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  • CLASSES

    Calcium Supplements
    Mineral Binding Agents

    DEA CLASS

    Rx, OTC

    DESCRIPTION

    Essential for the maintenance of the nervous, muscular, and skeletal systems, and for cell membrane and capillary permeability. See separate monograph for Calcium Carbonate.

    COMMON BRAND NAMES

    Calcitrate, Calphron, Eliphos, Oysco 500, PhosLo, Phoslyra

    HOW SUPPLIED

    Calcitrate/Calcium/Calcium Acetate/Calcium Citrate/Calcium Gluconate/Calphron/Eliphos/Oysco 500/PhosLo Oral Tab: 84mg, 200mg, 500mg, 667mg, 668mg, 950mg
    Calcium/Calcium Acetate/PhosLo Oral Cap: 667mg
    Calcium/Calcium Chloride/Calcium Gluconate Intravenous Inj Sol: 1mL, 10%, 100mg
    Calcium/Calcium Glubionate/Phoslyra Oral Sol: 1.8g, 5mL, 667mg

    DOSAGE & INDICATIONS

    For the treatment of hypocalcemia.
    For the treatment of acute hypocalcemia.
    NOTE: IV dosages should be used in patients with tetany. 
    NOTE: Monitor ionized serum calcium concentrations to individualize dosage.
    NOTE: For the treatment of ionized hypocalcemia during CPR, see dosing for CPR. 
    Intravenous dosage (calcium chloride 10%)
    Adults

    0.5—1 g of calcium chloride salt, give IV slowly at a rate not exceeding 1 ml/min (27.2 mg of elemental calcium/minute). For tetany, give over 5—10 minutes. Repeat every 4—6 hours, as needed, as determined by serum calcium concentrations and patient response. Alternatively, an intravenous infusion of 15 mg/kg of elemental calcium (37.5 mg/kg calcium chloride) over 4—6 hours may be administered if symptoms recur after initial IV calcium replacement. 

    Children and Infants

    The manufacturer's suggested dosage for treating hypocalcemic disorders ranges from 2.7—5 mg/kg/dose of calcium chloride salt (0.027—0.05 ml/kg/dose of 10% calcium chloride injection). For tetany, give 10 mg/kg/dose IV slowly over 5—10 minutes. May repeat initial dosage in 4—6 hours, if needed. Adjust dosage based on serum calcium concentrations and patient response. Alternatively, the initial dose can be followed by a continuous infusion with a maximum dose of 200 mg/kg/day IV. NOTE: This salt is less commonly used for pediatric patients. 

    Intravenous dosage (calcium gluconate)
    Adults

    2—3 g IV slowly at a rate not exceeding 5 ml/min (47.5 mg/min of calcium ion). For tetany, give over 5—10 minutes. Repeat every 6 hours, as needed, as determined by serum calcium concentrations and patient response. Maximum dosage is 15 g/day. Alternatively, an intravenous infusion of 15 mg/kg of elemental calcium (167 mg/kg calcium gluconate) over 4—6 hours may be administered if symptoms recur after initial IV calcium replacement. 

    Children and Infants

    200—500 mg/kg/day IV as a continuous infusion or given in 4 divided doses, at a rate not exceeding 5 ml/min (47.5 mg/min of calcium ion). For tetany, an initial dose of 100—200 mg/kg IV given over 5—10 minutes is recommended. This dose may be repeated after 6 hours or followed by 500 mg/kg/day IV as a continuous infusion or given in 3—4 divided doses. 

    Neonates

    200—800 mg/kg/day IV as a continuous infusion or administered in 3—4 divided doses. For tetany, initial doses of 100—200 mg/kg IV are recommended, followed by 500 mg/kg/day IV as a continuous infusion or given in 3—4 divided doses. 

    Intramuscular dosage (calcium glycerophosphate or calcium lactate)
    Adults

    10 ml IM once or twice a week for 4—5 weeks. May repeat if needed to raise serum calcium concentrations. 

    Oral dosage (calcium citrate)
    Adults

    9.5—19 g/day PO in divided doses 2—4 times a day after meals. This dose provides about 2—4 grams of elemental calcium per day. 

