cyanocobalamin (vitamin B₁₂)
Bedoz ◆ , Cobex, Crystamine, Cyanoject, Cyomin, Rubesol-1000, Rubramin PC, Vibal

hydroxocobalamin (vitamin B₁₂)
Hydrobexan, Hydro-Cobex, LA-12

Available forms
Available by prescription only
Injection: 100 mcg/ml, 1,000 mcg/ml
Tablets: 25 mcg, 50 mcg, 100 mcg, 250 mcg, 500 mcg, 1,000 mcg

Indications and dosages
 RDA for vitamin B₁₂. Neonates and infants up to age 6 months: 0.4 mcg
Infants ages 6 months to 1 year: 0.5 mcg
Children ages 1 to 3: 0.9 mcg
Children ages 4 to 8: 1.2 mcg
Children ages 9 to 13: 1.8 mcg
Adults and children age 14 and older: 2.4 mcg
Pregnant women: 2.6 mcg
Breast-feeding women: 2.8 mcg
 Vitamin B₁₂ deficiency from any cause except malabsorption related to pernicious anemia or other GI disease. Adults: 30 mcg S.C. or I.M. daily for 5 to 10 days, depending on severity of deficiency. Maintenance dosage is 100 to 200 mcg I.M. once monthly. For subsequent prophylaxis, advise adequate nutrition and daily RDA vitamin B₁₂ supplements.
Children: 1 to 5 mg given in single doses of 100 mcg I.M. or S.C. over 2 or more weeks. Maintenance dosage is 60 mcg/month I.M. or S.C.
 Schilling test flushing dose. Adults and children: 1,000 mcg I.M. in a single dose.

Pharmacodynamics
Nutritional action: Vitamin B₁₂ can be converted to coenzyme B₁₂ in tissues and, as such, is essential for conversion of methylmalonate to succinate and synthesis of methionine from homocystine, a reaction that also requires folate. Without coenzyme B₁₂, folate deficiency occurs. Vitamin B₁₂ also facilitates fat and carbohydrate metabolism and protein synthesis. Cells characterized by rapid division (epithelial cells, bone marrow, and myeloid cells) appear to have the greatest requirement for vitamin B₁₂.
 Vitamin B₁₂ deficiency may cause megaloblastic anemia, GI lesions, and neurologic damage; it begins with an inability to produce myelin followed by gradual degeneration of the axon and nerve. Parenteral administration of vitamin B₁₂ completely reverses the megaloblastic anemia and GI symptoms of vitamin B₁₂ deficiency.

Pharmacokinetics
Absorption: After oral administration, vitamin B₁₂ is absorbed irregularly from the distal small intestine. Vitamin B₁₂ is protein-bound, and this bond must be split by proteolysis and gastric acid before absorption. Absorption depends on sufficient intrinsic factor and calcium. Vitamin B₁₂ is inadequate in malabsorptive states and in pernicious anemia. After oral administration of doses of less than 3 mcg, peak plasma levels aren’t reached for 8 to 12 hours. Distribution: Distributed into the liver, bone marrow, and other tissues, including the placenta. At birth, the vitamin B₁₂ level in neonates is three to five times that in the mother. Vitamin B₁₂ appears in breast milk in levels about equal to the maternal vitamin B₁₂ level. Unlike cyanocobalamin, hydroxocobalamin is absorbed more slowly parenterally and may be taken up by the liver in larger quantities; it also produces a greater increase in serum cobalamin levels and less urinary excretion.
Metabolism: Cyanocobalamin and hydroxocobalamin are metabolized in the liver.
Excretion: In healthy people receiving only dietary vitamin B₁₂, about 3 to 8 mcg of the vitamin is secreted into the GI tract daily, mainly from bile, and all but about 1 mcg is reabsorbed; less than 0.25 mcg is usually excreted in the urine daily. When vitamin B₁₂ is administered in amounts that exceed the binding capacity of plasma, the liver, and other tissues, it’s free in the blood for urinary excretion.

Contraindications and precautions
Contraindicated in patients hypersensitive to vitamin B₁₂ or cobalt and in patients with early Leber’s disease. Use cautiously in anemic patients with cardiac, pulmonary, or hypertensive disease and in those with severe vitamin B₁₂-dependent deficiencies.

Interactions
Drug-drug. Aminoglycosides, aminosalicylic acid and its salts, anticonvulsants, cobalt irradiation of the small bowel, colchicine, extended-release potassium preparations: Decreases vitamin B₁₂ absorption from GI tract. Don’t use together.
Ascorbic acid: May destroy vitamin B₁₂. Don’t administer within 1 hour of giving vitamin B₁₂.
Chloramphenicol: Antagonizes hematopoietic response. Don’t give together.
Colchicine: Increases neomycin-induced malabsorption of vitamin B₁₂. Don’t use together.
Drug-lifestyle. Alcohol use: Decreases vitamin B₁₂ absorption from GI tract. Discourage alcohol use.
Smoking: Increases vitamin B₁₂ requirement. Discourage smoking.

