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Medically reviewed by Last updated on Jul 3, 2019.


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Index Terms

  • Vitamin B12a

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intramuscular, as acetate:

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.


Vdss:Free cobalamins-(III): 280.7 to 349.5 L; Total cobalamins-(III): 21.8 to 25.6 L


Does not undergo metabolism


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

Half-Life Elimination

26 to 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: Note: Oral cobalamin (eg, cyanocobalamin) may be used for less severe deficiencies and/or maintenance therapy (Devalia 2014).

Mild: IM: 1,000 mcg once weekly (usual dose) or up to 3 times weekly, until deficiency is corrected, then follow with a maintenance dose of 1,000 mcg every other month; longer intervals (eg, every 3 months) for maintenance dosing may also be used (Devalia 2014; Schrier 2019).

Severe: IM: 1,000 mcg every other day for up to 3 weeks then evaluate need for continuation of every other day administration; then follow with a maintenance dose of 1,000 mcg every other month (Devalia 2014).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Verify dosing units due to large difference in dose for different indications; pediatric dosage may be presented in mg or mcg.

Cyanide poisoning (Cyanokit): Limited data available: Infants, Children, and Adolescents: Note: If cyanide poisoning is suspected, antidotal therapy must be given immediately: IV/Intraosseous: 70 mg/kg as a single infusion; maximum dose: 5,000 mg/dose; may repeat a second dose of 70 mg/kg (maximum dose: 5,000 mg/dose) depending on the severity of poisoning and clinical response (Mintegi 2013)

Pernicious anemia: Note: Concurrent folic acid supplementation may also be needed.

Mild to moderate: Infants, Children, and Adolescents: IM: Initial: 100 mcg/day for ≥2 weeks to target total dose range: 1,000 to 5,000 mcg; maintenance: 30 to 50 mcg/month.

Severe, complicated (eg, neurologic involvement): Multiple regimens reported, optimal dose not established: Infants, Children, and Adolescents: IM: Initial: 1,000 mcg daily for 7 days or every other day for 7 to 14 days (Devalia 2014; Goraya 2015; Orkin 2015; Skouby 1987; Stabler 2013); some experts suggest treatment until clinical improvement of neurologic symptoms observed (Devalia 2014); then follow with maintenance: 1,000 mcg every 2 to 3 months (Devalia 2014; Stabler 2013). For infants and young children, some experts have recommended doses as low as 50 to 100 mcg (Orkin 2015).

Vitamin B12 deficiency: Limited data available; dosing regimens variable:

Dietary deficiency: Infants (breastfed with vitamin B12 deficient mothers): Infants ≥6 weeks: IM: 400 mcg once (Bjørke-Monsen 2008; Bjørke-Monsen 2011; Torsvik 2015)

Malabsorption: Infants, Children, and Adolescents: IM: 250 to 1,000 mcg daily or every other day for 1 week, then weekly for 4 to 8 weeks, and then monthly for life; younger children should receive monthly doses of 100 mcg (Bjørke-Monsen 2011; Kliegman 2016; Stabler 2013). For infants and young children, some experts have recommended doses as low as 50 to 100 mcg (Orkin 2015).


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, Intraosseous: 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 and efficacy of coadministration are not established)


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 (Systemic): 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 turn both the plasma and urine a pinkish color and interfere with colorimetric or spectrophotometric tests (Wong 2016); may 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: Pruritus, skin rash (transient)

Gastrointestinal: Diarrhea (mild, transient)

Hypersensitivity: Anaphylaxis

Local: Pain at injection site

Miscellaneous: Swelling (feeling of swelling of the entire body)

IV infusion:


Cardiovascular: Increased blood pressure (18% to 28%)

Central nervous system: Headache (6% to 33%)

Dermatologic: Erythema (94% to 100%; may last up to 2 weeks), skin rash (20% to 44%; predominantly acneiform eruption; can appear 7 to 28 days after administration and usually resolves within a few weeks)

Gastrointestinal: Nausea (6% to 11%)

Genitourinary: Urine discoloration (100%; may last up to 5 weeks after administration), calcium oxalate nephrolithiasis (56% to 61%)

Hematologic & oncologic: Lymphocytopenia (8% to 17%)

Local: Infusion site reaction (6% to 39%)

Frequency not defined:

Cardiovascular: Chest discomfort, peripheral edema

Central nervous system: Dizziness, memory impairment, restlessness

Dermatologic: Pruritus, urticaria

Endocrine & Metabolic: Hot flash

Gastrointestinal: Abdominal distress, diarrhea, dyspepsia, dysphagia, hematochezia, vomiting

Hypersensitivity: Hypersensitivity reaction

Ophthalmic: Eye irritation, eye redness, swelling of eye

Respiratory: Dry throat, dyspnea, pharyngeal edema

<1%, postmarketing, and/or case reports: Acute renal failure, acute tubular necrosis, angioedema, calcium oxalate nephrolithiasis (Legrand 2016), methemoglobinemia (Jiwani 2017), renal insufficiency


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; monitor blood pressure during treatment.

• Photosensitivity: May cause photosensitivity; avoid direct sunlight while skin remains discolored.

• Renal injury: Renal injury, requiring hemodialysis for recovery in some cases, has been reported and may include acute renal failure with acute tubular necrosis, renal impairment, and urine calcium oxalate crystals; monitor renal function for ≥7 days following therapy.

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. Renal function, including but not limited to BUN and SCr, for ≥7 days following therapy.

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 Considerations

Hydroxocobalamin crosses the placenta (Huemer 2005; Roderique 2012).

Data on the use of hydroxocobalamin in pregnancy for the treatment of cyanide poisoning and cobalamin defects are limited (Brunel-Guitton 2010; Huemer 2005; Roderique 2012).

Cyanide crosses the placenta. Cyanide poisoning can be fatal for the pregnant female and fetus if untreated; treatment should not be withheld due to pregnancy. In general, medications used as antidotes should take into consideration the health and prognosis of the mother; antidotes should be administered to pregnant females 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, injection site irritation, heartburn, flushing, agitation, or acne. Have patient report immediately to prescriber signs of low potassium (muscle pain or weakness, muscle cramps, or an abnormal heartbeat); signs of kidney problems (urinary retention, hematuria, change in amount of urine passed, or weight gain); edema; severe headache; severe dizziness; passing out; black, tarry, or bloody stools; difficulty swallowing; memory impairment; vision changes; or severe eye irritation (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 health care 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.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.