Vitamin B12

Who should not take this medication? Patients with early hereditary optic nerve atrophy, cyanocobalmin hypersensitivity, and those who are pregnant. Your health care provider needs to know if you have any of these conditions: kidney disease; Leber’s disease; megaloblastic anemia; an unusual or allergic reaction to methylcobalamin, cobalt, other medicines, foods, dyes, or preservatives; pregnant or trying to get pregnant; breastfeeding.

Methylcobalamin is contraindicated in patients with methylcobalamin hypersensitivity or hypersensitivity to any of the medication components. Methylcobalamin is also contraindicated in patients with cobalt hypersensitivity because methylcobalamin contains cobalt. In the case of suspected cobalt hypersensitivity, an intradermal test dose should be administered because anaphylactic shock and death have followed parenteral administration of methylcobalamin.

Methylcobalamin should not be used in patients with early hereditary optic nerve atrophy (Leber’s disease). Optic nerve atrophy can worsen in patients whose methylcobalamin levels are already elevated. Hydroxocobalamin is the preferred agent in this patient population (see separate monograph in Less Common Drugs).

Most formulations of methylcobalamin injection contain benzyl alcohol as a preservative. Benzyl alcohol may cause allergic reactions. Methylcobalamin injections should be used cautiously in those patients with benzyl alcohol hypersensitivity. Methylcobalamin, vitamin B12 preparations containing benzyl alcohol should be avoided in premature neonates because benzyl alcohol has been associated with ‘gasping syndrome,’ a potentially fatal condition characterized by metabolic acidosis and CNS, respiratory, circulatory, and renal dysfunction.

Vitamin B12 deficiency can suppress the symptoms of polycythemia vera. Treatment with methylcobalamin or hydroxocobalamin may unmask this condition.

Folic Acid, vitamin B9 is not a substitute for methylcobalamin, vitamin B12 deficiency, although it may improve vitamin B12 megaloblastic anemia. However, exclusive use of folic acid in treating vitamin B12 deficient megaloblastic anemia could result in progressive and irreversible neurologic damage. Before receiving folic acid or methylcobalamin, patients should be assessed for deficiency and appropriate therapy started concurrently. The intranasal formulations are not approved to treat acute B12 deficiency; all hematologic parameters should be normal before beginning the methylcobalamin intranasal formulations. Concurrent iron-deficiency anemia and folic acid deficiency may result in a blunted or impeded response to methylcobalamin therapy.

Certain conditions may blunt or impede therapeutic response to methylcobalamin therapy. These include serious infection, uremia or renal failure, drugs with bone marrow suppression properties (e.g., chloramphenicol), or concurrent undiagnosed folic acid or iron deficiency anemia. The mechanism appears to be interference with erythropoiesis. Patients with vitamin B12 deficiency and concurrent renal or hepatic disease may require increased doses or more frequent administration of methylcobalamin.

Clinical reports have not identified differences in responses between elderly and younger patients. Generally, dose selection for elderly patients should be done with caution. Elderly patients tend to have a greater frequency of decreased hepatic, renal, or cardiac function, and also have concomitant disease or receiving other drug therapy. Start with doses at the lower end of the dosing range.

Vitamin B12, or methylcobalamin, is essential to growth, cell reproduction, hematopoiesis, and nucleoprotein and myelin synthesis. Cells characterized by rapid division (epithelial cells, bone marrow, myeloid cells) appear to have the greatest requirement for methylcobalamin. Vitamin B12 can be converted to coenzyme B12 in tissues; in this form it is essential for conversion of methylmalonate to succinate and synthesis of methionine from homocysteine (a reaction which also requires folate). In the absence of coenzyme B12, tetrahydrofolate cannot be regenerated from its inactive storage form, 5-methyl tetrahydrofolate, resulting in functional folate deficiency. 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. Vitamin B12 deficiency results in megaloblastic anemia, GI lesions, and neurologic damage (which begins with an inability to produce myelin and is followed by gradual degeneration of the axon and nerve head). Vitamin B12 requires an intrinsic factor-mediated active transport for absorption, therefore, lack of or inhibition of intrinsic factor results in pernicious anemia.