What is the recommended intramuscular dosing regimen of cyanocobalamin or hydroxocobalamin for an adult with confirmed vitamin B12 deficiency?

Vitamin B12 Injection Dosing for Confirmed Deficiency

For adults with confirmed vitamin B12 deficiency, administer hydroxocobalamin 1000 µg intramuscularly three times weekly for 2 weeks if no neurological symptoms are present, then continue with 1000 µg intramuscularly every 2–3 months for life. 1

Initial Loading Phase

Patients WITHOUT Neurological Involvement

• Give hydroxocobalamin 1000 µg intramuscularly three times weekly for 2 weeks as the initial loading regimen 1, 2
• This corrects biochemical deficiency while avoiding overtreatment in asymptomatic individuals 1

Patients WITH Neurological Involvement

• Administer hydroxocobalamin 1000 µg intramuscularly on alternate days until neurological improvement plateaus (typically several weeks to months) 1, 2
• Neurological manifestations include paresthesias, numbness, gait disturbances, cognitive difficulties, memory problems, and glossitis 1
• Aggressive alternate-day dosing is mandatory to achieve timely functional recovery and reduce the risk of permanent damage 1

Maintenance Therapy

After completing the loading phase, transition to hydroxocobalamin 1000 µg intramuscularly every 2–3 months for lifelong therapy. 1, 2

Alternative Monthly Dosing

• Monthly dosing (1000 µg IM monthly) is an acceptable alternative that may better meet metabolic requirements in some patients 1
• Consider monthly dosing for:
  • Patients with persistent symptoms despite standard dosing 1
  • Post-bariatric surgery patients 1
  • Patients with extensive ileal disease or resection 1

Special Populations Requiring Prophylactic Treatment

Ileal Resection or Crohn's Disease

• Patients with ileal resection >20 cm should receive prophylactic hydroxocobalamin 1000 µg IM monthly for life, even without documented deficiency 1, 2
• Patients with ileal Crohn's disease involving >30–60 cm require the same prophylactic monthly regimen 1, 2

Post-Bariatric Surgery

• Initiate routine prophylactic hydroxocobalamin 1000 µg IM every 3 months indefinitely, regardless of documented deficiency 1
• Alternative regimen: oral B12 1000–2000 µg daily or 1000 µg IM monthly 1

Formulation Selection Based on Renal Function

Normal Renal Function (eGFR ≥50 mL/min)

• Hydroxocobalamin is the preferred injectable form due to superior tissue retention and established dosing protocols 1
• Cyanocobalamin is an acceptable alternative 1

Impaired Renal Function (eGFR <50 mL/min)

• Use hydroxocobalamin or methylcobalamin; avoid cyanocobalamin 1
• Cyanocobalamin requires renal clearance of the cyanide moiety and is associated with doubled cardiovascular event risk (HR ≈2.0) in patients with diabetic nephropathy 1

Critical Safety Precautions

Folate Administration

• Never administer folic acid before correcting vitamin B12 deficiency 1, 2
• Folic acid can mask megaloblastic anemia while allowing irreversible subacute combined degeneration of the spinal cord to progress 1, 2
• Only after successful B12 repletion should folic acid 5 mg daily be added if concurrent folate deficiency is documented 1

Potassium Monitoring

• Monitor serum potassium closely during the first 48 hours of B12 repletion 2
• Provide potassium supplementation if hypokalemia develops 2

Monitoring Schedule

First Year

• Recheck serum B12 at 3 months, 6 months, and 12 months 1, 2
• At each visit, measure serum B12, complete blood count, methylmalonic acid (if B12 remains borderline), and homocysteine 1, 2

Ongoing Monitoring

• Once levels stabilize, transition to annual monitoring 1, 2
• Target homocysteine <10 µmol/L for optimal cardiovascular outcomes 1

Special Populations

• Post-bariatric surgery patients planning pregnancy require B12 checks every 3 months 1
• Patients with neurological involvement require clinical monitoring of symptoms, which is more important than laboratory values 1

Common Pitfalls to Avoid

• Do not stop monitoring after one normal result—patients with malabsorption require lifelong supplementation and can relapse 1, 2
• Do not rely solely on serum B12 to assess adequacy—up to 50% of patients with "normal" serum B12 have metabolic deficiency when measured by methylmalonic acid 1
• Do not discontinue injections even if levels normalize—patients with permanent malabsorption (pernicious anemia, post-bariatric surgery, ileal resection >20 cm) require lifelong therapy 1
• Do not use cyanocobalamin in patients with renal dysfunction (eGFR <50 mL/min) 1

Injection Site Considerations

• Avoid the buttock as a routine injection site due to potential sciatic nerve injury 1
• If the buttock must be used, inject only in the upper outer quadrant with the needle directed anteriorly 1