NONCLINICAL TOXICOLOGY SECTION.


13NONCLINICAL TOXICOLOGY 13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term studies in animals have not been conducted to evaluate the carcinogenic potential of Calcium Gluconate in Sodium Chloride Injection. Calcium gluconate was not mutagenic with or without metabolic activation in the Ames test with Salmonella typhimurium (strains TA-1535, TA-1537, and TA-1538) or Saccharomyces cerevisiae (Strain D4). Fertility studies in animals have not been conducted with calcium gluconate administered by the intravenous route.

OVERDOSAGE SECTION.


10OVERDOSAGE Overdosage of Calcium Gluconate in Sodium Chloride Injection may result in hypercalcemia. Symptoms of hypercalcemia typically develop when the total serum calcium concentration is >=12 mg/dL. Neurologic symptoms include depression, weakness, fatigue, and confusion at lower levels, with patients experiencing hallucinations, disorientation, hypotonicity, seizures, and coma. Effects on the kidney include diminished ability to concentrate urine and diuresis.If overdose of Calcium Gluconate in Sodium Chloride Injection occurs immediately discontinue administration and provide supportive treatments to restore intravascular volume as well as promote calcium excretion in the urine if necessary.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.


PACKAGE/LABEL PRINCIPAL DISPLAY PANEL NDC 44567-620-24Calcium Gluconate in Sodium Chloride Injection 1,000 mg per 50 mL (20 mg/mL). Calcium Gluconate in Sodium Chloride Injection 1,000 mg per 50 mL image.

ADVERSE REACTIONS SECTION.


6ADVERSE REACTIONS The following serious adverse reactions are also described elsewhere in the labeling:oArrhythmias with Concomitant Cardiac Glycoside Use [see Warnings and Precautions (5.1)] oEnd-Organ Damage due to Intravascular Ceftriaxone-Calcium Precipitates [see Warnings and Precautions (5.2)] oTissue Necrosis and Calcinosis [see Warnings and Precautions (5.3)] oHypotension, Bradycardia, and Cardiac Arrhythmias [see Warnings and Precautions (5.4)] oAluminum toxicity [see Warnings and Precautions (5.5)] The following adverse reactions associated with the use of calcium gluconate were identified in the literature. Because these reactions are reported voluntarily from population of uncertain size, it is not always possible to estimate their frequency reliably or to establish causal relationship to drug exposure.Cardiovascular: Vasodilation, decreased blood pressure, bradycardia, cardiac arrhythmia, syncope, cardiac arrestAdministration site reactions: Local soft tissue inflammation, local necrosis, calcinosis cutis and calcification due to extravasation. The most common adverse events with Calcium Gluconate Injection are local soft tissue inflammation and necrosis, calcinosis cutis and calcification that are related to extravasation. Other adverse events include vasodilation, decreased blood pressure, bradycardia, cardiac arrhythmia, syncope, and cardiac arrest. (6)To report SUSPECTED ADVERSE REACTIONS, contact WG Critical Care, LLC at 1-866-562-4708 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.


13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term studies in animals have not been conducted to evaluate the carcinogenic potential of Calcium Gluconate in Sodium Chloride Injection. Calcium gluconate was not mutagenic with or without metabolic activation in the Ames test with Salmonella typhimurium (strains TA-1535, TA-1537, and TA-1538) or Saccharomyces cerevisiae (Strain D4). Fertility studies in animals have not been conducted with calcium gluconate administered by the intravenous route.

CLINICAL PHARMACOLOGY SECTION.


12CLINICAL PHARMACOLOGY 12.1Mechanism of Action Intravenous administration of calcium gluconate increases serum ionized calcium level. Calcium gluconate dissociates into ionized calcium in plasma. Ionized calcium and gluconate are constituents of body fluids.. 12.3Pharmacokinetics AbsorptionCalcium Gluconate Injection is 100% bioavailable following intravenous injection.MetabolismCalcium itself does not undergo direct metabolism. The release of ionized calcium from intravenous administration of calcium gluconate is direct and does not seem to be affected by the first pass through the liver.DistributionCalcium in the body is distributed mainly in skeleton (99%). Only 1% of the total body calcium is distributed within the extracellular fluids and soft tissues. About 50% of total serum calcium is in the ionized form and represents the biologically active part. 8% to 10% serum calcium is bound to organic and inorganic acid and approximately 40% is protein-bound (primarily to albumin).EliminationStudies have shown relationship between urinary calcium excretion and the intravenous administration of calcium gluconate, with significant increase in urinary calcium excretion observed after the intravenous administration of calcium gluconate.

