Cyanocobalamin (Vitamin B12)

( Vitamin B 12 ) Pronunciation: (SYE-an-oh-koe-BAL-a-min)Class: Water-soluble vitamin

Trade Names:B-12 Dots- Tablets, sublingual 500 mcg

Trade Names:CaloMist- Spray, intranasal 25 mcg per 0.1 mL

Trade Names:Nascobal- Spray, intranasal 500 mcg per 0.1 mL

Trade Names:Rubesol-1000- Injection 1,000 mcg/mL

Trade Names:Twelve Resin-K- Tablets 1,000 mcg

Trade Names:Vitamin B 12- Tablets 50 mcg- Tablets 100 mcg- Tablets 500 mcg- Tablets 1,000 mcg- Tablets, sublingual 1,000 mcg- Tablets, sublingual 2,500 mcg- Tablets, sublingual 5,000 mcg- Lozenges 50 mcg- Lozenges 100 mcg- Lozenges 250 mcg- Lozenges 500 mcg

Trade Names:Vitamin B 12- Tablets, ER 1,500 mcg

Pharmacology

Involved in protein synthesis; Vitamin B 12 is essential to growth, cell reproduction, hematopoiesis, and nucleoprotein and myelin synthesis.

Pharmacokinetics

Absorption

IM

T max is 1 h.

Intranasal

T max is 1.25 h. C max is about 757.96 pg/mL.

Oral

Bound to intrinsic factor during transit through the stomach; separation occurs in the presence of calcium, and vitamin B 12 enters the mucosal cells for absorption.

Distribution

Distributed and stored primarily in the liver and bone marrow. In the blood, it is bound to trancobalam II.

Elimination

Unbound vitamin B 12 is rapidly eliminated in the urine.

IM

50% to 98% is excreted in the urine within 48 h.

Indications and Usage

Treatment of vitamin B 12 deficiency caused by inadequate utilization of vitamin B 12 ; dietary deficiency of vitamin B 12 occurring in strict vegetarians; malabsorption syndrome of various causes (eg, pernicious anemia, GI pathology, fish tapeworm infestation, malignancy of pancreas or bowel, gluten enteropathy, small bowel bacterial overgrowth, gastrectomy, concurrent folic acid deficiency); supplementation because of increased requirements (eg, associated with pregnancy, thyrotoxicosis, hemolytic anemia, hemorrhage, malignancy, hepatic and renal disease); vitamin B 12 absorption test (eg, Schilling test).

Intranasal

Maintenance of vitamin B 12 concentrations after normalization with IM vitamin B 12 therapy in patients with vitamin B 12 deficiency without nervous system involvement.

Nascobal

Malabsorption of vitamin B 12 resulting from structural or functional damage to the stomach, where intrinsic factor is secreted, or to the ileum, where intrinsic factor facilitates vitamin B 12 absorption (eg, AIDS, HIV infection, tropical sprue); inadequate secretion of intrinsic factor resulting from lesions that destroy the gastric mucosa (eg, ingestion of corrosives, extensive neoplasia) and conditions associated with variable degree of gastric atrophy (eg, multiple sclerosis, HIV infection, iron deficiency, total gastrectomy); competition for vitamin B 12 by intestinal parasites or bacteria (eg, fish tapeworm); inadequate utilization of vitamin B 12 (eg, antimetabolites for vitamin B 12 are employed in the treatment of neoplasia).

Contraindications

Hypersensitivity to cobalt, vitamin B 12 , or any component of these medications.

Dosage and Administration

Maintenance After NormalizationAdults Intranasal CaloMist

1 spray in each nostril once daily (25 mcg per nostril; total daily dose, 50 mcg). Increase the dose to 1 spray in each nostril twice daily (total daily dose, 100 mcg) for patients who have an inadequate response to once-daily dosing.

NascobalAdults

Intranasal 1 spray (500 mcg) in 1 nostril once weekly. Administer at least 1 h before or 1 h after ingestion of a hot food or liquid.

Children

Intranasal Dose should be in the amount recommended by the Food and Nutrition Board, National Academy of Science-National Research Council.

Recommended Dietary AllowanceAdults and Children 14 yr of age and older

PO 2.4 mcg/day.

Children 9 to 13 yr of age

PO or SL 1.8 mcg/day.

Children 4 to 8 yr of age

PO or SL 1.2 mcg/day.

Children 1 to 3 yr of age

PO or SL 0.9 mcg/day.

Pregnancy (14 to 50 yr of age)

PO or SL 2.6 mcg/day.

Lactation (14 to 50 yr of age)

PO or SL 2.8 mcg/day.

Adequate Intake for Children 7 to 12 mo

0.5 mcg/day.

Adequate Intake for Children 0 to 6 mo

0.4 mcg/day.

Dietary SupplementAdults

PO or SL 50 to 5,000 mcg/day.

Vitamin B 12 DeficiencyAdults

PO or SL 25 to 1,000 mcg/day.

IM or deep subcutaneous 30 mcg/day for 5 to 10 days followed by 100 to 200 mcg/mo.

Addisonian Pernicious AnemiaAdults

IM or deep subcutaneous 100 mcg/day for 6 to 7 days. If reticulocyte response occurs, give 100 mcg every other day for 7 doses, then give 100 mcg every 3 to 4 days for 2 to 3 wk. After this regimen, give 100 mcg/mo for life.

Children

IM or deep subcutaneous 0.5 to 3 mcg/day.

Shilling Test Flushing DoseAdults

IM 1,000 mcg (z-tract method preferred).

General Advice

  • Injection
  • Avoid using the IV route.
  • Sublingual
  • Place under tongue for 30 sec before swallowing.
  • CaloMist : Prime pump before the first use with 7 priming sprays. If 5 or more days elapse since last use, prime pump with 2 re-priming sprays.
  • Nascobal : Pump must be primed before each use. An intradermal test dose of parenteral vitamin B 12 is recommended before administration.

