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  1. Pharmacology. Hydroxocobalamin and cyanocobalamin are analogs of vitamin B12 that have been used for the treatment of pernicious anemia. Hydroxocobalamin was approved as an antidote for human cyanide poisoning in France in 1996 and is now available in the United States. Hydroxocobalamin rapidly exchanges its hydroxyl group with free cyanide to produce nontoxic, stable cyanocobalamin. When administered to patients with cyanide poisoning, it rapidly improves the heart rate and systolic blood pressure and decreases acidemia. In humans, outcome is best when hydroxocobalamin is administered before cardiopulmonary arrest occurs. Animal studies suggest enhanced antidotal efficacy if thiosulfate (See Thiosulfate, Sodium) is given in addition to hydroxocobalamin therapy, but the drugs are not compatible in the same IV line. In normal individuals given 5- and 10-g doses, the plasma half-life values of hydroxocobalamin average 26 and 31 hours, respectively. Oral absorption is extremely poor; intranasal absorption occurs with very small doses.

  2. Indications

    1. Treatment of acute cyanide poisoning or patients suspected to be at high risk for cyanide poisoning (eg, smoke inhalation victims; see VII. Formulations below).

    2. Prophylaxis against cyanide poisoning during nitroprusside infusion has been proposed.

  3. Contraindications. Use caution when managing patients with known hypersensitivity to hydroxocobalamin or cyanocobalamin, and consider alternative treatments.

  4. Adverse effects

    1. Adverse reactions in healthy volunteers include chromaturia (red-colored urine) in 100%, erythema in 94–100%, rash in 20-44%, increased blood pressure in 18–28%, nausea in 6–11%, headache in 6–33%, decreased lymphocyte percentage in 8–17%, and infusion site reaction in 6–39%. Although red-colored body fluids usually normalize within 2–7 days, erythema can last up to 2 weeks and chromaturia up to 35 days. A self-limiting acneform rash may occur 7–28 days after infusion.

    2. Allergic reactions have not been reported with acute intravenous therapy for cyanide poisoning. However, allergic reactions have been reported in patients using chronic IM therapy and in healthy volunteers unexposed to cyanide who were given IV hydroxocobalamin while participating in clinical safety trials.

    3. Use in pregnancy. FDA Category C. Pregnancy does not preclude the acute, short-term use of hydroxocobalamin for a seriously symptomatic, cyanide-poisoned patient (See Introduction in Section III), but it is probably preferable to use nitrite administration for cyanide poisoning.

  5. Drug or laboratory interactions

    1. Coloration of body fluids caused by cobalamins may interfere with colorimetric laboratory tests for periods ranging from 12 hours to 8 days; test results commonly affected are those for AST and serum creatinine (falsely decreased), and those for Mg and bilirubin (falsely increased). See package insert for detailed list. Currently, interference has not been documented in serum tests for the following: Na, K, Cl, Ca, BUN, and GGT (gamma-glutamyltransferase). Consider sampling and storing specimens before antidote administration in case additional laboratory analyses are considered later.

    2. To date, chemical or physical incompatibility has been documented for some drugs, which include diazepam, dobutamine, dopamine, fentanyl, nitroglyerin, pentobarbital, propofol, thiopental, sodium thiosulfate, sodium nitrate, and ascorbic acid. Administration of these and possibly other drugs should be through a separate IV line.

    3. Hydroxocobalamin has been reported to falsely ...

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