CONTRAINDICATIONS SECTION.


4CONTRAINDICATIONS Calcium Gluconate in Sodium Chloride Injection is contraindicated in:oHypercalcemiaoNeonates (28 days of age or younger) receiving ceftriaxone [see Warnings and Precautions (5.2)] o Hypercalcemia (4)o Neonates (28 days of age or younger) receiving ceftriaxone (4).

DESCRIPTION SECTION.


11DESCRIPTION Calcium Gluconate in Sodium Chloride Injection is sterile, preservative-free, nonpyrogenic solution of calcium gluconate, form of calcium, for intravenous use.Calcium Gluconate is calcium D-gluconate (1:2) monohydrate. The structural formula is:Molecular formula: C12H22CaO14o H2OMolecular weight: 448.39Solubility in water: 3.5 g/100 mL at 25CCalcium Gluconate in Sodium Chloride Injection is available as 1,000 mg per 50 mL (equivalent to 18.8 mg per mL calcium gluconate anhydrous) 1,000 mg per 100 mL (equivalent to 9.4 mg per mL calcium gluconate anhydrous) or 2,000 mg per 100 mL (equivalent to 18.8 mg per mL calcium gluconate anhydrous) in single-dose bags.Table 3. Calcium Gluconate Formulations1,000 mg per 50 mL1,000 mg per 100 mL 2,000 mg per 100 mLCalcium Gluconate20 mg per mL10 mg per mL20 mg per mLElemental Calcium1.86 mg per mL0.93 mg per mL1.86 mg per mL Sodium Chloride6.75 mg per mL8 mg per mL6.75 mg per mL Hydrochloric Acid or Sodium HydroxidepH adjusted 6.0 to 8.2. calcium gluconate structural formula.

DOSAGE & ADMINISTRATION SECTION.


