Hydroxocobalamin

Trade Names:
Cyanokit
- Powder for injection, lyophilized 2.5 g

Pharmacology

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Binds with cyanide ions to form cyanocobalamin, which is excreted in the urine.

Pharmacokinetics

Absorption

Following IV administration of hydroxocobalamin 5 g, the C _max of mean free and total cobalamins is 113 and 579 mcg eq/mL, respectively. Following IV administration of hydroxocobalamin 10 g, the C _max of mean free and total cobalamins are 197 and 995 mcg eq/mL, respectively.

Elimination

Mean t _½ of free and total cobalamins for administration of hydroxocobalamin 5 and 10 g is 26 to 31 h. Overall, total urinary excretion of cobalamin is 60% to 70% and the majority is excreted in the first 24 h.

Indications and Usage

Treatment of cyanide poisoning.

Contraindications

None.

Dosage and Administration

IV Start with 5 g as an infusion over 15 min. Depending on the severity of the poisoning and clinical response, a second 5 g dose may be infused over 15 min to 2 h, as clinically indicated.

General Advice

• Reconstitute each 2.5 g vial of hydroxocobalamin with 100 mL of diluent using the supplied sterile transfer spike.
• The recommended diluent is sodium chloride 0.9% injection, but Ringer's lactate and dextrose 5% injection may be used if sodium chloride 0.9% is not available.
• After addition of diluent to the lyophilized powder, each vial should be repeatedly inverted or rocked, not shaken, for at least 30 sec prior to infusion.
• Visually inspect the solution for particulate matter and color prior to administration. If the solution is not dark red or if particulate matter is seen after appropriate mixing, discard the solution.
• Diazepam, dobutamine, dopamine, fentanyl, nitroglycerin, pentobarbital, propofol, and thiopental are physically incompatible (particle formation) with hydroxocobalamin and should not be administered simultaneously through the same IV line as hydroxocobalamin.
• Ascorbic acid, sodium nitrite, and sodium thiosulfate are chemically incompatible with hydroxocobalamin and should not be administered simultaneously through the same IV line as hydroxocobalamin.
• It is recommended that blood products (eg, whole blood, packed red cells, platelet concentrate, fresh frozen plasma) not be given through the same IV line as hydroxocobalamin. However, blood products and hydroxocobalamin can be given simultaneously using separate IV lines, preferably on contralateral extremities, if peripheral lines are being used.

Storage/Stability

Store at 59° to 86°F. Reconstituted solution may be stored up to 6 h at a temperature not exceeding 104°F. Do not freeze. Discard unused portion after 6 h.

Drug Interactions

None well documented.

Laboratory Test Interactions

May interfere with colorimetric determination of certain laboratory parameters (eg, clinical chemistry, coagulation, hematology, urine parameters).

Adverse Reactions

Cardiovascular

Increased BP (28%); hot flash, increased heart rate, ventricular extrasystoles.

CNS

Headache (33%); dizziness, impaired memory, restlessness.

Dermatologic

Erythema (94% to 100%); rash (44%); pruritus, urticaria.

EENT

Eye swelling, irritation, and redness; dry throat; throat tightness.

GI

Nausea (11%); abdominal discomfort, diarrhea, dyspepsia, dysphagia, hematochezia, vomiting.

Genitourinary

Red-colored urine (100%).

Hematologic-Lymphatic

Decreased lymphocytes (17%).

Lab Tests

ECG repolarization abnormality.

Local

Infusion-site reactions (39%).

Respiratory

Dyspnea, pleural effusion.

Miscellaneous

Allergic reactions, chest discomfort, peripheral edema.

Precautions

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Renal Function

Safety and efficacy not established.

Hepatic Function

Safety and efficacy not established.

Allergy

Use with caution in patients with known anaphylactic reactions to hydroxocobalamin or cyanocobalamin; consider alternative therapy.

Blood cyanide assay

Pretreatment blood sample may be useful in documenting cyanide poisoning.

Blood pressure

Many patients with cyanide poisoning will be hypotensive; however, transient hypertension may also occur.

Overdosage

Symptoms

No data available.

Patient Information

• Advise patient to read the patient information leaflet.
• Advise patient that skin redness may last up to 2 wk and urine color may last up to 5 wk after treatment.
• Advise patient to avoid direct sun while skin remains discolored.
• Advise patient that acneiform rash may occur 7 to 28 days after treatment and will usually resolve within a few weeks.

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