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. 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 ) Limitations of Use The safety of Calcium Gluconate Injection for long term use has not been established.

2 DOSAGE AND ADMINISTRATION Contains 20 mg of calcium gluconate per mL which contains 1.86 mg (0.093 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 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 2 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 Calcium Gluconate in Sodium Chloride Injection contains 20 mg of calcium gluconate per mL which contains 1.86 mg (i.e. 0.093 mEq) of elemental calcium. See Table 1 for amounts of elemental calcium in Calcium Gluconate in Sodium Chloride Injection. Table 1. Amount of Calcium Gluconate and Elemental Calcium Total Strength per Total Volume Strength 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 93 mg per 50 mL 4.65 mEq per 50 mL 2,000 mg per 100 mL 20 mg/mL 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. [see Dosage and Administration ( 2.5 )]. 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 2 [see Dosage and Administration ( 2.2 )] and monitor patients, vitals, calcium and ECG during the infusion [see Warnings and Precautions ( 5.4 )] . Check solution container composition, lot number, and expiry date. Do not admix with other drugs. Do not use solution containers in series connections. The intact port cap provides visual tamper evidence. Do not use if port cap is prematurely removed. Maintain strict aseptic technique during handling. INSTRUCTIONS FOR USE: Always inspect the solution container before and after removal from the overwrap. Place the solution container on a clean, flat surface. Remove the solution container from the overwrap. Check the solution container for leaks by squeezing firmly. If leaks are found, discard. Do not use if the solution is cloudy or a precipitate is present. To Prepare for Administration: Immediately before inserting the infusion set, break off BLUE Infusion Port Cap with the arrow pointing away from the solution container. Use a non-vented infusion set or close the air-inlet on a vented set. Close the roller clamp of the infusion set Hold the base of the BLUE infusion port, twist and push spike until fully inserted. The BLUE infusion port contains a self-sealing septum that helps prevent leakage after removing the spike. The infusion port is not intended to be spiked more than once. Suspend solution container from hanger hole. For Single Use Only. Discard unused portion. 2.2 Recommended Dosage Individualize the dose of Calcium Gluconate in Sodium Chloride Injection within the recommended range depending on the severity of …

3 DOSAGE FORMS AND STRENGTHS Calcium Gluconate Injection USP is a clear, colorless to slightly yellow, solution available in the following: • Single dose vial: 1,000 mg per 10 mL (100 mg per mL) • Single dose vial: 5,000 mg per 50 mL (100 mg per mL) • Pharmacy bulk package: 10,000 mg per 100 mL (100 mg per mL) Each mL of Calcium Gluconate Injection contains 9.3 mg (0.465 mEq) of elemental calcium. Calcium Gluconate Injection, USP ( 3 ) • Single-dose vial: 1,000 mg per 10 mL (100 mg per mL) • Single-dose vial: 5,000 mg per 50 mL (100 mg per mL) • Pharmacy bulk package: 10,000 mg per 100 mL (100 mg per mL)

4 CONTRAINDICATIONS Calcium Gluconate in Sodium Chloride 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 )

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 Glenmark Pharmaceuticals Inc., USA at 1 (888) 721-7115 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

7 DRUG INTERACTIONS 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 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. 7.2 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.

8 USE IN SPECIFIC POPULATIONS Geriatric use : Dosing in elderly patients should be cautious, usually starting at the low end of the dosage range. ( 8.5 ) Renal impairment: Initiate with the lower limit of the dosage range and monitor serum calcium levels every 4 hours. ( 8.6 , 2.4 ) 8.1 Pregnancy Risk summary Limited available data with Calcium Gluconate Injection use in pregnant women are insufficient to inform a 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 Considerations Disease-associated maternal risk Maternal hypocalcemia can result in an increased rate of spontaneous abortion, premature and dysfunctional labor, and possibly preeclampsia. Fetal/Neonatal adverse reactions Infants 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. 8.2 Lactation Risk summary Calcium is present in human milk as a natural component of human milk. It is not known whether intravenous administration of Calcium Gluconate 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 mother’s clinical need for Calcium Gluconate Injection and any potential adverse effects on the breastfed child from Calcium Gluconate Injection or from the underlying maternal condition. 8.4 Pediatric Use The safety and effectiveness of Calcium Gluconate Injection have been established in pediatric patients for the treatment of acute, symptomatic hypocalcemia. Pediatric approval for Calcium Gluconate 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 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 a compatible fluid [ see Contraindications ( 4 ) and Warnings and Precautions ( 5.2 )] . This product contains up to 512 mcg/L aluminum which may be toxic, particularly for premature neonates due to immature renal function. Parenteral administration of aluminum greater than 4 to 5 mcg/kg/day is associated with central nervous system and bone toxicity [see Warnings and Precautions ( 5.5 )] . 8.5 Geriatric 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. 8.6 Renal Impairment For patients with renal impairment, initiate Calcium Gluconate Injection at the lowest dose of the recommended dose ranges across all age groups. Monitor serum calcium levels every 4 hours [see Dosage and Administration ( 2.4 )]. 8.7 Hepatic Impairment Hep …

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 normal constituents of body fluids.

11 DESCRIPTION Calcium gluconate injection USP, 100 mg per mL is a sterile, clear, colorless to slightly yellow, preservative-free, nonpyrogenic, supersaturated solution of calcium gluconate, a form of calcium, for intravenous use. The chemical name of calcium gluconate monohydrate, USP 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 g/mol Solubility in water: 3.5 g/100 mL at 25°C Calcium gluconate monohydrate, USP is a white, crystalline granules or powder. It is soluble in boiling water, sparingly soluble in water and insoluble in alcohol. 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. 1

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.

HOW SUPPLIED/STORAGE AND HANDLING Calcium Gluconate Injection, USP is a clear, colorless to slightly yellow solution supplied as follows: Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Do not freeze. Preservative Free. Discard any unused portion in the single-dose vial immediately or the Pharmacy Bulk Package vial within 4 hours after initial closure puncture. Each dose dispensed from the Pharmacy Bulk Package vial must be used immediately. The diluted solution must be used immediately. NOTE: Supersaturated solutions are prone to precipitation. The precipitate, if present, may be dissolved by warming the vial to 60° to 80°C, with occasional agitation, until the solution becomes clear. Shake vigorously. Allow to cool to room temperature before dispensing. Use injection only if clear immediately prior to use. Product repackaged by: Henry Schein, Inc., Bastian, VA 24314 From Original Manufacturer/Distributor's NDC and Unit of Sale To Henry Schein Repackaged Product NDC and Unit of Sale Total Strength/Total Volume (Concentration) per unit NDC 63323-360-19 25 x 10 mL single dose vials NDC 0404-9831-10 1 10 mL single dose vial in a bag (Vial bears NDC 63323-360-01) 1,000 mg calcium gluconate per 10 mL (100 mg per mL) NDC 63323-360-59 25 x 50 mL single dose vials NDC 0404-9831-50 1 50 mL single dose vial in a bag (Vial bears NDC 63323-360-03) 5,000 mg calcium gluconate per 50 mL (100 mg per mL) Image2.jpg