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Calcium Gluconate

Mode Of Action

In its use as poisoning antidote, calcium antagonizes blockade of calcium channels by drugs besides altering membrane polarization and chelating fluoride ions.

Drug Indication Magnesium toxicity; severe hyperkalaemia not related to digoxin toxicity; acute calcium channel blocker poisoning with heart block and burns from hydrofluoric acid.
Side Effects Hypersensitivity

Medication Safety Issues
Sound-alike/look-alike issues:

Calcium gluconate may be confused with calcium glubionate

Pharmacologic Category
  • Calcium Salt;
  • Electrolyte Supplement, Oral;
  • Electrolyte Supplement, Parenteral
Dosing: Adult

Adequate Intake (as elemental calcium):

Adults, Male/Female:

19-50 years: 1000 mg/day

≥51 years: 1200 mg/day

Female: Pregnancy/Lactating: Same as for Adults, Male/Female

Dosage note: Calcium chloride has 3 times more elemental calcium than calcium gluconate. Calcium chloride is 27% elemental calcium; calcium gluconate is 9% elemental calcium. One gram of calcium chloride is equal to 270 mg of elemental calcium; 1 gram of calcium gluconate is equal to 90 mg of elemental calcium. The following dosages are expressed in terms of the calcium gluconate salt based on a solution concentration of 100 mg/mL (10%) containing 0.465 mEq (9.3 mg)/mL elemental calcium:

Hypocalcemia:

I.V.: 2-15 g/24 hours as a continuous infusion or in divided doses

Oral: 500 mg to 2 g 2-4 times/day

Hypocalcemia secondary to citrated blood infusion: I.V.: 500 mg to 1 g per 500 mL of citrated blood (infused into another vein). Single doses up to 2 g have also been recommended.

Note: Routine administration of calcium, in the absence of signs/symptoms of hypocalcemia, is generally not recommended. A number of recommendations have been published seeking to address potential hypocalcemia during massive transfusion of citrated blood; however, many practitioners recommend replacement only as guided by clinical evidence of hypocalcemia and/or serial monitoring of ionized calcium.

Hypocalcemic tetany: I.V.: 1-3 g/dose may be administered until therapeutic response occurs

Magnesium intoxication or cardiac arrest in the presence of hyperkalemia or hypocalcemia: I.V.: 500-800 mg/dose (maximum: 3 g/dose)

Maintenance electrolyte requirements for TPN: I.V.: Daily requirements: 1.7-3.4 g/1000 kcal/24 hours

Calcium channel blocker overdose (unlabeled use): I.V. infusion: 10% solution: 0.6-1.2 mL/kg/hour or I.V. 0.2-0.5 ml/kg every 15-20 minutes for 4 doses (maximum: 2-3 g/dose). In life-threatening situations, 1 g has been given every 1-10 minutes until clinical effect is achieved (case reports of resistant hypotension reported use of 12-18 g total).

Dosing: Pediatric

Adequate Intake (as elemental calcium):

0-6 months: 210 mg/day

7-12 months: 270 mg/day

1-3 years: 500 mg/day

4-8 years: 800 mg/day

9-18 years: 1300 mg/day

Dosage note: Calcium chloride has 3 times more elemental calcium than calcium gluconate. Calcium chloride is 27% elemental calcium; calcium gluconate is (9% elemental calcium). One gram of calcium chloride is equal to 270 mg of elemental calcium; 1 gram of calcium gluconate is equal to 90 mg of elemental calcium. The following dosages are expressed in terms of the calcium gluconate salt based on a solution concentration of 100 mg/mL (10%) containing 0.465 mEq (9.3 mg)/mL elemental calcium:

Hypocalcemia:

I.V.:

Neonates: 200-800 mg/kg/day as a continuous infusion or in 4 divided doses (maximum: 1 g/dose)

Infants and Children: 200-500 mg/kg/day as a continuous infusion or in 4 divided doses (maximum: 2-3 g/dose)

Oral: Children: 200-500 mg/kg/day divided every 6 hours

Hypocalcemia secondary to citrated blood infusion: I.V.: Neonates, Infants, and Children: Give 98 mg (0.45 mEq elemental calcium) for each 100 mL citrated blood infused.

Note: Routine administration of calcium, in the absence of signs/symptoms of hypocalcemia, is generally not recommended. A number of recommendations have been published seeking to address potential hypocalcemia during massive transfusion of citrated blood; however, many practitioners recommend replacement only as guided by clinical evidence of hypocalcemia and/or serial monitoring of ionized calcium.

Hypocalcemic tetany: I.V.: Infants and Children: 100-200 mg/kg/dose over 5-10 minutes; may repeat every 6-8 hours or follow with an infusion of 500 mg/kg/day

Magnesium intoxication or cardiac arrest in the presence of hyperkalemia or hypocalcemia: I.V.: Infants and Children: 60-100 mg/kg/dose (maximum: 3 g/dose)

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment

Clcr <25 mL/minute: Dosage adjustments may be necessary depending on the serum calcium levels.

Dosage Forms: U.S.

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

Capsule, oral:

Cal-G: 700 mg [gluten free; equivalent to elemental calcium 65 mg]

Cal-GLU™: 515 mg [dye free, sugar free; equivalent to elemental calcium 50 mg]

Injection, solution [preservative free]: 10% (10 mL, 50 mL, 100 mL) [equivalent to elemental calcium 9.3 mg (0.465 mEq)/mL]

Powder, oral: (480 g)

Tablet, oral: 500 mg [equivalent to elemental calcium 45 mg], 648 mg [equivalent to elemental calcium 60 mg], 972 mg [DSC] [equivalent to elemental calcium 90 mg]

Generic Equivalent Available: U.S.

Yes

Administration

Not for I.M. or SubQ administration. For I.V. administration only; administer slowly (∼1.5 mL calcium gluconate 10% per minute) through a small needle into a large vein in order to avoid too rapid increased in serum calcium and extravasation.

Extravasation treatment example: Hyaluronidase: Add 1 mL NS to 150 unit vial to make 150 units/mL of concentration; mix 0.1 mL of above with 0.9 mL NS in 1 mL syringe to make final concentration = 15 units/mL

Compatibility

Stable in D5LR, D5NS, D5W, D10W, D20W, LR, NS; incompatible in fat emulsion 10%.

Y-site administration: Compatible: Aldesleukin, allopurinol, amifostine, aztreonam, cefazolin, cefepime, ciprofloxacin, cisatracurium, cladribine, dobutamine, docetaxel, doxorubicin liposome, enalaprilat, epinephrine, etoposide, famotidine, filgrastim, gatifloxacin, gemcitabine, granisetron, heparin with hydrocortisone sodium succinate, labetalol, linezolid, melphalan, midazolam, milrinone, piperacillin/tazobactam, potassium chloride, prochlorperazine edisylate, propofol, remifentanil, sargramostim, tacrolimus, teniposide, thiotepa, tolazoline, vinorelbine, vitamin B complex with C. Incompatible: Amphotericin B cholesteryl sulfate complex, fluconazole, indomethacin. Variable (consult detailed reference): Ampicillin, meropenem.

Compatibility in syringe: Incompatible: Metoclopramide.

Compatibility when admixed: Compatible: Amikacin, aminophylline, ascorbic acid injection, bretylium, chloramphenicol, corticotropin, dimenhydrinate, furosemide, heparin, hydrocortisone sodium succinate, lidocaine, magnesium sulfate, norepinephrine, penicillin G potassium, penicillin G sodium, phenobarbital, potassium chloride, tobramycin, vancomycin, verapamil, vitamin B complex with C. Incompatible: Amphotericin B, cefamandole, cefazolin, clindamycin, dobutamine, floxacillin, methylprednisolone sodium succinate. Variable (consult detailed reference): Folic acid, potassium phosphate, prochlorperazine edisylate, sodium bicarbonate; maximum concentration in parenteral nutrition solutions is variable depending upon concentration and solubility.

Use

Treatment and prevention of hypocalcemia; treatment of tetany, cardiac disturbances of hyperkalemia, cardiac resuscitation when epinephrine fails to improve myocardial contractions, hypocalcemia; calcium supplementation; hydrofluoric acid (HF) burns

Use - Unlabeled/Investigational

Calcium channel blocker overdose

Adverse Reactions Significant

Frequency not defined.

