Martindale: The Complete Drug Reference

Transcripción

Vitamin B12 Substances
Date of monograph review: 23-Apr-1998; 06-Sep-1999; 30-Oct-2001; 25-May-2004;
08-Mar-2006; 24-Jul-2006; 18-Aug-2008; 20-May-2009; 23-Aug-2010; (latest
modification: 14-Nov-2011)
Drug Nomenclature (Latest modification: 23-Sep-2011)
Synonyms: Vitamina B12; ビタミンB12 (vitamin B12); Витамины Группы B12
Drug Profile (Latest modification: 21-Mar-2004)
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)
Cobamamide
Date of monograph review: 03-Mar-2006; 08-Mar-2006; 24-Jul-2006; 18-Aug-2008;
20-May-2009; 23-Aug-2010; (latest modification: 14-Nov-2011)
Drug Nomenclature (Latest modification: 13-Aug-2011)
Synonyms: Adenosylcobalamin; Coenzyme B12; Dibencozide; Dibenzcozamide;
Dimebenzcozamide; Kobamamid; コバマミド
INN: Cobamamide [pINN (en)]
INN: Cobamamida [pINN (es)]
INN: Cobamamide [pINN (fr)]
INN: Cobamamidum [pINN (la)]
INN: Кобамамид [pINN (ru)]
INN: ‫[ ك وب امام يد‬pINN (ar)]
INN: 腺苷钴胺 [pINN (cn)]
Chemical name: Inner salt of the Co-(5′-deoxyadenosine-5′) derivative of the 3′-ester
of cobinamide phosphate with 5,6-dimethyl-1-α-D-ribofuranosylbenzimidazole
Molecular formula: C72H100CoN18O17P =1579.6
CAS: 13870-90-1
ATC code: B03BA04
ATC code (veterinary): QB03BA04
Pharmacopoeias:
In Chin.
Cyanocobalamin
Drug Nomenclature (Latest modification: 05-Dec-2011)
Synonyms: Κυανοκοβαλαμίνη; Cianocobalamina; Cianokobalamin; Cianokobalaminas;
Cobamin; Cyanocobalamine; Cyanocobalaminum; Cyanokobalamin; Cycobemin;
Cyjanokobalamina; Kyanokobalamin; Siyanokobalamin; Syanokobalamiini;
シアノコバラミン
BAN: Cyanocobalamin
INN: Cyanocobalamin [rINN (en)]
INN: Cianocobalamina [rINN (es)]
INN: Cyanocobalamine [rINN (fr)]
INN: Cyanocobalaminum [rINN (la)]
INN: Цианокобаламин [rINN (ru)]
INN: ‫[ س يان وك وب االم ين‬rINN (ar)]
INN: 维生素B12 [rINN (cn)]
Chemical name: Coα-[α-(5,6-Dimethylbenzimidazolyl)]-Coβ-cyanocobamide
CAS: 68-19-9
ATC code: B03BA01
UNII code: P6YC3EG204
Chemical Structure of Cyanocobalamin
Pharmacopoeias:
In Chin., Eur. (see
), Int., Jpn, US, and Viet.
Ph. Eur. 7 (Cyanocobalamin). A dark red, crystalline powder or dark red crystals. The
anhydrous substance is very hygroscopic. Sparingly soluble in water and in alcohol;
practically insoluble in acetone. Store in airtight containers. Protect from light.
USP 35 (Cyanocobalamin). Dark red crystals or amorphous or crystalline red powder. In
the anhydrous form it is very hygroscopic and when exposed to air it may absorb about
12% of water. Soluble 1 in 80 of water; soluble in alcohol; insoluble in acetone, in
chloroform, and in ether. Store in airtight containers. Protect from light.
Hydroxocobalamin
Synonyms: Υδποξυκοβαλαμίνη; Hidroksokobalamin; Hidroxocobalamina;
Hydroksikobalamiini; Hydroxikobalamin; Hydroxocobalaminum; Hydroxycobalaminum;
Idrossocobalamina; ヒドロキソコバラミン
BAN: Hydroxocobalamin
USAN: Hydroxocobalamin
INN: Hydroxocobalamin [rINN (en)]
INN: Hidroxocobalamina [rINN (es)]
INN: Hydroxocobalamine [rINN (fr)]
INN: Hydroxocobalaminum [rINN (la)]
INN: Гидроксокобаламин [rINN (ru)]
INN: ‫[ ه يدروك سوك وب االم ين‬rINN (ar)]
INN: 羟钴胺 [rINN (cn)]
Chemical name: Coα-[α-(5,6-Dimethylbenzimidazolyl)]-Coβ-hydroxocobamide
CAS: 13422-51-0
ATC code: B03BA03; V03AB33
ATC code (veterinary): QB03BA03; QV03AB33
UNII code: Q40X8H422O
Chemical Structure of Hydroxocobalamin
NOTE:
The hydrated form of hydroxocobalamin has been referred to as aquocobalamin.
Pharmacopoeias:
In Int. and US.
USP 35 (Hydroxocobalamin). Dark red crystals or red crystalline powder. Is odourless or
has not more than a slight acetone odour. The anhydrous form is very hygroscopic.
Soluble 1 in 50 of water and 1 in 100 of alcohol; practically insoluble in acetone, in
chloroform, in ether, and in benzene; sparingly soluble in methyl alcohol. pH of a 2%
solution in water is between 8.0 and 10.0. Store in airtight containers at a temperature
of 8 degrees to 15 degrees. Protect from light.
