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Cyanocobalamin, Vitamin B12

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Jan.14.2022

Cyanocobalamin, Vitamin B12

Indications/Dosage

Labeled

  • macrocytic anemia
  • nutritional supplementation
  • pernicious anemia
  • vitamin B12 deficiency
  • vitamin B12 deficiency diagnosis
  • vitamin B12 deficiency megaloblastic anemia

NOTE: Hematocrit, reticulocyte count, vitamin B12, folate, and iron concentrations should be obtained prior to treatment. If folate concentrations are low in a patient with low B12 concentrations, folic acid should only be administered in combination with B12. Vitamin blood concentrations and peripheral blood counts should be monitored at one month of treatment and then at intervals of 3 to 6 months.[30895]

Off-Label

  • methylmalonic aciduria
† Off-label indication

For nutritional supplementation

Oral dosage

Adults and Adolescent pregnant females

2.6 mcg orally daily.

Adults and Adolescent lactating females

2.8 mcg orally daily.

Adults and Adolescents >= 14 years

2.4 mcg PO daily. NOTE: Due to malabsorption of food-bound vitamin B12, individuals older than age 50 years are advised to meet their recommended daily allowance mainly by taking vitamin B12-containing supplements or through foods fortified with vitamin B12.[27866]

Children 9—13 years

1.8 mcg PO daily.

Children 4—8 years

1.2 mcg PO daily.

Children 1—3 years

0.9 mcg PO daily.

Infants 7—12 months

0.5 mcg/day PO is the adequate intake. Recommended daily allowance has not been established.

Infants 0—6 months

0.4 mcg/day PO is the adequate intake. Recommended daily allowance has not been established.

Intranasal dosage

Adults and Adolescents

500 mcg intranasally into 1 nostril once weekly. The intranasal route is for maintenance of adequate nutritional intake in patients who cannot absorb vitamin B12 via the oral route.

Children and Infants

Safety and efficacy of intranasal use have not established; see oral dosage guidelines from the Institute of Medicine.

For the treatment and prevention of vitamin B12 deficiency or for the treatment of vitamin B12 deficiency megaloblastic anemia or macrocytic anemia thought to be due to vitamin B12 deficiency

Oral dosage

Adults

1,000 to 2,000 mcg/day PO for 1 to 2 weeks, followed by 500 to 1,000 mcg/day PO.[59569] [60922]

Adolescents

1,000 to 2,000 mcg/day PO for 1 to 2 weeks, followed by 500 to 1,000 mcg/day PO.[59569] [60922]

Intramuscular or Subcutaneous dosage

Adults

1,000 mcg IM given daily or every other day for 1 week, then weekly for 4 to 8 weeks, then monthly until recovery is the usual dosage.[43996] [43997] [60922] 100 mcg IM/subcutaneously once daily for 6 or 7 days is the FDA-approved dosage. After clinical improvement and if a reticulocyte response is seen, give 100 mcg IM/subcutaneously on alternate days for 7 doses, then every 3 to 4 days for another 2 to 3 weeks, then 100 mcg IM/subcutaneously monthly. Administer with folic acid, if needed.[43995]

Adolescents†

1,000 mcg IM given daily or every other day for 1 week, then weekly for 4 to 8 weeks, then monthly until recovery is the usual dosage.[43997] [60922]

Children†

Dosing is not well established in pediatric patients and should be guided by clinical response and laboratory measurements.[60926] [60930] 1,000 mcg IM daily for 2 to 7 days, then 100 mcg IM/subcutaneously weekly for 4 weeks, then monthly until recovery has been recommended and used in children.[60922] [60925] [60928] [60929] [60930] The adult dosage (1,000 mcg IM given daily or every other day for 1 week, then weekly for 4 to 8 weeks, then monthly) has also been used in children.[60922] [60939] [62570]

Infants†

Dosing is not well established in pediatric patients and should be guided by clinical response and laboratory measurements.[60926] [60930] 250 to 1,000 mcg IM daily for 4 to 10 days, followed by 100 to 1,000 mcg IM weekly or monthly until recovery, has been recommended and used in infants in case reports.[60922] [60923] [60924] [60925] [60937] [60942] [62570]

Intranasal dosage

Adults

Initial dose is 500 mcg intranasally into 1 nostril once weekly. Consider increasing the dose if serum concentrations of B12 decrease after one month of therapy. Assess serum B12 concentrations one month after each dosage adjustment. Continued low serum concentrations may indicate that the patient may need alternative therapy (i.e., IM or subcutaneous B12 administration).[30895]

For the treatment of pernicious anemia

NOTE: Patients with pernicious anemia are 3 times more likely to develop carcinoma of the stomach than the general population, necessitating an appropriate work-up.

Intramuscular or Subcutaneous dosage

Adults

1,000 mcg IM given daily or every other day for 1 week, then weekly for 4 to 8 weeks, then monthly for life is the usual dosage.[43996] [43997] [60922] 100 mcg IM/subcutaneously once daily for 6 or 7 days is the FDA-approved dosage. After clinical improvement and if a reticulocyte response is seen, give 100 mcg IM/subcutaneously on alternate days for 7 doses, then every 3 to 4 days for another 2 to 3 weeks, then 100 mcg IM/subcutaneously monthly for life. Administer with folic acid, if needed.[43995]

Adolescents†

1,000 mcg IM given daily or every other day for 1 week, then weekly for 4 to 8 weeks, then monthly for life is the usual dosage.[43997] [60922]

Children†

Dosing is not well established in pediatric patients and should be guided by clinical response and laboratory measurements.[60926] [60930] 1,000 mcg IM daily for 2 to 7 days, then 100 mcg IM weekly for 4 weeks, then monthly has been recommended and used in children.[60922] [60925] [60928] [60929] [60930] The adult dosage (1,000 mcg IM given daily or every other day for 1 week, then weekly for 4 to 8 weeks, then monthly for life) has also been used in children.[60922] [60926] [60939] [60941] [62570]

Infants†

Dosing is not well established in pediatric patients and should be guided by clinical response and laboratory measurements.[60926] [60930] 250 to 1,000 mcg IM daily for 4 to 10 days, followed by 100 to 1,000 mcg IM weekly or monthly, has been recommended and used in infants in case reports.[60922] [60923] [60924] [60925] [60937] [60942] [62570]

Oral dosage†

Adults

1,000 to 2,000 mcg/day PO for life.[59569] [60922]

Adolescents

1,000 to 2,000 mcg/day PO for life.[59569] [60922]

for the treatment of pernicious anemia in patients who are in hematologic remission with no nervous system involvement

Intranasal dosage

Adults

Initial dose is 500 mcg intranasally into 1 nostril once weekly. Consider increasing the dose if serum concentrations of B12 decrease after one month of therapy. Assess serum B12 concentration one month after each dosage adjustment. Continued low serum concentrations may indicate that the patient may need alternative therapy (i.e., IM or subcutaneous B12 administration).[30895]

For the treatment of methylmalonic aciduria†

Intramuscular dosage

Neonates

1,000 mcg intramuscularly once daily for 11 days with a protein-restricted diet.

For vitamin B12 deficiency diagnosis

Intramuscular dosage

Adults

1,000 mcg IM once is the flushing dose for Schilling test/vitamin B12 absorption test.[43995]

Therapeutic Drug Monitoring

Maximum Dosage Limits

    Patients with Hepatic Impairment Dosing

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Patients with Renal Impairment Dosing

    Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

     

    Intermittent hemodialysis

    Specific guidelines are not available; it appears that no dosage adjustments are needed.

    † Off-label indication
    Revision Date: 01/14/2022, 11:13:17 AM

    References

    27866 - Standing Committee on the Scientific Evaluation of Dietary Reference Intakes-Panel on Folate, Other B Vitamins, and Choline and the Subcommittee on Upper Reference Levels of Nutrients, Food and Nutrition Board, Institute of Medicine (IOM). Dietary Reference Intakes for Thiamine, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin and Choline. 1999, 2000. The National Academy of Sciences Press, Washington DC.30895 - Nascobal (cyanocobalamin, vitamin B-12) nasal spray package insert. Spring Valley, NY: Par Pharmaceutical Companies, Inc.; 2018 Nov.43995 - Cyanocobalamin injection package insert. Shirley, NY: American Regent, Inc.; 2014 Apr.43996 - Andres E, Loukili NH, Noel E, et al. Vitamin B12 (cobalamin) deficiency in elderly patients. CMAJ 2004;171(3):251-9.43997 - Bolaman Z, Kadikoylu G, Yukselen V, et al. Oral Versus Intramuscular Cobalamin Treatment in Megaloblastic Anemia: A Single-Center, Prospective, Randomized, Open-Label Study. Clin Ther 2003;25:3124–3134.59569 - Oh RC, Brown DL. Vitamin B12 deficiency. Am Fam Physician 2003;67:979-986.60922 - Stabler SP. Vitamin B12 deficiency. New Engl J Med 2013;368:149-160.60923 - Roumeliotis N, Drix D, Lipson A. Vitamin B12 deficiency in infants secondary to maternal causes. CMAJ 2012;184;1593-1598.60924 - Banka S, Roberts R, Plews D, et al. Early diagnosis and treatment of cobalamin deficiency of infancy owing to occult maternal pernicious anemia. J Pediatr Hematol Oncol 2010;32:319-322.60925 - Monagle PT, Tauro GP. Long term follow up of patients with transcobalamin II deficiency. Arch Dis Child 1995;72:237-238.60926 - van Loon M, Postels DG, Heikens GT, et al. Severe pernicious anaemia in an 8-year-old African girl. Ann Trop Paediatr 2009;29:231-244.60928 - Crawford JR, Say D. Vitamin B12 deficiency presenting as acute ataxia. BMJ Case Rep 2013;1-4.60929 - Carman KB, Belgemen T, Yis U. Involuntary movements misdiagnosed as seizure during vitamin B12 treatment. Pediatr Emer Care 2013;29:1223-1224.60930 - Rasmussen SA, Fernhoff PM, Scanlon KS. Vitamin B12 deficiency in children and adolescents. J Pediatr 2001;138:10-17.60937 - Ide E, Van Biervliet S, Thijs J, et al. Solid food refusal as the presenting sign of vitamin B12 deficiency in a breastfed infant. Eur J Pediatr 2011;170:1453-1455.60939 - Chakrabarty B, Dubey R, Gulati S, et al. Isolated cerebellar involvement in vitamin B12 deficiency: A case report. J Child Neurol 2014;29:NP161-163.60941 - Yoganathan S, Thomas MM, Mathai S, et al. Neuroregression as an initial manifestation in a toddler with acquired pernicious anemia. BMJ Case Rep 2015;1-4.60942 - McNeil K, Chowdhury D, Penney L, et al. Vitamin B12 deficiency with intrinsic factor antibodies in an infant with poor growth and developmental delay. Paediatr Child Health 2014;19:84-86.62570 - Glaser K, Girschick HJ, Schropp C, et al. Psychomotor development following early treatment of severe infantile vitamin B12 deficiency and West syndrome - Is everything fine? A case report and review of literature. Brain Dev 2015;37:347-351.

    How Supplied

    Vitamin B12 (Cyanocobalamin) Nasal gel

    Nascobal 500mcg/0.1mL Nasal Gel (57459-1972) (Adhera Therapeutics, Inc., formerly Marina Biotech) (off market)

    Vitamin B12 (Cyanocobalamin) Nasal gel

    Nascobal 500mcg/0.1mL Nasal Gel (57459-1002) (Adhera Therapeutics, Inc., formerly Marina Biotech) (off market)Nascobal 500mcg/0.1mL Nasal Gel package photo

    Vitamin B12 (Cyanocobalamin) Nasal gel

    Nascobal 500mcg/0.1mL Nasal Gel (63004-7732) (Mallinckrodt Pharmaceuticals, formerly Questcor Pharmaceuticals Inc) (off market)Nascobal 500mcg/0.1mL Nasal Gel package photo

    Vitamin B12 (Cyanocobalamin) Nasal gel

    Nascobal 500mcg/0.1mL Nasal Gel (67871-7732) (QOL Medical, LLC) (off market)

    Vitamin B12 (Cyanocobalamin) Nasal gel

    Nascobal 500mcg/0.1mL Nasal Gel (00091-7033) (UCB Pharma Inc) (off market)

    Vitamin B12 (Cyanocobalamin) Nasal spray, solution

    CaloMist 25mcg/0.1ml Nasal Spray (00256-0203) (Fleming Pharmaceuticals) (off market)CaloMist 25mcg/0.1ml Nasal Spray package photo

    Vitamin B12 (Cyanocobalamin) Nasal spray, solution

    CaloMist 25mcg/0.1ml Nasal Spray (00256-0203) (Fleming Pharmaceuticals) (off market)

    Vitamin B12 (Cyanocobalamin) Nasal spray, solution

    Cyanocobalamin 500mcg/0.1mL Nasal Spray (43386-0237) (Gavis Pharmaceuticals, LLC, wholly owned subsidiary of Lupin) null

    Vitamin B12 (Cyanocobalamin) Nasal spray, solution

    Cyanocobalamin 500mcg/0.1mL Nasal Spray (45802-0491) (Padagis US LLC) nullCyanocobalamin 500mcg/0.1mL Nasal Spray package photo

    Vitamin B12 (Cyanocobalamin) Nasal spray, solution

    Nascobal 500mcg/0.1ml Nasal Spray (67871-7733) (Par Pharmaceuticals, an Endo Company) (off market)

    Vitamin B12 (Cyanocobalamin) Nasal spray, solution

    Nascobal 500mcg/0.1ml Nasal Spray (49884-0270) (Par Pharmaceuticals, an Endo Company) (off market)

    Vitamin B12 (Cyanocobalamin) Nasal spray, solution

    Nascobal 500mcg/0.1ml Nasal Spray (49884-0270) (Par Pharmaceuticals, an Endo Company) (off market)Nascobal 500mcg/0.1ml Nasal Spray package photo

    Vitamin B12 (Cyanocobalamin) Nasal spray, solution

    Nascobal 500mcg/0.1ml Nasal Spray (67871-7733) (QOL Medical, LLC) (off market)Nascobal 500mcg/0.1ml Nasal Spray package photo

    Vitamin B12 (Cyanocobalamin) Nasal spray, solution

    Nascobal 500mcg/0.1mL Nasal Spray (49884-0270) (Endo Pharmaceuticals Inc.) nullNascobal 500mcg/0.1mL Nasal Spray package photo

    Vitamin B12 (Cyanocobalamin) Nasal spray, solution

    Nascobal 500mcg/0.1mL Nasal Spray (49884-0270) (Par Pharmaceuticals, an Endo Company) (off market)

    Vitamin B12 (Cyanocobalamin) Oral capsule, liquid filled

    CVS Satin Collection Vitamin B12 1000mcg Softgel (null) (CVS Health) null

    Vitamin B12 (Cyanocobalamin) Oral drops, solution

    RITE AID Vitamin B-12 1000mcg Sublingual Liquid (null) (Rite Aid Corp) null

    Vitamin B12 (Cyanocobalamin) Oral drops, solution

    Vitamin B12 3000mcg Sublingual Drops (Raspberry) (null) (National Vitamin Company Inc) null

    Vitamin B12 (Cyanocobalamin) Oral drops, solution

    B-12 5000mcg Sublingual Liquid (null) (Natures Bounty, a subsidiary of NBTY, Inc.) null

    Vitamin B12 (Cyanocobalamin) Oral solution

    CVS B-12 1000mcg Liquid (null) (CVS Health) null

    Vitamin B12 (Cyanocobalamin) Oral solution

    CVS B12 1000mcg Liquid (Cherry) (null) (CVS Health) null

    Vitamin B12 (Cyanocobalamin) Oral tablet, extended release

    Vitamin B12 1500mcg Time Release Tablet (null) (Sundown Nutrition, a subsidiary of NBTY, Inc.) null

    Vitamin B12 (Cyanocobalamin) Soft chew

    CVS B12 500mcg Gummies (null) (CVS Health) null

    Vitamin B12 (Cyanocobalamin) Soft chew

    Vitamin B12 500mcg Gummies (null) (Sundown Nutrition, a subsidiary of NBTY, Inc.) null

    Vitamin B12 (Cyanocobalamin) Soft chew

    Vitamin B12 1500mcg Gummies (null) (Sundown Nutrition, a subsidiary of NBTY, Inc.) null

    Vitamin B12 (Cyanocobalamin) Soft chew

    CVS Vitamin B12 2500mcg Soft Chew (Mixed Berry) (null) (CVS Health) nullCVS Vitamin B12 2500mcg Soft Chew (Mixed Berry) package photo

    Vitamin B12 (Cyanocobalamin) Solution for injection

    B-12 Compliance Injection Kit (49836-0527) (Rx Pharma Pack Inc.) null

    Vitamin B12 (Cyanocobalamin) Solution for injection

    B-12 Injection Kit (69959-0112) (Maveron Health, LLC. ) null

    Vitamin B12 (Cyanocobalamin) Solution for injection

    Cyanocobalamin 10,000mcg/10mL Solution for Injection (00143-9620) (Hikma Pharmaceuticals USA inc.) nullCyanocobalamin 10,000mcg/10mL Solution for Injection package photo

    Vitamin B12 (Cyanocobalamin) Solution for injection

    Cyanocobalamin 10,000mcg/10mL Solution for Injection (16714-0302) (NorthStar Rx LLC) nullCyanocobalamin 10,000mcg/10mL Solution for Injection package photo

    Vitamin B12 (Cyanocobalamin) Solution for injection

    Cyanocobalamin 10,000mcg/10mL Solution for Injection (70710-1664) (Zydus Pharmaceuticals (USA) Inc.) nullCyanocobalamin 10,000mcg/10mL Solution for Injection package photo

    Vitamin B12 (Cyanocobalamin) Solution for injection

    Cyanocobalamin 10000mcg/10mL Solution for Injection (67457-0399) (Mylan Institutional LLC ) null

    Vitamin B12 (Cyanocobalamin) Solution for injection

    Cyanocobalamin 10000mcg/10mL Solution for Injection (69680-0113) (Vitruvias Therapeutics, Inc) null

    Vitamin B12 (Cyanocobalamin) Solution for injection

    Cyanocobalamin 1000mcg/ml Solution for Injection (00517-0032) (American Regent Inc, a division of Luitpold Pharmaceuticals) nullCyanocobalamin 1000mcg/ml Solution for Injection package photo

    Vitamin B12 (Cyanocobalamin) Solution for injection

    Cyanocobalamin 1000mcg/ml Solution for Injection (00517-0130) (American Regent Inc, a division of Luitpold Pharmaceuticals) nullCyanocobalamin 1000mcg/ml Solution for Injection package photo

    Vitamin B12 (Cyanocobalamin) Solution for injection

    Cyanocobalamin 1000mcg/ml Solution for Injection (00517-0031) (American Regent Inc, a division of Luitpold Pharmaceuticals) nullCyanocobalamin 1000mcg/ml Solution for Injection package photo

    Vitamin B12 (Cyanocobalamin) Solution for injection

    Cyanocobalamin 1000mcg/ml Solution for Injection (00641-0370) (Baxter Anesthesia/Critical Care) (off market)

    Vitamin B12 (Cyanocobalamin) Solution for injection

    Cyanocobalamin 1000mcg/ml Solution for Injection (63323-0044) (Fresenius Kabi AG) nullCyanocobalamin 1000mcg/ml Solution for Injection package photo

    Vitamin B12 (Cyanocobalamin) Solution for injection

    Cyanocobalamin 1000mcg/ml Solution for Injection (63739-0476) (McKesson Packaging Inc) (off market)

    Vitamin B12 (Cyanocobalamin) Solution for injection

    Cyanocobalamin 1000mcg/ml Solution for Injection (49727-0722) (Vita-Rx Corporation) (off market)

    Vitamin B12 (Cyanocobalamin) Solution for injection

    Cyanocobalamin 1000mcg/mL Solution for Injection (68001-0542) (BluePoint Lab Injectables) nullCyanocobalamin 1000mcg/mL Solution for Injection package photo

    Vitamin B12 (Cyanocobalamin) Solution for injection

    Cyanocobalamin 1000mcg/mL Solution for Injection (68001-0509) (BluePoint Laboratories) (off market)

    Vitamin B12 (Cyanocobalamin) Solution for injection

    Cyanocobalamin 1000mcg/mL Solution for Injection (55150-0364) (Eugia US LLC fka AuroMedics Pharma LLC) null

    Vitamin B12 (Cyanocobalamin) Solution for injection

    Cyanocobalamin 1000mcg/mL Solution for Injection (00143-9621) (Hikma Pharmaceuticals USA inc.) nullCyanocobalamin 1000mcg/mL Solution for Injection package photo

    Vitamin B12 (Cyanocobalamin) Solution for injection

    Cyanocobalamin 1000mcg/mL Solution for Injection (71288-0303) (Meitheal Pharmaceuticals, Inc.) null

    Vitamin B12 (Cyanocobalamin) Solution for injection

    Cyanocobalamin 1000mcg/mL Solution for Injection (16714-0165) (NorthStar Rx LLC) nullCyanocobalamin 1000mcg/mL Solution for Injection package photo

    Vitamin B12 (Cyanocobalamin) Solution for injection

    Cyanocobalamin 1000mcg/mL Solution for Injection (25021-0502) (Sagent Pharmaceuticals) null

    Vitamin B12 (Cyanocobalamin) Solution for injection

    Cyanocobalamin 1000mcg/mL Solution for Injection (70512-0840) (Sola Pharmaceuticals) null

    Vitamin B12 (Cyanocobalamin) Solution for injection

    Cyanocobalamin 1000mcg/mL Solution for Injection (70069-0005) (Somerset Therapeutics, LLC) nullCyanocobalamin 1000mcg/mL Solution for Injection package photo

    Vitamin B12 (Cyanocobalamin) Solution for injection

    Cyanocobalamin 1000mcg/mL Solution for Injection (70069-0172) (Somerset Therapeutics, LLC) nullCyanocobalamin 1000mcg/mL Solution for Injection package photo

    Vitamin B12 (Cyanocobalamin) Solution for injection

    Cyanocobalamin 1000mcg/mL Solution for Injection (69680-0112) (Vitruvias Therapeutics, Inc) null

