CALCIUM GLUCONATE

Calcium Gluconate Injection, USP is a sterile, preservative-free, nonpyrogenic, supersaturated solution of calcium gluconate, a form of calcium, for intravenous use. Calcium Gluconate is calcium D-gluconate (1:2) monohydrate. The structural formula is: Molecular formula: C 12 H 22 CaO 14 • H 2 O Molecular weight: 448.39 Solubility in water: 3.5 g/100 mL at 25°C Calcium Gluconate Injection, USP is available as 1,000 mg per 10 mL (100 mg per mL) or 5,000 mg per 50 mL (100 mg per mL) in a single-dose vial, or 10,000 mg per 100 mL (100 mg per mL) in a pharmacy bulk package. Each mL of Calcium Gluconate Injection, USP contains 100 mg of calcium gluconate (equivalent to 94 mg of calcium gluconate and 4.5 mg of calcium saccharate tetrahydrate), hydrochloric acid and/or sodium hydroxide for pH adjustment (6.0 to 8.2) and sterile water for injection, q.s. It contains no antimicrobial agent. Each mL of Calcium Gluconate Injection, USP contains 9.3 mg (0.465 mEq) of elemental calcium. Structural Formula

Calcium Gluconate Injection is indicated for pediatric and adult patients for the treatment of acute symptomatic hypocalcemia. Calcium Gluconate 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 ) Limitations of Use The safety of Calcium Gluconate Injection for long term use has not been established.

Contains 100 mg of calcium gluconate per mL which contains 9.3 mg (0.465 mEq) of elemental calcium ( 2.1 ) Administer intravenously (bolus or continuous infusion) via a secure intravenous line ( 2.1 ) See Full Prescribing Information (FPI) for dilution instructions, administration rates, and appropriate monitoring ( 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 ) Supplied in a single-dose vial or pharmacy bulk package (PBP). For PBP, dispense single doses to many patients in a pharmacy admixture program; use within 4 hours of puncture ( 2.6 ) 2.1 Important Administration Instructions Calcium Gluconate Injection contains 100 mg of calcium gluconate per mL which contains 9.3 mg (i.e., 0.465 mEq) of elemental calcium. Dilute Calcium Gluconate Injection prior to use in 5% dextrose or normal saline and assess for potential drug or IV fluid incompatibilities [see Dosage and Administration ( 2.5 )]. Inspect Calcium Gluconate Injection visually prior to administration. The solution should appear clear and colorless to slightly yellow. Do not administer if there is particulate matter or discoloration. Use the diluted solution immediately after preparation. Administer Calcium Gluconate Injection intravenously via a secure intravenous line to avoid calcinosis cutis and tissue necrosis [see Warnings and Precautions ( 5.3 )] . Administer Calcium Gluconate Injection by bolus administration or continuous infusion: For bolus intravenous administration: Dilute the dose [see Dosage and Administration ( 2.2 )] of Calcium Gluconate Injection in 5% dextrose or normal saline to a concentration of 10-50 mg/mL prior to administration. Administer the dose slowly and DO NOT exceed an infusion rate of 200 mg/minute in adults or 100 mg/minute in pediatric patients, including neonates. Monitor patients, vitals and electrocardiograph (ECG) during administration [see Warnings and Precautions ( 5.4 )] . For continuous intravenous infusion: Dilute Calcium Gluconate Injection in 5% dextrose or normal saline to a concentration of 5.8-10 mg/mL prior to administration. Administer 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 )] . Calcium Gluconate Injection is supplied in single-dose vials and pharmacy bulk packages [see Dosage and Administration ( 2.6 )]. 2.2 Recommended Dosage Individualize the dose of Calcium Gluconate 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 1 provides dosing recommendations for Calcium Gluconate Injection in mg of calcium gluconate for neonates, pediatric and adult patients. Table 1. Dosing Recommendations in mg of Calcium Gluconate for Neonate, Pediatric, and Adult Patients Patient Population Initial Dose Subsequent Doses (if needed) Bolus Continuous Infusion Neonate (≤ 1 month) 100 – 200 mg/kg 100 - 200 mg/kg every 6 hours Initiate at 17-33 mg/kg/hour Pediatric (> 1 month to < 17 years) 29 - 60 mg/kg 29 - 60 mg/kg every 6 hours Initiate at 8-13 mg/kg/hour Adult 1000 - 2000 mg 1000 - 2000 mg every 6 hours Initiate at 5.4 - 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 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 Injection at the lowest dose of the recommended dose ranges for all age groups and monitor serum calcium levels every 4 hours. 2.5 Drug Incompatibilities Do not mix Calcium Gluconate Injection with ceftriaxone. Concurrent use of intravenous ceftriaxone and Calcium Gluconate 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 a compatible fluid. Ceftriaxone must not be administered simultaneously with intravenous calcium-containing solutions via a Y-site in any age group [see Warnings and Precautions ( 5.2 ), Drug Interactions ( 7.3 )]. Do not mix Calcium Gluconate 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. Do not mix Calcium Gluconate Injection with minocycline injection. Calcium complexes minocycline rendering it inactive. 2.6 Preparation of Pharmacy Bulk Package The pharmacy bulk package (PBP) of Calcium Gluconate Injection is intended for dispensing of single doses to multiple patients in a pharmacy admixture program. Penetrate the container closure only one time with a suitable sterile transfer device or dispensing set that allows measured dispensing of the contents. Use the PBP only in a suitable ISO Class 5 work area such as a laminar flow hood (or an equivalent clean air compounding area). Complete dispensing from the pharmacy bulk vial within 4 hours after the container closure is penetrated. Each dose dispensed from the Pharmacy Bulk Package vial must be used immediately.

Calcium Gluconate Injection is contraindicated in: Hypercalcemia 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 )

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 Fresenius Kabi USA, LLC at 1-800-551-7176 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Cardiac Glycoside : Synergistic arrhythmias may occur if calcium and cardiac glycosides are administered together. ( 7.1 ) Calcium Channel Blockers : Administration of calcium may reduce the response. ( 7.2 ) 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 ) 7.1 Cardiac 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 Injection in patients receiving cardiac glycosides; if considered necessary, administer Calcium Gluconate Injection slowly in small amounts and monitor ECG closely during administration. 7.2 Calcium Channel Blockers Administration of calcium may reduce the response to calcium channel blockers. 7.3 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.