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Calcium Salts

Class: Replacement Preparations
- Antidotes
VA Class: TN420
CAS Number: 543-90-8
Brands: Alka-Mints, Calci-Chew, Calci-Mix, Caltrate, Chooz, Citracal, Liqui-Cal, Os-Cal, PhosLo, Posture, Posture-D, Titralac, Tums

Warning

    Pharmacy Bulk Packages
  • Pharmacy bulk packages are for preparation of IV mixtures only.

  • Not for direct IV infusion.

Introduction

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

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).

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

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.

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

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.

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. 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.

Some clinicians consider IV calcium chloride the calcium salt of choice to prevent hypocalcemia during transfusions with citrated blood. 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).

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

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

Calcium is administered in long-term electrolyte replacement regimens.

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

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

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

Hypocalcemic Tetany (IV therapy)

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

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.

Hypoparathyroidism, Chronic (oral therapy)

Calcium salts may be used for treatment of chronic hypoparathyroidism.

Latent Tetany (oral therapy)

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

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.

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.

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.

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

Glucocorticoid-induced Osteoporosis (oral therapy)

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

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).

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.

Osteomalacia (oral therapy)

Calcium salts may be used for treatment of osteomalacia.

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.

Rickets (oral therapy)

Calcium salts may be used for treatment of rickets.

Hyperphosphatemia in Chronic Renal Failure (oral therapy)

Calcium acetate and calcium carbonate are considered the salts of choice for chronic renal failure.

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.

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

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.

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.

Exercise caution in patients undergoing chronic hemodialysis to prevent hypophosphatemia.

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.

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

Chronic hypercalcemia also may lead to vascular and other soft-tissue calcification; periodic (e.g., twice weekly) monitoring of calcium concentrations is recommended during the initial dose adjustment. One manufacturer recommends that the serum calcium times phosphate (Ca × P) product should not exceed 66. Radiographic evaluation of a suspected anatomical region for early soft-tissue calcification may be useful.

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. When used in this setting, either calcium chloride or calcium gluconate may be administered.

Aminoglycoside Neuromuscular Blockade (IV therapy)

Calcium salts are used to antagonize neuromuscular blockade resulting from the use of aminoglycoside antibiotics (e.g., gentamicin, kanamycin, neomycin) with or without agents possessing neuromuscular blocking properties (e.g., gallamine triethiodide).

Magnesium Intoxication (IV therapy)

Calcium gluconate may be used in the treatment of magnesium sulfate overdosage.

Myasthenia Gravis (oral therapy)

Calcium salts are used as adjunctive treatment of myasthenia gravis.

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

Medullary Thyroid Carcinoma (IV therapy)

Calcium infusions (“calcium challenge”) are used in medullary thyroid carcinoma.

Acid Indigestion (oral therapy)

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

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.

Zollinger-Ellison Syndrome, Diagnosis (IV therapy)

Calcium infusions (“calcium challenge”) are used to diagnose the Zollinger-Ellison syndrome.

Eaton-Lambert Syndrome (oral therapy)

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

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

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.

Preeclampsia (oral therapy)

Although some evidence suggested a beneficial effect of calcium supplementation on preeclampsia, a large, well-designed study did not confirm a beneficial effect of calcium supplementation in preventing preeclampsia during pregnancy. 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.

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.

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

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.

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).

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

Calcium chloride also may be administered by intraosseous (IO) injection during pediatric resuscitation; onset of action and systemic concentrations are comparable to those achieved with venous administration.

Oral Administration

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

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

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).

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Calcium chloride or gluconate may be administered IV.

Calcium gluconate usually is administered IV as a 10% solution and calcium chloride as a 2–10% solution.

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.

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

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

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.

Dilution

Usually, administer IV undiluted.

Parenteral calcium salts also may be administered in a compatible large-volume IV infusion fluid. (See Solution Compatibility under Compatibility.)

Pharmacy bulk packages are for preparing IV admixtures only.

Rate of Administration

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

Stop the injection if the patient complains of discomfort.

Pharmacy bulk packages must not be infused IV directly.

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

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.

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

Although some manufacturers previously stated that calcium gluconate could be injected IM when IV administration was not possible, 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.

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

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.

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

One mEq of elemental calcium is equivalent to 20 mg.

