An official website of the United States government

Cobalamin

PubChem CID
46853873
Structure
Cobalamin_small.png
Molecular Formula
Synonyms
  • vitamin B12
  • cobalamin
  • cyanocobalamin
  • vitamin B-12
  • 68-19-9
Molecular Weight
1355.4 g/mol
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Parent Compound
Dates
  • Create:
    2010-08-30
  • Modify:
    2025-01-18
Description
Cyanocobalamin (commonly known as Vitamin B12) is a highly complex, essential vitamin, owing its name to the fact that it contains the mineral, cobalt. This vitamin is produced naturally by bacteria, and is necessary for DNA synthesis and cellular energy production. Vitamin B12 has many forms, including the cyano-, methyl-, deoxyadenosyl- and hydroxy-cobalamin forms. The cyano form, is the most widely used form in supplements and prescription drugs,. Several pharmaceutical forms of cyanocobalamin have been developed, including the tablet, injection, and nasal spray forms,,. This drug was initially approved by the FDA in 1942.
Cyanocobalamin is a metabolite found in or produced by Escherichia coli (strain K12, MG1655).
vitamin B12 is a metabolite found in or produced by Escherichia coli (strain K12, MG1655).
See also: vitamin B12 (preferred).

1 Structures

1.1 2D Structure

Chemical Structure Depiction
Cobalamin.png

1.2 3D Status

Conformer generation is disallowed since too many atoms, MMFF94s unsupported element, too flexible, mixture or salt

2 Names and Identifiers

2.1 Computed Descriptors

2.1.1 IUPAC Name

cobalt(3+);[(2R,3S,4R,5S)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2R)-1-[3-[(1R,2R,3R,4Z,7S,9Z,12S,13S,14Z,17S,18S,19R)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2,7,12,17-tetrahydro-1H-corrin-21-id-3-yl]propanoylamino]propan-2-yl] phosphate;cyanide
Computed by Lexichem TK 2.7.0 (PubChem release 2021.10.14)

2.1.2 InChI

InChI=1S/C62H90N13O14P.CN.Co/c1-29-20-39-40(21-30(29)2)75(28-70-39)57-52(84)53(41(27-76)87-57)89-90(85,86)88-31(3)26-69-49(83)18-19-59(8)37(22-46(66)80)56-62(11)61(10,25-48(68)82)36(14-17-45(65)79)51(74-62)33(5)55-60(9,24-47(67)81)34(12-15-43(63)77)38(71-55)23-42-58(6,7)35(13-16-44(64)78)50(72-42)32(4)54(59)73-56;1-2;/h20-21,23,28,31,34-37,41,52-53,56-57,76,84H,12-19,22,24-27H2,1-11H3,(H15,63,64,65,66,67,68,69,71,72,73,74,77,78,79,80,81,82,83,85,86);;/q;-1;+3/p-2/t31-,34-,35-,36-,37+,41-,52-,53-,56-,57+,59-,60+,61+,62+;;/m1../s1
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.3 InChIKey

FDJOLVPMNUYSCM-WZHZPDAFSA-L
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.4 SMILES

CC1=CC2=C(C=C1C)N(C=N2)[C@@H]3[C@@H]([C@@H]([C@H](O3)CO)OP(=O)([O-])O[C@H](C)CNC(=O)CC[C@@]\4([C@H]([C@@H]5[C@]6([C@@]([C@@H](C(=N6)/C(=C\7/[C@@]([C@@H](C(=N7)/C=C\8/C([C@@H](C(=N8)/C(=C4\[N-]5)/C)CCC(=O)N)(C)C)CCC(=O)N)(C)CC(=O)N)/C)CCC(=O)N)(C)CC(=O)N)C)CC(=O)N)C)O.[C-]#N.[Co+3]
Computed by OEChem 2.3.0 (PubChem release 2024.12.12)

2.2 Molecular Formula

C63H88CoN14O14P
Computed by PubChem 2.2 (PubChem release 2021.10.14)

2.3 Other Identifiers

2.3.1 CAS

68-19-9
13408-78-1

2.3.2 Deprecated CAS

11037-08-4, 24436-34-8, 8023-26-5, 8039-03-0

2.3.3 European Community (EC) Number

2.3.4 DrugBank ID

2.3.5 Metabolomics Workbench ID

2.3.6 NCI Thesaurus Code

2.3.7 RXCUI

2.3.8 Wikipedia

2.4 Synonyms

2.4.1 MeSH Entry Terms

  • B 12, Vitamin
  • B12, Vitamin
  • Cobalamin
  • Cobalamins
  • Cyanocobalamin
  • Eritron
  • Vitamin B 12
  • Vitamin B12

2.4.2 Depositor-Supplied Synonyms

3 Chemical and Physical Properties

3.1 Computed Properties

Property Name
Molecular Weight
Property Value
1355.4 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Donor Count
Property Value
9
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Acceptor Count
Property Value
21
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Rotatable Bond Count
Property Value
26
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Exact Mass
Property Value
1354.567399 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Monoisotopic Mass
Property Value
1354.567399 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Topological Polar Surface Area
Property Value
476 Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Heavy Atom Count
Property Value
93
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
3150
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Isotope Atom Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Atom Stereocenter Count
Property Value
14
Reference
Computed by PubChem
Property Name
Undefined Atom Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Bond Stereocenter Count
Property Value
3
Reference
Computed by PubChem
Property Name
Undefined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Covalently-Bonded Unit Count
Property Value
3
Reference
Computed by PubChem
Property Name
Compound Is Canonicalized
Property Value
Yes
Reference
Computed by PubChem (release 2021.10.14)

3.2 Experimental Properties

3.2.1 Physical Description

Dark red odorless solid; Hygroscopic; [Merck Index] Dark red powder; [Sigma-Aldrich MSDS]

3.2.2 Color / Form

Dark red crystals or an amorphous or crystalline red powder
American Hospital Formulary Service-Drug Information 88. Bethesda, MD: American Society of Hospital Pharmacists, 1988 (Plus supplements)., p. 2104
Dark-red crystals or red powder
Lewis, R.J., Sr (Ed.). Hawley's Condensed Chemical Dictionary. 13th ed. New York, NY: John Wiley & Sons, Inc. 1997., p. 320

3.2.3 Odor

Odorless
Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996., p. 1710

3.2.4 Taste

Tasteless
Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996., p. 1710

3.2.5 Boiling Point

> 300
> 300 °C
Weast, R.C. and M.J. Astle. CRC Handbook of Data on Organic Compounds. Volumes I and II. Boca Raton, FL: CRC Press Inc. 1985., p. V2 435

3.2.6 Melting Point

3.2.7 Solubility

12.5 mg/mL
Soluble in alcohol; insoluble in acetone, chloroform, ether.
Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996., p. 1710
In water, 1,25X10+4 mg/l @ 25 °C
Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996., p. 1710

