Calcium Salts (Monograph)

Brand names: Alka-Mints, Calci-Chew, Calci-Mix, Caltrate, Chooz, ... show all 13 brands Citracal, Liqui-Cal, Os-Cal, PhosLo, Posture, Posture-D, Titralac, Tums
Drug class: Replacement Preparations
- Antidotes

Introduction

Calcium salts are used as a source of calcium, an essential nutrient cation.^b

Uses for Calcium Salts

Dietary Requirements (oral therapy)

For maintaining an adequate intake of calcium to support the development and preservation of bone mass at a level sufficient to prevent fractures associated with osteopenia or osteoporosis in later life and of other calcified tissues (e.g., teeth).^{112 126 129 147 153}

Life long intake of adequate calcium is necessary for good bone health at any age; calcium requirements may increase among older individuals.^{147 148}

Adequate intakes of calcium can be accomplished through changes in food consumption behaviors, consumption of nutrient-fortified foodstuffs, use of dietary supplements, or a combination of these.^{112 147 153}

In the US and Canada, calcium principally is obtained from dairy products.¹¹² Other principal sources include fruits, vegetables, and grain products.¹¹² In addition, many healthy individuals take dietary supplements containing calcium.¹¹²

For specific information on currently recommended Dietary Reference Intakes (DRIs) of calcium for various life-stage and gender groups, see Dosage under Dosage and Administration.^b

Hypocalcemia (parenteral and oral therapy)

Calcium salts are used as a source of calcium cation for the treatment or prevention of calcium depletion when dietary measures are inadequate.^b Conditions associated with calcium deficiency include hypoparathyroidism, achlorhydria, chronic diarrhea, vitamin D deficiency, steatorrhea, sprue, pregnancy and lactation, menopause, pancreatitis, renal failure, alkalosis, and hyperphosphatemia.^b

Some clinicians consider IV calcium chloride the calcium salt of choice to prevent hypocalcemia during transfusions with citrated blood.^b In addition to being irritating, however, the chloride salt is acidifying and generally should not be used when acidosis coincides with hypocalcemia (e.g., renal failure).^b

The calcium glycerophosphate and calcium lactate fixed-combination injection is used IM to increase serum calcium concentrations.¹⁴²

Administration of certain drugs (e.g., some diuretics, anticonvulsants) may sometimes result in hypocalcemia, which may warrant calcium replacement therapy.^b

Calcium is administered in long-term electrolyte replacement regimens.^b

Use of calcium salts should not preclude the use of other measures intended to correct the underlying cause of calcium depletion.^b

Vitamin D analogs may be administered concomitantly with oral calcium salts for the treatment of chronic hypocalcemia, especially when caused by vitamin D deficiency.^b

Calcium salts may be used orally for the treatment of hypocalcemia secondary to the administration of anticonvulsant drugs.^b

Hypocalcemic Tetany (IV therapy)

IV calcium gluconate is considered the salt of choice for the treatment of acute hypocalcemia.^b

Calcium salts are used to treat acute hypocalcemic tetany secondary to renal failure, hypoparathyroidism, premature delivery, and/or maternal diabetes mellitus in infants, and poisoning with magnesium, oxalic acid, radiophosphorus, carbon tetrachloride, fluoride, phosphate, strontium, or radium.^b

Hypoparathyroidism, Chronic (oral therapy)

Calcium salts may be used for treatment of chronic hypoparathyroidism.^b

Latent Tetany (oral therapy)

Calcium salts may be used for the treatment of latent tetany.^b

Osteoporosis (oral therapy)

Calcium salts (e.g., calcium carbonate, calcium citrate) are used as supplements in the prevention and treatment of osteoporosis when dietary intake of calcium is insufficient.^{147 148}

Adequate intake of calcium and vitamin D (which increases absorption of calcium) is universally recommended for all individuals to diminish age-related bone loss and prevent osteoporosis.^{147 148}

In addition to lifestyle modifications (e.g., regular weight-bearing exercise, avoidance of excessive alcohol and tobacco use), the National Osteoporosis Foundation recommends a daily calcium intake of 1 g in men 50–70 years of age, and 1.2 g in women ≥51 years of age and men ≥71 years of age.¹⁴⁷

The combination of calcium and vitamin D has been shown to reduce risk of fractures.¹⁴⁷

Glucocorticoid-induced Osteoporosis (oral therapy)

Calcium salts are used for prevention of glucocorticoid-induced osteoporosis.⁶²²

The American College of Rheumatology (ACR) recommends optimizing dietary intake of calcium (1–1.2 g daily) and vitamin D (600–800 units daily) in all patients receiving long-term glucocorticoid therapy (defined as a daily dosage equivalent to 2.5 mg of prednisone or greater for ≥3 months).⁶²²

Because of concerns about potential harms (e.g., cardiovascular risks), ACR states that additional study is needed to determine potential benefits versus risks of calcium and vitamin D supplementation in patients receiving glucocorticoids.⁶²²

Osteomalacia (oral therapy)

Calcium salts may be used for treatment of osteomalacia.^b

Anticonvulsant-induced Hypocalcemia (oral therapy)

Calcium salts may be used for treatment of rickets, latent tetany, and hypocalcemia secondary to the administration of anticonvulsant drugs.^b

Rickets (oral therapy)

Calcium salts may be used for treatment of rickets.^b

Hyperphosphatemia in Chronic Renal Failure (oral therapy)

Calcium acetate and calcium carbonate are considered the salts of choice for chronic renal failure.^{113 126}

In addition to providing a source of calcium, calcium acetate or carbonate sequesters phosphate in the intestine by forming insoluble phosphates that are excreted fecally, thus reducing serum phosphate concentrations and secondary hyperparathyroidism.^b

Calcium carbonate partially corrects metabolic acidosis which may occur in chronic renal failure.^b

Because of the risk of aluminum accumulation and resultant neurotoxic and osteomalacic effects, most clinicians no longer use aluminum hydroxide to inhibit phosphorus absorption; instead calcium acetate or carbonate and/or non-calcium-, non-aluminum-, non-magnesium-containing phosphate binders (e.g., lanthanum carbonate, sevelamer hydrochloride) currently are used.^{127 130 131 132}

When taken with meals, calcium acetate or carbonate can contribute to controlling hyperphosphatemia in chronic renal failure by binding to and inhibiting absorption of phosphates in the GI tract.^{113 127}

Exercise caution in patients undergoing chronic hemodialysis to prevent hypophosphatemia.^b

Patients with end-stage renal failure may develop hypercalcemia when calcium is administered with meals; do not give calcium supplementation concomitantly when calcium salts are used to control hyperphosphatemia in such patients.¹¹³

Progressive hypercalcemia secondary to overdose of calcium salts can occur and may require emergency treatment measures.¹¹³

Chronic hypercalcemia also may lead to vascular and other soft-tissue calcification;^{113 126} periodic (e.g., twice weekly) monitoring of calcium concentrations is recommended during the initial dose adjustment.¹¹³ One manufacturer recommends that the serum calcium times phosphate (Ca × P) product should not exceed 66.¹¹³ Radiographic evaluation of a suspected anatomical region for early soft-tissue calcification may be useful.¹¹³

Advanced Cardiovascular Life Support (IV therapy)

Because of the lack of demonstrated benefit and potential for detrimental effects, calcium should not be used routinely during cardiac arrest unless there is documented hypocalcemia, calcium-channel blocker toxicity, hypermagnesemia, or hyperkalemia.^{196 400 401 403} When used in this setting, either calcium chloride or calcium gluconate may be administered.⁴⁰³

Aminoglycoside Neuromuscular Blockade (IV therapy)

Calcium salts are used to antagonize neuromuscular blockade^{† [off-label]} resulting from the use of aminoglycoside antibiotics (e.g., gentamicin, kanamycin, neomycin) with or without agents possessing neuromuscular blocking properties (e.g., gallamine triethiodide).^b

Magnesium Intoxication (IV therapy)

Calcium gluconate may be used in the treatment of magnesium sulfate overdosage.^{196 c}

Myasthenia Gravis (oral therapy)

Calcium salts are used as adjunctive treatment of myasthenia gravis.^b

In general, any oral calcium salt may be used for chronic replacement therapy.^b

Medullary Thyroid Carcinoma (IV therapy)