    Oral dosage (calcium glubionate)
    Adults, Adolescents, and Children over 4 years

    30—62 g/day PO in 3—4 divided doses. This dose provides about 2—4 grams of elemental calcium per day. 

    Children and Infants

    600—2000 mg/kg/day PO in 4 divided doses. Maximum dosage is 9 g/day. 

    Neonates

    1200 mg/kg/day PO in 4—6 divided doses. 

    Oral dosage (calcium gluconate)
    Adults

    22.5—45 g/day PO in 3—4 divided doses. This dose provides about 2—4 grams of elemental calcium per day. 

    Children and Infants

    500—725 mg/kg/day PO in 4 divided doses. 

    Neonates

    500—1500 mg/kg/day PO in 4—6 divided doses. 

    Oral dosage (calcium lactate)
    Adults

    15.4—30.8 g/day PO divided every 8 hours. This dose provides about 2—4 grams of elemental calcium per day. 

    Children

    345—500 mg/kg/day PO in divided doses every 6—8 hours. Maximum dosage is 9 g/day. 

    Infants

    400—500 mg/kg/day PO in divided doses every 4—6 hours. 

    Oral dosage (dibasic calcium phosphate)
    Adults

    8.6—17.4 g/day PO in divided doses with or after meals. This dose provides about 2—4 grams of elemental calcium per day. 

    Children

    200—280 mg/day PO in divided doses with or after meals. 

    Oral dosage (tribasic calcium phosphate)
    Adults

    5.2—10.5 g/day PO in divided doses with or after meals. This dose provides about 2—4 grams of elemental calcium per day. 

    For hypocalcemia secondary to citrated blood infusion.
    Intravenous dosage
    Adults, Children, and Neonates

    0.45 mEq elemental calcium for each 100 ml of citrated blood infused.

    For the treatment of hyperkalemia, hypermagnesemia, and ionized hypocalcemia.
    For the treatment of life-threatening cardiac arrhythmias or during cardiopulmonary resuscitation (CPR)† (cardiac arrest†) associated with suspected or documented hyperkalemia, hypermagnesemia, or ionized hypocalcemia.
    NOTE: Calcium salts are NOT recommended for routine treatment of cardiac arrest. No benefit has been demonstrated during cardiac arrest and hypercalcemia may occur following calcium administration.
    Intravenous dosage (calcium chloride 10%)
    Adults

    5 to 10 ml of a 10% solution (500—1000 mg) or 8—16 mg/kg IV administered by slow injection; may repeat if needed.

     Infants and Children

    20 mg/kg IV or intraosseous (0.2 ml/kg of a 10% solution); may repeat if needed.

    Intravenous dosage (calcium gluconate)
    Adults

    500—800 mg IV of 10% solution (5—8 ml). Maximum dose is 3 g IV.

    Infants and Children

    60—100 mg/kg IV or intraosseous (0.6—1 ml/kg). Maximum dose is 3 g IV.

    For the treatment of severe hyperkalemia (serum potassium > 7 mEq/L) or hypermagnesemia associated with toxic ECG changes.
    Intravenous dosage (calcium chloride 10%)
    Adults

    5—10 ml IV of 10% solution over 2—5 minutes to lower the risk of ventricular fibrillation due to hyperkalemia.

    For adjunctive therapy in the treatment of CNS depression due to hypermagnesemia.
    Intravenous dosage (calcium chloride 10%)
    Adults

    500 mg IV initially. Repeat doses should be based on clinical response.

    Intravenous dosage (calcium gluconate)
    Adults

    500—2000 mg IV slowly at a rate not exceeding 200 mg/min (2 ml/min of a 10% solution).

    For nutritional supplementation.
    The adequate intake (AI) of calcium for maximum calcium retention in healthy individuals and for osteoporosis prophylaxis.
    NOTE: Recommended dietary allowances (RDAs) for calcium have not been established. Adequate intakes (AIs) should be used in place of RDAs. 
    NOTE: Use dosage based on age for pregnant or lactating females and for prevention of osteoporosis.
     Oral dosage (any oral calcium salt; dosage expressed as elemental calcium)
    Adults >= 51 years of age

    1200 mg PO per day (range 1000—1500 mg/day PO). The IOM Food and Nutrition Board recommends using the AI for osteoporosis prophylaxis. The 2006 guidelines of the North American Menopause Society recommend a target intake of 1200 mg/day of elemental calcium PO in postmenopausal women.

