Vitamin B12 Injection Dosing Schedule
For patients with confirmed B12 deficiency, the standard maintenance regimen is hydroxocobalamin 1000 mcg intramuscularly every 2-3 months for life, though monthly dosing may be necessary for some patients to meet metabolic requirements. 1, 2
Initial Treatment Protocol
The treatment approach differs based on neurological involvement:
With Neurological Symptoms
- Administer hydroxocobalamin 1 mg IM on alternate days until no further improvement occurs 1, 3
- Then transition to maintenance dosing of 1 mg IM every 2 months for life 1, 3
- Neurological symptoms include peripheral neuropathy, paresthesias, cognitive impairment, gait disturbances, or tongue symptoms like glossitis 1
Without Neurological Symptoms
- Give hydroxocobalamin 1 mg IM three times weekly for 2 weeks 1, 3
- Then transition to maintenance of 1 mg IM every 2-3 months lifelong 1, 3
Maintenance Therapy Considerations
Monthly dosing (1000 mcg IM monthly) is an acceptable alternative to every 2-3 months and may better meet metabolic requirements in certain patients 1, 4:
- Patients with persistent symptoms despite standard dosing 1
- Post-bariatric surgery patients 1
- Patients with extensive ileal disease or resection >20 cm 1
- Those requiring individualized regimens to remain symptom-free 5
The evidence shows that with 1000 mcg injections, significantly greater amounts of vitamin are retained compared to 100 mcg doses, with no disadvantage in cost or toxicity 4.
Special Population Dosing
Post-Bariatric Surgery
- 1000 mcg IM monthly indefinitely OR 1000-2000 mcg daily orally 1, 3
- Check B12 levels every 3 months if planning pregnancy 1
Ileal Resection >20 cm or Crohn's Disease
- Prophylactic hydroxocobalamin 1000 mcg IM monthly for life, even without documented deficiency 1, 3
- Annual screening recommended 1
Renal Dysfunction
- Use hydroxocobalamin or methylcobalamin instead of cyanocobalamin 1
- Cyanocobalamin requires renal clearance of the cyanide moiety and is associated with increased cardiovascular events (HR 2.0) in diabetic nephropathy 1
Monitoring Schedule
Check serum B12 levels at 3 months, 6 months, and 12 months in the first year, then annually thereafter 1:
- At each visit, assess serum B12, complete blood count, and consider methylmalonic acid (MMA) if levels remain borderline or symptoms persist 1
- Target homocysteine <10 μmol/L for optimal outcomes 1
- Clinical monitoring of neurological symptoms is more important than laboratory values 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 1, 3, 6:
- Folic acid can mask the anemia while allowing irreversible neurological damage to progress, including subacute combined degeneration of the spinal cord 1, 6
- Once B12 treatment has begun, folic acid 1 mg orally daily for 3 months can be added if folate is also deficient 1
Do not discontinue B12 supplementation even if levels normalize 1, 3:
- Patients with malabsorption require lifelong therapy 1, 3
- Stopping injections after symptom improvement can lead to irreversible peripheral neuropathy 1
Do not rely on "titration" of injection frequency based on measuring biomarkers 5:
- Up to 50% of individuals require individualized injection regimens with more frequent administration (ranging from daily to every 2-4 weeks) to remain symptom-free 5
- Treatment should be tailored based on symptom control rather than laboratory values alone 1, 5
Formulation Preference
Hydroxocobalamin is the preferred formulation 1:
- Established dosing protocols across all major guidelines 1
- Superior tissue retention compared to other forms 1
- All guideline-recommended regimens specify hydroxocobalamin 1, 3
The FDA label for cyanocobalamin confirms that patients with pernicious anemia will require monthly injections of vitamin B12 for the remainder of their lives, and failure to do so will result in return of anemia and irreversible nerve damage 6.