Hydroxocobalamin

Pronunciation: hye-DROX-oh-koe-BAL-a-min
Class: Antidote, Vitamin

Trade Names

Cyanokit
- Injection, lyophilized powder for solution 2.5 g

Hydroxocobalamin
- Injection, solution 1,000 mcg/mL

Pharmacology

Vitamin B ₁₂ is essential to growth, cell reproduction, hematopoiesis, and nucleoprotein and myelin synthesis.

Slideshow: Top 10 Ways to Save on Your Medication Costs

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.

50% of the administered dose disappears from the injection site in 2.5 h.

Distribution

Hydroxocobalamin is bound to plasma proteins and stored in the liver.

Elimination

Excreted in the bile and undergoes some enterohepatic recycling.

Mean half-life 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.

Within 72 h of injection of 500 to 1,000 mcg, 16% to 66% of the dose may appear in the urine. The major portion is excreted in the first 24 h.

Special Populations

When normalized for body weight, men and women revealed no major pharmacokinetic differences.

Indications and Usage

Treatment of known or suspected cyanide poisoning.

For the treatment of pernicious anemia; dietary deficiency of vitamin B ₁₂ occurring in strict vegetarians and in their breast-fed infants; malabsorption of vitamin B ₁₂ resulting from structural or functional damage to the stomach or to the ileum; inadequate secretion of intrinsic factor; competition for vitamin B ₁₂ by intestinal parasites or bacteria; inadequate utilization of vitamin B ₁₂ . For use in the Schilling test.

Contraindications

Hypersensitivity to any component of the medication.

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.

IM 1,000 mcg.

IM 30 mcg daily for 5 to 10 days followed by 100 to 200 mcg monthly.

IM Initial total dose is 1 to 5 mg over a period of at least 2 wk in doses of 100 mcg. Maintenance dose is 30 to 50 mcg every 4 wk.

General Advice

• Cyanokit
• 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.
• Exercise caution when administering other cyanide antidotes simultaneously with hydroxocobalamin. If a decision is made to administer another cyanide antidote with hydroxocobalamin, do not administer these drugs concurrently with the same IV line.

Storage/Stability

Store between 59° and 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.

Store between 68° and 77°F. Protect from light.

Drug Interactions

None well documented.

Laboratory Test Interactions

Because of its deep red color, hydroxocobalamin may interfere with colorimetric determination of certain laboratory parameters (eg, clinical chemistry, coagulation, hematology, urine parameters).

Adverse Reactions

The following adverse reactions were observed with Cyanokit .

Cardiovascular

Increased BP (28%); ECG repolarization abnormality, hot flush, increased heart rate, ventricular extrasystoles.

CNS

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

Dermatologic

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

EENT

Dry throat; eye swelling, irritation, and redness; throat tightness.

GI

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

Genitourinary

Red-colored urine (100%).

Hematologic-Lymphatic

Decreased lymphocytes (17%).

Local

Infusion-site reactions (39%).

Respiratory

Dyspnea, pleural effusion.

Miscellaneous

Allergic reactions (including anaphylaxis, chest tightness, dyspnea, edema, pruritus, rash, and urticaria), chest discomfort, peripheral edema; angioneurotic edema (postmarketing).

Precautions

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established for Cyanokit .

Hypersensitivity

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

Renal Function

Safety and efficacy not established.

Hepatic Function

Safety and efficacy not established.

BP

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

Cyanide poisoning patients

In addition to hydroxocobalamin, treatment should include immediate attention to airway patency, adequacy of oxygenation and hydration, CV support, and management of any seizure activity.

Folic acid or vitamin B ₁₂ assays

Certain medications may interfere with the validity of folic acid and vitamin B ₁₂ assays. Consider this before relying on such tests for therapy.

Folic acid therapy

Folic acid therapy and vitamin B ₁₂ therapy are not substitutes for each other. Use of folic acid to treat vitamin B ₁₂ –deficient megaloblastic anemia could result in progressive and irreversible neurologic damage. Use of vitamin B ₁₂ to treat folic acid– deficient megaloblastic anemia may mask the true diagnosis.

Inadequate response

Blunted or impeded therapeutic response to vitamin B ₁₂ may be due to such conditions as infection, uremia, drugs having bone marrow–suppressant properties, and concurrent iron or folic acid therapy.

Photosensitivity

Advise patients to avoid sun exposure while their skin remains discolored.

Polycythemia vera

Treatment with vitamin B ₁₂ may unmask this condition.

Overdosage

Symptoms

No data available.

Patient Information

• Cyanokit
• 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.

Copyright © 2009 Wolters Kluwer Health.