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Uses and Administration
Vitamin B12, a water-soluble vitamin, occurs in the body mainly as methylcobalamin (mecobalamin) and as adenosylcobalamin (cobamamide) and hydroxocobalamin. Mecobalamin and cobamamide act as coenzymes in nucleic acid synthesis. Mecobalamin is also closely involved with folic acid in several important metabolic pathways.
Vitamin B12 deficiency can occur in strict vegetarians with an inadequate dietary intake, although it may take many years before a deficiency is produced. Deficiency is more likely in patients with malabsorption syndromes or metabolic disorders, nitrous oxide-induced megaloblastosis, or after gastrectomy or extensive ileal resection. Deficiency leads to the development of megaloblastic anaemias and demyelination and other neurological damage. A specific anaemia known as pernicious anaemia develops in patients with an absence of the intrinsic factor necessary for good absorption of the vitamin from dietary sources.
Vitamin B12 preparations are used in the treatment and prevention of vitamin B12 deficiency. It is essential to identify the exact cause of deficiency, preferably before starting therapy. Hydroxocobalamin is generally preferred to cyanocobalamin; it binds more firmly to plasma proteins and is retained in the body longer (see under Pharmacokinetics, Refer to ). Cyanocobalamin and hydroxocobalamin are generally given by the intramuscular route, although cyanocobalamin may be given orally or subcutaneously, or intranasally (see also under Administration, Refer to ). Oral cyanocobalamin may be used in treating or preventing vitamin B12 deficiency of dietary origin.
In the UK, recommended doses for pernicious anaemia and other megaloblastic anaemias are as follows:
in patients without neurological involvement doses are hydroxocobalamin (or cyanocobalamin) 250 to 1000 micrograms intramuscularly on alternate days for 1 to 2 weeks, then 250 micrograms weekly until the blood count returns to normal. Maintenance doses of 1000 micrograms are given every 2 to 3 months as hydroxocobalamin, or monthly as cyanocobalamin
if there is neurological involvement, hydroxocobalamin or cyanocobalamin may be given intramuscularly in doses of 1000 micrograms on alternate days and continued for as long as improvement occurs. Maintenance doses of 1000 micrograms are given every 2 months as hydroxocobalamin, or monthly as cyanocobalamin
for theprophylaxis of anaemia associated with vitamin B12deficiency resulting from gastrectomy or malabsorption syndromes hydroxocobalamin may be given in doses of 1000 micrograms intramuscularly every 2 or 3 months or cyanocobalamin in doses of 250 to 1000 micrograms intramuscularly each month
for vitamin B12deficiency of dietary origin, oral cyanocobalamin 50 to 150 micrograms may be taken daily between meals. For discussion of oral cyanocobalamin therapy for the treatment of pernicious anaemia, see Administration, Refer to
Lower doses of both cyanocobalamin and hydroxocobalamin are recommended for pernicious anaemia in the USA:
for treatment, the usual intramuscular or subcutaneous dose of cyanocobalamin is 100 micrograms daily for 6 or 7 days; if there is a response, a further 7 doses may be given on alternate days, then every 3 to 4 days for 2 to 3 weeks. For hydroxocobalamin the usual intramuscular dose is 30 micrograms daily for 5 to 10 days
for maintenance, monthly injections of cyanocobalamin 100 micrograms (intramuscularly or subcutaneously), or intramuscular hydroxocobalamin 100 to 200 micrograms are given. Intranasal preparations of cyanocobalamin are also available for maintenance therapy in those without neurological involvement. An initial dose of 500 micrograms (as one 500-microgram spray in one nostril) is given once weekly and then adjusted according to response. Alternatively, an initial dose of 50 micrograms (as one 25-microgram spray in each nostril) is given once daily, and can be increased to twice daily if required
in patients with normal gastrointestinal absorption, oral cyanocobalamin doses of 1 to 25 micrograms daily are considered sufficient as a dietary supplement(see also Administration, Refer to )
Treatment of vitamin B12 deficiency usually results in rapid haematological improvement and a striking clinical response. However, neurological symptoms respond more slowly and in some cases remission may not be complete.
Cobamamide and mecobalamin may also be used for vitamin B12 deficiency.
Hydroxocobalamin may also be given in the treatment of tobacco amblyopia and Leber's optic atrophy; initial doses are 1000 micrograms daily for 2 weeks intramuscularly followed by 1000 micrograms twice weekly for as long as improvement is maintained. Thereafter, 1000 micrograms is given every 1 to 3 months.
Hydroxocobalamin is also used for the treatment of known or suspected cyanide toxicity (see Refer to ). Each 2.5 g vial of hydroxocobalamin is reconstituted with 100 mL of diluent, preferably sodium chloride 0.9%. The starting dose for adults is 5 g intravenously over 15 minutes. Depending on the severity of the toxicity and the clinical response, a second dose of 5 g may be infused over 15 minutes to 2 hours.
For administration in children, see Refer to .
Cyanocobalamin and hydroxocobalamin are also used in the Schilling test to investigate vitamin B12 absorption and deficiency states. They are given in a non-radioactive form with cyanocobalamin radioactively-labelled with cobalt-57 (Refer to) or cobalt-58 (Refer to) and the amount of radioactivity excreted in the urine can be used to assess absorption status. A differential Schilling test, in which the forms of cyanocobalamin are given under different conditions (such as with intrinsic factor, antibacterials, or pancreatic enzymes) can provide information about the cause of the malabsorption.
(last reviewed 2010-08-23; last modified 2010-09-03)
Administration
The small amounts of vitamin B12 present in the diet are absorbed from the gastrointestinal tract by an active process that involves binding with intrinsic factor. As intrinsic factor is absent in patients who have developed pernicious anaemia it has often been assumed that oralvitamin B12 preparations will therefore be ineffective. However, about 1% of an oral dose is absorbed by passive diffusion, and with large doses this amount may be sufficient for therapy. Thus attention has been given again to the use of oral cobalamins for the treatment of pernicious anaemia.1-4 Oral cyanocobalamin 2000 micrograms daily was as effective as intramuscular therapy in patients with vitamin B12 deficiency in a comparative study.5 Some now consider that oral doses of 1000 micrograms daily,3,6or every 2 weeks for children,7are a suitable alternative to injections given at monthly or so intervals; others still deem oral use to be unjustified on the grounds of negligible oral absorption.8A systematic review9 of 2 studies found some evidence for a satisfactory haematological, biochemical, and clinical short-term response to oral replacement in some patients with conditions associated with malabsorption. Another review10 concluded that, while there is substantial evidence to support the use of 1000 to 2000 micrograms daily of oral cyanocobalamin as maintenance therapy, parenteral therapy is preferable for initial treatment of those with neurological symptoms. Oral formulations are being developed which use carrier molecules to enhance absorption.
Cyanocobalamin is also effective when given intranasally,11 with peak plasma concentrations greater than those achievable orally, and this may offer another alternative to injection. The intranasal absorption of hydroxocobalamin has been studied.12,13
Cyanocobalamin has also been givensublingually. Normalisation of serum cobalamin concentration has been reported in 18 patients given sublingual cyanocobalamin 2000 micrograms daily for 7 to 12 days;14 500 micrograms sublingually daily was found to be as effective as the same dose given orally in correcting deficiency.15
(last reviewed 2010-08-23; last modified 2010-08-24)
References
1. Lederle FA. Oral cobalamin for pernicious anemia: medicine's best kept secret?JAMA. 1991; 265: 94–5. PubMed
2. Hathcock JN, Troendle GJ. Oral cobalamin for treatment of pernicious anemia?JAMA. 1991; 265: 96–7. PubMed
3. Elia M. Oral or parenteral therapy for B12 deficiency.Lancet. 1998; 352: 1721–2. PubMed
4. Anonymous. Oral or intramuscular vitamin B12?Drug Ther Bull. 2009; 47: 19–21. PubMed
5. Kuzminski AM, et al.. Effective treatment of cobalamin deficiency with oral cobalamin.Blood. 1998; 92: 1191–8. PubMed
6. Andrès E, et al.. Usefulness of oral cyanocobalamin therapy in severe hematologic manifestations related to vitamin B12 deficiency.Ann Pharmacother. 2004; 38: 1086–7. PubMed
7. Çetin M, Altay C. Efficacy of oral vitamin B12 treatment in children.J Pediatr. 2001; 139: 754. PubMed
8. Van der Kuy P-HM, et al.. Bioavailability of oral hydroxocobalamin.Br J Clin Pharmacol. 2000; 49: 395P–396P.
9. Vidal-Alaball J, et al.. Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency. Available in The Cochrane Database of Systematic Reviews; Issue 3. Chichester: John Wiley; 2005 (accessed 05/09/06). PubMed
10. Lane LA, Rojas-Fernandez C. Treatment of Vitamin B12-deficiency anemia: oral versus parenteral therapy.Ann Pharmacother. 2002; 36: 1268–72. PubMed
11. Romeo VD, et al.. Intranasal cyanocobalamin.JAMA. 1992; 268: 1268–9. PubMed
12. van Asselt DZB, et al.. Nasal absorption of hydroxocobalamin in healthy elderly adults.Br J Clin Pharmacol. 1998; 45: 83–6. PubMed
13. Slot WB, et al.. Normalization of plasma vitamin B12 concentration by intranasal hydroxocobalamin in vitamin B12-deficient patients.Gastroenterology. 1997; 113: 430–3. PubMed
14. Delpre G, et al.. Sublingual therapy for cobalamin deficiency as an alternative to oral and parenteral cobalamin supplementation.Lancet. 1999; 354: 740–1. PubMed
15. Sharabi A, et al.. Replacement therapy for vitamin B12 deficiency: comparison between the sublingual and oral route.Br J Clin Pharmacol. 2003; 56: 635–8. PubMed
Administration in children
In neonates and children up to 17 years of age with congenital transcobalamin II deficiency, the BNFC suggests a dose of hydroxocobalamin 1 mg by intramuscular injection given three times weekly. After 1 year this may be reduced as appropriate to 1 mg once weekly.
In children aged from 1 month with megaloblastic anaemia ( Refer to ) or children with Leber's optic atrophy, hydroxocobalamin doses are similar to those used in adults in the UK, see Uses and Administration, Refer to .
Hydroxocobalamin is used as an antidote for cyanide poisoning in children. A dose of 70 mg/kg (maximum 5 g) is given by intravenous infusion over 15 minutes; a second dose may be infused over 15 minutes to 2 hours, depending on the severity of poisoning and clinical response.
Hydroxocobalamin can also be used in children with methylmalonic acidaemia and homocystinuria, see Amino Acid Metabolic Disorders, Refer to .
(last reviewed 2010-08-23; last modified 2017-01-05)
Amino acid metabolic disorders
References to the use of hydroxocobalamin in the treatment of inborn errors of vitamin B12metabolism.1-3 Some patients with homocystinuria ( Refer to ) or methylmalonic acidaemia have responded to cobalamins—the BNFC suggests an initial intramuscular dose of hydroxocobalamin 1 mg daily, for 5 to 7 days, in patients from one month of age; this is reduced, according to response, to 1 mg once or twice weekly. Some children respond to maintenance with 5 to 10 mg hydroxocobalamin given orally once or twice weekly.
(last reviewed 2010-08-23; last modified 2016-12-22)
References
1. Linnell JC, Bhatt HR. Inherited errors of cobalamin metabolism and their management.Baillieres Clin Haematol. 1995; 8: 567–601. PubMed
2. Andersson HC, Shapira E. Biochemical and clinical response to hydroxocobalamin versus cyanocobalamin treatment in patients with methylmalonic acidemia and homocystinuria (cblC).J Pediatr. 1998; 132: 121–4. PubMed
3. Smith DL, Bodamer OA. Practical management of combined methylmalonicaciduria and homocystinuria.J Child Neurol. 2002; 17: 353–6. PubMed
Cardiovascular disease
For mention of the possible link between vitamin B12, hyperhomocysteinaemia, and cardiovascular disease, see under Folic Acid Refer to .