3.2.8 LogP

3.2.9 LogS

3.2.10 Stability / Shelf Life

HYDRATED CRYSTALS ARE STABLE TO AIR, MAX STABILITY IN PH RANGE 4.5-5
The Merck Index. 10th ed. Rahway, New Jersey: Merck Co., Inc., 1983., p. 1435
Solutions of cyanocobalamin in water or 0.9% sodium chloride are stable and can be autoclaved for short periods of time (15-20 minutes) at 121 °C.
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 2000.Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2000 (Plus Supplements)., p. 3325
Cyanocobalamin is light sensitive ... so protection from light is recommended. Exposure to light results in the organometallic bond being cleaved, with the extent of degradation generally incr with incr light intensity.
Trissel, L.A. Handbook on Injectable Drugs. 9th ed. Bethesda, MD. American Society of Health-System Pharmacists' Product Development. 1996., p. 298
Cyanocobalamin with ascorbic acid can be stored for 24 hours at room temperature protected from light without loss of activity.
Trissel, L.A. Handbook on Injectable Drugs. 9th ed. Bethesda, MD. American Society of Health-System Pharmacists' Product Development. 1996., p. 298

3.2.11 Optical Rotation

SPECIFIC OPTICAL ROTATION: -59 + or - 9 DEG @ 23 °C 656 NM (DILUTE AQ SOLN)
The Merck Index. 10th ed. Rahway, New Jersey: Merck Co., Inc., 1983., p. 1435

3.2.12 pH

Commercially available cyanocobalamin for injection has a pH of 4.5-7
American Hospital Formulary Service-Drug Information 88. Bethesda, MD: American Society of Hospital Pharmacists, 1988 (Plus supplements)., p. 2104

3.2.13 Dissociation Constants

3.2.14 Other Experimental Properties

Hygroscopic; when exposed to air, may absorb about 12% water; darkens at 210-220 °C; not melted at 300 °C
Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996., p. 1710
All vitamin B12 compounds contain the cobalt atom in its trivalent state. There are at least three active forms: cyanobalamin, hydroxycyanobalamin; nitrocobalamin
Sax, N.I. Dangerous Properties of Industrial Materials. Vol 1-3 7th ed. New York, NY: Van Nostrand Reinhold, 1989., p. 3483

3.3 Chemical Classes

Biological Agents -> Vitamins and Derivatives

3.3.1 Drugs

3.3.1.1 Human Drugs
Breast Feeding; Lactation; Milk, Human; Vitamin B Complex; Vitamins
Human drug -> Prescription; Discontinued; Active ingredient (CYANOCOBALAMIN)

3.3.2 Cosmetics

Skin conditioning
S13 | EUCOSMETICS | Combined Inventory of Ingredients Employed in Cosmetic Products (2000) and Revised Inventory (2006) | DOI:10.5281/zenodo.2624118

3.3.3 Food Additives

NUTRIENT SUPPLEMENT -> FDA Substance added to food

4 Spectral Information

4.1 1D NMR Spectra

1D NMR Spectra
NMR: 500 (Johnson and Jankowski, Carbon-13 NMR Spectra, John Wiley & Sons, New York)

4.2 UV Spectra

MAX ABSORPTION (WATER): 278 NM (A= 115, 1%, 1 CM); 361 NM (A= 204, 1%, 1 CM); 550 NM (A= 64, 1%, 1 CM)
The Merck Index. 10th ed. Rahway, New Jersey: Merck Co., Inc., 1983., p. 1435

4.3 IR Spectra

IR Spectra
IR: 5404 (Coblentz Society Spectral Collection)

6 Chemical Vendors

7 Drug and Medication Information

7.1 Drug Indication

**Nasal spray** The cyanocobalamin nasal spray is indicated for the maintenance of vitamin B12 concentrations after normalization with intramuscular vitamin B12 therapy in patients with deficiency of this vitamin who have no nervous system involvement. Note: CaloMist, the nasal spray form, has not been evaluated for the treatment of newly diagnosed vitamin B12 deficiency. **Injection forms (subcutaneous, intramuscular)** These forms are indicated for vitamin B12 deficiencies due to various causes, with or without neurologic manifestations. Vitamin B12 deficiency is frequently caused by malabsorption, which is often associated with the following conditions: Addisonian (pernicious) anemia Gastrointestinal pathology, dysfunction, or surgery, including gluten enteropathy or sprue, small bowel bacterial overgrowth, total or partial gastrectomy Fish tapeworm infestation Malignancy of the pancreas or bowel Folic acid deficiency **Oral forms** Vitamin B12 supplements are widely available and indicated in patients who require supplementation for various reasons. Dose requirements for vitamin B12 which are higher than normal (caused by pregnancy, thyrotoxicosis, hemolytic anemia, hemorrhage, malignancy, hepatic and renal disease) can usually be achieved with oral supplementation. Oral products of vitamin B12 are not recommended in patients with malabsorption, as these forms are primarily absorbed in the gastrointestinal tract.

7.2 Drug Classes

Breast Feeding; Lactation; Milk, Human; Vitamin B Complex; Vitamins

7.3 FDA Approved Drugs

7.4 FDA Orange Book

7.5 FDA National Drug Code Directory

7.6 Drug Labels

Drug and label
Active ingredient and drug
Active ingredient and drug

7.7 Clinical Trials

7.7.1 ClinicalTrials.gov

7.7.2 EU Clinical Trials Register

7.7.3 NIPH Clinical Trials Search of Japan

7.8 Therapeutic Uses

Hematinics
National Library of Medicine's Medical Subject Headings online file (MeSH, 1999)
Vitamin B12 is used in the treatment of pernicious anemia and other vitamin B12 deficiency states. ... Cyanocobalamin ... usually indicated in patients with malabsorption of vitamin B12, such as those with tropical or nontropical sprue (idiopathic steatorrhea, gluten-induced enteropathy); partial or total gastrectomy; regional enteritis; gastroenterostomy; ileal resection; or malignancies, granulomas, strictures, or anastomoses involving the ileum. When the secretion of intrinsic factor is decreased by lesions that destroy the gastric mucosa (eg, following ingestion of corrosives or in patients with extensive GI neoplasia) or by gastric atrophy secondary to multiple sclerosis, certain endocrine disorders, or iron deficiency, or when antibodies to intrinsic factor are present in gastric juice, absorption of vitamin B12 is decreased and cyanocobalamin ... may be required. Malabsorption of vitamin B12 may also be caused by competition for vitamin B12 by bacteria (blind loop syndrome) or by fish tapeworm, Diphyllobothrium latum, or by admin of certain drugs.
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 2000.Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2000 (Plus Supplements)., p. 3325
The individual with an uncomplicated pernicious anemia, in which the abnormality is restricted to a mild or moderate anemia ... will respond quite well to the admin of vitamin B12 alone.
Hardman, J.G., L.E. Limbird, P.B. Molinoff, R.W. Ruddon, A.G. Goodman (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill, 1996., p. 1332
... Patients with neurological change or severe leukopenia or thrombocytopenia associated with infection or bleeding require emergency treatment. The older individual with a severe anemia (hematocrit less than 20%) is likely to have tissue hypoxia, cerebrovascular insufficiency, and congestive heart failure. Effective therapy must not wait for detailed diagnostic tests. ... The patient should receive intramuscular injections of 100 ug of cyanocobalamin and 1 to 5 mg of folic acid.
Hardman, J.G., L.E. Limbird, P.B. Molinoff, R.W. Ruddon, A.G. Goodman (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill, 1996., p. 1332
For more Therapeutic Uses (Complete) data for CYANOCOBALAMIN (13 total), please visit the HSDB record page.

