Dextrose and Sodium Chloride

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

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 )

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 A …

3 DOSAGE FORMS AND STRENGTHS Dextrose and Sodium Chloride Injection are clear solutions in 250 mL, 500 mL and 1000 mL single-dose, flexible containers: 250 mL flexible container • 5% Dextrose and 0.2% Sodium Chloride Injection, USP 500 mL flexible container • 5% Dextrose and 0.45% Sodium Chloride Injection, USP • 5% Dextrose and 0.9% Sodium Chloride Injection, USP 1000 mL flexible container • 2.5% Dextrose and 0.45% Sodium Chloride Injection, USP • 5% Dextrose and 0.2% Sodium Chloride Injection, USP • 5% Dextrose and 0.45% Sodium Chloride Injection, USP • 5% Dextrose and 0.9% Sodium Chloride Injection, USP Dextrose and Sodium Chloride Injection is available in multiple strengths. See full prescribing information for detailed description of each product. ( 3 )

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 )

ADVERSE REACTIONS Reactions which may occur because of the solution or the technique of administration include febrile response, infection at the site of injection, venous thrombosis or phlebitis extending from the site of injection, extravasation and hypervolemia. Too rapid infusion of hypertonic solutions may cause local pain and venous irritation. Rate of administration should be adjusted according to tolerance. Use of the largest peripheral vein and a small bore needle is recommended. (See DOSAGE AND ADMINISTRATION .) Symptoms may result from an excess or deficit of one or more of the ions present in the solution; therefore, frequent monitoring of electrolyte levels is essential. Hypernatremia may be associated with edema and exacerbation of congestive heart failure due to the retention of water, resulting in an expanded extracellular fluid volume. If infused in large amounts, chloride ions may cause a loss of bicarbonate ions, resulting in an acidifying effect. The physician should also be alert to the possibility of adverse reactions to drug additives diluted and administered from the plastic container. Prescribing information for drug additives to be administered in this manner should be consulted. If an adverse reaction does occur, discontinue the infusion, evaluate the patient, institute appropriate therapeutic countermeasures, and save the remainder of the fluid for examination if deemed necessary.

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.

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 )] .

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.

DESCRIPTION (See chart below for quantitative information.) Dextrose and Sodium Chloride Injections USP are sterile, nonpyrogenic and contain no bacteriostatic or antimicrobial agents. These products are intended for intravenous administration. The formulas of the active ingredients are: Ingredients Molecular Formula Molecular Weight Sodium Chloride USP NaCl 58.44 Hydrous Dextrose USP 198.17 Composition – Each 100 mL contains: Concentration of Electrolytes (mEq/liter) Hydrous Dextrose USP Sodium Chloride USP Calories per liter Calculated Osmolarity mOsmol/liter pH Solution Sodium Chloride Water for Injection USP qs 3.3% Dextrose and 0.30% Sodium Chloride Injection USP 3.3 g 0.3 g 51 51 110 270 4.5 (3.5–6.5) 5% Dextrose and 0.9% Sodium Chloride Injection USP 5 g 0.9 g 154 154 170 560 4.4 (3.5–6.5) 5% Dextrose and 0.45% Sodium Chloride Injection USP 5 g 0.45 g 77 77 170 405 4.4 (3.5–6.5) 5% Dextrose and 0.33% Sodium Chloride Injection USP 5 g 0.33 g 56 56 170 365 4.4 (3.5–6.5) 5% Dextrose and 0.20% Sodium Chloride Injection USP 5 g 0.2 g 34 34 170 320 4.4 (3.5–6.5) 10% Dextrose and 0.45% Sodium Chloride Injection USP 10 g 0.45 g 77 77 340 660 4.3 (3.5–6.5) 10% Dextrose and 0.20% Sodium Chloride Injection USP 10 g 0.2 g 34 34 340 575 4.3 (3.5–6.5) Not made with natural rubber latex, PVC or DEHP. The plastic container is made from a multilayered film specifically developed for parenteral drugs. It contains no plasticizers and exhibits virtually no leachables. The solution contact layer is a rubberized copolymer of ethylene and propylene. The container is nontoxic and biologically inert. The container-solution unit is a closed system and is not dependent upon entry of external air during administration. The container is overwrapped to provide protection from the physical environment and to provide an additional moisture barrier when necessary. Addition of medication should be accomplished using complete aseptic technique. The closure system has two ports; the one for the administration set has a tamper evident plastic protector and the other is a medication addition site. Refer to the Directions for Use of the container. Chemical Structure

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.

HOW SUPPLIED Dextrose and Sodium Chloride Injection, USP are supplied in single-dose flexible plastic containers in various sizes and concentrations as shown in the accompanying Table. Content and Characteristics Grams/100 mL Per 1000 mL NDC No. Product Dextrose (hydrous) Sodium Chloride Sodium Na + Chloride Cl ̄ Caloric Value Tonicity Osmolarity mOsmol/L (calc) pH Container size (mL) 0409-7924-02 Manufactured by ICU Medical, Inc., Lake Forest, Illinois, 60045, USA 0990-7924-02 5% Dextrose and 0.225% Sodium Chloride Inj., USP 5 0.225 38.5 mEq 38.5 mEq 170 Hypertonic 329 4.3 (3.5 to 6.5) 250 0409-7924-03 Manufactured for ICU Medical, Inc., Lake Forest, Illinois, 60045, USA 0990-7924-03 , 5% Dextrose and 0.225% Sodium Chloride Inj., USP 5 0.225 38.5 mEq 38.5 mEq 170 Hypertonic 329 4.3 (3.5 to 6.5) 500 0409-7924-09 , 0990-7924-09 , 5% Dextrose and 0.225% Sodium Chloride Inj., USP 5 0.225 38.5 mEq 38.5 mEq 170 Hypertonic 329 4.3 (3.5 to 6.5) 1000 0409-7925-03 0990-7925-03 , 5% Dextrose and 0.3% Sodium Chloride Inj., USP 5 0.3 51 mEq 51 mEq 170 Hypertonic 355 4.3 (3.5 to 6.5) 500 0409-7925-09 , 0990-7925-09 , 5% Dextrose and 0.3% Sodium Chloride Inj., USP 5 0.3 51 mEq 51 mEq 170 Hypertonic 355 4.3 (3.5 to 6.5) 1000 0409-7926-02 0990-7926-02 5% Dextrose and 0.45% Sodium Chloride Inj., USP 5 0.45 77 mEq 77 mEq 170 Hypertonic 406 4.3 (3.5 to 6.5) 250 0409-7926-03 0990-7926-03 , 5% Dextrose and 0.45% Sodium Chloride Inj., USP 5 0.45 77 mEq 77 mEq 170 Hypertonic 406 4.3 (3.5 to 6.5) 500 0409-7926-09 , 0990-7926-09 , 5% Dextrose and 0.45% Sodium Chloride Inj., USP 5 0.45 77 mEq 77 mEq 170 Hypertonic 406 4.3 (3.5 to 6.5) 1000 0409-7941-03 0990-7941-03 , 5% Dextrose and 0.9% Sodium Chloride Inj., USP 5 0.9 154 mEq 154 mEq 170 Hypertonic 560 4.3 (3.5 to 6.5) 500 0409-7941-09 , 0990-7941-09 , 5% Dextrose and 0.9% Sodium Chloride Inj., USP 5 0.9 154 mEq 154 mEq 170 Hypertonic 560 4.3 (3.5 to 6.5) 1000 ICU Medical is transitioning NDC codes from "0409" to "0990" labeler code. Both NDC codes are expected to be in the market for a period of time. Protect from freezing. Store at 20 to 25°C (68 to 77°F). [See USP Controlled Room Temperature.] Revised: August, 2020 IFU0000261