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Cyanocobalamin

Pronunciation

Pronunciation

(sye an oh koe BAL a min)

Index Terms

  • CaloMist
  • Vitamin B12

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Kit, Injection:

B-12 Compliance Injection: 1000 mcg/mL [contains benzyl alcohol]

Physicians EZ Use B-12: 1000 mcg/mL [contains benzyl alcohol]

Vitamin Deficiency System-B12: 1000 mcg/mL [contains benzyl alcohol]

Generic: 1000 mcg/mL [DSC]

Liquid, Sublingual:

Generic: 3000 mcg/mL (52 mL)

Lozenge, Oral:

Generic: 50 mcg (100 ea); 100 mcg (100 ea); 250 mcg (100 ea, 250 ea); 500 mcg (100 ea, 250 ea)

Solution, Injection:

Generic: 1000 mcg/mL (1 mL, 10 mL, 30 mL)

Solution, Nasal:

Nascobal: 500 mcg/0.1 mL (1 ea, 1.3 mL [DSC]) [contains benzalkonium chloride]

Tablet, Oral:

Generic: 100 mcg, 250 mcg, 500 mcg, 1000 mcg

Tablet, Oral [preservative free]:

Generic: 100 mcg, 500 mcg, 1000 mcg

Tablet Extended Release, Oral:

Generic: 1000 mcg

Tablet Sublingual, Sublingual:

Generic: 2500 mcg

Tablet Sublingual, Sublingual [preservative free]:

Generic: 2500 mcg

Brand Names: U.S.

  • B-12 Compliance Injection
  • Nascobal
  • Physicians EZ Use B-12
  • Vitamin Deficiency System-B12

Pharmacologic Category

  • Vitamin, Water Soluble

Pharmacology

Coenzyme for various metabolic functions, including fat and carbohydrate metabolism and protein synthesis, used in cell replication and hematopoiesis

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

Metabolism

Converted in tissues to active coenzymes, methylcobalamin and deoxyadenosylcobalamin; undergoes some enterohepatic recycling

Excretion

Urine (50% to 98%, unchanged drug)

Onset of Action

Megaloblastic anemia: IM:

Conversion of megaloblastic to normoblastic erythroid hyperplasia within bone marrow: 8 hours

Increased reticulocytes: 2 to 5 days

Complicated vitamin B12 deficiency: IM, SubQ: Resolution of:

Psychiatric sequelae: 24 hours

Thrombocytopenia: 10 days

Granulocytopenia: 2 weeks

Time to Peak

Serum: IM, SubQ: 30 minutes to 2 hours; Intranasal: 1.6 hours

Protein Binding

Transcobalamins

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

Contraindications

Hypersensitivity to cyanocobalamin, cobalt, or any component of the formulation

Dosing: Adult

Recommended intake (IOM, 1998): 2.4 mcg daily

Pregnancy: 2.6 mcg daily

Lactation: 2.8 mcg daily

Vitamin B12 deficiency:

Intranasal (Nascobal): 500 mcg in one nostril once weekly

Oral: 1000-2000 mcg daily for 1-2 weeks; maintenance: 1000 mcg daily (Langan, 2011; Oh, 2003)

IM, deep SubQ: May use initial treatment similar to that for pernicious anemia depending on severity of deficiency: 100 mcg daily 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 monthly.

Note: Given the lack of toxicity associated with cyanocobalamin, higher doses may be preferred, especially in cases of severe deficiency. Alternate dosing regimens exist with initial doses ranging from 100-1000 mcg every day or every other day for 1-2 weeks and maintenance doses of 100-1000 mcg every 1-3 months (Oh, 2003).

Pernicious anemia: IM, deep SubQ (administer concomitantly with folic acid if needed, 1 mg daily for 1 month): 100 mcg daily 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 monthly.

Note: Given the lack of toxicity associated with cyanocobalamin, higher doses may be preferred, especially in cases of severe deficiency. Alternate dosing regimens exist with initial doses ranging from 100-1000 mcg every day or every other day for 1-2 weeks and maintenance doses of 100-1000 mcg every 1-3 months (Oh, 2003).

Hematologic remission (without evidence of nervous system involvement):

Intranasal (Nascobal): 500 mcg in one nostril once weekly

Oral: 1000-2000 mcg daily

IM, SubQ: 100-1000 mcg monthly

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Adequate intake (IOM, 1998):

Children:

0-6 months: 0.4 mcg daily

7-12 months: 0.5 mcg daily

Recommended intake (IOM, 1998):

Children:

1-3 years: 0.9 mcg daily

4-8 years: 1.2 mcg daily

9-13 years: 1.8 mcg daily

Adolescents >14 years: Refer to adult dosing.