The calcium content of the various calcium salts is approximately:

Calcium Salt

Calcium Content

calcium acetate

253 mg (12.7 mEq) per g

calcium carbonate

400 mg (20 mEq) per g

calcium chloride

270 mg (13.5 mEq) per g

calcium citrate

211 mg (10.6 mEq) per g

calcium gluceptate

82 mg (4.1 mEq) per g

calcium gluconate

90 mg (4.5 mEq) per g

calcium glycerophosphate

191 mg (9.6 mEq) per g

calcium lactate

130 mg (6.5 mEq) per g

calcium phosphate dibasic anhydrous

290 mg (14.5 mEq) per g

calcium phosphate dibasic dihydrate

230 mg (11.5 mEq) per g

calcium phosphate tribasic

400 mg (20 mEq) per g

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

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.

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. 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.

Infants <6 Months of Age:

AI of 200 mg daily (presumed to be met by human milk).

Infants 6–12 Months of Age:

AI of 260 mg daily (taking into account additional intake of calcium from food).

Children 1–3 Years of Age:

RDA of 700 mg daily.

Children 4–8 Years of Age:

RDA of 1 g daily.

Children 9–18 Years of Age:

RDA of 1.3 g daily.

Hypocalcemia

Calcium gluconate usually is administered IV as a 10% solution and calcium chloride as a 2–10% solution.

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

Prevention
Oral

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

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

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.

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.

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.

Hypocalcemic Tetany
IV

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

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

Exchange Transfusions of Citrated Blood
IV

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

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. In critically ill children, calcium chloride may provide a greater increase in ionized calcium than calcium gluconate.

Adults

Dietary Requirements
Oral

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

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

The RDAs of elemental calcium for healthy adults are:

Adults 19–50 Years of Age:

RDA of 1 g daily.

Adults 51–70 Years of Age:

Men 51–71 years of age: RDA of 1 g daily.

Women 51–70 years of age: RDA of 1.2 g daily.

Adults >70 Years of Age:

RDA of 1.2 g daily.

Pregnant or Lactating Women:

Generally, the usual RDA of calcium appropriate for their age.

Hypocalcemia

Calcium gluconate usually is administered IV as a 10% solution and calcium chloride as a 2–10% solution.

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

Prevention
Oral

Usually, about 1 g of elemental calcium daily.

Treatment
Oral

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

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.

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.

Hypocalcemic Tetany
IV

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

Exchange Transfusions of Citrated Blood
IV

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

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. Alternatively, 7–14 mEq of calcium as calcium chloride has been given. However, routine use not recommended. (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; increase dosage gradually according to serum phosphate concentrations, provided hypercalcemia does not occur.

Manufacturer states that most patients require about 2–2.67 g (about 500–680 mg of calcium) with each meal. 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.

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

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

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.

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.

Magnesium Intoxication
IV

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

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.

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.

Special Populations

Hepatic Impairment

No specific dosage recommendations for hepatic impairment.

Renal Impairment

No specific dosage recommendations for renal impairment.

Geriatric Patients

No specific geriatric dosage recommendations.

Cautions for Calcium Salts

Contraindications

  • Ventricular fibrillation.

  • Hypercalcemia.

  • Hypophosphatemia.

  • Renal calculi.

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

Warnings/Precautions

Warnings

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

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

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

Calcium Monitoring

Frequently perform determinations of serum calcium concentrations.

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

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

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

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. In these patients, however, most of the excess calcium is bound to citrate and is inactive; therefore, serious toxicity usually does not result.

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

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. (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.

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.

Cardiovascular Effects

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

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.

GI Effects

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

Calcium salts are constipating.

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.

Hypercalcemia

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

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

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.

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).

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

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.

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.

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.

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.

Lactation

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

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

Pediatric Use

Give calcium cautiously to children by IV route.

Geriatric Use

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

Common Adverse Effects

Constipation, nausea, vein irritation.