7.9 Drug Warnings

Cyanocobalamin injection is extremely safe when given by the intramuscular or deep subcutaneous route, but it should never be given intravenously.
Hardman, J.G., L.E. Limbird, P.B. Molinoff, R.W. Ruddon, A.G. Goodman (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill, 1996., p. 1331
Cyanocobalamin should not be used in patients with early Leber's disease (hereditary optic nerve atrophy), since rapid optic nerve atrophy has been reported following admin of the drug to these patients. Vitamin B12 is contraindicated in patients who have experienced hypersensitivity reactions to the vitamin or to cobalt.
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 2000.Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2000 (Plus Supplements)., p. 3326
/"SHOTGUN"/ ... VITAMIN THERAPY IN TREATMENT OF ... DEFICIENCY CAN BE DANGEROUS. ... THERE IS DANGER THAT SUFFICIENT FOLIC ACID WILL BE GIVEN TO RESULT IN HEMATOLOGICAL RECOVERY; HOWEVER, THIS MAY MASK CONTINUED VIT-B DEFICIENCY & NEUROLOGICAL DAMAGE WILL DEVELOP OR PROGRESS IF ALREADY PRESENT.
Hardman, J.G., L.E. Limbird, P.B. Molinoff, R.W. Ruddon, A.G. Goodman (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill, 1996., p. 1332
Maternal Medication usually Compatible with Breast-Feeding: B12: Reported Sign or Symptom in Infant or Effect on Lactation: None. /from Table 6/
Report of the American Academy of Pediatrics Committee on Drugs in Pediatrics 93 (1): 140 (1994)
Serum potassium concn should be monitored during early vitamin B12 therapy & potassium admin is necessary, since fatal hypokalemia could occur upon conversion of megaloblastic anemia to normal erythropoesis with vitamin B12 as a result of increased erythrocyte potassium requirements. Because vitamin B12 deficiency may suppress the signs of polycythemia vera, treatment with cyanocobalamin may unmask this condition. The increase in nucleic acid degradation produced by admin vitamin B12 to vitamin B12- deficient patients could result in gout in susceptible individuals. Therapeutic response to vitamin B12 may be impaired by concurrent infection, uremia, folic acid or iron deficiency, or by drugs having bone marrow suppressant effects. Folic acid should be admin with extreme caution to patients with undiagnosed anemia, since folic acid may obscure the diagnosis of pernicious anemia by alleviating hematologic manifestations of the disease while allowing neurologic complications to progress. This may result in severe nervous system damage before the correct diagnosis is made. Vitamin preparations containing folic acid should be avoided by patients with pernicious anemia because folic acid may actually potentiate neurologic complications of vitamin B12 deficiency. Conversely, doses of cyanocobalamin exceeding 10 micrograms daily may improve folate-deficient megaloblastic anemia and obscure the true diagnosis.
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 2000.Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2000 (Plus Supplements)., p. 3326

8 Food Additives and Ingredients

8.1 FDA Substances Added to Food

Substance
Used for (Technical Effect)
NUTRIENT SUPPLEMENT
Document Number (21 eCFR)

9 Pharmacology and Biochemistry

9.1 Pharmacodynamics

**General effects** Cyanocobalamin corrects vitamin B12 deficiency and improves the symptoms and laboratory abnormalities associated with pernicious anemia (megaloblastic indices, gastrointestinal lesions, and neurologic damage). This drug aids in growth, cell reproduction, hematopoiesis, nucleoprotein, and myelin synthesis. It also plays an important role in fat metabolism, carbohydrate metabolism, as well as protein synthesis. Cells that undergo rapid division (for example, epithelial cells, bone marrow, and myeloid cells) have a high demand for vitamin B12. **Parenteral cyanocobalamin effects** The parenteral administration of vitamin B12 rapidly and completely reverses the megaloblastic anemia and gastrointestinal symptoms of vitamin B12 deficiency. Rapid parenteral administration of vitamin B12 in deficiency related neurological damage prevents the progression of this condition. **Nasal spray effects** In 24 vitamin B12 deficient patients who were already stabilized on intramuscular (IM) vitamin B12 therapy, single daily doses of intranasal cyanocobalamin for 8 weeks lead to serum vitamin B12 concentrations that were within the target therapeutic range (>200 ng/L).

9.2 MeSH Pharmacological Classification

Vitamin B Complex
A group of water-soluble vitamins, some of which are COENZYMES. (See all compounds classified as Vitamin B Complex.)

9.3 FDA Pharmacological Classification

Non-Proprietary Name
CYANOCOBALAMIN
Pharmacological Classes

9.4 ATC Code

B - Blood and blood forming organs

B03 - Antianemic preparations

B03B - Vitamin b12 and folic acid

B03BA - Vitamin b12 (cyanocobalamin and analogues)

B03BA01 - Cyanocobalamin

9.5 Bionecessity

Vitamin B12 deficiency is recognized clinically by its impact on both the hematopoietic and the nervous systems. The sensitivity of the hematopoietic system relates to its high rate of turnover of cells. ... As a result of an inadequate supply of vitamin B12, DNA replication becomes highly abnormal.
Hardman, J.G., L.E. Limbird, P.B. Molinoff, R.W. Ruddon, A.G. Goodman (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill, 1996., p. 1330
Vitamin B12 deficiency can result in irreversible damage to the nervous system. Progressive swelling of myelinated neurons, demyelination, and cell death are seen in the spinal column and cerebral cortex. This causes a wide range of neurological signs and symptoms, including paresthesias of the hands and feet, diminution of sensation of vibration and position with resultant unsteadiness, decreased deep-tendon reflexes, and, in the later stages, loss of memory, confusion, moodiness, and even a loss of central vision. The patient may exhibit delusions, hallucinations, or even an overt psychosis.
Hardman, J.G., L.E. Limbird, P.B. Molinoff, R.W. Ruddon, A.G. Goodman (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill, 1996., p. 1331
Recommended daily allowance of food & nutrition board (1980) for vitamin B-12 ranges from 0.5-3.0 ug; lower value for infants, & higher value for males and females between 7-51+ years of age. Pregnant and lactating individuals require +1.0 ug. /From table/
Hardman, J.G., L.E. Limbird, P.B. Molinoff, R.W. Ruddon, A.G. Goodman (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill, 1996., p. 1549
(VET): CHRONIC DEFICIENCIES IN MONKEYS ARE ASSOCIATED WITH SPINAL CORD DEGENERATION OF PERIPHERAL NERVES. DEFICIENCIES IN PREGNANT RATS ARE ASSOCIATED WITH HYDROCEPHALUS, DEMYELINATION OF PERIPHERAL NERVES, ADRENAL DEGENERATION ... IN THE OFFSPRING.
Rossoff, I.S. Handbook of Veterinary Drugs. New York: Springer Publishing Company, 1974., p. 649
For more Bionecessity (Complete) data for CYANOCOBALAMIN (9 total), please visit the HSDB record page.

