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Calcium Gluconate

Pronunciation

Pronunciation

(KAL see um GLOO koe nate)

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Capsule, Oral [preservative free]:

Cal-Glu: 500 mg [dye free]

Solution, Intravenous:

Generic: 10% (10 mL, 50 mL, 100 mL, 200 mL [DSC])

Solution, Intravenous [preservative free]:

Generic: 10% (100 mL)

Tablet, Oral:

Generic: 50 mg, 500 mg, 648 mg [DSC]

Brand Names: U.S.

  • Cal-Glu [OTC]

Pharmacologic Category

  • Calcium Salt
  • Electrolyte Supplement, Oral
  • Electrolyte Supplement, Parenteral

Pharmacology

Moderates nerve and muscle performance via action potential threshold regulation.

In hydrogen fluoride exposures, calcium gluconate provides a source of calcium ions to complex free fluoride ions and prevent or reduce toxicity; administration also helps to correct fluoride-induced hypocalcemia.

Absorption

Oral: Minimal unless chronic, high doses are given; predominantly in the duodenum and dependent on calcitriol and vitamin D; mean absorption of calcium intake varies with age (infants 60%, prepubertal children 28%, pubertal children 34%, adults 25%); during pregnancy, calcium absorption doubles; calcium is absorbed in soluble, ionized form; solubility of calcium is increased in an acidic environment (IOM 2011); decreased absorption occurs in patients with achlorhydria, renal osteodystrophy, steatorrhea, or uremia

Distribution

Primarily in bones, teeth (IOM 2011)

Excretion

Primarily feces (75%; as unabsorbed calcium salts); urine (20%) (IOM 2011)

Protein Binding

~40%, primarily to albumin (Wills 1971)

Use: Labeled Indications

IV: Treatment of hypocalcemia and conditions secondary to hypocalcemia (eg, tetany, seizures, arrhythmias); treatment of cardiac disturbances secondary to hyperkalemia; adjunctive treatment of rickets, osteomalacia, and magnesium sulfate overdose; decrease capillary permeability in allergic conditions, nonthrombocytopenic purpura, and exudative dermatoses (eg, dermatitis herpetiformis, pruritus secondary to certain drugs); treatment of black widow spider bites to relieve muscle cramping

Oral: Dietary calcium supplementation

Use: Unlabeled

Calcium channel blocker overdose; treatment of hydrofluoric acid exposure; supplement in total parenteral nutrition admixtures

Contraindications

Ventricular fibrillation; hypercalcemia; concomitant use of IV calcium gluconate and ceftriaxone in neonates

Dosing: Adult

Note: One gram of calcium gluconate salt is equal to 93 mg of elemental calcium.

Dosages are expressed in terms of the calcium gluconate salt (unless otherwise specified as elemental calcium). Dosages expressed in terms of the calcium gluconate salt are based on a solution concentration of 100 mg/mL (10%) containing 0.465 mEq (9.3 mg)/mL elemental calcium, except where noted.

Dietary Reference Intake for Calcium (IOM, 2011): Oral: Note: Dose expressed as elemental calcium:

Adults, Females/Males: RDA:

19 to 50 years: 1000 mg elemental calcium daily

≥51 years, females: 1200 mg elemental calcium daily

51 to 70 years, males: 1000 mg elemental calcium daily

Females: Pregnancy/Lactating: RDA: Requirements are the same as in nonpregnant or nonlactating females

Hypocalcemia: IV:

Mild (ionized calcium: 4 to 5 mg/dL [1 to 1.2 mmol/L]): 1000 to 2000 mg over 2 hours; asymptomatic patients may be given oral calcium (Ariyan, 2004; French, 2012)

Moderate-to-severe (without seizure or tetany; ionized calcium: <4 mg/dL [<1 mmol/L]): 4000 mg over 4 hours (French, 2012)

Severe symptomatic (eg, seizure, tetany): 1000 to 2000 mg over 10 minutes; repeat every 60 minutes until symptoms resolve (French, 2012)

Note: Repeat ionized calcium measurement 6 to 10 hours after completion of administration. Check for hypomagnesemia and correct if present. Consider continuous infusion if hypocalcemia is likely to recur due to ongoing losses (French, 2012).

