Calcium Chloride

INDICATIONS AND USAGE Calcium Chloride Injection, USP, 10% is indicated: In the treatment of hypocalcemia in conditions requiring a prompt increase in plasma calcium levels (e.g., neonatal tetany and tetany due to parathyroid deficiency, vitamin D deficiency and alkalosis) and for prevention of hypocalcemia during exchange transfusions. As adjunctive therapy in the management of acute symptoms in lead colic. In the treatment of magnesium intoxication due to overdosage of magnesium sulfate. In severe hyperkalemia, to combat deleterious effects on electrocardiographic (ECG) function, pending correction of the potassium level in the extracellular fluid. In cardiac resuscitation, particularly after open heart surgery, when epinephrine fails to improve weak or ineffective myocardial contractions.

2 DOSAGE AND ADMINISTRATION • Administer Calcium Chloride Injection by slow intravenous infusion (not to exceed 1 mL/minute), in a central or deep vein. ( 2.1 ) • Do not use intramuscularly or subcutaneously. ( 2.1 ) • Do not administer unless solution is clear and seal is intact. ( 2.1 ) • Stop the administration if the patient complains of any administration-related discomfort, it may be resumed when symptoms disappear. ( 2.1 ) • The recommended adult dose is from 200 mg to 1,000 mg. ( 2.2 ) • The recommended pediatric dose is from 2.7 to 5 mg/kg of calcium chloride. ( 2.2 ) • Repeated injections may be required because of rapid calcium excretion. ( 2.2 ) • See the full prescribing information for the recommended starting dose in patients with renal impairment. ( 2.3 ) • Do not mix Calcium Chloride Injection with ceftriaxone or administer these products simultaneously via a Y-site because concurrent use can lead to the formation of ceftriaxone-calcium precipitates. ( 2.4 ) 2.1 Important Administration Instructions Administer Calcium Chloride Injection by slow intravenous infusion in a central or deep vein in adults and pediatric patients (with or without renal impairment); do not administer by bolus [see Warnings and Precautions ( 5.2 , 5.4 )] . The maximum recommended infusion rate is 1 mL/minute (100 mg/minute). Additional important administration instructions regarding Calcium Chloride Injection are as follows: • Do not use intramuscularly or subcutaneously to avoid tissue necrosis calcinosis cutis [see Warnings and Precautions ( 5.4 )] . • Visually inspect for particulate matter and discoloration prior to administration (the solution is clear, and the seal is intact). Do not administer if the solution is unclear or the seal is not intact. • Stop the administration if the patient complains of any administration-related discomfort; administration may be resumed when symptoms disappear. • Discard the unused portion. • If time permits, allow the solution to warm to body temperature. 2.2 Recommended Dosage and Administration The recommended dose range of Calcium Chloride Injection in: • Adults is from 200 mg to 1,000 mg. • Pediatric patients is from 2.7 to 5 mg/kg of calcium chloride. Dosing of this Calcium Chloride Injection product is not possible in patients who require doses less than 200 mg because the recommended dose cannot be achieved with the supplied syringe. For patients who require doses less than 200 mg, use another calcium chloride injection product that allows dosing of less than 200 mg. Individualize the dose for a patient within these dose ranges depending on serum ionized calcium level, severity of hypocalcemia symptoms, and the acuity of hypocalcemia onset. Repeated injections may be required because of rapid excretion of calcium. 2.3 Recommended Starting Dose in Patients with Renal Impairment The recommended starting dose of Calcium Chloride Injection in [see Use in Specific Populations ( 8.6 )]: • Adults with renal impairment is 200 mg. • Pediatric patients is 2.7 mg/kg of calcium chloride. 2.4 Drug Incompatibilities Do not mix Calcium Chloride Injection with other drugs simultaneously. Do not mix Calcium Chloride Injection with ceftriaxone or administer these products simultaneously via a Y-site because concurrent use can lead to the formation of ceftriaxone-calcium precipitates [see Warnings and Precautions ( 5.1 )]: • In neonates (28 days of age or younger), concomitant use of Calcium Chloride Injection and ceftriaxone is contraindicated [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.

