What is the recommended concentration and administration schedule for Injectible Methylcobalamin (Inj MCBM)?

Injectable Methylcobalamin (MCBM) Administration Protocol

Standard Concentration and Dosing

Injectable methylcobalamin should be administered at a concentration of 1000 mcg (1 mg) per dose via intramuscular or deep subcutaneous injection, avoiding the intravenous route as it results in almost complete urinary loss of the vitamin. 1

Initial Treatment Phase (Loading Dose)

For vitamin B12 deficiency treatment, the administration schedule depends on whether neurological symptoms are present:

Without Neurological Involvement:

• 1000 mcg (1 mg) intramuscularly three times weekly for 2 weeks 2
• Alternative FDA-approved regimen: 100 mcg daily for 6-7 days, then alternate days for seven doses, then every 3-4 days for 2-3 weeks 1
• However, the 1000 mcg dose is preferred as significantly greater amounts are retained compared to 100 mcg, with no disadvantage in cost or toxicity 3

With Neurological Involvement (including memory impairment, peripheral neuropathy):

• 1000 mcg (1 mg) intramuscularly on alternate days until no further improvement occurs 4, 2
• This more aggressive approach is critical because neurological damage can become irreversible if undertreated 4

Maintenance Therapy

After initial loading, administer 1000 mcg (1 mg) intramuscularly every 2-3 months for life when malabsorption is the underlying cause 2, 3

• The FDA label suggests 100 mcg monthly 1, but evidence supports that 1000 mcg dosing is necessary to meet metabolic requirements in many patients 3
• For post-bariatric surgery patients specifically: 1000 mcg every 3 months indefinitely 2

Critical Administration Guidelines

Route of Administration

• Use intramuscular or deep subcutaneous injection only 1
• Never use the intravenous route for standard treatment as it results in almost complete urinary excretion 1
• Exception: One case report demonstrated effectiveness of IV methylcobalamin (7.5 mg total over 5 weeks) for severe neurological complications unresponsive to IM therapy, though this is not standard practice 5

Concentration Considerations

• Standard vials contain 1000 mcg/mL 1
• Inspect visually for particulate matter and discoloration before administration 1
• A comparative study showed that 500 mcg three times weekly produces significantly higher serum cobalamin levels (1892 pg/mL) compared to 1500 mcg once weekly (1438 pg/mL), suggesting more frequent smaller doses may be more effective 6

Special Populations and Precautions

Renal Dysfunction

Avoid cyanocobalamin in patients with renal dysfunction; use methylcobalamin or hydroxocobalamin instead due to potential accumulation of the cyanide moiety and increased cardiovascular risk 7

Pregnancy After Bariatric Surgery

• Check B12 levels every 3 months throughout pregnancy 2
• Continue regular supplementation as malabsorption persists

Concomitant Therapy

• Never administer folic acid before treating B12 deficiency, as it may mask the deficiency while allowing irreversible neurological damage to progress 4
• If folic acid deficiency coexists, administer it concomitantly with B12 therapy 1

Monitoring Protocol

• Check serum B12 and homocysteine every 3 months until stabilization, then annually 4, 2
• Target homocysteine level <10 μmol/L for optimal neurological outcomes 4
• Assess for reticulocytosis between days 5-10 of treatment to confirm therapeutic response 8
• Monitor for improvement in specific symptoms: difficulty concentrating, short-term memory loss, peripheral neuropathy 4

Common Pitfalls to Avoid

• Do not discontinue therapy even if levels normalize when malabsorption is the cause—lifelong therapy is required 2
• Do not use inadequate dosing (100 mcg) when 1000 mcg provides superior retention without additional cost or toxicity 3
• Do not delay treatment in neurological cases—aggressive alternate-day dosing should continue until no further improvement 4
• If neurological symptoms recur during maintenance, increase injection frequency rather than assuming treatment failure 2