What is the protocol for intramuscular (IM) vitamin B12 supplementation?

From the Guidelines

Intramuscular vitamin B12 supplementation is recommended for patients with severe deficiency, pernicious anemia, or malabsorption issues, with a standard regimen of hydroxocobalamin 1 mg intramuscularly administered on alternate days until there is no further improvement, then hydroxocobalamin 1 mg intramuscularly administered every 2 months 1.

Key Considerations

• For people with neurological involvement, urgent specialist advice should be sought from a neurologist and haematologist, and treatment should be initiated immediately with hydroxocobalamin 1 mg intramuscularly on alternate days until there is no further improvement, then hydroxocobalamin 1 mg intramuscularly every 2 months 1.
• For people with no neurological involvement, treatment should be initiated with hydroxocobalamin 1 mg intramuscularly three times a week for 2 weeks, followed by maintenance treatment with 1 mg intramuscularly every 2–3 months for life 1.
• Blood levels should be monitored periodically, especially during initial treatment, to ensure adequate replacement 1.

Administration and Monitoring

• When administering, use a 1-inch, 22-25 gauge needle injected into the deltoid or vastus lateralis muscle.
• Common side effects include pain at the injection site, mild diarrhea, or itching; serious allergic reactions are rare.
• Patients should be informed that symptom improvement, particularly neurological symptoms, may take several months despite normalized blood levels.

Special Considerations

• Patients with a history of total gastrectomy or continuous malabsorptive diseases should receive high doses of 1000 mg cobalamin every second day for 2 weeks (or daily for 5 days) 1.
• Patients with inflammatory bowel disease (IBD) and ileal involvement and/or resection and/or clinical deficiency features should be screened yearly for vitamin B12 deficiency, and those with a clinical deficiency should receive 1000 mg of vitamin B12 by intramuscular injection every other day for a week and then every month for life 1.

From the FDA Drug Label

CLINICAL PHARMACOLOGY Vitamin B12 is essential to growth, cell reproduction, hematopoiesis, and nucleoprotein and myelin synthesis. Cyanocobalamin is quantitatively and rapidly absorbed from intramuscular and subcutaneous sites of injection; the plasma level of the compound reaches its peak within 1 hour after intramuscular injection Prompt parenteral administration of vitamin B12 prevents progression of neurologic damage. The main points about IM B12 supplementation are:

• Rapid absorption: Cyanocobalamin is quantitatively and rapidly absorbed from intramuscular sites of injection.
• Peak plasma level: The plasma level of the compound reaches its peak within 1 hour after intramuscular injection.
• Prevention of neurologic damage: Prompt parenteral administration of vitamin B12 prevents progression of neurologic damage 2.

From the Research

IM B12 Supplementation

• The effectiveness of intramuscular (IM) vitamin B12 supplementation has been compared to oral and sublingual administration in several studies 3, 4, 5.
• A 2005 study found that high oral doses of B12 (1000 mcg and 2000 mcg) were as effective as IM administration in achieving haematological and neurological responses 3.
• A 2019 study compared sublingual (SL) vs. IM administration of vitamin B12 and found that SL tablets were superior to IM injections in restoring B12 levels 4.
• A 2024 systematic review and network meta-analysis found that all IM, oral, and SL routes of administration of vitamin B12 can effectively increase the level of vitamin B12 without significant differences between them 5.
• The same study found that the IM route ranked first in increasing vitamin B12 levels, followed by the SL route, but these differences did not reach statistical significance 5.

Comparison of Administration Routes

• The studies suggest that different routes of vitamin B12 supplementation (IM, oral, and SL) can be effective in treating vitamin B12 deficiency 3, 4, 5.
• The choice of administration route may depend on various factors, including patient preference, convenience, and potential side effects 4.
• Further research is needed to determine the optimal route of administration for vitamin B12 supplementation 5.

Diagnosis and Treatment of Vitamin B12 Deficiency

• Vitamin B12 deficiency can be diagnosed using various tests, including serum B12, holotranscobalamin, serum methylmalonic acid, and plasma homocysteine measurements 6.
• The treatment of vitamin B12 deficiency typically involves supplementation with vitamin B12, which can be administered via IM, oral, or SL routes 3, 4, 5.
• The diagnosis and treatment of vitamin B12 deficiency require careful consideration of the patient's individual needs and circumstances 6.