Hydroxocobalamin Acetate
Date of monograph review: 25-May-2004; 08-Mar-2006; 24-Jul-2006; 18-Aug-2008;
Synonyms: Acetatocobalamin; Hidroksokobalamino acetatas; Hidroxocobalamina,
acetato de; Hidroxokobalamin-acetát; Hydroksokobalamiiniasetaatti;
Hydroxocobalaminacetat; Hydroxocobalamine, acétate d'; Hydroxocobalamini acetas;
Hydroxokobalamin acetát; Hydroxokobalaminacetat; ヒドロキソコバラミン酢酸塩
BAN: Hydroxocobalamin Acetate [BANM]
INN: Hydroxocobalamin Acetate [rINNM (en)]
INN: Acetato de hidroxocobalamina [rINNM (es)]
INN: Hydroxocobalamine, Acétate d' [rINNM (fr)]
INN: Hydroxocobalamini Acetas [rINNM (la)]
INN: Гидроксокобаламина Ацетат [rINNM (ru)]
CAS: 22465-48-1
UNII code: S535M27N3Q
Pharmacopoeias:
In Eur. (see
), Jpn, and Viet.
Ph. Eur. 7 (Hydroxocobalamin Acetate). A dark red, very hygroscopic, crystalline
powder or dark red crystals. Soluble in water. Some decomposition may occur on drying.
Store at a temperature between 2 degrees and 8 degrees in airtight containers. Protect
from light.
Hydroxocobalamin Chloride
Synonyms: Hidroksokobalamino chloridas; Hidroxocobalamina, cloruro de;
Hidroxokobalamin-klorid; Hydroksokobalamiinikloridi; Hydroxocobalamine, chlorure d';
Hydroxocobalaminhydrochlorid; Hydroxocobalamini Chloridum; Hydroxocobalamini
Hydrochloridum; Hydroxokobalamin hydrochlorid; Hydroxokobalaminklorid
BAN: Hydroxocobalamin Chloride [BANM]
INN: Hydroxocobalamin Chloride [rINNM (en)]
INN: Cloruro de hidroxocobalamina [rINNM (es)]
INN: Hydroxocobalamine, Chlorure d' [rINNM (fr)]
INN: Hydroxocobalamini Chloridum [rINNM (la)]
INN: Гидроксокобаламина Хлорид [rINNM (ru)]
Molecular formula: C62H90ClCoN13O15P =1382.8
Pharmacopoeias:
In Eur. (see
), Int., and Viet.
Ph. Eur. 7 (Hydroxocobalamin Chloride). A dark red, very hygroscopic, crystalline
powder or dark red crystals. Soluble in water. Some decomposition may occur on drying.
Store at a temperature between 2 degrees and 8 degrees in airtight containers. Protect
from light.
Hydroxocobalamin Sulfate
Synonyms: Hidroksokobalamino sulfatas; Hidroxocobalamina, sulfato de;
Hidroxokobalamin-szulfát; Hydroksokobalamiinisulfaatti; Hydroxocobalamin Sulphate;
Hydroxocobalamine, sulfate d'; Hydroxocobalamini Sulfas; Hydroxocobalaminsulfat;
Hydroxokobalamin sulfát; Hydroxokobalaminsulfat
BAN: Hydroxocobalamin Sulfate [BANM]
INN: Hydroxocobalamin Sulfate [rINNM (en)]
INN: Sulfato de hidroxocobalamina [rINNM (es)]
INN: Hydroxocobalamine, Sulfate d' [rINNM (fr)]
INN: Hydroxocobalamini Sulfas [rINNM (la)]
INN: Гидроксокобаламина Сульфат [rINNM (ru)]
Molecular formula: C124H180Co2N26O34 P2S =2790.8
Pharmacopoeias:
In Eur. (see
), Int., and Viet.
Ph. Eur. 7 (Hydroxocobalamin Sulfate). A dark red, very hygroscopic, crystalline powder
or dark red crystals. Soluble in water. Some decomposition may occur on drying. Store
at a temperature between 2 degrees and 8 degrees in airtight containers. Protect from
light.
Mecobalamin
Date of monograph review: 03-Mar-2006; 08-Mar-2006; 24-Jul-2006; 18-Aug-2008;
Drug Nomenclature (Latest modification: 13-Aug-2011)
Synonyms: Methylcobalamin; メコバラミン
BAN: Mecobalamin
USAN: Mecobalamin
INN: Mecobalamin [pINN (en)]
INN: Mecobalamina [pINN (es)]
INN: Mécobalamine [pINN (fr)]
INN: Mecobalaminum [pINN (la)]
INN: Мекобаламин [pINN (ru)]
INN: ‫[ م ي كوب االم ين‬pINN (ar)]
INN: 甲钴胺 [pINN (cn)]
Chemical name: Coα-[α-(5,6-Dimethylbenzimidazolyl)]-Coβ-methylcobamide
CAS: 13422-55-4
ATC code: B03BA05
UNII code: BR1SN1JS2W
Chemical Structure of Mecobalamin
Pharmacopoeias:
In Jpn.
Adverse Effects and Precautions (Latest modification: 09-Aug-2010)
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
).
Cyanocobalamin should not be used for Leber's disease or tobacco amblyopia since
these optic neuropathies may degenerate further.