Calcium infusions (“calcium challenge”) are used in medullary thyroid carcinoma^{† [off-label]}.^b

Acid Indigestion (oral therapy)

Calcium carbonate or phosphate may be used for self-medication for the relief of acid indigestion, heartburn, and sour stomach.^d

Colic, Renal, Biliary, Intestinal, or Lead (IV and IM therapy)

Calcium salts have been used IM or IV as adjunctive therapy to reduce spasms in renal, biliary, intestinal, or lead colic.^b

Zollinger-Ellison Syndrome, Diagnosis (IV therapy)

Calcium infusions (“calcium challenge”) are used to diagnose the Zollinger-Ellison syndrome^{† [off-label]}.^b

Eaton-Lambert Syndrome (oral therapy)

Calcium salts are used as adjunctive treatment of the Eaton-Lambert syndrome.^b

In general, any oral calcium salt may be used for chronic replacement therapy.^b

Insect Bites and Other Sensitivity Reactions (IV therapy)

Calcium salts have been used IV as adjuncts to relieve muscle cramps in the treatment of insect bites or stings (e.g., black widow spider) or to decrease capillary permeability in sensitivity reactions characterized by urticaria or angioedema and in allergic conditions, including nonthrombocytopenic purpura, dermatitis herpetiformis, drug-induced pruritus, hay fever, and asthma.^b

Preeclampsia (oral therapy)

Although some evidence suggested a beneficial effect of calcium supplementation on preeclampsia,^{117 118 125} a large, well-designed study did not confirm a beneficial effect of calcium supplementation in preventing preeclampsia during pregnancy.¹¹⁷ However, these findings do not obviate adequate dietary calcium intake during pregnancy nor do they address whether adequate or increased calcium intake can affect blood pressure favorably in pregnant women.^{105 118 125}

β-Adrenergic or Calcium-channel Blocking Agent Overdosage (IV therapy)

Some experts state that calcium salts may be considered in the treatment of calcium-channel blocking agent-induced toxicity.⁴⁰³

Also may be useful in the treatment of β-adrenergic blocking agent toxicity in patients with shock refractory to other treatment measures.¹⁹⁶

Diuresis (oral therapy)

Calcium chloride, an acid-forming salt, has been used to promote diuresis, however, because it is irritating and loses effectiveness after a few days, it is rarely used for this effect.^b

Calcium Salts Dosage and Administration

Administration

Administer calcium orally (as acetate, carbonate, citrate, gluconate, lactate, or phosphate salt) or IV (as chloride or gluconate salt).^{b j}

The fixed combination of calcium glycerophosphate and calcium lactate is injected IM.¹⁴²

Calcium chloride also may be administered by intraosseous (IO) injection^{† [off-label]} during pediatric resuscitation; onset of action and systemic concentrations are comparable to those achieved with venous administration.⁴⁰³

Oral Administration

Administer acetate, carbonate, citrate, gluconate, lactate, and phosphate salts of calcium orally.^b

Administer most oral calcium supplements 1–1.5 hours after meals or with a demulcent (e.g., milk).^{112 b} However, calcium carbonate powder generally should be administered with meals, since mixing the powder with food for administration is recommended.^b

Calcium salts used to bind dietary phosphate in patients with end-stage renal disease should be administered with meals (e.g., 10–15 minutes before, or during, the meal).¹³⁰

IV Administration

Calcium chloride or gluconate may be administered IV.^{b j}

Calcium gluconate usually is administered IV as a 10% solution and calcium chloride as a 2–10% solution.^{b j}

When injected IV, administer calcium salts slowly through a small needle into a large vein to avoid too rapid an increase in serum calcium and extravasation of calcium solution into the surrounding tissue with resultant necrosis.^b

Following IV injections, the patient should remain recumbent for a short time.^b

Close monitoring of serum calcium concentrations is essential during IV administration of calcium.^b

Children: Calcium salts should not be administered through scalp veins; oral administration of calcium supplements or calcium-rich foods should replace IV calcium therapy as soon as possible.^b

Dilution

Usually, administer IV undiluted.^{a b c}

Parenteral calcium salts also may be administered in a compatible large-volume IV infusion fluid.^b

Pharmacy bulk packages are for preparing IV admixtures only.^g

Rate of Administration

Administer IV calcium injections slowly at a rate not exceeding 0.7–1.8 mEq/minute.^b

Stop the injection if the patient complains of discomfort.^b

Pharmacy bulk packages must not be infused IV directly.^g

Administer pediatric dose for CPR by slow IV injection over 10–20 seconds.^b

IM or Sub-Q Injection

Calcium chloride should not be injected IM or into subcutaneous or perivascular tissue, since severe necrosis and sloughing may occur.^b

Although other calcium salts may cause mild to severe local reactions, they generally are less irritating than calcium chloride.^b (See Cautions.)

