Cyanocobalamin

Pharmacologic Category

Vitamin, Water Soluble

Dosing: Adult

Aphthous ulcers, recurrent (off-label use):

Oral (sublingual): 1,000 mcg once every evening for 6 months (Volkov 2009)

IM: 1,000 mcg once daily for 7 days, followed by weekly for 1 month, followed by monthly for 6 months (Gulcan 2008)

Vitamin B12 deficiency: Note: Folic acid supplementation may also be required.

Intranasal (Nascobal): 500 mcg in 1 nostril once weekly; may increase dose if vitamin B12 levels decline after 1 month of treatment. Alternate route (eg, IM, SubQ) should be considered if B12 levels are persistently low.

Oral: 1,000 to 2,000 mcg daily for 1 to 2 weeks; maintenance: 1,000 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 to 7 days; if improvement, administer same dose on alternate days for 7 doses, then every 3 to 4 days for 2 to 3 weeks; once hematologic values have returned to normal, maintenance dosage: 100 mcg monthly.

Note: Higher doses may be preferred, especially in cases of severe deficiency; consider alternate dosing regimens with initial doses ranging from 100 to 1,000 mcg every day or every other day for 1 to 2 weeks and maintenance doses of 100 to 1,000 mcg every 1 to 3 months (Oh 2003) or 1,000 mcg once a week for 8 weeks followed by 1,000 mcg once a month (Langan 2011).

Mild B12 deficiency (eg, malabsorption, atrophic gastritis, metformin use, chronic acid reducing medication use):

Oral: 500 to 1,000 mcg orally once daily (Stabler 2013)

IM: 1,000 mcg once daily or every other day for 1 week, then 1,000 mcg weekly for 4 to 8 weeks, and then 1,000 mcg monthly for life (Stabler 2013)

Pernicious anemia:

IM: 1,000 mcg once daily or every other day for 1 week, then 1,000 mcg weekly for 4 to 8 weeks, then 1,000 mcg once monthly for life (Stabler 2013) or 100 to 1,000 mcg every day or every other day for 1 to 2 weeks followed by 100 to 1,000 mcg every 1 to 3 months (Oh 2003) or 1,000 mcg once a week for 8 weeks followed by 1,000 mcg once a month for life (Langan 2011)

Oral: 1,000 to 2,000 mcg once daily for life (Stabler 2013)

IM, deep SubQ: Initial: 100 mcg once daily for 6 to 7 days; if improvement, administer same dose on alternate days for 7 doses, then every 3 to 4 days for 2 to 3 weeks; maintenance (once hematologic values have returned to normal): 100 mcg once monthly for life

Severe B12 deficiency (due to gastrectomy, ileal resection, inflammatory bowel disease, sprue):

IM: 1,000 mcg once daily or every other day for 1 week, then 1,000 mcg weekly for 4 to 8 weeks, then 1,000 mcg once monthly for life (Stabler 2013)

Oral: 1,000 to 2,000 mcg once daily for life (Stabler 2013).

Vitamin B12 repletion in gastric bypass surgery patients: IM or SubQ: 1,000 mcg once daily until normal B12 levels are achieved and then resume supplementations dosage (ASBMS [Parrott 2017]) or 1,000 mcg IM once daily or every other day for 1 week, then 1,000 mcg IM weekly for 4 to 8 weeks, followed by supplementation dosing (Stabler 2013).

Vitamin B12 supplementation in gastric bypass surgery patients:

IM or SubQ: 1,000 mcg once monthly (ASMBS [Parrott 2017]) or 1,000 mcg once monthly to 1,000 to 3,000 mcg once every 6 to 12 months (if oral or intranasal therapy are ineffective) (AACE/TOS/ACE [Mechanick 2013]) or 1,000 mcg IM once monthly for life (Stabler 2013).