Breast feeding (Latest modification: 07-Aug-2010)
Vitamin B12 is distributed into breast milk.1 The American Academy of Pediatrics
considers its use to be usually compatible with breast feeding.2
1. 1. Samson RR, McClelland DBL. Vitamin B12 in human colostrum and milk. Acta Paediatr
Scand 1980; 69: 93–9. PubMed
2. 2. American Academy of Pediatrics. The transfer of drugs and other chemicals into
human milk. Pediatrics 2001; 108: 776–89. PubMed [Retired May 2010] Correction.
ibid.; 1029. Also available at: online (accessed 09/01/06)
Hypersensitivity (Latest modification: 03-Oct-2006)
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
1. 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. 2. Heyworth-Smith D, Hogan PG. Allergy to hydroxycobalamin, with tolerance of
cyanocobalamin. Med J Aust 2002; 177: 162–3. PubMed
Local reactions (Latest modification: 03-Oct-2006)
After 3 years of monthly intramuscular vitamin B12 injections, 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.1 Fascial haematoma after vitamin B12 injection
leading to local compression (posterior arm compartment syndrome) has also been
reported.2
1. 1. Ho J, et al. Vitamin B12-associated localized scleroderma and its treatment. Dermatol
Surg 2004; 30: 1252–5. PubMed
2. 2. Knapke D, Truumees E. Posterior arm and deltoid compartment syndrome after
vitamin B12 injection. Orthopedics 2004; 27: 520–1. PubMed
Porphyria (Latest modification: 14-Nov-2011)
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
1. 1. The Drug Database for Acute Porphyria. Available at: online (accessed 07/10/11)
Interactions (Latest modification: 31-Jul-2008)
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.
Pharmacokinetics (Latest modification: 03-Oct-2006)
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.
Retention in the body (Latest modification: 11-May-2009)
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 100microgram 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.
1. 1. Anonymous. Time to drop cyanocobalamin? Drug Ther Bull 1984; 22: 43. PubMed
2. 2. Raymond P. Cyanocobalamin. Aust Prescriber 1988; 11: 13.
Human Requirements (Latest modification: 03-Oct-2006)
For adults, the daily requirement of vitamin B12 is probably about 1 to 2 micrograms and
this amount is present in most normal diets. Vitamin B12 occurs only in animal products;
it does not occur in vegetables, therefore strict vegetarian (vegan) diets that exclude
dairy products may provide an inadequate amount although it has been said that many
years of vegetarianism are necessary before a deficiency is produced, if at all. Meats,
especially liver and kidney, milk, eggs, and other dairy products, and fish are good
sources of vitamin B12.
UK and US recommended dietary intake (Latest modification: 01-May-2009)
In the UK1 dietary reference values (see
) have been published for vitamin B12 and
similarly in the USA recommended dietary allowances (RDAs) have been set.2 Differing
amounts are recommended for infants and children of varying ages, adults and pregnant
and lactating women. In the UK the reference nutrient intake (RNI) is 1.5 micrograms
daily for adult males and females and the estimated average requirement (EAR) is
1.25 micrograms daily. In the USA the RDA for adults is 2.4 micrograms daily.
1. 1. DoH. Dietary reference values for food energy and nutrients for the United Kingdom:
report of the panel on dietary reference values of the committee on medical aspects of
food policy. Report on health and social subjects 41. London: HMSO, 1991. PubMed
2. 2. Standing Committee on the Scientific Evaluation of Dietary Reference Intakes of the
Food and Nutrition Board. Dietary Reference Intakes for thiamin, riboflavin, niacin,
vitamin B6, folate, vitamin B12, pantothenic acid, biotin, and choline. Washington, DC:
National Academy Press, 2000. Also available at: online (accessed 21/07/08)
Uses and Administration (Latest modification: 03-Sep-2010)
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 oxideinduced 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,
). Cyanocobalamin and hydroxocobalamin are generally given by
the intramuscular route, although cyanocobalamin may be given orally or
subcutaneously, or intranasally (see also under Administration,
). 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 the prophylaxis of anaemia associated with vitamin B12 deficiency 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 B12 deficiency 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,
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,
)
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
). 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
.
Cyanocobalamin and hydroxocobalamin are also used in the Schilling test to
investigate vitamin B12 absorption and deficiency states. They are given in a nonradioactive form with cyanocobalamin radioactively-labelled with cobalt-57 (
cobalt-58 (
) or
) 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.
Administration (Latest modification: 24-Aug-2010)
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 oral vitamin 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,3,6 or every 2 weeks for children,7 are 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.8 A 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 given sublingually. 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
1. 1. Lederle FA. Oral cobalamin for pernicious anemia: medicine's best kept secret? JAMA
1991; 265: 94–5. PubMed
2. 2. Hathcock JN, Troendle GJ. Oral cobalamin for treatment of pernicious anemia? JAMA
1991; 265: 96–7. PubMed
3. 3. Elia M. Oral or parenteral therapy for B12 deficiency. Lancet 1998; 352: 1721–2.
PubMed
4. 4. Anonymous. Oral or intramuscular vitamin B12? Drug Ther Bull 2009; 47: 19–21.
PubMed
5. 5. Kuzminski AM, et al. Effective treatment of cobalamin deficiency with oral cobalamin.
Blood 1998; 92: 1191–8. PubMed
6. 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. 7. Çetin M, Altay C. Efficacy of oral vitamin B12 treatment in children. J Pediatr 2001;
139: 754. PubMed
8. 8. Van der Kuy P-HM, et al. Bioavailability of oral hydroxocobalamin. Br J Clin Pharmacol
2000; 49: 395P–396P.
