What is the recommended dose for Vitamin B12 (Cobalamin) injections?

Vitamin B12 Injection Dosing

For vitamin B12 deficiency, the standard intramuscular dose is hydroxocobalamin 1000 mcg (1 mg), with the frequency depending on whether neurological symptoms are present: alternate days until no further improvement if neurological involvement exists, or three times weekly for 2 weeks if no neurological symptoms, followed by maintenance dosing every 2-3 months for life. 1, 2, 3

Initial Treatment Protocol

With Neurological Involvement

• Administer hydroxocobalamin 1 mg intramuscularly on alternate days until no further improvement occurs 1, 2, 3
• Then transition to maintenance therapy of 1 mg intramuscularly every 2 months for life 1, 2
• Neurological symptoms include peripheral neuropathy, paresthesias, gait disturbances, cognitive impairment, or subacute combined degeneration of the spinal cord 1

Without Neurological Involvement

• Give hydroxocobalamin 1 mg intramuscularly three times weekly for 2 weeks 1, 2, 3
• Follow with maintenance therapy of 1 mg intramuscularly every 2-3 months for life 1, 2, 3

Maintenance Therapy

• The standard maintenance regimen is hydroxocobalamin 1000 mcg intramuscularly every 2-3 months for life 1, 2, 3
• Monthly dosing (1000 mcg IM every month) is an acceptable alternative and may be necessary to meet metabolic requirements in some patients 1, 4
• Hydroxocobalamin is preferred over cyanocobalamin due to superior tissue retention 1, 3

Special Population Dosing

Post-Bariatric Surgery

• 1000 mcg intramuscularly every 3 months OR 1000-2000 mcg orally daily 1, 3
• For pregnancy planning after bariatric surgery, check B12 levels every 3 months 1

Ileal Resection or Crohn's Disease

• Patients with >20 cm distal ileum resected require prophylactic 1000 mcg intramuscularly monthly for life 1, 2
• Those with ileal Crohn's disease involving >30-60 cm need annual screening and prophylactic supplementation 1, 3

Renal Dysfunction

• Use methylcobalamin or hydroxocobalamin instead of cyanocobalamin 1, 3
• Cyanocobalamin requires renal clearance of the cyanide moiety and is associated with increased cardiovascular events (HR 2.0) in diabetic nephropathy 1

Administration Details

Injection Site and Technique

• Preferred sites: deltoid or vastus lateralis muscle 3
• Avoid the buttock as a routine injection site due to sciatic nerve injury risk; if used, only the upper outer quadrant with needle directed anteriorly 1
• Route: intramuscular or deep subcutaneous 3

For Thrombocytopenia

• Safe with moderate thrombocytopenia (platelet count >50 × 10⁹/L) 1
• With severe thrombocytopenia (25-50 × 10⁹/L): use smaller gauge needles (25-27G) and apply prolonged pressure (5-10 minutes) 1
• Consider platelet transfusion if count <10 × 10⁹/L 1

Monitoring Strategy

First Year

• Check serum B12, complete blood count, and homocysteine at 3,6, and 12 months 1, 3
• Target homocysteine <10 μmol/L for optimal outcomes 1, 3
• Monitor for resolution of macrocytosis and neurological symptoms 1, 5

Ongoing Monitoring

• Annual monitoring once levels stabilize 1, 2, 3
• High-risk patients (ileal disease, post-bariatric surgery) require yearly screening 1, 2

Critical Pitfalls to Avoid

Never Give Folic Acid First

• Never administer folic acid before treating vitamin B12 deficiency, as it may mask anemia while allowing irreversible neurological damage (subacute combined degeneration of the spinal cord) to progress 1, 2, 5
• Doses of folic acid >0.1 mg daily can produce hematologic remission while neurological manifestations continue 5

Lifelong Therapy Required

• Do not discontinue B12 supplementation even if levels normalize when malabsorption is the cause 1, 2
• Patients with pernicious anemia require monthly injections for the remainder of their lives 5
• Failure to continue treatment results in return of anemia and irreversible nerve damage 5

Monitor for Treatment Failure

• If reticulocytes have not increased after treatment or do not continue at least twice normal while hematocrit <35%, reevaluate diagnosis or treatment 5
• Check for complicating conditions (iron deficiency, folate deficiency) that may inhibit marrow response 5

Oral Alternative

• Oral cyanocobalamin 1000-2000 mcg daily is therapeutically equivalent to parenteral therapy for most patients, including those with malabsorption 2, 4, 6, 7
• Recent evidence shows oral supplementation at 1000 mcg/day can effectively treat even pernicious anemia through passive absorption 7
• However, parenteral therapy remains the guideline-recommended standard for malabsorption conditions 1, 2, 3