What is the recommended dosage and frequency for vitamin B12 (cobalamin) 1000 mcg injections?

Vitamin B12 1000 mcg Injection Dosing

For vitamin B12 deficiency, administer hydroxocobalamin 1000 mcg (1 mg) intramuscularly with the frequency determined by presence or absence of neurological symptoms: alternate days until improvement for neurological involvement, or three times weekly for 2 weeks for non-neurological deficiency, followed by maintenance dosing every 2-3 months for life. 1

Initial Treatment Protocol

With Neurological Involvement

• Administer hydroxocobalamin 1000 mcg IM on alternate days until no further neurological improvement occurs 1, 2
• This aggressive approach prevents irreversible neurological damage including peripheral neuropathy, subacute combined degeneration of the spinal cord, and cognitive impairment 1
• After maximal improvement, transition to maintenance therapy of 1000 mcg IM every 2 months for life 1, 2

Without Neurological Involvement

• Give hydroxocobalamin 1000 mcg IM three times weekly for 2 weeks 1, 2
• Alternative loading regimen: daily injections for 5-6 doses 3
• Follow with maintenance therapy of 1000 mcg IM every 2-3 months lifelong 1, 2

Maintenance Therapy

The standard maintenance regimen is 1000 mcg hydroxocobalamin IM every 2-3 months for life 1, 2, 4

• Monthly dosing (every 4 weeks) is an acceptable alternative and may be necessary to meet metabolic requirements in some patients 1, 3
• Recent evidence suggests up to 50% of patients require more frequent individualized injection regimens (ranging from every 2-4 weeks) to remain symptom-free 5
• Never discontinue therapy even if levels normalize, as patients with malabsorption require lifelong treatment 1, 2

Special Population Dosing

Post-Bariatric Surgery

• 1000 mcg IM every 3 months indefinitely OR 1000-2000 mcg oral daily 1, 6
• Check B12 levels every 3 months if planning pregnancy 1

Ileal Resection >20 cm

• Prophylactic 1000 mcg IM monthly for life, even without documented deficiency 1, 6

Crohn's Disease with Ileal Involvement

• Screen yearly for deficiency 1
• If >30-60 cm ileal involvement: prophylactic supplementation with 1000 mcg IM monthly 1

Formulation Selection

Hydroxocobalamin is the preferred formulation over cyanocobalamin 1

• Hydroxocobalamin has superior tissue retention and established evidence-based dosing protocols 1
• In patients with renal dysfunction, avoid cyanocobalamin due to cyanide accumulation risk and associated increased cardiovascular events (HR 2.0) 1
• Use methylcobalamin or hydroxocobalamin instead in renal impairment 1, 6

Administration Technique

• Use intramuscular route via deltoid or vastus lateralis muscle 1
• Avoid buttock injection due to sciatic nerve injury risk; if used, only upper outer quadrant with needle directed anteriorly 1
• In severe thrombocytopenia (platelets 25-50 × 10⁹/L): use 25-27 gauge needle and apply pressure for 5-10 minutes 1
• Consider platelet transfusion if platelets <10 × 10⁹/L before injection 1

Monitoring Schedule

First year monitoring: 3 months, 6 months, and 12 months after initiating treatment 1

• At each visit, measure serum B12, complete blood count, and homocysteine (target <10 μmol/L) 1, 2
• Consider methylmalonic acid if B12 levels remain borderline or symptoms persist 1, 2
• After stabilization (two consecutive normal checks), transition to annual monitoring 1

Critical Pitfalls to Avoid

• Never administer folic acid before ensuring adequate B12 treatment, as it masks anemia while allowing irreversible neurological damage to progress 1, 2, 6
• Do not rely on serum B12 levels alone to adjust injection frequency; titration based on biomarkers should not be practiced 5
• Monitor for recurrent neurological symptoms (paresthesias, gait disturbances, cognitive changes) and increase injection frequency if symptoms return 1, 2
• Do not stop monitoring after one normal result, as patients with malabsorption can relapse 1

Oral Alternative Consideration

• High-dose oral cyanocobalamin (1000-2000 mcg daily) may be therapeutically equivalent to IM therapy for patients without neurological symptoms and after initial loading 7, 3, 8
• However, current evidence does not support that oral supplementation can safely replace injections in established malabsorption 5
• IM therapy remains preferred for malabsorption conditions and leads to more rapid improvement 7