Interactions for Calcium Salts

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

Specific Drugs and Laboratory Tests

Drug or Test

Interaction

Comments

Bisphosphonates, oral (e.g., alendronate, etidronate, ibandronate, risedronate)

Concomitant administration may result in reduced bisphosphonate absorption

Separate administration of the drugs

Digoxin

Inotropic and toxic effects are synergistic and arrhythmias may occur (particularly when calcium is given IV)

Iron preparations, oral

Concomitant administration may result in reduced iron absorption

Advise patients to take the drugs at different times, whenever possible

Levothyroxine

Calcium carbonate may form insoluble chelate with levothyroxine, resulting in decreased levothyroxine absorption and increased serum thyrotropin concentrations

Administer oral levothyroxine and calcium carbonate ≥4 hours apart

Quinolones

Concomitant administration of calcium salts and some fluoroquinolones (e.g., ciprofloxacin) may reduce oral bioavailability of the fluoroquinolone

Recommended timing of fluoroquinolone administration relative to the calcium dose may vary depending on the specific fluoroquinolone preparation used

Test, corticosteroids (Glenn-Nelson technique)

Transient elevations of plasma 11-hydroxycorticosteroid concentrations with IV calcium, but concentrations return to control values after 1 hour

Test, magnesium (serum and urine)

False-negative values as measured by the Titan yellow method

Tetracyclines

Calcium complexes tetracycline antibiotics rendering them inactive

Do not give the 2 drugs together orally nor should they be mixed for parenteral administration

Thiazide diuretics

Risk of hypercalcemia

Avoid concomitant use

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.

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

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

Absorption requires a soluble, ionized form.

An acidic intestinal pH is necessary for ionization of calcium; thus an alkaline pH impedes absorption.

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

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

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

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

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%.

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

Food

Calcium absorption is decreased in the absence of a meal.

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.

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).

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

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.

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.

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.

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

Hyperproteinemia is associated with increased total serum calcium concentrations.

Hypoproteinemia is associated with decreased total serum calcium concentrations.

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

Special Populations

Fractional calcium absorption varies with age as follows:

Infancy: about 60%.

Children, prepubertal: about 28%.

Early puberty: about 34%.

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

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

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

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

Distribution

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

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

Extent

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

Bone formation is not stimulated by calcium administration.

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).

Calcium crosses the placenta; reaches higher concentrations in fetal than maternal blood.

Calcium is distributed into milk.

Elimination

Elimination Route

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

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. Only small amounts of the cation are excreted in urine.

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.

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

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

Calcium also is excreted by the sweat glands.

Special Populations

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

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

Endogenous fecal calcium excretion does not change appreciably with aging.

Stability

Storage

Oral

Capsules

25°C (may be exposed to 15–30°C).

Solution

Tight container at 15–30°C.

Tablets

Cool, dry place at 15–30°C.

Parenteral

Injection

15–30°C; do not freeze.

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Interaction of calcium and phosphate in parenteral nutrition solutions is a complex phenomenon; various factors have been identified as playing a role in solubility or precipitation of a given combination. Calcium salts are conditionally compatible with phosphate in parenteral nutrition solutions; incompatibility dependent on a solubility and concentration phenomenon and not entirely predictable. Precipitation may occur during compounding or at some time after compounding is completed. Consult specialized references for specific stability and compatibility information.

