DEXTROSE AND SODIUM CHLORIDE

6 ADVERSE REACTIONS The following adverse reactions associated with the use of 2.5% Dextrose and 0.45% Sodium Chloride Injection were identified in postmarketing reports. Because 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. The following clinically significant adverse reactions are described elsewhere in the labeling: Hypersensitivity Reactions: anaphylaxis, rash and pruritus [see Warnings and Precautions ( 5.1 )] . Metabolism and Nutrition Disorders: hyperglycemia [see Warnings and Precautions ( 5.2 )] , hyponatremia and hyponatremic encephalopathy, for solutions containing less than 0.9% sodium chloride [see Warnings and Precautions ( 5.3 )] . Hypernatremia and hyperchloremia acidosis [see Warnings and Precautions ( 5.5 )] have been observed in solutions containing 0.9% sodium chloride. Infusion and/or Injection Site Reactions: phlebitis, injection site vesicles, infusion site pain, chills and pyrexia. Adverse reactions include electrolyte imbalances, hyperglycemia, and hypervolemia and injection site reactions. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC at 1-800-551-7176 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

4 CONTRAINDICATIONS 2.5% Dextrose and 0.45% Sodium Chloride Injection is contraindicated in patients with: known hypersensitivity to dextrose and/or sodium chloride [see Warnings and Precautions 5.1 )] clinically significant hyperglycemia [see Warnings and Precautions ( 5.2 )] Known hypersensitivity to dextrose, or sodium chloride ( 4 , 5.1 ) Clinically significant hyperglycemia ( 4 , 5.2 )

11 DESCRIPTION 2.5% Dextrose and 0.45% Sodium Chloride Injection, USP is a sterile, nonpyrogenic solution for fluid and electrolyte replenishment and caloric supply in single-dose containers for intravenous administration. It contains no antimicrobial agents. Composition, osmolarity, pH, ionic concentration and caloric content are shown in Table 1 . Table 1. * Normal physiologic osmolarity range is approximately 280 to 310 mOsmol/L. Size (mL) Composition (g/L) *Osmolarity (mOsmol/L) (calc.) pH Ionic Concentration (mEq/L) Caloric Content (kcal/L) **Dextrose Hydrous, USP Sodium Chloride, USP (NaCl) Sodium Chloride 2.5% Dextrose and 0.45% Sodium Chloride Injection, USP 1,000 25 4.5 280 4.5 (3.2 to 6.5) 77 77 85 Dextrose is derived from corn. The flexible plastic container is fabricated from a specially formulated non-plasticized, film containing polypropylene and thermoplastic elastomers ( free flex ® bag). The amount of water that can permeate from the container into the overwrap is insufficient to affect the solution significantly. Solutions in contact with the flexible container can leach out certain of the container's chemical components in very small amounts within the expiration period. The suitability of the container material has been confirmed by tests in animals according to USP biological tests for plastic containers. structural formula

