3/16/24, 11:35 AM Cyanocobalamin (Lexi-Drugs) - UpToDate® Lexidrug™ https://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/6669?cesid=a4fVkBbxsio&hitReason=international-brand-name&searchUrl=%2Flco%2Fa… 1/12 Cyanocobalamin (Lexi-Drugs) Pronunciation Vm P (sye an oh koe BAL a min) Brand Names: US B-12 Compliance Injection [DSC]; Dodex; Nascobal; Physicians EZ Use B-12; True Vitamin B12 [OTC]; Vitamin Deficiency System-B12 Brand Names: Canada Cobex [DSC]; Cyano Vit B12 [DSC]; JAMP-Cyanocobalamin [DSC] Pharmacologic Category Vitamin, Water Soluble Dosing: Adult Dosage guidance: Dosage form information: The cyanocobalamin content of over-the-counter products varies; it is generally higher in B-complex products (eg, 50 to 500 mcg) or products containing only vitamin B (eg, 500 to 1,000 mcg) than in multivitamin products (eg 25 mcg) ( ). Aphthous stomatitis, simple, recurrent Aphthous stomatitis, simple, recurrent (off-label use): Note: May consider use regardless of serum vitamin B levels ( ). Oral (sublingual): 1,000 mcg once daily for 6 months ( ). IM: 1,000 mcg once daily for 7 days, then 1,000 mcg once weekly for 1 month, then 1,000 mcg once monthly for 6 months ( ) Drug toxicity reduction Drug toxicity reduction: Pemetrexed: IM: 1,000 mcg every 9 weeks, beginning 1 to 3 weeks prior to pemetrexed treatment initiation ( ); in patients without preexisting anemia, some data suggest that pemetrexed and cyanocobalamin may be started simultaneously to avoid delaying pemetrexed initiation ( ). After the initial dose, may administer cyanocobalamin on the same day as pemetrexed; administer with oral folic acid supplementation. Pralatrexate: IM: 1,000 mcg every 8 to 10 weeks, beginning within 10 weeks prior to pralatrexate treatment initiation; administer with o folic acid supplementation ( ). After the initial dose, may administer cyanocobalamin on the same day as pralatrexat Vitamin B deficiency, treatment Vitamin B deficiency, treatment: Note: Folic acid supplementation may also be required. Severe/Symptomatic anemia or neurologic/neuropsychiatric findings: Initial therapy: IM, deep SUBQ: 1,000 mcg 1 to 3 times/week or once daily for 1 week, then 1,000 mcg once weekly for 4 to 8 weeks ( Alternatively, if neurologic symptoms are present, may initiate 1,000 mcg every other day for up to 3 weeks or unt further improvement in signs or symptoms, then switch to 1,000 mcg once weekly for up to 12 weeks ( ). 12 Ref 12 Ref Ref Ref Ref Ref Ref 12 12 R Ref
3/16/24, 11:35 AM Cyanocobalamin (Lexi-Drugs) - UpToDate® Lexidrug™ https://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/6669?cesid=a4fVkBbxsio&hitReason=international-brand-name&searchUrl=%2Flco%2Fa… 2/12 Maintenance therapy: Note: Continue parenteral therapy until the deficiency has been corrected and signs and symptoms have resolved bef switching to oral therapy ( ). IM, deep SUBQ: 1,000 mcg once monthly ( ). Oral, Sublingual: 1,000 to 2,000 mcg once daily ( ). Mild symptoms or asymptomatic: IM, deep SUBQ: Initial: 1,000 mcg once weekly for 4 to 8 weeks; maintenance dose: 1,000 mcg once monthly ( ). Oral, Sublingual: 1,000 to 2,000 mcg once daily ( ). Note: In patients with impaired GI absorption (eg, pernicious anemia bariatric surgery), or in whom adherence must be assured, parenteral administration may be required ( ). Intranasal (Nascobal): Initial: 500 mcg (1 spray) in 1 nostril once weekly. Consider an alternative route if vitamin B level persistently low after 1 month of treatment. Note: Some experts do not use intranasal formulations due to variable absorption ( ). Duration of therapy: Continue indefinitely in patients with pernicious anemia or other irreversible cause of deficiency (eg, bariatric surgery); may discontinue therapy if a reversible cause of deficiency (eg, reduced dietary intake) has been addres ( ). Vitamin B deficiency, prevention Vitamin B deficiency, prevention: Note: For use in patients with risk factors for vitamin B deficiency (eg, bariatric or gastric surgery, disorders of the stomach o terminal ileum, vegan or vegetarian diet) ( ). Oral, Sublingual: 350 to 1,000 mcg once daily; in patients with pernicious anemia, higher