Hydroxocobalamin


Generic Medicine Info
Indications and Dosage
Intramuscular
Leber's optic atrophy, Tobacco amblyopia
Adult: Initially, 1 mg daily for 2 weeks, followed by 1 mg twice weekly for as long as improvement is occurring. Maintenance: 1 mg every 1-3 months as required.

Intramuscular
Prophylaxis of macrocytic anaemia associated with vitamin B12 deficiency
Adult: In cases resulting from gastrectomy, ileal resection, certain malabsorption syndromes and nutritional deficiencies: 1 mg every 2 months or 3 months.
Child: Same as adult dose.

Intramuscular
Macrocytic anaemia associated with vitamin B12 deficiency, Pernicious anaemia
Adult: In cases without neurological involvement: Initially, 0.25-1 mg on alternate days for 1-2 weeks, then 0.25 mg weekly until blood count returns to normal. Maintenance: 1 mg every 2 months or 3 months. In cases with neurological involvement: Initially, 1 mg on alternate days, continued for as long as improvement occurs. Maintenance: 1 mg every 2 months. Dosage recommendations may vary among countries and individual products (refer to specific product guidelines).
Child: Same as adult dose.

Intravenous
Cyanide poisoning
Adult: Initially, 5 g via IV infusion over 15 minutes. Depending on the severity of poisoning and clinical response, a second dose of 5 g may be given via IV infusion over 15 minutes (for extremely unstable patients) to 2 hours. Max total dose: 10 g.
Child: Initially, 70 mg/kg (Max: 5,000 mg) via IV infusion over 15 minutes. Depending on the severity of poisoning and clinical response, a second dose of 70 mg/kg (Max: 5,000 mg) may be given via IV infusion over 15 minutes (for extremely unstable patients) to 2 hours. Max total dose: 140 mg/kg not exceeding 10,000 mg.
Reconstitution
IV: Reconstitute vial labelled as 2.5 g or 5 g with 100 mL or 200 mL of NaCl 0.9% inj, respectively, to provide a solution containing 25 mg/mL. Lactated Ringer's inj or dextrose 5% in water inj may also be used if NaCl 0.9% is unavailable. Gently invert or rock the vial for at least 30 seconds to mix. Do not shake. Reconstituted solution must be dark red.
Incompatibility
IV: Physically incompatible with diazepam, dobutamine, fentanyl, glyceryl trinitrate, pentobarbital, propofol, and thiopental Na. Chemically incompatible with ascorbic acid, Na thiosulfate, and Na nitrite. Simultaneous administration with blood products (fresh frozen plasma, platelet concentrate, whole blood and packed red cells) through the same IV line is not recommended.
Contraindications
IM: Hypersensitivity to hydroxocobalamin or cobalt.
Special Precautions
Concurrent infection, uraemia, or folic acid or iron deficiency may impair therapeutic response to vitamin B12. Renal impairment (particularly in patients who use haemodialysis machines that rely on colourimetric technology). Children. Pregnancy and lactation.
Adverse Reactions
Significant: Photosensitivity, allergic reactions (including anaphylaxis, angioneurotic oedema, urticaria, pruritus, and rash); cobalt sensitivity reactions (e.g. chronic or subacute allergic contact dermatitis, erythema multiforme-like eruption) which may be immediate or delayed to 12-72 hours after exposure; hypokalaemia, cardiac arrhythmias secondary to hypokalaemia; thrombocytosis (particularly in megaloblastic anaemia); transient increase in blood pressure, acute renal failure with acute tubular necrosis, renal impairment, and urine Ca oxalate crystals (IV).
Cardiac disorders: Ventricular extrasystoles (IV).
Eye disorders: Eye swelling, irritation, or redness (IV).
Gastrointestinal disorders: Nausea, diarrhoea, vomiting; abdominal discomfort, dysphagia, dyspepsia, haematochezia (IV).
General disorders and administration site conditions: Fever, chills, malaise, inj site reactions (e.g. pain, erythema, pruritus, induration, swelling, necrosis); infusion site reaction, peripheral oedema (IV).
Immune system disorders: Development of antibodies to hydroxocobalamin-transcobalamin II complex.
Investigations: Decreased percentage of lymphocytes (IV).
Nervous system disorders: Dizziness, tremor, headache, paraesthesia; memory impairment (IV).
Psychiatric disorders: Restlessness (IV).
Renal and urinary disorders: Chromaturia.
Respiratory, thoracic and mediastinal disorders: Dyspnoea, pleural effusion, chest discomfort, throat tightness, dry throat (IV).
Skin and subcutaneous tissue disorders: Acneiform and bullous eruptions; reversible red colouration of skin and mucous membranes (IV).
Vascular disorders: Hot flush.
IM/IV/Parenteral/SC: C
Patient Counseling Information
Avoid direct exposure to sunlight while skin remains discoloured. Hydroxocobalamin (a form of vitamin B12) contains cobalt; let your doctor know if you have a known cobalt allergy. If you develop allergic reactions (e.g. rash, hives, wheezing, difficulty breathing), inform your doctor immediately.
Monitoring Parameters
Confirm diagnosis of vitamin B12 deficiency before administration. Obtain sensitivity history from the patient prior to administration. Monitor vitamin B12, haematocrit, Hb, reticulocyte count, RBC count, folate and Fe levels (before and periodically during treatment); serum K and platelet counts (during treatment, particularly in the 1st 48 hours). For treatment of cyanide poisoning: blood pressure and heart rate (during and after infusion), serum lactate levels, venous-arterial partial pressure of oxygen (PO2) gradient; renal function (including BUN and serum creatinine; for ≥7 days after therapy). Assess for signs and symptoms of allergic reactions, including cobalt sensitivity-type reactions.
Drug Interactions
May decrease serum concentration with oral contraceptives. Effect in anaemia may be attenuated by parenteral chloramphenicol. May impair therapeutic response with folic acid. May reduce absorption with neomycin, aminosalicylic acid and its salts, colchicine, H2-antagonists, and omeprazole.
Lab Interference
May cause false elevation of bilirubin (for up to 4 days); albumin, alkaline phosphatase, cholesterol, creatinine, glucose, total protein, and triglycerides (for 24 hours); basophils, mean corpuscular Hb, mean corpuscular Hb concentration, and Hb (for 12-16 hours). May interfere with urinalysis resulting in false elevation of erythrocytes, glucose, ketones, leucocytes, nitrite, pH, protein, urobilinogen, and bilirubin (for 2-8 days). May cause false reduction of ALT and amylase (for 24 hours). Diagnostic microbiologic blood assays for vitamin B12 may be invalidated by methotrexate, pyrimethamine, and most anti-infectives.
Action
Description:
Mechanism of Action: Hydroxocobalamin is a synthetic form of vitamin B12. Vitamin B12 is essential for normal growth, maintenance of normal erythropoiesis, cell reproduction, nucleoprotein and myelin synthesis throughout the nervous system. In cyanide poisoning, hydroxocobalamin binds to cyanide ion by displacing it for the hydroxo ligand linked to the trivalent cobalt ion to form cyanocobalamin (non-toxic compound), which is excreted in the urine. Each hydroxocobalamin molecule can bind 1 cyanide ion.
Pharmacokinetics:
Distribution: Distributed into the liver, bone marrow and other tissues. Crosses the placenta and enters breast milk. Plasma protein binding: IM: Extensively bound to transcobalamin II; IV: Significantly bound to proteins and low molecular weight physiological compounds forming various cobalamin-(III) complexes.
Metabolism: Suspected to be converted to coenzyme form in the liver. Undergoes extensive enterohepatic recycling.
Excretion: IM: Via bile; urine (16-66%). IV: Via urine (60-70%). Elimination half-life: 26-31 hours.
Chemical Structure

