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Index Terms

  • Vitamin B12a

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Intramuscular:

Generic: 1000 mcg/mL (30 mL)

Solution Reconstituted, Intravenous:

Cyanokit: 5 g (1 ea)

Brand Names: U.S.

  • Cyanokit

Pharmacologic Category

  • Antidote
  • Vitamin, Water Soluble


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, which is then excreted in the urine.


Urine (50% to 60% within initial 72 hours)

Half-Life Elimination

26-31 hours

Protein Binding

Significant; forms various cobalamin-(III) complexes

Special Populations: Gender

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

Use: Labeled Indications

IM injection: Treatment of pernicious anemia; treatment of vitamin B12 deficiency due to dietary deficiencies or malabsorption diseases, inadequate secretion of intrinsic factor, competition for vitamin B12 by intestinal parasites/bacteria, or inadequate utilization of B12 (eg, during neoplastic treatment)

IV infusion (Cyanokit®): Treatment of cyanide poisoning (known or suspected)


IM: Hypersensitivity to hydroxocobalamin or any component of the formulation

IV (Cyanokit®): There are no contraindications listed in the manufacturer’s labeling.

Dosing: Adult

Cyanide poisoning: IV: Note: If cyanide poisoning is suspected, antidotal therapy must be given immediately. Initial: 5 g as single infusion; may repeat a second 5 g dose depending on the severity of poisoning and clinical response. Maximum cumulative dose: 10 g.

Vitamin B12 deficiency: IM: Initial: 30 mcg once daily for 5-10 days; maintenance: 100-200 mcg once per month. Note: Larger doses may be required in critically-ill patients or if patient has neurologic disease, an infectious disease, or hyperthyroidism.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Vitamin B12 deficiency: IM: 100 mcg once daily for ≥2 weeks (total dose: 1-5 mg); maintenance: 30-50 mcg once per month

Cyanide poisoning (off-label use): IV: Note: If cyanide poisoning is suspected, antidotal therapy must be given immediately; Initial: 70 mg/kg (maximum: 5 g) as a single infusion; may repeat a second dose of 35 mg/kg depending on the severity of poisoning and clinical response (Shepherd, 2008).

Dosing: Renal Impairment

No dosage adjustments provided in manufacturer's labeling (has not been studied).

Dosing: Hepatic Impairment

No dosage adjustments provided in manufacturer's labeling (has not been studied).


IV infusion (Cyanokit®): Reconstitute each 5 g vial with 200 mL of NS using provided sterile transfer spike. If NS is unavailable, may use LR or D5W. Invert or rock each vial for 60 seconds prior to infusion; do not shake. Discard if solution is not dark red.


IM: Administer 1000 mcg/mL solution IM only

IV: Cyanokit®: Administer initial dose by IV infusion over 15 minutes; if a second dose is needed, administer the second dose over 15 minutes to 2 hours; hydroxocobalamin is chemically incompatible with sodium thiosulfate and sodium nitrite and separate IV lines must be used if concomitant administration is desired (the safety of coadministration is not established)


Stable in NS (preferred), LR, D5W

Y-site administration: Incompatible with ascorbic acid, blood products, sodium nitrite, sodium thiosulfate.


Solution for IM injection: Store at 20°C to 25°C (68°F to 77°F). Protect from light.

IV 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.

Drug Interactions

Chloramphenicol: May diminish the therapeutic effect of Vitamin B12. Monitor therapy

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]


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.

Adverse Reactions

IM injection: Frequency not defined:

Dermatologic: Exanthema (transient), itching

Gastrointestinal: Diarrhea (mild, transient)

Local: Injection site pain

Miscellaneous: Anaphylaxis, feeling of swelling of the entire body

IV infusion (Cyanokit®):


Cardiovascular: Blood pressure increased (18% to 28%)

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


Concerns related to adverse effects:

• Hypertension: Cyanide poisoning: Increased blood pressure (≥180 mm Hg systolic or ≥110 mm Hg diastolic) may occur with infusion; elevations usually noted at the beginning of the infusion, peak toward the end of the infusion, and return to baseline within 4 hours following the end of the infusion. May offset hypotension induced by nitrite administration or cyanide.

• 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.

Special populations:

• Fire victims: Fire victims may present with both cyanide and carbon monoxide poisoning. In this scenario, hydroxocobalamin is the agent of choice for cyanide intoxication since the traditional cyanide antidote that contains sodium nitrite produces methemoglobinemia and may worsen tissue hypoxia. Hydroxocobalamin can discolor the skin and exudates, complicating the assessment of burn severity.

Dosage form specific concerns:

• Cyanokit: Use caution or consider alternatives in patients known to be allergic to, or who have experienced anaphylaxis with hydroxocobalamin or cyanocobalamin. Collection of pretreatment blood cyanide concentrations does not preclude administration and should not delay administration in the emergency management of suspected or confirmed cyanide toxicity. Only pretreatment cyanide concentrations may be useful since postinfusion concentrations may be inaccurate. Treatment of cyanide poisoning should include external decontamination and supportive therapy. Use caution with concurrent use of other cyanide antidotes; safety has not been established. Consider consultation with a poison control center at 1-800-222-1222.

• Solution for IM 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 IM injection only.

Other warnings/precautions:

• Administration: Hydroxocobalamin may interfere with and/or trip alarms in patients who use hemodialysis machines that rely on colorimetric technology.

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 poisoning: Blood pressure and heart rate during and after infusion, serum lactate levels, venous-arterial PO2 gradient. Pretreatment cyanide 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.

Pregnancy Risk Factor


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. In general, medications used as antidotes should take into consideration the health and prognosis of the mother; antidotes should be administered to pregnant women if there is a clear indication for use and should not be withheld because of fears of teratogenicity (Bailey, 2003).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience diarrhea, nausea, vomiting, abdominal pain, dizziness, agitation, or acne. Have patient report immediately to prescriber signs of low potassium (muscle pain or weakness, muscle cramps, or an abnormal heartbeat), injection site pain or irritation, swelling of arms or legs, severe headache; black, tarry, or bloody stools; dysphagia; memory impairment; vision changes; eye pain; severe eye irritation; arrhythmia; or tachycardia (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.