9. 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
10.10. Lane LA, Rojas-Fernandez C. Treatment of Vitamin B12-deficiency anemia: oral
versus parenteral therapy. Ann Pharmacother 2002; 36: 1268–72. PubMed
11.11. Romeo VD, et al. Intranasal cyanocobalamin. JAMA 1992; 268: 1268–9. PubMed
12.12. van Asselt DZB, et al. Nasal absorption of hydroxocobalamin in healthy elderly
adults. Br J Clin Pharmacol 1998; 45: 83–6. PubMed
13.13. Slot WB, et al. Normalization of plasma vitamin B12 concentration by intranasal
hydroxocobalamin in vitamin B12-deficient patients. Gastroenterology 1997; 113: 430–
3. PubMed
14.14. Delpre G, et al. Sublingual therapy for cobalamin deficiency as an alternative to oral
and parenteral cobalamin supplementation. Lancet 1999; 354: 740–1. PubMed
15.15. 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 (Latest modification: 02-Jan-2011)
In neonates and children up to 18 years with congenital transcobalamin II deficiency,
the BNFC 2009 suggests a dose of hydroxocobalamin 1 mg by intramuscular injection
given three times weekly. After 1 year this may be reduced to 1 mg once weekly.
In children aged from 1 month with megaloblastic anaemia (
) or children with
Leber's optic atrophy, hydroxocobalamin doses are similar to those used in adults in the
UK, see Uses and Administration,
.
Hydroxocobalamin is used as an antidote for cyanide poisoning in children. A dose of
70 mg/kg (maximum 5 g) by intravenous infusion is given once or twice according to
severity.
Hydroxocobalamin can also be used in children with methylmalonic acidaemia and
homocystinuria, see Amino Acid Metabolic Disorders,
.
Amino acid metabolic disorders (Latest modification: 02-Aug-2010)
References to the use of hydroxocobalamin in the treatment of inborn errors of vitamin
B12 metabolism.1-3 Some patients with homocystinuria (
) or methylmalonic acidaemia
have responded to cobalamins—the BNFC 2009 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.
1. 1. Linnell JC, Bhatt HR. Inherited errors of cobalamin metabolism and their
management. Baillieres Clin Haematol 1995; 8: 567–601. PubMed
2. 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. 3. Smith DL, Bodamer OA. Practical management of combined methylmalonicaciduria
and homocystinuria. J Child Neurol 2002; 17: 353–6. PubMed
Cardiovascular disease (Latest modification: 31-Jul-2008)
For mention of the possible link between vitamin B12, hyperhomocysteinaemia, and
cardiovascular disease, see under Folic Acid
.
Cyanide toxicity (Latest modification: 03-Sep-2010)
Hydroxocobalamin combines with cyanide to form cyanocobalamin, and thus may be
used as an antidote to cyanide toxicity (see under Hydrocyanic Acid,
).
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,
children, see Administration in Children,
, and in
.
1. 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. 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. 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. 4. Shepherd G, Velez LI. Role of hydroxocobalamin in acute cyanide poisoning. Ann
Pharmacother 2008; 42: 661–9. PubMed
Deficiency states (Latest modification: 24-Aug-2010)
The emergence of newer metabolic assays for homocysteine and methylmalonic acid has
led to the identification of subtle vitamin B12 deficiency1-3 without the overt
manifestations of megaloblastic anaemia (see
) 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,1,7 although suggestions for
management have been made.8 A study in elderly patients suggested that foodcobalamin 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.6 There have also been suggestions
that deficiency may be linked to some immunological impairment, identified as impaired
antibody responses to pneumococcal vaccine.9 Moreover, 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 of Folic Acid,
). 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 B12 concentrations) 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,
number of infants born with neural tube defects (
) to reduce the
) has created debate on the risks of
masking vitamin B12 deficiency, and fortification with vitamin B12 has also been
recommended, see under Folic Acid,
. 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,
.
1. 1. Carmel R. Subtle cobalamin deficiency. Ann Intern Med 1996; 124: 338–40. PubMed
2. 2. Green R. Screening for vitamin B12 deficiency: caveat emptor. Ann Intern Med 1996;
124: 509–11. PubMed
3. 3. Carmel R, et al. Update on cobalamin, folate, and homocysteine. Hematology (Am
Soc Hematol Educ Program) 2003; 62–81. PubMed
4. 4. Andrès E, et al. Vitamin B12 (cobalamin) deficiency in elderly patients. Can Med Assoc
J 2004; 171: 251–9. PubMed
5. 5. Clarke R. Prevention of vitamin B-12 deficiency in old age. Am J Clin Nutr 2001; 73:
151–2. PubMed
6. 6. Andrès E, et al. Food-cobalamin malabsorption in elderly patients: clinical
manifestations and treatment. Am J Med 2005; 118: 1154–9. PubMed
7. 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. 8. Carmel R. How I treat cobalamin (vitamin B12) deficiency. Blood 2008; 112: 2214–
21. PubMed
9. 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
10.10. 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
11.11. Emery ES, et al. Vitamin B12 deficiency: a cause of abnormal movements in infants.
Pediatrics 1997; 99: 255–6. PubMed
12.12. 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 (Latest modification: 03-Oct-2006)
A small study found that topical application of a preparation containing vitamin B12 was
more effective than placebo in patients with atopic eczema.1
1. 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 (Latest modification: 09-Aug-2010)
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,
). Dosage has not been well
established in children; the BNFC 2009 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 (
TREATMENT.
) if it occurs in pregnancy.
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,
.
General references.