(last reviewed 2010-08-23; last modified 2008-07-31)
Cyanide toxicity
Hydroxocobalamin combines with cyanide to form cyanocobalamin, and thus may be used as an antidote to cyanide toxicity (see under Hydrocyanic Acid, Refer to ). Hydroxocobalamin is reported to be effective in controlling cyanide toxicity due to nitroprusside infusion,1 and after exposure to inhaled combustion products in residential fires.2
It has been hypothesised that the amount of cyanocobalamin formed is limited by the number of cyanide ions present and the amount of hydroxocobalamin given. For a given dose of hydroxocobalamin a maximum concentration of cyanocobalamin would be reached, allowing measurement of cyanocobalamin as a surrogate emergency marker for cyanide levels, which are difficult and time-consuming to measure. For a 5-g dose of hydroxocobalamin given intravenously over 30 minutes, the authors of one study considered a cyanocobalamin concentration of about 300 micromoles/litre a sign that all the hydroxocobalamin had been used, and more should be given.2 They cautioned, however, that, unless antidote regimen and blood sampling were similar to that in their study, this concentration should not be extrapolated to other patient populations.
In another patient given hydroxocobalamin 5 g intravenously over 2 hours,3 plasma concentrations of cyanide rose 1 hour after treatment with hydroxocobalamin. The authors attributed this to hydroxocobalamin extracting cyanide from red blood cells to form cyanocobalamin in plasma, which was then measured as cyanide.
A review4 of the role of hydroxocobalamin in acute cyanide poisoning found insufficient evidence to routinely recommend empirical use for smoke inhalation, although some advantages over standard therapy were noted. Unlike nitrites, hydroxocobalamin does not cause methaemoglobinaemia, a particular risk after smoke inhalation. Additionally, its low toxicity may be beneficial for cyanide toxicity in children and pregnant women.
For doses of hydroxocobalamin used for cyanide toxicity in adults, see Uses and Administration, Refer to , and in children, see Administration in Children, Refer to .
(last reviewed 2010-08-23; last modified 2014-04-08)
References
1. Zerbe NF, Wagner BKJ. Use of vitamin B12 in the treatment and prevention of nitroprusside-induced cyanide toxicity.Crit Care Med. 1993; 21: 465–7. PubMed
2. Houeto P, et al.. Relation of blood cyanide to plasma cyanocobalamin concentration after a fixed dose of hydroxocobalamin in cyanide poisoning.Lancet. 1995; 346: 605–8. PubMed
3. Weng T-I, et al.. Elevated plasma cyanide after hydroxocobalamin infusion for cyanide poisoning.Am J Emerg Med. 2004; 22: 492–3. PubMed
4. Shepherd G, Velez LI. Role of hydroxocobalamin in acute cyanide poisoning.Ann Pharmacother. 2008; 42: 661–9. PubMed
Deficiency states
The emergence of newer metabolic assays for homocysteine and methylmalonic acid has led to the identification of subtle vitamin B12deficiency1-3 without the overt manifestations of megaloblastic anaemia (see Refer to ) or neurological disease; this condition appears to be particularly common in the elderly.1,4-6 At present, there is no clear clinical rationale for treating subtle deficiency,1,7although suggestions for management have been made.8A study in elderly patients suggested that food-cobalamin malabsorption, a disorder characterised by the inability to release vitamin B12 from food or its binding protein, might be to blame for this subtle deficiency; these patients had some neurological or haematological abnormalities, and treatment with oral or parenteral vitamin B12 was found to be effective.6There have also been suggestions that deficiency may be linked to some immunological impairment, identified as impaired antibody responses to pneumococcal vaccine.9Moreover, raised homocysteine concentrations have been identified as a risk factor for atherosclerosis and ischaemic heart disease, and there is increasing interest in the potential of B vitamins, including B12, to reduce homocysteine concentrations and therefore atherosclerotic outcomes (see Cardiovascular Disease, under Uses and Administration of Folic Acid, Refer to ). Evidence that hyperhomocysteinaemia may be a risk factor for dementia is limited.5 A systematic review concluded that evidence for efficacy of vitamin B12 in improving cognitive function of people with dementia (and low serum vitamin B12concentrations) was lacking.10
Dietary vitamin B12 deficiency in infants may lead to developmental abnormalities.11,12
The issue of fortification of food with folic acid (see under Folic Acid, Refer to ) to reduce the number of infants born with neural tube defects ( Refer to ) has created debate on the risks of masking vitamin B12 deficiency, and fortification with vitamin B12 has also been recommended, see under Folic Acid, Refer to . An independent association between low maternal vitamin B12 status and an increased risk of neural tube defects has also been reported, see Neural Tube Defects, Refer to .
(last reviewed 2010-08-23; last modified 2014-04-08)
References
1. Carmel R. Subtle cobalamin deficiency.Ann Intern Med. 1996; 124: 338–40. PubMed
2. Green R. Screening for vitamin B12deficiency: caveat emptor.Ann Intern Med. 1996; 124: 509–11. PubMed
3. Carmel R, et al.. Update on cobalamin, folate, and homocysteine.Hematology (Am Soc Hematol Educ Program). 2003; PubMed
4. Andrès E, et al.. Vitamin B12(cobalamin) deficiency in elderly patients.Can Med Assoc J. 2004; 171: 251–9. PubMed
5. Clarke R. Prevention of vitamin B-12 deficiency in old age.Am J Clin Nutr. 2001; 73: 151–2. PubMed
6. Andrès E, et al.. Food-cobalamin malabsorption in elderly patients: clinical manifestations and treatment.Am J Med. 2005; 118: 1154–9. PubMed
7. Metz J. What's the use of oral vitamin B12? A neglected but valid treatment route may have new uses in the future.Med J Aust. 1999; 170: 407. PubMed
8. Carmel R. How I treat cobalamin (vitamin B12) deficiency.Blood. 2008; 112: 2214–21. PubMed
9. Fata FT, et al.. Impaired antibody responses to pneumococcal polysaccharide in elderly patients with low serum vitamin B12 levels.Ann Intern Med. 1996; 124: 299–304. PubMed
10. Malouf R, Areosa Sastre A. Vitamin B12 for cognition. Available in The Cochrane Database of Systematic Reviews; Issue 3. Chichester: John Wiley; 2003 (accessed 09/01/06). PubMed
11. Emery ES, et al.. Vitamin B12 deficiency: a cause of abnormal movements in infants.Pediatrics. 1997; 99: 255–6. PubMed
12. von Schenck U, et al.. Persistence of neurological damage induced by dietary vitamin B-12 deficiency in infancy.Arch Dis Child. 1997; 77: 137–9. PubMed
Eczema
A small study found that topical application of a preparation containing vitamin B12 was more effective than placebo in patients with atopic eczema.1
(last reviewed 2010-08-23; last modified 2006-10-03)
References
1. Stücker M, et al.. Topical vitamin B12—a new therapeutic approach in atopic dermatitis—evaluation of efficacy and tolerability in a randomized placebo-controlled multicentre clinical trial.Br J Dermatol. 2004; 150: 977–83. PubMed
Megaloblastic anaemia
The megaloblastic anaemias are characterised by macrocytosis (an increased mean cell volume) and the production of distinctive morphological changes and abnormal maturation in developing haematopoietic cells in the bone marrow: white cell and platelet lines are affected as well as erythroid precursors, and in severe cases anaemia may be associated with leucopenia and thrombocytopenia. Megaloblastic anaemia is a consequence of impaired DNA biosynthesis in the bone marrow, usually due to a deficiency of vitamin B12 (cobalamins) or folate, both of which are essential for this process. Although the haematological symptoms of B12 deficiency and folate deficiency are similar it is important to distinguish between them since the use of folate alone in B12-deficient megaloblastic anaemia can improve haematological symptoms without preventing aggravation of accompanying neurological symptoms, and may lead to severe nervous system sequelae such as subacute combined degeneration of the spinal cord. Where it is desirable to start therapy immediately, combined treatment for both deficiencies may be started once suitable samples have been taken to permit diagnosis of the deficiency, and the patient converted to the appropriate treatment once the cause of the anaemia is known.
Vitamin B12 deficiency anaemia.Vitamin B12 deficiency and its associated symptoms may be due to malabsorption (including following gastrectomy), dietary deficiency (mainly in strict vegetarians), competition with intestinal bacteria or parasites, or to the effect of drugs such as nitrous oxide. In populations of northern European origin, pernicious anaemia, in which atrophy of the gastric mucosa results in a lack of the intrinsic factor essential for B12 absorption, is the most frequent cause. As body stores of the vitamin are large, it may take several years for signs of deficiency to manifest once the defect in absorption occurs.
In addition to megaloblastic anaemia, vitamin B12 deficiency may result in neurological damage, including peripheral neuropathy and effects on mental function ranging from mild neurosis to dementia.
TREATMENT. The treatment is with vitamin B12, almost always by the intramuscular or sometimes the deep subcutaneous route since in most patients absorption from the gastrointestinal tract is inadequate. Hydroxocobalamin is generally preferred to cyanocobalamin since it need be given less often. Regimens may vary, but hydroxocobalamin 1 mg every few days for 6 doses will restore normal body stores of the vitamin (see also Uses and Administration, Refer to ). Dosage has not been well established in children; the BNFC recommends similar hydroxocobalamin doses to those licensed in adults. The haematological response to therapy is rapid, with improvement in most parameters and symptoms beginning within 48 hours. Neurological abnormalities may take much longer to respond, and may not do so completely.
PROPHYLAXIS. Where the defect in B12 handling is irreversible, as in pernicious anaemia, maintenance therapy must continue for life to prevent a recurrence of the deficiency. Therapy must also be given prophylactically after total gastrectomy or total ileal resection, or where gastrointestinal surgery is shown to have impaired absorption of the vitamin. Typically, injection of hydroxocobalamin 1 mg every 3 months is used. In patients whose diet supplies inadequate B12, deficiency may be prevented, in the absence of other causes, by much lower oral doses given as a supplement; up to 150 micrograms of cyanocobalamin daily has been recommended.
Folate-deficiency anaemia. Deficiency of folate may be due to inadequate diet, or malabsorption syndromes (such as coeliac disease or sprue), to increased need (as in pregnancy, one of the most common causes of megaloblastic anaemia, or the increased haematopoiesis of haemolytic syndromes), to increased urinary loss or loss due to haemodialysis, or to an adverse effect of alcohol, antiepileptics, or other drugs.
The clinical features of folate-deficient megaloblastic anaemia are similar to those of disease due to vitamin-B12 deficiency except that the accompanying severe neuropathy does not occur, and deficiency may develop much more rapidly. Deficiency may also be associated with neural tube defects ( Refer to ) if it occurs in pregnancy.
TREATMENT. Once folate deficiency has been established the usual treatment in the UK is oral folic acid 5 mg daily. Lower doses of up to 1 mg are suggested in the USA. It is customary to continue therapy for at least 4 months, the time necessary for complete red cell replacement. In patients with malabsorption, therapy may require higher doses, up to 15 mg of folic acid daily. As in B12-deficiency anaemia, the response to therapy is rapid.
PROPHYLAXIS. Long-term maintenance is rarely needed, except in a few patients in whom the underlying cause of folate deficiency cannot be treated (for example in some severe haemolytic syndromes). Doses of 5 mg daily or even weekly have been suggested for prophylaxis in patients undergoing dialysis or with chronic haemolytic states, depending on the diet and rate of haemolysis; a dose of 400 micrograms daily is recommended in the USA.