Vitamin B12 deficiency: IM, deep SubQ: Dosage in children is not well established: 0.2 mcg/kg for 2 days, followed by 1000 mcg daily for 2-7 days, followed by 100 mcg weekly for 1 month; for malabsorptive causes of B12 deficiency, monthly maintenance doses of 100 mcg have been recommended or as an alternative 100 mcg daily for 10-15 days, then once or twice weekly for several months (Rasmussen, 2001).

Pernicious anemia: IM, deep SubQ (administer concomitantly with folic acid if needed, 1 mg daily for 1 month): 30-50 mcg daily for 2 or more weeks (to a total dose of 1000-5000 mcg), then follow with 100 mcg monthly as maintenance dosage

Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturer’s labeling. Use with caution; some formulations may also contain aluminum, which may accumulate in renal impairment.

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer’s labeling.

Administration

IM/SubQ: IM or deep SubQ are preferred routes of administration

Intranasal: Nasal spray (Nascobal): Administer 1 hour before or 1 hour after ingestion of hot foods/liquids.

Multi-dose bottle: 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. One bottle delivers 4 doses.

Unit dose spray device: Each device delivers 1 dose.

IV: Not recommended due to rapid elimination

Oral: Not recommended due to variable absorption; however, oral therapy of 1000-2000 mcg daily has been effective for anemia if IM/SubQ routes refused or not tolerated.

Dietary Considerations

Strict vegetarian diets (eg, without eggs or dairy products) may result in vitamin B12 deficiency.

Compatibility

Stable in dextran 6% in dextrose, dextran 6% in NS, D5LR, D51/4NS, D51/2NS, D5NS, D5W, D10W, D10NS, LR, 1/2NS, NS.

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.

Drug Interactions

Chloramphenicol: May diminish the therapeutic effect of Vitamin B12. Monitor therapy

Colchicine: May decrease the serum concentration of Cyanocobalamin. Monitor therapy

Test Interactions

Methotrexate, pyrimethamine, and most antibiotics invalidate folic acid and vitamin B12 diagnostic blood assays

Adverse Reactions

Frequency not defined.

Cardiovascular: Congestive heart failure, peripheral vascular disease, thrombosis (peripheral)

Central nervous system: Abnormal gait, anxiety, ataxia, dizziness, headache, hypoesthesia, nervousness, pain, paresthesia

Dermatologic: Pruritus, skin rash (transient), urticaria

Gastrointestinal: Diarrhea, dyspepsia, glossitis, nausea, sore throat, vomiting

Hematologic & Oncologic: Polycythemia vera

Hypersensitivity: Anaphylaxis (parenteral)

Infection: Infection

Neuromuscular & skeletal: Arthritis, back pain, myalgia, weakness

Respiratory: Dyspnea, pulmonary edema, rhinitis

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: IM/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: The parenteral product may contain aluminum; toxic aluminum concentrations may be seen with high doses, prolonged use, or renal dysfunction. Premature neonates are at higher risk due to immature renal function and aluminum intake from other parenteral sources. Parenteral aluminum exposure of >4 to 5 mcg/kg/day is associated with CNS and bone toxicity; tissue loading may occur at lower doses (Federal Register, 2002). See manufacturer’s labeling.

• Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension and cardiovascular collapse (AAP ["Inactive" 1997]; CDC, 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors, 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer’s labeling.

• Intranasal administration: Efficacy in patients with nasal pathology or with other concomitant intranasal therapy has not been determined. Use with caution.

Other warnings/precautions:

• IV 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.

Monitoring Parameters

Vitamin B12, hemoglobin, hematocrit, erythrocyte and 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

Pregnancy Considerations

Animal reproduction studies have not been conducted. Water soluble vitamins cross the placenta. Absorption of vitamin B12 may increase during pregnancy. Vitamin B12 requirements may be increased in pregnant women compared to nonpregnant women. Serum concentrations of vitamin B12 are higher in the neonate at birth than the mother (IOM, 1998).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience dizziness, headache, anxiety, vomiting, or nausea. Have patient report immediately to prescriber signs of DVT (edema, warmth, numbness, change in color, or pain in the extremities), severe diarrhea, severe loss of strength and energy, angina, abnormal heartbeat, muscle pain, muscle weakness, shortness of breath, swelling of arms or legs, bruising, or bleeding (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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