For further information on the substances mentioned above, see:
 Cyanocobalamin
 Folic
(see Vitamin B12 Substances,
)
Acid,
 Folinic
Acid,
 Hydroxocobalamin
(see Vitamin B12 Substances,
)
1. 1. Wickramasinghe SN. Folate and vitamin B12 deficiency and supplementation.
Prescribers' J 1997; 37: 88–95.
2. 2. Wickramasinghe SN. The wide spectrum and unresolved issues of megaloblastic
anemia. Semin Hematol 1999; 36: 3–18. PubMed
3. 3. Rasmussen SA, et al. Vitamin B12 deficiency in children and adolescents. J Pediatr
2001; 138: 10–17. PubMed
4. 4. Hoffbrand V, Provan D. Macrocytic anaemias. In: Provan D, ed. ABC of clinical
haematology. 2nd ed. London: BMJ Publishing Group, 2003.
5. 5. Stabler SP, Allen RH. Vitamin B12 deficiency as a worldwide problem. Annu Rev Nutr
2004; 24: 299–326. PubMed
Neural tube defects (Latest modification: 24-Aug-2010)
There is abnormality in homocysteine metabolism in many women who give birth to
children with neural tube defects (
); the enzyme methionine synthase, which
converts homocysteine to methionine, requires both folate and vitamin B12 as cofactors,
and low maternal vitamin B12 concentrations may be an independent risk factor for
neural tube defects.1 A 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.2 Decreased vitamin B12
concentrations, but no folate deficiency, were found in 3 women with pregnancies
affected by neural tube defects.3 A 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.5 An 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
1. 1. Mills JL, et al. Homocysteine metabolism in pregnancies complicated by neural-tube
defects. Lancet 1995; 345: 149–51. PubMed
2. 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. 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. 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. 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. 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. 7. Refsum H. Folate, vitamin B12 and homocysteine in relation to birth defects and
pregnancy outcome. Br J Nutr 2001; 85 (suppl): S109–S113. PubMed
Osteoporosis (Latest modification: 17-Jul-2007)
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,
). 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 B12 rather than the lowering of plasma
homocysteine.3,6
1. 1. van Meurs JBJ, et al. Homocysteine levels and the risk of osteoporotic fracture. N
Engl J Med 2004; 350: 2033–41. PubMed
2. 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. 3. van Meurs JBJ, Uitterlinden AG. Homocysteine and fracture prevention. JAMA 2005;
293: 1121–2. PubMed
4. 4. Sato Y, et al. Effect of folate and mecobalamin on hip fractures in patients with
stroke: a randomized controlled trial. JAMA 2005; 293: 1082–8. PubMed Correction.
ibid. 2006; 296: 396.
5. 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. 6. Sugiyama T, et al. Folate and vitamin B12 for hip fracture prevention after stroke.
JAMA 2005; 294: 792. PubMed
Rhinitis (Latest modification: 09-Aug-2010)
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.
Preparations (Latest modification: 06-Aug-2012)
Single-ingredient Preparations (Latest modification: 06-Aug-2012)
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¤;
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¤; Formula 1¤; Hydro Cobex; Prime¤; Rubion¤; Rubramin¤; Czech Republic: B12
Ankermann¤; Cyanokit; Neurobene; Denmark: Behepan¤; Betolvex; Cyanokit;
Vibeden; Finland: Betolvex; Cohemin; 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 Steigerwald; B12-Horfervit¤; B12 Ankermann; B12 Depot-Hevert¤; B12
Depot-Vicotrat¤; B12 Vicotrat¤; B12-ASmedic; Berubi-long¤; Chibro B12¤; CobalparenDepot¤; 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; Idroxocobalamina¤; Hong Kong: Cobalamin¤; Cobamin; Cyanokit;
Methycobal; Neo-Active Vit B-12¤; Triniscon¤; Hungary: Feroglobin-B12; No Shot;
India: Acmic; Acvit; Adee; Adenomin; Alnacob; Alphamix; Ameco; Atnuron; Axineuron;
Azed; Balcobal; Basix-OD; Bigvin; Biocobal; Biomic; Cabosoft; Chiny; Citon; Coba;
Cobaday; Cobal Forte; Cobal; Cobalom; Cobalvit 1ML; Cobalvit-D; Cobalvit-OD;
Cobamet-OD; 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; Nervic1500; 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; Interco; Kalmeco; Lanabal;
Lapibal; Magerix; Mecolin; Meconeuro; Megabal; Methycobal; Metifer; Mevrabal¤;
Nerfeco; Neulamin; Nufacobal; Oxicobal; Scanmecob; 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¤; Methycobal; Malaysia: Methycobal;
N-Cobal; Neuromethyn; Mexico: Axofor; Biocobal¤; Biotrefon L; Bissel 12;
Compensal¤; Doprit¤; Droxivit¤; Duradoce; Exorvit¤; Fortical; Hidrowil¤; Hidroxovit¤;
Lentorem¤; Leo-Doce¤; Maxibol; Nebal; Neribax¤; Neurofor; Parol¤; Plusvisol;
Rubrina¤; Sanovit; Selectofort¤; Valamin 12¤; Vidavit¤; Netherlands: Betolvex¤;
Cyanokit; Hydrocobamine; Norway: Betolvex; Cyanokit; New Zealand: Neo-B12; NeoCytamen; Philippines: Drexabion; Econvita; Geocobalamin; Heraclene; Hybutin; Jaga;
Lixtress; Mecovit; Meganerv; Methycobal; Nervafil; Nervilan; Neuro-B's; Neurobexol;
Neurobion; Neurolink; Polynerv; Rubramin¤; Supraneuron; Valcumin; Vineuron;
Poland: Cyanokit; Portugal: Algobaz¤; Bedoze¤; Co-Vibedoze¤; Cobamet¤; Cobaxid;
Cyanokit; Dozefol; Jaba B12; Made B12¤; OH B12; Permadoze; Tridocemine¤; Russia:
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; United Arab Emirates:
Cynovit; United Kingdom: Cemac B12¤; Cobalin-H; Cyanokit; Cytacon; Cytamen; NeoCytamen; United States: 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;
Multi-ingredient Preparations (Latest modification: 06-Aug-2012)
marketed.