Continuous infusion: 5 to 20 mg/kg/hour (Pai, 2011)

Cardiac arrest or cardiotoxicity in the presence of hyperkalemia, hypocalcemia, or hypermagnesemia: IV: 1500 to 3000 mg over 2 to 5 minutes (Vanden Hoek, 2010)

Note: Routine use in cardiac arrest is not recommended due to the lack of improved survival (Neumar, 2010):

Parenteral nutrition, maintenance requirement: IV (Mirtallo, 2004): Note: Expressed in terms of elemental calcium: 10 to 20 mEq elemental calcium daily

Calcium channel blocker overdose (off-label use): Hypotension/conduction disturbances: IV: 60 to 120 mg/kg/hour (Salhanick, 2003) or 60 mg/kg/dose over 5 minutes (maximum: 3000 to 6000 mg/dose) every 10 to 20 minutes; may repeat for 3 to 4 additional doses (Vanden Hoek, 2010; DeWitt, 2004). In life-threatening situations, 1000 mg has been administered every 2 to 3 minutes until clinical effect is achieved (Buckley, 1994). In one report, 18 g was administered over a 3-hour period (Luscher, 1994).

Hydrofluoric acid burns, treatment (off-label route/use):

SubQ (off-label route/use): 5% to 10% solution: 0.5 mL/cm2 of burned tissue (Dibbell, 1970; Hatzifotis, 2004; Kirkpatrick, 1995; Krenzelok, 1999). Infiltration should be carried 0.5 cm away from the margin of the injured tissue into the surrounding uninjured areas. Repeat if pain recurs. Local anesthesia may be required to perform procedure; pain resolution is the therapeutic endpoint and if a local anesthetic is utilized, it may be difficult to determine the success of therapy (Note: Never use calcium chloride for subcutaneous injection).

Intra-arterial (off-label route/use): Add 10 mL of a 10% solution to 50 mL of D5W. Infuse over 4 hours into the artery that provides the vascular supply to the affected area (Hatzifotis, 2004; Kirkpatrick, 1995). Pain usually resolves by the end of the infusion; repeat if pain recurs. This intervention should be used only by those accustomed to this technique. Extreme care should be taken to avoid the extravasation. A poison information center or clinical toxicologist should be consulted prior to implementation.

Inhalation (off-label route/use): 2.5% nebulization solution: Mix 1.5 mL of 10% calcium gluconate solution with 4.5 mL NS to make a 2.5% solution and administer via nebulization (Upfal 1990).

Dosing: Geriatric

Note: One gram of calcium gluconate salt is equal to 93 mg of elemental calcium.

Dosages are expressed in terms of the calcium gluconate salt (unless otherwise specified as elemental calcium). Dosages expressed in terms of the calcium gluconate salt are based on a solution concentration of 100 mg/mL (10%) containing 0.465 mEq (9.3 mg)/mL elemental calcium, except where noted.

Dietary Reference Intake for Calcium (IOM, 2011): Oral: Note: Dose expressed as elemental calcium: RDA

Females: Refer to adult dosing.

Males ≤70 years: Refer to adult dosing.

Males >70 years: 1200 mg elemental calcium daily

All other indications: Refer to adult dosing.

Dosing: Pediatric

Note: One gram of calcium gluconate salt is equal to 93 mg of elemental calcium.

Dosages are expressed in terms of the calcium gluconate salt (unless otherwise specified as elemental calcium). Dosages expressed in terms of the calcium gluconate salt are based on a solution concentration of 100 mg/mL (10%) containing 0.465 mEq (9.3 mg)/mL elemental calcium, except where noted.

