer, 24:1–9. Cham: Springer International Publishing.



Drew, R. H. 1983. “The Use of Hydroxocobalamin in the Prophylaxis and Treatment of Nitroprusside-Induced Cyanide Toxicity.” Veterinary and Human Toxicology 25 (5):342–45.

Fueyo L, Robles J, Aguilar I, Yanez AM, Socias M. Hemolysis index to detect degree of hydroxocobalamin interference with common laboratory tests. Journal of Clinical Laboratory Analysis 2017; 31(5):e22089.



Hall, Alan H., Richard Dart, and Gregory Bogdan. 2007. “Sodium Thiosulfate or Hydroxocobalamin for the Empiric Treatment of Cyanide Poisoning?” Annals of Emergency Medicine 49 (6):806–13.



Hamad, Eike, Kavita Babu, and Vikhyat S. Bebarta. 2016. “Case Files of the University of Massachusetts Toxicology Fellowship: Does This Smoke Inhalation Victim Require Treatment with Cyanide Antidote?” Journal of Medical Toxicology: Official Journal of the American College of Medical Toxicology 12 (2):192–98.



Krapez, J. R., C. J. Vesey, L. Adams, and P. V. Cole. 1981. “Effects of Cyanide Antidotes Used with Sodium Nitroprusside Infusions: Sodium Thiosulfate and Hydroxocobalamin given Prophylactically to Dogs.” British Journal of Anaesthesia 53 (8):793–804.



Pace, R., M. Bon Homme, R. S. Hoffman, and D. Lugassy. 2014. “Effects of Hydroxocobalamin on Carboxyhemoglobin Measured under Physiologic and Pathologic Conditions.” Clinical Toxicology 52 (7):647–50.



Shepherd, Greene, and Larissa I. Velez. 2008. “Role of Hydroxocobalamin in Acute Cyanide Poisoning.” The Annals of Pharmacotherapy 42 (5):661–69.



Thompson, John P., and Timothy C. Marrs. 2012. “Hydroxocobalamin in Cyanide Poisoning.” Clinical Toxicology 50 (10):875–85.



Uhl, Wolfgang, Arno Nolting, Georg Golor, Karl Ludwig Rost, and Andreas Kovar. 2006. “Safety of Hydroxocobalamin in Healthy Volunteers in a Randomized, Placebo-Controlled Study.” Clinical Toxicology 44 Suppl 1:17–28.



Zerbe, N. F., and B. K. Wagner. 1993. “Use of Vitamin B12 in the Treatment and Prevention of Nitroprusside-Induced Cyanide Toxicity.” Critical Care Medicine 21 (3):465–67.