9.6 Absorption, Distribution and Excretion

Absorption
Vitamin B12 is quickly absorbed from intramuscular (IM) and subcutaneous (SC) sites of injection; with peak plasma concentrations achieved about 1 hour after IM injection. Orally administered vitamin B12 binds to intrinsic factor (IF) during its transport through the stomach. The separation of Vitamin B12 and IF occurs in the terminal ileum when calcium is present, and vitamin B12 is then absorbed into the gastrointestinal mucosal cells. It is then transported by transcobalamin binding proteins. Passive diffusion through the intestinal wall can occur, however, high doses of vitamin B12 are required in this case (i.e. >1 mg). After the administration of oral doses less than 3 mcg, peak plasma concentrations are not reached for 8 to 12 hours, because the vitamin is temporarily retained in the wall of the lower ileum.
Route of Elimination
This drug is partially excreted in the urine. According to a clinical study, approximately 3-8 mcg of vitamin B12 is secreted into the gastrointestinal tract daily via the bile. In patients with adequate levels of intrinsic factor, all except approximately 1 mcg is reabsorbed. When vitamin B12 is administered in higher doses that saturate the binding capacity of plasma proteins and the liver, the unbound vitamin B12 is eliminated rapidly in the urine. The body storage of vitamin B12 is dose-dependent.
Volume of Distribution
Cobalamin is distributed to tissues and stored mainly in the liver and bone marrow.
Clearance
During vitamin loading, the kidney accumulates large amounts of unbound vitamin B12. This drug is cleared partially by the kidney, however, multiligand receptor _megalin_ promotes the reuptake and reabsorption of vitamin B12 into the body,.
IN MICE INJECTED IV WITH VITAMIN B12, THE VITAMIN ACCUMULATED RAPIDLY IN THE PLACENTA & WAS TRANSFERRED SLOWLY TO THE FETUSES. PEAK CONCN IN THE FETUSES WAS REACHED 24 HR AFTER DOSING, & FETAL ACCUMULATION WAS DOSE-DEPENDENT.
The Chemical Society. Foreign Compound Metabolism in Mammals Volume 3. London: The Chemical Society, 1975., p. 636
IN /MICE/ VITAMIN B12 PRESENTS UNUSUAL PATTERN OF PLACENTAL TRANSFER, FOR EVEN WITH 0.20 UG MATERNAL DOSE AVG FETAL CONCN IS 130 TIMES HIGHER THAN MATERNAL ONE. THIS INDICATES STRONGLY OPERATION OF SPECIFIC TRANSPORT MECHANISM FOR VITAMIN B12, POSSIBLY SIMILAR TO ITS GI ABSORPTION ...
The Chemical Society. Foreign Compound Metabolism in Mammals Volume 3. London: The Chemical Society, 1975., p. 636
IN RATS, PLACENTAL TRANSFER OF VITAMIN B12 WAS SHOWN TO INCR DURING GESTATION. ALTHOUGH QUANTITY TRANSPORTED EACH DAY WAS PROPORTIONAL TO FETAL WT, THE AMT TRANSPORTED PER G OF PLACENTA INCR TEN-FOLD FROM DAY 10 TO DAY 19.
The Chemical Society. Foreign Compound Metabolism in Mammals Volume 3. London: The Chemical Society, 1975., p. 636
Vitamin B12 is irregularly absorbed from the distal small intestine following oral administration. Dietary vitamin B12 is protein bound and this bond must be split by proteolysis and gastric acid before absorption. In the stomach, free vitamin B12 is attached to intrinsic factor; intrinsic factor a glycoprotein secreted by the gastric mucosa, is necessary for active absorption of the vitamin from the GI tract. The vitamin B12-intrinsic factor complex passes into the intestine, where much of the complex is transiently retained at specific receptor sites in the wall of the lower ileum before the vitamin B12 portion is absorbed into systemic circulation.
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 2000.Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2000 (Plus Supplements)., p. 3325
For more Absorption, Distribution and Excretion (Complete) data for CYANOCOBALAMIN (9 total), please visit the HSDB record page.

9.7 Metabolism / Metabolites

Vitamin B12 or cyanocobalamin obtained from food is initially bound by _haptocorrin_, a protein found in the saliva with high affinity for B12. This forms a _haptocorrin-B12_ complex. Cyanocobalamin passes through the stomach and is protected from acid degradation due to its binding to haptocorrin. In the duodenum, pancreatic _proteases_ release cobalamin from the _haptocorrin-B12 complex_ and from other proteins containing protein-bound B12 that have been ingested. Following this, the binding of cobalamin to a second glycoprotein, _intrinsic factor_, promotes its uptake by terminal ileum mucosal cells by a process called _cubilin_/AMN receptor-mediated endocytosis. After absorption into enterocytes, intrinsic factor is broken down in the lysosome, and cobalamin is then released into the bloodstream. The transporter ABCC1, found in the basolateral membrane of intestinal epithelial and other cells, exports cobalamin bound to transcobalamin out of the cell. Cyanocobalamin then passes through the portal vein in the liver, and then reaches the systemic circulation. The active forms of cyanocobalamin are _methylcobalamin_ and _adenosylcobalamin_,.
Vitamin B12 is believed to be converted to coenzyme form in the liver and is probably stored in tissues in this form.
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 2000.Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2000 (Plus Supplements)., p. 3325
Intracellular vitamin B12 is maintained as two active coenzymes methylcobalamin and deoxyadenasylcobalamin.
Hardman, J.G., L.E. Limbird, P.B. Molinoff, R.W. Ruddon, A.G. Goodman (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill, 1996., p. 1328

9.8 Biological Half-Life

Approximately 6 days (400 days in the liver).
HALF-LIFE OF IV ADMIN CYANOCOBALAMIN IN SERUM IS ABOUT 6 DAYS.
Evaluations of Drug Interactions. 2nd ed. and supplements. Washington, DC: American Pharmaceutical Assn., 1976, 1978., p. 450

9.9 Mechanism of Action

Vitamin B12 serves as a cofactor for _methionine synthase_ and _L-methylmalonyl-CoA mutase_ enzymes. Methionine synthase is essential for the synthesis of purines and pyrimidines that form DNA. L-methylmalonyl-CoA mutase converts L-methylmalonyl-CoA to _succinyl-CoA_ in the degradation of propionate, an important reaction required for both fat and protein metabolism. It is a lack of vitamin B12 cofactor in the above reaction and the resulting accumulation of methylmalonyl CoA that is believed to be responsible for the neurological manifestations of B12 deficiency. Succinyl-CoA is also necessary for the synthesis of hemoglobin. In tissues, vitamin B12 is required for the synthesis of _methionine_ from homocysteine. Methionine is required for the formation of S-adenosylmethionine, a methyl donor for nearly 100 substrates, comprised of DNA, RNA, hormones, proteins, as well as lipids. Without vitamin B12, tetrahydrofolate cannot be regenerated from 5-methyltetrahydrofolate, and this can lead to functional folate deficiency,. This reaction is dependent on methylcobalamin (vitamin B12) as a co-factor and is also dependent on folate, in which the methyl group of methyltetrahydrofolate is transferred to homocysteine to form _methionine_ and _tetrahydrofolate_. Vitamin B12 incorporates into circulating folic acid into growing red blood cells; retaining the folate in these cells. A deficiency of vitamin B12 and the interruption of this reaction leads to the development of megaloblastic anemia.
CYANOCOBALAMIN STIMULATES RETICULOCYTES, THUS PLAYING IMPORTANT ROLE IN HEMATOPOIESIS IN THAT, TOGETHER WITH FOLIC ACID, IT IS INVOLVED IN FORMATION OF DEOXYRIBONUCLEOTIDES FROM RIBONUCLEOTIDES.
Evaluations of Drug Interactions. 2nd ed. and supplements. Washington, DC: American Pharmaceutical Assn., 1976, 1978., p. 450
Vitamin B12 is converted to Coenzyme B12 in tissues, and as such is essential for conversion of methylmalonate to succinate and synthesis of methionine from homocysteine, a reaction which also requires folate. ... Vitamin B12 also may be involved in maintaining sulfhydryl (SH) groups in the reduced form required by many SH-activated enzyme systems. Through these reactions, vitamin B12 is associated with fat and carbohydrate metabolism and protein synthesis.
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 2000.Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2000 (Plus Supplements)., p. 3325

