Cyanocobalamin

Generic Name

Cyanocobalamin

Synonyms and Identifiers

Vitamin B12

Cobalamin

Hydroxycobalamin (closely related but different formulation)

Methylcobalamin and Adenosylcobalamin (active forms of vitamin B12 in the body)

Brand Names

Nascobal

Cytamen

Rubramin

Cobalin-H

Depo-Cobolin

Becozyme (in multivitamin preparations)

Also available in generic injectable, oral, nasal, and sublingual formulations

Drug Class

Water-soluble vitamin

Essential nutrient

Hematopoietic vitamin

Nutritional supplement

Mechanism of Action

Cyanocobalamin serves as a synthetic form of vitamin B12, which is converted in vivo to its active forms—methylcobalamin and 5-deoxyadenosylcobalamin

It is essential for two major enzymatic reactions:

1. Methylation of homocysteine to methionine (via methionine synthase)

2. Conversion of methylmalonyl-CoA to succinyl-CoA (via methylmalonyl-CoA mutase)
   These reactions are necessary for DNA synthesis, myelin synthesis and maintenance, red blood cell formation, and cellular energy metabolism
   Vitamin B12 also plays a critical role in neurological function and fatty acid metabolism

Sources and Absorption

Naturally found in animal products (meat, eggs, dairy, fish)

Absorption requires intrinsic factor (IF) secreted by gastric parietal cells

Absorbed in the ileum as a complex with intrinsic factor

Passive absorption also occurs with high oral doses (independent of IF but less efficient)

Indications

Approved Therapeutic Uses

Treatment and prevention of vitamin B12 deficiency

Pernicious anemia

Megaloblastic anemia secondary to B12 deficiency

B12 deficiency due to malabsorption syndromes (e.g., atrophic gastritis, ileal resection, Crohn’s disease)

Nutritional deficiency (vegans, elderly, alcoholics)

Post-gastrectomy or bariatric surgery B12 supplementation

Fish tapeworm infection (Diphyllobothrium latum) or bacterial overgrowth syndrome

Drug-induced deficiency (e.g., from metformin, proton pump inhibitors, or nitrous oxide exposure)

Congenital transcobalamin II deficiency

Optic neuropathy due to tobacco or Leber's disease (supportive role)

B12 replacement in strict vegetarians or vegans

Off-Label and Supportive Uses

Cognitive decline, dementia (uncertain benefit unless B12-deficient)

Neuropathy (e.g., diabetic neuropathy)

Fatigue or weakness of unclear etiology (only if deficient)

Male infertility (with low B12)

Adjunct in homocystinuria management

Supportive therapy in cyanide poisoning (as hydroxocobalamin)

Hair loss treatment (with other micronutrients)

Adjunct in tinnitus, depression, or glossitis related to B12 deficiency

Dosage and Administration

Oral B12 Replacement

Typical dose: 1000–2000 mcg/day

Used in mild deficiency or in individuals with intact absorption

High doses used to overcome poor IF-dependent absorption

Can maintain B12 levels even in pernicious anemia when used consistently

Intramuscular (IM) or Subcutaneous (SC) Injection

Pernicious anemia: 1000 mcg IM daily for 7 days, then every other day for 1–2 weeks, then weekly for 1 month, then monthly for life

Severe deficiency with neurological involvement: 1000 mcg IM every day or every other day for 1–2 weeks, then transition to maintenance

Maintenance: 1000 mcg monthly IM/SC lifelong if due to irreversible cause

Alternative regimens exist depending on region and protocol

Nasal Spray (Nascobal)

500 mcg intranasally once weekly

For maintenance only, not suitable for initial correction

Do not administer within 1 hour of hot food or beverages

Sublingual/Buccal Tablets

Doses typically range 500–2000 mcg/day

May be as effective as oral tablets

Preferred by some patients for convenience

Pediatric Dosing

Based on age and indication

Typical: 30–50 mcg/day orally

In congenital deficiencies: parenteral route preferred initially

Parenteral routes are preferred in cases of severe deficiency, neurologic symptoms, pernicious anemia, or malabsorption

Oral route may be sufficient for maintenance in compliant patients

Pharmacokinetics

Absorption: Dependent on intrinsic factor for physiological doses; passive diffusion at high doses