    Adults 19—50 years of age

    1000 mg PO per day. 

    Children and Adolescents 9—18 years of age

    1300 mg PO per day. 

    Children 4—8 years of age

    800 mg PO per day. 

    Children 1—3 years of age

    500 mg PO per day. 

    Infants 6—12 months of age

    270 mg PO per day based on total intake (consumption from breast milk/infant formula and solid food).

    Neonates and Infants < 6 months of age

    210 mg PO per day based on total intake (content in human milk/infant formula). Source of calcium intake should come from food/breast milk only in order to prevent high levels of intake.

    For nutritional supplementation to prevent hypocalcemia in patients receiving total parenteral nutrition (TPN).
    Intravenous dosage
    Adults

    10—15 mEq IV per day admixed with TPN. The choice of parenteral product and dosage depends upon the clinical condition of the patient (i.e. electrolyte balance, acid-base status) and compatibility with chosen parenteral fluids and additives. Several factors influence the amount of calcium that can be safely added to parenteral nutrition solutions. 

    Children and Infants, including premature Neonates

    The choice of parenteral product and dosage depends upon the age and clinical condition of the patient (i.e. electrolyte balance, acid-base status) and compatibility with chosen parenteral fluids and additives. Several factors influence the amount of calcium that can be safely added to parenteral nutrition solutions.

    For the treatment of hyperphosphatemia, especially in patients with chronic renal failure or end stage renal disease.
    NOTE: Calcium carbonate (see separate calcium carbonate monograph) has been designated as an orphan drug by the FDA for this indication. 
    Oral dosage (667 mg calcium acetate - PhosLo tablets, gelcaps or full-size capsules)
    Adults

    2 PhosLo tablets, gelcaps or full-size capsules PO with each meal. The dosage may be gradually increased to lower serum phosphate concentration < 6 mg/dl, as long as hypercalcemia does not develop. Do not give other calcium supplements with PhosLo to avoid hypercalcemia. Most patients require 3—4 tablets, gelcaps or full-size capsules with each meal. Each PhosLo tablet, gelcap, or full-size capsule contains 667 mg calcium acetate which is equivalent to 169 mg (8.45 mEq) calcium ion. 

    Oral dosage (calcium acetate 667 mg/5 ml oral solution)
    Adults

    The initial dose for dialysis patients is 10 ml PO with each meal. If hypercalcemia does not develop, increase the dose gradually every 2—3 weeks to lower serum phosphorus concentration to the target range. Most patients require 15—20 ml with each meal.

    For the treatment of verapamil toxicity or calcium antagonist toxicity (e.g., myocardial depression, hypotension, cardiac conduction defects or cardiac arrhythmias).
    Intravenous dosage (calcium chloride 10%)
    Adults

    2 ml of a 10% solution or 2—4 mg/kg IV. May repeat in 10 minutes if necessary. Another source recommends 1 g IV over 5 min, repeated every 10 to 20 minutes for 3—4 additional doses as needed.

    Infants and Children

    20 mg/kg IV. May repeat in 10 minutes if necessary.

    Intravenous dosage (calcium gluconate)
    Adults

    500—800 mg IV. Maximum dose is 3 g IV. NOTE: Calcium chloride is the preferred agent. 

    Infants and Children

    100 mg/kg IV. Maximum dose is 3 g IV. NOTE: Calcium chloride is the preferred agent.

    For exchange transfusion-induced hypocalcemia prophylaxis†.
    Intravenous dosage (calcium gluconate)
    Neonates

    97 mg IV after each 100 ml of citrated blood exchanged.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    Dependent on indication for therapy.

    Elderly

    Dependent on indication for therapy.

    Adolescents

    Dependent on indication for therapy.

    Children

    Dependent on indication for therapy.

    Infants

    Dependent on indication for therapy.

    DOSING CONSIDERATIONS

    Hepatic Impairment

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

    Renal Impairment

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

    ADMINISTRATION

    Oral Administration

    In general, administer with meals or feedings for improved absorption. Follow each dose with adequate fluids.
    Because calcium-containing products may interfere with the absorption of other medicines, separate administration of calcium from other medications according to recommendations for the potentially interacting medication.

