Vitamin B12 Intramuscular Dosage
For vitamin B12 deficiency with neurological involvement, administer hydroxocobalamin 1 mg intramuscularly on alternate days until no further improvement occurs, then transition to maintenance dosing of 1 mg every 2 months for life. 1
Treatment Protocol Based on Neurological Status
With Neurological Involvement
- Loading phase: Hydroxocobalamin 1 mg IM on alternate days until neurological symptoms stop improving 1, 2
- Maintenance phase: Hydroxocobalamin 1 mg IM every 2 months indefinitely 1, 2
- Seek urgent specialist consultation from neurology and hematology if unexplained sensory, motor, or gait symptoms are present 1
Without Neurological Involvement
- Loading phase: Hydroxocobalamin 1 mg IM three times weekly for 2 weeks 1, 2
- Maintenance phase: Hydroxocobalamin 1 mg IM every 2-3 months for life 1, 2
FDA-Approved Dosing (Alternative Regimen)
The FDA label provides a different dosing schedule that may be used: 3
- Initial treatment: 30 mcg daily for 5-10 days
- Maintenance: 100-200 mcg monthly IM
- For critically ill patients or those with neurologic disease: Considerably higher doses may be indicated, with current data suggesting that dosing sufficient to produce good hematologic response yields optimal neurologic outcomes 3
Special Population Dosing
Post-Bariatric Surgery
- Prophylactic maintenance: 1 mg IM every 3 months OR 1000-2000 mcg oral daily indefinitely 2
- Monitor B12 levels every 3 months if planning pregnancy 2
Crohn's Disease with Ileal Involvement
- If >20 cm ileum resected: 1000 mcg IM monthly indefinitely as prophylaxis 1, 4
- With documented deficiency: 1000 mcg IM every other day for one week, then monthly for life 1
- Screen yearly for B12 deficiency even without resection if >30-60 cm ileum involved 1, 2
Renal Dysfunction
- Preferred formulations: Use hydroxocobalamin or methylcobalamin instead of cyanocobalamin 2, 5
- Cyanocobalamin requires renal clearance of cyanide moiety and is associated with increased cardiovascular events (HR 2.0) in diabetic nephropathy 2
Practical Dosing Considerations
The 1000 mcg (1 mg) dose is strongly preferred over lower doses because significantly more vitamin is retained with 1000 mcg injections compared to 100 mcg, with no disadvantage in cost or toxicity 6. Monthly dosing of 1000 mcg IM is necessary to meet metabolic requirements in many patients 6.
Administration Details
- Route: Intramuscular or deep subcutaneous 5
- Preferred sites: Deltoid or vastus lateralis 5
- Avoid: Buttock region due to sciatic nerve injury risk; if used, only upper outer quadrant with needle directed anteriorly 2
- Protect from light 3
Monitoring Strategy
First Year
- Check serum B12, complete blood count, and homocysteine at 3,6, and 12 months 2, 5
- Target homocysteine <10 μmol/L for optimal outcomes 2, 5
After Stabilization
- Annual monitoring of B12 levels and homocysteine 2, 5
- For high-risk patients (ileal resection, Crohn's disease), screen yearly even if asymptomatic 1, 4
Critical Pitfalls to Avoid
Never administer folic acid before treating B12 deficiency, as it may mask underlying B12 deficiency while allowing irreversible subacute combined degeneration of the spinal cord to progress 1, 2, 4. Always check and treat B12 deficiency first 1.
Do not discontinue therapy even if levels normalize when malabsorption is the cause—patients require lifelong supplementation 2, 4. Stopping injections after symptom improvement can lead to irreversible peripheral neuropathy 2.
Do not "titrate" injection frequency based on serum B12 or MMA levels 7. Up to 50% of individuals require individualized injection regimens ranging from twice weekly to every 2-4 weeks to remain symptom-free, based on clinical response rather than biomarkers 7.
Oral Alternative (When Appropriate)
High-dose oral B12 (1000-2000 mcg daily) may be as effective as IM administration for patients without severe malabsorption 8, 9. However, for malabsorption conditions (pernicious anemia, ileal resection, bariatric surgery), parenteral therapy remains preferred and more reliable 5, 7.