Argentina: Acifol-B12; Algio Nervomax Fuerte; Algio Nervomax; Anemidox Ultra;
Anemidox-Ferrum; Anemidox-Solutab; Anemidox; Apeplus; Arteriotrat; Autrinic
Compuesto¤; Bago B1 B6 B12; Bago B6 B12 Folic; Betametasona B12; Bioneural B12¤;
Blastop Prevent; Blastop; Blokium B12; Buta Rut B12; Calcifort¤; Calcigenol B12;
Ciprovit Calcio; Cobenexol Forte; Cobenexol Fuerte; Coflic B6-B12; Corteroid Gesic; CVP
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Plus B12; Diclolabsa B12; Dioxaflex B12; Dolo Nervobion 10000; Dolo Nervobion;
Dorixina B1 B6 B12; Doxtran B12; E-Folic; Factofer B12; Ferranin Complex;
Ferrocebrina; Flexicamin B12; Flexicamin B12; Flogiatrin B12; Flogiatrin B12;
Glucocartiflex; Glucosamina Sport; Glucovitan Ginseng¤; Hierro Folico; ITE-B12 Forte;
Klosidol B1 B6 B12; Levoglutil Vitaminado; Magnesio Nectar Vital; Merebral; Milcobalin;
Nervobion Fuerte; Nervomax TB12; 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; SolocalmB; 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¤; Medinat PMTEze¤; Methyl Transfer; PM IQShield; PM LifePro Max for Men; PM LifePro Max for
Women; Prosense for Men¤; Prosense for Women¤; Tracel¤; Austria: Ambene N¤;
Ambene¤; Arca-Be; Beneuran compositum¤; Clinit¤; Delta-Tomanol¤; Diclovit;
Neurobion; Neuromerck¤; Neuromultivit; Pronerv; Rheumesser; Trinsicon¤; 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; 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¤;
Kalyamon B12; Kindcalcio¤; Lisan¤; Lisinvitan¤; Lisotox; Metiocolin B12; Metiocolin
Composto; Neuriberi¤; Nevrix; Nucleo CMP; Oscalcio¤; Plusapetit¤; 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; Emulsi Factors; Female Y; Femm¤; Folacin 12¤;
Formula C 36¤; Fortiplex¤; Heparos¤; Inner Shade¤; Live-Rite; Methischol¤; Nuclevit
B12; Oligofer¤; Penta-3B + C; Penta-3B; 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; Czech Republic: Aktiferrin Compositum; Dicopac¤; Feroglobin B12; FerroFolgamma; Milgamma N; Milgamma N; Milgamma; Neuromax; Neuromultivit;
Denmark: TrioBe; Finland: Neurobion; Neuromax; Neurovitan; Trineurin; TrioBe;
France: Algimax¤; Ascencyl¤; Ascorbamine¤; Bio-Marine Plus¤; Biovaline¤; 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¤; DoloNeurobion 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 IV; Medivitan; 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¤; Vitasprint B12¤;
Greece: Betrimine; Dynavita; Feaplex; Neurobion; Polinevrit; Tonotil-N; Triforte;
Trilagavit; Triplovit; Trividuran; Vioneurin-6; Hong Kong: 3B; Digezym; Epargriseovit¤;
Hepatofalk¤; Neuritis¤; Neuro B1-6-12¤; Neuro-Vit¤; Neurobion; Neurogen-E;
Neuromin; Neurorubine; Neurovit¤; Nevramin; Princi-B Fort¤; Rose Eye Ruby¤; Super
3B¤; Synbion¤; Trabit¤; Tribion; Vartelon-B; Vibion; Vida Neurotab¤; Vidaclofen-Plus¤;
Vitabion; Vitalic¤; Hungary: Atherovit; Ferro-Folgamma; Milgamma N; Milgamma;
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; Aminorich; Ancob;
Anemidox; Aneudox-12; Aneudox-12; Arion; Aristoneurol; Armet G; Armet Plus;
Atherochek-10; Atherochek-5; Atnuron; Atofast-M; Atovit; Autrin; Aviton; Avpro-XP; B12; 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; CalAid; Calcefol; Calcid; Calcila; Calcimark; Calcindon; Calcinol; Calfine; Calhem Plus;
Calibon-Z; Calorich-M; Calraze; Calsat; Calswift; Caltop; Canbol Plus; Canbol-F; Canbol;
Capin Plus; Capin-G; Capsovit; Carbifol; Carbiran; 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; Cherifer; Chiny-GP; Cinred; Cobal-F; Cobal-PG; Cobalip;
Cobals Plus; Cobalvit-GT; Cobanerve-G; Cobanerve-HR; Cobasoft; Cobaver-M; CobaverOD; Coblona; Cobsa-G; Complete-12; Comron; Conviron Forte; Conviron-TR; CoolJoint; 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; FelicitaOD; Femed; Femena-Z; Femicontin; Femina; Fenna; Fenna; Fenora-SF; Fephar; Fepot;
Feranid; Ferazin; Fered-C; Fered-C; Fereg-F; Fereg-Z; Ferfoz Plus; Ferglobin; FeribestL; 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; Ferrogen-Z;