2.1 Important Administration Instructions Administer Calcium Chloride Injection by slow intravenous infusion in a central or deep vein in adults and pediatric patients (with or without renal impairment); do not administer by bo …

3 DOSAGE FORMS AND STRENGTHS Calcium Chloride Injection, USP (single-dose) supplied as: • 10% (1,000 mg/10 mL) (100 mg/mL) in a Luer-JetTM Luer-Lock Prefilled Syringe The 100 mg/mL concentration represents 27 mg or 1.4 mEq of elemental calcium per mL of solution. Calcium Chloride Injection, USP (single-dose) is supplied as: ( 3 ) • 10% (1,000 mg/10 mL) (100 mg/mL) in a Luer-JetTM Luer-Lock Prefilled Syringe The 100 mg/mL concentration represents 27 mg or 1.4 mEq of elemental calcium per mL of solution. ( 3 )

4 CONTRAINDICATIONS Calcium Chloride Injection is contraindicated in: • Patients with ventricular fibrillation • Patients with asystole and electromechanical dissociation Newborns (up to 28 days of age) if they require (or are expected to require) ceftriaxone intravenous treatment because of the risk of precipitation of ceftriaxone-calcium, regardless of whether these products would be received at different times or through separate intravenous lines [see Warnings and Precautions ( 5.1 )] . Calcium Chloride Injection is contraindicated in: • Patients with ventricular fibrillation. ( 4 ) • Patients with asystole and electromechanical dissociation. ( 4 ) • Newborns (up to 28 days of age) if they require (or are expected to require) ceftriaxone intravenous treatment, regardless of whether these products would be received at different times or through separate intravenous lines. ( 4 , 5.1 )

6 ADVERSE REACTIONS The following serious adverse reactions are also described elsewhere in the labeling: • End-Organ Damage due to Intravascular Ceftriaxone-Calcium Precipitates [see Warnings and Precautions ( 5.1 )] • Hypotension, Bradycardia, Arrhythmias, and Syncope with Rapid Administration [see Warnings and Precautions ( 5.2 )] • Arrhythmias with Concomitant Digoxin Use [see Warnings and Precautions ( 5.3 )] • Tissue Necrosis and Calcinosis [see Warnings and Precautions ( 5.4 )] • Aluminum toxicity [see Warnings and Precautions ( 5.5 )] The following adverse reactions have been identified in literature and postmarketing reports of calcium chloride. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: • Nervous system disorders: Paraesthesia (upon rapid injection), calcium taste • General disorders and administration site conditions: Sense of oppression, sense of “heat wave”, local burning sensation, injection site extravasation, injection site reactions • Cardiovascular disorders: Peripheral vasodilatation, decreased blood pressure Adverse reactions have included paraesthesia (upon rapid injection), calcium taste, sense of oppression, sense of “heat wave”, local burning sensation, injection site extravasation, injection site reactions, peripheral vasodilatation, and decreased blood pressure. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Amphastar Pharmaceuticals, Inc. at 1-800-423-4136 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

7 DRUG INTERACTIONS • Digoxin: Avoid concomitant use with Calcium Chloride Injection. If concomitant use is unavoidable, monitor ECG closely during administration of Calcium Chloride Injection. ( 5.3 , 7.1 ) • Calcium Channel Blockers: Avoid concomitant use with Calcium Chloride Injection. If concomitant use is unavoidable, monitor blood pressure closely during administration of Calcium Chloride Injection. ( 7.2 ) • Drugs That Increase the Risk of Hypercalcemia: Increase the frequency of calcium concentration monitoring in patients taking Calcium Chloride Injection concomitantly with other drugs that increase the risk of hypercalcemia. ( 7.3 ) 7.1 Digoxin Avoid the concomitant use of Calcium Chloride Injection with digoxin. If concomitant use is unavoidable, monitor ECG closely during administration of Calcium Chloride Injection. Synergistic arrhythmias may occur with concomitant use. The use of Calcium Chloride Injection may result in hypercalcemia which increases the risk of digoxin toxicity [see Warnings and Precautions ( 5.3 )] . 7.2 Calcium Channel Blockers Concomitant use of Calcium Chloride Injection and calcium channel blockers may reduce the response to calcium channel blockers. Avoid concomitant use. If concomitant use is unavoidable, monitor blood pressure closely during administration of Calcium Chloride Injection. 7.3 Drugs That Increase the Risk of Hypercalcemia Increase frequency of monitoring of calcium concentrations in patients taking concomitant Calcium Chloride Injection and other drugs that increase the risk of hypercalcemia (e.g., calcipotriene, estrogen, lithium, parathyroid hormone, teriparatide, thiazide diuretics, Vitamin A, and Vitamin D).

