Lactate

1 INDICATIONS AND USAGE Potassium Chloride in Lactated Ringer’s and Dextrose (5%) Injection is indicated for use as a source of water, electrolytes, and calories or as an alkalinizing agent in adults and pediatric patients. Potassium Chloride in Lactated Ringer’s and Dextrose (5%) Injection is indicated for use as a source of water, electrolytes, and calories or as an alkalinizing agent in adults and pediatric patients. ( 1 )

12.1 Mechanism of Action Potassium Chloride in Lactated Ringer’s and Dextrose (5%) Injection is a source of water, electrolytes, and calories, and produces an alkalinizing effect. • 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. • Sodium lactate provides sodium and lactate ions. The lactate anion is in equilibrium with pyruvate and has an alkalinizing effect resulting from simultaneous removal by the liver of lactate and hydrogen ions. The sodium ion combines with bicarbonate ion produced from carbon dioxide of the body and thus retains bicarbonate to combat metabolic acidosis (bicarbonate deficiency). • Dextrose provides a source of calories. Dextrose may decrease losses of body protein and nitrogen, promotes glycogen deposition and decreases or prevents ketosis if sufficient doses are provided.

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 ) • Potassium Chloride in Lactated Ringer’s and Dextrose (5%) Injection is for intravenous use. ( 2.3 ) • Use a peripheral vein to administer if the final dextrose concentration is 5% or less, and the osmolarity is less than 900 mOsm/L. ( 2.3 ). • Consider using a central vein to administer hypertonic solutions with osmolarity of 900 mOsm/L or more to avoid venous irritation, including phlebitis. ( 2.3 ) • Do not administer Potassium Chloride in Lactated Ringer’s and Dextrose (5%) 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 Potassium Chloride in Lactated Ringer’s and Dextrose (5%) Injection is based on the patient’s age, weight, clinical condition, and concomitant therapy. Evaluate the patient’s clinical status and monitor changes in blood glucose and electrolyte concentrations especially during prolonged use of Potassium Chloride in Lactated Ringer’s and Dextrose (5%) Injection to optimize clinical status. 2.2 Important Preparation Instructions Visually inspect the Potassium Chloride in Lactated Ringer’s and Dextrose (5%) Injection solution for particulate matter and discoloration. Do not administer Potassium Chloride in Lactated Ringer’s and Dextrose (5%) Injection unless the solution is clear and the container seals are intact. If additives are determined to be compatible with Potassium Chloride in Lactated Ringer’s and Dextrose (5%) 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 preparation instructions for Potassium Chloride in Lactated Ringer’s and Dextrose (5%) Injection [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 Potassium Chloride in Lactated Ringer’s and Dextrose (5%) Injection, turn off the pump before the container is empty. Preparation Instructions 1. Tear overwrap downside at slit and remove solution container. 2. Visually inspect the container. o If the outlet port protector is damaged, detached, or not present, discard container as solution path sterility may be impaired. o Some opacity of the plastic due to moisture absorption during the sterilization process may be observed. This is normal and does not affect the solution quality or safety. The opacity will diminish gradually. 3. Check for minute leaks by squeezing inner bag firmly. If leaks are found, discard solution as sterility may be impaired. 4. If supplemental medication is desired, follow directions below [see Dosage and Administration (2.3) ] . Preparation for Administration 1. Suspend container from eyelet support. 2. Remove protector from outlet port at bottom of container. 3. Attach administration set according to its accompanying directions. 2.3 Important Administration Instructions Potassium Chloride in Lactated Ringer’s and Dextrose (5%) Injection is for intravenous use. Use immediately after removing the overwrap. Discard the unused portion. • Use a peripheral vein to administer Potassium Chloride in Lactated Ringer’s and Dextrose (5%)

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) ] • Neonatal Hypoglycemia [see Warnings and Precautions (5.6) ] • Hyperglycemia and Hyperosmolar Hyperglycemic State [see Warnings and Precautions (5.7) ] • Hypercalcemia [see Warnings and Precautions (5.8) ] • Fluid Overload [see Warnings and Precautions (5.9) ] • Acid/Base Imbalances [see Warnings and Precautions (5.10) ] The following adverse reactions have been identified during postapproval use of Lactated 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, and headache, laryngeal edema, sneezing, 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 Baxter Healthcare at 1-866-888-2472 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 Potassium Chloride in Lactated Ringer’s and Dextrose (5%) 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 Potassium Chloride in Lactated Ringer’s and Dextrose (5%) Injection infusion immediately if signs or symptoms of a hypersensitivity reaction develop. ( 5.3 ) • Potassium Imbalances, Hyponatremia, Neonatal Hypoglycemia, Hyperglycemia and Hyperosmolar Hyperglycemic State, Hypercalcemia, Fluid Overload, Acid-Base Imbalances, Interference with Interpretation of Serum Lactate Levels in Patients with Severe Metabolic Acidosis: See Full Prescribing Information for risk management recommendations. ( 5.4 , 5.5 , 5.6 , 5.7 , 5.8 , 5.9 , 5.10 , 5.11 ) 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 Potassium Chloride in Lactated Ringer’s and Dextrose (5%) 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. Potassium Chloride in Lactated Ringer’s and Dextrose (5%) 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 Potassium Chloride in Lactated Ringer’s and Dextrose (5%) 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. 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 Lactated Ringer’s solution. Stop the Potassium Chloride in Lactated Ringer’s and Dextrose (5%) 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 Potassium Chloride in Lactated Ringer’s and Dextrose (5%) 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,

4 CONTRAINDICATIONS Potassium Chloride in Lactated Ringer’s and Dextrose (5%) 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 of the components of Potassium Chloride in Lactated Ringer’s solution and Dextrose (5%) Injection [see Warnings and Precautions (5.3) ] . • Patients with clinically significant hyperkalemia [see Warnings and Precautions (5.4) ] . • Patients with clinically significant hyperglycemia [see Warnings and Precautions (5.7) ] . • Concomitant treatment with ceftriaxone in neonates (28 days of age or younger). ( 4 ) • Patients with known hypersensitivity to any of the components of Potassium Chloride in Lactated Ringer’s solution and Dextrose (5%) Injection ( 4 ) • Patients with clinically significant hyperkalemia ( 4 ). • Patients with clinically significant hyperglycemia ( 4 ).

10 OVERDOSAGE Excessive administration of Potassium Chloride in Lactated Ringer’s and Dextrose (5%) Injection can cause: • Hyperkalemia and hypernatremia, especially in patients with severe renal impairment. • Fluid overload (which can lead to pulmonary and/or peripheral edema). • Hyperglycemia, hyperosmolarity, and osmotic diuresis, dehydration, and electrolyte loss. • Metabolic alkalosis with or without hypokalemia. • Loss of bicarbonate with an acidifying effect. • Hypercalcemia. Overdose interventions include Potassium Chloride in Lactated Ringer’s and Dextrose (5%) Injection discontinuation, treatment of electrolyte imbalances, treatment of hyperglycemia, and close monitoring of fluid balance, electrolyte concentrations, and acid-base balance [see Warnings and Precautions (5.4 , 5.5 , 5.6 , 5.7 , 5.9 , 5.10 )]