With metformin
Safety flag
Long-term metformin use can reduce vitamin B12 absorption and serum B12 concentration.
Interaction evidence source All research profiles
Vitamin B12
Hydroxocobalamin
Prepared by the ezGLP team. Sources last checked . Profile reviewed .
Also known as Vitamin B12a
Routes represented in the knowledgebase: Subcutaneous (SubQ).
Educational overview
B12-replacement injections and the FDA-approved high-dose IV cyanide antidote are different products; do not treat them as interchangeable.
Hydroxocobalamin (vitamin B12a) is one of the cobalamins, a family of cobalt-containing compounds with vitamin B12 activity. It differs from cyanocobalamin only in the ligand attached to the central cobalt atom: a hydroxyl group rather than a cyanide group. In the body both forms are converted to the active coenzymes methylcobalamin and adenosylcobalamin, which are required for methionine synthase and methylmalonyl-CoA mutase, enzymes central to DNA synthesis, red blood cell formation, and myelin maintenance. Hydroxocobalamin binds plasma proteins more tightly than cyanocobalamin and is retained in tissues longer. It is also a cyanide scavenger, forming cyanocobalamin that is excreted in urine, which underlies its second, unrelated use as an antidote.
Evidence for hydroxocobalamin in vitamin B12 deficiency comes from decades of clinical use and comparative pharmacokinetic studies rather than from large modern randomized trials. Studies from the 1960s onward showed that intramuscular hydroxocobalamin produces more sustained serum concentrations than the same amount of cyanocobalamin, which is why several national guidelines, including the NICE guideline on vitamin B12 deficiency in adults, list it as the injectable form in the United Kingdom. A 2018 Cochrane review found that high-dose oral B12 appears as effective as intramuscular injection for correcting deficiency, though the evidence was of low quality. For cyanide poisoning, approval rested on open-label studies in smoke-inhalation and poisoning victims.
Two very different hydroxocobalamin products exist and are not interchangeable. In the United States, hydroxocobalamin injection at 1,000 micrograms per milliliter is an FDA-approved prescription drug for vitamin B12 deficiency states such as pernicious anemia, sold under generic labels on DailyMed. Cyanokit is an FDA-approved lyophilized 5-gram vial for intravenous infusion in known or suspected cyanide poisoning, first approved in 2006. In the United Kingdom and much of Europe, hydroxocobalamin is the standard prescription B12 injection and is not sold over the counter. Oral and sublingual hydroxocobalamin supplements exist but are less common than cyanocobalamin or methylcobalamin. Compounded injectable B12 blends sold through wellness clinics are not FDA-approved products.
Hydroxocobalamin solutions are deep red and light-sensitive; labels direct storage at controlled room temperature in the carton, protected from light, and single-dose vials are discarded after use. Cyanokit is stored at room temperature and has a shelf life that fire departments and hospitals track closely. For a dose log or inventory record, relevant details include the product name and concentration, the route (intramuscular for deficiency; intravenous only for the antidote), lot number and expiry, and the reason for treatment. Because hydroxocobalamin colors urine and skin red for days and interferes with colorimetric laboratory tests and pulse co-oximetry, noting the date of a dose helps interpret subsequent results.
- Category
- Vitamin B12
- Routes represented
- Subcutaneous (SubQ)
- Storage context
- Follow the product or pharmacy label; requirements vary by route and formulation.
Published literature
No verified PubMed or DOI link is available for this entry.
Safety evidence
Common or reported: injection-site reaction, rash or itching, mild diarrhea.
Serious or important: rare anaphylaxis, hypokalemia during rapid correction of severe deficiency.
Effects vary substantially by chemical form and route.
Safety evidence sourceInteraction evidence
These are general, pairwise evidence notes. Green identifies the potential-synergy category, while Lv3/Lv2/Lv1 communicates evidence strength; it does not guarantee benefit or cancel a safety warning.
Common questions
What is the difference between cyanocobalamin and hydroxocobalamin?
Both are forms of vitamin B12 that the body converts to the active coenzymes. Cyanocobalamin is synthetic, highly stable, inexpensive, and the form in most US supplements and injections. Hydroxocobalamin is the form found in food and made by bacteria; it binds plasma proteins more strongly and stays in the body longer after injection, which is why UK guidance favors it for maintenance injections. Neither has been shown superior for correcting deficiency in head-to-head trials of oral supplements.
Is hydroxocobalamin FDA approved?
Yes, in two separate forms. Generic hydroxocobalamin injection is an approved prescription drug for vitamin B12 deficiency and pernicious anemia, given intramuscularly. Cyanokit, a high-concentration hydroxocobalamin for intravenous infusion, was approved in 2006 for known or suspected cyanide poisoning. These are distinct products with different concentrations and routes. Injectable B12 products mixed with other vitamins or amino acids by compounding pharmacies or wellness clinics are not FDA-approved products.
Why does hydroxocobalamin turn urine red?
Hydroxocobalamin is an intensely red compound, and the fraction not bound to tissue is excreted unchanged by the kidneys. After an intramuscular B12 dose the effect is mild, but after the multi-gram Cyanokit dose used for cyanide poisoning, urine, skin, and mucous membranes turn dark red for several days. The label notes that this coloration can interfere with colorimetric laboratory assays, pulse co-oximetry, and hemodialysis equipment sensors during that period.
Can hydroxocobalamin be taken orally instead of injected?
Oral hydroxocobalamin supplements exist, though most oral B12 products contain cyanocobalamin or methylcobalamin. A 2018 Cochrane review concluded that high-dose oral vitamin B12 appears as effective as intramuscular injection for raising serum B12 in deficient adults, though the studies were small and of low quality. Guidelines generally reserve injections for people with malabsorption, pernicious anemia, or neurological symptoms, where reliable absorption cannot be assumed.
Further reading
- DailyMed, Hydroxocobalamin injection, solution (Actavis)
- DailyMed, Cyanokit (hydroxocobalamin) for injection
- NIH Office of Dietary Supplements, Vitamin B12 fact sheet for health professionals
- NICE guideline NG239, Vitamin B12 deficiency in over 16s (2024)
- Wang et al., oral versus intramuscular vitamin B12, Cochrane 2018
- NHS, Hydroxocobalamin medicine information
Summarised from published literature for reference only, with citations to the source. Evidence is graded as reported and is not a recommendation to combine, dose, or use any compound.
For personal tracking and education only. Not medical advice, diagnosis, or treatment, and not a medical device. Peptides may be prescription-only or unapproved where you live. Consult a licensed healthcare professional.