2DOSAGE AND ADMINISTRATION o Administer intravenously (bolus or continuous infusion) via secure intravenous line (2.1)o See Full Prescribing Information (FPI) for administration rates, and appropriate monitoring (2.1)o Do not dilute Calcium Gluconate in Sodium Chloride Injection prior to use. Any unused portion should be discarded (2.1)o Individualize the dose within the recommended range in adults and pediatric patients depending on the severity of symptoms of hypocalcemia, the serum calcium level, and the acuity of onset of hypocalcemia. See Table in the FPI for dosing recommendations in mg of calcium gluconate for neonates, pediatric and adult patients. (2.2)o Measure serum calcium during intermittent infusions every to hours and during continuous infusion every to hours. (2.3)o Calcium Gluconate Injection is not physically compatible with fluids containing phosphate or bicarbonate. Precipitation may result if mixed. See FPI for all drug incompatibilities. (2.5). 2.1Important Administration Instructions See Table for amounts of elemental calcium in Calcium Gluconate in Sodium Chloride Injection.Table 1. Amounts of Calcium Gluconate and Elemental CalciumTotal Strength per Total VolumeStrength per mLElemental Calcium (mg) per mLElemental Calcium (mEq) per mLTotal Amount of Elemental Calcium (mg) per Total VolumeTotal Amount of Elemental Calcium (mEq) per Total Volume1,000 mg per 50 mL 20 mg/mL1.86 mg0.093 mEq93 mg per 50 mL4.65 mEq per 50 mL1,000 mg per 100 mL10 mg/mL0.93 mg0.0465 mEq93 mg per 100 mL4.65 mEq per 100 mL2,000 mg per 100 mL20 mg/mL1.86 mg0.093 mEq186 mg per 100 mL9.3 mEq per 100 mLoDo not dilute Calcium Gluconate in Sodium Chloride Injection prior to use. Any unused portion should be discarded. oInspect Calcium Gluconate in Sodium Chloride Injection visually prior to administration. The solution should appear clear and colorless. Do not administer if there is particulate matter or discoloration. oAdminister Calcium Gluconate in Sodium Chloride Injection intravenously via secure intravenous line to avoid calcinosis cutis and tissue necrosis [see Warnings and Precautions (5.3)].Administer Calcium Gluconate in Sodium Chloride Injection by continuous infusion at the rate recommended in Table [see Dosage and Administration (2.2)] and monitor patients, vitals, calcium and ECG during the infusion [see Warnings and Precautions (5.4)].. See Table for amounts of elemental calcium in Calcium Gluconate in Sodium Chloride Injection.. oDo not dilute Calcium Gluconate in Sodium Chloride Injection prior to use. Any unused portion should be discarded. oInspect Calcium Gluconate in Sodium Chloride Injection visually prior to administration. The solution should appear clear and colorless. Do not administer if there is particulate matter or discoloration. oAdminister Calcium Gluconate in Sodium Chloride Injection intravenously via secure intravenous line to avoid calcinosis cutis and tissue necrosis [see Warnings and Precautions (5.3)].. 2.2Recommended Dosage Individualize the dose of Calcium Gluconate in Sodium Chloride Injection within the recommended range depending on the severity of symptoms of hypocalcemia, the serum calcium level, and the acuity of onset of hypocalcemia.Table provides dosing recommendations for Calcium Gluconate in Sodium Chloride Injection in mg of calcium gluconate for neonates, pediatric and adult patients.Table 2. Dosing Recommendations in mg of Calcium Gluconate for Neonate, Pediatric, and Adult PatientsPatientPopulationInitial DoseSubsequent Doses (if needed)BolusContinuous InfusionNeonate (less than1 month to month)100 mg/kg to 200 mg/kg100 mg/kg to 200 mg/kg every hoursInitiate at 17 mg/kg/hour to 33 mg/kg/hourPediatric (greater than month to less than 17 years)29 mg/kg to 60 mg/kg29 mg/kg to 60 mg/kg every hoursInitiate at mg/kg/hour to 13 mg/kg/hourAdult (17 years and greater)1,000 mg to 2,000 mg1,000 mg to 2,000 mg every hoursInitiate at 5.4 mg/kg/hour to 21.5 mg/kg/hourFor bolus administration, DO NOT exceed an infusion rate of: o200 mg/minute in adult patients o100 mg/minute in pediatric patients For continuous infusions, adjust rate as needed based on serum calcium levels. o200 mg/minute in adult patients. o100 mg/minute in pediatric patients. 2.3Serum Calcium Monitoring Measure serum calcium every to hours during intermittent infusions with Calcium Gluconate in Sodium Chloride Injection and measure serum calcium every to hours during continuous infusion.. 2.4Dosage in Renal Impairment For patients with renal impairment, initiate Calcium Gluconate in Sodium Chloride Injection at the lowest dose of the recommended dose ranges for all age groups and monitor serum calcium levels every hours.. 2.5Drug Incompatibilities oDo not mix Calcium Gluconate in Sodium Chloride Injection with ceftriaxone. Concurrent use of intravenous ceftriaxone and Calcium Gluconate in Sodium Chloride Injection can lead to the formation of ceftriaxone-calcium precipitates. Concomitant use of ceftriaxone and intravenous calcium-containing products is contraindicated in neonates (28 days of age or younger) [see Contraindications (4)]. In patients older than 28 days of age, ceftriaxone and calcium-containing products may be administered sequentially, provided the infusion lines are thoroughly flushed between infusions with compatible fluid. Ceftriaxone must not be administered simultaneously with intravenous calcium-containing solutions via Y-site in any age group [see Warnings and Precautions (5.2), Drug Interactions (7.3)]. oDo not mix Calcium Gluconate in Sodium Chloride Injection with fluids containing bicarbonate or phosphate. Calcium Gluconate Injection is not physically compatible with fluids containing phosphate or bicarbonate. Precipitation may result if mixed. oDo not mix Calcium Gluconate in Sodium Chloride Injection with minocycline injection. Calcium complexes minocycline rendering it inactive.. oDo not mix Calcium Gluconate in Sodium Chloride Injection with minocycline injection. Calcium complexes minocycline rendering it inactive.

DOSAGE FORMS & STRENGTHS SECTION.


3DOSAGE FORMS AND STRENGTHS Calcium Gluconate in Sodium Chloride Injection is clear, colorless solution available as:Injection:o Calcium gluconate 1,000 mg per 50 mL (20 mg/mL) single-dose bago Calcium gluconate 1,000 mg per 100 mL (10 mg/mL) single-dose bago Calcium gluconate 2,000 mg per 100 mL (20 mg/mL) single-dose bag. Injection:o Calcium gluconate 1,000 mg per 50 mL (20 mg/mL) single-dose bag (3)o Calcium gluconate 1,000 mg per 100 mL (10 mg/mL) single-dose bag (3)o Calcium gluconate 2,000 mg per 100 mL (20 mg/mL) single-dose bag (3).

DRUG INTERACTIONS SECTION.


7DRUG INTERACTIONS o Cardiac Glycoside: Synergistic arrhythmias may occur if calcium and cardiac glycosides are administered together. (7.1)o Calcium Channel Blockers: Administration of calcium may reduce the response. (7.2)o Drugs that may cause hypercalcemia: Vitamin D, vitamin A, thiazide diuretics, estrogen, calcipotriene and teriparatide administration may cause hypercalcemia. Monitor plasma calcium concentrations in patients taking these drugs concurrently. (7.3). 7.1Cardiac Glycosides Hypercalcemia increases the risk of digoxin toxicity, while digoxin may be therapeutically ineffective in the presence of hypocalcemia. Synergistic arrhythmias may occur if calcium and cardiac glycosides are administered together. Avoid administration of Calcium Gluconate in Sodium Chloride Injection in patients receiving cardiac glycosides; if considered necessary, administer Calcium Gluconate in Sodium Chloride Injection slowly in small amounts and monitor ECG closely during administration.. 7.2Calcium Channel Blockers Administration of calcium may reduce the response to calcium channel blockers.. 7.3Drugs that may cause Hypercalcemia Vitamin D, vitamin A, thiazide diuretics, estrogen, calcipotriene and teriparatide administration may cause hypercalcemia. Monitor plasma calcium concentrations in patients taking these drugs concurrently.

GERIATRIC USE SECTION.


8.5Geriatric Use In general dose selection for an elderly patient should start at the lowest dose of the recommended dose range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

HOW SUPPLIED SECTION.


16HOW SUPPLIED/STORAGE AND HANDLING Calcium Gluconate in Sodium Chloride Injection is clear, colorless solution supplied in single-dose bags with an aluminum overwrap available as: Total Strength per Total VolumeStrength per mL24 single-dose bags NDCBag and Overwrap NDC1,000 mg per 50 mL 20 mg/mL44567-620-2444567-620-011,000 mg per 100 mL 10 mg/mL44567-622-2444567-622-012,000 mg per 100 mL20 mg/mL44567-621-2444567-621-01partial fill container 50 mL volume in 100 mL container.Store at 20 to 25C (68 to 77F) [see USP Controlled Room Temperature]. Do not freeze. Product should be used within 60 days of removal from aluminum overwrap.Preservative-free. Discard any unused portion in the single-dose bag immediately.

INDICATIONS & USAGE SECTION.


1INDICATIONS AND USAGE Calcium Gluconate in Sodium Chloride Injection is indicated for pediatric and adult patients for the treatment of acute symptomatic hypocalcemia.Limitations of UseThe safety of Calcium Gluconate in Sodium Chloride Injection for long term use has not been established.. Calcium Gluconate in Sodium Chloride Injection is form of calcium indicated for pediatric and adult patients for the treatment of acute symptomatic hypocalcemia. (1)o Limitations of Use: The safety of Calcium Gluconate Injection for long term use has not been established. (1).

INFORMATION FOR PATIENTS SECTION.


17PATIENT COUNSELING INFORMATION Inform patients of the risks associated with infusion of Calcium Gluconate in Sodium Chloride Injection including local tissue inflammation, local necrosis and calcinosis. [see Warnings and Precautions (5.3)].Manufactured for:WG Critical Care, LLCParamus, NJ 07652Made in SwitzerlandU.S. Patent Numbers 10,342,813 and 10,130,646.

MECHANISM OF ACTION SECTION.


12.1Mechanism of Action Intravenous administration of calcium gluconate increases serum ionized calcium level. Calcium gluconate dissociates into ionized calcium in plasma. Ionized calcium and gluconate are constituents of body fluids.

PEDIATRIC USE SECTION.