Oral: 350 to 500 mcg (disintegrating tablet, sublingual, or liquid) once daily (ASMBS [Parrott 2017]) or ≥1,000 mcg once daily (AACE/TOS/ACE [Mechanick 2013]) or 1,000 to 2,000 mcg orally once daily for life (Stabler 2013)

Intranasal: 500 mcg in one nostril once weekly (ASMBS [Parrott 2017]; AACE/TOS/ACE [Mechanick 2013]).

Vitamin B12 supplementation to reduce toxicity associated with pemetrexed: IM: 1,000 mcg every 9 weeks, beginning 1 to 3 weeks prior to pemetrexed treatment initiation; continue for 3 weeks after last pemetrexed dose; administer with oral folic acid supplementation (Scagliotti 2008; Vogelzang 2003); may administer cyanocobalamin on the same day as pemetrexed.

Vitamin B12 supplementation to reduce toxicity associated with pralatrexate: IM: 1,000 mcg every 8 to 10 weeks; administer with oral folic acid supplementation (O'Connor 2011); begin cyanocobalamin within 10 weeks prior to pralatrexate treatment initiation. After the initial dose, may administer cyanocobalamin on the same day as pralatrexate.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling. Some formulations may also contain aluminum, which may accumulate in renal impairment.

Dosing: Hepatic Impairment: Adult

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

Dosing: Pediatric

Pernicious anemia: Note: Concurrent folic acid supplementation may also be needed.

Manufacturer's labeling: Infants, Children, and Adolescents: IM, SubQ: 100 mcg once daily for 6 to 7 days; if improvement occurs, administer 100 mcg on alternate days for 7 doses, then every 3 to 4 days for 2 to 3 weeks; once hematologic values have returned to normal, maintenance dose: 100 mcg monthly

Alternate dosing: Limited data available: Infants, Children, and Adolescents: IM, SubQ: Initial: 1,000 mcg/day for 2 to 7 days based upon clinical response; followed by 100 mcg once weekly for 4 weeks and then maintenance dose: 100 mcg/month; for severe anemia, a lower initial dose of 0.2 mcg/kg/dose for 2 days followed by the above regimen has been recommended due to potential hypokalemia observed during initial treatment of adults with severe anemia (Orkin 2015; Rasmussen 2001; Stabler 2013); however, in more recent experience, while some adult patients may experience hypokalemia with initial treatment, this is unlikely to be clinically significant (Carmel 2008). For infants and young children, some experts have recommended doses as low as 50 to 100 mcg (Orkin 2015).

Vitamin B12 deficiency, severe: Limited data available; dosing regimens variable:

Dietary deficiency: Infants (breastfed with vitamin B12 deficient mothers): IM: 250 to 1,000 mcg once daily for 1 to 2 weeks, followed by weekly dosing until patient recovers (Stabler 2013); patients with neurologic symptoms have been treated with doses of 1,000 mcg (Guez 2012; Roumeliotis 2012)

Malabsorption: Infants, Children, and Adolescents: IM: 250 to 1,000 mcg daily or every other day for 1 week, then weekly for 4 to 8 weeks, and then monthly for life; younger children should receive monthly doses of 100 mcg (Bjørke-Monsen 2011; Kliegman 2016; Stabler 2013). For infants and young children, some experts have recommended doses as low as 50 to 100 mcg (Orkin 2015).

Dosing: Renal Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling. Some formulations may also contain aluminum, which may accumulate in renal impairment.

Dosing: Hepatic Impairment: Pediatric

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

Use: Labeled Indications

Vitamin B12 deficiency: Treatment of pernicious anemia, vitamin B12 deficiency due to dietary deficiencies, gastrointestinal malabsorption, folic acid deficiency, parasitic infestation, inadequate secretion of intrinsic factor, and inadequate utilization of B12 (eg, during neoplastic treatment); treatment of increased B12 requirements due to pregnancy, thyrotoxicosis, hemorrhage, malignancy, liver or kidney disease

Use: Off-Label: Adult

Aphthous ulcers (recurrent)Level of Evidence [B]

Data from 2 small studies support the use of cyanocobalamin in reducing the frequency of recurrent aphthous ulcers in patients with normal or low serum vitamin B12 levels at baseline Ref.

