What is the recommended dose of vitamin B12 (cobalamin) injection for a patient with pernicious anemia?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: November 11, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

Vitamin B12 Injection Dosing for Pernicious Anemia

For maintenance therapy in pernicious anemia, administer 100 mcg intramuscularly every month for life, or alternatively, 1000 mcg intramuscularly every 2-3 months for life. 1, 2

Initial Loading Phase

Before starting maintenance therapy, patients require an initial loading regimen:

  • Administer 100 mcg daily for 6-7 days by intramuscular or deep subcutaneous injection 1
  • If clinical improvement and reticulocyte response occur, give the same dose on alternate days for seven doses 1
  • Then continue every 3-4 days for another 2-3 weeks until hematologic values normalize 1

Maintenance Therapy Options

After the loading phase, two evidence-based maintenance regimens exist:

FDA-Approved Standard Regimen

  • 100 mcg intramuscularly once monthly for life 1
  • This is the FDA-labeled dosing for pernicious anemia 1

Alternative Higher-Dose Regimen

  • 1000 mcg (1 mg) intramuscularly every 2-3 months for life 2, 3
  • This regimen is supported by current clinical guidelines and may be necessary to meet metabolic requirements in many patients 4
  • The higher dose provides greater vitamin retention with no disadvantage in cost or toxicity 4

Special Considerations for Neurological Involvement

If neurological symptoms are present at diagnosis:

  • Administer hydroxocobalamin 1 mg intramuscularly on alternate days until no further improvement 2, 3
  • Then transition to maintenance with 1 mg intramuscularly every 2 months for life 2, 3
  • The more aggressive initial dosing is critical because neurological sequelae may become irreversible despite later cobalamin replacement 5

Oral Alternative (If Patient Prefers)

While intramuscular therapy is the gold standard, oral therapy is an acceptable alternative:

  • 1000 mcg cyanocobalamin orally daily 6, 7, 4
  • This achieves adequate absorption through passive enteral absorption (1-2% of dose) despite intrinsic factor deficiency 6
  • A recent 2024 prospective cohort study demonstrated that 88.5% of pernicious anemia patients were no longer deficient after 1 month of oral supplementation at this dose 7
  • Oral therapy requires patient adherence and may need more frequent monitoring initially 6

Critical Pitfalls to Avoid

  • Never use the intravenous route - almost all vitamin will be lost in urine 1
  • Never administer folic acid before treating B12 deficiency - this may mask the deficiency and precipitate subacute combined degeneration of the spinal cord 3
  • Never discontinue therapy even if levels normalize - pernicious anemia requires lifelong treatment 2, 3
  • Avoid cyanocobalamin in patients with renal dysfunction - use methylcobalamin or hydroxocobalamin instead due to potential cyanide accumulation 2, 3

Monitoring Strategy

  • Check serum B12, homocysteine, and methylmalonic acid every 3 months until stabilization 2, 3
  • After stabilization, monitor once yearly 2, 3
  • Monitor for recurrent neurological symptoms and increase injection frequency if symptoms return 2
  • Target homocysteine <10 μmol/L for optimal outcomes 2, 3

References

Guideline

Approach to Vitamin B12 Deficiency

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Vitamin B12 Injection Guidelines

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Vitamin B12 replacement therapy: how much is enough?

Wisconsin medical journal, 1994

Research

Pernicious anemia: Pathophysiology and diagnostic difficulties.

Journal of evidence-based medicine, 2021

Research

Oral vitamin B12 supplementation in pernicious anemia: a prospective cohort study.

The American journal of clinical nutrition, 2024

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.