Dietary Reference Intake for Calcium (IOM, 2011): Oral: Note: Dose expressed as elemental calcium:

1 to 6 months: Adequate intake: 200 mg elemental calcium daily

7 to 12 months: Adequate intake: 260 mg elemental calcium daily

1 to 3 years: RDA: 700 mg elemental calcium daily

4 to 8 years: RDA: 1000 mg elemental calcium daily

9 to 18 years: RDA: 1300 mg elemental calcium daily

Females: Pregnancy/Lactating: RDA: Requirements are the same as in nonpregnant or nonlactating females

Hypocalcemia:

General dosing: Infants, Children, and Adolescents: IV: 200 to 500 mg/kg/day as a continuous infusion or in 4 divided doses (maximum dose: 1000 mg/dose [Infants, Children]; 2000 to 3000 mg/dose [Adolescents]) (Edmondson, 1990; Zhou, 2009)

Symptomatic (ie, seizures, tetany): Infants, Children, and Adolescents: IV: 100 to 200 mg/kg/dose over 5 to 10 minutes; usual adult dose: 1000 to 2000 mg/dose; may repeat after 6 hours or follow with a continuous infusion of 200 to 800 mg/kg/day (Edmondson, 1990; Kelly, 2013; Misra, 2008; Nelson, 1996; Zhou, 2009)

Cardiac arrest or cardiotoxicity in the presence of hyperkalemia, hypocalcemia, or hypermagnesemia: Infants, Children, and Adolescents: IV, intraosseous: 60 to 100 mg/kg/dose (maximum: 3000 mg/dose); may repeat in 10 minutes if necessary; if effective, consider IV infusion (Hegenbarth, 2008)

Note: Routine use in cardiac arrest is not recommended due to the lack of improved survival (Kleinman, 2010; Neumar, 2010)

Parenteral nutrition, maintenance requirement: IV:

Infants and Children (≤50 kg) (Mirtallo, 2004): Note: Dose expressed as elemental calcium: 0.5 to 4 mEq elemental calcium/kg/day

Children (>50 kg) and Adolescents: Refer to adult dosing.

Calcium channel blocker overdose (off-label use): Hypotension/conduction disturbances: Infants, Children, and Adolescents: IV, intraosseous: 60 mg/kg/dose administered over 30 to 60 minutes (Hegenbarth, 2008). Note: Calcium chloride may provide a more rapid increase of ionized calcium in critically-ill children. Calcium gluconate may be substituted if calcium chloride is not available.

Hydrofluoric acid burns, treatment (off-label route/use): Children and Adolescents: Refer to adult dosing.

Dosing: Renal Impairment

No initial dosage adjustment necessary; however, accumulation may occur with renal impairment and subsequent doses may require adjustment based on serum calcium concentrations.

Dosing: Hepatic Impairment

No initial dosage adjustment necessary; subsequent doses should be guided by serum calcium concentrations. In patients in the anhepatic stage of liver transplantation, equal rapid increases in ionized concentrations occur suggesting that calcium gluconate does not require hepatic metabolism for release of ionized calcium (Martin, 1990).

Reconstitution

IV: Observe the vial for the presence of particulates. If particulates are observed, place vial in a 60°C to 80°C water bath for 15 to 30 minutes (or until solution is clear); occasionally shake to dissolve; cool to body/room temperature before use. Do not use vial if particulates do not dissolve. Note: Due to the potential presence of particulates, American Regent, Inc recommends the use of a 5 micron filter when preparing calcium gluconate-containing IV solutions (Important Drug Administration Information, American Regent, 2013); a similar recommendation has not been noted by other manufacturers. Usual concentrations: 1 g/100 mL D5W or NS; 2 g/100 mL D5W or NS. Maximum concentration in parenteral nutrition solutions is variable depending upon concentration and solubility (consult detailed reference).

Inhalation: Treatment of hydrofluoric acid burns (off-label use): Mix 1.5 mL of 10% calcium gluconate solution with 4.5 mL NS to make a 2.5% solution (Upfal 1990).

Administration

Oral: Administer with plenty of fluids with or following meals. The 10% calcium gluconate injection may be administered orally in young pediatric patients (Mimouni, 1994).

