Hydroxocobalamin (antidote)

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Related FACEM curriculum (2022) learning objectives:

• ME 3.8.1.6(e) Principles of management of toxicological presentations including: Indications for antidotes
• ME 3.8.2.4 Identify the appropriate antidote or antivenom.

Presentations

• Cyanokit®: 2 vials of 2.5 g lyophilised powder with 2 vials of 100 mL normal saline for reconstitution.
• Hydroxocobalamin chloride 1 mg/mL ampoules.

Toxicological Indications

• Known cyanide poisoning with serious clinical effects:
  • Altered mental status, seizures, hypotension, lactic acidosis with normal oxygen saturation.
• Suspected cyanide poisoning with serious clinical effects.
  • Preferred antidote due to benign adverse effect profile, even in non-cyanide poisoning.

Contraindications

• Known hypersensitivity.

Mechanism of Action

• Central cobalt ion binds cyanide, forming cyanocobalamin, a non-toxic compound excreted in urine.
• Prevents cyanide from inhibiting cytochrome oxidase and reactivates inhibited cytochrome oxidase.

Pharmacokinetics

• Volume of distribution: 0.1–0.5 L/kg.
• Excreted unchanged in urine; elimination half-life: 1.5–26 hours.
• Cyanocobalamin half-life: ~9 hours in cyanide-poisoned patients.

Administration

Preparation and Dosage

• Reconstitute 2.5 g vial with 100 mL saline; infuse over 15 minutes.
• Repeat for total dose of 5 g; sufficient for binding 100 mg cyanide.
• Larger doses may be required for known larger ingestions.
• If no improvement in 15 minutes, repeat dose or consider sodium thiosulfate.

Therapeutic Endpoints

• Improved conscious state.
• Haemodynamic stability.
• Resolution of metabolic acidosis.

Adverse Drug Reactions

• Minor transient hypertension, bradycardia, or tachycardia.
• Orange-red discolouration of skin, mucous membranes, and fluids (12–48 hours).
• Acute allergic reactions unreported in high-dose therapy.

Specific Considerations

• Pregnancy: No restriction on use.
• Paediatric: Suggested starting dose 50 mg/kg.

Handy Tips

• Cyanokit® provides adequate therapeutic dose; alternative preparations unsuitable.
• Administer 5 g IV during resuscitation for cardiac arrest due to cyanide poisoning.
• Lack of response after first dose necessitates diagnostic review.
• Do not mix hydroxocobalamin and sodium thiosulfate in the same infusion.
• Discolouration may affect colorimetric lab tests, causing artefacts rarely of clinical concern.

Pitfalls

• Stocking inappropriate preparations.
• Failure to administer adequate dose.

Controversies

• High cost (~A$2000 per pack of 2 ampoules); limited utility necessitates careful stock management.
• Efficacy relative to supportive care and other antidotes debated.
• Necessity of sodium thiosulfate post-hydroxocobalamin administration questioned.