Dosage / Administration
The initial adult dose of hydroxocobalamin is 5 g. Each vial of 5 g is reconstituted with 200 ml of 0.9% normal saline (or Ringer's lactate or 5% dextrose with normal saline) and administered intravenously (IV) over 15 minutes. The reconstituted solution should be dark red and free of particulate matter, and it should be used within 6 hours of reconstitution.

A second dose of 5 g should be repeated as clinically necessary over 15 minutes to 2 hours.

Pediatric considerations: Pediatric dose is 70 mg/kg (not to exceed 5 g) over 15 minutes (15 mL/min). Reconstitute each 2.5 g vial with 100 mL of 0.9% saline or each 5 g vial with 200 mL of 0.9% saline (or equal volumes of Lactated Ringer's solution or 5% dextrose with normal saline).

A second dose of 70 mg/kg may be administered, if necessary, over 15 minutes (not to exceed 10 g total).

Indications
Hydroxocobalamin is US Food and Drug Administration (FDA) approved for acute cyanide poisoning.

It can be coadministered with sodium thiosulfate in cyanide poisoning, but hydroxocobalamin should take precedence. Sodium thiosulfate and hydroxocobalamin should not be coadministered simultaneously in the same IV line because the thiosulfate will inactivate the hydroxocobalamin.

Contraindications
No specific contraindication to hydroxocobalamin has been determined.

Hydroxocobalamin is FDA Pregnancy Category C. Animal studies are insufficient, and there are no controlled trials in pregnant women. Hydroxocobalamin should be used in pregnant women whose cyanide toxicity is presumed significant.

Monitoring
No blood levels are required for monitoring the antidote therapy. However, discoloration of body fluids with cobalamin can interfere with laboratory tests of blood and serum for 12-48 hours and urine for up to 8 days.

Many routine blood tests are affected by the colorimetric interference of hydroxocobalamin.

Hematological hemoglobin, mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and basophils are artificially increased.

The effect of hydroxocobalamin on measurement of carboxyhemoglobin gives falsely elevated as well as falsely low serum determinations.

The effects of hydroxocobalamin on measurement of lactate, creatine kinase (CK), and creatine kinase myocardial band (CK-MB) and coagulation tests are unpredictable.

Because of the inaccuracies in laboratory determinations, blood should be drawn before hydroxocobalamin administration whenever possible. This is particularly important in fire victims when carboxyhemoglobin (COHb) concentrations are necessary for management decisions.

Adverse Effects
Hydroxocobalamin has a wide therapeutic index.

Orange-to-red discoloration of urine can last for 12-48 hours.

An acneiform rash may develop that lasts up to 28 days. Hypertension, bradycardia, and tachycardia have been reported.

Acute allergic reactions have not been reported.

Patients should avoid direct sun exposure for a month.

Toxicity
There is no toxicity associated with hydroxocobalamin.

Mechanism of Action
Hydroxocobalamin rapidly exchanges its hydroxyl group with free cyanide and forms a nontoxic compound, cyanocobalamin (vitamin B12). This is done in mole-to-mole exchange in a 1:1 ratio. Cyanocobalamin is then excreted by the kidney.

Hydroxocobalamin prevents cyanide from entering tissues and binding to cytochrome oxidase and enhances reactivation of inhibited cytochrome oxidase by promoting removal of cyanide from the intracellular space.