What is the recommended weekly intramuscular (IM) dose of methylcobalamin (Vitamin B12) for a patient with a confirmed deficiency or increased demand, such as pernicious anemia?

Weekly Intramuscular Methylcobalamin Dosing

For confirmed B12 deficiency requiring intramuscular therapy, the standard weekly dose is 1000 mcg (1 mg) methylcobalamin IM, though this is not the guideline-recommended maintenance schedule—most patients should transition to every 2-3 months after initial loading. 1

Initial Loading Phase vs. Maintenance Therapy

The confusion about "weekly" dosing stems from misunderstanding treatment phases. Guidelines distinguish between initial intensive treatment and long-term maintenance:

For Patients WITHOUT Neurological Involvement

• Initial loading: Hydroxocobalamin 1 mg IM three times weekly for 2 weeks 1, 2
• Maintenance: 1 mg IM every 2-3 months for life 1, 2
• Weekly dosing is NOT the standard maintenance regimen 2

For Patients WITH Neurological Involvement

• Initial loading: Hydroxocobalamin 1 mg IM on alternate days until no further improvement 1, 2
• Maintenance: 1 mg IM every 2 months for life 1, 2

When Weekly Dosing May Be Appropriate

Weekly dosing (1000 mcg IM) is only appropriate during specific circumstances:

• Post-bariatric surgery patients: Some guidelines suggest 1000 mcg/week sublingual OR 1000 mcg/month IM as alternatives 1
• Transition phase: After initial loading but before establishing final maintenance schedule 1
• Individualized regimens: Up to 50% of patients may require more frequent dosing (ranging from twice weekly to every 2-4 weeks) to remain symptom-free, though this should be based on clinical response, not arbitrary weekly scheduling 3

Critical Dosing Considerations

FDA-Approved Methylcobalamin Dosing

The FDA label for methylcobalamin specifies for pernicious anemia: 100 mcg daily for 6-7 days IM, then alternate days for seven doses, then every 3-4 days for 2-3 weeks, followed by 100 mcg monthly for life 4. However, this 100 mcg dose is outdated—current guidelines universally recommend 1000 mcg (1 mg) doses 1, 2.

Hydroxocobalamin vs. Methylcobalamin

Hydroxocobalamin is the guideline-recommended formulation across all major medical societies, with established dosing protocols and superior tissue retention compared to methylcobalamin 1. Methylcobalamin or hydroxocobalamin are preferable to cyanocobalamin in patients with renal dysfunction 1.

Practical Dosing Algorithm

Step 1: Assess for neurological involvement

• Peripheral neuropathy, cognitive symptoms, ataxia, or glossitis = neurological involvement 1

Step 2: Initial treatment

• With neurological symptoms: 1000 mcg IM alternate days until no further improvement 1, 2
• Without neurological symptoms: 1000 mcg IM three times weekly for 2 weeks 1, 2

Step 3: Transition to maintenance

• Standard maintenance: 1000 mcg IM every 2-3 months for life 1, 2
• Monthly alternative: 1000 mcg IM monthly is acceptable and may better meet metabolic requirements in some patients 1

Step 4: Adjust based on clinical response

• Monitor for symptom recurrence, not laboratory values 3
• If symptoms return, increase frequency (every 2-4 weeks or more often) 3
• Do NOT use serum B12 or MMA levels to "titrate" injection frequency 3

Common Pitfalls to Avoid

• Never administer folic acid before treating B12 deficiency—it may mask anemia while allowing irreversible neurological damage to progress 1, 2
• Do not discontinue therapy even if levels normalize—patients with malabsorption require lifelong treatment 1, 2
• Avoid using serum B12 levels to guide injection frequency—clinical symptom control is the appropriate endpoint 3
• Do not assume weekly dosing is standard maintenance—this is not supported by guidelines and wastes resources 1, 2

Special Populations Requiring Modified Schedules

• Post-bariatric surgery: 1000 mcg IM monthly indefinitely OR 1000-2000 mcg oral daily 1, 2
• Ileal resection >20 cm: 1000 mcg IM monthly for life (prophylactic) 1, 2
• Crohn's disease with ileal involvement: 1000 mcg IM monthly with yearly screening 1, 2
• Pregnancy after bariatric surgery: Check B12 levels every 3 months throughout pregnancy 1

Monitoring Strategy

• First year: Check serum B12 at 3,6, and 12 months 1
• Ongoing: Annual monitoring once levels stabilize 1, 2
• Target homocysteine: <10 μmol/L for optimal outcomes 1
• Clinical monitoring: Assess neurological symptoms at each visit—more important than laboratory values 1, 3