CLASSES

Cyanocobalamin/Vitamin B12 and Analog Supplements
Injectable Vitamin B12 (Cyanocobalamin) Supplements
Non-injectable Vitamin B12 (Cyanocobalamin) Supplements
Vitamin B Complex Supplement Combinations

DEA CLASS

Rx, OTC

DESCRIPTION

Nasal/oral/parenteral B vitamin
Used to treat pernicious anemia and prevent and treat vitamin B12 deficiency, as well as to determine vitamin B12 absorption in the Schilling test
Equal in biologic activity to hydroxocobalamin

COMMON BRAND NAMES

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

HOW SUPPLIED

B-12 Compliance Kit/B-12 Injection Kit/Cyanocobalamin (Vitamin B12)/Cyomin/Dodex/LA-12/Nutri-Twelve/Physicians EZ Use B-12/Primabalt Intramuscular Inj Sol: 1mL, 1000mcg
B-12 Compliance Kit/B-12 Injection Kit/Cyanocobalamin (Vitamin B12)/Cyomin/Dodex/LA-12/Nutri-Twelve/Physicians EZ Use B-12/Primabalt Subcutaneous Inj Sol: 1mL, 1000mcg
Nascobal Nasal Spray Met: 0.1mL, 500mcg

DOSAGE & INDICATIONS

†Indicates off-label use

MAXIMUM DOSAGE

Upper tolerable intake levels in healthy, non-vitamin deficient individuals are not determinable due to a lack of data.

DOSING CONSIDERATIONS

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

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.

ADMINISTRATION

To increase oral absorption, administer on an empty stomach.

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.

STORAGE

Generic:
- Store at room temperature (between 59 to 86 degrees F)
- Store in a dry place
B-12 Compliance Kit:
- Discard product if it contains particulate matter, is cloudy, or discolored
- Protect from direct sunlight
- Protect from light
- Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
- Store in a cool, well ventilated, dry place
- Store in original container
- Store upright
B-12 Injection Kit:
- Discard product if it contains particulate matter, is cloudy, or discolored
- Protect from direct sunlight
- Protect from light
- Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
- Store in a cool, well ventilated, dry place
- Store in original container
- Store upright
CaloMist:
- Protect from freezing
- Protect from light
- Store at room temperature (between 59 to 86 degrees F)
- Store upright
Cyomin:
- Discard product if it contains particulate matter, is cloudy, or discolored
- Protect from direct sunlight
- Protect from light
- Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
- Store in a cool, well ventilated, dry place
- Store in original container
- Store upright
Dodex:
- Discard product if it contains particulate matter, is cloudy, or discolored
- Protect from direct sunlight
- Protect from light
- Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
- Store in a cool, well ventilated, dry place
- Store in original container
- Store upright
LA-12 :
- Discard product if it contains particulate matter, is cloudy, or discolored
- Protect from direct sunlight
- Protect from light
- Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
- Store in a cool, well ventilated, dry place
- Store in original container
- Store upright
Nascobal:
- Protect from freezing
- Protect from light
- Store at room temperature (between 59 to 86 degrees F)
- Store in carton until time of use
- Store upright
Nutri-Twelve :
- Discard product if it contains particulate matter, is cloudy, or discolored
- Protect from direct sunlight
- Protect from light
- Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
- Store in a cool, well ventilated, dry place
- Store in original container
- Store upright
Physicians EZ Use B-12:
- Discard product if it contains particulate matter, is cloudy, or discolored
- Protect from direct sunlight
- Protect from light
- Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
- Store in a cool, well ventilated, dry place
- Store in original container
- Store upright
Primabalt:
- Discard product if it contains particulate matter, is cloudy, or discolored
- Protect from direct sunlight
- Protect from light
- Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
- Store in a cool, well ventilated, dry place
- Store in original container
- Store upright

CONTRAINDICATIONS / PRECAUTIONS

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

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.

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.

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.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.

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). 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.

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. 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.

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. The American Academy of Pediatrics considers vitamin B12 to be compatible with breast-feeding. 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.