    Vitamin B12 (Cyanocobalamin) Solution for injection

    Cyanocobalamin 1000mcg/mL Solution for Injection (70710-1663) (Zydus Pharmaceuticals (USA) Inc.) nullCyanocobalamin 1000mcg/mL Solution for Injection package photo

    Vitamin B12 (Cyanocobalamin) Solution for injection

    Cyanocobalamin 1000mcg/mL Solution for Injection (PREMIER ProRx) (63323-0044) (Fresenius Kabi USA, LLC ) null

    Vitamin B12 (Cyanocobalamin) Solution for injection

    Cyanocobalamin 30,000mcg/30mL Solution for Injection (16714-0609) (NorthStar Rx LLC) nullCyanocobalamin 30,000mcg/30mL Solution for Injection package photo

    Vitamin B12 (Cyanocobalamin) Solution for injection

    Cyanocobalamin 30,000mcg/30mL Solution for Injection (70069-0171) (Somerset Therapeutics, LLC) null

    Vitamin B12 (Cyanocobalamin) Solution for injection

    Cyanocobalamin 30,000mcg/30mL Solution for Injection (69680-0121) (Vitruvias Therapeutics, Inc) null

    Vitamin B12 (Cyanocobalamin) Solution for injection

    Cyanocobalamin 30,000mcg/30mL Solution for Injection (70710-1665) (Zydus Pharmaceuticals (USA) Inc.) nullCyanocobalamin 30,000mcg/30mL Solution for Injection package photo

    Vitamin B12 (Cyanocobalamin) Solution for injection

    Cyanocobalamin 30000mcg/30mL Solution for Injection (00517-0130) (American Regent Inc, a division of Luitpold Pharmaceuticals) null

    Vitamin B12 (Cyanocobalamin) Solution for injection

    Cyanocobalamin 30000mcg/30mL Solution for Injection (00143-9619) (Hikma Pharmaceuticals USA inc.) nullCyanocobalamin 30000mcg/30mL Solution for Injection package photo

    Vitamin B12 (Cyanocobalamin) Solution for injection

    Cyanocobalamin 30000mcg/30mL Solution for Injection (67457-0400) (Mylan Institutional LLC ) null

    Vitamin B12 (Cyanocobalamin) Solution for injection

    Cyomin 1000mcg/ml Solution for Injection (00456-1015) (Allergan USA, Inc.) (off market)

    Vitamin B12 (Cyanocobalamin) Solution for injection

    Dodex 10,000mcg/10mL Solution for Injection (16729-0533) (Accord Healthcare, Inc.) null

    Vitamin B12 (Cyanocobalamin) Solution for injection

    Dodex 1000mcg/mL Solution for Injection (16729-0533) (Accord Healthcare, Inc.) null

    Vitamin B12 (Cyanocobalamin) Solution for injection

    Dodex 30,000mcg/30mL Solution for Injection (16729-0533) (Accord Healthcare, Inc.) null

    Vitamin B12 (Cyanocobalamin) Solution for injection

    LA-12 1000mcg/ml Solution for Injection (00314-0678) (Hyrex Pharmaceuticals) (off market)

    Vitamin B12 (Cyanocobalamin) Solution for injection

    Nutri-Twelve 1000mcg/ml Solution for Injection (49910-0029) (Gyn Nutriment Pharmacology) null

    Vitamin B12 (Cyanocobalamin) Solution for injection

    Physicians EZ Use B-12 Compliance Injection Kit (76420-0527) (Enovachem Manufacturing) null

    Vitamin B12 (Cyanocobalamin) Solution for injection

    Primabalt 1000mcg/ml Solution for Injection (00684-0123) (Primedics Laboratories) (off market)

    Vitamin B12 (Cyanocobalamin) Solution for injection

    Primabalt 1000mcg/ml Solution for Injection (00684-0153) (Primedics Laboratories) (off market)

    Description/Classification

    Description

    Cyanocobalamin, or vitamin B12, is a B-vitamin. It is found in a variety of foods such as fish, shellfish, meats, and dairy products. Although cyanocobalamin and vitamin B12 are terms used interchangeably, vitamin B12 is also available as hydroxocobalamin, a less commonly prescribed drug product. Cyanocobalamin is available nasally, orally, and parenterally, and is equal in biologic activity to hydroxocobalamin. Cyanocobalamin is used to treat pernicious anemia and prevent and treat vitamin B12 deficiency, as well as to determine vitamin B12 absorption in the Schilling test. Vitamin B12 is an essential vitamin found in foods such as meat, eggs, and dairy products. Deficiency in healthy individuals is rare; the elderly, strict vegetarians (i.e., vegan), and patients with malabsorption problems are more likely to become deficient. If vitamin B12 deficiency is not treated with a vitamin B12 supplement, then anemia, intestinal problems, and irreversible nerve damage may occur. Oral therapy is not always effective, as some persons lack intrinsic factor, an endogenous substance produced by the stomach and necessary for oral B12 absorption. Other patients may not be able to absorb oral vitamin B12 due to surgical removal or dysfunction of the intestines in the area where absorption of vitamin B12 occurs. Thus, parenteral or nasal therapy may be needed; however, intranasal therapy should only be instituted for maintenance treatment after control of the condition has been obtained by the parenteral route.[30895] [43995]

    Classifications

    • Alimentary Tract and Metabolism
      • Vitamin Supplements
        • Vitamin B Complex Supplements, including Combinations
          • Vitamin B Complex Supplement Combinations
    • Blood and Blood Forming Organs
      • Anti-anemic Agents
        • Cyanocobalamin/Vitamin B12 and Analog Supplements
    • Vitamins, Minerals, and Dietary or Nutritional Supplements
      • Vitamin and Mineral Supplements
        • Vitamin B Supplements
          • Vitamin B12 (Cyanocobalamin) Supplements
            • Injectable Vitamin B12 (Cyanocobalamin) Supplements
            • Non-injectable Vitamin B12 (Cyanocobalamin) Supplements
    Revision Date: 01/10/2019, 03:31:00 PM

    References

    30895 - Nascobal (cyanocobalamin, vitamin B-12) nasal spray package insert. Spring Valley, NY: Par Pharmaceutical Companies, Inc.; 2018 Nov.43995 - Cyanocobalamin injection package insert. Shirley, NY: American Regent, Inc.; 2014 Apr.

    Administration Information

    General Administration Information

    For storage information, see the specific product information within the How Supplied section.

    Route-Specific Administration

    Oral Administration

    • To increase oral absorption, administer on an empty stomach.[63836]

    Injectable Administration

    • Administer intramuscularly or by deep subcutaneous injection; intravenous (IV) injection is not recommended as cyanocobalamin is excreted more readily following IV injection.
    • Cyanocobalamin may be mixed with TPN solutions.
    • Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.[43995]

    Intramuscular Administration

    • Inject deeply into a large muscle mass.

    Subcutaneous Administration

    • Inject deeply into subcutaneous tissue taking care not to inject intradermally or into upper subcutaneous tissue.

    Inhalation Administration

    Intranasal Inhalation Administration

    • Administer intranasally.
    • Each unit contains only 1 spray; it is not necessary to prime before use.
    • Instruct patient on proper administration technique.
    • Administer at least one hour before or after ingestion of foods or liquids that may cause nasal congestion or rhinorrhea.
    • Delay administration in patients with active symptoms of nasal congestion, allergic rhinitis, or upper respiratory infection.
    • After administration, the spray may be discarded in usual trash.[30895]

    Clinical Pharmaceutics Information

    From Trissel's 2‚Ñ¢ Clinical Pharmaceutics Database

    Cyanocobalamin

    pH Range
    pH 4.5 to 7
    ReferencesAnon. Manufacturer's information and labeling. (Package insert).
    Osmolality/Osmolarity
    Cyanocobalamin 0.1-mg/mL injection had a measured osmolality of 446 mOsm/kg.
    ReferencesTrissel LA. Drug information- osmolalities. Data on file.
    Stability
    Cyanocobalamin injection is stable at room temperature and even when autoclaved at 121 degree C for short periods such as 15 to 20 minutes. Although compatible with a number of intravenous infusion solutions, intravenous administration is not recommended because of very rapid excretion of most of the cyanocobalamin in the urine. Vazquez et al. (2 reports) reported the stability of multiple vitamins injection (Cernevit, Baxter) diluted in three parenteral nutrition admixtures. Except for ascorbic acid, all of the vitamins, including cyanocobalamin, retained nearly 100% of the initial concentrations for 48 hours at ambient conditions.
    ReferencesAnon. Manufacturer's information and labeling. (Package insert).
    ReferencesMcEvoy GK (ed). AHFS Drug Information (current edition). Bethesda, MD: American Society of Health-System Pharmacists.
    ReferencesVazquez R, Hoang ML, Martin J, et al. Simultaneous quantification of water-soluble and fat-soluble vitamins in parenteral nutrition admixtures by HPLC-UV-MS/MS. Eur J Hosp Pharm Sci. 2009; 15
    ReferencesVazquez R, Rotival R, Calvez S, et al. Stability indicating assay method on vitamins: Application to their stability study in aprenetral nutrition admixtures. Chromatographia. 2009; 69
    pH Effects
    Cyanocobalamin is stable over the pH range of 3 to 7 with maximum stability exhibited at pH 4.5 to 5. It is unstable in alkaline solutions and very strongly acidic solutions.
    ReferencesConnors KA, Amidon GL, Stella VJ. Chemical stability of pharmaceuticals, A handbook for pharmacists. New York: John Wiley & Sons, 1986. 1986;
    ReferencesMcEvoy GK (ed). AHFS Drug Information (current edition). Bethesda, MD: American Society of Health-System Pharmacists.
    Light Exposure
    Cyanocobalamin is light sensitive; protection from exposure to light is recommended for storage. If exposed to light, the organometallic bond may be cleaved. The extent of the decomposition increases with increasing light intensity.
    ReferencesAnon. Manufacturer's information and labeling. (Package insert).
    ReferencesConnors KA, Amidon GL, Stella VJ. Chemical stability of pharmaceuticals, A handbook for pharmacists. New York: John Wiley & Sons, 1986. 1986;
    ReferencesMcEvoy GK (ed). AHFS Drug Information (current edition). Bethesda, MD: American Society of Health-System Pharmacists.
    ReferencesZhang J, Guo X. Effect of light on the stability of procaine hydrochloride, atropine sulfate, and vitamin B12. Yaooxue Tongbao. 1984; 19
    Filtration
    Cyanocobalamin from Wyeth at 1 mcg/mL in dextrose 5% and in sodium chloride 0.9% did not display substantial loss due to binding to a 0.22-micron Ivex-2 cellulose ester membrane filter when filtered over 6 hours at 120 mL/hour.
    ReferencesButler LD, Munson JM, DeLuca PP. Effect of inline filtration on the potency of low-dose drugs. Am J Hosp Pharm. 1980; 37
    Sorption Leaching
    Cyanocobalamin from Organon 30 mcg/mL did not exhibit substantial sorption over 24 hours to a polyvinyl chloride (PVC) plastic test strip.
    ReferencesMoorhatch P, Chiou WL. Interactions between drugs and plastic intravenous fluid bags, part I: sorption studies on 17 drugs. Am J Hosp Pharm. 1974; 31
    Other Information
    Ascorbic acid: Cyanocobalamin is variously reported to be compatible and incompatible with ascorbic acid. Coles and Lees indicated that cyanocobalamin combined with ascorbic acid may be stored for 24 hours at room temperature protected from exposure to light without loss of vitamin activity. However, Ichikawa et al. studied the degradation of cyanocobalamin in aqueous pH 4.8 acetate buffer solution. Degradation of cyanocobalamin was not observed in the absence of ascorbic acid. However, adding ascorbic acid to the solution was found to substantially increase the rate of cyanocobalamin decomposition along with ascorbic acid decomposition. This effect was inhibited by the addition of sodium halides to the solution as might be found in a parenteral nutrition admixture. Potassium, magnesium, and calcium halides also exerted the stabilizing effect. Other Drugs: Cyanocobalamin is stated to be incompatible with a number of drugs including chlorpromazine hydrochloride, dextrose, phytonadione, prochlorperazine edisylate, and warfarin sodium, although some reported incompatibilities may have been due to hydroxocobalamin formerly present in the injection as a contaminant. It is also incompatible with heavy metals and oxidizing and reducing agents. Cyanocobalamin is stated to be compatible with other B vitamins and iron dextran.
    ReferencesColes CLJ, Lees KA. Additives to intravenous fluids. Pharm J. 1971; 206
    ReferencesIchikawa M, Ide N, Shiraishi S, et al. Effect of various halide salts on the incompatibility of cyanocobalamin and ascorbic acid in aqueous solution. Chem Pharm Bull. 2005; 53
    ReferencesMcEvoy GK (ed). AHFS Drug Information (current edition). Bethesda, MD: American Society of Health-System Pharmacists.
      Revision Date: 12/18/2018, 03:17:20 PMCopyright 2004-2024 by Lawrence A. Trissel. All Rights Reserved.

