Introduction
Cyanocobalamin is a synthetic form of vitamin B12, an essential water-soluble vitamin that plays a critical role in DNA synthesis, red blood cell formation, and neurological function. As one of the most commonly prescribed vitamin B12 formulations, it is used to prevent and treat vitamin B12 deficiency states. Cyanocobalamin requires conversion to active coenzyme forms (methylcobalamin and adenosylcobalamin) in the body to exert its physiological effects.
Mechanism of Action
Cyanocobalamin functions as a cofactor for two essential enzymatic reactions: (1) methionine synthase, which converts homocysteine to methionine while simultaneously converting N5-methyltetrahydrofolate to tetrahydrofolate, and (2) methylmalonyl-CoA mutase, which converts methylmalonyl-CoA to succinyl-CoA. These reactions are crucial for DNA synthesis, red blood cell maturation, myelin synthesis, and energy production. Vitamin B12 deficiency impairs these metabolic pathways, leading to megaloblastic anemia and neurological dysfunction.
Indications
- Treatment of documented vitamin B12 deficiency
- Pernicious anemia (with intrinsic factor deficiency)
- Vitamin B12 deficiency due to dietary insufficiency
- Malabsorption syndromes (including gastric resection, ileal resection, Crohn's disease)
- Tapeworm infestation (Diphyllobothrium latum)
- Prophylactic use in patients with total gastrectomy or ileectomy
- Nutritional supplementation in strict vegans and elderly patients with inadequate dietary intake
Dosage and Administration
Initial treatment for severe deficiency:- 1000 mcg IM daily for 7 days, then
- 1000 mcg IM every week for 4 weeks, then
- 1000 mcg IM every month indefinitely
- Oral: 1000-2000 mcg daily
- Intranasal: 500 mcg once weekly
- IM: 1000 mcg monthly
- Renal impairment: No dosage adjustment required
- Hepatic impairment: No dosage adjustment required
- Pediatrics: 30-50 mcg IM daily for 2+ weeks, then 100 mcg monthly
- Elderly: Standard adult dosing; monitor for adequate response
Pharmacokinetics
Absorption: Oral absorption is limited by intrinsic factor-mediated process in the terminal ileum (approximately 1-2% of oral dose). IM administration provides complete bioavailability. Intranasal administration provides variable absorption (approximately 8-10% of dose). Distribution: Widely distributed to body tissues, with highest concentrations in liver, kidney, and adrenal glands. Crosses placenta and enters breast milk. Metabolism: Converted in tissues to active coenzymes methylcobalamin and adenosylcobalamin. The cyanide moiety is released and converted to thiocyanate. Elimination: Primarily excreted in urine (50-98% of dose). Biliary excretion occurs with enterohepatic recirculation. Elimination half-life: approximately 6 days.Contraindications
- Hypersensitivity to cyanocobalamin or any component of the formulation
- Hereditary optic neuropathy (Leber's disease) - may cause rapid optic atrophy
- Cobalt allergy (relative contraindication)
Warnings and Precautions
- Anaphylactic reactions have been reported (rare)
- Hypokalemia may occur during initial treatment of severe megaloblastic anemia
- May mask symptoms of folate deficiency
- Use caution in patients with renal impairment due to potential thiocyanate accumulation
- Polycythemia vera may be unmasked during treatment
- Patients with pernicious anemia require lifelong therapy
Drug Interactions
- Chloramphenicol: May decrease therapeutic response to cyanocobalamin
- Colchicine: May impair vitamin B12 absorption
- Aminosalicylic acid: May decrease absorption and serum levels
- Proton pump inhibitors/H2 blockers: May reduce vitamin B12 absorption
- Metformin: Long-term use may reduce vitamin B12 absorption
- Oral contraceptives: May decrease serum vitamin B12 levels
Adverse Effects
Common (≥1%):- Mild diarrhea
- Itching
- Rash
- Headache
- Injection site reactions (pain, redness, swelling)
- Anaphylaxis
- Pulmonary edema
- Congestive heart failure (with rapid administration)
- Hypokalemia
- Peripheral vascular thrombosis
- Polycythemia
Monitoring Parameters
- Hematologic parameters: CBC with indices (reticulocyte count initially)
- Serum vitamin B12 levels (target >300 pg/mL)
- Methylmalonic acid and homocysteine levels (functional indicators)
- Potassium levels during initial treatment
- Neurological examination and symptoms
- Iron studies (concomitant iron deficiency common)
- Renal function in patients with pre-existing renal disease
Patient Education
- Importance of adherence to prescribed regimen, especially for lifelong therapy
- Recognize signs of hypokalemia (muscle weakness, cramps, palpitations)
- Dietary sources of vitamin B12 (animal products, fortified cereals)
- Report any signs of allergic reaction (rash, itching, swelling, difficulty breathing)
- Do not self-treat with over-the-counter B12 without medical supervision
- Regular follow-up appointments for monitoring
- Proper storage of medication (room temperature, protected from light)
References
1. Green R. Vitamin B12 deficiency from the perspective of a practicing hematologist. Blood. 2017;129(19):2603-2611. 2. Office of Dietary Supplements - Vitamin B12. National Institutes of Health. Updated June 2023. 3. Cyanocobalamin [package insert]. Lake Forest, IL: Hospira Inc; 2022. 4. Andrès E, Serraj K, Zhu J, Vermorken AJ. The pathophysiology of elevated vitamin B12 in clinical practice. QJM. 2013;106(6):505-515. 5. Langan RC, Goodbred AJ. Vitamin B12 deficiency: recognition and management. Am Fam Physician. 2017;96(6):384-389. 6. Wolffenbuttel BHR, Wouters HJCM, Heiner-Fokkema MR, van der Klauw MM. The many faces of cobalamin (vitamin B12) deficiency. Mayo Clin Proc Innov Qual Outcomes. 2019;3(2):200-214.