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; FolDHA; Fol-G1; Fol-Thrive; Folcin-12 Combi; Folirange; Folium; 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-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-4; 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¤; 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; MarinolGB; 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-AF; Moblo-Plus; 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-CT; 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 GF; Neuroage Plus; Neuroage Plus; Neuroage-B; 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; 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; NuromaxPG; Nurosenz; Nurovir; Nurovole Plus; Nurovole-PG; Nurozac-OD; Nuthyl-AL; NuthylGB; Nutrared; Nutrex; Nutricobal Plus; Nutricom-NB; Nutrifol; OA Plus; Obrase;
Omegachek; Omilcal; Omilcal; Omron Plus; Onerve; 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 Caps; Siderfol; Sigmacalvit; Sioneuron; Tonoferon; Tonoferon; Vitamon;
Vitneurin; Indonesia: Abajos; Adfer; Afomix; 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; Dolo Scanneuron; Dolo-Licobion; DoloNeurobion; Dolofenac; Elsazym; Emibion; Emineton; Farbion; Fatigon; Femosa;
Folaplus; Foraneural; Forneuro; Fres Diab; Fundamin-E; Fundifar; Goralgin; Grahabion;
Gunabion¤; Habebion¤; Hemafort; Hemobion; Hexalgin; Ikaneuron Plus; Ikaneuron;
Inbion; Ingatol; Kalbion; Lactacin; LaktaFit; Lapibion; Licobion; Mecola; Mersibion;
Milmor; Miniceronal¤; Moloco + B12; Natabion; Neo Rheumacyl Neuro; Neofer;
Neogobion; Nerva Plus; Nerva; Nervitone E; Nervitone; Neuralgin RX; Neuraxon; Neuro
Panstop; Neuro-Beston; Neurobat A; Neurobat; Neurobion; Neurobiovit; Neurodex;
Neurohax; Neuromed; Neurophil; Neuropyramin¤; Neurosanbe Plus; Neurosanbe;
Neurotrat; Neurotropic Plus; Neurotropic; Neurovit E; Nevradin E; Nevradin¤; Nevramin;
Nichobion; Nichoviton; Novoneural¤; Nutrifar; Nuvoneural; Opibion; Osfit; Pankreon for
Children; Penagon; Ponconeuron; Prenamia; Primabion; Pritagesic; Pro ATP; Procalma;
Pronita; RaVita; Rebal Plus; Rejuvan¤; Remasal¤; Rindobion; Sangobion; Sangofer;
Sangovitin¤; Scanneuron; 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¤; 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¤; COB12 (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; 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¤; NeoEparbiol¤; 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: Neurovitan; Vitaneurin; Malaysia: 3B; Alinamin B12¤;
B-Cobal; 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; Ciprolisina; Cobotiaxina; Cromagen AF; Dexabion; Diclovith-B; Dodemina Tri;
Dolo Bedoyecta; Dolo-Neurobion; Dolo-Pangavit; Dolo-Tiaminal; Dolvifen; Doxemina¤;
Duciclon; Forvin; Gavindo; Gonakor; Innobion; Intrafer F-800; Iodarsolo B12¤; Macrox5; 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; Tribedoxyl¤; Trineurovita Compuesto; Trineurovita; Uni-Dox;
Vasobion; Votripax; Netherlands: Neurobion¤; Norway: TrioBe; New Zealand: TMG
Folic¤; Philippines: B-Com Nerve; B-Potent; B-Prime Plus; B-Prime; B3B; Beetab;
Beniforte; Bernacin; Betalbee; Capsugen; Centravim; Cramin Forte; Dolo-Neurobion;
Fer-Essence; Ferrovit; Folicard B-Plus; Foramefer; Glutaphos; Godex¤; Godex; Hanizyn;
Harvifer; Hemobion; Hemovin; Heralink; Hinuron-E; Leoron¤; M-Ron B; Meganerv F-A;
Mintribee; Mitocore; Mitodex; Mitonerb; Mivex; Mixigil; Nakaron; Natalac FeFol; Ner-BVite; Nervit B-Plus; Nervite; Neural-B; Neuro-Ace; Neurobase; Neurofenac; NeuroforteE; Neuroxel; Nevramin; Nuron-E; One-Six-Twelve; Oranerv; Osteo-4; Provinerv;
Ramavit; Rovita; Sangobion; SB-Plex; Super-B; TriHEMIC; Vibee; Vitagen; Vitanerv;
Zerru B-Plex; Poland: Additiva Ferrum¤; Milgamma N; Neurovit; Vegevit B12; Portugal:
Activarol¤; Anvitol¤; Ferquifa B12¤; Grisetin¤; Linamin Plus¤; Neobefol; Neurobion;
Nucleodoxina¤; Tot'Hema; Tridocemine¤; Vitasten¤; Russia: Ambene (Амбене);
Angiovit (Ангиовит); Benfolipen (Бенфолипен); Combilipen (Комбилипен);
CompligamV (КомплигамВ); Essliver Forte (Эссливер Форте); Fenules Zinc (Фенюльс