Although some manufacturers previously stated that calcium gluconate could be injected IM when IV administration was not possible,^b manufacturers of calcium gluconate currently state that the drug should not be injected IM or into subcutaneous tissue because of the potential for severe local reactions.^{140 141}

The fixed-combination of calcium glycerophosphate and calcium lactate is injected IM.¹⁴²

Dosage

Dosage of the oral calcium supplements usually is expressed in g or mg of elemental calcium and depends on the requirements of the individual patient.^b

Dosage of parenteral calcium replacements usually is expressed as mEq of calcium and depends on individual patient requirements.^b

One mEq of elemental calcium is equivalent to 20 mg.^b

The calcium content of the various calcium salts is approximately:^b

Oral calcium supplements usually are administered in 3 or 4 divided doses daily.^b

Optimum calcium absorption may require supplemental vitamin D in individuals with inadequate vitamin D intake, those with impaired renal activation of the vitamin, or those not receiving adequate exposure to sunlight.^{112 116}

Pediatric Patients

Dietary Requirements

Oral

Dietary reference intake values for elemental calcium currently recommended by the National Academy of Sciences (NAS) in healthy children are as follows.¹⁵³ Adequate intakes (AIs) are given for infants <1 year of age because of inadequate data to establish recommended daily allowances (RDAs) in this age group.¹⁵³

Hypocalcemia

Calcium gluconate usually is administered IV as a 10% solution and calcium chloride as a 2–10% solution.^{b j}

Calcium replacement requirements can be estimated by clinical condition and/or serum calcium determinations.^b

Prevention

Oral

Neonates: Usually, 50–150 mg/kg of elemental calcium daily; do not exceed 1 g daily.^b

Children: Usually, 45–65 mg/kg of elemental calcium daily.^b

Treatment When Prompt Elevation of Serum Calcium Is Required

IV

Infants: <0.93 mEq of calcium; may be repeated every 1–3 days depending on the patient’s response.^{140 141 b}

Children: Usually, initial dose of 0.93–2.3 mEq of calcium; may be repeated every 1–3 days depending on the patient’s response.^{140 141 b}

Alternatively, one manufacturer recommends a pediatric IV calcium dose of 0.272 mEq/kg, up to a maximum total daily dosage of 1.36–13.6 mEq, in the treatment of hypocalcemic disorders.¹³⁸

Hypocalcemic Tetany

IV

Neonates: May be treated with divided doses of calcium totaling about 2.4 mEq/kg daily.^b

Children: Usually, calcium dose of 0.5–0.7 mEq/kg administered IV 3 or 4 times daily or until tetany is controlled.^b

Exchange Transfusions of Citrated Blood

IV

Neonates: 0.45 mEq of calcium concurrently with each 100 mL of citrated blood.^b

ACLS

IV/IO

If calcium is indicated during pediatric resuscitation for treatment of hypocalcemia, calcium-channel blocker overdosage, hypermagnesemia, or hyperkalemia, experts recommend a dose of 0.272 mEq/kg administered slowly using calcium chloride.⁴⁰³ In critically ill children, calcium chloride may provide a greater increase in ionized calcium than calcium gluconate.⁴⁰³

Adults

Dietary Requirements

Oral

Calcium replacement requirements can be estimated by clinical condition and/or serum calcium determinations.^b

Prophylactic administration of calcium supplements may be necessary in some patients in order to maintain serum calcium >9 mg/dL.^b

The RDAs of elemental calcium for healthy adults are:

Hypocalcemia

Calcium gluconate usually is administered IV as a 10% solution and calcium chloride as a 2–10% solution.^{b j}