ADVERSE REACTIONS

anaphylactic shock / Rapid / Incidence not known
pulmonary edema / Early / Incidence not known
thrombosis / Delayed / Incidence not known
heart failure / Delayed / Incidence not known
aluminum toxicity / Delayed / Incidence not known

edema / Delayed / Incidence not known
polycythemia / Delayed / Incidence not known
hypokalemia / Delayed / Incidence not known
thrombocytosis / Delayed / Incidence not known
dyspnea / Early / Incidence not known
glossitis / Early / Incidence not known

rash / Early / Incidence not known
pruritus / Rapid / Incidence not known
back pain / Delayed / Incidence not known
myalgia / Early / Incidence not known
asthenia / Delayed / Incidence not known
infection / Delayed / Incidence not known
diarrhea / Early / Incidence not known
nausea / Early / Incidence not known
dyspepsia / Early / Incidence not known
vomiting / Early / Incidence not known
dizziness / Early / Incidence not known
hypoesthesia / Delayed / Incidence not known
anxiety / Delayed / Incidence not known
paresthesias / Delayed / Incidence not known
headache / Early / Incidence not known

DRUG INTERACTIONS

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.
Alendronate: (Moderate) Separate administration of alendronate and calcium-containing supplements by at least 30 minutes. Calcium will interfere with the absorption of alendronate.
Alendronate; Cholecalciferol: (Moderate) Separate administration of alendronate and calcium-containing supplements by at least 30 minutes. Calcium will interfere with the absorption of alendronate.
Aliskiren; 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.
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.
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.
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.
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.
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.
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. (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.
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.
Baloxavir Marboxil: (Major) Do not administer baloxavir with products that contain calcium. Polyvalent cations, such as calcium, can chelate with baloxavir, reducing its absorption.
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.
Bendroflumethiazide; Nadolol: (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.
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%.
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.
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.
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.
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).
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).
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.
Calcium Carbonate; 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.
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.
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.
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.
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.
Cardiac glycosides: (Moderate) Monitor for signs and symptoms of digoxin toxicity during concomitant calcium use. Sporadic case reports have suggested that hypercalcemia may predispose persons to digoxin toxicity. If calcium is administered intravenously rapidly in a person receiving digoxin, serious arrhythmias may occur.
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.
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.
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.
Chlorthalidone; Clonidine: (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.
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.
Colchicine: (Minor) Colchicine has been shown to induce reversible malabsorption of vitamin B12. Patients receiving these agents concurrently should be monitored for the desired therapeutic response to vitamin B12.
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.
Conjugated Estrogens: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Conjugated Estrogens; Bazedoxifene: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Conjugated Estrogens; Medroxyprogesterone: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
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.
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.
Desogestrel; Ethinyl Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Dienogest; Estradiol valerate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Diethylstilbestrol, DES: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
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.
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.
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.
Drospirenone; Estetrol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Drospirenone; Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Drospirenone; Ethinyl Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Edetate Calcium Disodium, Calcium EDTA: (Major) Because edetate disodium chelates and lowers serum calcium, oral or parenteral calcium salts should not be administered concomitantly.
Edetate Disodium, Disodium EDTA: (Major) Because edetate disodium chelates and lowers serum calcium, oral or parenteral calcium salts should not be administered concomitantly.
Elagolix; Estradiol; Norethindrone acetate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
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.
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.
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.
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.
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.
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.
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.
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.
Esterified Estrogens: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Esterified Estrogens; Methyltestosterone: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Estradiol Cypionate; Medroxyprogesterone: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Estradiol; Levonorgestrel: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Estradiol; Norethindrone: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Estradiol; Norgestimate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Estradiol; Progesterone: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
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.
Estrogens: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Estropipate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Ethinyl Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Ethinyl Estradiol; Norelgestromin: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Ethinyl Estradiol; Norethindrone Acetate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Ethinyl Estradiol; Norgestrel: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
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.
Ethynodiol Diacetate; Ethinyl Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
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.
Etonogestrel; Ethinyl Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
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.
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.
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.
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.
Hydralazine; 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.
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.
Hydrochlorothiazide, HCTZ; Methyldopa: (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.
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.
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.
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.
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.
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.
Levonorgestrel; Ethinyl Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
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.
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.
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.
Mestranol; Norethindrone: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
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.
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.
Metformin; Rosiglitazone: (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.
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.
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.
Methyclothiazide: (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.
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.
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.
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.
Neomycin: (Minor) Oral neomycin has been shown to inhibit the gastrointestinal absorption of cyanocobalamin, Vitamin B12. Caution is warranted with concomitant use.
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.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Norethindrone; Ethinyl Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Norgestimate; Ethinyl Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Octreotide: (Minor) Depressed levels of cyanocobalamin, vitamin B12, and abnormal Schilling's test have been reported in patients receiving octreotide.
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.
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.
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.
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.
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.
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.
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.
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.
Probenecid; Colchicine: (Minor) Colchicine has been shown to induce reversible malabsorption of vitamin B12. Patients receiving these agents concurrently should be monitored for the desired therapeutic response to vitamin B12.
Propranolol; 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.
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.
Relugolix; Estradiol; Norethindrone acetate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
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.
Segesterone Acetate; Ethinyl Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.

PREGNANCY AND LACTATION

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. 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.

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. The American Academy of Pediatrics considers vitamin B12 to be compatible with breast-feeding. 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.

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.

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.