What is the recommended dose of cyanocobalamin (Vitamin B12) for a patient with confirmed Vitamin B12 deficiency?

Cyanocobalamin Dosing for Vitamin B12 Deficiency

For confirmed B12 deficiency, the standard treatment is hydroxocobalamin 1 mg intramuscularly three times weekly for 2 weeks (without neurological involvement) or on alternate days until no further improvement (with neurological involvement), followed by maintenance therapy of 1 mg intramuscularly every 2-3 months for life. 1

Initial Treatment Protocol

Without Neurological Involvement

• Administer hydroxocobalamin 1 mg intramuscularly three times per week for 2 weeks as the loading phase 1
• This regimen corrects the deficiency and replenishes tissue stores 1

With Neurological Involvement

• Administer hydroxocobalamin 1 mg intramuscularly on alternate days until no further improvement occurs 1
• Neurological symptoms include peripheral neuropathy, paresthesias, cognitive difficulties, gait disturbances, glossitis, or visual problems 1, 2
• More aggressive initial therapy is critical because neurological damage can become irreversible if treatment is delayed 1, 3

Maintenance Therapy

After completing the loading phase, transition to hydroxocobalamin 1 mg intramuscularly every 2-3 months for life 1, 4

Alternative Maintenance Dosing

• Monthly dosing (1000 mcg IM monthly) is an acceptable alternative that may better meet metabolic requirements in some patients 1
• This is particularly relevant for patients with persistent symptoms despite standard dosing, post-bariatric surgery patients, or those with extensive ileal disease 1

Oral vs. Intramuscular Administration

Oral high-dose vitamin B12 (1000-2000 mcg daily) is as effective as intramuscular administration for most patients 5, 4, but intramuscular therapy should be prioritized in specific situations:

• Severe deficiency with B12 <150 pmol/L 1, 2
• Any neurological manifestations present 5, 2
• Confirmed malabsorption (pernicious anemia, ileal resection >20 cm, post-bariatric surgery) 1, 5
• Failure of oral therapy to normalize levels 2

Formulation Selection: Critical Consideration

Avoid cyanocobalamin in patients with renal dysfunction; use methylcobalamin or hydroxocobalamin instead 1

• Cyanocobalamin requires renal clearance of the cyanide moiety and is associated with increased cardiovascular events (hazard ratio 2.0) in patients with diabetic nephropathy 1
• Hydroxocobalamin is the guideline-recommended formulation across major medical societies 1
• Hydroxocobalamin has superior tissue retention compared to other formulations 1

Special Population Dosing

Post-Bariatric Surgery

• 1 mg intramuscularly every 3 months OR 1000 mcg orally daily indefinitely 1
• After Roux-en-Y gastric bypass or biliopancreatic diversion: 1000-2000 mcg/day sublingual OR 1000 mcg/month IM 1
• After sleeve gastrectomy or gastric banding: 250-350 mcg/day oral OR 1000 mcg/week sublingual 1

Ileal Resection or Crohn's Disease

• Patients with >20 cm of distal ileum resected require prophylactic vitamin B12 injections (1000 mcg) monthly for life 1
• Ileal Crohn's disease involving >30-60 cm puts patients at risk even without resection and requires annual screening 1

Elderly Patients (>75 years)

• Consider prophylactic treatment with hydroxocobalamin 1000 mcg IM monthly indefinitely, even without documented deficiency, given the 18.1% prevalence of metabolic deficiency in those >80 years 1

Monitoring Schedule

Recheck serum B12 levels at 3 months after initiating supplementation, then at 6 and 12 months in the first year, followed by annual monitoring 1

At each monitoring point, assess:

• Serum B12 levels as the primary marker 1
• Complete blood count to evaluate for resolution of megaloblastic anemia 1
• Methylmalonic acid (MMA) if B12 levels remain borderline or symptoms persist 1
• Homocysteine with target <10 μmol/L for optimal outcomes 1

Once B12 levels stabilize within normal range for two consecutive checks (typically by 6-12 months), transition to annual monitoring 1

Critical Pitfalls to Avoid

• Never administer folic acid before treating B12 deficiency, as it may mask anemia while allowing irreversible neurological damage to progress (subacute combined degeneration of the spinal cord) 1, 5, 3
• Do not discontinue B12 supplementation even if levels normalize—patients with malabsorption require lifelong therapy 1
• Do not stop monitoring after one normal result, as patients can relapse 1
• In thrombocytopenia with platelet count <25 × 10⁹/L and neurological symptoms, prioritize treatment despite low platelets 1
• For severe thrombocytopenia (25-50 × 10⁹/L), use smaller gauge needles (25-27G) and apply prolonged pressure (5-10 minutes) at injection site 1

Treatment Adjustment Based on Response

Clinical monitoring of neurological symptoms is more important than laboratory values 1

• Pain and paresthesias often improve before motor symptoms 1
• If symptoms recur despite normal B12 levels, consider increasing frequency of injections or switching from oral to injectable form 1
• Up to 50% of individuals may require individualized injection regimens with more frequent administration (ranging from twice weekly to every 2-4 weeks) to remain symptom-free 3