Hydroxocobalamin as a Cyanide Antidote: Safety, Efficacy and Pharmacokinetics in Heavily Smoking Normal Volunteers

Abstract

The safety, efficacy and pharmacokinetic parameters of 5 g of hydroxocobalamin given intravenously, alone or in combination with 12.5 g of sodium thiosulfate, were evaluated in healthy adult men who were heavy smokers. Sodium thiosulfate caused nausea, vomiting, and localized burning, muscle cramping, or twitching at the infusion site. Hydroxocobalamin was associated with a transient reddish discoloration of the skin, mucous membranes, and urine, and when administered alone produced mean elevations of 13.6% in systolic and 25.9% in diastolic blood pressure, with a concomitant 16.3% decrease in heart rate. No other clinically significant adverse effects were noted. Hydroxocobalamin alone decreased whole blood cyanide levels by 59% and increased urinary cyanide excretion. Pharmacokinetic parameters of hydroxocobalamin were best defined in the group who received both antidotes: t1/2 (alpha), 0.52 h; t1/2 (beta), 2.83 h; Vd (beta), 0.24 L/kg; and mean peak serum concentration 753 mcg/mL (560 mumol/L) at 0-50 minutes after completion of infusion. Hydroxocobalamin is safe when administered in a 5 gram intravenous dose, and effectively decreases the low whole blood cyanide levels found in heavy smokers.

Part 12: Cardiac Arrest in Special Situations

“…387,390,391 Sodium thiosulfate is associated with vomiting but has no other significant toxicity. 398 Therefore, based on the best evidence available, a treatment regimen of 100% oxygen and hydroxocobalamin, with or without sodium thiosulfate, is recommended (Class I, LOE B).…”

Enhancing Public Health Preparedness for a Terrorist Attack Involving Cyanide

“…Hydroxocobalamin, which directly chelates the cyanide from hemoglobin on an equimolar basis, does not induce methemoglobinemia nor cause hemodynamic instability. Its most common side effects include discoloration of urine and mucous membranes and abnormalities in specific laboratory tests, particularly aspartate aminotransferase, bilirubin, magnesium, creatinine, and iron (25)(26)(27). These effects are transient (lasting 1 to 2 days) and do not seem to reflect clinically meaningful changes.…”

“…These effects are transient (lasting 1 to 2 days) and do not seem to reflect clinically meaningful changes. In a study in heavily smoking healthy volunteers, most changes in laboratory values occurred within the normal reference ranges (27).…”

Intoxicación por gases

“…El EDTA de cobalto es muy efectivo a nivel experimental 7 , pero se acompaña de una muy mala tolerancia hemodinámica, por lo que actualmente se desaconseja su utilización 8 . Actualmente, la hidroxocobalamina (vitamina B 12 ) es el antídoto de elección en el tratamiento de la intoxicación por cianuro 43,44 , ya que su comienzo de acción es muy rápido 41 , con una margen terapeútico muy amplio 44 . Estas características farmacológicas hacen que la hidroxocobalamina sea un medicamento muy seguro, lo cual…”