Цинк); Ferro-Folgamma (Ферро-Фольгамма); Foliber (Фолибер); Magnesium Plus
(Магний Плюс); Milgamma (Мильгамма); Multi-Tabs B-Complex (Мульти-Табс ВКомплекс); Neurobion (Нейробион); Neurodiclovit (Нейродикловит); Neuromultivit
(Нейромультивит); Pician (Пициан); Prohepar (Прогепар); Trigamma (Тригамма);
Triovit Kardio (Триовит Кардио); Unigamma (Юнигамма); South Africa: Aktivakid¤;
Autrin; Foliglobin; Maxitone¤; Neurobion; Prohep¤; Revaton¤; Sentinel Ulcer Mixture¤;
Trinsicon¤; Vigour S¤; Singapore: 3B¤; Alinamin B12¤; Appelin-B12; Beafort; Beaplex;
Daneuron; Floron; Hemacaps; Iron Melts; Neogobion; Neuro-B; Neurobion; Neurodex;
Neuroforte; Neurogen-E; Neuromin-3; Neurorubine; Neurosanbe; Neurovit; Neuroxel;
Nevramin; Opibion; Princi-B Fort; Sangobion; Vibee; 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 B12;
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; BioLogos; Bio-Sprint¤; Biovigor; Blastoidin R.C.¤; Clinit¤; Ferrum Fol B Hausmann¤;
Neurorubin; Neurotrat¤; Resoferon fol B¤; Tonique-B12¤; Tribeton¤; Trilagavit; VitaLogos¤; Vitasprint B12; Vitasprint Complex¤; Thailand: 3-Vitabee; 3B; Alinamin B12¤;
BAF-2; BAF; Bee three; Beromin; Betex; Chaibolant; Cilfer-12-F¤; Cori-3B; CydoxmineB¤; Cyriamine; Douzabox; Ferromin; Genavit; 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; Re-B Forte; Saebin F 1-6-12; Sambee;
Sangobion; Thidomin; Three-B; Trabit¤; Tri-B-Vit; Tribemed; Tribemine; Tribesian;
Tricortin¤; Trinsicon¤; 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: Benexol B12; Blood Builder; Epargriseovit; Gyno Ferro; Neurogriseovit;
Tribeksol; United Arab Emirates: 3V; United Kingdom: Ce-Cobalin¤; Dicopac¤;
Florisene; Hematinic; Neurozan; Ukraine: B-Complex Multi-Tabs (B-Комплекс МультиТабс)¤; Cardonat (Кардонат); Cocarnit (Кокарнит); Decamevit (Декамевит); Fitoval
Capsules (Фитовал капсулы); Haemoferon (Гемоферон); Hemsyneral-TD (ГемсинералТД)¤; Hepadif (Гепадиф); Hepadif (Гепадиф); Laktovit Forte (Лактовит Форте)¤;
Levasil (Левасил); Milgamma (Мильгамма); Neiron (Нейрон)¤; Nerviplex
(Нервиплекс); Neurobex (Неуробекс); Neurobion (Нейробион); 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:
Albafort; Anemagen¤; Animi-3; B-12; Bevitamel; BiferaRx; Calafol; Cardiotek Rx;
CenFol; Cerefolin NAC; Cerefolin¤; Chromagen FA; Chromagen Forte; Chromagen¤;
ComBgen¤; Contrin; Fe-Tinic Forte; FeoGen FA; FeoGen; Ferotrinsic; Ferralet 90;
Ferralet Plus¤; Ferrex Forte Plus; Ferrex Forte; Ferrogels Forte; Fetrin; Folgard; Folpace;
FOLTX; Fumatinic; Hem Fe; Hemocyte-F; Icar-C Plus; iFerex Forte; Iron 100 Plus;
Livitrinsic-f¤; Metanx; MTX Support; Multigen; Nervidox 6¤; Nervidox¤; Neuro B-12¤;
Neurobion¤; Niferex Forte; Nu-Iron Plus¤; Nutra Tear¤; Perihemin¤; Poly-Iron Forte;
PremesisRx¤; 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; VitaFeron¤; Vitagen Advance; 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; Mega-Neubion; Miovit; NaIodina Compuesta¤; Neubion; Neuribe; Rubrinal; Rubrinex; Tega¤; Tianex¤; Tres-Be;
Tres-Be;
Pharmacopoeial Preparations (Latest modification: 06-Dec-2011)
BP 2012: Cyanocobalamin Tablets; Hydroxocobalamin Injection; USP 35:
Cyanocobalamin Injection; Hydroxocobalamin Injection; 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; Water-soluble Vitamins Capsules; Water-soluble Vitamins Tablets;
Water-soluble Vitamins with Minerals Capsules; Water-soluble Vitamins with Minerals
Tablets;
Homoeopathic Preparations (Latest modification: 14-Jun-2011)
marketed.
Germany: Anabol-Injektopas¤; AntiFocal N¤; AntiFocal¤; Gelenk- und Rheumatropfen¤;
Hepar comp; Infi-China; Infi-Symphytum; Infihepan; NeyDil 66N (Revitorgan-Dilutionen
Nr. 66 N)¤; NeyDil Nr 66; NeyFoc Nr 69; NeyGero Nr 64; NeyGeront (Revitorgan-Lingual
Nr 64)¤; NeyGeront N (Revitorgan-Dilutionen N Nr 64)¤; NeyGeront Vitalkapsein A;
NeyGeront-Vitalkapseln¤; NeyLing (Revitorgan-Lingual Nr.66)¤; NeyLing Nr 66;
Ukraine: Hepar Compositum (Гепар Композитум)¤

Martindale: The Complete Drug Reference

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