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Sunday, July 27, 2025

Hydroxocobalamin


Hydroxocobalamin is a parenteral form of vitamin B12, a water-soluble vitamin essential for DNA synthesis, red blood cell formation, and neurological function. It is used primarily for the treatment and prevention of vitamin B12 deficiency, including pernicious anemia, and also has a critical role in cyanide poisoning management. It is preferred over other forms of vitamin B12 (like cyanocobalamin) in certain clinical settings due to its longer retention time in tissues, higher bioavailability, and better binding affinity to plasma proteins.

Pharmacological Classification

  • Class: Vitamin B12 analog

  • ATC Code: B03BA03

  • Drug Type: Water-soluble vitamin, hematinic, antidote (for cyanide poisoning)

  • Formulation: Injectable solution (IM or IV)

  • Chemical Formula: C₆₂H₈₉CoN₁₃O₁₅P

Mechanism of Action

Hydroxocobalamin acts as a coenzyme in various metabolic functions:

  1. Methylation of homocysteine to methionine:

    • Involves methionine synthase, essential for DNA and myelin synthesis

  2. Conversion of methylmalonyl-CoA to succinyl-CoA:

    • Aids in fatty acid and amino acid metabolism

In cyanide toxicity:

  • Hydroxocobalamin binds cyanide ions to form cyanocobalamin, which is excreted in urine, detoxifying the system rapidly.

Therapeutic Indications

Licensed Indications

  • Treatment of vitamin B12 deficiency due to:

    • Pernicious anemia (autoimmune gastritis)

    • Gastrectomy or ileal resection

    • Malabsorption (e.g., Crohn’s disease, coeliac disease)

    • Inborn errors (e.g., transcobalamin II deficiency)

    • Dietary insufficiency (rare)

  • Cyanide poisoning (emergency treatment)

    • Often part of cyanide antidote kits

Off-Label or Additional Uses

  • Nitric oxide–induced methemoglobinemia

  • Adjunct in Leber’s optic neuropathy

  • Congenital methylmalonic acidemia or homocystinuria

Formulations and Dosage

Available Forms

  • 1 mg/mL or 5 mg/mL ampoules/vials

  • Administered intramuscularly (IM) or intravenously (IV)

For Vitamin B12 Deficiency (IM)

Pernicious Anemia / Malabsorption

  • Loading dose: 1 mg IM every 2–3 days for 1–2 weeks

  • Maintenance: 1 mg IM every 2–3 months for life

Dietary Deficiency (e.g., veganism)

  • 1 mg IM monthly (if oral route contraindicated or malabsorbed)

For Cyanide Poisoning (IV)

  • Adults: 5 g IV infusion over 15 minutes (can repeat for total of 10 g)

  • Children: 70 mg/kg IV (max 5 g), infused over 15 minutes

May be repeated depending on severity of poisoning and response.

Pharmacokinetics

  • Absorption: 100% bioavailable via IM/IV routes

  • Distribution: High affinity to plasma proteins (transcobalamin II); stored in liver

  • Half-life: ~6 days (for B12 replenishment); 26–31 hours (cyanide binding)

  • Excretion: Renal (in urine as free B12 or cyanocobalamin)

  • Onset (cyanide antidote): Within minutes

Contraindications

  • Hypersensitivity to hydroxocobalamin or cobalamins

  • Caution in patients with Leber's optic atrophy (may worsen due to increased cyanide load)

  • Known cobalt hypersensitivity

Precautions

  • Allergic reactions: Risk of anaphylaxis, urticaria, bronchospasm

  • Color interference:

    • Red discoloration of urine, skin, and mucous membranes

    • Can interfere with colorimetric lab tests (e.g., creatinine, bilirubin, glucose)

  • Iron and folate status: Assess to rule out coexisting deficiencies

  • Hypokalemia may develop during treatment due to increased erythropoiesis

  • In cyanide treatment, rapid IV infusion may cause hypertensive episodes

Adverse Effects

Common (≥1%)

  • Injection site pain or redness

  • Headache

  • Nausea

  • Red discoloration of urine or skin

  • Itching

  • Dizziness

Uncommon to Rare

  • Anaphylaxis (IM/IV)

  • Acneiform rash

  • Erythema multiforme

  • Hypokalemia

  • Chest tightness

  • Pulmonary edema (high-dose IV use)

Drug Interactions

Hydroxocobalamin generally has few clinically significant drug interactions, but:

  • Chloramphenicol: May reduce response to B12 in anemia

  • Alcohol and oral contraceptives: Can reduce B12 absorption

  • Nitrous oxide anesthesia: Can inactivate B12, leading to deficiency

  • Lab test interference: Hydroxocobalamin (especially at high doses) can falsely alter:

    • Creatinine

    • Bilirubin

    • Glucose

    • Oxygen saturation (by interfering with co-oximetry)

Monitoring Parameters

  • CBC: For improvement in megaloblastic anemia

  • Serum B12: Reassess after initial replacement

  • Homocysteine and methylmalonic acid: Optional markers for B12 function

  • Serum potassium: Monitor due to erythropoiesis-induced shifts

  • Neurologic symptoms: Follow-up for resolution of paresthesias or cognitive changes

Use in Special Populations

Pregnancy

  • Category A (Australia)

  • No known teratogenicity; essential for fetal neural development

  • Recommended in maternal B12 deficiency

Breastfeeding

  • Safe

  • Hydroxocobalamin is excreted in breast milk, but in beneficial amounts

Pediatrics

  • Safe and effective in neonates, children with inherited B12 disorders or poisoning

Elderly

  • Common population for B12 replacement due to atrophic gastritis and absorption issues

Clinical Advantages Over Cyanocobalamin

  • Longer retention in tissues (less frequent dosing)

  • Better protein binding

  • Effective in cyanide toxicity

  • Does not require conversion via cyanide-detox pathways (vs. cyanocobalamin)

Comparison with Methylcobalamin and Cyanocobalamin

  • Methylcobalamin:

    • Active coenzyme form of B12

    • Often used in neuropathy

    • Oral, sublingual, or injectable forms

  • Cyanocobalamin:

    • Synthetic form

    • Requires conversion in body to active forms

    • Not suitable for cyanide poisoning

Hydroxocobalamin:

  • Injectable only

  • Preferred for parenteral therapy, severe deficiency, or cyanide toxicity

Patient Counseling Points

  • Explain possible red urine and skin discoloration (harmless)

  • Inform lab staff if recent high-dose administration (may affect test results)

  • For long-term therapy: Discuss lifetime adherence, especially in pernicious anemia

  • Instruct on IM injection technique if self-administered

  • Report breathlessness, edema, or allergic reactions immediately

Availability

  • Branded: Cyanokit® (for cyanide poisoning), Neo-B12®, Hydroxocobalamin Injection BP

  • Available in:

    • 1 mg/mL ampoules (IM use)

    • 2.5–5 g IV vials (cyanide antidote use)



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