For primary prophylaxis of megaloblastic anaemia in pregnancy, folic acid is given in the UK in a usual dose of 500 micrograms daily, often with a ferrous salt for prophylaxis of iron deficiency.
Drugs that act as inhibitors of dihydrofolate reductase, such as methotrexate, may produce severe megaloblastic anaemia which cannot be reversed by therapy with folic acid. The adverse effects of such drugs may be largely prevented or reversed by therapy with folinic acid, which can be incorporated into folate metabolism without the need for reduction by the inhibited enzyme. For details of such 'folinic acid rescue', see under Folinic Acid, Refer to .
General references.
(last reviewed 2010-08-23; last modified 2013-09-24)
For further information on the substances mentioned above, see:
Cyanocobalamin (see Vitamin B Substances, Refer to; Folic Acid, Refer to; Folinic Acid, Refer to; Hydroxocobalamin (see Vitamin B Substances, Refer to
References
1. Wickramasinghe SN. Folate and vitamin B12 deficiency and supplementation.Prescribers' J. 1997; 37: 88–95.
2. Wickramasinghe SN. The wide spectrum and unresolved issues of megaloblastic anemia.Semin Hematol. 1999; 36: 3–18. PubMed
3. Rasmussen SA, et al.. Vitamin B12deficiency in children and adolescents.J Pediatr. 2001; 138: 10–17. PubMed
4. Hoffbrand V, Provan D. Macrocytic anaemias. In: Provan D, ed. ABC of clinical haematology. 2nd ed. London: BMJ Publishing Group, 2003.
5. Stabler SP, Allen RH. Vitamin B12 deficiency as a worldwide problem.Annu Rev Nutr. 2004; 24: 299–326. PubMed
Neural tube defects
There is abnormality in homocysteine metabolism in many women who give birth to children with neural tube defects ( Refer to ); the enzyme methionine synthase, which converts homocysteine to methionine, requires both folate and vitamin B12 as cofactors, and low maternal vitamin B12concentrations may be an independent risk factor for neural tube defects.1A case-control study found elevated mid-trimester methylmalonic acid concentrations in women with pregnancies affected by neural tube defects, suggesting that abnormalities of cobalamin metabolism, and subsequent methylation, may be involved in the aetiology of neural tube defects.2Decreased vitamin B12 concentrations, but no folate deficiency, were found in 3 women with pregnancies affected by neural tube defects.3A review4 of case-control studies found a moderate association between low maternal vitamin B12 status and the risk of fetal neural tube defects, and results from a Canadian population, largely after folic acid supplementation was implemented, suggested a threefold increase in the risk of neural tube defect in offspring of women with vitamin B12 status in the lowest quartile.5An Irish study6 produced similar results. If confirmed by controlled prospective studies, this would suggest that additional supplementation with cobalamins may be warranted.3-5,7
(last reviewed 2010-08-23; last modified 2010-08-24)
References
1. Mills JL, et al.. Homocysteine metabolism in pregnancies complicated by neural-tube defects.Lancet. 1995; 345: 149–51. PubMed
2. Adams MJ, et al.. Elevated midtrimester serum methylmalonic acid levels as a risk factor for neural tube defects.Teratology. 1995; 51: 311–17. PubMed
3. Candito M, et al.. Anomalies du tube neural et vitamine B12: à propos de trois cas.Ann Biol Clin (Paris). 2004; 62: 235–8. PubMed
4. Ray JG, Blom HJ. Vitamin B12 insufficiency and the risk of fetal neural tube defects.Q J Med. 2003; 96: 289–95. PubMed
5. Thompson MD, et al.. Vitamin B-12 and neural tube defects: the Canadian experience.Am J Clin Nutr. 2009; 89: 697S–701S. PubMed
6. Molloy AM, et al.. Maternal vitamin B12 status and risk of neural tube defects in a population with high neural tube defect prevalence and no folic acid fortification.Pediatrics. 2009; 123: 917–23. PubMed
7. Refsum H. Folate, vitamin B12 and homocysteine in relation to birth defects and pregnancy outcome.Br J Nutr. 2001; 85 109–S113. PubMed
Osteoporosis
An elevated serum homocysteine concentration appears to be a risk factor for osteoporotic fractures in older men and women.1-3 Treatment with vitamin B12 and folate can reduce plasma homocysteine concentrations (see Cardiovascular Disease, under Folic Acid, Refer to ). In a placebo-controlled study of patients with hemiplegia following stroke (and at increased risk of hip fracture),4 those given folate and vitamin B12 were found to have a significantly reduced risk of hip fracture despite a lack of effect on bone mineral density. Vitamin B12 status has been associated with bone health in a number of studies,3,5 and it was suggested that the observed effects on fracture might be due to increased concentrations of vitamin B12rather than the lowering of plasma homocysteine.3,6
(last reviewed 2010-08-23; last modified 2007-07-17)
References
1. van Meurs JBJ, et al.. Homocysteine levels and the risk of osteoporotic fracture.N Engl J Med. 2004; 350: 2033–41. PubMed
2. McLean RR, et al.. Homocysteine as a predictive factor for hip fracture in older persons.N Engl J Med. 2004; 350: 2042–9. PubMed
3. van Meurs JBJ, Uitterlinden AG. Homocysteine and fracture prevention.JAMA. 2005; 293: 1121–2. PubMed
4. Sato Y, et al.. Effect of folate and mecobalamin on hip fractures in patients with stroke: a randomized controlled trial.JAMA ibid.. 2005; 293: 296: 1082–8. PubMed
5. Dhonukshe-Rutten RAM, et al.. Vitamin B-12 status is associated with bone mineral content and bone mineral density in frail elderly women but not in men.J Nutr. 2003; 133: 801–7. PubMed
6. Sugiyama T, et al.. Folate and vitamin B12 for hip fracture prevention after stroke.JAMA. 2005; 294: 792. PubMed
Rhinitis
A sublingual formulation of cyanocobalamin (PreHistin ; Cobalis, USA) has been reported to be under investigation in the management of seasonal allergic rhinitis, but published studies are lacking.
(last reviewed 2010-08-23; last modified 2010-08-09)
Drug Profile
Vitamin B12 is the name generally used for a group of related cobalt-containing compounds, also known as cobalamins , of which cyanocobalamin and hydroxocobalamin are the principal forms in clinical use.
(last reviewed 2010-08-23; last modified 2004-03-21)
Adverse Effects, Treatment and Precautions
Adverse Effects and Precautions
Allergic hypersensitivity reactions have occurred rarely after cyanocobalamin and hydroxocobalamin and include skin reactions such as rash and itching, and anaphylaxis. Patients who are hypersensitive to cyanocobalamin injection may be able to take oral cyanocobalamin. Antibodies to hydroxocobalamin-transcobalamin II complex have developed during hydroxocobalamin therapy.
Arrhythmias secondary to hypokalaemia have occurred at the beginning of parenteral treatment with hydroxocobalamin. Injection site reactions including pain, erythema, pruritus, induration, swelling, and necrosis can occur.
Intranasal cyanocobalamin may cause arthralgia, dizziness, headache, nasopharyngitis, and rhinitis; epistaxis has also been reported.
Other adverse effects reported with cyanocobalamin and hydroxocobalamin include gastrointestinal disturbances, fever, chills, hot flushing, dizziness, malaise, acneform and bullous eruptions, and tremor. Headaches, paraesthesia, and chromaturia have occurred with hydroxocobalamin.
Cyanocobalamin or hydroxocobalamin should, if possible, not be given to patients with suspected vitamin B12 deficiency without first confirming the diagnosis. Regular monitoring of the blood is advisable. Use of doses greater than 10 micrograms daily may produce a haematological response in patients with folate deficiency; indiscriminate use may mask the precise diagnosis. Conversely, folate may mask vitamin B12 deficiency (see Refer to ).
Cyanocobalamin should not be used for Leber's disease or tobacco amblyopia since these optic neuropathies may degenerate further.
(last reviewed 2010-08-23; last modified 2010-08-09)
Breast feeding
Vitamin B12 is distributed into breast milk.1 The American Academy of Pediatrics considers its use to be usually compatible with breast feeding.2
(last reviewed 2010-08-23; last modified 2010-08-07)
References
1. Samson RR, McClelland DBL. Vitamin B12 in human colostrum and milk.Acta Paediatr Scand. 1980; 69: 93–9. PubMed
2. American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk.Pediatrics ibid.. 2001; 108: 776–89. PubMed online
Hypersensitivity
Analysis, by the Boston Collaborative Drug Surveillance Program, of data on 15 438 patients hospitalised between 1975 and 1982 detected 3 allergic skin reactions attributed to cyanocobalamin among 168 recipients of the drug.1 For the purposes of the study, reactions were defined as being generalised morbilliform exanthems, urticaria, or generalised pruritus only.
In a patient with a generalised pruritic reaction to hydroxocobalamin (with subsequent urticaria, bronchospasm, and oropharyngeal angioedema), cyanocobalamin was relatively well-tolerated, with only one episode of delayed urticaria.2
(last reviewed 2010-08-23; last modified 2006-10-03)
References
1. Bigby M, et al. Drug-induced cutaneous reactions: a report from the Boston Collaborative Drug Surveillance Program on 15 438 consecutive inpatients, 1975 to 1982.JAMA. 1986; 256: 3358–63. PubMed
2. Heyworth-Smith D, Hogan PG. Allergy to hydroxycobalamin, with tolerance of cyanocobalamin.Med J Aust. 2002; 177: 162–3. PubMed
Local reactions
After 3 years of monthly intramuscular vitamin B12injections, a patient presented with a sclerotic plaque at the injection site, which was successfully treated by excision and local fat transfer. It was unclear as to whether the patient had reacted to the vehicle, the preservative, or to the cyanocobalamin.1Fascial haematoma after vitamin B12 injection leading to local compression (posterior arm compartment syndrome) has also been reported.2
(last reviewed 2010-08-23; last modified 2006-10-03)
References
1. Ho J, et al.. Vitamin B12-associated localized scleroderma and its treatment.Dermatol Surg. 2004; 30: 1252–5. PubMed
2. Knapke D, Truumees E. Posterior arm and deltoid compartment syndrome after vitamin B12 injection.Orthopedics. 2004; 27: 520–1. PubMed
Porphyria
The Drug Database for Acute Porphyria, compiled by the Norwegian Porphyria Centre (NAPOS) and the Porphyria Centre Sweden, classifies cyanocobalamin and hydroxocobalamin as not porphyrinogenic; either drug may be used as a drug of first choice and no precautions are needed. Cobamamide and mecobalamin are not classified.1
(last reviewed 2010-08-23; last modified 2011-11-14)
References
1. The Drug Database for Acute Porphyria. Available at: Link (accessed 07/10/11)
Interactions
Absorption of vitamin B12 from the gastrointestinal tract may be reduced by neomycin, aminosalicylic acid, histamine H2-antagonists, omeprazole, and colchicine. Serum concentrations may be decreased by use of oral contraceptives. Many of these interactions are unlikely to be of clinical significance but should be taken into account when performing assays for blood concentrations. Parenteral chloramphenicol may attenuate the effect of vitamin B12 in anaemia.
(last reviewed 2010-08-23; last modified 2008-07-31)
Pharmacokinetics
Vitamin B12 substances bind to intrinsic factor, a glycoprotein secreted by the gastric mucosa, and are then actively absorbed from the gastrointestinal tract. Absorption is impaired in patients with an absence of intrinsic factor, with a malabsorption syndrome or with disease or abnormality of the gut, or after gastrectomy. Absorption from the gastrointestinal tract can also occur by passive diffusion; little of the vitamin present in food is absorbed in this manner although the process becomes increasingly important with larger amounts such as those used therapeutically. After intranasal dosage, peak plasma concentrations of cyanocobalamin have been reached in 1 to 2 hours. The bioavailability of the intranasal preparation is about 7 to 11% of that by intramuscular injection.
