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Pronunciation
(hye droks oh koe BAL a min)
Generic Available (U.S.)
Yes: Excludes powder for injection
Index Terms
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Use: Labeled Indications
Treatment of pernicious anemia, vitamin B12 deficiency due to dietary deficiencies or malabsorption diseases, inadequate secretion of intrinsic factor, and inadequate utilization of B12 (eg, during neoplastic treatment); diagnostic agent for Schilling test
Cyanokit®: Treatment of cyanide poisoning (known or suspected)
Use: Unlabeled
Neuropathies
Pregnancy Risk Factor
C
Pregnancy Considerations
Animal studies are insufficient to determine the effect, if any, on pregnancy or fetal development. There are no adequate and well-controlled studies in pregnant women. Data on the use of hydroxocobalamin in pregnancy for the treatment of cyanide poisoning and cobalamin defects are limited.
Lactation
Excretion in breast milk unknown/use caution
Contraindications
Hypersensitivity to hydroxocobalamin, cyanocobalamin, cobalt, or any component of the formulation
Warnings/Precautions
Concerns related to adverse effects:
• Hypertension: Cyanide poisoning: Increased blood pressure (≥180 mm Hg systolic or ≥110 mm Hg diastolic) is associated with infusion; elevations usually noted at beginning of infusion, peak toward the end of infusion and return to baseline within 4 hours of infusion.
• Photosensitivity: May cause photosensitivity; avoid direct sunlight while skin remains discolored.
Disease-related concerns:
• Anemia: Appropriate use: Neurologic manifestations of vitamin B12 deficiency will not be prevented with folic acid unless vitamin B12 is also given; spinal cord degeneration might also occur when folic acid is used as a substitute for vitamin B12 in anemia prevention.
• Polycythemia vera: Vitamin B12 deficiency masks signs of polycythemia vera; vitamin B12 administration may unmask this condition.
Dosage form specific concerns:
• Cyanokit®: Use caution or consider alternatives in patients with known allergic reactions, including anaphylaxis to hydroxocobalamin or cyanocobalamin. Collection of pretreatment blood cyanide concentrations does not preclude administration and should not delay administration in the emergency management of highly suspected or confirmed cyanide toxicity. Pretreatment levels may be useful as post infusion levels may be inaccurate. Treatment of cyanide poisoning should include decontamination and supportive therapy. Use caution with concurrent use of other cyanide antidotes; safety has not been established.
• Solution for I.M. injection: Treatment of severe vitamin B12 megaloblastic anemia may result in thrombocytosis and severe hypokalemia, sometimes fatal, due to intracellular potassium shift upon anemia resolution. Use caution in folic acid deficient megaloblastic anemia; administration of vitamin B12 alone is not a substitute for folic acid and might mask true diagnosis. Blunted therapeutic response to vitamin B12 may occur in certain conditions (eg, infection, uremia, concurrent iron or folic acid deficiency) or in patients on medications with bone marrow suppressant properties (eg, chloramphenicol). Approved for use as I.M. injection only.
Adverse Reactions
I.M. injection: Frequency not defined:
Dermatologic: Exanthema (transient), itching
Gastrointestinal: Diarrhea (mild, transient)
Local: Injection site pain
Miscellaneous: Anaphylaxis
I.V. infusion (Cyanokit®):
>10%:
Cardiovascular: Hypertension
Central nervous system: Headache (6% to 33%)
Dermatologic: Erythema (94% to 100%; may last up to 2 weeks), rash (predominantly acneiform; 20% to 44%; can appear 7-28 days after administration and usually resolves within a few weeks)
Gastrointestinal: Nausea (6% to 11%)
Genitourinary: Chromaturia (100%; may last up to 5 weeks after administration)
Hematologic: Lymphocytes decreased (8% to 17%)
Local: Infusion site reaction (6% to 39%)
Frequency not defined:
Cardiovascular: Chest discomfort, hot flashes, peripheral edema
Central nervous system: Dizziness, memory impairment, restlessness
Dermatologic: Pruritus, urticaria
Gastrointestinal: Abdominal discomfort, diarrhea, dyspepsia, dysphagia, hematochezia, vomiting
Ocular: Irritation, redness, swelling
Respiratory: Dry throat, dyspnea, throat tightness
Miscellaneous: Allergic reaction (including anaphylaxis)
Postmarketing and/or case reports: Angioneurotic edema
Metabolism/Transport Effects
None known.
