Dextrose

1 INDICATIONS AND USAGE Dextrose Injection 20%, 30%, 40%, 50% and 70%, mixed with amino acids or other compatible intravenous fluids, is indicated as a source of calories for patients requiring parenteral nutrition when oral or enteral nutrition is not possible, insufficient, or contraindicated. Dextrose Injection 20%, 30%, 40%, 50% and 70%, mixed with amino acids or other compatible intravenous fluids, is indicated as a source of calories for patients requiring parenteral nutrition when oral or enteral nutrition is not possible, insufficient or contraindicated ( 1 )

2 DOSAGE AND ADMINISTRATION • Must be diluted with compatible intravenous fluids or used as admixture, prior to administration. Not for direct intravenous infusion . ( 2.1 ) • Only for slow intravenous infusion only into a: ( 2.1 ) o Central vein , if final dextrose concentration is greater than 5% or osmolality is greater than 900 mOsm/L o Peripheral vein , if final dextrose concentration 5% or less and osmolality is less than 900 mOsm/L • Individualize dosage based on the patient's clinical condition, body weight, nutritional/fluid requirements, as well as additional energy given orally/enterally ( 2.2 ) • Discontinue infusion of concentrated dextrose solutions slowly and/or administer 5% dextrose ( 2.3 ) 2.1 Important Preparation and Administration Instructions Dextrose Injection is supplied in the following five strengths: 20%, 30%, 40%, 50% and 70% [see How Supplied/Storage and Handling ( 16 )] . Prior to administration, Dextrose Injection must be diluted with other compatible intravenous fluids or used as an admixture with amino acids. It is not for direct intravenous infusion . Preparation Prior to Administration • Because additives may be incompatible, evaluate all additions to the plastic container for compatibility and stability of the resulting preparation. Consult with a pharmacist, if available. If it is deemed advisable to introduce additives, use aseptic technique and mix thoroughly. • Inspect Dextrose Injection to ensure precipitates have not formed during the mixing or addition of additives. Discard the bag if precipitates are observed. Some opacity of the plastic container (due to moisture absorption during sterilization process) may be observed. This is normal and does not affect the solution quality or safety. The opacity will diminish gradually. • Use promptly after admixing or dilution. • For single use only; discard unused portion Important Administration Instructions • Set the vent to the closed position on a vented intravenous administration set to prevent air embolism. • Use a dedicated line without any connections to avoid air embolism. • 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. • The choice of a central or peripheral venous route of infusion should depend on the osmolarity of the final infusate. Solutions with greater than 5% dextrose or with osmolarity of greater than or equal to 900 mOsm/L must be infused through a central catheter [see Warnings and Precautions ( 5.5 )] . 2.2 Dosing Information Caution: Dextrose Injection is not for direct intravenous infusion. Prior to administration, Dextrose Injection must be diluted with other compatible intravenous fluids or used as an admixture with amino acids. Individualize the dosage of Dextrose Injection based on the patient's clinical condition (ability to adequately metabolize dextrose), body weight, nutritional and fluid requirements, as well as additional energy given orally or enterally to the patient. The administration rate should be governed, especially during the first few day of therapy, by the patient's tolerance to dextrose. Daily intake of amino acids and dextrose should be increased gradually to the maximum required dose as indicated by frequent determinations of blood glucose levels. 2.3 Discontinuation of Dextrose Injection To reduce the risk of hypoglycemia, a gradual decrease in flow rate in the last hour of infusion should be considered.