Calcium replacement requirements can be estimated by clinical condition and/or serum calcium determinations.^b

Prevention

Oral

Usually, about 1 g of elemental calcium daily.^b

Treatment

Oral

Usually, 1–2 g or more of elemental calcium daily.^b

IM

Usually, 0.8 mEq of calcium as the calcium glycerophosphate and calcium lactate fixed-combination preparation 1–4 times weekly or as directed by a clinician.¹⁴²

Treatment When Prompt Elevation of Serum Calcium Is Required

IV

Usual initial dose of 2.3–14 mEq of calcium; doses may be repeated every 1–3 days depending on the patient’s response.^{136 137 138 139 140 141 b}

Hypocalcemic Tetany

IV

4.5–16 mEq doses of calcium, administered until therapeutic response occurs.^b

Exchange Transfusions of Citrated Blood

IV

About 1.35 mEq of calcium concurrently with each 100 mL of citrated blood.^b

ACLS

IV

If calcium is necessary during cardiac arrest, a dose of 0.109–0.218 mEq/kg (repeated as necessary) using calcium chloride has been recommended.¹⁷⁵ Alternatively, 7–14 mEq of calcium as calcium chloride has been given.^b However, routine use not recommended.^{400 401 403} (See Uses.)

Hyperphosphatemia in Chronic Renal Failure

Oral

Usual initial dose of 1.334 g of calcium acetate (338 mg of calcium) with each meal;¹¹³ increase dosage gradually according to serum phosphate concentrations, provided hypercalcemia does not occur.¹¹³

Manufacturer states that most patients require about 2–2.67 g (about 500–680 mg of calcium) with each meal.¹¹³ However, some experts recommend limiting dosage of calcium provided by phosphate binders to ≤1.5 g daily and limiting total calcium intake (including dietary calcium) to ≤2 g daily; dialysis patients who remain hyperphosphatemic despite such therapy should receive a calcium-containing phosphate binder in combination with a non-calcium-, non-aluminum-, non-magnesium-containing phosphate binder.¹³⁰

Monitor serum calcium concentrations twice weekly during initiation of therapy and subsequent dosage adjustment; also monitor serum phosphorus concentrations periodically.¹¹³

If hypercalcemia occurs, reduce dosage or withhold the salt.¹¹³ If severe hypercalcemia occurs, specific measures (e.g., hemodialysis) for the management of overdosage may be necessary.¹¹³

Zollinger-Ellison Syndrome, Diagnosis

IV

Usually, 0.25 mEq/kg of calcium per hour for a 3-hour period; serum gastrin concentrations are determined 30 minutes before the infusion, at the start of the infusion, and at 30-minute intervals thereafter for 4 hours.^b

In most patients with Zollinger-Ellison syndrome, preinfusion serum gastrin concentrations increase by more than 50% or by greater than 500 pg/mL during the infusion.^b

Magnesium Intoxication

IV

Initially, 7 mEq of calcium; adjust subsequent doses according to patient response.^b

Medullary Thyroid Carcinoma, Diagnosis

IV

Usually, about 7 mEq of calcium over 5–10 minutes; in patients with medullary thyroid carcinoma, plasma calcitonin concentrations are elevated above normal basal concentrations.^b

Osteoporosis

Oral

For prevention and treatment of osteoporosis, the National Osteoporosis Foundation recommends a calcium intake of 1 g daily in men 50–70 years of age, and a calcium intake of 1.2 g daily in women ≥51 years of age and men ≥71 years of age.¹⁴⁷

Special Populations

Hepatic Impairment

No specific dosage recommendations for hepatic impairment.^{a b c}

Renal Impairment

No specific dosage recommendations for renal impairment.^{a b c}

Geriatric Patients

No specific geriatric dosage recommendations.^a

Cautions for Calcium Salts

Contraindications

• Ventricular fibrillation.^b

• Hypercalcemia.^b

• Hypophosphatemia.^b

• Renal calculi.^b

• IV administration contraindicated when serum calcium concentrations are above normal.^b

Warnings/Precautions

Warnings

Use calcium salts cautiously, if at all, in sarcoidosis,^b renal or cardiac disease,^b or patients receiving cardiac glycosides (see Digoxin under Interactions).^b