2 DOSAGE AND ADMINISTRATION Only for intravenous infusion. ( 2.1 ) See full prescribing information for information on preparation, administration, dosing considerations and instructions for use. ( 2.1 , 2.2 , 2.3 ) 2.1 Important Administration Instructions 2.5% Dextrose and 0.45% Sodium Chloride Injection is only for intravenous infusion. The osmolarity of 2.5% Dextrose and 0.45% Sodium Chloride Injection, is 280 mOsmol/L (calc). Peripheral administration is generally acceptable; however; consider central vein administration if there is peripheral vein irritation, phlebitis, and/or associated pain. Do not administer 2.5% Dextrose and 0.45% Sodium Chloride Injection simultaneously with blood products through the same administration set because of the possibility of pseudoagglutination or hemolysis. To prevent air embolism, use a non-vented infusion set or close the vent on a vented set, avoid multiple connections, do not connect flexible containers in series, fully evacuate residual gas in the container prior to administration, do not pressurize the flexible container to increase flow rates, and if administration is controlled by a pumping device, turn off pump before the container runs dry. Prior to infusion, visually inspect the solution for particulate matter. The solution should be clear and there should be no precipitates. Do not administer unless solution is clear and container is undamaged. Use of a final filter is recommended during administration of parenteral solutions, where possible. 2.2 Recommended Dosage The choice of the specific, sodium chloride, and dextrose concentrations, rate and volume depends on the age, weight, clinical and metabolic conditions of the patient and concomitant therapy. Electrolyte supplementation may be indicated according to the clinical needs of the patient. The administration rate should be governed, especially for premature infants with low birth weight, during the first few days of therapy, by the patient's tolerance to dextrose. Increase the infusion rate gradually as indicated by frequent monitoring of blood glucose concentrations [see Warnings and Precautions ( 5.2 ), Use in Specific Populations ( 8.4 )] . 2.3 Instructions for Use Check flexible container solution composition, lot number, and expiry date. Do not remove solution container from its overwrap until immediately before use. Use sterile equipment and aseptic technique. Flexible Plastic Container ( free flex ® bag) To Open Turn solution container over so that the text is face down. Using the pre-cut corner tabs, peel open the overwrap and remove solution container. Check the solution container for leaks by squeezing firmly. If leaks are found, or if the seal is not intact, discard the solution. Check to ensure the solution is clear and there are no precipitates. Discard if there is a color change and/or the appearance of precipitates. Preparation for Administration Immediately before inserting the infusion set, break off BLUE Infusion Port Cap with the arrow pointing away from 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 BLUE Infusion Port. Insert spike through BLUE Infusion Port by rotating wrist slightly until the spike is inserted. NOTE: See full directions accompanying administration set. Suspend solution container from hanger hole. To Add Medication Additives may be incompatible. Complete information is not available. Do not use additives known or determined to be incompatible. Consult with pharmacist, if available. If, in the informed judgment of the healthcare provider, it is deemed advisable to introduce additives, use aseptic technique. When introducing additives, consult the instructions for use of the medication to be added and other relevant literature. Before adding a substance or medication, verify that it is soluble and/or stable in this drug product and that the pH range of this drug product is appropriate. To Add Medication Prior to Solution Administration Identify WHITE Additive Port with arrow pointing toward container. Immediately before injecting additives, break off WHITE Additive Port Cap with the arrow pointing toward container. Hold base of WHITE Additive Port horizontally. Prepare medication site Insert an 18 to 23 gauge needle horizontally through the center of WHITE Additive Port's septum and inject additives. Mix container contents thoroughly. For high density medication such as potassium chloride, squeeze ports while ports are upright and mix thoroughly. After addition, check to ensure the solution is clear and there are no precipitates. Discard if there is a color change and/or the appearance of precipitates. To Add Medication During Solution Administration Close the clamp on the set Identify WHITE Additive Port with arrow pointing toward container Immediately before injecting additives, if the Cap has not been broken off, break off WHITE Additive Port cap with the arrow pointing toward container. Hold base of WHITE Additive Port horizontally. Prepare medication site. Using a syringe with an 18 to 23 gauge needle, horizontally insert through the center of WHITE Additive Port's septum and inject additives. Remove container from IV pole and/or turn to an upright position. Mix container contents thoroughly. After addition, check to ensure the solution is clear and there are no precipitates. Discard if there is a color change and/or the appearance of precipitates. Using aseptic technique, repeat steps 4-7 as necessary. Return container to in use position and continue administration. Storage Use promptly; do not store solutions containing additives. Single-dose container. Discard any unused portion.

1 INDICATIONS AND USAGE 2.5% Dextrose and 0.45% Sodium Chloride Injection is indicated as a source of water, electrolytes and calories. 2.5% Dextrose and 0.45% Sodium Chloride Injection is indicated as a source of water, electrolytes and calories. ( 1 )

10 OVERDOSAGE Excessive administration of 2.5% Dextrose and 0.45% Sodium Chloride Injection can cause: Electrolyte and Fluid Disorders Hyperglycemia, hyperosmolality, and adverse effects on water and electrolyte balance, and corresponding complications, which can be fatal [see Warnings and Precautions ( 5.2 )] . Hyponatremia, manifestations may include seizures, coma, cerebral edema and death) [see Warnings and Precautions ( 5.3 )] . Hypernatremia, especially in patients with severe renal impairment [see Warnings and Precautions ( 5.5 )] . Fluid overload (which can lead to central and/or peripheral edema) [see Warnings and Precautions ( 5.6 )] . When assessing an overdose, any additives in the solution must also be considered. Clinically significant overdose of 2.5% Dextrose and 0.45% Sodium Chloride Injection may, therefore, constitute a medical emergency. The effects of an overdose may require immediate medical attention and treatment. Interventions include discontinuation of the infusion, dose reduction, monitoring of fluid balance, electrolyte concentrations and acid-base balance and institution of appropriate corrective measures such as administration of exogenous insulin.