Drug Interactions
There are no known significant interactions.
Storage
Solution for I.M. injection: Store at 20°C to 25°C (68°F to 77°F). Protect from light.
I.V. infusion (Cyanokit®): Prior to reconstitution, store at 25°C (77°F): excursions permitted to 15°C to 30°C (59°F to 86°F).
Temperature variation exposure allowed for transport of lyophilized form:
Usual transport: ≤15 days at 5°C to 40°C (41°F to 104°F)
Desert transport: ≤4 days at 5°C to 60°C (41°F to 140°F)
Freezing/defrosting cycles: ≤15 days at -20°C to 40°C (-4°F to 104°F)
Following reconstitution, store up to 6 hours at ≤40°C (104°F); do not freeze. Discard any remaining solution after 6 hours.
Reconstitution
I.V. infusion (Cyanokit®): Reconstitute each 2.5 g vial with 100 mL of NS or 5 g vial with 200 mL of NS using provided sterile transfer spike. If NS unavailable, may use LR or D5W. Invert or rock each 2.5 g vial for at least 30 seconds or 5 g vial for 60 seconds prior to infusion; do not shake. Discard if solution is not dark red.
Compatibility
Stable in NS (preferred), LR, D5W
Y-site administration: Incompatible with ascorbic acid, blood products, sodium nitrite, sodium thiosulfate.
Mechanism of Action
Hydroxocobalamin (vitamin B12a) is a precursor to cyanocobalamin (vitamin B12). Cyanocobalamin acts as a coenzyme for various metabolic functions, including fat and carbohydrate metabolism and protein synthesis, used in cell replication and hematopoiesis. In the presence of cyanide, each hydroxocobalamin molecule can bind one cyanide ion by displacing it for the hydroxo ligand linked to the trivalent cobalt ion, forming cyanocobalamin.
Pharmacodynamics/Kinetics
Following I.V. administration of Cyanokit®:
Protein binding: Significant; forms various cobalamin-(III) complexes
Half-life elimination: 26-31 hours
Excretion: Urine (50% to 60% within initial 72 hours)
Dosage
Vitamin B12 deficiency: I.M.:
Children: 100 mcg once daily for 2 or more weeks (total dose: 1-5 mg); maintenance: 30-50 mcg/month
Adults: 30 mcg/day for 5-10 days, followed by 100-200 mcg/month
Note: Larger doses may be required in critically-ill patients or if patient has neurologic disease, an infectious disease, or hyperthyroidism.
Schilling test: I.M.: Adults: 1000 mcg
Cyanide toxicity (Cyanokit®): I.V.: Adults: Initial: 5 g as single infusion; may repeat a second 5 g dose depending on severity of poisoning and clinical response. Maximum cumulative dose: 10 g. Note: If suspected, antidotal therapy must be given immediately.
Administration: I.M.
Solution for I.M. injection: Administer 1000 mcg/mL solution I.M. only
Administration: I.V.
Cyanokit®: Administer by I.V. infusion over 15 minutes; if repeat dose needed, administer second dose over 15 minutes to 2 hours
Monitoring Parameters
Vitamin B12, hematocrit, hemoglobin, reticulocyte count, red blood cell counts, folate and iron levels should be obtained prior to treatment and periodically during treatment.
Cyanide toxicity: Blood pressure and heart rate during and after infusion, serum lactate levels, venous-arterial PO2 gradient. Pretreatment levels may be useful as post infusion levels may be inaccurate.
Megaloblastic anemia: In addition to normal hematological parameters, serum potassium and platelet counts should be monitored during therapy, particularly in the first 48 hours of treatment.
Test Interactions
The following values may be affected, in vitro, following hydroxocobalamin 5 g dose. Interference following hydroxocobalamin 10 g dose can be expected to last up to an additional 24 hours. Note: Extent and duration of interference dependent on analyzer used and patient variability.