Because it is acidifying, use calcium chloride cautiously in cor pulmonale,^b respiratory acidosis,^b renal disease,^b or respiratory failure.^b

Non-lipid-soluble drugs (e.g., calcium) may injure the airway; avoid endotracheal administration.⁴⁰³

Calcium Monitoring

Frequently perform determinations of serum calcium concentrations.^b

Maintain serum calcium concentrations at 9–10.4 mg/dL (4.5–5.2 mEq/L).^b Some clinicians prefer to maintain serum calcium at slightly lower concentrations.^b

Usually, do not allow serum calcium concentrations to exceed 12 mg/dL.^b

Determinations of urine calcium are generally unreliable and hypercalciuria can occur in the presence of hypocalcemia.^b Forcing fluids may produce increased urine volume and thus prevent the formation of renal stones in patients with hypercalciuria.^b

Citrated Blood Transfusion

Administration of calcium in patients who have received transfusions of citrated blood may result in higher than normal total serum calcium concentrations.^b In these patients, however, most of the excess calcium is bound to citrate and is inactive; therefore, serious toxicity usually does not result.^b

Discontinuing calcium when hypercalcemia occurs usually is sufficient to return serum calcium concentrations to normal.^b

Local Effects

Calcium salts are irritating to tissue when administered by IM or sub-Q injection and cause mild to severe local reactions including burning, necrosis and sloughing of tissue, cellulitis, and soft tissue calcification; venous irritation may occur with IV administration.^b (See IV Administration and also see IM or Sub-Q Injection, under Dosage and Administration.)

IV Injection Effects

Extravasation of calcium solution into surrounding tissues during IV injection can cause necrosis.^b

Patients may complain of tingling sensations, a sense of oppression or heat waves, and a calcium or chalky taste following IV administration of calcium salts.^b

Cardiovascular Effects

Rapid IV injection of calcium salts may cause vasodilation, decreased BP, bradycardia, cardiac arrhythmias, syncope, and cardiac arrest.^b

Inadvertent injection of calcium into the myocardium during attempted intracardiac injection into the ventricular cavity can result in lacerated coronary arteries, cardiac tamponade or pneumothorax, and intractable ventricular fibrillation may result.^b

GI Effects

Orally administered calcium salts may be irritating to the GI tract.^b

Calcium salts are constipating.^b

Calcium chloride, by any route of administration, produces more irritation than the other calcium salts and has been reported to cause GI hemorrhage when taken orally.^b

Hypercalcemia

Hypercalcemia is rarely produced by administration of calcium alone, but may occur with large doses in patients with chronic renal failure.^b

Avoid overtreatment of hypocalcemia since hypercalcemia may be more dangerous than hypocalcemia.^b

Mild hypercalcemia may be asymptomatic or manifest as constipation, anorexia, nausea, and vomiting, with mental changes such as confusion, delirium, stupor, and coma becoming evident as the degree of hypercalcemia increases.¹¹³

Mild hypercalcemia usually is readily controlled by reducing calcium intake (e.g., decreasing the dose of or avoiding supplemental calcium); more severe hypercalcemia may require specific management (e.g., hemodialysis).¹¹³

Dialysis patients with chronic renal failure receiving calcium salts may require adjustments in calcium concentrations in the dialysate to reduce the risk of hypercalcemia.^{113 126}

Long-term effects of chronic calcium administration (e.g., for hyperphosphatemia in chronic renal failure) on progression of vascular or soft-tissue calcification is unknown.^{113 127}

Renal Calculi

High dietary intake of calcium has long been suspected as contributing to the risk of renal calculi, and restriction of calcium intake (i.e., low-calcium diets) had long been considered a reasonable measure in an attempt to prevent calculi formation in patients with idiopathic hypocalciuria.^{122 123 124}

Recent evidence indicates that high dietary intake of calcium actually decreases the risk of symptomatic renal calculi, while intake of supplemental calcium may increase the risk of symptomatic stones.^{122 123 124}

General Precautions

Use of Fixed Combination

When used in fixed combination with other agents, consider the cautions, precautions, and contraindications associated with the concomitant agents.