doses (eg, 1,000 to 2,000 mcg/day) a required ( ). IM, deep SUBQ: 1,000 mcg once monthly or 1,000 to 3,000 mcg once every 6 to 12 months ( ). Note: May be preferred in pat with impaired GI absorption (eg, pernicious anemia, bariatric surgery), or for whom adherence to oral therapy is challengi ( ). Intranasal (Nascobal): 500 mcg (1 spray) in 1 nostril once weekly. Consider an alternative route if adequate vitamin B levels cannot be maintained. Note: Some experts do not use intranasal formulations due to variable absorption ( ). Duration of therapy: Continue indefinitely in patients with pernicious anemia or other irreversible cause of deficiency (eg, bariatric surgery); may discontinue therapy if a reversible cause of deficiency (eg, reduced dietary intake) has been addres ( ). Dosing: Older Adult Refer to adult dosing. Dosing: Altered Kidney Function: Adult There are no dosage adjustments provided in the manufacturer's labeling. Some formulations may also contain aluminum, which ma accumulate in renal impairment. Dosing: Hepatic Impairment: Adult There are no dosage adjustments provided in the manufacturer's labeling. Dosing: Pediatric Pernicious anemia 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 occur 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. Ref Ref Ref Ref Ref Ref 12 Ref Ref 12 12 12 Ref Ref Ref Ref 12 Ref Ref
3/16/24, 11:35 AM Cyanocobalamin (Lexi-Drugs) - UpToDate® Lexidrug™ https://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/6669?cesid=a4fVkBbxsio&hitReason=international-brand-name&searchUrl=%2Flco%2Fa… 3/12 Alternate dosing: Limited data available: Infants, Children, and Adolescents: IM, SubQ: Initial: 1,000 mcg/day for 2 to 7 days bas upon clinical response; followed by 100 mcg once weekly for 4 weeks and then maintenance dose: 100 mcg/month; for sev 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 ( ); however, in more recent experi while some adult patients may experience hypokalemia with initial treatment, this is unlikely to be clinically significant ( infants and young children, some experts have recommended doses as low as 50 to 100 mcg ( ). Vitamin B12 deficiency, severe 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, follo by weekly dosing until patient recovers ( ); patients with neurologic symptoms have been treated with doses of 1,000 mc ( ). Malabsorption: Infants, Children, and Adolescents: IM: 250 to 1,000 mcg daily or every other day for 1 week, then weekly for 4 t weeks, and then monthly for life; younger children should receive monthly doses of 100 mcg ( ). For infants and young children, some experts have recommended doses as low as 50 to 100 mcg ( ). Dosing: Altered Kidney Function: Pediatric There are no dosage adjustments provided in the manufacturer's labeling. Some formulations may also contain aluminum, which ma accumulate in renal impairment. Dosing: Hepatic Impairment: Pediatric There are no dosage adjustments provided in the manufacturer's labeling. Use: Labeled Indications Vitamin B deficiency: Treatment of pernicious anemia or vitamin B deficiency due to dietary deficiencies, gastrointestinal malabsorption, folic acid deficiency, parasitic infestation, inadequate secretion of intrinsic factor, or inadequate utilization of B (eg, d neoplastic treatment); prevention of vitamin B deficiency in patients with increased B requirements (eg, due to pregnancy, thyroto hemorrhage, malignancy, liver or kidney disease). Use: Off-Label: Adult Aphthous stomatitis, simple, recurrent Level of Evidence [B] Data from 2 small studies support the use of cyanocobalamin in reducing the frequency of recurrent aphthous ulcers in patien with normal or low serum vitamin B levels at baseline ( ). Access Full Off-Label Monograph Level of Evidence Definitions Level of Evidence Scale A - Consistent evidence from well-performed randomized, controlled trials or overwhelming evidence of some other form (eg, results of the introduction of penicillin treatment) to support the off-label use. Further research is unlikely to change confidence in the estimate of benefit. B - Evidence from randomized, controlled trials with important limitations (inconsistent