I.V.:

Cardiovascular: Arrhythmia, bradycardia, cardiac arrest, hypotension, vasodilation, and syncope may occur following rapid I.V. injection

Central nervous system: Sense of oppression

Gastrointestinal: Chalky taste

Local: Abscess and necrosis following I.M. administration

Neuromuscular & skeletal: Tingling sensation

Miscellaneous: Heat waves

Postmarketing and/or case reports: Calcinosis cutis

Oral: Gastrointestinal: Constipation

Contraindications

Hypersensitivity to calcium gluconate or any component of the formulation; ventricular fibrillation during cardiac resuscitation; digitalis toxicity or suspected digoxin toxicity; hypercalcemia

Warnings/Precautions

Concerns related to adverse effects:

• Cardiac arrest: May produce cardiac arrest.

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

Disease-related concerns:

• Acidosis: Use with caution in patients with respiratory acidosis, renal impairment, or respiratory failure; acidifying effect of calcium chloride may potentiate acidosis.

• Hyperphosphatemia: Use with caution in patients with severe hyperphosphatemia.

• 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 renal failure to avoid hypercalcemia; frequent monitoring of serum calcium and phosphorus is necessary.

Concurrent drug therapy issues:

• Digitalis: Use with caution in digitalized patients; hypercalcemia may precipitate cardiac arrhythmias.

• Minerals/other oral drugs: Calcium administration interferes with absorption of some minerals and drugs; use with caution.

• Vitamin D: It is recommended to concomitantly administer vitamin D for optimal calcium absorption.

Dosage form specific issues:

• Absorption: Taking oral calcium (≤500 mg) with food improves absorption.

• Aluminum: Solutions may contain aluminum; toxic levels may occur following prolonged administration in premature neonates or patients with renal impairment.

• I.V. administration: For I.V. use only; do not inject SubQ or I.M. Avoid too rapid I.V. administration and avoid extravasation.

Drug Interactions

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 ibandronate; or 30 minutes after alendronate/risedronate.Exceptions: Pamidronate; Zoledronic Acid.Risk D: Consider therapy modification

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

Calcium Channel Blockers: Calcium Salts may diminish the therapeutic effect of Calcium Channel Blockers. Risk C: 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.Risk D: Consider therapy modification

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

Eltrombopag: Calcium Salts may decrease the serum concentration of Eltrombopag. Management: Separate administration of eltrombopag and any polyvalent cation (e.g., calcium-containing products) by at least 4 hours.Risk D: Consider therapy modification

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

Phosphate Supplements: Calcium Salts may decrease the absorption of Phosphate Supplements. Exceptions: Potassium Phosphate.Risk D: Consider therapy modification

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

Thiazide Diuretics: May decrease the excretion of Calcium Salts. Continued concomitant use can also result in metabolic alkalosis.Risk C: 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.Risk D: Consider therapy modification

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

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

Pregnancy Risk Factor

C (show table)

Pregnancy Implications

Reproduction studies have not been completed.

Lactation

Enters breast milk

Breast-Feeding Considerations

Endogenous calcium is excreted in breast milk.

Reference Range

Serum calcium: 8.4-10.2 mg/dL: Monitor plasma calcium levels if using calcium salts as electrolyte supplements for deficiency

Due to a poor correlation between the serum ionized calcium (free) and total serum calcium, particularly in states of low albumin or acid/base imbalances, direct measurement of ionized calcium is recommended

In low albumin states, the corrected total serum calcium may be estimated by: Corrected total calcium = total serum calcium + 0.8 (4.0 - measured serum albumin)

Mechanism of Action

As dietary supplement, used to prevent or treat negative calcium balance; in osteoporosis, it helps to prevent or decrease the rate of bone loss. The calcium in calcium salts moderates nerve and muscle performance and allows normal cardiac function.

Pharmacodynamics/Kinetics

Absorption: Requires vitamin D; calcium is absorbed in soluble, ionized form; solubility of calcium is increased in an acid environment

Distribution: Primarily in bones and teeth; crosses placenta; enters breast milk

Protein binding: Primarily albumin

Excretion: Primarily feces (as unabsorbed calcium); urine (20%)