7.1 Digoxin Avoid the concomitant use of Calcium Chloride Injection with digoxin. If concomitant use is unavoidable, monitor ECG closely during administration of Calcium Chloride Injection. Synergistic arrhythmias may occur with concomitant use. The use of Calcium Chloride Injection may result in hypercalcemia which increases the risk of digoxin toxicity [see Warnings and Precautions ( 5.3 )] .

7.2 Calcium Channel Blockers Concomitant use of Calcium Chloride Injection and calcium channel blockers may reduce the response to calcium channel blockers. Avoid concomitant use. If concomitant use is unavoidable, monitor blood pressure closely during administration of Calcium Chloride Injection.

7.3 Drugs That Increase the Risk of Hypercalcemia Increase frequency of monitoring of calcium concentrations in patients taking concomitant Calcium Chloride Injection and other drugs that increase the risk of hypercalcemia (e.g., calcipotriene, estrogen, lithium, parathyroid hormone, teriparatide, thiazide diuretics, Vitamin A, and Vitamin D).

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary Administration of Calcium Chloride Injection for the treatment of acute symptomatic hypocalcemia during pregnancy is not expected to cause major birth defects, miscarriage, or adverse maternal or fetal outcomes. There are risks to the mother and the fetus associated with development of hypocalcemia during pregnancy (see Clinical Considerations) . Animal reproduction studies have not been conducted with Calcium Chloride Injection. The estimated background risk of major birth defects and miscarriage for the indicated populations are unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-associated Maternal and/or Embryo/Fetal/Neonatal Risk Maternal hypocalcemia can result in an increased rate of spontaneous abortion, premature and dysfunctional labor, and possibly preeclampsia. Infants born to mothers with hypocalcemia can develop fetal and neonatal hyperparathyroidism, which in turn can cause fetal and neonatal skeletal demineralization, subperiosteal bone resorption, osteitis fibrosa cystica and neonatal seizures. 8.2 Lactation Risk Summary Calcium is present in human milk. Administration of the approved recommended dose of Calcium Chloride Injection to the mother is not expected to cause harm to a breastfed infant. There is no information on the effects of Calcium Chloride 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 Chloride Injection and any potential adverse effects on the breastfed infant from Calcium Chloride Injection or from the underlying maternal condition. 8.4 Pediatric Use The safety and effectiveness of Calcium Chloride Injection for the treatment of acute symptomatic hypocalcemia have been established in pediatric patients. The use of Calcium Chloride Injection is contraindicated in newborns if they require (or are expected to require) ceftriaxone intravenous treatment because of the risk of precipitation of ceftriaxone-calcium, regardless of whether these products would be received at different times or through separate intravenous lines [see Contraindications ( 4 ) and Warnings and Precautions ( 5.1 )] . In pediatric patients older than 28 days of age, Calcium Chloride Injection and ceftriaxone intravenous solutions may be administered sequentially one after another if infusion lines at different sites are used, infusion lines are replaced, or infusion lines are thoroughly flushed between infusions with physiological salt solution to avoid precipitation. Do not mix or administer Calcium Chloride Injection simultaneously with ceftriaxone, even if using different infusion lines or different infusion sites as it can lead to precipitation of ceftriaxone-calcium. Calcium Chloride Injection contains aluminum that may be associated with central nervous system and bone toxicity. Because of immature renal function, preterm infants receiving prolonged parenteral nutrition treatment with Calcium Chloride Injection may be at higher risk of aluminum toxicity [see Warnings and Precautions ( 5.2 )] . 8.5 Geriatric Use Clinical studies of Calcium Chloride Injection did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger adult patients. 8.6 Renal Impairment The use of Calcium Chloride Injection in patients with renal impairment may increase the risk of a higher calcium-phosphorus product. For patients with renal impairment, initiate Calcium Chloride Injection at the lowest recommended dose within the recommended dose range [see Dosage and Administration ( 2.2 )] . Monitor serum calcium levels frequently based on t …