10 Use and Manufacturing

10.1 Uses

Sources/Uses
Produced by bacteria, cobalamins (hydroxocobalamin and cyanocobalamin) are analogs of vitamin B12 that differ only in the beta-ligand of the cobalt; Found in fish, meat, liver, and dairy products, but not in plants; Also occur naturally in soil, water, activated sewage sludge, and manure; Used as a vitamin (hematopoietic); [Merck Index] Used as a nutritional supplement and stabilizer or thickener for foods; [FDA] Permitted for use as an inert ingredient in non-food pesticide products; [EPA] Used to perform Schilling's test (pernicious anemia or other malabsorption disorders), as a medicine, nutrient, and animal feed supplement; [HSDB] Hydroxocabalamin is used to treat cyanide poisoning. [Olson, p. 563]
Merck Index - O'Neil MJ, Heckelman PE, Dobbelaar PH, Roman KJ (eds). The Merck Index, An Encyclopedia of Chemicals, Drugs, and Biologicals, 15th Ed. Cambridge, UK: The Royal Society of Chemistry, 2013.
Olson - Olson KR (ed). Poisoning & Drug Overdose, 7th Ed. New York: Lange Medical Books/McGraw-Hill, 2018., p. 563
Industrial Processes with risk of exposure
Farming (Feed Additives) [Category: Industry]
MEDICATION
MEDICATION (VET):
Used to perform Schilling's test for pernicious anemia or other malabsorption disorders
American Medical Association, Department of Drugs. Drug Evaluations. 6th ed. Chicago, Ill: American Medical Association, 1986., p. 596
Medicine (blood and nerve treatment), nutrition, animal-feed supplements.
Lewis, R.J., Sr (Ed.). Hawley's Condensed Chemical Dictionary. 13th ed. New York, NY: John Wiley & Sons, Inc. 1997., p. 320

Use (kg; approx.) in Germany (2009): >75

Consumption (g per capita; approx.) in Germany (2009): 0.000916

10.1.1 Use Classification

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients
Cosmetics -> Skin conditioning
S13 | EUCOSMETICS | Combined Inventory of Ingredients Employed in Cosmetic Products (2000) and Revised Inventory (2006) | DOI:10.5281/zenodo.2624118

10.1.2 Household Products

Household & Commercial/Institutional Products

Information on 3 consumer products that contain Cyanocobalamin in the following categories is provided:

• Personal Care

10.2 Methods of Manufacturing

Isoln from mammalian liver: E.L. Rickes et al, Science 107, 396 (1948); from cultures of Streptomyces griseus: eidem, ibid 108, 634 (1948); E.L. Rickes, T. R. Wood, US pat 2,563,794 (1951 to Merck & Co)
Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996., p. 1710
BERNHAUER ET AL, US PATENT 3,120,509 (1962 TO HOFFMANN-LA ROCHE).
The Merck Index. 10th ed. Rahway, New Jersey: Merck Co., Inc., 1983., p. 1435
Purification from sewage sludge: Van Melle, US patent 3,057,851 (1962 to Armour)
Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996., p. 1710
Total synthesis: R.B. Woodward, Pure Appl Chem 33, 145 (1973)
Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996., p. 1710
Secondary metabolic product /of/ Propionibacterium species, Streptomyces species, large scale submerged culture
Gerhartz, W. (exec ed.). Ullmann's Encyclopedia of Industrial Chemistry. 5th ed.Vol A1: Deerfield Beach, FL: VCH Publishers, 1985 to Present., p. VA4 (85) 149

10.3 Formulations / Preparations

Vitamin B12 is available in pure form for injection or oral admin or in combination with other vitamins and minerals for oral admin.
Hardman, J.G., L.E. Limbird, P.B. Molinoff, R.W. Ruddon, A.G. Goodman (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill, 1996., p. 1331
Grade: USP, radioactive
Lewis, R.J., Sr (Ed.). Hawley's Condensed Chemical Dictionary. 13th ed. New York, NY: John Wiley & Sons, Inc. 1997., p. 319
Cyanocobalamin injection (Redisol, rubramin PC) ... available in concentrations of 1 to 1000 ug/ml.
Hardman, J.G., L.E. Limbird, P.B. Molinoff, R.W. Ruddon, A.G. Goodman (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill, 1996., p. 1331
Ce-cobalin syrup contains in each ml cyanocobalamin 6 ug and ascorbic acid 2 mg; Cytacon: cyanocobalamin available as liquid containing 35 ug in each 5 ml (suggested diluent, syrup) and as tablets of 50 ug; Cytamen: Cyanocobalamin, available as injection containing 250 or 1000 ug per ml in ampules of 1 ml; Hepacon-B12: Cyanocobalamin, available as injection containing 100 or 1000 ug per ml in ampules of 1 ml; Hepanorm tablets: each contains cyanocobalamin 7.5 mg, intrinsic factor concentrate 25 mg, folic acid 2.5 mg, and liver fraction 150 mg.
Reynolds, J.E.F., Prasad, A.B. (eds.) Martindale-The Extra Pharmacopoeia. 28th ed. London: The Pharmaceutical Press, 1982., p. 1645
Chromagen capsules: each capsule contains ... cyanocobalamin 10 ug; Fergon plus: each capsule contains ... vitamin B12 with intrinsic factor concentrate NF 1/2 unit; Heptune plus: each capsule contains ... vitamin B12 concentrate 25 ug; Iberet: each tablet contains ... cyanocobalamin 25 ug; Iberol: each tablet contains ... cyanocobalamin 12.5 ug; Iromin-G: each tablet contains ... vitamin B12 (crystalline or resin) 2 ug. Niferex forte: each capsule contains ... vitamin B12 25 ug; Nu-Iron plus: each 5 ml of elixir contains ... vitamin B12 25 ug; Perhemin: each capsule contains ... cyanocobalamin 50 ug; Peritinic: each tablet contains ... vitamin B12 5 ug; Pronemia: each capsule contains ... vitamin B12 (as cobalamin concentrate) 15 ug.
American Medical Association, Department of Drugs. Drug Evaluations. 6th ed. Chicago, Ill: American Medical Association, 1986., p. 600

