Vitamin B12 - Drug Monograph

Introduction

Vitamin B12 (cobalamin) is an essential water-soluble vitamin that plays a crucial role in neurological function, red blood cell formation, and DNA synthesis. As a vital nutrient that cannot be synthesized by the human body, it must be obtained through dietary sources or supplementation. Vitamin B12 deficiency can lead to significant hematological and neurological complications, making proper understanding of this nutrient essential for healthcare professionals and patients alike.

Mechanism of Action

Vitamin B12 functions as a coenzyme in two critical metabolic pathways:

• As methylcobalamin: Serves as a cofactor for methionine synthase in the conversion of homocysteine to methionine, which is essential for DNA synthesis and methylation reactions
• As adenosylcobalamin: Functions as a cofactor for methylmalonyl-CoA mutase in the conversion of methylmalonyl-CoA to succinyl-CoA, which is important for energy production

These enzymatic reactions are essential for:

• Erythropoiesis and normal red blood cell maturation
• Maintenance of myelin sheath integrity in the nervous system
• DNA synthesis and cellular replication
• Homocysteine metabolism

Indications

• Treatment of documented vitamin B12 deficiency
• Pernicious anemia
• Nutritional vitamin B12 deficiency

• Prophylaxis in patients with malabsorption syndromes (Crohn's disease, celiac disease)
• Post-gastrectomy or bariatric surgery patients
• Chronic pancreatic insufficiency
• Vegan or strict vegetarian diets with inadequate B12 intake
• Elderly patients with atrophic gastritis
• Patients on long-term proton pump inhibitors or metformin therapy

Dosage and Administration

• Adults: 1000-2000 mcg daily for deficiency treatment; 50-100 mcg daily for maintenance
• Children: Dosing based on age and severity of deficiency

• Initial treatment: 1000 mcg IM or deep subcutaneous daily for 7 days
• Maintenance: 1000 mcg IM monthly (range: 100-1000 mcg monthly)
• Severe deficiency with neurological symptoms: 1000 mcg IM daily for 7-14 days, then twice weekly for 1 month

• Geriatric: No dosage adjustment required
• Renal impairment: No dosage adjustment required
• Hepatic impairment: No dosage adjustment required
• Pregnancy: Recommended dietary allowance increases to 2.6 mcg daily
• Lactation: Recommended dietary allowance increases to 2.8 mcg daily

Pharmacokinetics

• Requires intrinsic factor (IF) for absorption in the terminal ileum
• Oral bioavailability: Approximately 1.2% without IF; up to 50-60% with IF
• IM administration: Rapid and complete absorption

• Bound to transcobalamin I, II, and III in plasma
• Stored primarily in the liver (up to 2-5 mg total body stores)
• Crosses placenta and enters breast milk

• Hepatic metabolism via enzymatic decyanation
• Converted to active forms: methylcobalamin and adenosylcobalamin

• Primarily excreted in bile; undergoes enterohepatic recirculation
• Renal excretion increases with higher plasma concentrations
• Half-life: Approximately 6 days

Contraindications

• Hypersensitivity to cobalt or cobalamin
• History of anaphylactic reaction to vitamin B12 preparations
• Leber's disease (hereditary optic nerve atrophy) - may accelerate atrophy

Warnings and Precautions

• Hypokalemia: May occur during initial treatment of severe deficiency due to increased erythropoiesis
• Polycythemia vera: Use with caution as it may stimulate erythropoiesis
• Folate deficiency: Vitamin B12 may correct hematological abnormalities while masking ongoing neurological damage from B12 deficiency
• Iron deficiency: May become apparent during treatment as erythropoiesis increases
• Allergic reactions: Although rare, anaphylactoid reactions have been reported

Drug Interactions

• Chloramphenicol: May decrease the hematological response to vitamin B12
• Proton pump inhibitors/H2 receptor antagonists: May decrease absorption of protein-bound vitamin B12 from food
• Metformin: Long-term use may reduce vitamin B12 absorption
• Colchicine: May reduce vitamin B12 absorption
• Aminosalicylic acid: May reduce vitamin B12 absorption
• Oral contraceptives: May decrease serum vitamin B12 concentrations

Adverse Effects

• Mild diarrhea
• Itching
• Rash
• Headache

• Hypokalemia (during initial treatment)
• Peripheral vascular thrombosis
• Pulmonary edema
• Congestive heart failure (in patients with pre-existing cardiac disease)
• Anaphylactoid reactions (rare)

• Pain, redness, or swelling at injection site
• Mild, transient diarrhea

Monitoring Parameters

• Baseline:

- Complete blood count with indices - Serum vitamin B12 level - Methylmalonic acid (MMA) level - Homocysteine level (if available) - Serum potassium level

• During Treatment:

- Hematocrit/hemoglobin weekly until normalized - Reticulocyte count (should increase within 3-5 days of initiation) - Potassium levels during first week of treatment - Neurological assessment regularly - Serum MMA and homocysteine to assess treatment response

• Long-term Monitoring:

- Annual B12 levels in patients on chronic therapy - Periodic assessment of neurological function

Patient Education

• Explain the importance of adherence to prescribed regimen
• Dietary counseling on B12-rich foods (animal products, fortified cereals)
• For oral supplementation: Take with food to enhance absorption
• Report any signs of hypokalemia (muscle weakness, cramping)
• Inform all healthcare providers about B12 supplementation
• Understand that treatment may be lifelong for certain conditions
• Recognize that improvement in neurological symptoms may be slow and incomplete
• Store supplements properly away from light and moisture

References

1. Green R. Vitamin B12 deficiency from the perspective of a practicing hematologist. Blood. 2017;129(19):2603-2611. 2. Langan RC, Goodbred AJ. Vitamin B12 Deficiency: Recognition and Management. Am Fam Physician. 2017;96(6):384-389. 3. Office of Dietary Supplements - Vitamin B12. National Institutes of Health. Updated June 2021. 4. Andrès E, et al. Vitamin B12 (cobalamin) deficiency in elderly patients. CMAJ. 2004;171(3):251-259. 5. Shipton MJ, Thachil J. Vitamin B12 deficiency - A 21st century perspective. Clin Med (Lond). 2015;15(2):145-150. 6. Vitamin B12. In: Lexi-Drugs. Hudson, OH: Lexicomp, 2022. 7. Stabler SP. Vitamin B12 deficiency. N Engl J Med. 2013;368(2):149-160. 8. Drug Facts and Comparisons. Facts & Comparisons [database online]. St. Louis, MO: Wolters Kluwer Health, 2022.