IV: Administer slowly (~1.5 mL calcium gluconate 10% per minute; not to exceed 200 mg/minute except in emergency situations) through a small needle into a large vein in order to avoid too rapid increases in the serum calcium and extravasation. Note: Due to the potential presence of particulates, American Regent, Inc recommends the use of a 0.22 micron inline filter for IV administration (1.2 micron filter if admixture contains lipids) (Important Drug Administration Information, American Regent, 2013); a similar recommendation has not been noted by other manufacturers. Not for IM administration. In acute situations of symptomatic hypocalcemia, infusions over 5 to 10 minutes have been described in pediatric patients (Kelly, 2013; Misra, 2008).

Vesicant; ensure proper needle or catheter placement prior to and during IV infusion. Avoid extravasation.

Extravasation management: If extravasation occurs, stop infusion immediately and disconnect (leave needle/cannula in place); gently aspirate extravasated solution (do NOT flush the line); initiate hyaluronidase antidote; remove needle/cannula; apply dry cold compresses (Hurst, 2004); elevate extremity.

Hyaluronidase: Intradermal or SubQ: Inject a total of 1 mL (15 units/mL) as five separate 0.2 mL injections (using a 25-gauge needle) into area of extravasation at the leading edge in a clockwise manner (MacCara, 1983; Zenk, 1981).

Treatment of hydrofluoric acid burns (off-label use):

SubQ infiltration (off-label route): Using a 27- or 30-gauge needle, approach the wound from the distal point of injury and infiltrate directly into the affected dermis and subcutaneous tissue. The infiltration should be carried 0.5 cm away from the margin of the injured tissue into the surrounding uninjured areas (Dibbell, 1970). Avoid excessive administration as it can cause compartment syndrome and further exacerbate tissue damage. Following subungual exposure, administer to the affected area via the lateral or volar route through the fat pad (under digital nerve block); administration may also require removal of the nailbed, splitting the distal nail from the nailbed, or trimming the nail to the nailbed to reach the affected area (Kirkpatrick, 1995; Roberts, 1989).

Intra-arterial (off-label route): Requires radiology to place an arterial catheter in an artery supplying blood to the area of exposure; infuse over four hours (Vance, 1986). This intervention should be used only by those accustomed to this technique. Care should be taken to avoid the extravasation. A poison information center or clinical toxicologist should be consulted prior to implementation.

Inhalation: Dilute 10% calcium gluconate solution to a 2.5% solution and administer via nebulization.

Compatibility

Stable in D5LR, D51/4NS, D51/2NS, D5NS, D5R, D5W, D10W, D20W, LR, NS; incompatible in fat emulsion 10%.

Y-site administration: Incompatible with amphotericin B cholesteryl sulfate complex, fluconazole, indomethacin, lansoprazole, pemetrexed.

Storage

IV: Store intact vials at 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F). Do not freeze. Calcium-phosphate stability in parenteral nutrition solutions is dependent upon the pH of the solution, temperature, and relative concentration of each ion. The pH of the solution is primarily dependent upon the amino acid concentration. The higher the percentage amino acids the lower the pH, the more soluble the calcium and phosphate. Individual commercially available amino acid solutions vary significantly with respect to pH lowering potential and consequent calcium phosphate compatibility.

Oral: Store at room temperature; consult product labeling for specific requirements.

Drug Interactions

Alpha-Lipoic Acid: Calcium Salts may decrease the absorption of Alpha-Lipoic Acid. Alpha-Lipoic Acid may decrease the absorption of Calcium Salts. Consider therapy modification

Bisphosphonate Derivatives: Calcium Salts may decrease the serum concentration of Bisphosphonate Derivatives. Management: Avoid administration of oral calcium supplements within: 2 hours before or after tiludronate/clodronate/etidronate; 60 minutes after oral ibandronate; or 30 minutes after alendronate/risedronate. Exceptions: Pamidronate; Zoledronic Acid. Consider therapy modification

Calcium Acetate: Calcium Salts may enhance the adverse/toxic effect of Calcium Acetate. Avoid combination