10.4 U.S. Imports

(1983) 8.04X10+7 g
USITC. IMPORTS OF BENZENOID CHEM & PROD 1983 p.88
(1986) 2.36X10+5 lb
BUREAU OF THE CENSUS. US IMPORTS FOR CONSUMPTION AND GENERAL IMPORTS 1986 p.1-509

10.5 U.S. Exports

(1987) 3.78X10+3 lb
BUREAU OF THE CENSUS. U. S. EXPORTS, SCHEDULE E, OCTOBER 1987, P.2-103

10.6 General Manufacturing Information

EPA TSCA Commercial Activity Status
Vitamin B12: ACTIVE
TALC HAS A TENACIOUS AFFINTIY FOR VITAMIN B12; ALTHOUGH THIS IS NOT AN INCOMPATIBILITY, IT PRECLUDES USE OF TALC AS A FILTER AID OR LUBRICANT FOR TABLETS, PARTICULARLY IN VIEW OF POSSIBLE ASSAY DIFFICULTIES.
The Merck Index. 10th ed. Rahway, New Jersey: Merck Co., Inc., 1983., p. 1435
Prototype of the family of naturally occurring cobalt coordination cmpds known as corrinoids.
Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996., p. 1710
Source: (Food) Liver, eggs, milk, meats, and fish. Commercial source: produced by microbial action on various nutrients (spent antibiotic liquors, sugarbeet molasses, whey), also from sewage sludge.
Lewis, R.J., Sr (Ed.). Hawley's Condensed Chemical Dictionary. 13th ed. New York, NY: John Wiley & Sons, Inc. 1997., p. 320

10.7 Sampling Procedures

Analyte: Cobalt; Matrix: air; Sampler: filter (0.8 um cellulose ester membrane); Flow rate: 1 to 3 l/min; Vol: min: 30 l @ 0.1 mg/cu m, max: 1500 l; Stability: stable /Cobalt and cmpd as Co/
U.S. Department of Health and Human Services, Public Health Service. Centers for Disease Control, National Institute for Occupational Safety and Health. NIOSH Manual of Analytical Methods, 3rd ed. Volumes 1 and 2 with 1985 supplement, and revisions. Washington, DC: U.S. Government Printing Office, February 1984., p. V1 7027-1
Analyte: Cobalt; Specimen: Blood or tissue; Vol: 10 ml blood, or 1 g tissue; Preservative: Heparin for blood, none for tissue; Controls: collect 3 blood specimens from unexposed workers; Stability: not established /Elements in blood or tissue, Cobalt/
U.S. Department of Health and Human Services, Public Health Service. Centers for Disease Control, National Institute for Occupational Safety and Health. NIOSH Manual of Analytical Methods, 3rd ed. Volumes 1 and 2 with 1985 supplement, and revisions. Washington, DC: U.S. Government Printing Office, February 1984., p. V1 8005-1

11 Identification

11.1 Analytic Laboratory Methods

SEPARATION OF COBALAMINES & OF COENZYME B12 BY HIGH-PRESSURE LIQUID CHROMATOGRAPHY.
MOUROT ET AL; ANN PHARM FR 37 (5-6): 235 (1979)
A SEPARATION METHOD USING REVERSED PHASE HIGH PERFORMANCE LIQUID CHROMATOGRAPHY ON VITAMIN B12 ANALOGS (MECOBALAMIN, COBAMIDE, CYANOCOBALAMIN & HYDROXOCOBALAMIN) WAS DESCRIBED.
HATTORI ET AL; YAKUGAKU ZASSHI 100 (APRIL): 386 (1980)
Vitamin B1, vitamin B2, vitamin B6, and vitamin B12 were simultaneously detected in pharmaceuticals by high performance liquid chromatography on a LiChrosorb RP-18 column with a methanol-water (80:20 and 50:50) mobile phase and ultra violet detection at 254 nm. Linear relations between the peak areas and the concn for the vitamins were observed in the following ranges: 10-50 and 50-250 ng for vitamin B1, and 20-100 and 100-500 ng for vitamins B2, B6, and B12. The relative standard deviation was 4.2%.
Amin M, Reusch J; J Chromatog 390 (2): 448-53 (1987)
ANALYSIS OF VITAMIN B12 BY FLAMELESS ATOMIC ABSORPTION.
PECK E; ANAL LETT B11 (2): 103 (1978)

11.2 Clinical Laboratory Methods

A RADIOASSAY FOR ESTIMATION OF SERUM VITAMIN B12 IN PRESENCE OF NATURALLY OCCURRING VITAMIN B12 ANALOGS CAN BE OPERATED IF SERUM TRANSCOBALAMIN II IS USED AS THE BINDING PROTEIN.
PALTRIDGE ET AL; ANN CLIN BIOCHEM 17 (6): 287 (1980)

12 Safety and Hazards

12.1 Hazards Identification

12.1.1 GHS Classification

Note
This chemical does not meet GHS hazard criteria for 99.3% (133 of 134) of all reports. Pictograms displayed are for 0.7% (1 of 134) of reports that indicate hazard statements.
GHS Hazard Statements

Not Classified

Reported as not meeting GHS hazard criteria by 133 of 134 companies (only 0.7% companies provided GHS information). For more detailed information, please visit ECHA C&L website.

ECHA C&L Notifications Summary

Aggregated GHS information provided per 134 reports by companies from 2 notifications to the ECHA C&L Inventory.

Reported as not meeting GHS hazard criteria per 133 of 134 reports by companies. For more detailed information, please visit ECHA C&L website.

There is 1 notification provided by 1 of 134 reports by companies with hazard statement code(s).

Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.

12.1.2 Hazard Classes and Categories

Not Classified

12.1.3 Hazards Summary

Patients treated with IV hydroxocobalamin have red urine and erythema; [Olson, p. 563] May cause irritation; [Sigma-Aldrich MSDS]
Olson - Olson KR (ed). Poisoning & Drug Overdose, 7th Ed. New York: Lange Medical Books/McGraw-Hill, 2018., p. 563

12.2 Accidental Release Measures

12.2.1 Disposal Methods

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

12.3 Handling and Storage

12.3.1 Storage Conditions

Cyanocobalamin ... should be protected from light.
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 2000.Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2000 (Plus Supplements)., p. 3325

12.4 Regulatory Information

The Australian Inventory of Industrial Chemicals
Chemical: Vitamin B12
REACH Registered Substance
New Zealand EPA Inventory of Chemical Status
Vitamin B12: Does not have an individual approval but may be used under an appropriate group standard

12.4.1 Atmospheric Standards

Listed as a hazardous air pollutant (HAP) generally known or suspected to cause serious health problems. The Clean Air Act, as amended in 1990, directs EPA to set standards requiring major sources to sharply reduce routine emissions of toxic pollutants. EPA is required to establish and phase in specific performance based standards for all air emission sources that emit one or more of the listed pollutants. Cyanocobalamin is included on this list.
Clean Air Act as amended in 1990, Sect. 112 (b) (1) Public Law 101-549 Nov. 15, 1990