7 DRUG INTERACTIONS Other Products that Affect Glycemic Control, Vasopressin or Fluid and/or Electrolyte Balance: Monitor blood glucose concentrations, fluid balance serum electrolyte concentrations and acid-base balance. ( 7.1 ) Lithium: Decreased lithium concentrations with concomitant use; monitor serum lithium concentrations. ( 7.2 ) 7.1 Other Products that Affect Glycemic Control, Vasopressin or Fluid and/or Electrolyte Balance 2.5% Dextrose and 0.45% Sodium Chloride Injection can affect glycemic control, vasopressin and fluid and/or electrolyte balance [see Warnings and Precautions ( 5.2 , 5.3 , 5.4 , 5.5 , 5.6 )] . Monitor blood glucose concentrations, fluid balance, serum electrolyte concentrations and acid-base balance when using 2.5% Dextrose and 0.45% Sodium Chloride Injection in patients treated with other substances that affect glycemic control, vasopressin or fluid and/or electrolyte balance. 7.2 Lithium Renal sodium and lithium clearance may be increased during administration of 2.5% Dextrose and 0.45% Sodium Chloride Injection resulting in decreased serum lithium concentrations. Monitor serum lithium concentrations during concomitant use.

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action 2.5% Dextrose and 0.45% Sodium Chloride Injection is a source of water, electrolytes and calories. It is capable of inducing diuresis depending on the clinical condition of the patient.

12.1 Mechanism of Action 2.5% Dextrose and 0.45% Sodium Chloride Injection is a source of water, electrolytes and calories. It is capable of inducing diuresis depending on the clinical condition of the patient.

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4

3 DOSAGE FORMS AND STRENGTHS 2.5% Dextrose and 0.45% Sodium Chloride Injection is a clear solution in 1000 mL single dose, flexible containers. 2.5% Dextrose and 0.45% Sodium Chloride Injection is a clear solution in 1000 mL single dose, flexible containers. ( 3 )

DEXTROSE AND SODIUM CHLORIDE DEXTROSE MONOHYDRATE, SODIUM CHLORIDE DEXTROSE MONOHYDRATE ANHYDROUS DEXTROSE SODIUM CHLORIDE SODIUM CATION WATER

ANDA211190

DEXTROSE AND SODIUM CHLORIDE

DEXTROSE MONOHYDRATE, SODIUM CHLORIDE

63323-874

HUMAN PRESCRIPTION DRUG

INTRAVENOUS

PACKAGE LABEL - PRINCIPAL DISPLAY –2.5% Dextrose and 0.45% Sodium Chloride Bag Label NDC 63323-874-10 free flex® 1000 mL 2.5% Dextrose and 0.45% Sodium Chloride Injection, USP For intravenous use. Rx only PACKAGE LABEL - PRINCIPAL DISPLAY –2.5% Dextrose and 0.45% Sodium

Contraindications ( 4 ) 08/2019 Warnings and Precautions ( 5.1 , 5.2 , 5.3 , 5.4 , 5.5 , 5.6 , 5.7 ) 08/2019

17 PATIENT COUNSELING INFORMATION Inform patients, caregivers or home healthcare providers of the following risks of 2.5% Dextrose and 0.45% Sodium Chloride Injection: Hypersensitivity reactions [see Warnings and Precautions ( 5.1 )] Hyperglycemia and hyperosmolar hyperglycemic state [see Warnings and Precautions ( 5.2 )] Hyponatremia [see Warnings and Precautions ( 5.3 )] Hypokalemia [see Warnings and Precautions ( 5.4 )] Hypernatremia and hyperchloremia [see Warnings and Precautions ( 5.5 )] Fluid overload [see Warnings and Precautions ( 5.6 )] Refeeding syndrome [see Warnings and Precautions ( 5.7 )] Manufactured for: Lake Zurich, Illinois 60047 Made in Germany 451655A www.fresenius-kabi.com/us Revised: April 2020 Logo

