What is the recommended treatment for a patient with a confirmed vitamin B12 deficiency?

Prescription for Vitamin B12 Supplementation in Confirmed Deficiency

For confirmed vitamin B12 deficiency without neurological involvement, prescribe hydroxocobalamin 1 mg intramuscularly three times weekly for 2 weeks, followed by maintenance therapy of 1 mg intramuscularly every 2-3 months for life. 1, 2, 3

Initial Treatment Protocol

Without Neurological Involvement

• Hydroxocobalamin 1 mg IM three times weekly for 2 weeks (total of 6 doses during loading phase) 1, 2, 3
• This is the guideline-recommended first-line approach for standard B12 deficiency 1, 2

With Neurological Involvement (paresthesias, neuropathy, gait disturbance, cognitive changes)

• Hydroxocobalamin 1 mg IM on alternate days until no further improvement 1, 2, 3
• This more aggressive regimen is critical to prevent irreversible neurological damage 1, 2
• After maximum improvement, transition to hydroxocobalamin 1 mg IM every 2 months for life 1, 2

Maintenance Therapy

After the loading phase, prescribe hydroxocobalamin 1 mg IM every 2-3 months indefinitely 1, 2, 3

• The British National Formulary supports every 2 months as standard maintenance 4
• Some patients may require more frequent dosing (monthly or every 2-4 weeks) if symptoms recur, though this should be based on clinical response, not lab values 4
• Never discontinue therapy even if B12 levels normalize, as patients with malabsorption require lifelong treatment 1

Alternative Oral Therapy Option

For patients who prefer oral therapy or have contraindications to IM injections: cyanocobalamin 1000-2000 mcg orally daily 1, 5, 6

• High-dose oral B12 (1000-2000 mcg daily) is therapeutically equivalent to parenteral therapy for most patients, including those with malabsorption 1, 5, 6
• A Cochrane review confirmed that 2000 mcg oral daily achieves comparable hematological and neurological responses to IM administration 6
• However, parenteral therapy is preferred for severe deficiency or neurological symptoms to ensure rapid improvement 5

Special Population Considerations

Post-Bariatric Surgery

• Hydroxocobalamin 1 mg IM every 3 months OR cyanocobalamin 1000-2000 mcg orally daily indefinitely 1, 2
• Check B12 levels every 3 months if planning pregnancy 1

Ileal Resection (>20 cm)

• Prophylactic hydroxocobalamin 1000 mcg IM monthly for life, even without documented deficiency 2, 3
• Annual screening for B12 deficiency is mandatory 1

Crohn's Disease with Ileal Involvement

• Hydroxocobalamin 1000 mcg IM monthly OR oral cyanocobalamin 1200 mg daily 1
• Annual screening required 2

Renal Dysfunction

• Use hydroxocobalamin or methylcobalamin instead of cyanocobalamin 1, 2
• Cyanocobalamin requires renal clearance of the cyanide moiety and is associated with increased cardiovascular events (HR 2.0) in diabetic nephropathy 1, 2

Critical Safety Considerations

Never administer folic acid before or without adequate B12 treatment 2, 3

• Folic acid can mask the anemia of B12 deficiency while allowing irreversible neurological damage (subacute combined degeneration of the spinal cord) to progress 2, 3
• Always check both B12 and folate levels, as deficiencies may coexist 3

Monitoring Schedule

• First recheck at 3 months: measure serum B12, complete blood count, methylmalonic acid (if borderline), and homocysteine 1, 2
• Second recheck at 6 months: same parameters 1
• Third recheck at 12 months: same parameters 1
• Annual monitoring thereafter once levels stabilize 1, 2
• Target homocysteine <10 μmol/L for optimal outcomes 1, 2

Common Pitfalls to Avoid

• Do not stop monitoring after one normal result - patients with malabsorption can relapse and require ongoing supplementation 1
• Do not titrate injection frequency based on serum B12 or MMA levels - base adjustments on clinical symptoms only 4
• Do not stop injections after symptoms improve - this can lead to irreversible peripheral neuropathy 1
• Monitor for recurrent neurological symptoms and increase injection frequency if symptoms return 1

Formulation Preference

Hydroxocobalamin is the preferred formulation over cyanocobalamin or methylcobalamin 2

• Superior tissue retention compared to other forms 2
• Established dosing protocols with evidence-based regimens 2
• All major guidelines provide specific recommendations for hydroxocobalamin 2

Sample Prescription

Rx: Hydroxocobalamin 1 mg/mL injection

• Sig: Inject 1 mL (1 mg) intramuscularly three times weekly for 2 weeks (6 doses total)
• Then: Inject 1 mL (1 mg) intramuscularly every 2-3 months indefinitely
• Dispense: #6 vials for loading, then #4 vials for annual maintenance
• Refills: Lifelong therapy required