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Pronunciation
(sye an oh koe BAL a min)
U.S. Brand Names
Index Terms
Generic Available
Yes: Excludes nasal spray
Pharmacologic Category
Use: Labeled Indications
Treatment of pernicious anemia; vitamin B12 deficiency due to dietary deficiencies or malabsorption diseases, inadequate secretion of intrinsic factor, and inadequate utilization of B12 (eg, during neoplastic treatment); increased B12 requirements due to pregnancy, thyrotoxicosis, hemorrhage, malignancy, liver or kidney disease
CaloMist™: Maintenance of vitamin B12 concentrations after initial correction in patients with B12 deficiency without CNS involvement
Pregnancy Risk Factor
A/C (dose exceeding RDA recommendation); C (intranasal)
Lactation
Enters breast milk/compatible
Breast-Feeding Considerations
Vegetarian diets which contain no animal products do not supply any vitamin B12. Deficiency recognized in infants of vegetarian mothers who were breast-fed; consider supplementation during breast-feeding.
Contraindications
Hypersensitivity to cyanocobalamin, cobalt, or any component of the formulation
Warnings/Precautions
Concerns related to adverse effects:
• CNS effects: Vitamin B12 deficiency for >3 months results in irreversible degenerative CNS lesions; neurologic manifestations will not be prevented with folic acid unless vitamin B12 is also given. Spinal cord degeneration might also occur when folic acid used as a substitute for vitamin B12 in anemia prevention.
• Hypokalemia: Treatment of severe vitamin B12 megaloblastic anemia may result in severe hypokalemia, sometimes fatal, due to intracellular potassium shift upon anemia resolution.
• Thrombocytosis: Treatment of severe vitamin B12 megaloblastic anemia may result in thrombocytosis.
Disease-related concerns:
• Leber's disease: Use with caution in patients with Leber's disease patients; B12 treatment may result in rapid optic atrophy.
• Pernicious anemia: Appropriate use: I.M./SubQ routes are used to treat pernicious anemia; oral and intranasal administration are not indicated until hematologic remission and no signs of nervous system involvement.
• Polycythemia vera: Vitamin B12 deficiency masks signs of polycythemia vera; vitamin B12 administration may unmask this condition.
Dosage form specific issues:
• Aluminum: Some parenteral products contain aluminum; use caution in patients with impaired renal function and neonates.
• Benzyl alcohol: Some products contain benzyl alcohol which has been associated with "gasping syndrome" in neonates.
• Intranasal administration: Efficacy in patients with nasal pathology or with other concomitant intranasal therapy has not been determined. Use with caution.
Special populations:
• Pediatrics: CaloMist™: Safety and efficacy have not been established in children.
Other warnings/precautions:
• I.V. administration: Avoid intravenous route; anaphylactic shock has occurred.
• Test dose: Intradermal test dose of vitamin B12 is recommended for any patient suspected of cyanocobalamin sensitivity prior to intranasal or injectable administration.
Adverse Reactions
Frequency not defined.
Cardiovascular: CHF, peripheral vascular disorder, peripheral vascular thrombosis
Central nervous system: Anxiety, dizziness, headache, hypoesthesia, incoordination, pain, nervousness
Dermatologic: Itching, urticaria, exanthema (transient)
Gastrointestinal: Diarrhea, dyspepsia, glossitis, nausea, sore throat, vomiting
Hematologic: Polycythemia vera
Neuromuscular & skeletal: Abnormal gait, arthritis, back pain, myalgia, paresthesia, weakness
Respiratory: Dyspnea, pulmonary edema, rhinitis
Miscellaneous: Anaphylaxis (parenteral) and infection
Drug Interactions
Chloramphenicol: May diminish the therapeutic effect of Cyanocobalamin. The expected hematologic response for the treatment of anemia may be opposed. Risk D: Consider therapy modification
Ethanol/Nutrition/Herb Interactions
Ethanol: Heavy consumption >2 weeks may impair vitamin B12 absorption.
