Dextrose

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

1 INDICATIONS AND USAGE Dextrose Injection is indicated as source of water and calories and may also be used as diluent for reconstitution of a powdered or liquid (up to 10 mL) drug product packaged in a vial with a 13 mm or 20 mm closure. Dextrose Injection is indicated as a source of calories and water and may also be used as diluent for reconstitution of a powdered or liquid (up to 10 mL) drug product packaged in a vial with a 13 mm or 20 mm closure. ( 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 • Dextrose Injection is intended for intravenous use. • Peripheral administration of 5% dextrose is generally acceptable, however, consider central vein when administering more than 5% dextrose or with an osmolarity of at least 900 mOsm/L or when there is peripheral vein irritation, phlebitis, and/or associated pain [see Warnings and Precautions (5.3) ] . • Do not administer Dextrose 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, 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 diluted dextrose 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 dextrose concentration, 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 (5.1) , Use in Specific Populations (8.4) ] . 2.3 Instructions for Use To Open • Do not remove from overpouch until ready to use. • Tear overwrap sharply down from the slit and remove solution container. Small amounts of moisture may be found on the solution container from water permeating from inside the container. The amount of permeated water is insufficient to affect the solution significantly. If larger amounts of water are found, the container should be checked for tears or leaks. • Visually inspect the container. 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. Evaluate the following: • If the outlet port protector is damaged, detached, or not present, discard container. • 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, insoluble complexes or crystals. • Check for minute leaks by separately squeezing the inner bag firmly. If leaks are found, discard container. • Check that the vial adaptor cover is intact. If the vial adaptor cover is not intact, discard product. Preparation for Administration • Instructions for Assembly and Reconstitution: (Steps 1-3 for Assembly and steps 4-6 for Reconstitution) Step 1: Remove vial cover and disinfect stopper. Step 2: Peel off foil cover. Inspect adaptor for moisture. Discard if moisture is found. Step 3: Place vial upright and hold firmly. Push adaptor down until vial snaps in place. DO NOT TWIST. Pull vial to ensure fully seated. Step 4: Squeeze the bag and check vial. Use only if vial is fully seated and dry. Bend adaptor tube up and down to fully break and create a visible gap in the seal. Step 5: For liquid drug vials proceed directly to Step 6. For powdered drug vials: Hold bag with vial down. Squeeze solution into vial until …

3 DOSAGE FORMS AND STRENGTHS Dextrose Injection, USP is a clear, sterile, non-pyrogenic solution of 5 grams of dextrose hydrous per 100 mL (0.05 grams/mL) in 50 mL and 100 mL single-dose, partial-fill flexible containers. Injection: 5% (0.05 grams/mL), 5 grams of dextrose hydrous per 100 mL in 50 mL and 100 mL single-dose, partial-fill flexible containers: ( 3 )

4 CONTRAINDICATIONS The use of Dextrose Injection is contraindicated in patients with: • Clinically significant hyperglycemia [see Warnings and Precautions (5.1) ]. • Known hypersensitivity to dextrose [see Warnings and Precautions (5.2) ]. • Clinically significant hyperglycemia. ( 4 ) • Known hypersensitivity to dextrose. ( 4 )

6 ADVERSE REACTIONS The following adverse reactions associated with the use of dextrose injection were identified in clinical trials or post-marketing reports. Because these reactions were reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency, reliably, or to establish a causal relationship to drug exposure. The following clinically significant adverse reactions are described elsewhere in the labeling: • Hyperglycemia and hyperosmolar hyperglycemic state [see Warnings and Precautions (5.1) ] • Hypersensitivity reactions: anaphylaxis, pruritis, bronchospasm, cyanosis, angioedema, hypotension, pyrexia, chills, and rash [see Warnings and Precautions (5.2) ] • Infusion Site Reactions: infusion site phlebitis, infusion site erythema, vein damage and thrombosis [see Warnings and Precautions (5.3) ] • Hyponatremia and hyponatremic encephalopathy [see Warnings and Precautions (5.4) ] • Refeeding syndrome [see Warnings and Precautions (5.6) ] • Electrolyte imbalance, fluid overload and hypervolemia [see Warnings and Precautions (5.5) ] The most common adverse reactions are, hyperglycemia, hypersensitivity reactions, hyponatremia, infection both systemic and at the injection site, vein thrombosis or phlebitis, and electrolyte imbalance. ( 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.

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 ) 7.1 Other Products that Affect Glycemic Control or Fluid and/or Electrolyte Balance Dextrose Injection can affect glycemic control, vasopressin and fluid and/or electrolyte balance [see Warnings and Precautions ( 5.1 , 5.4 , 5.5 )] . Monitor blood glucose concentrations, fluid balance, serum electrolyte concentrations and acid-base balance when using Dextrose Injection in patients treated with other substances that affect glycemic control, vasopressin or fluid and/or electrolyte balance.