Level of Evidence Definitions

Level of Evidence Scale

Administration: IM

IM or deep SubQ are preferred routes of administration. IV administration is not recommended.

Administration: Injectable Detail

pH: 4.5 to 7

Administration: Oral

Oral administration is not generally recommended due to variable absorption; however, oral therapy in appropriate doses has been effective for anemia if IM/SubQ routes refused or not tolerated. Some tablets are available for sublingual administration.

Bariatric surgery: Tablet, extended release: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. Do not cut, crush, or chew. Switch to an IR tablet, chewable tablet, orally disintegrating or sublingual tablet, oral solution drops, or a nonoral formulation such as injection or nasal spray.

Administration: Subcutaneous

IM or deep SubQ are preferred routes of administration. IV administration is not recommended.

Administration: Intranasal

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

Administration: Pediatric

Oral: Not generally recommended for treatment of severe vitamin B12 deficiency due to poor oral absorption (lack of intrinsic factor); oral administration may be used in less severe deficiencies and maintenance therapy; may be administered without regard to food

Parenteral: IM or deep SubQ are preferred routes of administration: Avoid IV administration due to a more rapid system elimination with resulting decreased utilization

Dietary Considerations

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

Adequate intake (IOM 1998):

1 to 6 months: 0.4 mcg daily

7 to 12 months: 0.5 mcg daily

Recommended intake (IOM 1998):

1 to 3 years: 0.9 mcg daily

4 to 8 years: 1.2 mcg daily

9 to 13 years: 1.8 mcg daily

≥14 years: 2.4 mcg daily

Pregnancy: 2.6 mcg daily

Lactation: 2.8 mcg daily

Storage/Stability

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

See Trissel’s IV Compatibility Database

Open Trissel's IV Compatibility

Medication Patient Education with HCAHPS Considerations

What is this drug used for?

• It is used to help with some kinds of anemia.

• It is used to treat or prevent low vitamin B12.

• It may be given to you for other reasons. Talk with the doctor.

Frequently reported side effects of this drug

• Dizziness

• Headache

• Loss of strength and energy

• Anxiety

• Common cold symptoms

• Runny nose

• Diarrhea

• Vomiting

• Nausea

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Low potassium like muscle pain or weakness, muscle cramps, or an abnormal heartbeat.

• DVT like edema, warmth, numbness, change in color, or pain in the extremities.

• Vision changes

• Shortness of breath

• Burning or numbness feeling

• Excessive weight gain

• Change in balance

• Swelling of arms or legs

• Signs of a significant reaction like 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. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Contraindications

Hypersensitivity to cyanocobalamin (vitamin B12), 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: According to the manufacturer, treatment of severe vitamin B12 megaloblastic anemia may result in severe hypokalemia, sometimes fatal, due to intracellular potassium shift upon anemia resolution; however, in more recent experience, while some patients may experience hypokalemia with initial treatment, this is unlikely to be clinically significant (Carmel 2008).

• Thrombocytosis: Treatment of severe vitamin B12 megaloblastic anemia may result in thrombocytosis.

Disease-related concerns:

• Leber disease: Patients with Leber disease who received B12 treatment have suffered from severe rapid optic atrophy. Use of cyanocobalamin in these patients is not recommended.

• Megaloblastic anemia: Vitamin B12 doses >10 mcg daily may produce a hematologic response in patients with folate deficient megaloblastic anemia and mask previously unrecognized folate deficiency; vitamin B12 is not a substitute for folic acid.

• 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: The effectiveness of intranasal cyanocobalamin in patients with allergic rhinitis, nasal congestion, and upper respiratory tract infections has not been determined. Defer treatment until symptoms have subsided.

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 hypersensitivity prior to intranasal or injectable administration.