Onset of action: hematologic improvement within days

Peak effect: Neurologic response may take weeks

Distribution: Stored in liver (up to 2–5 mg); sufficient for 3–5 years in healthy individuals

Excretion: Renal (low doses), increased loss in deficiency states

Contraindications

Known hypersensitivity to cyanocobalamin or cobalt

Early Leber's optic atrophy (risk of optic nerve damage)

Caution in polycythemia vera (B12 may stimulate erythropoiesis)

Warnings and Precautions

Hypokalemia may occur during treatment of severe anemia due to rapid cell production

Unmasking of folate deficiency—correct both if present

Allergic reactions (rare): rash, itching, anaphylaxis in injectable form

Injection site reactions or pain possible

Repeated exposure to preservatives in injectable B12 may cause sensitivity

Chronic use of metformin, colchicine, antacids, and PPIs may increase risk of deficiency

Caution in patients receiving concurrent folic acid: B12 must be corrected first to prevent masking of neurologic damage

Adverse Effects

Common

Injection site pain

Mild diarrhea

Headache

Nausea

Uncommon

Rash or urticaria

Dizziness

Anxiety

Pruritus

Rare but Serious

Anaphylaxis (parenteral route)

Hypokalemia

Thrombocytosis or polycythemia in early stages

Peripheral vascular thrombosis

Optic nerve damage in Leber’s disease

Pregnancy and Lactation

Pregnancy Category A (US FDA)

Considered safe during pregnancy

Essential for fetal neural development

Deficiency during pregnancy increases risk of neural tube defects and preterm birth

Lactation

Excreted into breast milk

Supplementation may be needed in B12-deficient breastfeeding mothers to prevent deficiency in the infant

Infants of vegetarian mothers should be monitored closely

Drug Interactions

Metformin

Long-term use may reduce B12 absorption—monitor levels regularly

Proton Pump Inhibitors (PPIs) and H2 Receptor Antagonists

Reduce gastric acid required for release of B12 from food proteins

Monitor in long-term use

Chloramphenicol

May interfere with hematologic response to B12

Alcohol

Chronic use impairs absorption and storage of B12

Oral Contraceptives

May lower serum levels of B12-binding proteins—clinical significance is unclear

Potassium Supplements

Can reduce B12 absorption by interfering with bacterial synthesis in the gut

Nitrous Oxide (N2O)

Oxidizes B12, rendering it inactive—can precipitate deficiency after anesthesia exposure

Monitoring Parameters

Baseline and follow-up serum B12 levels

Methylmalonic acid (MMA) and homocysteine levels if borderline deficiency suspected

Reticulocyte count (should rise within 3–5 days of initiating therapy)

Hemoglobin, hematocrit, and MCV (macrocytosis resolves in weeks)

Neurologic function

Serum potassium in initial phases of correction

Folate levels to exclude concurrent folate deficiency

Counseling Points

Explain the lifelong nature of treatment in pernicious anemia

Teach correct injection technique if self-administered

Advise against abrupt discontinuation in deficiency states

Nasal spray not for initial correction or for patients with nasal pathology

Oral B12 must be taken consistently and in adequate doses for efficacy

Encourage dietary intake of B12 if not contraindicated

Alert healthcare provider if signs of numbness, tingling, fatigue, or glossitis return

Comparative Notes

Cyanocobalamin vs Hydroxocobalamin

Hydroxocobalamin has longer duration of action and may require less frequent injections

Used as first-line in UK; cyanocobalamin more common in the US

Hydroxocobalamin preferred in cyanide poisoning

Cyanocobalamin vs Methylcobalamin

Methylcobalamin is a biologically active form

Some studies suggest better neurological outcomes, though both are effective for deficiency correction

Methylcobalamin available in oral and injectable forms in Asia and Europe

Cyanocobalamin vs Oral B12

Oral therapy effective if compliance is good and malabsorption is not severe

Parenteral route is essential in severe deficiency or neurologic involvement

Legal and Regulatory Status

Prescription and over-the-counter (depending on dose and country)

Listed in WHO Model List of Essential Medicines

Approved by FDA, EMA, MHRA, and global agencies