Storage/Stability

Store upright at 59° to 86°F. Protect from light and freezing.

Drug Interactions

Chloramphenicol

Decreases hematologic effects of vitamin B 12 in patients with pernicious anemia.

Colchicine, excessive alcohol intake (more than 2 wk), para-aminosalicylic acid

Decreases GI absorption of vitamin B 12 .

Food

Hot foods may cause nasal secretions, resulting in loss of medication; therefore, administer intranasal dose form at least 1 h before or after ingestion of hot foods or liquids.

Laboratory Test Interactions

Methotrexate, pyrimethamine, and most antibiotics

May invalidate vitamin B 12 diagnostic microbiological blood assays.

May mask the true diagnosis of megaloblastic anemia or folate deficiency.

Adverse Reactions

Cardiovascular

Parenteral

Peripheral vascular disorder (1%); CHF; peripheral vascular thrombosis; pulmonary edema.

CNS

Intranasal

Dizziness, headache (12%); asthenia, hypersomnia, malaise, pyrexia, sinus headache (4%); paresthesia (1%).

Parenteral

Headache (11%); asthenia (4%); dizziness, nervousness (3%); incoordination (2%); abnormal gait, anxiety, hypoesthesia, paresthesia (1%).

Dermatologic

Intranasal

Rash (8%).

Parenteral

Itching, transitory exanthema.

EENT

Intranasal

Nasopharyngitis, rhinorrhea (12%); nasal discomfort (8%); epistaxis, pharyngolaryngeal pain, postnasal drip (4%); rhinitis (1%).

Parenteral

Rhinitis (2%).

GI

Intranasal

Tooth abscess (4%) glossitis, nausea (1%).

Parenteral

Dyspepsia (2%); nausea, nausea and vomiting, vomiting (1%); mild transient diarrhea.

Hematologic-Lymphatic

Parenteral

Polycythemia vera.

Musculoskeletal

Intranasal

Arthralgia (12%); back pain (4%).

Parenteral

Arthritis (2%); back pain, myalgia (1%).

Respiratory

Intranasal

Bronchitis (8%); asthma, cough, sinusitis (4%).

Parenteral

Dyspnea (1%).

Miscellaneous

Intranasal

Pain (8%); infection, influenza-like illness, procedural pain, scab (4%).

Parenteral

Generalized pain, infection (3%); anaphylactic shock, death, feeling of swelling of entire body.

Postmarketing

Angioedema, angioedema-like reactions.

Precautions

Monitor

Obtain all hematologic parameters, including hemacrit, reticulocyte count, and vitamin B 12 , folate, and iron levels, at the beginning of vitamin B 12 treatment. Monitor serum potassium levels during therapy.

Periodically monitor serum B 12 levels to establish adequacy of therapy. Monitor vitamin B 12 concentrations and CBC 1 month after starting treatment and at 3- to 6-month intervals thereafter. Patients with declining or abnormally low vitamin B 12 concentrations despite maximal doses of intranasal treatment should be switched to IM vitamin B 12 .

Pregnancy

Category A ( Category C in doses that exceed the RDA, Nascobal , CaloMist , injection).

Lactation

Excreted.

Children

CaloMist

Safety and efficacy not established.

Elderly

Use with caution, usually starting at the low end of the dosage range, because of the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant diseases or other drug therapy.

Hypersensitivity

Anaphylactic shock and death have been associated with parenteral use.

Renal Function

Patients with vitamin B 12 deficiency may require an increased dose or more frequent therapy.

Hepatic Function

Patients with vitamin B 12 deficiency may require an increased dose or more frequent therapy.

Special Risk Patients

Patients with early Leber disease (hereditary optic nerve atrophy) suffered severe and rapid optic atrophy when treated with cyanocobalamin. Do not use cyanocobalamin in these patients. Infection, uremia, concurrent iron or folic acid deficiency, and drugs with bone marrow–suppressant properties may blunt the therapeutic response to cyanocobalamin.

Aluminum

Parenteral form contains aluminum that may be toxic, especially in patients with renal function impairment.

Benzyl alcohol

Injection may contain benzyl alcohol, which has been associated with fatal “gasping syndrome” in premature infants.

Hypokalemia and thrombocytosis

Could occur upon conversion of severe megaloblastic to normal erythropoiesis with vitamin B 12 .

Nasal conditions

Cyanocobalamin nasal administration has not been evaluated in patients with nasal congestion, allergic rhinitis, upper respiratory tract infections, or other nasal pathologies.

Overdosage

Symptoms

Overdosage has not been reported.

Patient Information

  • Instruct patient with pernicious anemia of need to continue therapy throughout lifetime.
  • Advise patient to administer intranasal gel at least 1 h before or 1 h after ingestion of hot foods or liquids.
  • Advise patient with nasal congestion, allergic rhinitis, or upper respiratory tract infection to defer treatment with intranasal gel until symptoms have subsided.
  • Teach patient of need to maintain well-balanced diet. Remind patient of the following good sources of vitamin B 12 : seafood, egg yolks, organ meats, fortified breakfast cereals, meat, cheeses, milk, other dairy products.
  • Advise patient that folic acid is not a substitute for vitamin B 12 , but may be taken concurrently.
  • Instruct vegetarians who do not use animal products of need for daily oral vitamin B 12 .
  • Instruct patients using intranasal form on the method for priming the pump.
  • Inform patient with pernicious anemia of need to have periodic GI evaluations.
  • Instruct patient to report the following symptoms to health care provider: irregular heartbeat, muscle weakness, shortness of breath, vision disturbances.

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