Geriatric Considerations

About one-quarter of individuals with vitamin B12 deficiency, particularly the elderly, will present with neurologic manifestations, yet hematologic indices won't appear reflective of a megaloblastic anemia (Lindenbaum 1988). Evidence exists to support replacing vitamin B12 in those whose vitamin B12 levels are at the low end of normal (<300 pg/mL has been suggested), especially given the relative safety of replacement doses (Smith 2009).

Long-term treatment with metformin, proton pump inhibitors and H2 receptor blockers has shown to be associated with an increased risk of vitamin B12 deficiency. Therefore, monitoring vitamin B12 is a prudent recommendation for older adults who are receiving any of these therapies long term (Andres 2002; Lam 2013).

Pregnancy Considerations

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).

Breast-Feeding Considerations

Vitamin B12 is found in breast milk. Milk concentrations are similar to maternal serum concentrations and concentrations may be decreased in women who are vegetarians. Vitamin B12 requirements may be increased in nursing women compared to nonbreastfeeding women (IOM 1998).

Briggs' Drugs in Pregnancy & Lactation

• Vitamin B12

Adverse Reactions

>10%:

Central nervous system: Headache (IM: 20%; intranasal: 4%)

Infection: Infection (12% to 13%)

Neuromuscular & skeletal: Asthenia (IM: 16%; intranasal: 4%)

1% to 10%:

Central nervous system: Paresthesia (4%)

Gastrointestinal: Glossitis (nasal: 4%), nausea (4%)

Respiratory: Rhinitis (4% to 8%)

Frequency not defined:

Cardiovascular: Cardiac failure, thrombosis (peripheral)

Dermatologic: Pruritus, skin rash (transient)

Endocrine & metabolic: Hypokalemia

Gastrointestinal: Diarrhea

Hematologic & oncologic: Polycythemia vera, thrombocythemia

Hypersensitivity: Anaphylactic shock (IM/SubQ)

Respiratory: Pulmonary edema

Miscellaneous: Swelling

Allergy and Idiosyncratic Reactions

• Cyanocobalamin Allergy

Metabolism/Transport Effects

None known.

Drug Interactions Open Interactions

Chloramphenicol (Systemic): May diminish the therapeutic effect of Vitamin B12. Risk C: Monitor therapy

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

Food Interactions

Heavy ethanol consumption >2 weeks may impair vitamin B12 absorption.

Test Interactions

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

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 (and vitamin B12 1 month after each dosage adjustment if using intranasal formulation), then every 3 to 6 months thereafter.

Evaluate serum methylmalonic acid and total homocysteine levels at baseline (prior to supplementation) in untreated patients to confirm vitamin B12 deficiency (and extent of deficiency); repeat to confirm adequate supplementation (Stabler 2013).

Megaloblastic/pernicious anemia: In addition to normal hematological parameters, serum potassium and platelet counts should be monitored during therapy. Note: Some patients may develop hypokalemia during initial treatment; however, this is unlikely to be clinically significant (Carmel 2008).

Bariatric surgery: Vitamin B12 levels at baseline and once a year postoperatively then every 3 to 6 months if supplemented; every trimester in pregnant females (Mechanick 2013). In patients on chronic administration of medications known to increase risk of B12 deficiency (eg, colchicine, metformin, neomycin, nitrous oxide, proton pump inhibitors, seizure medication), screen every 3 months for the initial postoperative year and then annually (Parrott 2017). Serum methylmalonic acid (MMA) is the recommended assay to evaluate vitamin B12 levels for patients who are asymptomatic, symptomatic, have a history of B12 deficiency, or preexisting neuropathy (Parrott 2017). Monitor for early signs/symptoms of B12 deficiency, including pernicious anemia (pale skin/eyes, glossitis, fatigue, anorexia, diarrhea) or neuropathy (numbness, paresthesia in extremities, ataxia, decreased reflexes), lightheadedness or vertigo, dyspnea, tinnitus, palpitations, and /or increased HR; monitor for advanced signs/symptoms of B12 deficiency, including angina, HF symptoms and/or mental status changes (Parrott 2017).