Storage
Injection: Clear pink to red solutions are stable at room temperature. Protect from light.
Intranasal spray: Store at 15°C to 30°C (59°F to 86°F); do not freeze. Protect from light.
Compatibility
Stable in dextran 6% in dextrose, dextran 6% in NS, D5LR, D51/4NS, D51/2NS, D5NS, D5W, D10W, D10NS, LR, 1/2NS, NS; variable stability (consult detailed reference) in TPN.
Y-site administration: Compatible: Heparin, hydrocortisone sodium succinate, potassium chloride, vitamin B complex with C.
Compatibility when admixed: Compatible: Ascorbic acid injection, chloramphenicol, metaraminol, vitamin B complex with C. Incompatible Chlorpromazine, phytonadione, prochlorperazine edisylate, warfarin.
Mechanism of Action
Coenzyme for various metabolic functions, including fat and carbohydrate metabolism and protein synthesis, used in cell replication and hematopoiesis
Pharmacodynamics/Kinetics
Absorption: Oral: Variable from the terminal ileum; requires the presence of calcium and gastric “intrinsic factor” to transfer the compound across the intestinal mucosa
Distribution: Principally stored in the liver and bone marrow, also stored in the kidneys and adrenals
Protein binding: Transcobalamins
Metabolism: Converted in tissues to active coenzymes, methylcobalamin and deoxyadenosylcobalamin; undergoes some enterohepatic recycling
Bioavailability: Intranasal solution: Nascobal®: 6.1% (relative to I.M.)
Dosage
Adequate intake:
Children:
0-6 months: 0.4 mcg/day
7-12 months: 0.5 mcg/day
Recommended intake:
Children:
1-3 years: 0.9 mcg/day
4-8 years: 1.2 mcg/day
9-13 years: 1.8 mcg/day
Children >14 years and Adults: 2.4 mcg/day
Pregnancy: 2.6 mcg/day
Lactation: 2.8 mcg/day
Vitamin B12 deficiency:
I.M., deep SubQ:
Children (dosage not well established): 0.2 mcg/kg for 2 days, followed by 1000 mcg/day for 2-7 days, followed by 100 mcg/week for one month; for malabsorptive causes of B12 deficiency, monthly maintenance doses of 100 mcg have been recommended or as an alternative 100 mcg/day for 10-15 days, then once or twice weekly for several months
Adults: Initial: 30 mcg/day for 5-10 days; maintenance: 100-200 mcg/month
Intranasal: Adults:
Nascobal®: 500 mcg in one nostril once weekly
CaloMist™: Maintenance therapy (following correction of vitamin B12 deficiency): 25 mcg in each nostril daily (50 mcg/day). If inadequate response, 25 mcg in each nostril twice daily (100 mcg/day).
Oral: Adults: 250 mcg/day
Pernicious anemia: I.M., deep SubQ (administer concomitantly with folic acid if needed, 1 mg/day for 1 month):
Children: 30-50 mcg/day for 2 or more weeks (to a total dose of 1000-5000 mcg), then follow with 100 mcg/month as maintenance dosage
Adults: 100 mcg/day for 6-7 days; if improvement, administer same dose on alternate days for 7 doses, then every 3-4 days for 2-3 weeks; once hematologic values have returned to normal, maintenance dosage: 100 mcg/month. Note: Alternative dosing of 1000 mcg/day for 5 days (followed by 500-1000 mcg/month) has been used.
Hematologic remission (without evidence of nervous system involvement): Adults:
Intranasal (Nascobal®): 500 mcg in one nostril once weekly
Oral: 1000-2000 mcg/day
I.M., SubQ: 100-1000 mcg/month
Schilling test: Adults: I.M.: 1000 mcg
Administration: Oral
Not recommended due to variable absorption; however, oral therapy of 1000-2000 mcg/day has been effective for anemia if I.M./SubQ routes refused or not tolerated.
Administration: I.M.
I.M. or deep SubQ are preferred routes of administration.
Administration: I.V.