Vitamin B12 is extensively bound to specific plasma proteins called transcobalamins; transcobalamin II appears to be involved in the rapid transport of the cobalamins to tissues. Vitamin B12 is stored in the liver, excreted in the bile, and undergoes extensive enterohepatic recycling; part of a dose is excreted in the urine, most of it in the first 8 hours; urinary excretion, however, accounts for only a small fraction in the reduction of total body stores acquired by dietary means. Vitamin B12 diffuses across the placenta and also appears in breast milk.
(last reviewed 2010-08-23; last modified 2006-10-03)
Retention in the body
A short review1 in 1984 noted that after injection of cyanocobalamin a large proportion was excreted in the urine within 24 hours; the body retained only 55% of a 100-microgram dose and 15% of a 1000-microgram dose. Body stores of vitamin B12 amounted to 2000 to 3000 micrograms which was believed to be enough for 3 to 4 years. If 1000 micrograms is injected monthly, the 150 micrograms retained lasts for about 1 month. Hydroxocobalamin was better retained than cyanocobalamin; the review stated that 90% of a 100-microgram dose and 30% of a 1000-microgram dose were retained which was believed to be enough for 2 to 10 months. While UK licensed product information supports these figures, it has been pointed out2 that the latter figure was misquoted by the review from its original source, which claimed that 30% of a 1000 microgram-dose was excreted and 70% retained, hence allowing for the longer dosing interval.
(last reviewed 2010-08-23; last modified 2009-05-11)
References
1. Anonymous. Time to drop cyanocobalamin?Drug Ther Bull. 1984; 22: 43. PubMed
2. Raymond P. Cyanocobalamin.Aust Prescriber. 1988; 11: 13.
Preparations: Single-Ingredient
The following preparations list represents a compilation of all available salt forms or related substances for this drug product.
The symbol ¤ denotes a preparation which is discontinued or no longer actively marketed.
ARGENTINA: Benzoral¤; Difenac Forte; Lisoneurin B12¤; Methycobal¤; Reedvit; SL B12; Vitam Doce;AUSTRALIA: Cytacon¤; Cytamen¤; Hydroxo-B12; Neo-B12; Neo-Cytamen¤; Vita-B12;AUSTRIA: Cyanokit; Diclo-B¤; Erycytol; Hepavit¤;BELGIUM: Cyanokit; Forta B¤; Hydroxo¤; Novobedouze¤;BRAZIL: Bedozil; Cianon B12¤; Cronobe; Enzicoba; Methycobal¤; Rubranova; Vitadoze¤; Xantox¤; Zinabol¤;CANADA: Anacobin¤; Athlete¤; Bedoz¤; Cobex¤; Cyanokit; Formula 1¤; Hydro Cobex¤; Nurocare; Prime¤; Rubion¤; Rubramin¤;CHINA: Ai Ke Bao (爱柯保); Ai Xin Bao (爱昕保); Bo Di Tong (博迪同); Bo Ke Bao (博可保); Cheng Qiang (成强); Dai Fang (代芳); Fanminbu (泛敏补); He Bao (禾保); Jia Li Bao (加利保); Le Kang (乐亢); LiWei (力维)¤; Luo Tang (洛唐); Mai Tuo (麦拓); Methycobal (弥可保); Mi Er Shen (弥尔神); Mi Nuo (弥诺); Ouwei (欧维); Qi Xin (奇信); Qu Li (曲力); Runjie (润洁); Sancoba (散克巴); Shi Er Xin (实尔新); Tang Xin (唐信); Tuo Pu You (托普优); Wei Ke Da (威可达); Yi Shen Bao (怡神保); Yi Wei Kang (怡维康); Yu Hai Xiang (郁海香); Yue Min Xing (悦敏兴); Zhao Min Xin (兆敏欣);CZECH REPUBLIC: B12 Ankermann¤; Cyanokit; Neurobene¤;DENMARK: Behepan¤; Betolvex; Cyanokit; Permadoze; Vibeden;FINLAND: Betolvex¤; Cohemin; Cyanokit; Novavita;FRANCE: Algobaz¤; Cobanzyme¤; Cyanokit; Dibencozan¤; Docemine¤; Dodecavit; Dolonevran¤; Ecovitamine B12; Epithea¤; Heraclene¤; Hydroxo¤; Indusil T¤; Nevrizide¤; Novobedouze¤; Paxom¤;GERMANY: Ambe 12¤; Aquo-Cytobion¤; B 12-L 90¤; B12 Depot-Rotexmedica¤; B12 Ehrl¤; B12 Rotexmedica¤; B12-ASmedic; B12-Horfervit¤; B12-Steigerwald; B12 Ankermann; B12 Depot-Hevert¤; B12 Depot-Vicotrat¤; B12 Vicotrat¤; Berubi-long¤; Cefavit B12; Chibro B12¤; Cobalparen-Depot¤; Cobalparen¤; Cytobion¤; Depogamma¤; Hamo-Vibolex¤; Hydroxobase¤; Lophakomp-B 12 Depot; Lophakomp-B 12; Millevit¤; Neurotrat B12¤; Novidroxin¤; Novirell B12¤; Rowo Vitamin B12 (Rowo-12)¤; Vicapan N¤; Vit-Alboform¤; Vita-Brachont¤;GREECE: Articlox; Bedoc¤; Cyanokit; Idroxocobalamina¤;HONG KONG: Ampavit; Bitamin; Bitomet; Cobalamin; Cobamin; Comesgen; Cyanokit; Hycobal; Lichein; Mecomin; Methycobal; Neo-Active Vitamin B12; Norcobal; Subilie; Sunferbol; Sunvita; Triniscon¤; Vidalic;HUNGARY: Feroglobin-B12; No Shot¤;INDIA: Acmic; Acvit; Adenomin; Alnacob; Alphamix; Ameco; Atnuron; Axineuron; Azed; Balcobal; Basix-OD; Betaneuron OD; Bigvin; Biocobal; Biomic; Cabosoft; Canbol; Chiny; Citon; Coba; Cobaday; Cobal Forte; Cobal; Cobalom; Cobalvit 1ML; Cobalvit-D; Cobalvit-OD; Cobamet; Cobanerve OD; Cobanerve; Cobaver; Coblona; Cobsa; Compicare; Cubal; Cumee; Diabanerve; Diacobal; E-Cob; Ecobal-OD; Efcoba; Electa; Elmecob; Glomec; Hydrox-12; Ingavit B12; Intacob; Juvinate; Keeneuron; L-Vit-12; Lameco-OD; Logy; Maddox; Malamin; Marinol; Matilda; MB-12; MCB; MCBit; MCBM¤; Me-12; Mecatin-MD; Mecmin; Mecoba; Mecobal; Mecobest; Mecoflash; Mecofol; Mecolife; Mecomed; Mecona; Meconerv; Meconeuron; Meconovit-OD; Mecophar; Mecoriv; Mecovit¤; Mecovon; Mecze; Medhamin; Medinerv; Mego; Melife-OD; Mericobal; Metherlin; Methico; Methiloc; Methyco; Methycobal; Methygard¤; Methyneuron; Mewin; Mezen; Mico-B; Miko; Moblo; Mycobal; Mycol; Myconova; Mycotop; Mycovit-OD; Myelogen; Mynuron; Necob; Nervic-1500¤; Nervicin; Nervon-M; Nervup; Neucobal; Neuractin; Neuratab-M Forte; Neuroage; Neurolac-MD; Neuromed; Neuromin; Neuroswift; Neurotone; Neurotop-M; Neurovig-M; Neutron; Nifabol; Niscobal; Novomine; Nurobex; Nuroclad; Nuroday; Nurokind; Nuromas; Nuromax; Nurovole; Nuroz-OD; Nuthyal Plus; OB-12; Odicoba¤; Omybal;INDONESIA: Arcored; Berthyco; Cobazim; Ethigobal; Icobal; Interco; Kalmeco; Lanabal; Lapibal; Magerix; Mecolin; Meconeuro; Megabal; Methycobal; Metifer; Mevrabal¤; Mobafer; Nerfeco; Neulamin; Nufacobal; Oxicobal; Scanmecob; Simcobal; Sohobal;IRELAND: Cyanokit; Cytacon¤; Cytamen¤; Neo-Cytamen;ISRAEL: Bedodeka; Bevitex¤; Nascobal¤;ITALY: Anabasi¤; Cobaforte; Cobamide¤; Cobergon¤; Cyanokit; Dobetin; Eritrovit B12¤; Fravit B12¤; Idrobamina¤; Idrossamina¤; Indusil; Maximal¤; Natur B12¤; Neo-Cytamen; OH B12; Reticulogen¤; Zidovit¤;JAPAN: Calomide-S¤; Cobaltamin-S¤; Comesgen¤; Hitocobamin M¤; Hycobal; Mecolamin; Methycobal; Methycobide; Neumethycole; Reticolan;MALAYSIA: Mecovit; Methycobal; N-Cobal; Neuromethyn; Vecobal;MEXICO: Anevit; Axofor; Biocobal¤; Biotrefon L; Bissel 12; Compensal¤; Doprit¤; Droxivit; Duradoce¤; Exorvit¤; Fortical; Hidrowil¤; Hidroxovit¤; Lentorem¤; Leo-Doce¤; Maxibol; Nebal; Neribax¤; Neuralin Relief; Neurofor; Parol¤; Plusvisol; Quimpaphil; Rubrina¤; Sanovit; Selectofort¤; Valamin 12¤; Vidavit¤;NETHERLANDS: Betolvex¤; Cyanokit; Hydrocobamine;NORWAY: Behepan; Betolvex¤; Cyanokit;NEW ZEALAND: Neo-B12; Neo-Cytamen¤;PHILIPPINES: Cobalamin; Drexabion; Ecobal; Econvita; Geocobalamin; Heraclene; Hybutin¤; Jaga; Mebaal; Mecobin; Mecovit; Meganerv; Methycobal; Nervafil; Nervilan; Neuro-B's; Neurobexol; Neurobion; Neurolink; Neuromet¤; Polynerv; Rubramin¤; Supraneuron; Valcumin¤; Vineuron;POLAND: Cyanokit;PORTUGAL: Algobaz¤; Bedoze¤; Co-Vibedoze¤; Cobamet¤; Cobaxid; Cyanokit; Dozefol; Jaba B12; Made B12¤; OH B12¤; Permadoze; Tridocemine¤;RUSSIAN FEDERATION: Cicomin (Цикомин); Vitagamma (Витагамма);SOUTH AFRICA: Betolvex¤; Cobalatec¤; Cytacon¤; Cytamen¤; Norivite-12¤; Nubee 12¤;SINGAPORE: Hidomin¤; Methycobal; Neuromethyn;SPAIN: Ambritan¤; Anabolizante Hermes¤; Asimil B12¤; B12 Latino Depot¤; Co Vitam B12¤; Cobaldocemetil¤; Cromatonbic B12; Cyanokit; Indusil¤; Isopto B 12; Lifaton B12¤; Megamilbedoce; Optovite B12; Panhor¤; Reticulogen Fortificado¤; Sorbevit B12¤; Surgevit B12¤; Zimadoce¤;SWEDEN: Behepan; Behepan; Betolvex; Betolvidon; Cyanokit;SWITZERLAND: Arcored¤; Betolvex¤; Cobazymase¤; Cyanokit; Hydroxo¤; Novobedouze¤; Vitarubin;THAILAND: Ampavit; B Twelve P; Balamine; Hitocobamin M¤; Mecoba; Mecobal; Mecobin; Mecze; Merabin; Methycobal; Neuromet; Redisol; Sicobal¤;TURKEY: Aktibol; Betolvex; Dodex; Monovit B12; Vitakobal;UNITED ARAB EMIRATES: Cynovit;UNITED KINGDOM: Cemac B12¤; Cobalin-H; Cyanokit; Cytacon; Cytamen; Neo-Cytamen;UNITED STATES: B-12 Dots; B-12 SL; B-12; CaloMist¤; Cobolin-M¤; Crystamine¤; Crysti 1000¤; Cyanoject¤; Cyanokit; Cyomin¤; Ener-B¤; Hydro Cobex¤; Hydro-Crysti-12¤; Hydrobexan¤; LA-12¤; Nascobal; Rapid B-12 Energy; Redisol¤; Rubesol-1000¤; Rubramin PC¤; Twelve Resin-K;VENEZUELA: Bedovit Simple; Beplus; Cristadoce; Dobetin; Docebe B12¤; Droxofor¤; Hidro-Doce; Ibedox; Maxibol;
Preparations: Multi-Ingredient
The following preparations list represents a compilation of all available salt forms or related substances for this drug product.