results, methodological flaws, indirect imprecise), or very strong evidence of some other research design. Further research (if performed) is likely to have an imp on confidence in the estimate of benefit and risk and may change the estimate. C - Evidence from observational studies (eg, retrospective case series/reports providing significant impact on patient care), unsystematic clinical experience, or from potentially flawed randomized, controlled trials (eg, when limited options exist fo condition). Any estimate of effect is uncertain. G - Use has been substantiated by inclusion in at least one evidence-based or consensus-based clinical practice guideline. Ref Ref Ref Ref Ref Ref Ref 12 12 12 12 12 12 Ref
3/16/24, 11:35 AM Cyanocobalamin (Lexi-Drugs) - UpToDate® Lexidrug™ https://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/6669?cesid=a4fVkBbxsio&hitReason=international-brand-name&searchUrl=%2Flco%2Fa… 4/12 Administration: IM For IM or deep SUBQ administration only; do not administer IV. Administration: Injectable Detail pH: 4.5 to 7 Administration: Oral Some tablets are available for sublingual administration. Bariatric surgery: Tablet, extended release: Some institutions may have specific protocols that conflict with these recommendations; r 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 For IM or deep SUBQ administration only; do not administer IV. 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); 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 w resulting decreased utilization Dietary Considerations Strict vegetarian or vegan diets (eg, without eggs or dairy products) may result in vitamin B deficiency (NIH 2021; manufacturer's la 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: Store between 20°C and 25°C (68°F and 77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F). Protect fro Intranasal spray: Store at 15°C to 30°C (59°F to 86°F); do not freeze. Protect from light. IV Compatibility See Trissel’s IV Compatibility Database Patient Counseling Points 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 B . 12 12
3/16/24, 11:35 AM Cyanocobalamin (Lexi-Drugs) - UpToDate® Lexidrug™ https://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/6669?cesid=a4fVkBbxsio&hitReason=international-brand-name&searchUrl=%2Flco%2Fa… 5/12 • It may be given to you for other reasons. Talk with the doctor. All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor medical help if any of these side effects or any other side effects bother you or do not go away: All products: • Feeling dizzy, tired, or weak • Headache • Feeling nervous and excitable • Diarrhea, upset stomach, or throwing up • Joint pain • Signs of a common cold Nose spray: • Nose or throat irritation WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when ta drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be rela very bad side effect: • Low potassium levels like muscle pain or weakness, muscle cramps, or a heartbeat that does not feel normal • Chest pain • Feeling cold in the arms or legs • Swelling, warmth, numbness, change of color, or pain in a leg or arm • Shortness of breath, a big weight gain, or swelling in the arms or legs • Change in balance • A burning, numbness, or tingling feeling that is not normal • Change in eyesight • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tigh the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongu 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 other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patien information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a l summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensiv limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, a effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment an not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and be of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet. Contraindications Hypersensitivity to cyanocobalamin (vitamin B ), cobalt, or any component of the formulation Warnings/Precautions Concerns related to adverse effects: • CNS effects: Vitamin B deficiency for >3 months results in irreversible degenerative CNS lesions; neurologic