Chemical Structure Image
Hydroxocobalamin

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 44475014, Hydroxocobalamin. https://pubchem.ncbi.nlm.nih.gov/compound/Hydroxocobalamin. Accessed Jan. 26, 2024.

Storage
IM: Store between 20-25°C. Protect from light. IV: Store intact vial between 15-30°C. Once reconstituted, may store up to 6 hours at ≤40°C. Do not freeze.
MIMS Class
Antidotes & Detoxifying Agents / Vitamin B-Complex / with C
ATC Classification
B03BA03 - hydroxocobalamin ; Belongs to the class of vitamin B12 (cyanocobalamin and analogues). Used in the treatment of anemia.
V03AB33 - hydroxocobalamin ; Belongs to the class of antidotes. Used in the management of cyanide poisoning.
References
Anon. Hydroxocobalamin. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 08/01/2024.

Anon. Vitamin B12. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 08/01/2024.

Buckingham R (ed). Vitamin B12 Substances. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 06/10/2023.

Cobalin-H 1,000 microgram/mL Injection (Amdipharm UK Limited). MHRA. https://products.mhra.gov.uk. Accessed 06/10/2023.

Cyanokit 2.5 g Powder for Solution for Infusion (Serb S.A.). MHRA. https://products.mhra.gov.uk. Accessed 06/10/2023.

Cyanokit Injection, Powder, Lyophilized, for Solution (BTG International Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 06/10/2023.

Hydroxocobalamin 1 mg/mL Solution for Injection (Mercury Pharmaceuticals Ltd). MHRA. https://products.mhra.gov.uk. Accessed 08/01/2024.

Hydroxocobalamin. Gold Standard Drug Database in ClinicalKey [online]. Elsevier Inc. https://www.clinicalkey.com. Accessed 06/10/2023.

Joint Formulary Committee. Hydroxocobalamin. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 06/10/2023.

Pfizer New Zealand Limited. Neo-B12 Injection 1,000 microgram/1 mL data sheet 31 October 2022. Medsafe. http://www.medsafe.govt.nz. Accessed 06/10/2023.

Vitamin B12 (Hydroxocobalamin, Cyanocobalamin): Advise Patients with Known Cobalt Allergy to be Vigilant for Sensitivity Reactions. Medicines & Healthcare products Regulatory Agency. https://www.gov.uk/drug-safety-update. Accessed 08/01/2024.

Disclaimer: This information is independently developed by MIMS based on Hydroxocobalamin from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2024 MIMS. All rights reserved. Powered by MIMS.com
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