The symbol ¤ denotes a preparation which is discontinued or no longer actively marketed.
ARGENTINA: Acifol Fe; Acifol-B12; Algio Nervomax Fuerte; Algio Nervomax; Anemidox Solutab; Anemidox Ultra; Anemidox-Ferrum; Anemidox; Apeplus; Arteriotrat; Autrinic Compuesto¤; Bago B1 B6 B12 Detox; Bago B1 B6 B12; Bago B6 B12 Folic; Betametasona B12; Bioneural B12¤; Blastop Prevent; Blastop; Blokium B12; Bronax Cort; Buta Rut B12; Calcifort¤; Calcigenol B12; Ciprovit Calcio; Cobenexol Fuerte; Coflic B6-B12; Corteroid Gesic; CVP B1 B6 B12¤; Dapoder; Dastonil; Delta Tomanil B12; Dexabion¤; Dexabion; Diclogesic Plus B12; Diclolabsa B12; Dioxaflex B12; Dioxaflex Complex; Dolo Nervobion 10000; Dolo Nervobion; Dorixina B1 B6 B12; Doxtran B12; E-Folic; Factofer B12; Ferranin Complex; Ferrocebrina; Ferrofolgamma; Flexicamin B12; Flexicamin B12; Flexiplen B12; Flogiatrin B12; Flogiatrin B12; Glucocartiflex; Glucosamina Sport; Glucovitan Ginseng¤; Hemovit; Hepagris; Hierro Folico; ITE-B12 Forte; Klosidol B1 B6 B12; Lafefolic-B; Levoglutil Vitaminado; Magnesio Nectar Vital¤; Merebral; Metaflex B12; Milcobalin; Milgamma N¤; Nervobion Fuerte; Nervomax TB12; Nexovital Complex; Nucleo CMP¤; Oxa B12; Panclo B12; Polper B12; Polper Ginseng¤; Polper Vascular; Potencil; Presterin; Rodinac B12; Rubiron; Rucaten Prednisolona; Siderblut Complex; Sindrolen¤; Solocalm Plus; Solocalm Plus; Solocalm-B; Stimulnerv; Tanvimil Aminoacidos; Tenvic; Tiamidon; Trisel; Tunik B12; Vesalion B12; Virobron B12 NF; Vitalix Complex; Xedenol B12; Yectafer Complex;AUSTRALIA: Bio ACE Excell; Bio Iron; Ethical Nutrients Antioxidant Fish Oil Garlic Plus¤; Homme-F; Medinat PMT-Eze¤; Methyl Transfer¤; PM IQShield; PM LifePro Max for Men¤; PM LifePro Max for Women¤; Prosense for Men¤; Prosense for Women¤; Red-Life for Men; Red-Life for Women; Tracel¤;AUSTRIA: Ambene N¤; Ambene¤; Arca-Be; Beneuran compositum¤; Clinit¤; Delta-Tomanol¤; Diclovit; Neurobion; Neuromerck; Neuromultivit; Pronerv; Rheumesser;BELGIUM: Activarol¤; Ferrifol B12¤; Neo Genyl¤; Neurobion; Rubraton¤; TriBvit; Vioneurin¤;BRAZIL: Acromax¤; Alginac; Aminocid¤; Anemofer¤; Betinjectol¤; Bicavine¤; Biocalcio¤; Bituelve¤; Buclamin¤; Bucliamin¤; Buclifen-Vit¤; Calci-Ped; Calciferol B12¤; Calciferol Composto¤; Calciferol¤; Calcifix B12¤; Calcifix Composto B12; Calcigenol B12¤; Calcinol Complexo; Calcio Vitaminado B12¤; Calcio Vitaminado¤; Calciobion¤; Calciofar; Calciovital Irradiado¤; Calcitran B12¤; Calferon¤; Calvita B12¤; Cianotrat-Dexa; Citoneurin; Cobactin; Cobaglobal; Cobalplex¤; Cobavit; Cobavital; Coraben¤; Crescicalcio¤; Deficical B12; Dexa-Citoneurin; Dexa-Cronobe; Dexa-Neuriberi¤; Dexacobal; Dexador; Dexadoze; Dexagil; Dexalgen; Dexaneurin; Dexanevral¤; Dozbe¤; Dozeneurin; Enzivital¤; Ergohepat B12¤; Etna; Ferroplex¤; Ferrotrat B12 Plus; Ferrotrat B12¤; Ferrotrat; Fol Sang¤; Folix-Mater¤; Forten; Glucal B12¤; Hematiase B12; Hepanisan¤; Hepasedan¤; Hepatogenol¤; Hepatotris¤; Hepavirmo¤; Hypercalcio¤; Iloban; Infiltran B12¤; Iodacif; Kalyamon Kids; Kindcalcio¤; Lisan¤; Lisinvitan¤; Lisotox; Metiocolin B12; Metiocolin Composto; Neuriberi¤; Nevrix; Nucleo CMP; Oscalcio¤; Plusapetit¤; Policalcio B12; Profol; Provical¤; Psicoglut¤; Puravit Multi; Rheumafim¤; Rubizuel¤; Rubrargil; Seikivita¤; Selectocalcio¤; Sorbecal¤; Stin¤; Suavit Calcio¤; Tenavit; Trinalgen¤; Trinevral¤; Trirubin¤; Vi-Ferrin; Vibetrat Dexa¤; Vibetrat¤; Vigonal¤; Vipirim¤; Vitaler¤; Vitaneuron¤; Vitatonus¤; Xantinon Complex;CANADA: Acti-B12; Coldbuster Formula; Daily Energy Booster; Emulsi Factors; Female Y; Femm¤; Ferrasorb; Ferrocaps B12¤; Folacin 12¤; Formula C 36¤; Fortiplex¤; Heparos¤; Inner Shade¤; Live-Rite; Methischol¤; Nuclevit B12; Oligofer¤; Penta-3B + C¤; Penta-3B¤; Sleepsense; Total BRN Formula¤; Trinsicon¤;CHILE: Becomplina Fuerte¤; Benutrex 1000¤; Betonvit¤; Citoneuron; Confer; Cronoferril¤; Dolo-Neurobionta; Dolotol 12¤; Ener B; Ferranem; Ferranim; Ferroral Fol¤; Foli Doce¤; Folifer; Maltofer Fol Plus; Nefersil B; Neurobionta; Neurocam; Neurosande; Tol 12 Plus; Tol 12; Vitabral;CHINA: Guan Xin Ke (贯新克); Jinquan (金泉);CZECH REPUBLIC: Aktiferrin Compositum¤; Dicopac¤; Feroglobin B12¤; Ferro-Folgamma; Milgamma N; Milgamma N; Milgamma; Neiraxin; Neuromax; Neuromultivit;DENMARK: TriBvit; TrioBe;FINLAND: Neurobion; Neuromax; Neurovitan¤; Trineurin; TrioBe;FRANCE: Algimax¤; Ascencyl¤; Ascorbamine¤; Bio-Marine Plus¤; Biovaline¤; Easymagnevie Memo+; Inadrox¤; Lysivit B12 a l'inositol¤; Neoparyl-B12¤; Nergitone¤; Nuclevit B12¤; Thiobanzyme¤; Vibalgan¤; Vitanevril B6-B12¤;GERMANY: Ambene Comp¤; B 12 compositum N¤; B 12 Nervinfant¤; B-Komplex forte¤; B12 Fol-Vicotrat¤; B12-Intrinsic-Vicotrat¤; Causat B12 N¤; Corbiovin¤; Corneregen N¤; Dimaestad plus¤; Dodecatol N¤; Dodecatol¤; Dolo-Neurobion forte¤; Eisenkapseln¤; Eryfer comp¤; Eukalisan forte¤; Eukalisan N¤; FegaCoren N¤; Ferro sanol comp; Ferro-B 12 Ehrl¤; Ferro-Folgamma; Floradix Krauterblut¤; Folgamma; Hepa-Uvocal¤; Hepagrisevit Forte-N¤; Hepagrisevit SP¤; Hepagrisevit-Depot¤; Hepasteril¤; Hepatofalk¤; Hepavis¤; Hepsan¤; Hewedolor B¤; Jatamansin¤; Magopsor¤; Medivitan iM; Medivitan iV; Medyn; Milgamma N; Milneuron Plus¤; mono-Hepagrisevit¤; Nervisal¤; Neuro-Demoplas¤; Neuro-ratiopharm¤; Neurobion; Neurogamma¤; Neurotrat¤; NeyNormin (Revitorgan-Lingual Nr 65)¤; NeyNormin N (Revitorgan-Dilutionen N Nr 65)¤; NeyTumorin (Revitorgan-Lingual Nr 66)¤; NeyTumorin N (Revitorgan-Dilutionen N Nr 66)¤; Norphenovit N¤; Novirell B¤; Nurdelin¤; Pankreon fur Kinder¤; Pernaemyl¤; Pernical¤; Prohepar¤; Rulofer¤; Rutibal¤; Selectafer N¤; Supertendin 3000¤; Sympatovit¤; Telbibur N¤; Vitaject¤; Vitamin B Komplex; Vitasprint B12¤;GREECE: Avramin; Betrimine; Dynavita¤; Feaplex¤; Neurobion; Polinevrit¤; Tonotil-N¤; Triforte; Trilagavit¤; Triplovit¤; Trividuran¤; Vioneurin-6;HONG KONG: 3B; Aktivbion; Aktivtrebe; Alinamin EX Plus; Ammi-Vita; Anaton; ANC Iron Plus Folic Acid; ANC Milk Thistle Plus; Anehemo Iron Plus Folic Acid; Anoran; Assana-B; Atrofin-A; AV Liver Iron Plus Vitamin B12; B-Comfor; Balsamin; Becobin; Beetona; Best-Liver; Betex; BF-Lipotin; Biolon-B; Buffori; Calcalcin; Calon Tri-B; Candy-B; Carlvit; Chinling; Cimpalex-B; Daneuron; Digezym; Docepine; Duma-B; Epargriseovit¤; Esenphos; Essen-B; Eurobion; Eurovit-B; Evergreen Liver Iron Plus Vitamin B12; Eye-Ruby Rose; Fermarate; Ferohome; Feronken; Forever B12 Plus; Forzyiron; Healfu; Hemofum; Hepa-Support; Hepafort-Extra; Hepaloxan; Hepatofalk¤; Hepatoswiss; Heprotect; Herba-Liver; Hi-Vitaminen; Hibestrol; Intelplus; Jav Livibron; Joinlok; Kam's Antirheumatic; Kaplaxe; Kavibol; Koucon; Kynchinau; Lermacine; Leva Guard; Liobigen; Lipotin; Mays; Megahetic; Metabotrim; Neuritis¤; Neuro B1-6-12¤; Neuro-Vit¤; Neurobion; Neurogen-E; Neuromin; Neurorubine; Neurovit; Neurowel; Neutrebe; Nevramin; New Wetco; New-Pain-Q; Noarl Fresh; Noarl N; Noarl One N; Nurebe; Nurose; Nurotrebe; Nutribion; Nutriobe; Poteno; Princi-B Fort¤; Pro-Livermin; Pro-Vita Iron; Rato Iron; Redoxan; Ronkodi; Rose Eye Ruby; Roxanne; Strong Tri-B; Super 