manifestations wil prevented with folic acid unless vitamin B is also given. Spinal cord degeneration might also occur when folic acid used as a substitute for vitamin B in anemia prevention. • Hypokalemia: According to the manufacturer, treatment of severe vitamin B megaloblastic anemia may result in severe hypok sometimes fatal, due to intracellular potassium shift upon anemia resolution; however, in more recent experience, while som patients may experience hypokalemia with initial treatment, this is unlikely to be clinically significant (Carmel 2008). • Thrombocytosis: Treatment of severe vitamin B megaloblastic anemia may result in thrombocytosis. 12 12 12 12 12 12
3/16/24, 11:35 AM Cyanocobalamin (Lexi-Drugs) - UpToDate® Lexidrug™ https://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/6669?cesid=a4fVkBbxsio&hitReason=international-brand-name&searchUrl=%2Flco%2Fa… 6/12 Disease-related concerns: • Leber disease: Patients with Leber disease who received vitamin B treatment have suffered from severe rapid optic atrophy. U cyanocobalamin in these patients is not recommended. • Megaloblastic anemia: Vitamin B doses >10 mcg daily may produce a hematologic response in patients with folate deficient megaloblastic anemia and mask previously unrecognized folate deficiency; vitamin B is not a substitute for folic acid. • Polycythemia vera: Vitamin B deficiency masks signs of polycythemia vera; vitamin B administration may unmask this condit Dosage form specific issues: • Aluminum: The parenteral product may contain aluminum; toxic aluminum concentrations may be seen with high doses, prolon use, or renal dysfunction. Premature neonates are at higher risk due to immature renal function and aluminum intake from o parenteral sources. Parenteral aluminum exposure of >4 to 5 mcg/kg/day is associated with CNS and bone toxicity; tissue loa 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/da been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabo acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypote and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from pro binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacture labeling. • Intranasal administration: The effectiveness of intranasal cyanocobalamin in patients with allergic rhinitis, nasal congestion, and 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 B is recommended for any patient suspected of cyanocobalamin hypersensitivity p administration. Older Adult Considerations About one-quarter of individuals with vitamin B 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 vitam in those whose vitamin B levels are at the low end of normal (<300 pg/mL has been suggested), especially given the relative safety o replacement doses (Smith 2009). Long-term treatment with metformin, proton pump inhibitors and H2 receptor blockers has shown to be associated with an increased vitamin B deficiency. Therefore, monitoring vitamin B is a prudent recommendation for older adults who are receiving any of thes therapies long term (Andres 2002; Lam 2013). Pregnancy Considerations Water soluble vitamins cross the placenta. Absorption of vitamin B may increase during pregnancy. Vitamin B requirements may b increased in pregnant women compared to nonpregnant women. Serum concentrations of vitamin B are higher in the neonate at b than the mother (IOM 1998). Breastfeeding Considerations Vitamin B is found in breast milk. Milk concentrations are similar to maternal serum concentrations and concentrations may be dec in women who are vegetarians. Vitamin B requirements may be increased in nursing women compared to nonbreastfeeding wo (IOM 1998). Briggs' Drugs in Pregnancy & Lactation Vitamin B Adverse Reactions The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. >10%: Central nervous system: Headache (IM: 20%; intranasal: 4%) Infection: Infection (12% to 13%) Neuromuscular & skeletal: Asthenia (IM: 16%; intranasal: 4%) 12 12 12 12 12 12 12 12 12 12 12 12 12 12 12 12