Specific Populations

Pregnancy

Category C.^{c i}

Lactation

Manufacturers state that it is not known whether calcium salts are distributed into milk,^{a c} and to observe caution with parenteral therapy.^c

Calcium is an important component of human milk in women not receiving supplemental calcium salts,¹¹² and maternal calcium supplementation does not substantially affect milk calcium concentrations since the principal source is from maternal bone resorption.¹¹²

Pediatric Use

Give calcium cautiously to children by IV route.^PDH

Geriatric Use

Calcium absorption (after oral administration) may be decreased in geriatric patients.^PDH

Common Adverse Effects

Constipation, nausea, vein irritation.^PDH

Drug Interactions

Consider the possibility that other drug interactions reported with antacids could occur.^k

Specific Drugs and Laboratory Tests

Calcium Salts Pharmacokinetics

Absorption

Oral bioavailability of calcium from nonfood sources and supplements depends on intestinal pH, the presence or absence of a meal, and the dose.¹¹²

Calcium is actively absorbed in the duodenum and proximal jejunum and, to a lesser extent, in the more distal segments of the small intestine.^b

Degree of absorption depends on a number of factors; absorption from the intestine is never complete.^b

Absorption requires a soluble, ionized form.^b

An acidic intestinal pH is necessary for ionization of calcium; thus an alkaline pH impedes absorption.^{b 112}

Vitamin D, in its activated forms, is required for calcium absorption and increases the capability of the absorptive mechanisms.^b

Decreased absorption with hypocalcemia secondary to deficiency of either parathyroid hormone or vitamin D.^b

IM or IV administered calcium salts are absorbed directly into the blood stream.^b

Glucocorticoids and low serum concentrations of calcitonin may depress calcium absorption.^b

Bioavailability

When a 250-mg dose of calcium is administered with a standardized breakfast, average oral bioavailability in adults ranges from 25–35% with various salts; under the same conditions, absorption from milk is about 29%.¹¹²

Extent of calcium absorption from supplements is greatest when taken in doses ≤500 mg.¹¹²

Food

Calcium absorption is decreased in the absence of a meal.¹¹²

Calcium absorption is retarded by certain anions (e.g., oxalates, phytates, sulfates) and by fatty acids which precipitate or complex calcium ions; however, an intestinal pH of 5–7 facilitates maximal dissolution and dissociation of these complexes.^b

Calcium may be poorly absorbed from foods rich in oxalic acid (e.g., spinach, sweet potatoes, rhubarb, beans) or phytic acid (e.g., unleavened bread, raw beans, seeds, nuts, grains, soy isolates).¹¹²

Although soybeans contain high concentrations of phytic acid, calcium absorption is relatively high from this food.¹¹²

Plasma Concentrations

Following IV injection of calcium salts, serum calcium concentrations increase almost immediately and may return to previous values in 30 minutes to 2 hours.^b

Normal total serum calcium concentrations range from 9–10.4 mg/dL (4.5–5.2 mEq/L), but only ionized calcium is physiologically active.^b

Serum calcium concentrations are not necessarily accurate indications of total body calcium; total body calcium may be decreased in the presence of hypercalcemia, and hypocalcemia can occur even though total body calcium is increased.^b

Of total serum calcium concentration, 50% is in the ionic form and 5% is complexed by phosphates, citrates, and other anions.^b

Hyperproteinemia is associated with increased total serum calcium concentrations.^b

Hypoproteinemia is associated with decreased total serum calcium concentrations.^b

Acidosis results in increased concentrations of ionic calcium, while alkalosis promotes a decrease in the ionic serum calcium concentration.^b

Special Populations

Fractional calcium absorption varies with age as follows:

Infancy: about 60%.¹¹²

Children, prepubertal: about 28%.¹¹²

Early puberty: about 34%.¹¹²

Young adults: about 25%, although it increases during the last 2 trimesters of pregnancy.¹¹²

Fractional absorption declines with aging, decreasing on average by 0.21% annually in postmenopausal women.¹¹² Similar declines with aging in men.¹¹²

Absorption is decreased in certain disease states such as achlorhydria, renal osteodystrophy, steatorrhea, or uremia.^b

Efficiency of intestinal calcium absorption may be increased when calcium intake is reduced and during pregnancy^{112 b} but not lactation (maternal bone resorption is principal source)¹¹² when calcium requirements are higher than normal.^b