3B; Synbion¤; Teling; Tetralon-B; Trabit¤; Trebebion; Trebetrum; Tri-B; Tribion; Trilagavit; Triobetrum; Triple-B; Trivito; Valsa; Vartelon-B; Vibion; Vida-Neurotab; Vidaclofen-Plus¤; Vitabion; Vitacomb; Vitalic¤; Vitatone; Vitbion; Vittis; Waifulsin; Waiysin; Wei Le Sheng; Weilesheng;HUNGARY: Atherovit; Ferro-Folgamma; Milgamma N; Milgamma; Neuro Vita; Neurobion; Neuromultivit; Sclerovit;INDIA: Abrovit-Cal; Acmic-Alpha; Acmic-S; Acmic; Adcal; Adenofer; Adfe-C; Adfe; Adifer-Z; Adrovit-LB; Aglozyme; AHb-15; Alcobal; Alcrin-M; Alfariz; Alfariz; Alfe; Almecol; Alnacob-G; Alnacob-OD; Alnacob-P; Alnaferon; Alphamix-BT; Alphamix; Alphaneuron; Alvit; Ameco Plus; Ameco; Ancob Plus; Ancob; Anemidox; Aneudox-12; Aneudox-12; Arion; Aristoneurol; Armet G; Armet Plus; Atherochek-10¤; Atherochek-5¤; Atnuron; Atofast-M¤; Atovit; Autrin; Aviton; Avpro-XP; B-12; B-12; Balofer; Barochem; Barohem; Barovit; Bavitam; Beetone; Benerv Forte; Benfage Plus; Benfree; Betamore; Bevidox; Bigjoint; Bigvin Forte; Bigvin-F; Blosyn; Blosyn; Blush; Bm-Vita; Bone-C Plus; Bonrich-Z; C-Haem; C-Haem; Cadeno-ZF; Cal-Aid¤; Calcefol; Calcid; Calcila; Calcimark; Calcindon; Calcinol; Calfine; Calhem Plus; Calibon-Z; Calorich-M; Calraze; Calsat; Calswift; Caltop; Canbol Plus; Canbol-F; Capin Plus; Capin-G; Capsovit; Carbifol; Carbiran; Carbo Plus; Carbofen Forte; Carboflot; Carbomax Plus; Carbona; Carbophar; Carboron; Carbozin; Carbozin; Carfol-Z; Carfol-Z; Cario; Carista; Carnyl-FE; Caroneg; Carron; CB-12; Cecure; Chelferron; Chelferron; Chemofer-12; Chemofer-12; Cheri; Cherifer; Chiny-GP; Cinred; Cobal Plus; Cobal-F; Cobal-PG; Cobalip; Cobals Plus; Cobalvit-GT; Cobanerve-G; Cobanerve-HR; Cobanerve; Cobasoft; Cobaver-M; Cobaver-OD; Coblona; Cobsa-G; Complete-12; Comron; Conviron Forte; Conviron-TR; Cool-Joint; Cromofer-OD; Cumee-A; Cyfol; Cyfolac; Cynobac; Cyron; D-Gard; Decalvit; Deferon; Delphicol¤; Dexorange; Dexorange; Disiorange; Doloneuron-PG; Doloneuron; Dulane-M; Duotop; Duzela-M; E-Cod Plus; Ecobal; Ecogab; Ecome-LY; Edge-P Plus; Efcoba Plus; Efcoba-F; Efcoben; Elcarb; Eldervit-ZC; Electa-GP; Elferri-TR; Elferri-Z; Elneuro; Elnutra-M; Emorange; Encentin Plus; Encentin-AM; Encentin-M; Enhance Femme; Ep-Iron Fol; Eucobal; Evaglow Plus; Evaglow-M; Exacor; Extrafer; Fab-12; Facicap; Faxtra; Fe-Glow; Fearo-FD; Fearo; Febex; Feday; Fef-OD; Fefo; Fejet; Felicita-OD; Femed; Femena-Z; Femicontin; Femina; Fenna; Fenna; Fenora-SF; Fephar; Fepot; Feranid; Ferazin; Fered-C; Fered-C; Fereg-F; Fereg-Z; Ferfoz Plus; Ferglobin; Feribest-L¤; Ferich; Ferich; Ferid-C; Ferimax; Ferimax; Ferimax; Feripro-Z; Feripro; Ferisan; Feristar; Feritol; Feriz-SF; Ferizest; Ferobid-Z; Ferofast; Ferolact; Ferolact; Feromax; Feronez; Ferose Tab; Ferose; Ferox; Ferox; Ferozinc; Ferricos; Ferril; Ferrisun; Ferritop Iron Tonic; Ferritop Iron; Ferritop Paed; Ferritop-Z; Ferritop; Ferro Hepatine; Ferro-Plan Kit; Ferro; Ferrochelate; Ferrocin C B12 Plus; Ferrocin C B12; Ferrofit; Fervit¤; Ferycare; Ferywel; Ferz; Fesoft; Festo-TR; Fexid-Z; Fexid; Fexid; Fezlina; Fezocaps; Fezocar; Fezys-SM; Fezza; FHB-12; Fifa-AD; Fifa; Fifa; Fifolar; Fleefer; Fol-DHA; Fol-G1; Fol-Thrive; Folcin-12 Combi; Folirange; Folsafe; Foncal; Fopymin; Fotia-F; Fremov-ME; Fruitovit; Ftol-12; G-Care; G-Neuro¤; Gaba-MC; Gaba-PM; Gabafact; Gabafix-M; Gabaneuron; Gabanez-M; Gabapentin Forte¤; Gabastar M; Gabatop; Gabator-M; Gabaz; Gabil; Gabin-M; Gabion-M; Gabsoft-M; Galinerve-M; Game; Gamet; Gardian; GB-29; GBN-M; GCobal; Gefer; Gelina-M; Genfol; Gentin-MC; Gibi Forte; Gic-M; Ginkoriv Plus; GLA-M; Glentona Plus; Globac-Z; Globac; Globifex; Globiron-C; Globiron-Z; Glohar-C; Glohem-TR; Glowcarb-Z; Glowcarb; Glowcarb; Glozy; GMab Plus; Goldcare; Grandfer; Haem Up-Z; Haem Up; Haem-F¤; Haem-Up Gems; Haem-Up; Haem-XT; Haematinga; Haematinga; Haemaze; Haemglow; Haemgrow; Haemo-Z; Haemocare; Haemplus; Haemrise; Haems; HB Fast-Z; HB Plus; HB Rich; HB-Act; HB-Norm; HB-Norm; HB-Nova; HB-Orange; HB-Orange; HB-Plan Kit; Hb-Rich; HB-Up; HB-Up; Hem-12; Hemacor; Hemadex; Hemadex; Hembran Plus; Hembran-Fe; Hemex; Hemfast; Hemfer; Hemfer; Hemfer; Hemforte; Hemifolin-Z; Hemo-G; Hemofer-Z; Hemprovit-Fe; Hemral-CB; Hemral; Hemral; Hemsi; Hemsyneral-TD; Hepasules-F; Hepasules¤; Hepatoglobine Mikros; Hepatoglobine; Hepatoglobine; Hepp Forte; Hepp-Tone; Hevit; Hicobal; Hosit Plus; Hosit-L; Hosit; Hycalvit; Hyteron-M; Icrate; Idiglobin; Ifycarb-Z; Ifycarb; Imax; Imferon F-12; Imferon Forte; Incobal Plus; Incobal-OD; Ind-Orange; Indcobal; Infer-Z; Infer-Z; Insiron-AD; Irex-12 Tonic; Irex-12; Irex-TR; Irex; Iro-Life; Iro-Life; Irocafe; Irofact-SF; Irofol-AZ; Irolar; Iromost; Iron-Gold; Irona; Ironac-S; Ironac; Ironate; Ironeed; Ironifol; Ironup; Irorange; Irossgold; Irossgold; Irotel; Irovista; Irum; Irum; Isofer; Jecktofer Plus¤; Jectocos Plus; Jectocos¤; Jetositol; Kairfee; Kairfee; Kairfee; Keeneuron; Kefive Plus; Kelcer; Kiron-UP; Kobit-M; L-Bex; Lameco Plus; Lancitone-CS; Leclub; Lenova-MF¤; Lenyl-C; Leogab-M; Levicarb; Levineuro; Lexfer-Z; Lipidrop-V; Lipifol Plus¤; Liquiron; Liquiron; Litcal; Liton-Z; Liton; Litron; Livosil-B; Logic; Lutamin; Lutivit; Lycobal Forte; Lycogold; Lyconerve; Maconeuron-OD; Macraberin-M; Macraberin-P; Maddox-AL; Magic-M; Mahagaba-M; Malzix-GB; Marinol-GB; Maxgalin-M; Maxo-Fe; Maxo-Fe; Maxoza; MCBM 69 Fe¤; MCBM 69¤; Me Plus; Me-12; Me-Gab; Mecap-P; Mecoba Alpha; Mecoba-OD; Mecobal-GB; Mecobil-P; Mecobion-P; Mecocad; Mecocas-Ortho; Mecoday-G; Mecoday-PG; Mecona Plus; Meconerv Forte; Meconerv Plus; Meconerv; Meconeuron-HR; Mecoriv-G; Mecosa-OD; Mecze-FL; Medifer; Medofer¤; Mefol; Meganeuron; Mego-XL; Mego-XL; Melan; Melan; Melife-G; Mepik; Mericobal-G; Mericobal; Met-Neurobion; Metalin-Z; Methico-AL; Methipas-GP; Methoneuron-C; Methovit¤; Methycal¤; Methygard-OD¤; Mewin-GB; Mexivit; Mexivit; Mezen; MGTec-P; Microdol Forte; Mighty Plus¤; Mighty-SF¤; Mighty¤; Miko-G; Miko-OD; Minadex; Miol-P; Miproten; Moblo Plus; Moblo-AF; Mokia-G; Molu Plus; Monocobal-AD; Motrin GB; MSA; Mufe; Mumcal; Mycotop; Mycovit-GB; Mycovit; Myglo-CS; Myglo; Mytifer; N-Meedia; Natfer; Neo-Hepatex; Neogadine SG; Nerfit; Nerjuwin-P; Nervelin-M¤; Nervic-G; Nervicin-G; Nervicin; Nervijen-P; Nervim-P; Nervimax-G; Nervion; Nervon-GM; Nervon-PM; Nervonic-P¤; Nervonic¤; Nervoptin; Nervup Forte; Nervup-ER; Nervup-OD; Nervup-PG; Nervup; Nervuptin; Nervz-B; Nervz-G; Nervz; Nerwin-GT; Netfer; Neucobal Forte; Neufer-Z; Neupreg Forte; Neurica-M; Neuro-GM; Neuroage Plus; Neuroage Plus; Neuroage-B; Neuroage-GF; Neuroage; Neurocap-G; Neurocap-OD; Neurochek¤; Neurocit; Neuroforte; Neurogab; Neuroglow-B; Neuroglow; Neurokab-OD; Neurokair; Neuromas-G; Neuromed-GF; Neuromed; Neuromed; Neuromed; Neuromin-M; Neurophosphates¤; Neuropill; Neurosoz-MC; Neurotop Plus; Neurotop-G; Neurotrat; Neuroxin-12; Neurozen; Neutron-OD; Neuvesca; New Nervijen-CT; Nexcob Plus; Nexcob-G; Nicofer; Nid-XT; Nitizest; Nocad; Nodyfer; Novomine-AD; Novomine-GB; NTOmec-G; Nufervit; Numeth; Nurifier; Nuro-M Plus; Nuro-M; Nuro-M; Nurobest; Nurocare-PG; Nuroclad-GB; Nuroclad-Plus; Nurokind Hart; Nurokind Ortho; Nurokind Plus; Nurokind Plus; Nurokind-G; Nurokind-More; Nuromas-PG; Nuromax-OD; Nuromax-PG; Nurosenz; Nurovir; Nurovole