3/16/24, 11:35 AM Cyanocobalamin (Lexi-Drugs) - UpToDate® Lexidrug™ https://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/6669?cesid=a4fVkBbxsio&hitReason=international-brand-name&searchUrl=%2Flco%2Fa… 7/12 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 Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within "CYP Inducers [Strong]" are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the "Open Interactions" button above. Chloramphenicol (Systemic): May diminish the therapeutic effect of Vitamin B12. Risk C: Monitor therapy Food Interactions Heavy ethanol consumption >2 weeks may impair vitamin B absorption. Test Interactions Methotrexate, pyrimethamine, and most antibiotics invalidate folic acid and vitamin B diagnostic blood assays Monitoring Parameters Vitamin B , hemoglobin, hematocrit, erythrocyte and reticulocyte count; obtain serum folate and iron levels prior to treatment; vitam and peripheral blood counts should be monitored 1 month after beginning treatment (and vitamin B 1 month after each dosag 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 confi vitamin B 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 B levels at baseline and once a year postoperatively then every 3 to 6 months if supplemented; every trim during pregnancy (Mechanick 2020). In patients on chronic administration of medications known to increase risk of B deficiency colchicine, metformin, neomycin, nitrous oxide, proton pump inhibitors, seizure medication), screen every 3 months for the initia postoperative year and then annually (Parrott 2017). Serum methylmalonic acid is the recommended assay to evaluate vitamin B for patients who are asymptomatic, symptomatic, have a history of B deficiency, or preexisting neuropathy (Parrott 2017). Moni early signs/symptoms of B deficiency, including pernicious anemia (pale skin/eyes, glossitis, fatigue, anorexia, diarrhea) or neur (numbness, paresthesia in extremities, ataxia, decreased reflexes), lightheadedness or vertigo, dyspnea, tinnitus, palpitations, an increased heart rate; monitor for advanced signs/symptoms of B deficiency, including angina, heart failure symptoms and/or m status changes (Parrott 2017). 12 12 12 12 12 12 12 1 12 12 12
3/16/24, 11:35 AM Cyanocobalamin (Lexi-Drugs) - UpToDate® Lexidrug™ https://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/6669?cesid=a4fVkBbxsio&hitReason=international-brand-name&searchUrl=%2Flco%2Fa… 8/12 Reference Range Normal range of serum B is 200 to 800 pg/mL (SI: 147.5 to 589.8 pmol/L); 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 se Occasional patients with significant neuropsychiatric abnormalities may have no hematologic abnormalities and normal serum cobalamin levels, 200 pg/mL (SI: 147.5 pmol/L), or more commonly between 100 to 200 pg/mL (SI: 73.7 to 147.5 pmol/L). Gastric bypass surgery patients: Normal B range: 200 to 1,000 pg/mL (SI: 147.5 to 737.3 pmol/L); Deficiency critical range: B : <400 (SI: <294.9 pmol/L) (suboptimal) and <200 pg/mL (SI: <147.5 pmol/L) (deficient) (Parrott 2017). Nursing Physical Assessment/Monitoring Provide patient appropriate nutritional counseling. Dosage Forms Considerations Note: Not all available strengths or formulations may be represented in Dosage Forms. Dosage Forms: US Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Disco product Kit, Injection: B-12 Compliance Injection: 1000 mcg/mL [DSC] [contains benzyl alcohol] Physicians EZ Use B-12: 1000 mcg/mL [contains benzyl alcohol] Vitamin Deficiency System-B12: 1000 mcg/mL [contains benzyl alcohol] 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: Dodex: 1000 mcg/mL (1 mL, 10 mL, 30 mL) [contains benzyl alcohol] Generic: 1000 mcg/mL (1 mL, 10 mL, 30 mL) Solution, Nasal: Nascobal: 500 mcg/0.1 mL (1 ea) [contains benzalkonium chloride] Generic: 500 mcg/0.1 mL (1 ea) Tablet, Oral: True Vitamin B12: 500 mcg, 1000 mcg Generic: 100 mcg, 250 mcg, 500 mcg, 1000 mcg Tablet, Oral [preservative free]: Generic: 1000 mcg Tablet Extended Release, Oral: Generic: 1000 mcg Tablet Sublingual, Sublingual [preservative free]: Generic: 2500 mcg Dosage Forms: Canada Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Disco product Solution, Injection: Cobex: 1000 mcg/mL ([DSC]) Generic: 100 mcg/mL ([DSC]); 1000 mcg/mL (1 mL, 10 mL, 30 mL) 12 12 12
