Calcium Chloride

1 INDICATIONS AND USAGE Ringer’s Injection is indicated for use as a source of water and electrolytes in adults and pediatric patients. Ringer’s Injection is indicated for use as a source of water and electrolytes in adults and pediatric patients. ( 1 )

12.1 Mechanism of Action Ringer’s Injection is a source of water, and electrolytes. Sodium, the major cation of the extracellular fluid, functions primarily in the control of water distribution, fluid balance, and osmotic pressure of body fluids. Sodium is also associated with chloride and bicarbonate in the regulation of the acid-base equilibrium of body fluid. Potassium, the principal cation of intracellular fluid, participates in carbohydrate utilization and protein synthesis and is critical in the regulation of nerve conduction and muscle contraction, particularly in the heart. Chloride, the major extracellular anion, closely follows the metabolism of sodium, and changes in the acid-base balance of the body are reflected by changes in the chloride concentration. Calcium, an important cation, provides the framework of bones and teeth in the form of calcium phosphate and calcium carbonate. In the ionized form, calcium is essential for the functional mechanism of the clotting of blood, normal cardiac function, and regulation of neuromuscular irritability.

2 DOSAGE AND ADMINISTRATION The recommended dosage and duration are based on the patient’s age, weight, clinical condition, and concomitant therapy. ( 2.1 ) To reduce the risk of air embolism, adhere to the preparation instructions. ( 2.2 , 5.2 ) Ringer’s Injection is for intravenous use ( 2.3 ) Do not administer Ringer’s Injection simultaneously with ceftriaxone in neonates (28 days of age or younger) due to serious risks. ( 2.4 ) See full prescribing information for information dosage considerations, preparation, administration, and drug incompatibilities. ( 2 ) 2.1 Dosage Considerations The recommended dosage and duration of Ringer’s Injection is based on the patient’s age, weight, clinical condition, and concomitant therapy. Evaluate the patient’s clinical status and monitor changes in electrolyte concentrations especially during prolonged use of Ringer’s Injection to optimize clinical status. Fluid administration should be based on calculated maintenance or replacement fluid requirements for each patient. 2.2 Important Preparation Instructions Visually inspect the Ringer’s Injection solution for particulate matter and discoloration. Do not administer Ringer’s Injection unless the solution is clear and the container seals are intact. If additives are determined to be compatible with Ringer’s Injection, then using aseptic technique, mix thoroughly; do not store solutions containing additives. After mixing, do not use if there is discoloration or formation of precipitates. To reduce the risk of air embolism, adhere to the following Ringer’s Injection preparation instructions [see Warnings and Precautions (5.2) ] : Use a non-vented infusion set or close the vent on a vented set. Use a dedicated line without any connections (do not connect flexible containers in series). The use of pressure infusion is not recommended as a method to increase flow rates. However, if pressure infusion is required, ensure that any air within the bag is fully evacuated prior to initiation of infusion. If using a pumping device to administer Ringer’s Injection, turn off the pump before the container is empty. Preparation Instructions for EXCEL ® Containers Tear overwrap down at notch and remove solution container. Check for minute leaks by squeezing solution container firmly. If leaks are found, discard solution as sterility may be impaired. If supplemental medication is desired, follow directions below before preparing for administration. Inspect each container. Read the label. Ensure solution is the one ordered and is within the expiration date. Invert container and carefully inspect the solution in good light for cloudiness, haze, or particulate matter. Any container which is suspect should not be used. If supplemental medication is desired, follow directions below [see Dosage and Administration (2.3) ] . Preparation for Administration Remove plastic protector from sterile set port at bottom of container. Attach administration set according to its accompanying directions. 2.3 Important Administration Instructions Ringer’s Injection is for intravenous use. Use immediately after opening the container. Discard the unused portion. It is recommended that intravenous administration apparatus be replaced at least once every 24 hours. Some additives may be incompatible [see Dosage and Administration (2.4) ] . To Add Medication Before Solution Administration Prepare medication site. Using syringe with 18-22 gauge needle, puncture medication port and inner diaphragm and inject. Squeeze and tap ports while ports are upright and mix solution and medication thoroughly. To Add Medication During Solution Administration Close clamp on the set. Prepare medication site. Using syringe with 18-22 gauge needle of appropriate length (at least 5/8 inch), puncture resealable medication port and inner diaphragm and inject. Remove container from IV pole and/or turn to an upright position. Evacuate both ports by tapping and squeezing them while container is in the upright

6 ADVERSE REACTIONS The following serious adverse reactions are discussed in greater detail in other sections of the labeling: Serious Risk with Concomitant Use with Ceftriaxone [see Warnings and Precautions (5.1) ] Air Embolism [see Warnings and Precautions (5.2) ] Hypersensitivity Reactions [see Warnings and Precautions (5.3) ] Potassium Imbalances [see Warnings and Precautions (5.4) ] Hyponatremia [see Warnings and Precautions (5.5) ] Hypercalcemia [see Warnings and Precautions (5.6) ] Fluid Overload [see Warnings and Precautions (5.7) ] The following adverse reactions have been identified during postapproval use of Ringer’s Products. Because these reactions are 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: General Disorders and Administration Site Conditions : Phlebitis, extravasation, infusion site inflammation, infusion site swelling, infusion site rash, infusion site pruritus, infusion site erythema, infusion site pain, infusion site burning, and infusion site hypoaesthesia. Hypersensitivity Reactions and Infusion Reactions : Angioedema, chest pain/discomfort, bradycardia or tachycardia, hypotension, respiratory distress, bronchospasm, dyspnea, cough, urticaria, rash, pruritus, erythema, flushing, throat irritation, paresthesia, oral hypoesthesia, dysgeusia, nausea, anxiety, pyrexia, headache, laryngeal edema, sneezing, and injection site infection. Metabolism and Nutrition Disorders : Hyperkalemia, hyponatremia, and hypervolemia. Nervous System Disorders : Hyponatremic encephalopathy. Common adverse reactions include infusion site reactions and symptoms of hypersensitivity reactions (e.g., pruritus, dyspnea, urticaria, rash, cough). ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact B. Braun Medical Inc. at 1-833-425-1464 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