Calcium Chloride

Parenteral
Solution CompatibilityHID

Incompatible

Fat emulsion 10%, IV

Drug Compatibility
Admixture CompatibilityHID

Compatible

Amikacin sulfate

Ascorbic acid injection

Chloramphenicol sodium succinate

Dopamine HCl

Hydrocortisone sodium succinate

Isoproterenol HCl

Lidocaine HCl

Norepinephrine bitartrate

Penicillin G potassium

Penicillin G sodium

Pentobarbital sodium

Phenobarbital sodium

Verapamil HCl

Incompatible

Amphotericin B

Ceftriaxone sodium

Magnesium sulfate

Variable

Dobutamine HCl

Sodium bicarbonate

Y-site CompatibilityHID

Compatible

Amiodarone HCl

Ceftaroline fosamil

Dobutamine HCl

Doxapram HCl

Epinephrine HCl

Esmolol HCl

Hydroxyethyl starch 130/0.4 in sodium chloride 0.9%

Micafungin sodium

Milrinone lactate

Morphine sulfate

Paclitaxel

Sodium nitroprusside

Incompatible

Amphotericin B cholesteryl sulfate complex

Propofol

Sodium bicarbonate

Calcium Gluconate

Parenteral
Solution CompatibilityHID

Compatible

Alcohol 5%, dextrose 5%

Amino acids 4%, dextrose 25%

Dextrose 5% in Ringer’s injection, lactated

Dextrose 5% in sodium chloride 0.9%

Dextrose 5% in water

Dextrose 10% in sodium chloride 0.18%

Dextrose 10 or 20% in water

Fructose 10% in water

Invert sugar 10% in Electrolyte #1 or #2

Polysal M with dextrose 5%

Ringer’s injection, lactated

Sodium chloride 0.9%

Sodium lactate 1/6 M

Incompatible

Fat emulsion 10%, IV

Drug Compatibility
Admixture CompatibilityHID

Compatible

Amikacin sulfate

Aminophylline

Ascorbic acid injection

Chloramphenicol sodium succinate

Furosemide

Heparin sodium

Hydrocortisone sodium succinate

Lidocaine HCl

Norepinephrine bitartrate

Penicillin G potassium

Penicillin G sodium

Phenobarbital sodium

Potassium chloride

Prochlorperazine edisylate

Tobramycin sulfate

Vancomycin HCl

Verapamil HCl

Incompatible

Amphotericin B

Ceftriaxone sodium

Dobutamine HCl

Methylprednisolone sodium succinate

Variable

Magnesium sulfate

Y-Site CompatibilityHID

Compatible

Aldesleukin

Allopurinol sodium

Amifostine

Amiodarone HCl

Aztreonam

Bivalirudin

Cefazolin sodium

Ceftaroline fosamil

Ciprofloxacin

Cisatracurium besylate

Cladribine

Dexmedetomidine HCl

Dobutamine HCl

Docetaxel

Doripenem

Doxapram HCl

Doxorubicin HCl liposome injection

Enalaprilat

Epinephrine HCl

Etoposide phosphate

Famotidine

Fenoldopam mesylate

Filgrastim

Gemcitabine HCl

Granisetron HCl

Heparin sodium with hydrocortisone sodium succinate

Hetastarch in lactated electrolyte injection (Hextend)

Hydroxyethyl starch 130/0.4 in sodium chloride 0.9%

Labetalol HCl

Linezolid

Melphalan HCl

Micafungin sodium

Midazolam HCl

Milrinone lactate

Nicardipine HCl

Oxaliplatin

Piperacillin sodium–tazobactam sodium

Potassium chloride

Prochlorperazine edisylate

Propofol

Remifentanil HCl

Sargramostim

Tacrolimus

Telavancin HCl

Teniposide

Thiotepa

Vinorelbine tartrate

Incompatible

Amphotericin B cholesteryl sulfate complex

Fluconazole

Indomethacin sodium trihydrate

Pemetrexed disodium

Variable

Ampicillin sodium

Meropenem

Actions

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

  • 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.

  • 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.

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

  • 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.

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

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

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

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.

  • Advise patients of importance of taking calcium with meals or milk for maximum absorption.

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

  • Advise patients of potential manifestations of hypercalcemia.

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

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.

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

  • Importance of informing patients of other important precautionary information. (See Cautions.)

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.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Calcium Acetate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Bulk

Powder*

Calcium Acetate Powder

Oral

Capsules

667 mg (169 mg calcium; 8.45 mEq of Ca++)*

Calcium Acetate Capsules

PhosLo GelCaps

Fresenius

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Calcium Carbonate, Precipitated

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Bulk

Powder*

Calcium Carbonate, Precipitated Powder

Oral

Capsules

1.25 g (500 mg calcium)

Calcium Carbonate, Precipitated Calci-Mix

Watson

Capsules, liquid-filled

600 mg (240 mg of calcium)

Liqui-Cal Softgels

Advanced Nutritional Technology

Suspension

1.25 g (500 mg calcium) per 5 mL*

Calcium Carbonate Suspension

Tablets

650 mg (260 mg calcium)*

Calcium Carbonate Tablets

1.25 g (500 mg calcium)*

Calcium Carbonate Tablets

Os-Cal 500

GlaxoSmithKline

Tablets, chewable

420 mg (168 mg calcium)

Titralac

3M

500 mg (200 mg calcium)

Chooz

Insight

Tums

GlaxoSmithKline

750 mg (300 mg calcium)