3/16/24, 11:35 AM Cyanocobalamin (Lexi-Drugs) - UpToDate® Lexidrug™ https://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/6669?cesid=a4fVkBbxsio&hitReason=international-brand-name&searchUrl=%2Flco%2Fa… 9/12 Anatomic Therapeutic Chemical (ATC) Classification B03BA01 Generic Available (US) Yes Pricing: US Solution (Cyanocobalamin Injection) 1000 mcg/mL (per mL): $2.14 - $8.74 Solution (Cyanocobalamin Nasal) 500 mcg/0.1 mL (per each): $191.51 Solution (Dodex Injection) 1000 mcg/mL (per mL): $8.52 Solution (Nascobal Nasal) 500 mcg/0.1 mL (per each): $212.79 Tablet, controlled release (Vitamin B-12 ER Oral) 1000 mcg (per each): $0.07 Tablets (Vitamin B-12 Oral) 1000 mcg (per each): $0.04 - $0.22 Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provid when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determ range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate a prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Mediexpressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential d 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 a hematopoiesis Pharmacokinetics (Adult Data Unless Noted) 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 B 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 comp 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 enterohepa 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). 12
3/16/24, 11:35 AM Cyanocobalamin (Lexi-Drugs) - UpToDate® Lexidrug™ https://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/6669?cesid=a4fVkBbxsio&hitReason=international-brand-name&searchUrl=%2Flco%2F… 10/12 Dental: Local Anesthetic/Vasoconstrictor Precautions No information available to require special precautions Dental: Effects on Dental Treatment No significant effects or complications reported Dental: Effects on Bleeding No information available to require special precautions Index Terms CaloMist; Vitamin B Brand Names: International Find brand name(s) by country (for United States and Canada see separate Brand Names sections) For country code abbreviations ( show table ) 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 codifie CFR §201.323. Andres E, Noel E, and Goichot B, “Metformin-Associated Vitamin B Deficiency,” Arch Intern Med, 2002, 162(19):2251-2.[PubMed 12390 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 and Prevention (CDC). Neonatal deaths associated with use of benzyl alcohol—United States. MMWR Morb Wkly Rep. 1982;31(22):290-291. http://www.cdc.gov/mmwr/preview/mmwrhtml/00001109.htm. Last accessed: May 4, 2017.[PubMed 6 Carmel R. How I treat cobalamin (vitamin B12) deficiency. Blood. 2008;112(6):2214-2221. doi: 10.1182/blood-2008-03-040253.[PubMed 18606874] Chan CQ, Low LL, Lee KH. Oral vitamin B12 replacement for the treatment of pernicious anemia. Front Med (Lausanne). 2016;3:38. doi:10.3389/fmed.2016.00038[PubMed 27602354] Cyanocobalamin injection [prescribing information]. E. Windsor, NJ: AuroMedics Pharma LLC; May 2020. 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 B Limits Too Low?,” J Am Geriatr Soc, 1996, 44(10):1274-5.[PubMed 88560 Guez S, Chiarelli G, Menni F, Salera S, Principi N, Esposito S. Severe vitamin B12 deficiency in an exclusively breastfed 5-month-old Itali infant born to a mother receiving multivitamin supplementation during pregnancy. BMC Pediatr. 2012;12:85.[PubMed 22726312] Gulcan E, Toker S, Hatipoğlu H, Gulcan A, Toker A. Cyanocobalamin may be beneficial in the treatment of recurrent aphthous ulcers ev when vitamin B12 levels are normal. Am J Med Sci. 2008;336(5):379-382. doi:10.1097/MAJ.0b013e31816a05f2[PubMed 19011392] Horwitz SM, Kim YH, Foss F, et al. Identification of an active, well-tolerated dose of pralatrexate in patients with relapsed or refractory cutaneous T-cell lymphoma. Blood. 2012;119(18):4115-4122. doi:10.1182/blood-2011-11-390211[PubMed 22394596] "Inactive" ingredients in pharmaceutical products: update (subject review). American Academy of Pediatrics (AAP) Committee on Drug Pediatrics. 1997;99(2):268-278.[PubMed 9024461] IOM (Institute of Medicine), Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B , Folate, Vitamin B , Pantothenic Acid, Biot Choline, Washington, DC: National Academy Press, 1998. Kaushansky K, Kipps TJ. Hematopoietic Agents: Growth Factors, Minerals, and Vitamins. Goodman & Gilman's: The Pharmacological Basi Therapeutics, 12e New York, NY: McGraw-Hill; . http://accessmedicine.mhmedical.com/content.aspx?bookid=1613§ionid=10216150 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; 201 12 Enter a Country or Country Code 12 12 6 12
