What is the recommended dose and administration protocol for intramuscular (IM) or intravenous (IV) Vitamin B12 (Cobalamin) infusion?

How to Administer Vitamin B12 Injection

For vitamin B12 deficiency, administer hydroxocobalamin 1 mg intramuscularly using either a loading protocol followed by maintenance therapy, with the specific regimen determined by the presence or absence of neurological symptoms. 1, 2, 3

Preparation and Route

• Use hydroxocobalamin 1000 mcg (1 mg) per injection as the preferred formulation due to superior tissue retention compared to cyanocobalamin 3
• Administer via intramuscular (IM) or deep subcutaneous injection 3, 4
• Preferred injection sites are the deltoid muscle or vastus lateralis (thigh) 3
• Avoid the buttock as a routine injection site due to potential sciatic nerve injury risk; if used, only inject in the upper outer quadrant with the needle directed anteriorly 2

Loading Phase Protocol

With Neurological Involvement

• Administer hydroxocobalamin 1 mg IM on alternate days until no further improvement occurs 1, 2, 3
• This aggressive initial treatment is critical to prevent irreversible neurological damage 2

Without Neurological Involvement

• Administer hydroxocobalamin 1 mg IM three times weekly for 2 weeks 1, 2, 3
• Alternative acceptable regimen: daily administration for 10 days 1

Maintenance Phase Protocol

Standard Maintenance

• After loading, transition to hydroxocobalamin 1 mg IM every 2-3 months for life 1, 2, 3
• For patients with neurological involvement, use every 2 months 1, 2
• For patients without neurological involvement, every 2-3 months is acceptable 1, 2

Special Populations Requiring Modified Dosing

• Post-bariatric surgery patients: 1 mg IM every 3 months OR 1000-2000 mcg oral daily indefinitely 1, 2
• Ileal resection >20 cm or Crohn's disease with ileal involvement: 1000 mcg IM monthly for life 1, 2
• Patients with renal dysfunction: use hydroxocobalamin or methylcobalamin instead of cyanocobalamin to avoid cyanide accumulation and increased cardiovascular risk 2, 3

Critical Pitfalls to Avoid

• Never administer folic acid before ensuring adequate B12 treatment, as it can mask anemia while allowing irreversible neurological damage (subacute combined degeneration of the spinal cord) to progress 2, 3
• Never discontinue therapy even if levels normalize, as patients with malabsorption require lifelong supplementation 1, 2
• Do not stop injections after symptoms improve, as this can lead to irreversible peripheral neuropathy 2

Monitoring Strategy

First Year

• Check serum B12, complete blood count, and homocysteine at 3,6, and 12 months after initiating treatment 2, 3
• Target homocysteine level <10 μmol/L for optimal outcomes 2, 3

After Stabilization

• Transition to annual monitoring of B12 levels and homocysteine once levels stabilize 1, 2, 3
• Monitor for recurrent neurological symptoms (paresthesias, gait disturbances, cognitive changes) and increase injection frequency if symptoms return 1, 2

Special Considerations for Thrombocytopenia

• Moderate thrombocytopenia (platelets >50 × 10⁹/L): standard IM administration is safe 2
• Severe thrombocytopenia (platelets 25-50 × 10⁹/L): use smaller gauge needles (25-27G) and apply prolonged pressure (5-10 minutes) at injection site 2
• Critical thrombocytopenia (platelets <10 × 10⁹/L): consider platelet transfusion support before IM administration 2
• Monitor injection sites for hematoma formation after administration 2

Alternative to Injections

• Oral cyanocobalamin 1000-2000 mcg daily is therapeutically equivalent to parenteral therapy for most patients, including those with malabsorption 1, 5
• However, IM therapy leads to more rapid improvement and should be prioritized in patients with severe deficiency or severe neurological symptoms 5
• Some patients may require up to 50% more frequent injections than standard protocols to remain symptom-free 6