What is the appropriate dosing schedule for intramuscular vitamin B12 (cyanocobalamin or hydroxocobalamin) in an adult with documented deficiency (e.g., pernicious anemia, malabsorption, or post‑gastrectomy), including loading and maintenance phases and recommendations for severe neurologic symptoms?

B12 Injection Dosing

For adults with documented vitamin B12 deficiency, administer hydroxocobalamin 1000 mcg intramuscularly on alternate days until neurological improvement plateaus if neurological symptoms are present, then maintain with 1000 mcg IM every 2 months for life; if no neurological symptoms exist, give 1000 mcg IM three times weekly for 2 weeks, then 1000 mcg IM every 2–3 months for life. 1, 2

Loading Phase Protocols

Patients WITH Neurological Symptoms

• Administer hydroxocobalamin 1000 mcg intramuscularly on alternate days until no further neurological improvement is observed (typically requiring several weeks to months). 3, 1, 2
• Neurological manifestations requiring this intensive regimen include paresthesias, numbness, gait disturbances, cognitive difficulties, memory problems, glossitis, and peripheral neuropathy. 1, 2
• This aggressive alternate-day schedule is mandatory to achieve timely functional recovery and reduce the risk of permanent neurological damage. 1, 2

Patients WITHOUT Neurological Symptoms

• Give hydroxocobalamin 1000 mcg intramuscularly three times weekly for 2 weeks as the initial loading phase. 3, 1, 2
• This shorter loading regimen corrects biochemical deficiency while avoiding overtreatment in asymptomatic individuals. 1

Maintenance Phase

• After neurological recovery has plateaued or after completing the 2-week loading phase, transition to hydroxocobalamin 1000 mcg intramuscularly every 2–3 months for life. 3, 1, 2
• Monthly dosing (1000 mcg IM monthly) is an acceptable alternative that may better meet metabolic requirements in some patients, particularly those with persistent symptoms despite standard dosing, post-bariatric surgery patients, or patients with extensive ileal disease or resection. 3, 1, 2, 4
• The FDA-approved cyanocobalamin regimen is 100 mcg daily for 6–7 days IM, then alternate days for seven doses, then every 3–4 days for 2–3 weeks, followed by 100 mcg monthly for life; however, current evidence supports using 1000 mcg doses instead. 5, 4

Special Population Dosing

Post-Bariatric Surgery

• Initiate routine prophylactic hydroxocobalamin 1000 mcg intramuscularly every 3 months indefinitely, irrespective of documented deficiency, to prevent malabsorption-related B12 loss. 1, 2
• Alternative regimens include 1000–2000 mcg oral daily or 1000 mcg IM monthly for life. 1, 2

Ileal Resection or Crohn's Disease

• Patients with ileal resection >20 cm should receive prophylactic hydroxocobalamin 1000 mcg IM monthly for life, even without documented deficiency. 3, 1, 2
• Patients with ileal Crohn's disease involving >30–60 cm require the same prophylactic regimen. 3, 2

Formulation Selection Based on Renal Function

• Hydroxocobalamin is the guideline-recommended first-line injectable for adult vitamin B12 deficiency, with superior tissue retention compared to cyanocobalamin. 1, 2
• In patients with renal dysfunction (estimated GFR <50 mL/min), use hydroxocobalamin or methylcobalamin instead of cyanocobalamin, as cyanocobalamin requires renal clearance of the cyanide moiety and is associated with increased cardiovascular events (hazard ratio ≈2.0 in diabetic nephropathy). 1, 2
• Cyanocobalamin should be avoided in patients with impaired renal function due to accumulation of cyanide-derived thiocyanate and consequent rise in cardiovascular risk. 1, 2

Critical Safety Precautions

• Never administer folic acid before correcting vitamin B12 deficiency, as folic acid can mask megaloblastic anemia while allowing irreversible subacute combined degeneration of the spinal cord to progress. 3, 1, 2
• Only after successful B12 repletion should folic acid 5 mg daily be added if concurrent folate deficiency is documented. 1, 2
• Monitor serum potassium closely during the first 48 hours of treatment and administer potassium if necessary, as repletion therapy can precipitate hypokalemia. 3, 6

Route of Administration

• Intramuscular (or deep subcutaneous) injection is the definitive parenteral route; intravenous administration is not recommended in current guidelines because almost all of the vitamin is lost in urine. 1, 5, 6
• The intramuscular route is mandatory for patients with severe neurological involvement, confirmed malabsorption (pernicious anemia, total gastrectomy, ileal resection >20 cm, atrophic gastritis), or after bariatric surgery. 1, 2, 6

Monitoring Schedule

• Recheck serum B12 at 3 months, 6 months, and 12 months in the first year, then annually once levels stabilize. 1, 2
• At follow-up, measure serum B12, complete blood count, methylmalonic acid (MMA), and homocysteine to assess treatment response. 1, 2
• Target homocysteine <10 μmol/L for optimal cardiovascular outcomes. 1, 2
• For patients receiving monthly injections, measure serum B12 directly before the next scheduled injection (at trough) to identify potential under-dosing. 2

Common Pitfalls to Avoid

• Do not stop treatment after one normal result, as patients with malabsorption or dietary insufficiency require lifelong supplementation and can relapse. 1, 2
• Do not rely solely on serum B12 to rule out deficiency, as standard serum B12 testing misses functional deficiency in up to 50% of cases. 1, 7
• Do not use cyanocobalamin in patients with renal dysfunction, as it requires renal clearance and is associated with increased cardiovascular events. 1, 2
• Do not postpone therapy in any patient whose B12 level is <180 pg/mL and who exhibits macrocytic anemia; immediate treatment is mandated regardless of pending ancillary test results. 2