2.3 Instructions for Use Check flexible container solution composition, lot number, and expiry date. Do not remove solution container from its overwrap until immediately before use. Use sterile equipment and aseptic technique. Flexible Plastic Container ( free flex ® bag) To Open Turn solution container over so that the text is face down. Using the pre-cut corner tabs, peel open the overwrap and remove solution container. Check the solution container for leaks by squeezing firmly. If leaks are found, or if the seal is not intact, discard the solution. Check to ensure the solution is clear and there are no precipitates. Discard if there is a color change and/or the appearance of precipitates. Preparation for Administration Immediately before inserting the infusion set, break off BLUE Infusion Port Cap with the arrow pointing away from 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 BLUE Infusion Port. Insert spike through BLUE Infusion Port by rotating wrist slightly until the spike is inserted. NOTE: See full directions accompanying administration set. Suspend solution container from hanger hole. To Add Medication Additives may be incompatible. Complete information is not available. Do not use additives known or determined to be incompatible. Consult with pharmacist, if available. If, in the informed judgment of the healthcare provider, it is deemed advisable to introduce additives, use aseptic technique. When introducing additives, consult the instructions for use of the medication to be added and other relevant literature. Before adding a substance or medication, verify that it is soluble and/or stable in this drug product and that the pH range of this drug product is appropriate. To Add Medication Prior to Solution Administration Identify WHITE Additive Port with arrow pointing toward container. Immediately before injecting additives, break off WHITE Additive Port Cap with the arrow pointing toward container. Hold base of WHITE Additive Port horizontally. Prepare medication site Insert an 18 to 23 gauge needle horizontally through the center of WHITE Additive Port's septum and inject additives. Mix container contents thoroughly. For high density medication such as potassium chloride, squeeze ports while ports are upright and mix thoroughly. After addition, check to ensure the solution is clear and there are no precipitates. Discard if there is a color change and/or the appearance of precipitates. To Add Medication During Solution Administration Close the clamp on the set Identify WHITE Additive Port with arrow pointing toward container Immediately before injecting additives, if the Cap has not been broken off, break off WHITE Additive Port cap with the arrow pointing toward container. Hold base of WHITE Additive Port horizontally. Prepare medication site. Using a syringe with an 18 to 23 gauge needle, horizontally insert through the center of WHITE Additive Port's septum and inject additives. Remove container from IV pole and/or turn to an upright position. Mix container contents thoroughly. After addition, check to ensure the solution is clear and there are no precipitates. Discard if there is a color change and/or the appearance of precipitates. Using aseptic technique, repeat steps 4-7 as necessary. Return container to in use position and continue administration. Storage Use promptly; do not store solutions containing additives. Single-dose container. Discard any unused portion.

8.5 Geriatric Use Clinical studies of 2.5% Dextrose and 0.45% Sodium Chloride Injection did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Elderly patients are at increased risk of developing hyponatremia as well as for developing hyponatremic encephalopathy [see Warnings and Precautions ( 5.3 )] . 2.5% Dextrose and 0.45% Sodium Chloride Injection is known to be substantially excreted by the kidney, and the risk of adverse reactions to this product may be greater in patients with impaired renal function [see Warnings and Precautions ( 5.2 , 5.5 )] . Dose selection for an elderly patient should be cautious, starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

8.4 Pediatric Use The safety profile of 2.5% Dextrose and 0.45% Sodium Chloride Injection in pediatric patients is similar to adults. Neonates, especially premature infants with low birth weight, are at increased risk of developing hypo- or hyperglycemia and therefore need close monitoring during treatment with intravenous glucose solutions to ensure adequate glycemic control in order to avoid potential long-term adverse effects. Closely monitor plasma electrolyte concentrations in pediatric patients who may have impaired ability to regulate fluids and electrolytes. In very low birth weight infants, excessive or rapid administration of 2.5% Dextrose and 0.45% Sodium Chloride Injection may result in increased serum osmolality and risk of intracerebral hemorrhage. Children (including neonates and older children) are at increased risk of developing hyponatremia as well as for developing hyponatremic encephalopathy.