Tums E-X 750

GlaxoSmithKline

850 mg (340 mg calcium)

Alka-Mints

Bayer

1 g (400 mg calcium)

Tums Ultra 1000

GlaxoSmithKline

1.25 g (500 mg calcium)*

Calcium Carbonate Chewable Tablets

Calci-Chew

Watson

Os-Cal 500

GlaxoSmithKline

Tablets, film-coated

1.5 g (600 mg calcium)*

Calcium Carbonate Tablets

Caltrate 600

Wyeth

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Calcium Carbonate, Precipitated, Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Pieces, chewable

1.25 g (500 mg calcium) with Cholecalciferol 100 units and Phytonadione 40 mcg

Viactiv Soft Calcium Chews

McNeil

Tablets

Calcium Carbonate 240 mg with Calcium Gluconate 240 mg, Calcium Lactate 240 mg (152.8 mg calcium), and Cholecalciferol 100 units

Calcet

Mission

1.25 g (500 mg calcium) with Cholecalciferol 200 units*

Calcium Carbonate, Precipitated, and Cholecalciferol Tablets

Os-Cal 500+D

GlaxoSmithKline

1.5 g (600 mg calcium) with Cholecalciferol 125 units*

Calcium Carbonate, Precipitated, and Cholecalciferol Tablets

1.5 g (600 mg calcium) with Cholecalciferol 280 units*

Calcium Carbonate, Precipitated, and Cholecalciferol Tablets

Healthy Woman (scored)

Personal Products

Tablets, film-coated

1.5 g (600 mg calcium) with Cholecalciferol 400 units

Caltrate 600 + Vitamin D

Wyeth

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Calcium Chloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Bulk

Powder*

Calcium Chloride Powder

Parenteral

Injection

10% (1.36–1.4 mEq of Ca++ and Cl per mL)*

Calcium Chloride Injection

Calcium Citrate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

950 mg (200 mg calcium)

Citracal

Bayer

Calcium Citrate Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

1.5 g (315 mg calcium) with Cholecalciferol 250 units

Citracal + D Caplets

Bayer

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Calcium Gluceptate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Bulk

Powder*

Calcium Gluceptate Powder

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Calcium Gluconate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Bulk

Powder*

Calcium Gluconate Powder

Oral

Tablets

500 mg (45 mg calcium)*

Calcium Gluconate Tablets

650 mg (58.5 mg calcium)*

Calcium Gluconate Tablets

1 g (90 mg calcium)*

Calcium Gluconate Tablets

Parenteral

Injection

10% (0.45–0.48 mEq of Ca++ per mL provided by calcium gluconate and other calcium salt stabilizers)*

Calcium Gluconate Injection

Injection, for preparation of IV admixtures

10% (0.45–0.48 mEq of Ca++ per mL provided by calcium gluconate and calcium saccharate or other calcium salts stabilizers) pharmacy bulk package*

Calcium Gluconate Injection Pharmacy Bulk Package

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Calcium Glycerophosphate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Bulk

Powder*

Calcium Glycerophosphate Powder

Calcium Glycerophosphate and Calcium Lactate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection

0.08 mEq of Ca++ (provided by calcium glycerophosphate 5 mg and calcium lactate 5 mg) per mL

Calphosan

Glenwood

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Calcium Lactate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Bulk

Powder*

Calcium Lactate Powder

Oral

Tablets

325 mg (42.25 mg calcium)*

Calcium Lactate Tablets

650 mg (84.5 mg calcium)*

Calcium Lactate Tablets

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Calcium Phosphate Dibasic

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Bulk

Powder*

Calcium Phosphate Dibasic Powder

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Calcium Phosphate Tribasic

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Bulk

Powder*

Calcium Phosphate Tribasic Powder

Oral

Tablets, film-coated

1.5652 g (600 mg calcium)

Posture (scored)

Inverness

Calcium Phosphate Tribasic Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

1.5652 g (600 mg calcium) with Cholecalciferol 125 units

Posture-D (scored)

Inverness

Calcium salts are also commercially available in combination with vitamins, minerals, electrolytes, and antacids.

AHFS DI Essentials™. © Copyright 2021, Selected Revisions January 7, 2019. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

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