Plus; Nurovole-PG; Nurozac-OD; Nuthyl-AL; Nuthyl-GB; Nutrared; Nutrex; Nutricobal Plus; Nutricom-NB; Nutrifol; O-Nerve; OA Plus; Obrase; Omegachek¤; Omilcal; Omilcal; Omron Plus; Optifer; Optisulin; Oracalcid-B12; Orofer; Orogab-M; Orymax; Oscal-12; Oscal-12; Oscob Forte; Osiron; Osoferon; Osteochek¤; Osteoz-FR; Ostocalcium; Ovipro-MF; Oxi-Red; Oxy-V; Oxyglobin; Plastules B-12; Probofex Cap; Siderfol; Sigmacalvit; Sioneuron; Tonoferon; Tonoferon; Vitamon; Vitneurin;INDONESIA: Abajos; Adfer; Afomix; Alabetic; Arsinal; Artovit; Asten¤; Aviter; Baliin Q10; Betrion¤; Bicitron¤; Biocombin; Bioferron; Biomega; Biomex; Bionemi; Bioneuron; Biosanbe; Cardiavit; Cardiomin; Cetalgin-T; Cinula¤; Corobion; Corsaneuron; Corsanural; Dactron¤; Daneuron¤; Dansera¤; Diabion; Diklovit; Dolo Neuromin; Dolo Scanneuron; Dolo-Licobion; Dolo-Neurobion; Dolofenac¤; Elsazym¤; Emibion; Emineton; Farbion; Fatigon C-Plus; Fatigon; Femosa; Ferospat; Folaplus; Folda; Foraneural; Forneuro; Fundamin-E; Fundifar; Good Life Fres Diab; Goralgin; Grahabion; Gunabion¤; Habebion¤; Hemafort; Hemobion; Hexalgin; Ikaneuron Plus; Ikaneuron; Inbion; Ingatol; Jointace Active; Jointace Collagen; Kalbion; Katusi; Lactacin; LaktaFit; Lapibion; Licobion; Mecola; Mersibion; Milmor; Miniceronal¤; Minowell; Molaneuron; Moloco + B12; Natabion; Neo Rheumacyl Neuro; Neofer; Neogobion; Nerva Plus; Nerva; Nervitone E; Nervitone; Neumed; Neuralgin RX; Neuraxon; Neuro Panstop; Neurobat A; Neurobat; Neurobeston; Neurobion; Neurobiovit; Neuroboran; Neurodex; Neurohax; Neuromed; Neuromin; Neurophil; Neuropyramin¤; Neuropyron V; Neurosanbe Plus; Neurosanbe; Neurotrat; Neurotropic Plus; Neurotropic; Neurovit E; Nevradin E; Nevradin¤; Nevramin; Nichobion; Nichoviton; Novoneural¤; Nutralix; Nutrifar¤; Nuvoneural; Opibion; Osfit; Pankreon for Children; Penagon; Ponconeuron; Prenamia; Primabion¤; Pritagesic; Pro ATP; Procalma; Pronita; RaVita; Rebal Plus; Rejuvan¤; Remasal¤; Rindobion; Sangobion Femine¤; Sangobion Fit; Sangobion; Sangofer; Sangotonik; Sangovitin¤; Scanneuron; Serbion; Sohobion; Solaneuron; Stavit; Stileran; Suprabion; Tiola; Tocobion; Tonikum Bayer; Trimate-E; Triomin-E; Tropifer; Tropineuron; Veroscan; Viron; Vitabion; Vitadrop¤; Vitala; Vitalex; Vitaneuron; Xepaneuron;IRELAND: Cyfol¤; Ketovite;ISRAEL: Betrivit¤; Shalosh B; Tribemin; Tricardia; Triple B¤; Trivitamin¤;ITALY: Activarol¤; Adeneurina¤; Adenobeta¤; Adenoplex; Adenovit¤; Adinepar¤; Algoneurina B12¤; Amico¤; Artrobetin¤; Atlantis; Benexol B12; Benexol B12; Beta-Cortex B12¤; Betascor B12¤; Binevrilplus¤; Bio-Rex¤; Brain¤; Briogen¤; Calci-ostelin B12¤; Calcio Colloidale con Ostelin con Vit¤; Calcio Dobetin; Cebran¤; Cerebrix¤; Citicortex¤; Citoglutar¤; CO-B12 (Cobidodici)¤; Co-Carnetina B12; Cobalton¤; Cortepar B12¤; Cromex¤; Dinamozim¤; Disepavit; Disintox Cortex¤; Dobetin Totale; Dopatox¤; Efargen¤; Emazian B12¤; Emazian Cortex¤; Emoantitossina¤; Emofol¤; Emonucleosina Cortex¤; Emopon; Endoepacort B12¤; Energon Rende¤; Epaglifer¤; Epaplex¤; Epargriseovit; Eparmefolin; Epartonno¤; Epaviten; Ergon; Exepin Cortex¤; Fegacorten¤; Fegato¤; Ferrofolin Venti¤; Ferromina; Fevital¤; Fibronevrina; Firmavit¤; Fitepar Cortex¤; Folepar B12; Folinemic Cortex¤; Folinemic¤; For Liver¤; Fosfo Plus; Fosfoutipi Vitaminico¤; Fosfozimin¤; Fruttidasi¤; Gliviton¤; Globuleno¤; Gluserin B12¤; Gluta Complex¤; Glutacortin¤; Glutamin Fosforo; Glutestere B-Complesso¤; Hepa-Factor Complex¤; Hepa-Factor; Hepatos B12; Liedasi¤; Liverasten¤; Liverest¤; Memoserina S¤; Memovisus¤; Memovit B12; Menalgon B6¤; Menalgon¤; Mionevrasi Forte¤; Mionevrasi; Mnemina Fosforo¤; Natalben; NE 300¤; Neo-Cromaton Cortex¤; Neo-Epa¤; Neo-Eparbiol; Neo-Geynevral¤; Nepatim¤; Neuraben; Neurobionta¤; Nevrazon¤; Nevril¤; Nevrostenina B12¤; Nevrum¤; Novaneurina B12¤; Nucleodoxina¤; Nucleonevrina¤; OH B12 B1¤; Oro B12¤; Oromag B12¤; Pavephos¤; Porfirin 12¤; Porfirin 12; Protidepar 100¤; Protidepar¤; Redinon Cortex¤; Ribocort B12¤; Ricoliver¤; Ricortex¤; Rossocorten¤; Rubrocortex¤; Seriglutan B12¤; Sideritrina¤; Sinevrile¤; Tonicum B12; Tonogen; Tonoliver 10000¤; Tonoliver Ferro¤; Toxepasi Complex¤; Trebi¤; Tricortin; Tridodilan¤; Triferon¤; Trinevrina B6; Trivitepar B12¤; Uridinvit Forte¤; Urimiodin¤; Vitalion¤; Vitalmix Junior; Vitamucin con Ferro¤; Vitamucin Semplice¤; Vitasprint Complex¤; Vitasprint¤;JAPAN: Alithia; Daimedin 3B; Diainamix; Neurovitan; Proheparum¤; Shigmabitan; Tridocelan; Vitadan; Vitamaru; Vitamedin; Vitaneurin;MALAYSIA: 3B; Alinamin B12¤; B-Cobal; Daneuron; Ferrovit¤; Flavettes Neuroforte; Fundamin-E¤; Neuro B¤; Neurobine; Neurobion; Neurogen-E; Neurorubine; Neurovit¤; Nevramin¤; Nevramin; Opibion; Princi-B Fort; Re-B; Sangobion; Valobion; Vibee; Vitabion; Vitadrop¤; Vitamin B Forte;MEXICO: Ariflam Forte¤; Autrin; B1-12-15¤; Bedoce-Cal; Bedocil¤; Benexol B12; Besvital; Betrox; Biotrivin; Ciprolisina; Cobotiaxina; Combesteral; Cromagen AF; Dexabion; Diclovith-B; Dodemina Tri¤; Dolo Bedoyecta; Dolo-Neurobion; Dolo-Pangavit; Dolo-Tiaminal; Dolvifen; Doxemina¤; Duciclon; Forvin; Gavindo; Gonakor; Hemamina; Innobion; Intrafer F-800; Iodarsolo B12¤; Macrox-5¤; Meli B; Milbeta; Neuralin; Neurobion; Neuroflax; Nuro-B; Odexan; Orafer Comp; Pangavit B; Pangavit Hypak; Pangavit Pediatrico; Revitaliv-C¤; Selectadoce; Solsavit¤; Suma-B; Tiabexol¤; Tiamidexal; Tiaminal B12 Trivalente; Tiaminal B12; Tioxal¤; Triban¤; Tribedoce Compuesto; Tribedoce DX; Tribedoce; Tribedoxyl¤; Trineurovita Compuesto¤; Trineurovita; Uni-Dox; Vasobion¤; Vitalen; Votripax;NETHERLANDS: Neiraxin; Neurobion¤;NORWAY: TrioBe;NEW ZEALAND: TMG Folic¤;PHILIPPINES: Aminofer FA; B-Com Nerve; B-Potent; B-Prime Plus; B-Prime; B3B¤; Bee-All; Beenostel; Beetab; Beniforte; Bernacin; Betalbee; Biovid Forte; Capsugen¤; Centravim; Cramin Forte; Dolo-Jaga; Dolo-Neurobion; Fer-Essence; Fericap; Ferro-B; Ferrovit¤; Foliage B-Plus; Folicard B-Plus; Foramefer; Glutaphos; Godex¤; Godex; Hanizyn; Harvifer¤; Hemarate FA; Hemobion¤; Hemovin; Heralink; Hinuron-E; Keltican; Leal Vits; Leoron¤; Liv-Assure; Lixtress; Lyvit-Z; M-Ron B; Maxi-B; Medvit-OB; Meganerv F-A; Mintribee; Mitocore; Mitodex; Mitonerb; Mivex; Mixigil; Nakaron; Natalac FeFol; Ner-B-Vite; NervAid; Nervaxon; Nervit B-Plus; Nervite; Neural-B; Neuro-Ace; Neurobase; Neurobiz; Neurofenac; Neuroforte-E; Neurogen-E; Neurovit; Neuroxel; Nevramin; Nuramine; Nuron-E; Obycon; One-Six-Twelve; Oranerv; Osteo-4; Polynerv Forte; Pregmax M; Pronerv; Provinerv; Ramavit; Rovita¤; Sangobion Prenatal FA; Sangobion; SB-Plex¤; Sqvit Multivitamins + Iron + Lysine; Sqvit Vitamins + Iron + Lysine; Super-B; TriHEMIC; Vibee; Vineuron Plus; Vitabit; Vitagen; Vitanerv¤; Zerru B-Plex;POLAND: Actiferol Fe; Additiva Ferrum¤; Bexon; Chela-Ferr Bio-Complex¤; Chela-Ferr Forte¤; Dolonerv; Milgamma N; Miositogyn; Neiraxin B; Neurovit; Pronerv¤; Vegevit B12¤;PORTUGAL: Activarol¤; Anvitol¤; Ferquifa B12¤; Folyoben; Grisetin¤; Linamin Plus¤; Neobefol; Neurobion; Nucleodoxina¤; Suplefol; Tot'Hema¤; Tridocemine¤; Vitasten¤;RUSSIAN FEDERATION: Ambene (Амбене); Angiovit (Ангиовит); Benfolipen (Бенфолипен)¤; Binavit (Бинавит); Cocarnit (Кокарнит); Combilipen (Комбилипен); CompligamV (КомплигамВ); Essliver Forte (Эссливер Форте); Fenules Zinc (Фенюльс Цинк); Ferro-Folgamma (Ферро-Фольгамма); Foliber (Фолибер); Iodilife (Йодилайф); Magnesium Plus (Магний Плюс); Medivitan (Медивитан); Milgamma (Мильгамма); Multi-Tabs B-Complex (Мульти-Табс В-Комплекс); Neurobion (Нейробион); Neurodiclovit (Нейродикловит); Neuromultivit (Нейромультивит); Pician (Пициан)¤; Prohepar (Прогепар); Trigamma (Тригамма); Triovit Kardio (Триовит Кардио); Unigamma (Юнигамма); Vitaxon (Витаксон);SOUTH AFRICA: Aktivakid¤; Autrin¤; Foliglobin; Maxitone¤; Neurobion¤; Prohep¤; Revaton¤; Sentinel Ulcer Mixture¤; Trinsicon¤; Vigour S¤;SINGAPORE: 3B¤; Alinamin B12¤; Appelin-B12; Beafort; Beaplex; Biofolic DHA; Daneuron; Docolix; Floron; Hemacaps¤; Iron Melts¤; LactaGreek; Neogobion; Neuro-B; Neurobion; Neurodex¤; Neuroforte; Neurogen-E; Neuromin-3; Neurorubine; Neurosanbe; Neurovit; Neuroxel; Neutron OD; Nevramin; Opibion; Princi-B Fort; Sangobion; Vibee; Vitalic; Wanse;SPAIN: Acinetil Bebible¤; Anemotron¤; Antineurina; Ascorbamina 1500¤; Ascorbamina Infantil¤; Benexol B1 B6 B12; Besinergial¤; Bester Complex; Betriple¤; Biomax¤; Calcio 20 Coenzimas¤; Calcio 20 Complex¤; Cocardoce A M P¤; Cocardoce¤; Cortinorex¤; Cotrizima¤; Covitasa; Cromaton Cortex¤; Cromatonbic 5000 Ferro¤; Cromatonbic 5000¤; Dalamon¤; Doneurina¤; Duplicalcio B12¤; Elmuten¤; Enoton¤; Ferriwas B12 Fuerte¤; Ferrocoban B12¤; Foli Doce; Gammamida Complex¤; Glotone¤; Grovixim¤; Hegama¤; Hepa Factor¤; Hidroxil B12 B6 B1; Histiotone¤; Imferon B12¤; Inzitan¤; Ledovit C B12¤; Malandil¤; Mederebro Compuesto¤; Mederebro¤; Menalgil B6¤; Menalgil¤; Meneparol Sol¤; Meneparol¤; Metabolicum¤; Metilema¤; Milbedoce Anabolico¤; Natifar; Natimed; Nervobion; Neurocatavin¤; Neuromade; Neurostop Complex¤; Prodessal¤; Rakivit Hepatico¤; Raquivit¤; Refulgin¤; Rekord B12¤; Rubrocortin¤; Sedionbel¤; Sorbeglucal¤; Stolina¤; Sugarceton¤; Supertonic¤; Taurobetina¤; Teovit¤; Tomevit¤; Toniasten¤; Tonico Juventus; Tonozime UTP¤; Transfusine Infantil¤; Trifosfaneurina B2 B12¤; Trifosfaneurina B6¤; Trinsicon¤; Trofalgon; Trofi Milina¤; Troforex Pepsico¤; Ultravital¤; Viadetres¤; Vita Menal¤; Vitafardi C B12¤; Vitallon 3B¤; Vitonisan B¤; Yectofer Compuesto¤; Yodocefol; Yoduk Complex; Yofolvit;SWEDEN: Neurobion; TrioBe;SWITZERLAND: Arconeurine¤; B-OM Forte¤; B-OM¤; B12 compositum¤; Benexol B12; Bio-Logos; Bio-Sprint¤; Biovigor; Blastoidin R.C.¤; Clinit¤; Ferrum Fol B Hausmann¤; Neurorubin; Neurotrat¤; Resoferon fol B¤; Tonique-B12¤; Tribeton¤; Trilagavit; Vita-Logos¤; Vitasprint B12; Vitasprint Complex¤;THAILAND: 3-Vitabee¤; 3B; Alinamin B12; Ammi-Vita; B1 B6 B12; B1-6-12; BAF-2; BAF; Bee three; Beromin; Betex; Bio-Marine Plus; Chaibolant; Cilfer-12-F¤; Cori-3B; Cydoxmine-B¤; Cyriamine; Douzabox; Ferromin; Genavit; Hello-B; Hemolax¤; Masa 3B; Med-3B; Neubee; Neurobex; Neurobion¤; Neuviplex; Nevramin; Nuro-B; Nuvit; One-Six-Twelve; OST Vit; OST; Ostone-B12; Patar 3 B; Princi-B Fort; Re-B Forte; Saebin F 1-6-12; Sambee; Sangobion¤; Thidomin; Three-B; Trabit¤; Tri-B-Vit; Tribemed; Tribemine; Tribesian; Tricortin¤; Triple-B; Trivico; Trivit-B; Trivon¤; Uto Vitavit; V 1-6-12; V Day 1612; V Day Vit; Viboral; Vioneurin¤; Vita-B; Vitabion; Vitamedin¤; Vitelsix; Vitron;TURKEY: Baxant Plus B12; Befull; Beneday; Benexol B12; Bevit B12; Bitavin B12; Blood Builder¤; Epargriseovit; Folidoce; Gynoferro; Hepargrizovim; Multi-B; Neurogriseovit; Norogrizovim; Pagamax Plus; Preplus B12; Tribeksol;UNITED ARAB EMIRATES: 3V;UNITED KINGDOM: Ce-Cobalin¤; Dicopac¤; Florisene; Hematinic; Neurozan;UKRAINE: B-Complex Multi-Tabs (B-Комплекс Мульти-Табс)¤; Cardonat (Кардонат); Cocarnit (Кокарнит); Decamevit (Декамевит); Fitoval Capsules (Фитовал капсулы)¤; Haemoferon (Гемоферон); Hemsyneral-TD (Гемсинерал-ТД)¤; Hepadif (Гепадиф); Hepadif (Гепадиф); Herbastress (Гербастресс)¤; Insuvit (Инсувит); Laktovit Forte (Лактовит Форте); Levasil (Левасил); Milgamma (Мильгамма); Neiron (Нейрон)¤; Neovitam (Неовитам); Nerviplex (Нервиплекс); Neurobex (Неуробекс); Neurobion (Нейробион); Neurodiclovit (Нейродикловит); Neurolek (Невролек); Neuromultivit (Нейромультивит); Neurorubine (Нейрорубин); Neurovitan (Нейровитан); Ranferon-12 (Ранферон-12)¤; Ranferon-12 (Ранферон-12); Trimetabol (Триметабол); Vimifor Multivitamin with Beta-Carotene (Віміфор Мультивітамін З Бета-каротином)¤; Vitaxon (Витаксон);UNITED STATES: Adrenoid; Albafort; ALZ-NAC; Anemagen¤; Animi-3; B-12; B-Serene; Bevitamel; BiferaRx; Calafol; Cardiotek Rx; CenFol; Cerefolin NAC; Cerefolin¤; Chromagen FA; Chromagen Forte; Chromagen¤; ComBgen¤; Contrin; Corvite FE; Corvite; FE Plus; Fe-Tinic Forte; FeoGen FA¤; FeoGen; FeRivaFA with Quatrefolic; Ferotrinsic; Ferralet 90; Ferralet Plus¤; Ferrex Forte Plus¤; Ferrex Forte; Ferrogels Forte; Fetrin; Folastin; Folbic RF; Folgard; Folpace; Foltanx RF; Foltx; Fumatinic¤; Healthy Heart Complex; Hem Fe; HemeTab; Hemocyte-F; Icar-C Plus; iFerex Forte; Iron 100 Plus; Iron Complex; L-Methyl-B6-B12; L-Methyl-MC; Livitrinsic-f¤; LMTHF/Pyridoxine HCl/Cyanocobalamin; Metanx; MTX Support; Multigen; Nervidox 6¤; Nervidox¤; Neuro B-12¤; Neurobion¤; Niferex Forte; Nu-Iron Plus¤; Nutra Tear¤; Perihemin¤; Poly-Iron Forte; PremesisRx¤; Prenate AM with Quatrefolic; Pronemia Hematinic; Repliva¤; REQ49+; Reticulex¤; Rx Support Heartburn & Acid Reflux Plus Aloe; Rx Support Heartburn & Acid Reflux; Tia Doce¤; TL Icon; Tolfrinic; TriHEMIC; Trimagen¤; Trinsicon¤; Udamin SP; Udamin; Vesselvite; Virt-Vite Forte; Virt-Vite; Vita-Feron¤; VitaCirc-B; Vitagen Advance; VitaMed MD Iron 21/7;VENEZUELA: Autrin¤; Bedovit Compuesto; Bedoyecta; Beferron; Befol; Befosfin; Briomet; Cianofer; Cobalfer; Complejo B Compositum; Corubin B1¤; Deca-Lentermina Complex; Dinitrile Ormovit¤; Dinitrile-Vit; Dobetin Compuesto; Fefol; Fercobre B-12¤; Fercor¤; Ferroce B12; Ferroliver; Folifer B-12; Hepafol con B-12; Hepafol; Intafer; Lentermina Complex; Meganeubion; Miovit; Na-Iodina Compuesta¤; Neubion; Neuribe; Neuroalfa; Neurosande; Rubrinal; Rubrinex; Tega¤; Tianex¤; Tres-Be; Tres-Be;
Preparations: Pharmacopoeial
The following preparations list represents a compilation of all available salt forms or related substances for this drug product.
BP 2019: Cyanocobalamin Oral Solution; Cyanocobalamin Tablets; Hydroxocobalamin Injection;USP 42: Cyanocobalamin Injection; Cyanocobalamin Tablets; Hydroxocobalamin Injection; Methylcobalamin Tablets; Oil- and Water-soluble Vitamins Capsules; Oil- and Water-soluble Vitamins Oral Solution; Oil- and Water-soluble Vitamins Tablets; Oil- and Water-soluble Vitamins with Minerals Capsules; Oil- and Water-soluble Vitamins with Minerals Oral Solution; Oil- and Water-soluble Vitamins with Minerals Tablets; Vitamins with Minerals Oral Powder; Water-soluble Vitamins Capsules; Water-soluble Vitamins Tablets; Water-soluble Vitamins with Minerals Capsules; Water-soluble Vitamins with Minerals Tablets;
Therapeutic Use
- Nutritional Agents and Vitamins
Last Updated 1/21/20
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