11 DESCRIPTION 10% Calcium Chloride Injection, USP is a sterile, nonpyrogenic, hypertonic solution for single administration only. Each mL contains 100 mg (1.4 mEq/mL) of calcium chloride, dihydrate (1.4 mEq each of Ca ++ and Cl − ) in water for injection. It is provided in a 10 mL single-dose syringe for intravenous injection. The solution contains no bacteriostat, antimicrobial agent or added buffer. The pH of 10% Calcium Chloride Injection, USP is 5.5 to 7.5 when diluted with water for injection to make a 5% solution. May contain hydrochloric acid and/or sodium hydroxide for pH adjustment. The osmolar concentration is 2.04 mOsmol/mL (calc.). 10% Calcium Chloride Injection, USP is oxygen sensitive. Calcium Chloride, USP dihydrate is chemically designated CaCl 2 • 2H 2 O (dihydrate) and is described as white, odorless fragments or granules freely soluble in water. Calcium Chloride Injection, USP contains no more than 1,000 mcg/L of aluminum [see Warnings and Precautions ( 5.2 )] .

10 OVERDOSAGE Overdosage of Calcium Chloride Injection may lead to hypercalcemia. Symptoms of hypercalcemia typically develop when the total serum calcium concentration is ≥12 mg/dL, and include shortening of QT interval, bradycardia, hypertension, anorexia, nausea, vomiting, bowel hypomotility and constipation, muscle weakness, bone pain, decreased concentration, depression, weakness, fatigue, confusion, hallucinations, disorientation, hypotonicity, seizures, and coma. Hypercalcemia effects on kidney include diminished ability to concentrate urine and diuresis. In the event of overdosage, promptly discontinue Calcium Chloride Injection, the patient should be reevaluated and appropriate countermeasures should be instituted, if necessary [see Warnings and Precautions ( 5 ), Adverse Reactions ( 6 )] .

HOW SUPPLIED 10% CALCIUM CHLORIDE INJECTION, USP is supplied in the following dosage forms. NDC 51662-1379-1 10% CALCIUM CHLORIDE INJECTION, USP 1 g/10 mL (100 mg/ mL) (1.4 mEq/mL) LUER-JETTM SYR NDC 51662-1379-2 10% CALCIUM CHLORIDE INJECTION, USP 1 g/10 mL (100 mg/ mL) (1.4 mEq/mL) LUER-JETTM SYR in a POUCH NDC 51662-1379-3 10% CALCIUM CHLORIDE INJECTION, USP 1 g/10 mL (100 mg/ mL) (1.4 mEq/mL) LUER-JETTM SYR in a Pouch, 10 Pouches per Case HF Acquisition Co LLC, DBA HealthFirst Mukilteo, WA 98275 Also supplied in the following manufacture supplied dosage forms 10% Calcium Chloride Injection, USP is supplied in single-dose containers as follows: One shrink wrapped package containing 10 unit cartons, each containing a Luer-JetTM Luer-Lock Prefilled Syringe. Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Syringe Assembly Directions: USE ASEPTIC TECHNIQUE Do not assemble until ready to use. *CAUTION: IMPROPER ENGAGING MAY CAUSE GLASS BREAKAGE AND SUBSEQUENT INJURY. HOW SUPPLIED HOW SUPPLIED IMAGE