      References

      30895 - Nascobal (cyanocobalamin, vitamin B-12) nasal spray package insert. Spring Valley, NY: Par Pharmaceutical Companies, Inc.; 2018 Nov.43995 - Cyanocobalamin injection package insert. Shirley, NY: American Regent, Inc.; 2014 Apr.63836 - Bahadir A, Reis PG, Erduran E. Oral vitamin B12 treatment is effective for children with nutritional vitamin B12 deficiency. J Paediatr Child Health 2014;50:721-725.

      Adverse Reactions

      Severe

      • aluminum toxicity
      • anaphylactic shock
      • heart failure
      • pulmonary edema
      • thrombosis

      Mild

      • anxiety
      • asthenia
      • diarrhea
      • dizziness
      • dyspepsia
      • headache
      • hypoesthesia
      • infection
      • myalgia
      • nausea
      • paresthesias
      • pruritus
      • rash
      • vomiting

      0

      • back pain

      Moderate

      • dyspnea
      • edema
      • glossitis
      • hypokalemia
      • polycythemia
      • thrombocytosis

      In most cases, cyanocobalamin is nontoxic, even in large doses. Pruritus, transitory exanthema (rash), and a feeling of swelling (edema) of the entire body have been reported after IM injection.[30895] [43995] Some patients have also experienced a hypersensitivity reaction after IM injection that has resulted in anaphylactic shock and death.[43995]

      Pulmonary edema and congestive heart failure have been reported early in treatment with parenteral cyanocobalamin. Peripheral vascular thrombosis and peripheral vascular disorder have also occurred.[30895] [43995]

      Hypokalemia and thrombocytosis could occur upon conversion of severe megaloblastic anemia to normal erythropoiesis with intensive cyanocobalamin therapy. Monitor platelet count and serum potassium concentrations during therapy. Polycythemia vera has also been reported with parenteral cyanocobalamin.[30895] [43995]

      Musculoskeletal adverse reactions associated with cyanocobalamin administration include arthritis, asthenia, back pain, generalized pain, myalgia, abnormal gait.[30895]

      Respiratory adverse reactions reported with cyanocobalamin administration include dyspnea and rhinitis. Infection (i.e., common cold, sore throat) has also been reported.[30895]

      Gastrointestinal adverse reactions reported with cyanocobalamin administration include dyspepsia, glossitis, nausea, vomiting, and mild transient diarrhea.[30895] [43995]

      CNS adverse reactions including anxiety, dizziness, headache, hypoesthesia, incoordination, nervousness, and paresthesias have been reported with cyanocobalamin administration.[30895]

      Cyanocobalamin injection contains aluminum, and aluminum toxicity may occur with prolonged administration in high-risk patients, including those with renal impairment and premature neonates. Premature neonates are at particular risk for aluminum toxicity because of immature renal function, and they require large amounts of calcium and phosphate solutions, which contain aluminum. Research indicates that patients with renal impairment, who receive parenteral aluminum at more than 4 to 5 mcg/kg/day, may develop aluminum-related CNS and bone toxicities. Tissue loading may occur at lower administration rates.[43995]

      Revision Date: 05/02/2018, 08:09:12 AM

      References

      30895 - Nascobal (cyanocobalamin, vitamin B-12) nasal spray package insert. Spring Valley, NY: Par Pharmaceutical Companies, Inc.; 2018 Nov.43995 - Cyanocobalamin injection package insert. Shirley, NY: American Regent, Inc.; 2014 Apr.

      Contraindications/Precautions

      Absolute contraindications are italicized.

      • anemia
      • benzyl alcohol hypersensitivity
      • bone marrow suppression
      • breast-feeding
      • folate deficiency
      • geriatric
      • hereditary optic nerve atrophy (Leber's disease)
      • hypokalemia
      • infection
      • iron-deficiency anemia
      • neonates
      • polycythemia vera
      • pregnancy
      • renal failure
      • respiratory infection
      • rhinorrhea
      • uremia

      Cyanocobalamin is contraindicated in patients with cyanocobalamin hypersensitivity or hypersensitivity to any of the medication components. Cyanocobalamin is also contraindicated in patients with cobalt hypersensitivity because cyanocobalamin contains cobalt. In the case of suspected cobalt hypersensitivity, an intradermal test dose should be administered because anaphylactic shock and death have followed parenteral administration of cyanocobalamin.[30895][43995]

       

      Intranasal formulations of cyanocobalamin are not suitable for vitamin B12 absorption test (Schilling Test).[30895]

      Cyanocobalamin should not be used in patients with early hereditary optic nerve atrophy (Leber's disease). Optic nerve atrophy can worsen in patients whose cyanocobalamin levels are already elevated. Hydroxocobalamin is the preferred agent in this patient population.[30895]

      Most formulations of cyanocobalamin injection contain benzyl alcohol as a preservative. Benzyl alcohol may cause allergic reactions. Cyanocobalamin injections should be used cautiously in those patients with benzyl alcohol hypersensitivity. Cyanocobalamin preparations containing benzyl alcohol should be avoided in premature neonates because benzyl alcohol has been associated with 'gasping syndrome,' a potentially fatal condition characterized by metabolic acidosis and CNS, respiratory, circulatory, and renal dysfunction.[43995]

      Vitamin B12 deficiency can suppress the symptoms of polycythemia vera. Treatment with cyanocobalamin may unmask this condition.[30895]

      Folic acid is not a substitute for cyanocobalamin in the treatment of vitamin B12 deficiency, although it may improve vitamin B12 megaloblastic anemia. However, exclusive use of folic acid in treating vitamin B12 deficient megaloblastic anemia could result in progressive and irreversible neurologic damage. Additionally, exclusive use of cyanocobalamin in treating folate deficient megaloblastic anemia could delay or mask the real diagnosis. Before receiving folic acid or cyanocobalamin, patients should be assessed for deficiency and appropriate therapy started concurrently. The intranasal formulations are not approved to treat acute B12 deficiency; all hematologic parameters should be normal before beginning the cyanocobalamin intranasal formulations. Concurrent iron-deficiency anemia and folate deficiency may result in a blunted or impeded response to cyanocobalamin therapy.[30895] Secondary to an increase in red cell production with cyanocobalamin therapy, there is a corresponding increase in iron requirements; thus, patients should be closely monitored for the development of iron deficiency and treated accordingly.[33671]

      Certain conditions may blunt or impede therapeutic response to cyanocobalamin therapy, such as serious infection, uremia or renal failure, or drugs with bone marrow suppression properties (e.g., chloramphenicol).[33665] The mechanism appears to be interference with erythropoiesis.

      Patients with rhinorrhea (rhinitis) who are receiving the intranasal formulations of cyanocobalamin may experience decreased medication absorption secondary to nasal discharge. These patients may experience a blunted or impeded response to the intranasal medication. Treatment with intranasal cyanocobalamin should be delayed until symptoms resolve in patients with nasal congestion, allergic rhinitis, and upper respiratory infection. Intranasal cyanocobalamin therapy is not ideal for patients with chronic nasal symptoms or significant nasal pathology. If used in these patients, more frequent monitoring is required because of the potential for erratic or blunted absorption.[30895]

      Adequate studies in humans have not been conducted; however, no maternal or fetal complications have been associated with doses that are recommended during pregnancy, and appropriate treatment should not be withheld from pregnant women with vitamin B12 responsive anemias. Conversely, pernicious anemia resulting from vitamin B12 deficiency may cause infertility or poor pregnancy outcomes.[49221] Vitamin B12 deficiency has occurred in breast-fed infants of vegetarian mothers whose diets contain no animal products (e.g., eggs, dairy), even though the mothers had no symptoms of deficiency at the time. Maternal requirements for vitamin B12 increase during pregnancy. The usual daily recommended amounts of cyanocobalamin, vitamin B12 either through dietary intake or supplementation should be taken during pregnancy.[43995]

      Cyanocobalamin is distributed into breast milk in amounts similar to those in maternal plasma, and distribution in breast milk allows for adequate intakes of cyanocobalamin by breast-feeding infants. Adequate maternal intake is important for both the mother and infant during nursing, and maternal requirements for vitamin B12 increase during lactation. According to the manufacturer, the usual daily recommended amounts of cyanocobalamin, vitamin B12 for lactating women should be taken maternally during breast-feeding.[43995] The American Academy of Pediatrics considers vitamin B12 to be compatible with breast-feeding.[27500] Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

      Studies of intranasal cyanocobalamin did not include sufficient numbers of geriatric patients aged >= 65 years to determine whether the clinical response differs from that of younger patients. Other clinical reports have not identified differences in responses between elderly and younger patients. Generally, dose selection for elderly patients should be done with caution. Elderly patients tend to have a greater frequency of decreased hepatic, renal, or cardiac function, and also have concomitant disease or receiving other drug therapy. Start with doses at the lower end of the dosing range.