12.4.2 FDA Requirements

Substance added directly to human food affirmed as generally recognized as safe (GRAS).
21 CFR 184.1945 (4/1/2000)
Vitamin B12 used as a nutrient and/or dietary supplement in animal drugs, feeds, and related products is generally recognized as safe when used in accordance with good manufacturing or feeding practice.
21 CFR 582.5945 (4/1/2000)

13 Toxicity

13.1 Toxicological Information

13.1.1 Effects During Pregnancy and Lactation

◉ Summary of Use during Lactation

Vitamin B12 is a normal component of human milk. The recommended daily intake in lactating women is 2.8 mcg and for infants aged 6 months or less is 0.4 mcg. Some authorities recommend 5.5 mcg per day during lactation. Supplementation may be necessary to achieve these recommended daily intakes or to correct a known deficiency. Low doses (1 to 10 mcg) of vitamin B12 found in B complex or prenatal vitamins increase milk levels only slightly. Higher daily doses of 50 to 250 mcg are needed in cases of maternal deficiency. The breastfed infant is not exposed to excessive vitamin B12 in such cases, and their vitamin B12 status should improve if it was previously inadequate.

Poor health outcomes in infants with vitamin B12 deficiency include anemia, abnormal skin and hair development, convulsions, weak muscle tone, failure to thrive, mental developmental delay, and potentially abnormal movements. Well-recognized at risk groups are exclusively breastfed infants of mothers with B12 deficiency due to minimal or no dietary intake of animal products or pernicious anemia caused by a maternal malabsorption of B12. Infant vitamin B12 status can be improved through maternal B12 supplementation during pregnancy and lactation. Deficient mothers who miss the opportunity to supplement during pregnancy should still be encouraged to supplement during early lactation since infant vitamin B12 status correlates with milk vitamin B12 levels in breastfed infants up to 6 months of age. Although there are cases reported of exclusively breastfed infants with vitamin B12 deficiency having biochemical and clinical improvement through adequate maternal supplementation alone, direct supplementation of the infant is recommended when such treatments are available.

◉ Effects in Breastfed Infants

Twelve exclusively breastfed infants between 4 and 11 months of age had biochemical, hematological and clinical findings consistent with vitamin B12 deficiency. Their mothers received a 50 mcg single dose of intramuscular vitamin B12. Within 5 to 8 days after the dose, the infants experienced significantly increased hemoglobin and reticulocyte counts, normoblastic erythropoiesis, improved mental status, regression of abnormal skin pigmentation, and reduction in tremors.

Three hundred sixty-six pregnant women in India received 50 mcg of oral vitamin B12 or placebo capsules once daily beginning during their first trimester of pregnancy and continuing until 6 weeks postpartum. Among 218 infants that underwent neurodevelopment testing at 30 months of age, those born to mothers randomized to vitamin B12 had higher expressive language scores than the placebo group when adjusted for baseline maternal vitamin B12 deficiency. Cognitive, receptive language and motor scores were not different between the two groups. Neurophysiological assessments were then conducted at 6 years of age and there were no differences in the measured brain activity between the two groups.

◉ Effects on Lactation and Breastmilk

Relevant published information was not found as of the revision date.

13.1.2 Interactions

ABSORPTION OF VITAMINE B12 FROM THE GI TRACT MAY BE DECR BY AMINOGLYCOSIDE ANTIBIOTICS, COLCHICINE, EXTENTED-RELEASE POTASSIUM PREPN, AMINOSALICYLIC ACID & ITS SALTS, ANTICONVULSANTS (EG, PHENYTOIN, PHENOBARBITAL, PRIMADONE), COBALT IRRADIATION OF THE SMALL BOWEL, & BY EXCESSIVE ALCOHOL INTAKE LASTING LONGER THAN 2 WK.
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 2000.Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2000 (Plus Supplements)., p. 3326
The gastrointestinal absorption of vitamin B12 can be considerably decreased by oral neomycin. Colchicine administration appears to increase neomycin-induced malabsorption of vitamin B12.
Hansten P.D. Drug Interactions. 5th ed. Philadelphia: Lea and Febiger, 1985., p. 199
The decreased vitamin B12 absorption induced by aminosalicylic acid may be due to the mild malabsorption syndrome that occurs in some patients treated with aminosalicylic acid (PAS).
Hansten P.D. Drug Interactions. 5th ed. Philadelphia: Lea and Febiger, 1985., p. 202
Patients with pernicious anemia ... respond poorly to vitamin B12 therapy if chloroamphenicol is given concomitantly.
Hansten P.D. Drug Interactions. 5th ed. Philadelphia: Lea and Febiger, 1985., p. 207
For more Interactions (Complete) data for CYANOCOBALAMIN (7 total), please visit the HSDB record page.

13.1.3 Human Toxicity Excerpts

Vitamin B12 is usually nontoxic even in large doses; however, mild transient diarrhea, peripheral vascular thrombosis, itching, transitory exanthema, urticaria, feeling of swelling of the entire body, anaphylaxis, and death have been reported. Although allergic reactions to vitamin B12 have generally been attributed to impurities in the preparation, a few patients have reacted positively to skin testing with purified cyanocobalamin ... .
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 2000.Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2000 (Plus Supplements)., p. 3326

13.1.4 Non-Human Toxicity Excerpts

Convulsions, followed by cardiac or respiratory failure, have been described in mice given 1.5-3 mg/kg body weight of vitamin B12; clinical signs were not thought to be due to hypersensitivity.
Clarke, M. L., D. G. Harvey and D. J. Humphreys. Veterinary Toxicology. 2nd ed. London: Bailliere Tindall, 1981., p. 126

13.1.5 Protein Binding

Very high (to specific plasma proteins called transcobalamins); binding of hydroxocobalamin is slightly higher than cyanocobalamin [FDA label.

13.2 Ecological Information

13.2.1 Natural Pollution Sources

/Isolated from/ Streptomyces griseus or Streptomyces aureofaciens
Kirk-Othmer Encyclopedia of Chemical Technology. 3rd ed., Volumes 1-26. New York, NY: John Wiley and Sons, 1978-1984., p. 5(79) 159
In foods, vitamin B12 occurs only in animal products.
Kirk-Othmer Encyclopedia of Chemical Technology. 3rd ed., Volumes 1-26. New York, NY: John Wiley and Sons, 1978-1984., p. 15(81) 597
In nature, primary sources are certain microorganisms that grow in soil, sewage, water, or the intestinal lumen of animals, and that synthesize the vitamin.
Hardman, J.G., L.E. Limbird, P.B. Molinoff, R.W. Ruddon, A.G. Goodman (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill, 1996., p. 1329
Synthesized almost exclusively by bacteria. ... Also found in soil and water, richest sources being activated sewage sludge ... or manure.
Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996., p. 1710

13.2.2 Milk Concentrations

Vitamin B12 is excreted into human breast milk. In the first 48 hours after delivery, mean colostrum levels were 2431 pg/ml & then fell rapidly to concn comparable to those of normal serum. One group of investigators also observed very high colostrum levels, ranging from 6-17.5 times that of milk. Milk:plasma ratios are approx 1.0 during lactation. Reported milk concn of B12 vary widely.
Briggs, G.G, R.K. Freeman, S.J. Yaffe. A Reference Guide to Fetal and Neonatal Risk. Drugs in Pregnancy and Lactation. 4th ed. Baltimore, MD: Williams & Wilkins 1994., p. 892