Reference Range

Normal range of serum B12 is 150 to 900 pg/mL; this represents 0.1% of total body content. Metabolic requirements are 2 to 5 mcg/day; years of deficiency are 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 to 200 pg/mL (SI: 75 to 150 pmol/L).

Gastric bypass surgery patients: Normal B12 range: 200 to 1,000 pg/mL; Deficiency critical range: B12: <400 pg/mL (suboptimal) and <200 pg/mL (deficient) (Parrott 2017).

Advanced Practitioners Physical Assessment/Monitoring

Provide patient appropriate nutritional counseling.

Nursing Physical Assessment/Monitoring

Provide patient appropriate nutritional counseling.

Dosage Forms: US

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) [contains benzalkonium chloride]

Tablet, Oral:

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

Tablet, Oral [preservative free]:

Generic: 100 mcg [DSC], 500 mcg [DSC], 1000 mcg

Tablet Extended Release, Oral:

Generic: 1000 mcg

Tablet Sublingual, Sublingual:

Generic: 2500 mcg [DSC]

Tablet Sublingual, Sublingual [preservative free]:

Generic: 2500 mcg

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Injection:

Cobex: 1000 mcg/mL (10 mL, 30 mL)

Generic: 100 mcg/mL (1 mL); 1000 mcg/mL (1 mL, 10 mL, 30 mL, 100 mL)

Anatomic Therapeutic Chemical (ATC) Classification

• B03BA01

Generic Available (US)

Yes

Pricing: US

Solution (Cyanocobalamin Injection)

1000 mcg/mL (per mL): $3.86 - $8.74

Solution (Nascobal Nasal)

500 mcg/0.1 mL (per each): $184.35

Tablet, controlled release (Vitamin B-12 ER Oral)

1000 mcg (per each): $0.05

Tablets (Vitamin B-12 Oral)

250 mcg (per each): $0.03

1000 mcg (per each): $0.06 - $0.21

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Mechanism of Action

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

Pharmacodynamics/Kinetics

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

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 (Nascobal): 6.1% (relative to IM); Oral: Pernicious anemia: 1.2%

Time to peak, serum: IM, SubQ: 30 minutes to 2 hours; Intranasal: 1.25 ± 1.9 hours

Excretion: Urine (50% to 98%, unchanged drug)

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Effects on Dental Treatment

No significant effects or complications reported

Effects on Bleeding

No information available to require special precautions

Index Terms

CaloMist; Vitamin B12

References

Ahlfors CE. Benzyl alcohol, kernicterus, and unbound bilirubin. J Pediatr. 2001;139(2):317-319.[PubMed 11487763]

Aluminum in large and small volume parenterals used in total parenteral nutrition. Fed Regist. 2002;67(244):77792-77793. To be codified at 21 CFR §201.323.

Andres E, Noel E, and Goichot B, “Metformin-Associated Vitamin B12 Deficiency,” Arch Intern Med, 2002, 162(19):2251-2.[PubMed 12390080]

Bjørke-Monsen AL and Ueland PM. Cobalamin status in children. J Inherit Metab Dis. 2011;34(1):111-119.[PubMed 20508991]

Centers for Disease Control (CDC). Neonatal deaths associated with use of benzyl alcohol—United States. MMWR Morb Mortal Wkly Rep. 1982;31(22):290-291. http://www.cdc.gov/mmwr/preview/mmwrhtml/00001109.htm. Last accessed: May 4, 2017.[PubMed 6810084]

Carmel R. How I treat cobalamin (vitamin B12) deficiency. Blood. 2008;112(6):2214-2221. doi: 10.1182/blood-2008-03-040253.[PubMed 18606874]

Cyanocobalamin injection [prescribing information]. Shirley, NY: American Regent, Inc; October 2018.

Department Health and Human Services, Food Drug Administration. Aluminum in large and small volume parenterals used in total parenteral nutrition. Federal Register. 2000;65(17):4103-4111.