      Treatment of severe megaloblastic anemia with cyanocobalamin results in the conversion to normal erythropoiesis. The change to normal erythropoiesis may cause secondary development of hypokalemia and thrombocytosis, therefore, potassium levels and platelet counts should be closely monitored.[30895]

      Revision Date: 01/10/2019, 04:26:30 PM

      References

      27500 - American Academy of Pediatrics (AAP) Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics 2001;108(3):776-789.30895 - Nascobal (cyanocobalamin, vitamin B-12) nasal spray package insert. Spring Valley, NY: Par Pharmaceutical Companies, Inc.; 2018 Nov.33665 - Hydroxocobalamin injection package insert. Parsippany, NJ: Actavis Pharma, Inc.; 2017 Jan.33671 - Hvas AM. Diagnosis and treatment of vitamin b12 deficiency. An update. Haematologica 2006;91:1506-12.43995 - Cyanocobalamin injection package insert. Shirley, NY: American Regent, Inc.; 2014 Apr.49221 - Briggs GG, Freeman RK, Yaffee SJ. Vitamin B12. In: Drugs in pregnancy and lactation: a reference guide to fetal and neonatal risk. 8th ed. Philadelphia: Lippincott Williams & Wilkins: 2008;1969-21.

      Mechanism of Action

      Vitamin B12, or cyanocolbalamin, is essential to growth, cell reproduction, hematopoiesis, and nucleoprotein and myelin synthesis. Cells characterized by rapid division (epithelial cells, bone marrow, myeloid cells) appear to have the greatest requirement for cyanocobalamin. Vitamin B12 can be converted to coenzyme B12 in tissues; in this form it is essential for conversion of methylmalonate to succinate and synthesis of methionine from homocysteine (a reaction which also requires folate). In the absence of coenzyme B12, tetrahydrofolate cannot be regenerated from its inactive storage form, 5-methyl tetrahydrofolate, resulting in functional folate deficiency. Vitamin B12 also may be involved in maintaining sulfhydryl (SH) groups in the reduced form required by many SH-activated enzyme systems. Through these reactions, vitamin B12 is associated with fat and carbohydrate metabolism and protein synthesis. Vitamin B12 deficiency results in megaloblastic anemia, GI lesions, and neurologic damage (which begins with an inability to produce myelin and is followed by gradual degeneration of the axon and nerve head). Vitamin B12 requires an intrinsic factor-mediated active transport for absorption, therefore, lack of or inhibition of intrinsic factor results in pernicious anemia.

      Revision Date: 07/17/2015, 03:57:45 PM

      References

      Pharmacokinetics

      Cyanocobalamin is administered intranasally, orally, and parenterally, while hydroxocobalamin is administered only parenterally. Once absorbed, vitamin B12 is highly bound to transcobalamin II, a specific B-globulin carrier protein and is distributed and stored primarily in the liver as coenzyme B12. The bone marrow also stores a significant amount of the absorbed vitamin B12. Vitamin B12 crosses the placenta and is distributed into breast milk. Enterohepatic recirculation conserves systemic stores. Elimination is primarily through the bile; however, excess cyanocobalamin is excreted unchanged in the urine.[30895][43995]

      Route-Specific Pharmacokinetics

      Oral Route

      Oral absorption of vitamin B12 from the GI tract depends on the presence of adequate intrinsic factor, which is secreted from gastric mucosa. Drugs like the proton pump inhibitors (PPIs) (e.g., omeprazole and lansoprazole) have the potential for interfering with B12 absorption, presumably by impairing gastric acid and pepsin secretion, which are thought to be necessary for releasing B12 from its protein-binding sites in food.[23614] A vitamin B12-intrinsic factor complex is formed in the stomach following removal of cobalamin from dietary sources. This complex passes to the small intestine where attachment to receptor sites occurs on the ileal mucosa, and vitamin B12 is actively transported to portal plasma. Calcium and a pH greater than 6 are required for attachment to the receptor sites. When the receptor sites become saturated, absorption through passive diffusion occurs. Initially, oral doses of B12 and intrinsic factor (IF) will increase cobalamin levels in patients with pernicious anemia; however, 50% of patients develop intestinal antibodies to IF. After oral administration, peak plasma levels are attained in 8 to 12 hours.

      Intramuscular Route

      Peak plasma levels of cyanocobalamin are achieved within 1 hour after intramuscular injection. Within 48 hours after injection, 50% to 98% of the dose is excreted in the urine, with the majority within the first 8 hours.[43995]

      Other Route(s)

      Intranasal Route

      Cyanocobalamin is passively absorbed through the highly vascular nasal mucosa. In a pharmacokinetic study (n = 25) comparing the bioavailability of vitamin B12 intranasal spray to the intranasal gel, peak concentrations for the nasal spray were achieved within 1 to 2 hours of administration with a mean peak plasma concentration of approximately 748 +/- 549 pg/mL. Bioavailability of the intranasal spray was found to be 10% less than the intranasal gel. Because the intranasal forms have a lower absorption than the IM dosage form, intranasal B12 forms are administered once weekly. After 1 month of treatment in pernicious anemia patients, once weekly dosing of 500 mcg of B12 intranasal gel resulted in a statistically significant increase in B12 concentrations when compared to a once monthly 100 mcg IM dose.[30895]

      Revision Date: 01/10/2019, 03:39:04 PM

      References

      23614 - Marcuard SP, Albernaz L, Khazanie PG. Omeprazole therapy causes malabsorption of cyanocobalamin (vitamin B12). Ann Intern Med 1994;120:211-5.30895 - Nascobal (cyanocobalamin, vitamin B-12) nasal spray package insert. Spring Valley, NY: Par Pharmaceutical Companies, Inc.; 2018 Nov.43995 - Cyanocobalamin injection package insert. Shirley, NY: American Regent, Inc.; 2014 Apr.

      Pregnancy/Breast-feeding

      pregnancy

      Adequate studies in humans have not been conducted; however, no maternal or fetal complications have been associated with doses that are recommended during pregnancy, and appropriate treatment should not be withheld from pregnant women with vitamin B12 responsive anemias. Conversely, pernicious anemia resulting from vitamin B12 deficiency may cause infertility or poor pregnancy outcomes.[49221] Vitamin B12 deficiency has occurred in breast-fed infants of vegetarian mothers whose diets contain no animal products (e.g., eggs, dairy), even though the mothers had no symptoms of deficiency at the time. Maternal requirements for vitamin B12 increase during pregnancy. The usual daily recommended amounts of cyanocobalamin, vitamin B12 either through dietary intake or supplementation should be taken during pregnancy.[43995]

      breast-feeding

      Cyanocobalamin is distributed into breast milk in amounts similar to those in maternal plasma, and distribution in breast milk allows for adequate intakes of cyanocobalamin by breast-feeding infants. Adequate maternal intake is important for both the mother and infant during nursing, and maternal requirements for vitamin B12 increase during lactation. According to the manufacturer, the usual daily recommended amounts of cyanocobalamin, vitamin B12 for lactating women should be taken maternally during breast-feeding.[43995] The American Academy of Pediatrics considers vitamin B12 to be compatible with breast-feeding.[27500] Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

      Revision Date: 01/10/2019, 04:26:30 PM

      References

      27500 - American Academy of Pediatrics (AAP) Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics 2001;108(3):776-789.30895 - Nascobal (cyanocobalamin, vitamin B-12) nasal spray package insert. Spring Valley, NY: Par Pharmaceutical Companies, Inc.; 2018 Nov.43995 - Cyanocobalamin injection package insert. Shirley, NY: American Regent, Inc.; 2014 Apr.49221 - Briggs GG, Freeman RK, Yaffee SJ. Vitamin B12. In: Drugs in pregnancy and lactation: a reference guide to fetal and neonatal risk. 8th ed. Philadelphia: Lippincott Williams & Wilkins: 2008;1969-21.

      Interactions

      Level 2 (Major)

      • Baloxavir Marboxil
      • Delafloxacin
      • Edetate Calcium Disodium, Calcium EDTA
      • Eltrombopag
      • Estramustine
      • Ethotoin
      • Moxifloxacin
      • Trientine

      Level 3 (Moderate)

      • Abacavir; Dolutegravir; Lamivudine
      • Alendronate
      • Alendronate; Cholecalciferol
      • Aliskiren; Hydrochlorothiazide, HCTZ
      • Amiloride; Hydrochlorothiazide, HCTZ
      • Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ
      • Atenolol; Chlorthalidone
      • Atracurium
      • Azilsartan; Chlorthalidone
      • Benazepril; Hydrochlorothiazide, HCTZ
      • Bictegravir; Emtricitabine; Tenofovir Alafenamide
      • Bismuth Subcitrate Potassium; Metronidazole; Tetracycline
      • Bismuth Subsalicylate; Metronidazole; Tetracycline
      • Bisoprolol; Hydrochlorothiazide, HCTZ
      • Cabotegravir
      • Cabotegravir; Rilpivirine
      • Calcifediol
      • Calcitonin
      • Calcitriol
      • Calcium Phosphate, Supersaturated
      • Candesartan; Hydrochlorothiazide, HCTZ
      • Captopril; Hydrochlorothiazide, HCTZ
      • Cardiac glycosides
      • Chloramphenicol
      • Chlorothiazide
      • Chlorthalidone
      • Ciprofloxacin
      • Cisatracurium
      • Colesevelam
      • Demeclocycline
      • Digoxin
      • Dolutegravir
      • Dolutegravir; Lamivudine
      • Dolutegravir; Rilpivirine
      • Doxercalciferol
      • Doxycycline
      • Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide
      • Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate
      • Enalapril; Hydrochlorothiazide, HCTZ
      • Eprosartan; Hydrochlorothiazide, HCTZ
      • Etidronate
      • Fosinopril; Hydrochlorothiazide, HCTZ
      • Hydrochlorothiazide, HCTZ
      • Hydrochlorothiazide, HCTZ; Moexipril
      • Ibandronate
      • Ibritumomab Tiuxetan
      • Irbesartan; Hydrochlorothiazide, HCTZ
      • Levofloxacin
      • Levothyroxine
      • Levothyroxine; Liothyronine (Porcine)
      • Levothyroxine; Liothyronine (Synthetic)
      • Liothyronine
      • Lisinopril; Hydrochlorothiazide, HCTZ
      • Lithium
      • Losartan; Hydrochlorothiazide, HCTZ
      • Metolazone
      • Metoprolol; Hydrochlorothiazide, HCTZ
      • Minocycline
      • Neuromuscular blockers
      • Ofloxacin
      • Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ
      • Olmesartan; Hydrochlorothiazide, HCTZ
      • Omadacycline
      • Pancuronium
      • Parathyroid Hormone
      • Paricalcitol
      • Phosphorated Carbohydrate Solution
      • Phosphorus
      • Potassium Phosphate
      • Potassium Phosphate; Sodium Phosphate
      • Quinapril; Hydrochlorothiazide, HCTZ
      • Risedronate
      • Rocuronium
      • Sarecycline
      • Sodium Fluoride
      • Sodium Phosphate Monobasic Monohydrate; Sodium Phosphate Dibasic Anhydrous
      • Spironolactone; Hydrochlorothiazide, HCTZ
      • Succinylcholine
      • Telmisartan; Hydrochlorothiazide, HCTZ
      • Teriparatide
      • Tetracycline
      • Tetracyclines
      • Thiazide diuretics
      • Thyroid hormones
      • Triamterene; Hydrochlorothiazide, HCTZ
      • Valsartan; Hydrochlorothiazide, HCTZ
      • Vecuronium
      • Vitamin D analogs

      Level 4 (Minor)