    Oral Solid Formulations

    Chewable tablets: Instruct patient to chew thoroughly before swallowing.
    Effervescent tablets: Dissolve each dose in a full glass of water as directed in the product label.

    Oral Liquid Formulations

    Measure doses with an oral syringe or other calibrated oral device to ensure accurate dosing.
     
    Calcium glubionate oral solution (e.g., Calcionate syrup): Due to the hyperosmolarity of this syrup, dilute infant and neonatal doses in small amounts of feedings and monitor for feeding intolerance.
     
    The parenteral formulation of calcium gluconate has been diluted in feedings for oral administration to neonates and infants.

    Injectable Administration

    Administered intravenously as the gluconate or chloride salts. Do NOT administer intramuscularly or subcutaneously.
    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
    Calcium chloride and calcium gluconate 10% (100 mg/mL) contain 27.2 mg/mL and 9 mg/mL of elemental calcium, respectively.

    Intravenous Administration

    Intermittent IV Infusion
    May dilute in compatible IV solution (i.e., 0.9% Sodium Chloride injection, 5% Dextrose injection, 10% Dextrose injection) to a usual concentration of 10 to 40 mg/mL.
    For calcium chloride, administration into a large vein or a central line is preferred; avoid extravasation. In a safety analysis of peripheral intravenous administration of calcium chloride solutions to adult patients, concentrations of approximately 3 mg/mL resulted in a low incidence of infusion site reactions. Concentrations of 1 mg/mL or less have been recommended for peripheral lines for neonates.
    For calcium gluconate, a recommended concentration for peripheral lines is 3 mg/mL for neonates; however, concentrations as high as 100 mg/mL have been used for bolus doses. Observe the infusion line closely. Higher concentrations have been given via central lines.
    Do not administer via scalp vein catheter.
    Generally, infuse a bolus dose over 30 to 60 minutes. Calcium gluconate may be administered at a rate not exceeding 200 mg/minute. Calcium chloride may be administered at a rate not exceeding 100 mg/minute.
     
    IV Push
    In general, inject IV 10% calcium gluconate products slowly, at a rate of 1.5 mL/minute (150 mg/minute) or less to avoid adverse reactions. The absolute maximum rate of 2 mL/minute (200 mg/minute) should not be exceeded. Administer through a small needle into a large vein.
    Inject IV 10% calcium chloride by slow IV injection. Do not to exceed 1 mL/minute (100 mg/minute), preferably in a deep or central vein. Following injection, the patient should remain recumbent for a short time.

    Other Injectable Administration

    Intraosseous Route
    NOTE: Calcium chloride and calcium gluconate are not approved by the FDA for intraosseous administration.
    During cardiopulmonary resuscitation in pediatrics, calcium chloride or calcium gluconate may be given via the intraosseous route when IV access is not available.
     
    Intracardiac Route
    In cardiac resuscitation, calcium chloride, in the appropriate intracardiac dose, can be injected into the ventricular cavity. Care should be taken to avoid injection into the cardiac muscle.

    STORAGE

    Generic:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Discard unused portion 4 hours after initial puncture of container
    - Do not freeze
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Calcitrate:
    - Store at room temperature (between 59 to 86 degrees F)
    - Store in a dry place
    Calphron:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Eliphos:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Oysco 500 :
    - Store at room temperature (between 59 to 86 degrees F)
    PhosLo:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Phoslyra:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    NOTE: Calcium carbonate is discussed in a separate monograph.

    Hypercalcemia

    Calcium salts are contraindicated in patients with preexisting hypercalcemia.

    Hypercalciuria

    Calcium salts should not be used in patients with preexisting hypercalciuria, especially if renal calculi are present.

    Sarcoidosis

    Calcium salts should not be used in patients with sarcoidosis because hypercalcemia can occur.

    Extravasation, intramuscular administration, subcutaneous administration

    Calcium chloride and calcium gluconate injections should not be given by intramuscular administration or subcutaneous administration. Severe necrosis and sloughing may occur. Caution should be undertaken to avoid extravasation or accidental injection into perivascular tissues.