8.4Pediatric Use The safety and effectiveness of Calcium Gluconate in Sodium Chloride Injection have been established in pediatric patients for the treatment of acute, symptomatic hypocalcemia.Pediatric approval for Calcium Gluconate in Sodium Chloride Injection, including doses, is not based on adequate and well-controlled clinical studies. Safety and dosing recommendations in pediatric patients are based on published literature and clinical experience [see Dosage and Administration (2.2)].Concomitant use of ceftriaxone and Calcium Gluconate in Sodium Chloride Injection is contraindicated in neonates (28 days of age or younger) due to reports of fatal outcomes associated with the presence of lung and kidney ceftriaxone-calcium precipitates. In patients older than 28 days of age, ceftriaxone and Calcium Gluconate Injection may be administered sequentially, provided the infusion lines are thoroughly flushed between infusions with compatible fluid [see Contraindications (4) and Warnings and Precautions (5.2)]. This product contains up to 25 mcg/L aluminum which may be toxic, particularly for premature neonates due to immature renal function. Parenteral administration of aluminum greater than mcg/kg/day to mcg/kg/day is associated with central nervous system and bone toxicity [see Warnings and Precautions (5.5)].

PHARMACOKINETICS SECTION.


12.3Pharmacokinetics AbsorptionCalcium Gluconate Injection is 100% bioavailable following intravenous injection.MetabolismCalcium itself does not undergo direct metabolism. The release of ionized calcium from intravenous administration of calcium gluconate is direct and does not seem to be affected by the first pass through the liver.DistributionCalcium in the body is distributed mainly in skeleton (99%). Only 1% of the total body calcium is distributed within the extracellular fluids and soft tissues. About 50% of total serum calcium is in the ionized form and represents the biologically active part. 8% to 10% serum calcium is bound to organic and inorganic acid and approximately 40% is protein-bound (primarily to albumin).EliminationStudies have shown relationship between urinary calcium excretion and the intravenous administration of calcium gluconate, with significant increase in urinary calcium excretion observed after the intravenous administration of calcium gluconate.

PREGNANCY SECTION.


8.1Pregnancy Risk summaryLimited available data with Calcium Gluconate Injection use in pregnant women are insufficient to inform drug associated risk of adverse developmental outcomes. There are risks to the mother and the fetus associated with hypocalcemia in pregnancy [see Clinical Considerations].The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.Clinical ConsiderationsDisease-associated maternal riskMaternal hypocalcemia can result in an increased rate of spontaneous abortion, premature and dysfunctional labor, and possibly preeclampsia.Fetal/Neonatal adverse reactionsInfants born to mothers with hypocalcemia can have associated fetal and neonatal hyperparathyroidism, which in turn can cause fetal and neonatal skeletal demineralization, subperiosteal bone resorption, osteitis fibrosa cystica and neonatal seizures. Infants born to mothers with hypocalcemia should be carefully monitored for signs of hypocalcemia or hypercalcemia, including neuromuscular irritability, apnea, cyanosis and cardiac rhythm disorders.

SPL UNCLASSIFIED SECTION.


2.1Important Administration Instructions See Table for amounts of elemental calcium in Calcium Gluconate in Sodium Chloride Injection.Table 1. Amounts of Calcium Gluconate and Elemental CalciumTotal Strength per Total VolumeStrength per mLElemental Calcium (mg) per mLElemental Calcium (mEq) per mLTotal Amount of Elemental Calcium (mg) per Total VolumeTotal Amount of Elemental Calcium (mEq) per Total Volume1,000 mg per 50 mL 20 mg/mL1.86 mg0.093 mEq93 mg per 50 mL4.65 mEq per 50 mL1,000 mg per 100 mL10 mg/mL0.93 mg0.0465 mEq93 mg per 100 mL4.65 mEq per 100 mL2,000 mg per 100 mL20 mg/mL1.86 mg0.093 mEq186 mg per 100 mL9.3 mEq per 100 mLoDo not dilute Calcium Gluconate in Sodium Chloride Injection prior to use. Any unused portion should be discarded. oInspect Calcium Gluconate in Sodium Chloride Injection visually prior to administration. The solution should appear clear and colorless. Do not administer if there is particulate matter or discoloration. oAdminister Calcium Gluconate in Sodium Chloride Injection intravenously via secure intravenous line to avoid calcinosis cutis and tissue necrosis [see Warnings and Precautions (5.3)].Administer Calcium Gluconate in Sodium Chloride Injection by continuous infusion at the rate recommended in Table [see Dosage and Administration (2.2)] and monitor patients, vitals, calcium and ECG during the infusion [see Warnings and Precautions (5.4)].. See Table for amounts of elemental calcium in Calcium Gluconate in Sodium Chloride Injection.. oDo not dilute Calcium Gluconate in Sodium Chloride Injection prior to use. Any unused portion should be discarded. oInspect Calcium Gluconate in Sodium Chloride Injection visually prior to administration. The solution should appear clear and colorless. Do not administer if there is particulate matter or discoloration. oAdminister Calcium Gluconate in Sodium Chloride Injection intravenously via secure intravenous line to avoid calcinosis cutis and tissue necrosis [see Warnings and Precautions (5.3)].