      • Alogliptin; Metformin
      • Amlodipine
      • Amlodipine; Atorvastatin
      • Amlodipine; Benazepril
      • Amlodipine; Celecoxib
      • Amlodipine; Olmesartan
      • Amlodipine; Valsartan
      • Atenolol
      • Calcipotriene
      • Calcipotriene; Betamethasone
      • Calcium-channel blockers
      • Canagliflozin; Metformin
      • Clevidipine
      • Conjugated Estrogens
      • Conjugated Estrogens; Bazedoxifene
      • Conjugated Estrogens; Medroxyprogesterone
      • Dapagliflozin; Metformin
      • Desogestrel; Ethinyl Estradiol
      • Dienogest; Estradiol valerate
      • Diltiazem
      • Drospirenone; Estetrol
      • Drospirenone; Estradiol
      • Drospirenone; Ethinyl Estradiol
      • Drospirenone; Ethinyl Estradiol; Levomefolate
      • Elagolix; Estradiol; Norethindrone acetate
      • Empagliflozin; Linagliptin; Metformin
      • Empagliflozin; Metformin
      • Ertugliflozin; Metformin
      • Esterified Estrogens
      • Esterified Estrogens; Methyltestosterone
      • Estradiol
      • Estradiol; Levonorgestrel
      • Estradiol; Norethindrone
      • Estradiol; Norgestimate
      • Estradiol; Progesterone
      • Estrogens
      • Estropipate
      • Ethinyl Estradiol; Norelgestromin
      • Ethinyl Estradiol; Norethindrone Acetate
      • Ethinyl Estradiol; Norgestrel
      • Ethynodiol Diacetate; Ethinyl Estradiol
      • Etonogestrel; Ethinyl Estradiol
      • Felodipine
      • food
      • Glipizide; Metformin
      • Glyburide; Metformin
      • Isradipine
      • Levamlodipine
      • Levonorgestrel; Ethinyl Estradiol
      • Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate
      • Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate
      • Linagliptin; Metformin
      • Metformin
      • Metformin; Repaglinide
      • Metformin; Saxagliptin
      • Metformin; Sitagliptin
      • Neomycin
      • Nicardipine
      • Nifedipine
      • Nimodipine
      • Nisoldipine
      • Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate
      • Norethindrone; Ethinyl Estradiol
      • Norethindrone; Ethinyl Estradiol; Ferrous fumarate
      • Norgestimate; Ethinyl Estradiol
      • Octreotide
      • Perindopril; Amlodipine
      • Pioglitazone; Metformin
      • Relugolix; Estradiol; Norethindrone acetate
      • Segesterone Acetate; Ethinyl Estradiol
      • Telmisartan; Amlodipine
      • Trandolapril; Verapamil
      • Verapamil
      • Vitamin A
      Abacavir; Dolutegravir; Lamivudine: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking supplements containing calcium if given under fasting conditions. When taken with food, dolutegravir and supplements containing calcium can be taken at the same time. Simultaneous administration under fasted conditions may result in reduced bioavailability of dolutegravir. [55594] Alendronate: (Moderate) Separate administration of alendronate and calcium-containing supplements by at least 30 minutes. Calcium will interfere with the absorption of alendronate. [28644] [52249] Alendronate; Cholecalciferol: (Moderate) Separate administration of alendronate and calcium-containing supplements by at least 30 minutes. Calcium will interfere with the absorption of alendronate. [28644] [52249] Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium. [48850] [63883] Alogliptin; Metformin: (Minor) Metformin may result in suboptimal oral vitamin B12 absorption by competitively blocking the calcium-dependent binding of the intrinsic factor-vitamin B12 complex to its receptor. Regular measurement of hematologic parameters is recommended in all patients on chronic metformin treatment; abnormalities should be investigated. [5280] Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium. [48850] [63883] Amlodipine: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers. [53985] [69004] Amlodipine; Atorvastatin: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers. [53985] [69004] Amlodipine; Benazepril: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers. [53985] [69004] Amlodipine; Celecoxib: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers. [53985] [69004] Amlodipine; Olmesartan: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers. [53985] [69004] Amlodipine; Valsartan: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers. [53985] [69004] Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium. [48850] [63883] (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers. [53985] [69004] Atenolol: (Minor) Calcium antacids (e.g., calcium carbonate) and supplements (e.g., other oral calcium salts) have been reported to reduce the mean peak concentrations by 51% and the AUC of atenolol by 32%. In another study, antacids reduced the AUC of atenolol by 33%. Separate doses of atenolol and calcium-containing antacids or supplements by at least 2 hours to minimize this potential interaction,. However, most clinicians consider the interaction of atenolol with antacids to be of minor clinical significance, since clinical efficacy (heart rate and blood pressure parameters) appear to be unchanged under usual intermittent clinical use. [4382] [4384] Atenolol; Chlorthalidone: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium. [48850] [63883] (Minor) Calcium antacids (e.g., calcium carbonate) and supplements (e.g., other oral calcium salts) have been reported to reduce the mean peak concentrations by 51% and the AUC of atenolol by 32%. In another study, antacids reduced the AUC of atenolol by 33%. Separate doses of atenolol and calcium-containing antacids or supplements by at least 2 hours to minimize this potential interaction,. However, most clinicians consider the interaction of atenolol with antacids to be of minor clinical significance, since clinical efficacy (heart rate and blood pressure parameters) appear to be unchanged under usual intermittent clinical use. [4382] [4384] Atracurium: (Moderate) Concomitant use of neuromuscular blockers and calcium may result in resistance to neuromuscular blockade. Calcium antagonizes the potentiating effect of magnesium on neuromuscular blockade. Also, calcium triggers acetylcholine release, and therefore, may both reduce the sensitivity to neuromuscular blockers and decrease the duration of neuromuscular blockade. [65345] Azilsartan; Chlorthalidone: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium. [48850] [63883] Baloxavir Marboxil: (Major) Do not administer baloxavir with products that contain calcium. Polyvalent cations, such as calcium, can chelate with baloxavir, reducing its absorption. [63687] Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium. [48850] [63883] Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) Administer bictegravir with food at the same time as oral calcium supplements. Routine administration of bictegravir under fasting conditions simultaneously with, or 2 hours after, calcium supplements is not recommended. Calcium is a polyvalent cation that can bind bictegravir in the GI tract. Taking these drugs simultaneously without food results in reduced bioavailability of bictegravir. In drug interaction studies, simultaneous administration of bictegravir with another calcium supplement under fasted conditions decreased the mean AUC of bictegravir by approximately 33%. [62852] Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines. [4691] [6707] Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines. [4691] [6707] Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium. [48850] [63883] Cabotegravir: (Moderate) Administer oral calcium at least two hours before or four hours after taking oral cabotegravir. Calcium is a polyvalent cation that can bind cabotegravir in the GI tract. Taking these drugs simultaneously may result in reduced oral bioavailability of cabotegravir. [66315] Cabotegravir; Rilpivirine: (Moderate) Administer oral calcium at least two hours before or four hours after taking oral cabotegravir. Calcium is a polyvalent cation that can bind cabotegravir in the GI tract. Taking these drugs simultaneously may result in reduced oral bioavailability of cabotegravir. [66315] Calcifediol: (Moderate) Monitor serum calcium concentrations during concomitant use of high doses of calcium and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration. [28490] [30153] [60895] Calcipotriene: (Minor) There is evidence that calcipotriene can be absorbed in amounts that are sufficient to produce systemic effects, including elevated serum calcium; hypercalcemia has been observed in normal prescription use. Use calcipotriene cautiously with other agents that can produce hypercalcemia (e.g., calcium salts or supplements including calcium carbonate). [31986] Calcipotriene; Betamethasone: (Minor) There is evidence that calcipotriene can be absorbed in amounts that are sufficient to produce systemic effects, including elevated serum calcium; hypercalcemia has been observed in normal prescription use. Use calcipotriene cautiously with other agents that can produce hypercalcemia (e.g., calcium salts or supplements including calcium carbonate). [31986] Calcitonin: (Moderate) Calcitonin is given to hypercalcemic patients to reduce serum calcium concentrations. For the treatment of hypercalcemia, calcium supplements should be avoided. Calcium salts, including calcium carbonate, can elevate serum calcium concentrations and antagonize the effects of the calcitonin for this condition. For the treatment of osteoporosis adequate intake of calcium salts are necessary in conjunction with calcitonin. An increase in serum calcium concentrations helps to reduce bone resorption and loss of bone mass, and offsets the effect of calcitonin in lowering serum calcium levels. [27980] Calcitriol: (Moderate) Monitor serum calcium concentrations during concomitant use of high doses of calcium and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration. [28490] [30153] [60895] Calcium Phosphate, Supersaturated: (Moderate) The concomitant use of oral sodium phosphate monobasic monohydrate; sodium phosphate dibasic anhydrous preparations in conjunction with antacids containing calcium (e.g., calcium carbonate, calcium salts) may bind the phosphate in the stomach and reduce its absorption. If the patient requires multiple mineral supplements or concurrent use of antacids, it is prudent to separate the administration of sodium phosphate salts from calcium containing products by at least one hour. [7800] Calcium-channel blockers: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers. [53985] [69004] Canagliflozin; Metformin: (Minor) Metformin may result in suboptimal oral vitamin B12 absorption by competitively blocking the calcium-dependent binding of the intrinsic factor-vitamin B12 complex to its receptor. Regular measurement of hematologic parameters is recommended in all patients on chronic metformin treatment; abnormalities should be investigated. [5280] Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium. [48850] [63883] Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium. [48850] [63883] Cardiac glycosides: (Moderate) Monitor for signs and symptoms of digoxin toxicity during concomitant calcium use. Hypercalcemia may predispose persons to digoxin toxicity. If IV calcium is administered rapidly in a person receiving digoxin, serious arrhythmias may occur. Monitor ECG and calcium concentrations closely during IV calcium and digoxin administration. [28272] [53985] Chloramphenicol: (Moderate) If use together is necessary, monitor for reduced efficacy of cyanocobalamin (vitamin B12), and if needed, consider an alternative therapy. Chloramphenicol can cause bone marrow depression and inhibit red blood cell maturation, which may reduce the efficacy of vitamin B12 in the treatment of anemia. [29949] [30895] Chlorothiazide: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium. [48850] [63883] Chlorthalidone: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium. [48850] [63883] Ciprofloxacin: (Moderate) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain calcium. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain calcium. [43411] [43570] Cisatracurium: (Moderate) Concomitant use of neuromuscular blockers and calcium may result in resistance to neuromuscular blockade. Calcium antagonizes the potentiating effect of magnesium on neuromuscular blockade. Also, calcium triggers acetylcholine release, and therefore, may both reduce the sensitivity to neuromuscular blockers and decrease the duration of neuromuscular blockade. [65345] Clevidipine: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers. [53985] [69004] Colesevelam: (Moderate) It is not known if colesevelam can reduce the absorption of oral vitamin supplements including fat soluble vitamins A, D, E, and K. To minimize potential interactions, administer vitamins at least 4 hours before colesevelam. [7576] Conjugated Estrogens: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis. [6395] Conjugated Estrogens; Bazedoxifene: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis. [6395] Conjugated Estrogens; Medroxyprogesterone: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis. [6395] Dapagliflozin; Metformin: (Minor) Metformin may result in suboptimal oral vitamin B12 absorption by competitively blocking the calcium-dependent binding of the intrinsic factor-vitamin B12 complex to its receptor. Regular measurement of hematologic parameters is recommended in all patients on chronic metformin treatment; abnormalities should be investigated. [5280] Delafloxacin: (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after oral products that contain calcium. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with fluoroquinolone bioavailability include antacids and multivitamins that contain calcium. [62028] Demeclocycline: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines. [4691] [6707] Desogestrel; Ethinyl Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis. [6395] Dienogest; Estradiol valerate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis. [6395] Digoxin: (Moderate) Monitor for signs and symptoms of digoxin toxicity during concomitant calcium use. Hypercalcemia may predispose persons to digoxin toxicity. If IV calcium is administered rapidly in a person receiving digoxin, serious arrhythmias may occur. Monitor ECG and calcium concentrations closely during IV calcium and digoxin administration. [28272] [53985] Diltiazem: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers. [53985] [69004] Dolutegravir: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking supplements containing calcium if given under fasting conditions. When taken with food, dolutegravir and supplements containing calcium can be taken at the same time. Simultaneous administration under fasted conditions may result in reduced bioavailability of dolutegravir. [55594] Dolutegravir; Lamivudine: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking supplements containing calcium if given under fasting conditions. When taken with food, dolutegravir and supplements containing calcium can be taken at the same time. Simultaneous administration under fasted conditions may result in reduced bioavailability of dolutegravir. [55594] Dolutegravir; Rilpivirine: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking supplements containing calcium if given under fasting conditions. When taken with food, dolutegravir and supplements containing calcium can be taken at the same time. Simultaneous administration under fasted conditions may result in reduced bioavailability of dolutegravir. [55594] Doxercalciferol: (Moderate) Monitor serum calcium concentrations during concomitant use of high doses of calcium and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration. [28490] [30153] [60895] Doxycycline: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines. [4691] [6707] Drospirenone; Estetrol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis. [6395] Drospirenone; Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis. [6395] Drospirenone; Ethinyl Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis. [6395] Drospirenone; Ethinyl Estradiol; Levomefolate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis. [6395] Edetate Calcium Disodium, Calcium EDTA: (Major) Because edetate disodium chelates and lowers serum calcium, oral or parenteral calcium salts should not be administered concomitantly. [7090] Elagolix; Estradiol; Norethindrone acetate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis. [6395] Eltrombopag: (Major) Eltrombopag chelates polyvalent cations (e.g., calcium, aluminum, and magnesium) in food, mineral supplements, and antacids. In a clinical study, systemic exposure to eltrombopag was decreased by 70% when it was administered with a polyvalent cation-containing antacid. Administer eltrombopag at least 2 hours before or 4 hours after any oral products containing polyvalent cations, such as aluminum salts, (like aluminum hydroxide), calcium salts, (including calcium carbonate), and magnesium salts. [40392] Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Separate administration of elvitegravir and calcium by at least 2 hours. Due to the formation of ionic complexes in the gastrointestinal tract, simultaneous administration results in lower elvitegravir plasma concentrations. [51664] [58001] Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Separate administration of elvitegravir and calcium by at least 2 hours. Due to the formation of ionic complexes in the gastrointestinal tract, simultaneous administration results in lower elvitegravir plasma concentrations. [51664] [58001] Empagliflozin; Linagliptin; Metformin: (Minor) Metformin may result in suboptimal oral vitamin B12 absorption by competitively blocking the calcium-dependent binding of the intrinsic factor-vitamin B12 complex to its receptor. Regular measurement of hematologic parameters is recommended in all patients on chronic metformin treatment; abnormalities should be investigated. [5280] Empagliflozin; Metformin: (Minor) Metformin may result in suboptimal oral vitamin B12 absorption by competitively blocking the calcium-dependent binding of the intrinsic factor-vitamin B12 complex to its receptor. Regular measurement of hematologic parameters is recommended in all patients on chronic metformin treatment; abnormalities should be investigated. [5280] Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium. [48850] [63883] Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium. [48850] [63883] Ertugliflozin; Metformin: (Minor) Metformin may result in suboptimal oral vitamin B12 absorption by competitively blocking the calcium-dependent binding of the intrinsic factor-vitamin B12 complex to its receptor. Regular measurement of hematologic parameters is recommended in all patients on chronic metformin treatment; abnormalities should be investigated. [5280] Esterified Estrogens: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis. [6395] Esterified Estrogens; Methyltestosterone: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis. [6395] Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis. [6395] Estradiol; Levonorgestrel: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis. [6395] Estradiol; Norethindrone: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis. [6395] Estradiol; Norgestimate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis. [6395] Estradiol; Progesterone: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis. [6395] Estramustine: (Major) Administration of estramustine with calcium impairs the oral absorption of estramustine significantly, due to formation of a calcium-phosphate complex. Calcium-containing drugs must not be taken simultaneously with estramustine. Patients should be instructed to take estramustine with water at least 1 hour before or 2 hours after calcium supplements. [47275] Estrogens: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis. [6395] Estropipate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis. [6395] Ethinyl Estradiol; Norelgestromin: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis. [6395] Ethinyl Estradiol; Norethindrone Acetate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis. [6395] Ethinyl Estradiol; Norgestrel: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis. [6395] Ethotoin: (Major) Oral absorption of phenytoin can be reduced by calcium salts. Calcium salts can form complexes that are nonabsorbable. Separating the administration of phenytoin and calcium salts by at least 2 hours to help avoid this interaction. A similar interaction may occur with ethotoin. [23674] Ethynodiol Diacetate; Ethinyl Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis. [6395] Etidronate: (Moderate) Separate administration of oral etidronate and calcium-containing supplements by at least 2 hours. Calcium will interfere with the absorption of oral etidronate. [28655] Etonogestrel; Ethinyl Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis. [6395] Felodipine: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers. [53985] [69004] Food: (Minor) The intranasal forms of cyanocobalamin, vitamin B12, should be administered at least one hour before or one hour after ingestion of hot foods or liquids. Hot foods may cause nasal secretions and a resulting loss of medication or medication efficacy. Interactions between foods and oral or injectable forms of cyanocobalamin are not expected. [30895] Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium. [48850] [63883] Glipizide; Metformin: (Minor) Metformin may result in suboptimal oral vitamin B12 absorption by competitively blocking the calcium-dependent binding of the intrinsic factor-vitamin B12 complex to its receptor. Regular measurement of hematologic parameters is recommended in all patients on chronic metformin treatment; abnormalities should be investigated. [5280] Glyburide; Metformin: (Minor) Metformin may result in suboptimal oral vitamin B12 absorption by competitively blocking the calcium-dependent binding of the intrinsic factor-vitamin B12 complex to its receptor. Regular measurement of hematologic parameters is recommended in all patients on chronic metformin treatment; abnormalities should be investigated. [5280] Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium. [48850] [63883] Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium. [48850] [63883] Ibandronate: (Moderate) Separate administration of oral ibandronate and calcium-containing supplements by at least 1 hour. Calcium will interfere with the absorption of oral ibandronate. [29558] Ibritumomab Tiuxetan: (Moderate) The oral absorption of phosphorus is reduced by ingestion of pharmacologic doses of calcium carbonate or other phosphate-lowering calcium salts (e.g., calcium acetate). There is, however, no significant interference with phosphorus absorption by oral dietary calcium at intakes within the typical adult range. If the patient requires multiple calcium supplements or a calcium-containing antacid, it may be wise to separate the administration of phosphorus salts from calcium-containing products. In some instances the administration of calcium salts or calcium carbonate is used therapeutically (e.g., uremia) to decrease serum phosphorus levels, so the administration of phosphorus supplements would dynamically counteract the intended use of calcium in these settings, assuming hypophosphatemia is not present. Appropriate calcium-phosphorus ratios in vivo are important for proper calcium homeostasis in tissues and bone; if the serum ionized calcium concentration is elevated, the concomitant use of calcium salts and phosphorus salts may increase the risk of calcium deposition in soft tissue. [31028] [57713] [57714] [57715] Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium. [48850] [63883] Isradipine: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers. [53985] [69004] Levamlodipine: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers. [53985] [69004] Levofloxacin: (Moderate) Administer oral products that contain calcium at least 2 hours before or 2 hours after orally administered levofloxacin. Levofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Chelation of divalent cations with levofloxacin is less than with other quinolones. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain calcium. [27973] [40284] [40285] [40286] [40287] [65562] Levonorgestrel; Ethinyl Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis. [6395] Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis. [6395] Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis. [6395] Levothyroxine: (Moderate) Thyroid hormones should be administered at least 4 hours before or after the ingestion of oral calcium supplements. Calcium salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of thyroid hormones with oral calcium supplements. [27979] [43943] [44355] [53562] Levothyroxine; Liothyronine (Porcine): (Moderate) Thyroid hormones should be administered at least 4 hours before or after the ingestion of oral calcium supplements. Calcium salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of thyroid hormones with oral calcium supplements. [27979] [43943] [44355] [53562] Levothyroxine; Liothyronine (Synthetic): (Moderate) Thyroid hormones should be administered at least 4 hours before or after the ingestion of oral calcium supplements. Calcium salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of thyroid hormones with oral calcium supplements. [27979] [43943] [44355] [53562] Linagliptin; Metformin: (Minor) Metformin may result in suboptimal oral vitamin B12 absorption by competitively blocking the calcium-dependent binding of the intrinsic factor-vitamin B12 complex to its receptor. Regular measurement of hematologic parameters is recommended in all patients on chronic metformin treatment; abnormalities should be investigated. [5280] Liothyronine: (Moderate) Thyroid hormones should be administered at least 4 hours before or after the ingestion of oral calcium supplements. Calcium salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of thyroid hormones with oral calcium supplements. [27979] [43943] [44355] [53562] Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium. [48850] [63883] Lithium: (Moderate) Monitor serum calcium concentrations closely if concomitant use of calcium and lithium is necessary. Concomitant use may increase the risk of hypercalcemia. [53985] Losartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium. [48850] [63883] Metformin: (Minor) Metformin may result in suboptimal oral vitamin B12 absorption by competitively blocking the calcium-dependent binding of the intrinsic factor-vitamin B12 complex to its receptor. Regular measurement of hematologic parameters is recommended in all patients on chronic metformin treatment; abnormalities should be investigated. [5280] Metformin; Repaglinide: (Minor) Metformin may result in suboptimal oral vitamin B12 absorption by competitively blocking the calcium-dependent binding of the intrinsic factor-vitamin B12 complex to its receptor. Regular measurement of hematologic parameters is recommended in all patients on chronic metformin treatment; abnormalities should be investigated. [5280] Metformin; Saxagliptin: (Minor) Metformin may result in suboptimal oral vitamin B12 absorption by competitively blocking the calcium-dependent binding of the intrinsic factor-vitamin B12 complex to its receptor. Regular measurement of hematologic parameters is recommended in all patients on chronic metformin treatment; abnormalities should be investigated. [5280] Metformin; Sitagliptin: (Minor) Metformin may result in suboptimal oral vitamin B12 absorption by competitively blocking the calcium-dependent binding of the intrinsic factor-vitamin