Hydroxocobalamin: The Vitamin B12 Cyanide Antidote

Hydroxocobalamin, sold as Cyanokit, is the first-line antidote for severe cyanide poisoning. Its mechanism is one of the most elegant in clinical toxicology: it is a precursor to vitamin B12 (cobalamin) with a vacant coordination site on its central cobalt atom that binds cyanide (CN⁻) more tightly than cytochrome c oxidase does. When infused intravenously, hydroxocobalamin competes with Cytochrome c Oxidase: The Final Enzyme in Cellular Respiration for bound cyanide and wins. The cyanide transfers onto the cobalt, forming cyanocobalamin — which is literally vitamin B12. The resulting complex is excreted in urine, temporarily staining it bright red. This gives cyanide one of the most elegant antidote mechanisms in medicine: the poison is removed by sticking it onto a B-vitamin precursor and peeing out the result. Adjuncts: - Sodium thiosulfate provides the sulfur substrate for rhodanese, boosting natural cyanide-to-thiocyanate conversion ~30x. See Rhodanese: The Cyanide Detoxification Enzyme That Can't Save You from Poisoning for why rhodanese alone isn't enough in acute poisoning. - Sodium nitrite (older regimen) induces controlled methemoglobinemia — methemoglobin binds cyanide, but this is riskier because it reduces oxygen-carrying capacity. Hydroxocobalamin has largely displaced the older Lilly kit (amyl nitrite + sodium nitrite + sodium thiosulfate) in field and emergency use because it can be given before diagnosis is confirmed, works in smoke-inhalation victims with unknown cyanide exposure, and has a wide therapeutic window. Standard adult dose: 5g IV over 15 minutes, repeated once if needed. Shelf life ~30 months.