Goodman M, Chen XH, Daarwish D, “Are U.S. Lower Normal B12 Limits Too Low?,” J Am Geriatr Soc, 1996, 44(10):1274-5.[PubMed 8856015]

Guez S, Chiarelli G, Menni F, Salera S, Principi N, Esposito S. Severe vitamin B12 deficiency in an exclusively breastfed 5-month-old Italian infant born to a mother receiving multivitamin supplementation during pregnancy. BMC Pediatr. 2012;12:85.[PubMed 22726312]

Gulcan E, Toker S, Hatipoglu H, et al. Cyanocobalamin may be beneficial in the treatment of recurrent aphthous ulcers even when vitamin B12 levels are normal. Am J Med Sci. 2008;336(5):379-382.[PubMed 19011392]

"Inactive" ingredients in pharmaceutical products: update (subject review). American Academy of Pediatrics (AAP) Committee on Drugs. Pediatrics. 1997;99(2):268-278.[PubMed 9024461]

IOM (Institute of Medicine), Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin and Choline, Washington, DC: National Academy Press, 1998.

Kaushansky K, Kipps TJ. Hematopoietic Agents: Growth Factors, Minerals, and Vitamins. Goodman & Gilman's: The Pharmacological Basis of Therapeutics, 12e New York, NY: McGraw-Hill; . http://accessmedicine.mhmedical.com/content.aspx?bookid=1613&sectionid=102161502. Accessed November 27, 2017.

Kliegman RM, Stanton BMD, St. Geme J, Schor NF, eds. Nelson' s Textbook of Pediatrics. 20th ed. Philadelphia, PA: Saunders Elsevier; 2016.

Lam JR, Schneider JL, Zhao W, Corley DA. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. JAMA. 2013;310(22):2435-2442.[PubMed 24327038]

Lane LA and Rojas-Fernandez C, “Treatment of Vitamin B12-Deficiency Anemia: Oral versus Parenteral Therapy,” Ann Pharmacother, 2002, 36(7-8):1268-72.[PubMed 12086562]

Langan RC and Zawistoski KJ, “Update on Vitamin B12 Deficiency,” Am Fam Physician, 2011, 83(12):1425-30.[PubMed 21671542]

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.[PubMed 3374544]

Mangels AR and Messina V, "Considerations in Planning Vegan Diets: Infants," J Am Diet Assoc, 2001, 101(6):670-7.[PubMed 11424546]

Mechanick JI, Youdim A, Jones DB, et al. Clinical practice guidelines for the perioperative nutritional, metabolic, and nonsurgical support of the bariatric surgery patient--2013 update: cosponsored by American Association of Clinical Endocrinologists, the Obesity Society, and American Society for Metabolic & Bariatric Surgery. Surg Obes Relat Dis. 2013;9(2):159-191.[PubMed 23537696]

Nascobal (cyanocobalamin) [prescribing information]. Chestnut Ridge, NY: Par Pharmaceutical Companies; November 2018.

Nelson Textbook of Pediatrics, 17th ed, Behrman RE, Kliegman RM, and Jenson HB, eds, Philadelphia, PA: WB Saunders Co, 2004.

O'Connor OA, Pro B, Pinter-Brown L, et al. Pralatrexate in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma: Results from the Pivotal PROPEL Study. J Clin Oncol. 2011;29(9):1182-1189.[PubMed 21245435]

Oh R and Brown DL, “Vitamin B12 Deficiency,” Am Fam Physician, 2003, 67(5):979-86.[PubMed 12643357]

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.[PubMed 2930611]

Orkin S, Nathan D, Ginsbirg, D, et al, eds. Nathan and Oski's Hematology and Oncology of Infancy and Childhood. 8th ed. Saunders; 2015.