B12 complex to its receptor. Regular measurement of hematologic parameters is recommended in all patients on chronic metformin treatment; abnormalities should be investigated. [5280] Metolazone: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium. [48850] [63883] Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium. [48850] [63883] Minocycline: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines. [4691] [6707] Moxifloxacin: (Major) Administer oral moxifloxacin at least 4 hours before or 8 hours after oral products that contain calcium. Moxifloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain calcium. [27973] [28423] [40284] [40285] [40286] [40287] Neomycin: (Minor) Oral neomycin has been shown to inhibit the gastrointestinal absorption of cyanocobalamin, Vitamin B12. Caution is warranted with concomitant use. [40041] Neuromuscular blockers: (Moderate) Concomitant use of neuromuscular blockers and calcium may result in resistance to neuromuscular blockade. Calcium antagonizes the potentiating effect of magnesium on neuromuscular blockade. Also, calcium triggers acetylcholine release, and therefore, may both reduce the sensitivity to neuromuscular blockers and decrease the duration of neuromuscular blockade. [65345] Nicardipine: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers. [53985] [69004] NIFEdipine: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers. [53985] [69004] Nimodipine: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers. [53985] [69004] Nisoldipine: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers. [53985] [69004] Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis. [6395] Norethindrone; Ethinyl Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis. [6395] Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis. [6395] Norgestimate; Ethinyl Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis. [6395] Octreotide: (Minor) Depressed levels of cyanocobalamin, vitamin B12, and abnormal Schilling's test have been reported in patients receiving octreotide. [7659] Ofloxacin: (Moderate) Administer oral products that contain calcium at least 2 hours before or 2 hours after ofloxacin. Ofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain calcium. [30738] Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium. [48850] [63883] (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers. [53985] [69004] Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium. [48850] [63883] Omadacycline: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines. [4691] [6707] Pancuronium: (Moderate) Concomitant use of neuromuscular blockers and calcium may result in resistance to neuromuscular blockade. Calcium antagonizes the potentiating effect of magnesium on neuromuscular blockade. Also, calcium triggers acetylcholine release, and therefore, may both reduce the sensitivity to neuromuscular blockers and decrease the duration of neuromuscular blockade. [65345] Parathyroid Hormone: (Moderate) Monitor serum calcium concentrations closely if concomitant use of calcium and parathyroid hormone is necessary. Concomitant use may increase the risk of hypercalcemia. [53985] Paricalcitol: (Moderate) Monitor serum calcium concentrations during concomitant use of high doses of calcium and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration. [28490] [30153] [60895] Perindopril; Amlodipine: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers. [53985] [69004] Phosphorated Carbohydrate Solution: (Moderate) The oral absorption of phosphorus is reduced by ingestion of pharmacologic doses of calcium carbonate or other phosphate-lowering calcium salts (e.g., calcium acetate). There is, however, no significant interference with phosphorus absorption by oral dietary calcium at intakes within the typical adult range. If the patient requires multiple calcium supplements or a calcium-containing antacid, it may be wise to separate the administration of phosphorus salts from calcium-containing products. In some instances the administration of calcium salts or calcium carbonate is used therapeutically (e.g., uremia) to decrease serum phosphorus levels, so the administration of phosphorus supplements would dynamically counteract the intended use of calcium in these settings, assuming hypophosphatemia is not present. Appropriate calcium-phosphorus ratios in vivo are important for proper calcium homeostasis in tissues and bone; if the serum ionized calcium concentration is elevated, the concomitant use of calcium salts and phosphorus salts may increase the risk of calcium deposition in soft tissue. [31028] [57713] [57714] [57715] Phosphorus: (Moderate) The oral absorption of phosphorus is reduced by ingestion of pharmacologic doses of calcium carbonate or other phosphate-lowering calcium salts (e.g., calcium acetate). There is, however, no significant interference with phosphorus absorption by oral dietary calcium at intakes within the typical adult range. If the patient requires multiple calcium supplements or a calcium-containing antacid, it may be wise to separate the administration of phosphorus salts from calcium-containing products. In some instances the administration of calcium salts or calcium carbonate is used therapeutically (e.g., uremia) to decrease serum phosphorus levels, so the administration of phosphorus supplements would dynamically counteract the intended use of calcium in these settings, assuming hypophosphatemia is not present. Appropriate calcium-phosphorus ratios in vivo are important for proper calcium homeostasis in tissues and bone; if the serum ionized calcium concentration is elevated, the concomitant use of calcium salts and phosphorus salts may increase the risk of calcium deposition in soft tissue. [31028] [57713] [57714] [57715] Pioglitazone; Metformin: (Minor) Metformin may result in suboptimal oral vitamin B12 absorption by competitively blocking the calcium-dependent binding of the intrinsic factor-vitamin B12 complex to its receptor. Regular measurement of hematologic parameters is recommended in all patients on chronic metformin treatment; abnormalities should be investigated. [5280] Potassium Phosphate: (Moderate) The oral absorption of phosphorus is reduced by ingestion of pharmacologic doses of calcium carbonate or other phosphate-lowering calcium salts (e.g., calcium acetate). There is, however, no significant interference with phosphorus absorption by oral dietary calcium at intakes within the typical adult range. If the patient requires multiple calcium supplements or a calcium-containing antacid, it may be wise to separate the administration of phosphorus salts from calcium-containing products. In some instances the administration of calcium salts or calcium carbonate is used therapeutically (e.g., uremia) to decrease serum phosphorus levels, so the administration of phosphorus supplements would dynamically counteract the intended use of calcium in these settings, assuming hypophosphatemia is not present. Appropriate calcium-phosphorus ratios in vivo are important for proper calcium homeostasis in tissues and bone; if the serum ionized calcium concentration is elevated, the concomitant use of calcium salts and phosphorus salts may increase the risk of calcium deposition in soft tissue. [31028] [57713] [57714] [57715] Potassium Phosphate; Sodium Phosphate: (Moderate) The oral absorption of phosphorus is reduced by ingestion of pharmacologic doses of calcium carbonate or other phosphate-lowering calcium salts (e.g., calcium acetate). There is, however, no significant interference with phosphorus absorption by oral dietary calcium at intakes within the typical adult range. If the patient requires multiple calcium supplements or a calcium-containing antacid, it may be wise to separate the administration of phosphorus salts from calcium-containing products. In some instances the administration of calcium salts or calcium carbonate is used therapeutically (e.g., uremia) to decrease serum phosphorus levels, so the administration of phosphorus supplements would dynamically counteract the intended use of calcium in these settings, assuming hypophosphatemia is not present. Appropriate calcium-phosphorus ratios in vivo are important for proper calcium homeostasis in tissues and bone; if the serum ionized calcium concentration is elevated, the concomitant use of calcium salts and phosphorus salts may increase the risk of calcium deposition in soft tissue. [31028] [57713] [57714] [57715] Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium. [48850] [63883] Relugolix; Estradiol; Norethindrone acetate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis. [6395] Risedronate: (Moderate) Separate administration of oral risedronate and calcium-containing supplements by at least 2 hours. Calcium will interfere with the absorption of oral risedronate. [29352] [42080] Rocuronium: (Moderate) Concomitant use of neuromuscular blockers and calcium may result in resistance to neuromuscular blockade. Calcium antagonizes the potentiating effect of magnesium on neuromuscular blockade. Also, calcium triggers acetylcholine release, and therefore, may both reduce the sensitivity to neuromuscular blockers and decrease the duration of neuromuscular blockade. [65345] Sarecycline: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines. [4691] [6707] Segesterone Acetate; Ethinyl Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis. [6395] Sodium Fluoride: (Moderate) Absorption of sodium fluoride may be reduced by concomitant use of antacids that contain magnesium, aluminum, or calcium. An interval of at least 2 hours is advisable between administration of sodium fluoride and antacids. [6085] Sodium Phosphate Monobasic Monohydrate; Sodium Phosphate Dibasic Anhydrous: (Moderate) The concomitant use of oral sodium phosphate monobasic monohydrate; sodium phosphate dibasic anhydrous preparations in conjunction with antacids containing calcium (e.g., calcium carbonate, calcium salts) may bind the phosphate in the stomach and reduce its absorption. If the patient requires multiple mineral supplements or concurrent use of antacids, it is prudent to separate the administration of sodium phosphate salts from calcium containing products by at least one hour. [7800] Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium. [48850] [63883] Succinylcholine: (Moderate) Concomitant use of neuromuscular blockers and calcium may result in resistance to neuromuscular blockade. Calcium antagonizes the potentiating effect of magnesium on neuromuscular blockade. Also, calcium triggers acetylcholine release, and therefore, may both reduce the sensitivity to neuromuscular blockers and decrease the duration of neuromuscular blockade. [65345] Telmisartan; Amlodipine: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers. [53985] [69004] Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium. [48850] [63883] Teriparatide: (Moderate) Monitor serum calcium concentrations closely if concomitant use of calcium and teriparatide is necessary. Concomitant use may increase the risk of hypercalcemia. [53985] Tetracycline: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines. [4691] [6707] Tetracyclines: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines. [4691] [6707] Thiazide diuretics: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium. [48850] [63883] Thyroid hormones: (Moderate) Thyroid hormones should be administered at least 4 hours before or after the ingestion of oral calcium supplements. Calcium salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of thyroid hormones with oral calcium supplements. [27979] [43943] [44355] [53562] Trandolapril; Verapamil: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers. [53985] [69004] Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium. [48850] [63883] Trientine: (Major) In general, oral mineral supplements should not be given since they may block the oral absorption of trientine. However, iron deficiency may develop, especially in children and menstruating or pregnant women, or as a result of the low copper diet recommended for Wilson's disease. If necessary, iron may be given in short courses, but since iron and trientine each inhibit oral absorption of the other, 2 hours should elapse between administration of trientine and iron doses. [10005] [41825] Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium. [48850] [63883] Vecuronium: (Moderate) Concomitant use of neuromuscular blockers and calcium may result in resistance to neuromuscular blockade. Calcium antagonizes the potentiating effect of magnesium on neuromuscular blockade. Also, calcium triggers acetylcholine release, and therefore, may both reduce the sensitivity to neuromuscular blockers and decrease the duration of neuromuscular blockade. [65345] Verapamil: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers. [53985] [69004] Vitamin A: (Minor) Doses in excess of 1,500 to 2,000 mcg per day of Vitamin A may lead to bone loss and will counteract the effects of supplementation with calcium salts. [8242] [8257] Vitamin D analogs: (Moderate) Monitor serum calcium concentrations during concomitant use of high doses of calcium and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration. [28490] [30153] [60895]
      Revision Date: 01/11/2024, 04:54:00 PM

      References

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      Monitoring Parameters

      • hemoglobin/hematocrit
      • MCV
      • platelet count
      • reticulocyte count
      • serum folate concentration
      • serum iron
      • serum potassium
      • serum vitamin B12 (cyanocobalamin) concentrations

      US Drug Names

      • B-12 Compliance Kit
      • B-12 Injection Kit
      • CaloMist
      • Cyomin
      • Dodex
      • LA-12
      • Nascobal
      • Nutri-Twelve
      • Physicians EZ Use B-12
      • Primabalt
      ;