Falsely elevated:
Basophils, hemoglobin, MCH, and MCHC [duration: 12-16 hours]
Albumin, alkaline phosphatase, cholesterol, creatinine, glucose, total protein, and triglycerides [duration: 24 hours]
Bilirubin [duration: up to 4 days]
Urinalysis: Glucose, protein, erythrocytes, leukocytes, ketones, bilirubin, urobilinogen, nitrite [duration: 2-8 days]
Falsely decreased: ALT and amylase [duration: 24 hours]
Unpredictable:
AST, CK, CKMB, LDH, phosphate, and uric acid [duration: 24 hours]
PT (quick or INR) and aPTT [duration: 24-48 hours]
Urine pH [duration: 2-8 days]
May also interfere with colorimetric tests and cause hemodialysis machines to shut down due to false detection of a blood leak from the blood-like appearance of the solution.
Patient Education
Pernicious anemia may require monthly injections for life. Report skin rash; swelling, pain, or redness in extremities; or acute persistent diarrhea. Cyanokit®: May cause headache, redness of skin (can last up to 2 weeks; avoid exposure to sun while skin is red), skin lesions (can appear 7-28 days after infusion), and red urine (can last for 5 weeks).
Geriatric Considerations
Evidence exists that people, particularly elderly, whose serum cobalamin concentrations are <500 pg/mL, should receive replacement parenteral therapy. This recommendation is based upon neuropsychiatric disorders and cardiovascular disorders associated with lower sodium cobalamin concentrations.
Additional Information
Expert advice from a regional poison control center for appropriate use may be obtained (1-800-222-1222). Cyanide is a clear colorless gas or liquid with a faint bitter almond odor. Cyanide reacts with trivalent ions in cytochrome oxidase in the mitochondria leading to histotoxic hypoxia and lactic acidosis. Signs and symptoms of cyanide toxicity include headache, altered mental status, dyspnea, mydriasis, chest tightness, nausea, vomiting, tachycardia/hypertension (initially), bradycardia/hypotension (later), seizures, cardiovascular collapse, or coma.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
None reported
Mental Health: Effects on Psychiatric Treatment
None reported
Nursing: Physical Assessment/Monitoring
Teach patient appropriate injection technique and needle disposal and appropriate nutrition. Cyanide toxicity: Monitor blood pressure and heart rate during infusion.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Injection, powder for reconstitution:
Cyanokit®: 2.5 g [DSC], 5 g
Injection, solution: 1000 mcg/mL (30 mL)
References
Curry SC, Connor DA, and Raschke RA, “Effect of the Cyanide Antidote Hydroxocobalamin on Commonly Ordered Serum Chemistry Studies,” Ann Emerg Med, 1994, 24(1):65-7.
Holland MA and Kozlowski LM, “Clinical Features and Management of Cyanide Poisoning,” Clin Pharm, 1986, 5(9):737-41.
Huermer M, Simma B, Fowler B, et al, “Prenatal and Postnatal Treatment in Cobalamin C Defect,” J Pediatr, 2005, 147(4):469-72.
Kayser SR and Kurisu S, “Hydroxocobalamin in Nitroprusside Induced Cyanide Toxicity,” Drug Intell Clin Pharm, 1986, 20:365-6.
Lindenbaum J, Healton EB, Savage DG, et al, “Neuropsychiatric Disorders Caused by Cobalamin Deficiency in the Absence of Anemia or Macrocytosis,” N Engl J Med, 1988, 318(26):1720-8.
Olszewski AJ, Szostak WB, Bialkowska M, et al, “Reduction of Plasma Lipid and Homocysteine Levels by Pyridoxine, Folate, Cobalamin, Choline, Riboflavin, and Troxerutin in Atherosclerosis,” Atherosclerosis, 1989, 75(1):1-6.
Regland B, Gottfries CG, and Lindstedt G, “Dementia Patients With Low Serum Cobalamin Concentration: Relationship to Atrophic Gastritis,” Aging (Milano), 1992, 4(1):35-41.
Sauer SW and Keim ME, “Hydroxocobalamin: Improved Public Health Readiness for Cyanide Disasters,” Ann Emerg Med, 2001, 37(6):635-41.
International Brand Names
Lexi-Comp.com
Last full review/revision March 2012
Content last modified March 2012
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