13.2.3 Body Burden

Normal serum vitamin B12 concentrations have been reported to range from 200-900 pg/ml, with a mean normal plasma concentration of 450 pg/ml.
American Hospital Formulary Service-Drug Information 88. Bethesda, MD: American Society of Hospital Pharmacists, 1988 (Plus supplements)., p. 2105

14 Associated Disorders and Diseases

15 Literature

15.1 Consolidated References

15.2 NLM Curated PubMed Citations

15.3 Chemical Co-Occurrences in Literature

15.4 Chemical-Gene Co-Occurrences in Literature

15.5 Chemical-Disease Co-Occurrences in Literature

16 Patents

16.1 Depositor-Supplied Patent Identifiers

16.2 FDA Orange Book Patents

16.3 Chemical Co-Occurrences in Patents

16.4 Chemical-Disease Co-Occurrences in Patents

16.5 Chemical-Gene Co-Occurrences in Patents

17 Interactions and Pathways

17.1 Chemical-Target Interactions

17.2 Drug-Drug Interactions

17.3 Drug-Food Interactions

Take with or without food. Recommendations vary from product to product - consult individual product monographs for additional information.

18 Taxonomy

19 Classification

19.1 MeSH Tree

19.2 WHO ATC Classification System

19.3 UN GHS Classification

19.4 NORMAN Suspect List Exchange Classification

19.5 Consumer Product Information Database Classification

19.6 EPA TSCA and CDR Classification

19.7 FDA Drug Type and Pharmacologic Classification

20 Information Sources

  1. Australian Industrial Chemicals Introduction Scheme (AICIS)
  2. DrugBank
    LICENSE
    Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode)
    https://www.drugbank.ca/legal/terms_of_use
  3. EPA Chemicals under the TSCA
    EPA TSCA Classification
    https://www.epa.gov/tsca-inventory
  4. European Chemicals Agency (ECHA)
    LICENSE
    Use of the information, documents and data from the ECHA website is subject to the terms and conditions of this Legal Notice, and subject to other binding limitations provided for under applicable law, the information, documents and data made available on the ECHA website may be reproduced, distributed and/or used, totally or in part, for non-commercial purposes provided that ECHA is acknowledged as the source: "Source: European Chemicals Agency, http://echa.europa.eu/". Such acknowledgement must be included in each copy of the material. ECHA permits and encourages organisations and individuals to create links to the ECHA website under the following cumulative conditions: Links can only be made to webpages that provide a link to the Legal Notice page.
    https://echa.europa.eu/web/guest/legal-notice
  5. Hazardous Substances Data Bank (HSDB)
  6. New Zealand Environmental Protection Authority (EPA)
    LICENSE
    This work is licensed under the Creative Commons Attribution-ShareAlike 4.0 International licence.
    https://www.epa.govt.nz/about-this-site/general-copyright-statement/
  7. ClinicalTrials.gov
    LICENSE
    The ClinicalTrials.gov data carry an international copyright outside the United States and its Territories or Possessions. Some ClinicalTrials.gov data may be subject to the copyright of third parties; you should consult these entities for any additional terms of use.
    https://clinicaltrials.gov/ct2/about-site/terms-conditions#Use
  8. Comparative Toxicogenomics Database (CTD)
    LICENSE
    It is to be used only for research and educational purposes. Any reproduction or use for commercial purpose is prohibited without the prior express written permission of NC State University.
    http://ctdbase.org/about/legal.jsp
  9. Consumer Product Information Database (CPID)
    LICENSE
    Copyright (c) 2024 DeLima Associates. All rights reserved. Unless otherwise indicated, all materials from CPID are copyrighted by DeLima Associates. No part of these materials, either text or image may be used for any purpose other than for personal use. Therefore, reproduction, modification, storage in a retrieval system or retransmission, in any form or by any means, electronic, mechanical or otherwise, for reasons other than personal use, is strictly prohibited without prior written permission.
    https://www.whatsinproducts.com/contents/view/1/6
    Consumer Products Category Classification
    https://www.whatsinproducts.com/
  10. DailyMed
  11. E. coli Metabolome Database (ECMDB)
    LICENSE
    ECMDB is offered to the public as a freely available resource.
    https://ecmdb.ca/citations
  12. NCI Thesaurus (NCIt)
    LICENSE
    Unless otherwise indicated, all text within NCI products is free of copyright and may be reused without our permission. Credit the National Cancer Institute as the source.
    https://www.cancer.gov/policies/copyright-reuse
  13. Yeast Metabolome Database (YMDB)
    LICENSE
    YMDB is offered to the public as a freely available resource.
    http://www.ymdb.ca/downloads
  14. Drugs and Lactation Database (LactMed)
  15. Drugs@FDA
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  16. EU Clinical Trials Register
  17. FDA Orange Book
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  18. NORMAN Suspect List Exchange
    LICENSE
    Data: CC-BY 4.0; Code (hosted by ECI, LCSB): Artistic-2.0
    https://creativecommons.org/licenses/by/4.0/
    NORMAN Suspect List Exchange Classification
    https://www.norman-network.com/nds/SLE/
  19. FDA Substances Added to Food
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  20. Haz-Map, Information on Hazardous Chemicals and Occupational Diseases
    LICENSE
    Copyright (c) 2022 Haz-Map(R). All rights reserved. Unless otherwise indicated, all materials from Haz-Map are copyrighted by Haz-Map(R). No part of these materials, either text or image may be used for any purpose other than for personal use. Therefore, reproduction, modification, storage in a retrieval system or retransmission, in any form or by any means, electronic, mechanical or otherwise, for reasons other than personal use, is strictly prohibited without prior written permission.
    https://haz-map.com/About
  21. Metabolomics Workbench
  22. National Drug Code (NDC) Directory
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  23. Natural Product Activity and Species Source (NPASS)
  24. NIPH Clinical Trials Search of Japan
  25. NLM RxNorm Terminology
    LICENSE
    The RxNorm Terminology is created by the National Library of Medicine (NLM) and is in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from NLM. Credit to the U.S. National Library of Medicine as the source is appreciated but not required. The full RxNorm dataset requires a free license.
    https://www.nlm.nih.gov/research/umls/rxnorm/docs/termsofservice.html
  26. WHO Anatomical Therapeutic Chemical (ATC) Classification
    LICENSE
    Use of all or parts of the material requires reference to the WHO Collaborating Centre for Drug Statistics Methodology. Copying and distribution for commercial purposes is not allowed. Changing or manipulating the material is not allowed.
    https://www.whocc.no/copyright_disclaimer/
  27. Wikipedia
  28. Medical Subject Headings (MeSH)
    LICENSE
    Works produced by the U.S. government are not subject to copyright protection in the United States. Any such works found on National Library of Medicine (NLM) Web sites may be freely used or reproduced without permission in the U.S.
    https://www.nlm.nih.gov/copyright.html
  29. PubChem
  30. GHS Classification (UNECE)
  31. NCBI
CONTENTS