What is the recommended dose for Vitamin B12 (Cobalamin) intramuscular (IM) supplementation?

Vitamin B12 Intramuscular Supplementation Dosing

For vitamin B12 deficiency with neurological involvement, administer hydroxocobalamin 1 mg IM on alternate days until no further improvement, then transition to maintenance with 1 mg IM every 2 months for life. 1

Initial Treatment Protocol

With Neurological Symptoms

• Hydroxocobalamin 1 mg IM on alternate days until no further clinical improvement is observed 1, 2
• This aggressive initial regimen is critical because neurological damage can become irreversible if undertreated 1
• Continue the alternate-day dosing until symptoms plateau, which may take several weeks 1

Without Neurological Symptoms

• Hydroxocobalamin 1 mg IM three times weekly for 2 weeks (or daily for days 1-10) 1, 2
• This loading phase ensures adequate tissue saturation before transitioning to maintenance 1

Maintenance Therapy

The standard maintenance regimen is hydroxocobalamin 1 mg IM every 2-3 months for life for patients without neurological involvement 1, 2

For patients with neurological involvement, maintenance is 1 mg IM every 2 months 1, 2

Important Dosing Considerations

• Some patients require monthly dosing (1000 mcg IM) to meet metabolic requirements and remain symptom-free 2, 3
• Up to 50% of individuals require more frequent administration ranging from every 2-4 weeks based on symptom control 4
• Never titrate injection frequency based on serum B12 or methylmalonic acid levels—base adjustments solely on clinical symptoms 4

Special Population Dosing

Post-Bariatric Surgery

• 1 mg IM every 3 months OR 1000-2000 mcg daily orally indefinitely 1, 2
• For pregnancy after bariatric surgery: check B12 levels every 3 months throughout pregnancy 1

Crohn's Disease with Ileal Resection >20 cm

• 1000 mcg IM monthly indefinitely for prophylaxis 1, 2
• Screen yearly for B12 deficiency 1

Formulation Selection

Hydroxocobalamin is the preferred formulation over cyanocobalamin, particularly in patients with renal dysfunction 2, 5

• Cyanocobalamin requires renal clearance of the cyanide moiety and is associated with increased cardiovascular events (HR 2.0) in diabetic nephropathy 2
• Methylcobalamin or hydroxocobalamin should be used instead of cyanocobalamin in renal disease 1, 2
• The FDA-approved cyanocobalamin formulation is available as 1000 mcg/mL for IM or subcutaneous use 6

Oral Alternative

Oral cyanocobalamin 1000-2000 mcg daily is therapeutically equivalent to parenteral therapy for most patients, including those with malabsorption 1, 7, 5

However, intramuscular administration should be prioritized when:

• Severe neurological manifestations are present 5
• Malabsorption is confirmed 5
• Oral therapy fails to normalize levels 5

Critical Pitfalls to Avoid

• Never administer folic acid before treating B12 deficiency—it may mask anemia while allowing irreversible neurological damage to progress 2, 8
• Never discontinue therapy even if levels normalize—patients with malabsorption require lifelong treatment 1, 2
• Do not rely on laboratory values alone to determine injection frequency—clinical symptom control is paramount 4
• Monitor for recurrent neurological symptoms and increase injection frequency if symptoms return 1

Monitoring Strategy

• Check serum B12, homocysteine, and methylmalonic acid every 3 months until stabilization, then once yearly 1, 2
• Target homocysteine <10 μmol/L for optimal outcomes 1, 2
• Screen high-risk patients yearly for B12 deficiency 1