Calcium Channel Blockers: Calcium Salts may diminish the therapeutic effect of Calcium Channel Blockers. Monitor therapy

Cardiac Glycosides: Calcium Salts may enhance the arrhythmogenic effect of Cardiac Glycosides. Monitor therapy

CefTRIAXone: Calcium Salts (Intravenous) may enhance the adverse/toxic effect of CefTRIAXone. Ceftriaxone binds to calcium forming an insoluble precipitate. Management: Use of ceftriaxone with calcium-containing solutions within 48 hours of one another is contraindicated in neonates (28 days of age or younger). In older patients, flush lines with compatible fluid between administration. Consider therapy modification

Deferiprone: Calcium Salts may decrease the serum concentration of Deferiprone. Management: Separate administration of deferiprone and oral medications or supplements that contain polyvalent cations by at least 4 hours. Consider therapy modification

DOBUTamine: Calcium Salts may diminish the therapeutic effect of DOBUTamine. Monitor therapy

Dolutegravir: Calcium Salts may decrease the serum concentration of Dolutegravir. Management: Administer dolutegravir at least 2 hours before or 6 hours after oral calcium. Alternatively, dolutegravir and oral calcium can be taken together with food. Consider therapy modification

Eltrombopag: Calcium Salts may decrease the serum concentration of Eltrombopag. Management: Administer eltrombopag at least 2 hours before or 4 hours after oral administration of any calcium-containing product. Consider therapy modification

Estramustine: Calcium Salts may decrease the absorption of Estramustine. Consider therapy modification

Multivitamins/Fluoride (with ADE): May increase the serum concentration of Calcium Salts. Calcium Salts may decrease the serum concentration of Multivitamins/Fluoride (with ADE). More specifically, calcium salts may impair the absorption of fluoride. Management: Avoid eating or drinking dairy products or consuming vitamins or supplements with calcium salts one hour before or after of the administration of fluoride. Consider therapy modification

Multivitamins/Minerals (with ADEK, Folate, Iron): May increase the serum concentration of Calcium Salts. Monitor therapy

Phosphate Supplements: Calcium Salts may decrease the absorption of Phosphate Supplements. Management: This applies only to oral phosphate and calcium administration. Administering oral phosphate supplements as far apart from the administration of an oral calcium salt as possible may be able to minimize the significance of the interaction. Exceptions: Sodium Glycerophosphate Pentahydrate. Consider therapy modification

Quinolone Antibiotics: Calcium Salts may decrease the absorption of Quinolone Antibiotics. Of concern only with oral administration of both agents. Exceptions: LevoFLOXacin (Oral Inhalation); Moxifloxacin (Systemic). Consider therapy modification

Strontium Ranelate: Calcium Salts may decrease the serum concentration of Strontium Ranelate. Management: Separate administration of strontium ranelate and oral calcium salts by at least 2 hours in order to minimize this interaction. Consider therapy modification

Tetracycline Derivatives: Calcium Salts may decrease the serum concentration of Tetracycline Derivatives. Management: If coadministration of oral calcium with oral tetracyclines can not be avoided, consider separating administration of each agent by several hours. Consider therapy modification

Thiazide and Thiazide-Like Diuretics: May decrease the excretion of Calcium Salts. Continued concomitant use can also result in metabolic alkalosis. Monitor therapy

Thyroid Products: Calcium Salts may diminish the therapeutic effect of Thyroid Products. Management: Separate the doses of the thyroid product and the oral calcium supplement by at least 4 hours. Consider therapy modification

Trientine: Calcium Salts may decrease the serum concentration of Trientine. Trientine may decrease the serum concentration of Calcium Salts. Consider therapy modification

Vitamin D Analogs: Calcium Salts may enhance the adverse/toxic effect of Vitamin D Analogs. Monitor therapy

Test Interactions

IV administration may produce falsely decreased serum and urine magnesium concentrations

Adverse Reactions

Frequency not defined.

IV:

Cardiovascular (with rapid IV injection): Arrhythmia, bradycardia, cardiac arrest, hypotension, syncope, vasodilation

Central nervous system: Sense of oppression (with rapid IV injection)

Endocrine & metabolic: Hypercalcemia

Gastrointestinal: Chalky taste

Neuromuscular & skeletal: Tingling sensation (with rapid IV injection)

Miscellaneous: Heat waves (with rapid IV injection)

Postmarketing and/or case reports: Calcinosis cutis

Oral: Gastrointestinal: Constipation

Warnings/Precautions

Concerns related to adverse effects:

• Gastrointestinal effects: Constipation, bloating, and gas are common with oral calcium supplements (especially carbonate salt).

Disease-related concerns:

• Hyperphosphatemia: Use with caution in patients with severe hyperphosphatemia as elevated levels of phosphorus and calcium may result in soft tissue and pulmonary arterial calcium-phosphate precipitation.

• Hypokalemia: Use with caution in patients with severe hypokalemia as acute rises in serum calcium levels may result in life-threatening cardiac arrhythmias.

• Hypomagnesemia: Hypomagnesemia is a common cause of hypocalcemia; therefore, correction of hypocalcemia may be difficult in patients with concomitant hypomagnesemia. Evaluate serum magnesium and correct hypomagnesemia (if necessary), particularly if initial treatment of hypocalcemia is refractory.

• Kidney stones (calcium-containing): Use caution when administering calcium supplements to patients with a history of kidney stones.

• Renal impairment: Use with caution in patients with chronic renal failure to avoid hypercalcemia; frequent monitoring of serum calcium and phosphorus is necessary.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Dosage form specific issues:

• Aluminum: The parenteral product may contain aluminum; toxic aluminum concentrations may be seen with high doses, prolonged use, or renal dysfunction. Premature neonates are at higher risk due to immature renal function and aluminum intake from other parenteral sources. Parenteral aluminum exposure of >4 to 5 mcg/kg/day is associated with CNS and bone toxicity; tissue loading may occur at lower doses (Federal Register, 2002). See manufacturer’s labeling.

• Appropriate product selection: Multiple salt forms of calcium exist; close attention must be paid to the salt form when ordering and administering calcium; incorrect selection or substitution of one salt for another without proper dosage adjustment may result in serious over or under dosing.

• IV administration: Avoid too rapid IV administration (do not exceed 200 mg/minute except in emergency situations); may result in vasodilation, hypotension, bradycardia, arrhythmias, and cardiac arrest. Parenteral calcium is a vesicant; ensure proper catheter or needle position prior to and during infusion. Avoid extravasation; adverse events from extravasation can be devastating (eg, profound tissue necrosis). Monitor the IV site closely.

• Oral administration: Administering oral calcium with food and vitamin D will optimize calcium absorption.

• Tartrazine: Some products may contain tartrazine which may cause allergic reactions in susceptible individuals.

Pregnancy Risk Factor

C

Pregnancy Considerations

Animal reproduction studies have not been conducted. Calcium crosses the placenta. The amount of calcium reaching the fetus is determined by maternal physiological changes. Calcium requirements are the same in pregnant and nonpregnant females (IOM 2011). Information related to use as an antidote in pregnancy is limited. In general, medications used as antidotes should take into consideration the health and prognosis of the mother; antidotes should be administered to pregnant women if there is a clear indication for use and should not be withheld because of fears of teratogenicity (Bailey 2003). Medications used for the treatment of cardiac arrest in pregnancy are the same as in the non-pregnant woman. Doses and indications should follow current Advanced Cardiovascular Life Support guidelines. Appropriate medications should not be withheld due to concerns of fetal teratogenicity (Jeejeebhoy [AHA] 2015).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience constipation, sensation of warmth, tingling, or bad taste. Have patient report immediately to prescriber signs of high calcium (weakness, confusion, fatigue, headache, nausea and vomiting, constipation, or bone pain), flushing, severe dizziness, passing out, bradycardia, abnormal heartbeat, or severe injection site pain, redness, burning, edema, or irritation (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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