What is the recommended dose of vitamin B12 (cyanocobalamin) for a patient with vitamin B12 deficiency and anemia?

Vitamin B12 Dosing for Deficiency with Anemia

For vitamin B12 deficiency with anemia, administer hydroxocobalamin 1 mg intramuscularly three times weekly for 2 weeks, followed by maintenance therapy of 1 mg intramuscularly every 2-3 months for life. 1, 2

Initial Treatment Protocol

Without Neurological Involvement

• Hydroxocobalamin 1 mg IM three times weekly for 2 weeks (or daily for days 1-10) 1, 2
• This loading phase ensures rapid correction of deficiency and replenishment of body stores 1
• After the initial 2-week period, transition immediately to maintenance therapy 1, 2

With Neurological Involvement

• Hydroxocobalamin 1 mg IM on alternate days until no further improvement 1, 2
• Neurological symptoms (paresthesias, numbness, cognitive changes, gait disturbances) require more aggressive initial treatment to prevent irreversible damage 1, 2
• Once symptoms stabilize, transition to maintenance with 1 mg IM every 2 months 1, 2

Maintenance Therapy

Standard maintenance: Hydroxocobalamin 1 mg IM every 2-3 months for life 1, 2

• Some patients may require monthly dosing (1000 mcg IM monthly) to meet metabolic requirements, particularly those with persistent symptoms, post-bariatric surgery patients, or extensive ileal disease 2, 3
• Monthly dosing is an acceptable alternative that may better maintain adequate B12 levels in certain patients 2, 3

Oral Alternative

Oral cyanocobalamin 1000-2000 mcg daily is therapeutically equivalent to parenteral therapy for most patients, including those with malabsorption 1, 4, 5, 3

• A recent 2024 prospective cohort study demonstrated that oral cyanocobalamin 1000 mcg daily effectively reversed B12 deficiency in pernicious anemia patients, with 88.5% no longer deficient after 1 month 4
• Oral therapy works through passive absorption (1-2% of dose absorbed regardless of intrinsic factor) 4, 5
• Consider oral therapy for patients who prefer it, have difficulty accessing injections, or have needle phobia 4, 5

Critical Formulation Considerations

Use hydroxocobalamin or methylcobalamin instead of cyanocobalamin in patients with renal dysfunction 1, 2

• Cyanocobalamin requires renal clearance of the cyanide moiety and is associated with increased cardiovascular events (HR 2.0) in diabetic nephropathy 1, 2
• The FDA label notes that cyanocobalamin is the only B12 preparation available in the United States for injection, but hydroxocobalamin is preferred in guidelines 6, 2

Monitoring Strategy

• Check serum B12, homocysteine, and methylmalonic acid at 3 months, then every 3 months until stabilization 1, 2
• Once stabilized, monitor annually 1, 2
• Target homocysteine <10 μmol/L for optimal outcomes 1, 2
• Complete blood count should show normalization of hemoglobin within 2 months and MCV improvement 4, 7
• Reticulocyte count should increase within 5-7 days of treatment initiation 6, 7

Critical Pitfalls to Avoid

Never administer folic acid before or without adequate B12 treatment 1, 2, 6

• Folic acid can mask the anemia while allowing irreversible neurological damage to progress, potentially precipitating subacute combined degeneration of the spinal cord 1, 2, 6
• If folate deficiency coexists, start B12 first, then add folic acid 1 mg orally daily for 3 months once B12 treatment has begun 2

Do not discontinue therapy even if levels normalize 1, 2

• Patients with malabsorption require lifelong therapy 1, 2
• Stopping injections after symptom improvement can lead to irreversible peripheral neuropathy 2

Monitor serum potassium closely during the first 48 hours of treatment 6

• Rapid hematologic response can cause hypokalemia as potassium is taken up by newly formed red blood cells 6
• Replace potassium if necessary during initial treatment 6

Special Population Dosing

Post-Bariatric Surgery

• 1 mg IM every 3 months OR 1000-2000 mcg orally daily indefinitely 1, 2
• Check B12 levels every 3 months throughout pregnancy for post-bariatric surgery patients 1

Ileal Resection >20 cm or Crohn's Disease with Ileal Involvement

• Prophylactic hydroxocobalamin 1000 mcg IM monthly for life, even without documented deficiency 1, 2
• Resection <20 cm typically does not cause deficiency 2

Pregnancy and Lactation

• Requirements increase to 4-5 mcg daily during pregnancy and 4 mcg daily during lactation 6
• Ensure adequate supplementation as deficiency can occur in breastfed infants of vegetarian mothers 6