Parrott J, Frank L, Rabena R, et al. American Society for Metabolic and Bariatric Surgery Integrated Health Nutritional Guidelines for the Surgical Weight Loss Patient 2016 Update: Micronutrients. Surg Obes Relat Dis. 2017;13(5):727-741.[PubMed 28392254]

Rasmussen SA, Fernhoff PM, and Scanlon KS, “Vitamin B12 Deficiency in Children and Adolescents,” J Pediatr, 2001, 138(1):10-17.[PubMed 11148506]

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.[PubMed 1627675]

Roumeliotis N, Dix D, Lipson A. Vitamin B(12) deficiency in infants secondary to maternal causes. CMAJ. 2012;184(14):1593-1598.[PubMed 22711730]

Scagliotti GV, Parikh P, von Pawel J, et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol. 2008;26(21):3543-3551.[PubMed 18506025]

Schjonsby H, “Vitamin B12 Absorption and Malabsorption,” Gut, 1989, 30(12):1986-91.[PubMed 2693230]

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.[PubMed 12190367]

Silbergleit R and Lee DC, “Bowel Obstruction and Radiopaque Vitamin B12 “Pseudobezoar”,” Am J Emerg Med, 1995, 13(1):112-3.[PubMed 7832937]

Smith AD, Refsum H. Vitamin B-12 and cognition in the elderly. Am J Clin Nutr. 2009;89(2):707S-711S.[PubMed 19116332]

Stabler SP. Clinical practice. Vitamin B12 deficiency. N Engl J Med. 2013;368(2):149-160.[PubMed 23301732]

Vogelzang NJ, Rusthoven JJ, Symanowski J, et al. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol. 2003;21(14):2636-2644.[PubMed 12860938]

Volkov I, Rudoy I, Freud T, et al. Effectiveness of vitamin B12 in treating recurrent aphthous stomatitis: a randomized, double-blind, placebo-controlled trial. J Am Board Fam Med. 2009;22(1):9-16.[PubMed 19124628]

Worthington-White DA, Behnke M, and Gross S, "Premature Infants Require Additional Folate and Vitamin B12 to Reduce the Severity of the Anemia of Prematurity," Am J Clin Nutr, 1994, 60(6):930-5.[PubMed 7985636]

Brand Names: International

Ambe 12 (LU); Ampavit (TH); Arcored (ID); B 12 SR (EG); B12 Ankermann (PL); Bedoc (GR); Bedodeka (IL); Bedoze (PT); Bedozil (BR); Behepan (SE); Betolvex (CH, DK, EG, FI, SE); Betolvex[inj.] (SE); Cianocobalamina B12 Davi (PT); Coba 1000 (LK); Cobalin (AE, CY, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Cobamin Ophth Soln (HK); Creliverol-12 (PE); Cromatonbic B12 (ES); Cynovit (BH); Cytacon (LK); Cytamen (AU, GB); Dobetin (IT, VE); Dodec (TR); Ecavit B12 (EG); Ecovitamine B12 (FR); Isopto B12 (ES); Kiddi Pharmaton (MX); Lagavit B12 (AE, BB, BM, BS, BZ, CY, GY, IQ, IR, JM, JO, KW, LB, LY, NL, OM, PR, QA, SA, SR, SY, TT, YE); Ledoxina (MX); Mono Vitamine B12 (FR); Neurobene (CZ, HN); Norivite-12 (ZA); Optovite B12 (ES); Oravit B12 SR (EG); Parecon Forte (ZW); Permadoze (PT); Permadoze oral (PT); Reedvit 10000 (AR); Reticulogen (ES); Rojamin (EC); Rubramin (PH); Sancoba (JP); Tribedoce DX (MX); Vegevit B12 (PL); Vicapan N (DE); Vitalen (MX); Vitam-Doce (AR); Vitamin B!1!2 (HR); Vitamin B12 (HU); Vitamin B12 Lannacher (AT); Vitamin B12 Recip (SE); Vitamina B12-Ecar (CO); Vitamine B12-Dulcis (LU); Vitaminum B12 (PL); Vitarubin (CH)

Last Updated 3/20/20