8 USE IN SPECIFIC POPULATIONS Pediatric Use : Increased risk of hypoglycemia/hyperglycemia; monitor serum glucose concentrations. ( 8.4 ) 8.1 Pregnancy Risk Summary Appropriate administration of Dextrose Injection during pregnancy is not expected to cause adverse developmental outcomes, including congenital malformations. Animal reproduction studies have not been conducted with injectable dextrose solutions. 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 There are no data on the presence of dextrose in human milk, the effects on a breastfed infant, or the effects on milk production. The lack of clinical data during lactation precludes a clear determination of the risk of Dextrose Injection to an infant during lactation; therefore, the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Dextrose Injection and any potential adverse effects on the breastfed infant from Dextrose Injection or from the underlying maternal condition. 8.4 Pediatric Use The safety profile of Dextrose 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 infusions 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 Dextrose 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 [see Warnings and Precautions (5.4) ] . 8.5 Geriatric Use Clinical studies of Dextrose 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 (5.4) ] . Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually 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. Dextrose is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

12.1 Mechanism of Action Dextrose oxidized to carbon dioxide and water, yielding energy.

11 DESCRIPTION Dextrose Injection, 5% USP is a clear, sterile, non-pyrogenic solution of Dextrose, USP in Water for Injection in a polyvinylchloride flexible plastic container for intravenous administration after admixture with a single dose powdered or liquid (up to 10 mL) drug vial [see Dosage and Administration (2.1) ] . Flexible containers, designed to facilitate admixture, are available in 50 mL and 100 mL sizes. See Table 1 for the content and characteristics of this solution. The solution contains no bacteriostatic, antimicrobial agent or added buffer and is intended only for use as a single-dose injection. The pH range is 4.0 (3.2 to 6.5). Water can permeate from inside the container into the overwrap but not in amounts sufficient to affect the solution significantly. Table 1. Contents and Characteristics of Dextrose Injection 5%, USP Strength Fill Volume Amount of Dextrose Hydrous per Container kcal Caloric value calculated on the basis of 3.4 kcal/g of dextrose, hydrous per Container mOsmol per liter Dextrose Injection 5%, USP (0.05 grams/mL) 100 mL Single Pack 5 grams 17 252 50 mL Single Pack 2.5 grams 8.5 252 Dextrose, USP is chemically designated D-glucose, monohydrate (C 6 H 12 O 6 • H 2 O), a hexose sugar freely soluble in water. The molecular weight of dextrose (D-glucose) monohydrate is 198.17. It has the following structural formula: Water for Injection, USP is chemically designated H 2 O. Dextrose is derived from corn. The MINI-BAG Plus Container is a standard diluent container with an integral drug vial adaptor. It allows for drug admixture after connection to a single dose powdered or liquid (up to 10 mL) drug vial having a 20 mm closure. A breakaway seal in the tube between the vial adaptor and the container is broken to allow transfer of the diluent into the vial and reconstitution of the drug. The Mini-Bag Plus product mechanically prohibits the transfer of contaminants into and out of the system during and after docking, minimizing environmental and personal exposure. The reconstituted drug is then transferred from the vial into the container diluent and mixed to result in an admixture for delivery to the patient. The VIAFLEX Plus plastic container is fabricated from a specially formulated polyvinyl chloride (PL 146 Plastic). VIAFLEX Plus on the container indicates the presence of a drug additive in a drug vehicle. The VIAFLEX Plus plastic container system utilizes the same container as the VIAFLEX plastic container system. The amount of water that can permeate from inside the container into the overwrap is insufficient to affect the solution significantly. Solutions in contact with the plastic container can leach out certain of its chemical components in very small amounts within the expiration period, e.g., di-2-ethylhexyl phthalate (DEHP), up to 5 parts per million. However, the safety of the plastic has been confirmed in tests in animals according to USP biological tests for plastic containers as well as by tissue culture toxicity studies. Dextrose Hydrous Structural Formula

10 OVERDOSAGE An increased infusion rate of Dextrose Injection or administration of dextrose solutions can cause hyperglycemia, hyperosmolality, and adverse effects on water and electrolyte balance [see Warnings and Precautions (5.1 , 5.5) ] . Severe hyperglycemia and severe dilutional hyponatremia, and their complications, can be fatal. Discontinue infusion, reduce dose and institute appropriate corrective measures such as administration of exogenous insulin. Discontinue infusion and institute appropriate corrective measures in the event of overhydration or solute overload during therapy, with particular attention to CNS, respiratory and cardiovascular systems. If over-exposure occurs, call your Poison Control Center at 1-800-222-1222 for current information on the management of poisoning or overdosage.

16 HOW SUPPLIED/STORAGE AND HANDLING Dextrose Injection 5%, USP is a clear, sterile solution of dextrose supplied in single-dose, flexible containers. The product is available as single packs (1 unit per overpouch). Table 2 lists single pack presentation compatible with vials with a 13 mm closure, and Table 3 lists single pack presentation compatible with vials with a 20 mm closure. Table 2. Presentations of Dextrose Injection Compatible with Vials with a 13 mm Closure Product Description Size Vial Adaptor Size Configuration Code NDC Dextrose Injection 5%, USP (0.05 grams/mL) 50 mL 13 mm single pack EZPB0036LF 0338-0170-01 100 mL 13 mm single pack EZPB0037LF 0338-0172-01 Table 3. Presentations of Dextrose Injection Compatible with Vials with a 20 mm Closure Product Description Size Vial Adaptor Size Configuration Code NDC Dextrose Injection 5%, USP (0.05 grams/mL) 50 mL 20 mm single pack EZPB0040LF 0338-0174-01 100 mL 20 mm single pack EZPB0041LF 0338-0176-01 Do not remove container from the overwrap until intended for use. Minimize exposure of Dextrose Injection to heat. Avoid excessive heat. Store at room temperature (25°C/77°F).