Adverse reactions
CV: peripheral vascular thrombosis, heart failure.
GI: transient diarrhea.
Respiratory: pulmonary edema.
Skin: itching, transitory exanthema, urticaria; pain and burning at S.C. or I.M. injection site.
Other: anaphylaxis with parenteral administration.

Effects on lab test results
None reported.

Overdose and treatment
Not applicable. Even in large doses, vitamin B₁₂ isn’t usually toxic.

Special considerations
• Determine patient’s diet and drug history, including patterns of alcohol use, to identify poor nutritional habits.
• Administer oral solution promptly after mixing with fruit juice. Ascorbic acid causes instability of vitamin B₁₂. Protect oral solution from light.
• Administer oral vitamin B₁₂ with meals to increase absorption.
• Don’t mix the parenteral form with dextrose solutions, alkaline or strongly acidic solutions, or oxidizing and reducing agents, because anaphylaxis may occur with I.V. use.
• Parenteral therapy is preferred for patients with pernicious anemia because oral administration may be unreliable. In patients with neurologic complications, prolonged inadequate oral therapy may lead to permanent spinal cord damage. Oral therapy is appropriate for mild conditions without neurologic signs and for patients who refuse or are sensitive to the parenteral form.
• Patients with a history of sensitivities and those suspected of being sensitive to vitamin B₁₂ should receive an intradermal test dose before therapy begins. Sensitization to vitamin B₁₂ may develop after as many as 8 years of treatment.
• Expect therapeutic response to occur within 48 hours; it’s measured by laboratory values and effect on fatigue, GI symptoms, anorexia, pallid or yellow complexion, glossitis, distaste for meat, dyspnea on exertion, palpitations, neurologic degeneration (paresthesia, loss of vibratory and position sense and deep reflexes, incoordination), psychotic behavior, anosmia, and visual disturbances.
• Therapeutic response to vitamin B₁₂ may be impaired by concurrent infection, uremia, folic acid or iron deficiency, or drugs having bone marrow suppressant effects. Large doses of vitamin B₁₂ may improve folate-deficient megaloblastic anemia.
• Patients with mild peripheral neurologic defects may respond to concomitant physical therapy. Usually, neurologic damage that doesn’t improve after 12 to 18 months of therapy is considered irreversible. Severe vitamin B₁₂ deficiency that persists for 3 months or longer may cause permanent spinal cord degeneration.
• Vitamin B₁₂ therapy may cause false-positive results for intrinsic factor antibodies, which are present in the blood of half of all patients with pernicious anemia.
• Methotrexate, pyrimethamine, and most anti-infectives invalidate diagnostic blood assays for vitamin B₁₂.
• Monitor vital signs in patients with cardiac disease and in those receiving parenteral vitamin B₁₂. Watch for symptoms of pulmonary edema, which tend to develop early in therapy.
• Expect reticulocyte level to rise in 3 to 4 days, peak in 5 to 8 days, and then gradually decline as erythrocyte count and hemoglobin rise to normal levels (in 4 to 6 weeks).
• Monitor potassium levels during the first 48 hours, especially in patients with pernicious anemia or megaloblastic anemia. Potassium supplements may be required. Conversion to normal erythropoiesis increases erythrocyte potassium requirement and can result in fatal hypokalemia in these patients.
Breast-feeding patients
• Vitamin B₁₂ appears in breast milk in levels that approximate the maternal vitamin B₁₂ level. The Food and Nutrition Board of the National Academy of Sciences-National Research Council recommends that breast-feeding women consume 2.8 mcg of vitamin B₁₂ daily.
Pediatric patients
• Safety and efficacy of vitamin B₁₂ for use in children haven’t been established. Intake for children should be 0.4 to 2.4 mcg daily, as recommended by the Food and Nutrition Board of the National Academy of Sciences, National Research Council.
• Some of these products contain benzyl alcohol, which has been linked to a fatal "gasping syndrome" in premature infants.

Patient education
• Emphasize importance of a well-balanced diet. To prevent progression of subacute combined degeneration, don’t use folic acid instead of vitamin B₁₂ to prevent anemia.
• Instruct patient to report infection or disease in case his condition requires increased dosage of vitamin B₁₂.
• Tell patient with pernicious anemia that he must have lifelong treatment with vitamin B₁₂ to prevent recurring symptoms and the risk of incapacitating and irreversible spinal cord damage.
• Instruct patient to store tablets in a tightly closed container at room temperature.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use