Not recommended
Administration: Other
Intranasal: Nasal spray:
Nascobal®: Prior to initial dose, activate (prime) spray nozzle by pumping unit quickly and firmly until first appearance of spray, then prime twice more. The unit must be reprimed once immediately before each subsequent use. Administer 1 hour before or after ingestion of hot foods/liquids.
CaloMist™: Prime unit by spraying 7 times. If ?5 days since use, reprime with 2 sprays. Separate from other intranasal medications by several hours.
Administration: I.V. Detail
pH: 4.5-7.0
Monitoring Parameters
Vitamin B12, hematocrit, reticulocyte count, folate and iron levels should be obtained prior to treatment; vitamin B12 and peripheral blood counts should be monitored 1 month after beginning treatment, then every 3-6 months thereafter.
Megaloblastic anemia: In addition to normal hematological parameters, serum potassium and platelet counts should be monitored during therapy
CaloMist™: If vitamin B12 levels declining despite maximum doses then should return to I.M. dosing
Reference Range
Normal range of serum B12 is 150-750 pg/mL; this represents 0.1% of total body content. Metabolic requirements are 2-5 mcg/day; years of deficiency required before hematologic and neurologic signs and symptoms are seen. Occasional patients with significant neuropsychiatric abnormalities may have no hematologic abnormalities and normal serum cobalamin levels, 200 pg/mL (SI: >150 pmol/L), or more commonly between 100-200 pg/mL (SI: 75-150 pmol/L).
Test Interactions
Methotrexate, pyrimethamine, and most antibiotics invalidate folic acid and vitamin B12 diagnostic blood assays
Dietary Considerations
Strict vegetarian diets (eg, without eggs or dairy products) may result in vitamin B12 deficiency.
Patient Education
Use exactly as directed. Pernicious anemia may require treatment for life. Report skin rash; swelling, pain, or redness of extremities; or acute persistent diarrhea. Pregnancy precaution: Inform prescriber if you are pregnant.
Geriatric Considerations
There exists evidence that people, particularly elderly whose serum cobalamin concentrations are <500 pg/mL, should receive replacement parenteral therapy or oral replacement (1000 mcg daily). This recommendation is based upon neuropsychiatric disorders and cardiovascular disorders associated with lower sodium cobalamin concentrations.
Cardiovascular Considerations
Epidemiological evidence suggests that total plasma homocysteine level may be an independent cardiovascular risk factor. Plasma homocysteine levels are strongly influenced by genetics and diet (folic acid, pyridoxine/vitamin B6, and cyanocobalamine/vitamin B12). These vitamins help to break down homocysteine in the body.
Schnyder, et al, studied the effects of homocysteine-lowering therapy (folic acid 1 mg/day, vitamin B6 10 mg/day, vitamin B12 0.4 mg/day) in patients with coronary artery disease after successful angioplasty in the Swiss Heart Study. This randomized, double-blind, placebo-controlled trial looked at a composite endpoint (death, nonfatal MI, repeat revascularization) 6 months and 1 year after angioplasty. Homocysteine-lowering therapy significantly decreased the incidence of major adverse events, primarily due to a reduced rate of target lesion revascularization. Investigators in the Folate After Coronary Intervention Trial randomized patients who underwent successful coronary stenting procedures to placebo or folic acid (1.2 mg/day), vitamin B6 (4.8 mg/day), and vitamin B12 (0.06 mg/day). Vitamin supplementation was associated with increased restenosis in these PCI patients.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