5 WARNINGS AND PRECAUTIONS • Hyperglycemia or Hyperosmolar Hyperglycemic State : Monitor blood glucose and administer insulin as needed ( 5.1 ) • Hypersensitivity Reactions : Monitor for signs and symptoms and discontinue infusion if reactions occur ( 5.2 ) • Risk of Infection : Monitor for signs and symptoms and laboratory parameters ( 5.3 ) • Refeeding Syndrome : Monitory laboratory parameters ( 5.4 ) • Vein Damage and Thrombosis : Administer solutions containing more than 5% dextrose as the final concentration or solutions with an osmolarity ≥ 900 mOsm/L through a central vein ( 2.1 , 5.5 ) • Aluminum Toxicity : Dextrose Injection contains aluminum that may be toxic. Patients with impaired renal function, and preterm infants, at higher risk. Limit aluminum to less than 4 mcg/kg/day ( 5.6 , 8.4 ) • Parenteral Nutrition Associated Liver Disease : increased risk in patients who receive parenteral nutrition for extended periods of time, especially preterm infants; monitor liver function tests, if abnormalities occur consider discontinuation or dosage reduction. ( 5.7 , 8.4 ) • Electrolyte Imbalance and Fluid Overload : monitor daily fluid balance, blood electrolyte levels, correct as needed. ( 5.8 , 8.4 ) 5.1 Hyperglycemia and Hyperosmolar Hyperglycemic State The use of dextrose infusions in patients with diabetes mellitus or impaired glucose tolerance may worsen hyperglycemia. Administration of dextrose at a rate exceeding the patient's utilization rate may lead to hyperglycemia, coma, and death. Patients with underlying confusion and renal impairment who receive dextrose infusions, may be at greater risk of developing hyperosmolar hyperglycemic state. Monitor blood glucose levels and treat hyperglycemia to maintain optimum levels while administering Dextrose Injection. Insulin may be administered or adjusted to maintain optimal blood glucose levels during Dextrose Injection administration. 5.2 Hypersensitivity Reactions Hypersensitivity reactions including anaphylaxis have been reported with dextrose infusions. Stop infusion immediately and treat patient accordingly if signs or symptoms of a hypersensitivity reaction develop. Signs or symptoms may include: tachypnea, dyspnea, hypoxia, bronchospasm, tachycardia, hypotension, cyanosis, vomiting, nausea, headache, sweating, dizziness, altered mentation, flushing, rash, urticaria, erythema, pyrexia, and chills. 5.3 Risk of Infections Patients who require parenteral nutrition are at high risk of infections because the nutritional components of these solutions can support microbial growth. The risk of infection is increased in patients with malnutrition-associated immunosuppression, hyperglycemia exacerbated by dextrose infusion, long-term use and poor maintenance of intravenous catheters, or immunosuppressive effects of other concomitant conditions, drugs, or other components of the parenteral formulation (e.g., lipid emulsion). To decrease the risk of infectious complications, ensure aseptic technique in catheter placement and maintenance, as well as aseptic technique in the preparation and administration of the nutritional formula. Monitor for signs and symptoms (including fever and chills) of early infections, including laboratory test results (including leukocytosis and hyperglycemia) and frequent checks of the parenteral access device and insertion site for edema, redness and discharge. 5.4 Refeeding Syndrome Refeeding severely undernourished patients may result in refeeding syndrome, characterized by the intracellular shift of potassium, phosphorus, and magnesium as the patient becomes anabolic. Thiamine deficiency and fluid retention may also develop. To prevent these complications, monitor severely undernourished patients and slowly increase nutrient intakes. 5.5 Vein Damage and Thrombosis Dextrose Injection is for admixture with amino acids or dilution with other compatible intravenous fluids. It is not for direct intravenous infusion. Administer solutions containing more…

4 CONTRAINDICATIONS The use of Dextrose Injection is contraindicated in patients: • who are severely dehydrated as hypertonic dextrose solution can worsen the patient's hyperosmolar state. • with known hypersensitivity to dextrose [see Warnings and Precautions (5.2) ] . • Severe dehydration ( 4 ) • Known hypersensitivity to dextrose ( 4 )

8.1 Pregnancy Risk Summary There are no data with Dextrose Injection in pregnant women. In addition, animal reproduction studies have not been conducted with dextrose. 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. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Consider parenteral nutrition in cases of severe maternal malnutrition where nutritional requirements cannot be fulfilled by the enteral route because of the risks to the fetus associated with severe malnutrition, including preterm delivery, low birth weight, intrauterine growth restriction, congenital malformations, and perinatal mortality.

6 ADVERSE REACTIONS The following adverse reactions from voluntary reports or clinical studies have been reported with Dextrose Injection. Because many of 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. • Hyperglycemia and hyperosmolar hyperglycemic state [see Warnings and Precautions ( 5.1 )] . • Hypersensitivity reactions [see Warnings and Precautions ( 5.2 )] . • Risk of infections [see Warnings and Precautions ( 5.3 )] . • Refeeding syndrome [see Warnings and Precautions ( 5.4 )] . • Vein damage and thrombosis [see Warnings and Precautions ( 5.5 )] . • Aluminum toxicity [see Warnings and Precautions ( 5.6 )] . • Risk of parenteral nutrition associated liver disease [see Warnings and Precautions ( 5.7 )] . • Electrolyte imbalance and fluid overload [see Warnings and Precautions ( 5.8 )] . The most common adverse reactions are hyperosmolar syndrome, infection both systemic and at the injection site, vein thrombosis or phlebitis, and hypervolemia. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact ICU Medical, Inc. at 1-800-441-4100, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .