Calcium Gluconate

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

2 Dosage and Administration 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. 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 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. 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 intr…

5 Warnings and Precautions 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 Injection should be avoided in patients receiving cardiac glycosides. If concomitant therapy is necessary, Calcium Gluconate Injection should be given slowly in small amounts and with close ECG monitoring [see Drug Interactions (7.3)]. 5.2 End-Organ Damage due to Intravascular Ceftriaxone-Calcium Precipitates Concomitant use of ceftriaxone and Calcium Gluconate 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 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 Injection via a Y-site in any age group. 5.3 Tissue Necrosis and Calcinosis Intravenous administration of Calcium Gluconate 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 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 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 Injection should be diluted with 5% dextrose or normal saline and 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)]. 5.5 Aluminum Toxicity Calcium Gluconate Injection contains aluminum, up to 400 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 4 mcg/kg/day to 5 mcg/kg/day accumulate aluminum levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration. Arrhythmias with Concomitant Cardiac Glycoside Use: If concomitant therapy is necessary, Calcium Gluconate 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. Cases of fatal outcomes in neonates have occurred. (4, 5.2) Tissue Nec…

4 Contraindications 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)

7 Drug Interactions 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. 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)

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 Hikma Pharmaceuticals USA Inc. at 1-877-845-0689 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.