USE IN SPECIFIC POPULATIONS SECTION.


8USE IN SPECIFIC POPULATIONS o Geriatric use: Dosing in elderly patients should be cautious, usually starting at the low end of the dosage range. (8.5)o Renal impairment: Initiate with the lower limit of the dosage range and monitor serum calcium levels every hours. (8.6, 2.4). 8.1Pregnancy Risk summaryLimited available data with Calcium Gluconate Injection use in pregnant women are insufficient to inform drug associated risk of adverse developmental outcomes. There are risks to the mother and the fetus associated with hypocalcemia in pregnancy [see Clinical Considerations].The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.Clinical ConsiderationsDisease-associated maternal riskMaternal hypocalcemia can result in an increased rate of spontaneous abortion, premature and dysfunctional labor, and possibly preeclampsia.Fetal/Neonatal adverse reactionsInfants born to mothers with hypocalcemia can have associated fetal and neonatal hyperparathyroidism, which in turn can cause fetal and neonatal skeletal demineralization, subperiosteal bone resorption, osteitis fibrosa cystica and neonatal seizures. Infants born to mothers with hypocalcemia should be carefully monitored for signs of hypocalcemia or hypercalcemia, including neuromuscular irritability, apnea, cyanosis and cardiac rhythm disorders.. 8.2Lactation Risk summaryCalcium is present in human milk as natural component of human milk. It is not known whether intravenous administration of Calcium Gluconate in Sodium Chloride Injection can alter calcium concentration in human milk. There are no data on the effects of Calcium Gluconate Injection on the breastfed infant, or on milk production. The developmental and health benefits of breastfeeding should be considered along with the mothers clinical need for Calcium Gluconate in Sodium Chloride Injection and any potential adverse effects on the breastfed child from Calcium Gluconate in Sodium Chloride Injection or from the underlying maternal condition.. 8.4Pediatric Use The safety and effectiveness of Calcium Gluconate in Sodium Chloride Injection have been established in pediatric patients for the treatment of acute, symptomatic hypocalcemia.Pediatric approval for Calcium Gluconate in Sodium Chloride Injection, including doses, is not based on adequate and well-controlled clinical studies. Safety and dosing recommendations in pediatric patients are based on published literature and clinical experience [see Dosage and Administration (2.2)].Concomitant use of ceftriaxone and Calcium Gluconate in Sodium Chloride Injection is contraindicated in neonates (28 days of age or younger) due to reports of fatal outcomes associated with the presence of lung and kidney ceftriaxone-calcium precipitates. In patients older than 28 days of age, ceftriaxone and Calcium Gluconate Injection may be administered sequentially, provided the infusion lines are thoroughly flushed between infusions with compatible fluid [see Contraindications (4) and Warnings and Precautions (5.2)]. This product contains up to 25 mcg/L aluminum which may be toxic, particularly for premature neonates due to immature renal function. Parenteral administration of aluminum greater than mcg/kg/day to mcg/kg/day is associated with central nervous system and bone toxicity [see Warnings and Precautions (5.5)].. 8.5Geriatric Use In general dose selection for an elderly patient should start at the lowest dose of the recommended dose range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.. 8.6Renal Impairment For patients with renal impairment, initiate Calcium Gluconate in Sodium Chloride Injection at the lowest dose of the recommended dose ranges across all age groups. Monitor serum calcium levels every hours [see Dosage and Administration (2.4)]. 8.7Hepatic Impairment Hepatic function does not impact the availability of ionized calcium after calcium gluconate intravenous administration. Dose adjustment in hepatically impaired patients may not be necessary.

WARNINGS AND PRECAUTIONS SECTION.