    Cardiac arrhythmias, digitalis toxicity, ventricular fibrillation

    Parenteral calcium salts are contraindicated in patients with ventricular fibrillation and should be used cautiously in patients with preexisting cardiac arrhythmias. Calcium salts are no longer recommended for ACLS algorithms for pulseless electrical activity or asystole during cardiopulmonary resuscitation, except when indications exist to counterbalance electrolyte disturbances. Parenteral calcium salts should not be used in patients with digitalis toxicity because of an increased risk of developing arrhythmias. Cardiac glycosides and calcium salts both increase intracellular calcium, so calcium salts can worsen digitalis toxicity. Cardiac glycoside therapy, however, does not preclude the use of calcium salts.

    Dehydration

    Calcium supplements should be used with caution in patients with dehydration.

    Diarrhea

    Calcium supplements should be used with caution in patients with diarrhea or malabsorption because fecal excretion can be increased.

    Hyperphosphatemia, hypoparathyroidism

    Calcium supplements should be used with caution in patients with chronic renal failure due to the increased risk of developing hypercalcemia. Oral calcium salts, however, are often used to treat hyperphosphatemia in these patients; when administered with meals, the calcium binds with phosphate within the intestine and is excreted. To avoid transiently increasing the calcium-phosphate product, many clinicians first attempt to lower the serum phosphate with aluminum-based phosphate 'binders' and then substitute them with calcium-based phosphate binders. Calcium phosphate should not be used in patients with hypoparathyroidism or renal disease because there is an increased risk of developing hyperphosphatemia.

    Vitamin D toxicity

    Calcium salts should be used cautiously, if at all, in patients with vitamin D toxicity or hyperparathyroidism. Hypercalcemia is likely to occur in either of these conditions.

    Pregnancy

    Adverse effects have not been reported with the normal daily intake of calcium salts within the recommended dietary daily intakes for a pregnant female. The use of calcium salts in excess of the recommended dietary allowance during normal pregnancy should be avoided unless, in the judgment of the physician, potential benefits in a specific, unique case outweigh the significant hazards involved.

    Breast-feeding

    Calcium salts appear to be safe and effective to use during breast-feeding to help meet maternal nutritional requirements. Human breast milk naturally contains calcium and other minerals; maternal calcium intake appears to have no significant effect on the amount of calcium normally found in human milk. 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 administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    Necrotizing enterocolitis

    In infants at high risk for necrotizing enterocolitis, oral liquid calcium formulations should be avoided due to the high osmolality.

    ADVERSE REACTIONS

    Severe

    tissue necrosis / Early / Incidence not known
    AV block / Early / Incidence not known
    cardiac arrest / Early / Incidence not known
    coma / Early / Incidence not known
    bradycardia / Rapid / Incidence not known
    ventricular fibrillation / Early / Incidence not known
    milk-alkali syndrome / Delayed / Incidence not known

    Moderate

    delirium / Early / Incidence not known
    hypertension / Early / Incidence not known
    constipation / Delayed / Incidence not known
    premature ventricular contractions (PVCs) / Early / Incidence not known
    hypotension / Rapid / Incidence not known
    confusion / Early / Incidence not known
    hypercalcemia / Delayed / Incidence not known
    nephrolithiasis / Delayed / Incidence not known
    hypophosphatemia / Delayed / Incidence not known

    Mild

    diarrhea / Early / 13.2-13.2
    injection site reaction / Rapid / Incidence not known
    syncope / Early / Incidence not known
    dizziness / Early / Incidence not known
    flushing / Rapid / Incidence not known
    polyuria / Early / Incidence not known
    vomiting / Early / Incidence not known
    nausea / Early / Incidence not known
    anorexia / Delayed / Incidence not known
    drowsiness / Early / Incidence not known
    paresthesias / Delayed / Incidence not known
    dysgeusia / Early / Incidence not known
    pruritus / Rapid / Incidence not known
    muscle cramps / Delayed / Incidence not known

    DRUG INTERACTIONS

    Abacavir; Dolutegravir; Lamivudine: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking cation-containing antacids. The chemical structure of these antacids contain either magnesium or aluminum which can bind dolutegravir in the GI tract. Taking these drugs simultaneously may result in reduced bioavailability of dolutegravir.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    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) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended. (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.
    Atracurium: (Moderate) Calcium salts may antagonize the effects of nondepolarizing neuromuscular blockers.
    Azilsartan; Chlorthalidone: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Bendroflumethiazide; Nadolol: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Beta-Carotene: (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.
    Betamethasone; 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).
    Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Bisphosphonates: (Moderate) Separating times of administration of the oral bisphosphonate from calcium-containing supplements and medications will maximize absorption and clinical benefit. Calcium will interfere with the absorption of the orally administered bisphosphonates alendronate, etidronate, ibandronate, risedronate, and tiludronate. At least 30 minutes should elapse after the oral administration of alendronate before taking any calcium containing product. At least 1 hour should elapse after the oral administration of ibandronate before taking any calcium containing product. At least 2 hours should elapse after the oral administration of etidronate, risedronate, or tiludronate before administering any calcium containing product.
    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).
    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 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.
    Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Captopril; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Cardiac glycosides: (Major) Calcium salts augment the actions of digoxin. In addition, when calcium is administered via rapid intravenous injection, the risk of serious arrhythmias in digitalized patients is increased. It is recommended that serum calcium be monitored regularly in patients receiving digoxin.
    Ceftriaxone: (Moderate) Ceftriaxone must NOT be mixed or administered simultaneously with IV solutions containing calcium salts, including certain TPN formulas of amino acids with electrolytes formulas. There have been no reports of an interaction between ceftriaxone and oral calcium-containing products or between intramuscular ceftriaxone and any calcium-containing products. Fatal reactions involving ceftriaxone-calcium precipitates in lung and kidneys have been reported in both term and premature neonates. Two in vitro studies, one using adult plasma and the other using neonatal plasma from umbilical cord blood, assessed ceftriaxone concentrations up to 1 mM (higher concentrations expected in vivo after the administration of 2 g) in combination with calcium concentrations up to 12 mM (48 mg/dl). A reduced concentration of ceftriaxone in plasma was noted with calcium concentrations of 6 mM (24 mg/dl) and higher in adult plasma or 4 mM (16 mg/dl) and higher in neonatal plasma. This may be a result of ceftriaxone-calcium precipitation.
    Chlorothiazide: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Chlorthalidone: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Chlorthalidone; Clonidine: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Ciprofloxacin: (Major) 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.
    Cisatracurium: (Moderate) Calcium salts may antagonize the effects of nondepolarizing neuromuscular blockers.
    Cod Liver Oil: (Moderate) Concomitant cod liver oil and calcium supplementation should be undertaken with caution. The vitamin D contained within cod liver oil can increase serum calcium concentrations; the combination may result in hypercalcemia. Additionally, doses in excess of 1,500 to 2,000 mcg/day of vitamin A may lead to bone loss and can counteract the effects of supplementation with calcium salts. (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.
    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.
    Cyanocobalamin, Vitamin B12: (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.
    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.
    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.
    Diphenhydramine; Naproxen: (Minor) Concomitant administration of antacids can delay the absorption of naproxen. Periodic antacid use should not be problematic as long as the antacid and enteric-coated naproxen administration are separated by at least 2 hours.
    Dolutegravir: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking cation-containing antacids. The chemical structure of these antacids contain either magnesium or aluminum which can bind dolutegravir in the GI tract. Taking these drugs simultaneously may result in reduced bioavailability of dolutegravir.
    Dolutegravir; Rilpivirine: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking cation-containing antacids. The chemical structure of these antacids contain either magnesium or aluminum which can bind dolutegravir in the GI tract. Taking these drugs simultaneously may result in reduced bioavailability of dolutegravir.
    Doxacurium: (Moderate) Calcium salts may antagonize the neuromuscular blocking effects of doxacurium.
    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.
    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.
    Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Esomeprazole; Naproxen: (Minor) Concomitant administration of antacids can delay the absorption of naproxen. Periodic antacid use should not be problematic as long as the antacid and enteric-coated naproxen administration are separated by at least 2 hours.
    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.
    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; Desogestrel: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Ethinyl Estradiol; Ethynodiol Diacetate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Ethinyl Estradiol; Etonogestrel: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Ethinyl Estradiol; Levonorgestrel: (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; Norethindrone Acetate; Ferrous fumarate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Ethinyl Estradiol; Norethindrone: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Ethinyl Estradiol; Norethindrone; Ferrous fumarate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Ethinyl Estradiol; Norgestimate: (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.
    Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Gallium: (Moderate) Concurrent administration products containing calcium salts may antagonize the effects of gallium nitrate.
    Gemifloxacin: (Major) Administer oral products that contain calcium at least 2 hours before or 2 hours after gemifloxacin. Gemifloxacin 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.
    Hydralazine; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Hydrochlorothiazide, HCTZ; Irbesartan: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Hydrochlorothiazide, HCTZ; Lisinopril: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Hydrochlorothiazide, HCTZ; Losartan: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Hydrochlorothiazide, HCTZ; Metoprolol: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Hydrochlorothiazide, HCTZ; Olmesartan: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Hydrochlorothiazide, HCTZ; Propranolol: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Hydrochlorothiazide, HCTZ; Quinapril: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Hydrochlorothiazide, HCTZ; Spironolactone: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Hydrochlorothiazide, HCTZ; Telmisartan: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Hydrochlorothiazide, HCTZ; Triamterene: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Hydrochlorothiazide, HCTZ; Valsartan: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    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.
    Lansoprazole; Naproxen: (Minor) Concomitant administration of antacids can delay the absorption of naproxen. Periodic antacid use should not be problematic as long as the antacid and enteric-coated naproxen administration are separated by at least 2 hours.
    Levofloxacin: (Major) 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.
    Mestranol; Norethindrone: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Methyclothiazide: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Metolazone: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Mivacurium: (Moderate) Calcium salts may antagonize the neuromuscular blocking effects of mivacurium.
    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.
    Naproxen: (Minor) Concomitant administration of antacids can delay the absorption of naproxen. Periodic antacid use should not be problematic as long as the antacid and enteric-coated naproxen administration are separated by at least 2 hours.
    Naproxen; Pseudoephedrine: (Minor) Concomitant administration of antacids can delay the absorption of naproxen. Periodic antacid use should not be problematic as long as the antacid and enteric-coated naproxen administration are separated by at least 2 hours.
    Naproxen; Sumatriptan: (Minor) Concomitant administration of antacids can delay the absorption of naproxen. Periodic antacid use should not be problematic as long as the antacid and enteric-coated naproxen administration are separated by at least 2 hours.
    Norfloxacin: (Major) Administer oral products that contain calcium at least 2 hours before or 2 hours after norfloxacin. Norfloxacin 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.
    Ofloxacin: (Major) 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.
    Omeprazole; Sodium Bicarbonate: (Minor) Prolonged use of sodium bicarbonate along with calcium carbonate may result in milk-alkali syndrome.
    Pancuronium: (Moderate) Calcium salts usually reverse the effects of nondepolarizing neuromuscular blocking agents such as pancuronium.
    Phenytoin: (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 will help avoid this interaction. A similar interaction may occur with 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 will help avoid this interaction.
    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 Salts: (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.
    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.
    Rocuronium: (Moderate) Calcium salts may antagonize the effects of nondepolarizing neuromuscular blockers, such as rocuronium.
    Sodium Bicarbonate: (Minor) Prolonged use of sodium bicarbonate along with calcium carbonate may result in milk-alkali syndrome.
    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.
    Succinylcholine: (Moderate) Calcium salts may antagonize the effects of nondepolarizing neuromuscular blockers.
    Sucralfate: (Major) Calcium salts potentially interfere with gastric mucosal binding of sucralfate. This interaction can be minimized by staggering the doses of these agents as much as possible. (Major) Oral antacids, including calcium salts, potentially interfere with gastric mucosal binding of sucralfate. This interaction can be minimized by staggering the doses of these agents as much as possible.
    Tetracyclines: (Major) 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) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Thyroid hormones: (Major) 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. To avoid the interaction, thyroid hormones should be administered at least 4 hours before or after ingestion of oral calcium supplements.
    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.
    Tubocurarine: (Moderate) Calcium salts may antagonize the effects of nondepolarizing neuromuscular blockers.
    Vecuronium: (Moderate) Calcium salts may antagonize the effects of nondepolarizing neuromuscular blockers.
    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) Dose adjustment of vitamin D analogs may be necessary during coadministration with calcium salts. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and high doses of calcium-containing salts.

    PREGNANCY AND LACTATION

    Pregnancy

    Adverse effects have not been reported with the normal daily intake of calcium salts within the recommended dietary daily intakes for a pregnant female. The use of calcium salts in excess of the recommended dietary allowance during normal pregnancy should be avoided unless, in the judgment of the physician, potential benefits in a specific, unique case outweigh the significant hazards involved.

    Calcium salts appear to be safe and effective to use during breast-feeding to help meet maternal nutritional requirements. Human breast milk naturally contains calcium and other minerals; maternal calcium intake appears to have no significant effect on the amount of calcium normally found in human milk. 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 administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    Calcium is the primary component of skeletal tissue, providing structural integrity and support for individual growth. Bone undergoes constant remodeling and turnover. Mineral release during the process of bone resorption buffers hydrogen ions. Whereas, the formation of bone generates hydrogen ions. Thus, bone serves as a calcium depot and as a reservoir for electrolytes and buffers. Inhibition of bone resorption is primarily the function of the hormone, calcitonin. The control of plasma calcium concentration is primarily maintained by parathyroid hormone, thyroxine, and 1,25 dihydroxycholecalciferol. Ionized calcium is the physiologically active form. Basic metabolic functions involve the cardiac, neuromuscular, structural, and blood coagulation systems.
     
    Calcium acetate works as a phosphate binder. When taken with meals, it combines with dietary phosphate, forming an insoluble calcium-phosphate complex, which is then eliminated in the feces. This in turn lowers serum phosphorus concentrations.

    PHARMACOKINETICS

    Calcium is required by all body tissues. Approximately 98% of the body's calcium is stored in the bone, primarily as the hydroxyapatite. Constant bone remodeling and turnover of the skeleton release calcium into the systemic circulation which is then re-accumulated by the bone on a daily basis. Calcium is 40% bound to plasma proteins, primarily albumin, and 10% is in a chelated form. Approximately 50% of serum calcium is ionized, which is considered the physiologically active form. The ultrafiltratable calcium (nonprotein-bound) is distributed to the protein-poor regions of the body, such as the cerebrospinal and extracellular fluids. Calcium is primarily excreted in the feces and bile (80%). Urinary excretion accounts for the remainder (20%). However, approximately 99% of filtered calcium is reabsorbed by the kidney with less than 1% excreted. Parathyroid hormone, calcitonin, and 1,25 dihydroxycholecalciferol are primarily responsible for controlling calcium equilibrium. Insulin, thyroxine, growth hormone, androgens, estrogens, adrenal corticosteroids, and inorganic phosphate also contribute.
     
    Affected cytochrome P450 isoenzymes: none

    Oral Route

    Absorption of calcium is optimal when it is taken in a dose of <= 500 mg. Disintegration of tablet forms may differ between manufacturers, which may affect absorption. Optimal calcium absorption may require supplemental vitamin D in individuals with inadequate vitamin D intake, impaired renal function, or those with inadequate exposure to sunlight.
     
    Calcium acetate
    Calcium acetate absorption is approximately 40% and 30% under fasting and non-fasting conditions, respectively. Similar changes in serum calcium and phosphorus concentrations have been observed with calcium acetate, whether given as the oral solution, tablets, or gelcaps.
     
    Calcium citrate
    Bioavailability studies of calcium citrate compared to calcium carbonate have reported variable results. One study reported similar bioavailability between the 2 formulations (approximately 28% for 500-mg dose and 36% for 1000-mg dose). Another study reported better bioavailability with calcium citrate when given with food. Calcium citrate offers better absorption under achlorhydria conditions; therefore, this supplement is recommended in patients receiving proton-pump inhibitors or H2 blockers.

    Intravenous Route

    Calcium chloride
     
    Calcium chloride is more bioavailable than calcium gluconate and results in greater increases in serum ionized calcium concentrations than does calcium gluconate.