None reported
Mental Health: Effects on Psychiatric Treatment
Anticonvulsants may decrease the absorption of cyanocobalamin
Nursing: Physical Assessment/Monitoring
Assess effectiveness and interactions of other medications patient may be taking. Assess results of laboratory tests at beginning of therapy and periodically with long-term therapy. Teach patient proper administration, appropriate nutritional counseling, and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution: 1000 mcg/mL (1 mL, 10 mL, 30 mL) [may contain benzyl alcohol]
Lozenge: 50 mcg, 100 mcg, 250 mcg, 500 mcg
Lozenge, sublingual: 500 mcg
Solution, intranasal [spray]:
CaloMist™: 25 mcg/0.1 mL actuation (10.7 mL) [contains benzyl alcohol, benzalkonium chloride; 60 metered sprays]
Nascobal®: 500 mcg/0.1 mL actuation (2.3 mL) [contains benzalkonium chloride; delivers 8 sprays]
Tablet: 50 mcg, 100 mcg, 250 mcg, 500 mcg, 1000 mcg
Twelve Resin-K: 1000 mcg [may be used as oral, sublingual, or buccal]
Tablet, timed release: 1000 mcg, 1500 mcg
Tablet, sublingual: 1000 mcg, 2500 mcg, 5000 mcg
Pricing: U.S. (www.drugstore.com)
Gel (Nascobal)
500 mcg/0.1 mL (2.3): $146.96
Solution (Cyanocobalamin)
1000 mcg/mL (10): $13.99
1000 mcg/mL (25): $35.99
1000 mcg/mL (30): $19.99
Solution (Nascobal)
500 mcg/0.1 mL (2.3): $213.58
Tablets (Vitamin B-12)
500 mcg (100): $12.99
1000 mcg (100): $12.99
References
Andres E, Noel E, and Goichot B, “Metformin-Associated Vitamin B12 Deficiency,” Arch Intern Med, 2002, 162(19):2251-2.
“Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline,” (Chapter 9) available at http://books.nap.edu/openbook/0309065542/html/306.html. Last accessed February 22, 2005.
Goodman M, Chen XH, Daarwish D, “Are U.S. Lower Normal B12 Limits Too Low?,” J Am Geriatr Soc, 1996, 44(10):1274-5.
Lane LA and Rojas-Fernandez C, “Treatment of Vitamin B12-Deficiency Anemia: Oral Versus Parenteral Therapy,” Ann Pharmacother, 2002, 36(7-8):1268-72.
Lindenbaum J, Healton EB, Savage DG, et al, “Neuropsychiatric Disorders Caused by Cobalamin Deficiency in the Absence of Anemia or Macrocytosis,” N Engl J Med, 1988, 318(26):1720-8.
Nelson Textbook of Pediatrics, 17th ed, Behrman RE, Kliegman RM, and Jenson HB, eds, Philadelphia, PA: WB Saunders Co, 2004.
Oh R and Brown DL, “Vitamin B12 Deficiency,” Am Fam Physician, 2003, 67(5):979-86.
Olszewski AJ, Szostak WB, Bialkowska M, et al, “Reduction of Plasma Lipid and Homocysteine Levels by Pyridoxine, Folate, Cobalamin, Choline, Riboflavin, and Troxerutin in Atherosclerosis,” Atherosclerosis, 1989, 75(1):1-6.
Rasmussen SA, Fernhoff PM, and Scanlon KS, “Vitamin B12 Deficiency in Children and Adolescents,” J Pediatr, 2001, 138(1):10-17.
Regland B, Gottfries CG, and Lindstedt G, “Dementia Patients With Low Serum Cobalamin Concentration: Relationship to Atrophic Gastritis,” Aging (Milano), 1992, 4(1):35-41.
Schjonsby H, “Vitamin B12 Absorption and Malabsorption,” Gut, 1989, 30(12):1986-91.
Schnyder G, Roffi M, Flammer Y, et al, “Effect of Homocysteine-Lowering Therapy With Folic Acid, Vitamin B12, and Vitamin B6 on Clinical Outcome After Percutaneous Coronary Intervention: The Swiss Heart Study: A Randomized Controlled Trial,” JAMA, 2002, 288(8):973-9.
Silbergleit R and Lee DC, “Bowel Obstruction and Radiopaque Vitamin B12 “Pseudobezoar”,” Am J Emerg Med, 1995, 13(1):112-3.
International Brand Names
Lexi-Comp.com
Last full review/revision April 2009
Content last modified April 2009
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