8.1 Pregnancy Risk Summary Appropriate administration of 2.5% Dextrose and 0.45% Sodium Chloride Injection during pregnancy is not expected to cause adverse developmental outcomes, including congenital malformations. Animal reproduction studies have not been conducted with 2.5% Dextrose and 0.45% Sodium Chloride Injection. The estimated background risk of major birth defects and miscarriage for the indicated population is 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.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary Appropriate administration of 2.5% Dextrose and 0.45% Sodium Chloride Injection during pregnancy is not expected to cause adverse developmental outcomes, including congenital malformations. Animal reproduction studies have not been conducted with 2.5% Dextrose and 0.45% Sodium Chloride Injection. The estimated background risk of major birth defects and miscarriage for the indicated population is 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. 8.2 Lactation Risk Summary Sodium is present in human breast milk. There are no data on the effects of 2.5% Dextrose and 0.45% Sodium Chloride Injection on a breastfed infant or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for 2.5% Dextrose and 0.45% Sodium Chloride Injection and any potential adverse effects on the breastfed infant from 2.5% Dextrose and 0.45% Sodium Chloride Injection or from the underlying maternal condition. 8.4 Pediatric Use The safety profile of 2.5% Dextrose and 0.45% Sodium Chloride Injection in pediatric patients is similar to adults. Neonates, especially premature infants with low birth weight, are at increased risk of developing hypo- or hyperglycemia and therefore need close monitoring during treatment with intravenous glucose solutions to ensure adequate glycemic control in order to avoid potential long-term adverse effects. Closely monitor plasma electrolyte concentrations in pediatric patients who may have impaired ability to regulate fluids and electrolytes. In very low birth weight infants, excessive or rapid administration of 2.5% Dextrose and 0.45% Sodium Chloride Injection may result in increased serum osmolality and risk of intracerebral hemorrhage. Children (including neonates and older children) are at increased risk of developing hyponatremia as well as for developing hyponatremic encephalopathy. 8.5 Geriatric Use Clinical studies of 2.5% Dextrose and 0.45% Sodium Chloride Injection did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Elderly patients are at increased risk of developing hyponatremia as well as for developing hyponatremic encephalopathy [see Warnings and Precautions ( 5.3 )] . 2.5% Dextrose and 0.45% Sodium Chloride Injection is known to be substantially excreted by the kidney, and the risk of adverse reactions to this product may be greater in patients with impaired renal function [see Warnings and Precautions ( 5.2 , 5.5 )] . Dose selection for an elderly patient should be cautious, starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. 8.6 Renal Impairment Administration of 2.5% Dextrose and 0.45% Sodium Chloride Injection in patients with renal impairment may result in hyperosmolar hyperglycemic state, hyponatremia, and/or fluid overload. Monitor patients with renal impairment for development of these adverse reactions [see Warnings and Precautions ( 5.2 , 5.3 , 5.5 , 5.6 )] .

16 HOW SUPPLIED/STORAGE AND HANDLING 2.5% Dextrose and 0.45% Sodium Chloride is a clear solution in 1000 mL single-dose, flexible containers available as follows: Product Name Size (mL) Number per Carton NDC Product Code 2.5% Dextrose and 0.45% Sodium Chloride Injection, USP 1,000 10 63323-874-10 874010 Storage: Avoid excessive heat. Store at 20° to 25°C (68° to 77°F) [ see USP Controlled Room Temperature]; brief exposure up to 40°C/104°F does not adversely affect the product. The container closure is not made with natural rubber latex. Non-PVC, Non-DEHP, Sterile.

Storage: Avoid excessive heat. Store at 20° to 25°C (68° to 77°F) [ see USP Controlled Room Temperature]; brief exposure up to 40°C/104°F does not adversely affect the product. The container closure is not made with natural rubber latex. Non-PVC, Non-DEHP, Sterile.