5WARNINGS AND PRECAUTIONS o Arrhythmias with Concomitant Cardiac Glycoside Use: If concomitant therapy is necessary, Calcium Gluconate in Sodium Chloride Injection should be given slowly in small amounts and close ECG monitoring is recommended (5.1)o End-Organ Damage due to Intravascular Ceftriaxone-Calcium Precipitates: Concurrent use of intravenous ceftriaxone may cause life-threatening precipitates. Do not administer ceftriaxone simultaneously with Calcium Gluconate in Sodium Chloride Injection via Y-site in any age group. Cases of fatal outcomes in neonates have occurred. (4, 5.2)o Tissue Necrosis and Calcinosis: Calcinosis cutis can occur with or without extravasation of Calcium Gluconate in Sodium Chloride Injection. Tissue necrosis, ulceration, and secondary infection are the most serious complications. If extravasation occurs or clinical manifestations of calcinosis cutis are noted, immediately discontinue intravenous administration at that site and treat as needed. (5.3)o Hypotension, Bradycardia, and Cardiac Arrhythmias with Rapid Administration: To avoid adverse reactions that may follow rapid intravenous administration, Calcium Gluconate in Sodium Chloride Injection should be infused slowly, with careful ECG monitoring for cardiac arrhythmias. (5.4)o Aluminum Toxicity: This product contains aluminum, up to 25 mcg per liter, that may be toxic. (5.5). 5.1Arrhythmias with Concomitant Cardiac Glycoside Use Cardiac arrhythmias may occur if calcium and cardiac glycosides are administered together. Hypercalcemia increases the risk of digoxin toxicity. Administration of Calcium Gluconate in Sodium Chloride Injection should be avoided in patients receiving cardiac glycosides. If concomitant therapy is necessary, Calcium Gluconate in Sodium Chloride Injection should be given slowly in small amounts and with close ECG monitoring [see Drug Interactions (7.1)].. 5.2End-Organ Damage due to Intravascular Ceftriaxone-Calcium Precipitates Concomitant use of ceftriaxone and Calcium Gluconate in Sodium Chloride Injection is contraindicated in neonates (28 days of age or younger) due to cases of fatal outcomes in neonates in which crystalline material was observed in the lungs and kidneys at autopsy after ceftriaxone and calcium were administrated simultaneously through the same intravenous line. Concomitant administration can lead to the formation of ceftriaxone-calcium precipitates that may act as emboli, resulting in vascular spasm or infarction [see Contraindications (4)]. In patients older than 28 days of age, ceftriaxone and Calcium Gluconate in Sodium Chloride Injection may be administered sequentially, provided the infusion lines are thoroughly flushed between infusions with compatible fluid. Do not administer Ceftriaxone simultaneously with Calcium Gluconate in Sodium Chloride Injection via Y-site in any age group.. 5.3Tissue Necrosis and Calcinosis Intravenous administration of Calcium Gluconate in Sodium Chloride Injection and local trauma may result in calcinosis cutis due to transient increase in local calcium concentration. Calcinosis cutis can occur with or without extravasation of Calcium Gluconate in Sodium Chloride Injection, is characterized by abnormal dermal deposits of calcium salts, and clinically manifests as papules, plaques, or nodules that may be associated with erythema, swelling, or induration. Tissue necrosis, ulceration, and secondary infection are the most serious complications.If extravasation occurs or clinical manifestations of calcinosis cutis are noted, immediately discontinue intravenous administration at that site and treat as needed.. 5.4Hypotension, Bradycardia, and Cardiac Arrhythmias with Rapid Administration Rapid injection of Calcium Gluconate in Sodium Chloride Injection may cause vasodilation, decreased blood pressure, bradycardia, cardiac arrhythmias, syncope and cardiac arrest. To avoid adverse reactions that may follow rapid intravenous administration, Calcium Gluconate in Sodium Chloride Injection should be infused slowly. If rapid intravenous bolus of Calcium Gluconate Injection is required, the rate of intravenous administration should not exceed 200 mg/minute in adults and 100 mg/minute in pediatric patients and ECG monitoring during administration is recommended [see Dosage and Administration (2.1)].. 5.5Aluminum Toxicity Calcium Gluconate in Sodium Chloride Injection contains aluminum, up to 25 mcg per liter, that may be toxic. Aluminum may reach toxic levels with prolonged parenteral administration if kidney function is impaired. Premature neonates are particularly at risk because their kidneys are immature, and they require large amounts of calcium and phosphate solutions, which contain aluminum. Research indicates that patients with impaired kidney function, including premature neonates, who receive parenteral levels of aluminum at greater than mcg/kg/day to mcg/kg/day accumulate aluminum levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration.