Calcium Gluconate

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

12.1 Mechanism 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.

2 DOSAGE AND ADMINISTRATION • Administer intravenously (bolus or continuous infusion) via a secure intravenous line (2.1) • See Full Prescribing Information (FPI) for administration rates, and appropriate monitoring (2.1) • Do not dilute Calcium Gluconate in Sodium Chloride Injection prior to use. Any unused portion should be discarded (2.1) • 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 1 in the FPI for dosing recommendations in mg of calcium gluconate for neonates, pediatric and adult patients. (2.2) • Measure serum calcium during intermittent infusions every 4 to 6 hours and during continuous infusion every 1 to 4 hours. (2.3) • 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) 2.1 Important Administration Instructions See Table 1 for amounts of elemental calcium in Calcium Gluconate in Sodium Chloride Injection. Table 1. Amounts of Calcium Gluconate and Elemental Calcium Total Strength per Total Volume Strength per mL Elemental Calcium (mg) per mL Elemental Calcium (mEq) per mL Total Amount of Elemental Calcium (mg) per Total Volume Total Amount of Elemental Calcium (mEq) per Total Volume 1,000 mg per 50 mL 20 mg/mL 1.86 mg 0.093 mEq 93 mg per 50 mL 4.65 mEq per 50 mL 1,000 mg per 100 mL 10 mg/mL 0.93 mg 0.0465 mEq 93 mg per 100 mL 4.65 mEq per 100 mL 2,000 mg per 100 mL 20 mg/mL 1.86 mg 0.093 mEq 186 mg per 100 mL 9.3 mEq per 100 mL • Do not dilute Calcium Gluconate in Sodium Chloride Injection prior to use. Any unused portion should be discarded. • Inspect 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. • Administer Calcium Gluconate in Sodium Chloride Injection intravenously via a 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 1 [see Dosage and Administration (2.2)] and monitor patients, vitals, calcium and ECG during the infusion [see Warnings and Precautions (5.4)] . 2.2 Recommended 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 2 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 Patients PatientPopulation Initial Dose Subsequent Doses (if needed) Bolus Continuous Infusion Neonate (less than1 month to 1 month) 100 mg/kg to 200 mg/kg 100 mg/kg to 200 mg/kg every 6 hours Initiate at 17 mg/kg/hour to 33 mg/kg/hour Pediatric (greater than 1 month to less than 17 years) 29 mg/kg to 60 mg/kg 29 mg/kg to 60 mg/kg every 6 hours Initiate at 8 mg/kg/hour to 13 mg/kg/hour Adult (17 years and greater) 1,000 mg to 2,000 mg 1,000 mg to 2,000 mg every 6 hours Initiate at 5.4 mg/kg/hour to 21.5 mg/kg/hour For bolus administration, DO NOT exceed an infusion rate of: •200 mg/minute in adult patients •100 mg/minute in pediatric patients For continuous infusions, adjust rate as needed based on serum calcium levels 2.3 Serum Calcium Monitoring Measure serum calcium every 4 to 6 hours during intermittent infusions with Calcium Gluconate in Sodium Chloride Injection and measure serum calcium every 1 to 4 hours during continuous infusion. 2.4 Dosage in Renal Impairment For patients with renal impairment, initiate Calcium Gluconate in Sodium Chl

6 ADVERSE REACTIONS The following serious adverse reactions are also described elsewhere in the labeling: • Arrhythmias with Concomitant Cardiac Glycoside Use [see Warnings and Precautions (5.1)] • End-Organ Damage due to Intravascular Ceftriaxone-Calcium Precipitates [see Warnings and Precautions (5.2)] • Tissue Necrosis and Calcinosis [see Warnings and Precautions (5.3)] • Hypotension, Bradycardia, and Cardiac Arrhythmias [see Warnings and Precautions (5.4)] • Aluminum 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 a population of uncertain size, it is not always possible to estimate their frequency reliably or to establish a causal relationship to drug exposure. Cardiovascular : Vasodilation, decreased blood pressure, bradycardia, cardiac arrhythmia, syncope, cardiac arrest Administration 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.

5 WARNINGS AND PRECAUTIONS • 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) • 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 a Y-site in any age group. Cases of fatal outcomes in neonates have occurred. (4, 5.2) • 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) • 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) • Aluminum Toxicity: This product contains aluminum, up to 25 mcg per liter, that may be toxic. (5.5) 5.1 Arrhythmias 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)] . 5.2 End-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 a 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 a compatible fluid. Do not administer Ceftriaxone simultaneously with Calcium Gluconate in Sodium Chloride Injection via a Y-site in any age group. 5.3 Tissue 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. 5.4 Hypotension, 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

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

10 OVERDOSAGE 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.