5 WARNINGS AND PRECAUTIONS Serious Risks with Inappropriate Use with Ceftriaxone : Deaths have occurred in neonates (28 days of age or younger) who received concomitant intravenous calcium-containing solutions with ceftriaxone. In patients older than 28 days, ceftriaxone and Ringer’s Injection may be administered sequentially if the infusion lines are thoroughly flushed between infusions. ( 4 , 5.1 , 8.4 ) Air Embolism : Use a non-vented infusion set or close the vent on a vented set and use a dedicated line without any connections. Pressure infusion is not recommended to increase flow rates, but if necessary, remove all air from the bag prior to initiating infusion. ( 5.2 ) Hypersensitivity Reactions : Stop the Ringer’s Injection infusion immediately if signs or symptoms of a hypersensitivity reaction develop. ( 5.3 ) Potassium Imbalances, Hyponatremia, Hypercalcemia, Fluid Overload : See Full Prescribing Information for risk management recommendations. ( 5.4 , 5.5 , 5.6 , 5.7 ) 5.1 Serious Risk with Concomitant Use with Ceftriaxone Precipitation of ceftriaxone-calcium can occur when ceftriaxone is mixed with calcium-containing solutions, such as Ringer’s Injection in the same intravenous administration line. Deaths have occurred in neonates (28 days of age or younger) who received concomitant intravenous calcium-containing solutions with ceftriaxone resulting from calcium-ceftriaxone precipitates in the lungs and kidneys, even when separate infusion lines were used. Ringer’s Injection is contraindicated in neonates who receive ceftriaxone [see Contraindications (4) , Use in Specific Populations (8.4) ]. However, in patients older than 28 days, ceftriaxone and Ringer’s Injection may be administered sequentially if the infusion lines are thoroughly flushed between infusions with a compatible fluid. 5.2 Air Embolism Cases of air embolism have been reported with pressurized administration of intravenous fluids. Air embolism may result in stroke, organ ischemia and/or infarction, and death. Use a non-vented infusion set or close the vent on a vented set and use a dedicated line without any connections. If administration is controlled by a pumping device, care must be taken to discontinue the pumping action before the container is empty. Pressure infusion is not recommended to increase flow rates, but if necessary, ensure all air is removed from the bag before infusion. Refrain from applying excessive pressure (>300mmHg) causing distortion to the container such as wringing or twisting. Such handling could result in breakage of the container [see Dosage and Administration (2.2) ] . 5.3 Hypersensitivity Reactions Hypersensitivity reactions, including anaphylaxis and angioedema, have been reported with Ringer’s Injection . Stop the Ringer’s Injection infusion immediately and treat patient accordingly if signs or symptoms of a hypersensitivity reaction develop. Initiate appropriate treatment as clinically indicated. 5.4 Potassium Imbalances Hyperkalemia Potassium-containing solutions, including Ringer’s Injection , may increase the risk of hyperkalemia. This risk is increased in patients predisposed to hyperkalemia including those with severe renal impairment, acute dehydration, extensive tissue injury or burns, heart failure, or in those using concomitant drugs that are associated with hyperkalemia. Avoid use of Ringer’s Injection in patients with, or at increased risk for, hyperkalemia. If use cannot be avoided in these patients, closely monitor serum potassium concentrations. Hypokalemia The potassium concentration in Ringer’s Injection is similar to the concentration in plasma. It is insufficient to normalize the serum potassium in patients with severe hypokalemia. 5.5 Hyponatremia Ringer’s Injection may cause hyponatremia. Hyponatremia can lead to acute hyponatremic encephalopathy characterized by headache, nausea, seizures, lethargy and vomiting. The risk of hospital-acquired hyponatremia is increased in younger pediatric patien

4 CONTRAINDICATIONS Ringer’s Injection is contraindicated in: Neonates (28 days of age or younger) who are receiving concomitant treatment with ceftriaxone, even if separate infusion lines are used, due to the risk of fatal ceftriaxone-calcium salt precipitation in the neonate’s bloodstream [see Warnings and Precautions (5.1) and Specific Populations (8.4) ] . Patients with known hypersensitivity to any components of Ringer’s Injection [see Warnings and Precautions (5.3) ]. Concomitant treatment with ceftriaxone in neonates (28 days of age or younger). ( 4) Patients with known hypersensitivity to Ringer’s Injection. ( 4 )

10 OVERDOSAGE Excessive administration of Ringer’s Injection can cause: Hyperkalemia and hypernatremia, especially in patients with severe renal impairment. Fluid overload (which can lead to pulmonary and/or peripheral edema). Hypercalcemia Overdose interventions include Ringer’s Injection discontinuation, treatment of electrolyte imbalances, and close monitoring of fluid balance and electrolyte concentrations [see Warnings and Precautions ( 5.4 , 5.5 , 5.6 , 5.7 )].