3/16/24, 11:35 AM Cyanocobalamin (Lexi-Drugs) - UpToDate® Lexidrug™ https://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/6669?cesid=a4fVkBbxsio&hitReason=international-brand-name&searchUrl=%2Flco%2F… 11/12 Lam JR, Schneider JL, Zhao W, Corley DA. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. J 2013;310(22):2435-2442.[PubMed 24327038] Lane LA and Rojas-Fernandez C, “Treatment of Vitamin B -Deficiency Anemia: Oral versus Parenteral Therapy,” Ann Pharmacother, 200 8):1268-72.[PubMed 12086562] Langan RC, Goodbred AJ. Vitamin B12 deficiency: recognition and management. Am Fam Physician. 2017;96(6):384-389.[PubMed 2892 Langan RC, 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 o 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] Means RT, Fairfield KM. Treatment of vitamin B12 and folate deficiencies. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. https://www.uptodate.com. Accessed January 12, 2023. Mechanick JI, Apovian C, Brethauer S, et al. Clinical practice guidelines for the perioperative nutrition, metabolic, and nonsurgical sup patients undergoing bariatric procedures - 2019 update: cosponsored by American Association of Clinical Endocrinologists/American of Endocrinology, The Obesity Society, American Society for Metabolic & Bariatric Surgery, Obesity Medicine Association, and America Society of Anesthesiologists. Surg Obes Relat Dis. 2020;16(2):175-247. doi:10.1016/j.soard.2019.10.025[PubMed 31917200] Nascobal (cyanocobalamin) [prescribing information]. Chestnut Ridge, NY: Par Pharmaceutical Companies; November 2018. National Institutes of Health (NIH). Vitamin B12 - health professional. https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessiona Updated April 6, 2021. Accessed August 30, 2021. Nelson Textbook of Pediatrics, 17th ed, Behrman RE, Kliegman RM, and Jenson HB, eds, Philadelphia, PA: WB Saunders Co, 2004. Oh R, Brown DL. Vitamin B deficiency. Am Fam Physician. 2003;67(5):979-986.[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 th 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 B Deficiency in Children and Adolescents,” J Pediatr, 2001, 138(1):10-17.[PubM 11148506] Refer to manufacturer's labeling. Regland B, Gottfries CG, and Lindstedt G, “Dementia Patients With Low Serum Cobalamin Concentration: Relationship to Atrophic Gas 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.[PubM 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. doi:10.1200/JCO.2007.15.0375[PubMed 18506025] Schjonsby H, “Vitamin B 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 Clini 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 B “Pseudobezoar”,” Am J Emerg Med, 1995, 13(1):112-3.[PubMe 7832937] Singh N, Baldi M, Kaur J, et al. Timing of folic acid/vitamin B12 supplementation and hematologic toxicity during first-line treatment of patients with nonsquamous non-small cell lung cancer using pemetrexed-based chemotherapy: the PEMVITASTART randomized trial. 2019;125(13):2203-2212. doi:10.1002/cncr.32028[PubMed 30825389] 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. doi:10.1056/NEJMcp1113996[PubMed 23301732 Vogelzang NJ, Rusthoven JJ, Symanowski J, et al. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in p with malignant pleural mesothelioma. 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3/16/24, 11:35 AM Cyanocobalamin (Lexi-Drugs) - UpToDate® Lexidrug™ https://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/6669?cesid=a4fVkBbxsio&hitReason=international-brand-name&searchUrl=%2Flco%2F… 12/12 © 2024 UpToDate, Inc. and its affiliates and/or licensors. All Right Worthington-White DA, Behnke M, and Gross S, "Premature Infants Require Additional Folate and Vitamin B to Reduce the Severity o Anemia of Prematurity," Am J Clin Nutr, 1994, 60(6):930-5.[PubMed 7985636] Last Updated 2/29/24 12