Distribution

CSF concentrations of calcium are about 50% of serum concentrations and tend to reflect ionized serum calcium concentrations.^b

Calcium enters extracellular fluid and is incorporated rapidly into skeletal tissue.^b Bone contains 99% of total calcium; 1% is distributed equally between the intracellular and extracellular fluids.^b

Extent

Following absorption, calcium first enters the extracellular fluid and is then rapidly incorporated into skeletal tissue.^b

Bone formation is not stimulated by calcium administration.^b

Plasma Protein Binding

Approximately 45%; for a change in serum albumin of 1 g/dL, serum calcium concentration may change about 0.8 mg/dL (0.04 mEq/dL).^b

Calcium crosses the placenta; reaches higher concentrations in fetal than maternal blood.^{b 112}

Calcium is distributed into milk.^b

Elimination

Elimination Route

Excreted mainly in the feces as unabsorbed calcium and that secreted via bile and pancreatic juice into the GI tract lumen.^b

Most of the calcium filtered by renal glomeruli is reabsorbed in the ascending limb of the loop of Henle and proximal and distal convoluted tubules.^b Only small amounts of the cation are excreted in urine.^b

Parathyroid hormone, vitamin D, and thiazide diuretics decrease urinary excretion of calcium, whereas other diuretics, calcitonin, and growth hormone promote renal excretion of the cation.^b

Urinary excretion decreases with reduction of ionic serum concentrations but is proportionately increased as serum ionized concentrations increase.^b

In healthy adults on a regular diet, urinary excretion of calcium may be as high as 250–300 mg daily.^b With low calcium diets, urinary excretion usually does not exceed 150 mg daily.^b

Calcium also is excreted by the sweat glands.^b

Special Populations

Urinary excretion of calcium decreases during pregnancy and in the early stages of renal failure.^b

Urinary excretion decreases with aging, possibly because of age-related decreases in intestinal calcium absorption efficiency and an associated decrease in filtered calcium load.¹¹²

Endogenous fecal calcium excretion does not change appreciably with aging.¹¹²

Stability

Storage

Oral

Capsules

25°C (may be exposed to 15–30°C).ⁱ

Solution

Tight container at 15–30°C.^f

Tablets

Cool, dry place at 15–30°C.^e

Parenteral

Injection

15–30°C; do not freeze.^{a c j}

Actions

• Calcium is essential for maintenance of the functional integrity of nervous, muscular, and skeletal systems and cell-membrane and capillary permeability.^b

• Calcium is an important activator in many enzymatic reactions and essential to a number of physiologic processes including transmission of nerve impulses; contraction of cardiac, smooth, and skeletal muscles; renal function; respiration; and blood coagulation.^b

• Calcium plays regulatory roles in the release and storage of neurotransmitters and hormones, in the uptake and binding of amino acids, and in cyanocobalamin (vitamin B₁₂) absorption and gastrin secretion.^b

• Calcium accounts for 1–2% of adult body weight, and more than 99% of total body calcium is found in bone and teeth.¹¹²

• Calcium is present in blood, extracellular fluid, muscle, and other tissues where it has roles in mediating vascular contraction and vasodilation, muscle contraction, nerve transmission, and glandular secretion.¹¹²

• Skeleton serves as a reservoir for calcium in addition to serving as a structural support for the body.¹¹²

• Conditions associated with reduced concentrations of circulating estrogen alter calcium homeostasis.¹¹²

• Reduced estrogen concentrations are associated with reduced calcium absorption efficiency and increased bone turnover rates.¹¹²

Advice to Patients

• Advise patients of the importance of dosage compliance, adherence to instructions about diet, and avoidance of concomitant use of antacids or other preparations containing clinically important concentrations of calcium.^{113 127 i PDH}

• Advise patients of importance of taking calcium with meals or milk for maximum absorption.^{112 b}

• Advise patients that daily supplemental intake >2 g is unlikely to provide additional benefit.^h

• Advise patients of potential manifestations of hypercalcemia.¹¹³

• Warn patients not to use bone meal or dolomite as a source of calcium; they may contain lead.^PDH

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.^{a b}

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^a

• Importance of informing patients of other important precautionary information.^{a b j} (See Cautions.)

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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