Hydroxocobalamin or Vitamin B-12a is used in the treatment and prevention of vitamin B12 deficiency anemia and neurological manifestations caused by B-12 deficiency. It is also used in the treatment and prevention of cyanide poisoning. It is considered to be a more effective and drug choice in the treatment of Vitamin B-12 deficiency anemia when compared to cyanocobalamin.

Hydroxocobalamin Uses:

• IM injection:
  • It is used in the 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 known or suspected cyanide poisoning.

Hydroxocobalamin Dose in Adults

Hydroxocobalamin Dose in the treatment of Cyanide poisoning: IV:

Note: If cyanide poisoning is suspected, antidotal therapy must be given as early as possible.

• Initial: 5 g as a single infusion;
• The dose may be repeated. The second dose is given as 5 gms, depending on the severity of poisoning and clinical response.
  • Maximum cumulative dose: 10 g.

Hydroxocobalamin Dose in the treatment of Vitamin B12 deficiency:

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

• Mild:

  • IM: 1,000 mcg once in a weak  (usual dose) or up to thrice times a week, until the 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.

• Severe:

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

Hydroxocobalamin Dose in Childrens

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

Dose in the treatment of Cyanide poisoning (Cyanokit):

• 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;
  • The maximum dose:
    • 5,000 mg/dose;
  • The dose may be repeated. The second dose is administered in a dose of 70 mg/kg (maximum dose: 5,000 mg/dose) depending on the severity of poisoning and clinical response.

Hydroxocobalamin Dose in the treatment of 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 or more to target total dose range: 1,000 to 5,000 mcg;
    • maintenance: 30 to 50 mcg/month.

• Severe, complicated (e.g, neurologic involvement):

  • Infants, Children, and Adolescents: IM:
    • Initial: 1,000 mcg daily for a weak or every other day for 7 to 14 days;
    • Some experts suggest treatment until clinical improvement of neurologic symptoms observed; then follow with maintenance: 1,000 mcg every 2 to 3 months.
    • For infants and young children, some experts have recommended doses as low as 50 to 100 mcg.

Hydroxocobalamin Dose in the treatment of Vitamin B12 deficiency:

• Dietary deficiency:

  • Infants (breastfed with vitamin B-12 deficient mothers):
    • Infants ≥6 weeks:
      • IM: 400 mcg once.

• 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.
    • For newborns and young children, some experts have recommended doses as low as 50 to 100 mcg.

Hydroxocobalamin Pregnancy Category: C

• Hydroxocobalamin crosses over to the placenta.
• Limited data are available on the use and safety of hydroxocobalamin during pregnancy to treat cyanide poisoning or cobalamin defects.
• The placenta is crossed by Cyanide
• If left untreated, cyanide poisoning can cause death in the pregnant woman and her baby.
• Antidotes used in general should be considered the health and prognosis for the mother.
• Pregnant women should only be given antidotes if they have a clear indication and should not be withheld due to fears of teratogenicity.

Hydroxocobalamin use during breastfeeding:

• Breast milk contains hydroxocobalamin.
• The maternal serum levels of endogenous vitamin B milk are comparable to the mothers'.
• Manufacturers do not recommend breastfeeding during treatment for maternal cyanide poisoning.
• Hydroxocobalamin can be used to treat anemia and is compatible with breastfeeding.

Dose in Kidney Disease:

The manufacturer's labeling doesn't provide any dosage adjustments (has not been studied).

Dose in Liver disease:

The manufacturer's labeling doesn't provide any dosage adjustments (has not been studied).

Side effects of Hydroxocobalamin following 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)

Common Side Effects of Hydroxocobalamin following IV infusion:

• Cardiovascular:

  • Increased Blood Pressure

• Central Nervous System:

  • Headache

• Dermatologic:

  • Erythema
  • Skin Rash

• Gastrointestinal:

  • Nausea

• Genitourinary:

  • Urine Discoloration
  • Calcium Oxalate Nephrolithiasis

• Hematologic & Oncologic:

  • Lymphocytopenia

• Local:

  • Infusion Site Reaction

Frequency of side effects 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

Contraindications to Hydroxocobalamin:

IM:

• Hypersensitivity to hydroxocobalamin and any component of the formulation

IV (Cyanokit):

• The manufacturer has not listed any contraindications.

Warnings and precautions

• Hypertension:

  • Cyanide poisoning
    • Infusions can cause an increase in blood pressure of >=180 mm Hg Systolic or >=110mm Hg Diastolic.
    • Blood pressure elevations are usually noticed at the beginning of an infusion. They peak towards the end and then return to baseline within four hours.
    • Hypotension may be compensated by nitrite or cyanide administration. Monitor blood pressure during treatment.

• Photosensitivity

  • Photosensitivity can occur; avoid direct sunlight if the skin is still discolored.

• Renal injury:

  • Some cases of renal injury have required hemodialysis to recover.
  • These include acute tubular necrosis, renal impairment and renal damage.
  • After treatment, monitor renal function for seven days or longer.

• Anemia:

  • Use it in the right way:
    • Folic acid alone will not prevent neurologic manifestations from vitamin B-12 deficiency. Vitamin B-12 must also be taken.
    • Folic acid can also be used to prevent anemia and cause spinal cord degeneration.

• Polycythemia vera

  • Vitamin B 12 deficiencies can mask signs of polycythemia. Vitamin B-12 administration could unmask the condition.

Hydroxocobalamin (vitamin B12a supplement and cyanide antidote): Drug Interaction

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 PO gradient.
• Pretreatment cyanide levels may be useful as post-infusion levels may be inaccurate.
• Renal function, not limited to BUN and SCr, for a weak or more than a weak 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.

How to administer Hydroxocobalamin?

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 not compatible  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)

Mechanism of action of Hydroxocobalamin:

• The precursor to cyanocobalamin, vitamin B12a is hydroxocobalamin.
• Cyanocobalamin is a coenzyme that performs a variety of metabolic functions including fat and carbohydrate metabolism, protein synthesis, cell replication, and hematopoiesis.
• Each hydroxocobalamin molecule may bind one cyanide by dislodging it for the hydroxoligand linked with the trivalent cobalt.
• This forms cyanocobalamin which is then excreted from the urine.

Pharmacodynamics and Pharmacokinetics Following IV administration of Cyanokit:

Protein binding:

• Significant; forms various cobalamin-(III) complexes

Metabolism:

• Does not undergo metabolism

Half-life elimination:

• 26 to 31 hours

Excretion:

• Urine (50 percent  to 60 percent  within initial 72 hours)

International Brands of Hydroxocobalamin:

• Cyanokit
• Hydro Cobex
• Hydroxy Cobal
• Aquo-Cytobion
• Articlox
• B12 Depot-Rotexmedica
• B12-Depot-Hevert
• B12Depot-Vicotrat
• Behepan
• Benzoral
• Berubi-long
• Bradirubra
• Cobalamin Depot
• Cobalin-H
• Cobalparen
• Cobalvit
• Cohemin Depot
• Cyano Kit
• Cyanokit
• Cynomin H
• Depovit-B 12
• Depovit-B12
• Dodecavit
• Doleven
• Dosixbe
• Emicobal
• Forta B 5.000
• Forta B12
• Hepavit
• Hycomin
• Hydrocobamine
• Hydroxo 5.000
• Hydroxo-B 12
• Idroxocobalamina
• Lanobin
• Lisoneurin
• Lophakomp-B 12 Depot
• Megamilbedoce
• Minedrox
• Neo-B12
• Neo-Cytamen
• Novidroxin
• Novobedouze
• OH B12
• OHB12
• Rasedon 500
• Rubranova
• Tarupain
• Twelvmin-s
• Vibeden
• Vitamin B12 Depot
• Vitamin B12-Depot-Injektopas
• Vitarubin-Depot
• Westhidroxo

Hydroxocobalamin Brands Names in Pakistan:

There is no brand available in Pakistan.