Dextrose

1 INDICATIONS AND USAGE Dextrose Injection (5%) is indicated as a source of water and calories in adult and pediatric patients and may also be used as a diluent for reconstitution of a powder or liquid drug product. Dextrose Injection (5%) is indicated as a source of water and calories in adult and pediatric patients and may also be used as a diluent for reconstitution of a powder or liquid drug product. ( 1 )

2 DOSAGE AND ADMINISTRATION • Only for intravenous infusion. ( 2.1 ) • Infusion rate depends on the age, weight, clinical, and metabolic conditions of the patient and concomitant therapy. See full prescribing information for more information on preparation, administration, and dosing considerations. ( 2.1 , 2.2 , 2.3 ) 2.1 Important Administration Instructions Dextrose Injection (5%) is intended for intravenous use. • Use a peripheral vein to administer if the final dextrose concentration is 5% or less and the osmolarity is less than 900 mOsm/L. • To avoid venous irritation, consider using a central vein to administer hypertonic solutions with osmolarity of 900 mOsm/L or greater [see Warnings and Precautions (5.4) ] . • Do not administer Dextrose Injection (5%) simultaneously with blood products through the same administration set because of the possibility of pseudoagglutination or hemolysis. • Use of a final filter is recommended during administration of parenteral solutions, where possible. • Discard the unused portion. • Do not use the Dextrose Injection (5%) ADD-Vantage TM diluent containers with chemotherapy agents. 2.2 Important Preparation Information Visually inspect the Dextrose Injection (5%) for particulate matter and discoloration. Do not administer Dextrose Injection (5%) if the solution is cloudy, there are precipitates, and the container is damaged. To reduce the risk of air embolism, adhere to the following preparation instructions for Dextrose Injection (5%): • 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). • Do not pressurize the flexible container to increase flow rates. • If using a pumping device to administer Dextrose Injection (5%), turn off the pump before the container is empty. To Open : • Peel overwrap at corner and remove solution container. o Use unit within 30 days of opening overwrap, as long as the use date does not exceed the printed expiration date. • 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. To Assemble Vial and Flexible Diluent Container : 1. Remove the protective covers from the top of the vial and the vial port on the diluent container as follows: a. To remove the breakaway vial cap, swing the pull ring over the top of the vial and pull down far enough to start the opening (SEE FIGURE 1.), then pull straight up to remove the cap. (SEE FIGURE 2.) NOTE: Once the breakaway cap has been removed, do not access the vial with the syringe. b. To remove the vial port cover, grasp the tab on the pull ring, pull up to break the three tie strings, then pull back to remove the cover. (SEE FIGURE 3.) 2. Screw the vial into the vial port until it will go no further. THE VIAL MUST BE SCREWED IN TIGHTLY TO ASSURE A SEAL. This occurs approximately 1/2 turn (180°) after the first audible click. (SEE FIGURE 4.) The clicking sound does not assure a seal; the vial must be turned as far as it will go. NOTE: Once vial is seated, do not attempt to remove. (SEE FIGURE 4.) 3. Recheck the vial to assure that it is tight by trying to turn it further in the direction of assembly. 4. Label appropriately. To Reconstitute the Drug : 1. Squeeze the bottom of the diluent container gently to inflate the portion of the container surrounding the end of the drug vial. 2. With the other hand, push the drug vial down into the container telescoping the walls of the container. Grasp the inner cap of the vial through the walls of the container. (SEE FIGURE 5.) 3. Pull the inner cap from the drug vial. (SEE FIGURE 6.) Verify that the rubber stopper has been pulled out, allowing the drug and diluent to mix. 4. Mix container contents thoroughly and use within the specified time. 5. Look through the bottom of the vial to verify that the stopper has been removed…

5 WARNINGS AND PRECAUTIONS • Neonatal Hypoglycemia : Closely monitor blood glucose concentration to ensure adequate glycemic control. ( 5.1 ) • Hyperglycemia and Hyperosmolar Hyperglycemic State : Use with caution in patients with known subclinical or overt diabetes mellitus. ( 5.2 ) • Hypersensitivity Reactions : Monitor for signs and symptoms and discontinue infusion immediately if reaction occurs. ( 5.3 ) • Phlebitis and Thrombosis : Remove catheter as soon as possible if thrombophlebitis develops. ( 2.1 , 5.4 ) • Hyponatremia : Monitor serum sodium and chloride concentrations, fluid status, acid-base balance, and neurologic status. ( 5.5 ) • Electrolyte Imbalance and Fluid Overload : Monitor changes in fluid balance, electrolyte concentrations, and acid-base balance during administration. ( 5.6 ) • Refeeding Syndrome : Monitory laboratory parameters. ( 5.7 ) 5.1 Neonatal Hypoglycemia Neonates, especially preterm neonates with low birth weight, are at increased risk of developing hypoglycemia. Closely monitor blood glucose concentration during treatment with Dextrose Injection (5%) to ensure adequate glycemic control in order to avoid potential long-term adverse effects. 5.2 Hyperglycemia and Hyperosmolar Hyperglycemic State The use of Dextrose Injection (5%) in patients with 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. Hyperglycemia is associated with an increase in serum osmolality, resulting in osmotic diuresis, dehydration, and electrolyte losses [see Warnings and Precautions (5.6) , Use in Specific Populations (8.4) ] . Patients with underlying CNS disease 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 levels within normal limits while administering Dextrose Injection (5%). Insulin may be administered or adjusted to maintain optimal blood glucose levels during Dextrose Injection (5%) administration. 5.3 Hypersensitivity Reactions Hypersensitivity reactions, including anaphylaxis, have been reported with Dextrose Injection (5%) administration [see Adverse Reactions (6) ] . Stop administration of Dextrose Injection (5%) immediately if signs or symptoms of a hypersensitivity reaction develop. Initiate appropriate treatment as clinically indicated. 5.4 Phlebitis and Thrombosis The infusion of hypertonic solutions into a peripheral vein may result in vein irritation, vein damage, and/or thrombosis [see Dosage and Administration (2.1) ] . If thrombophlebitis develops, remove the catheter as soon as possible. 5.5 Hyponatremia Dextrose Injection (5%) may cause hyponatremia. Hyponatremia can lead to acute hyponatremic encephalopathy characterized by headache, nausea, seizures, lethargy, and vomiting. The risk of hospital-acquired hyponatremia is increased in younger pediatric patients, geriatric patients, patients treated with diuretics, and patients with cardiac or pulmonary failure or with the syndrome of inappropriate antidiuretic hormone (SIADH) (e.g., postoperative patients, patients concomitantly treated with arginine vasopressin analogs or certain antiepileptic, psychotropic, and cytotoxic drugs) [see Drug Interactions (7.1) , Use in Specific Populations (8.4) ] . Avoid Dextrose Injection (5%) in patients with or at risk for hyponatremia. If use cannot be avoided, closely monitor serum sodium concentrations, chloride concentrations, fluid status, acid-base balance, and neurologic status [see Warnings and Precautions (5.6) ] . 5.6 Electrolyte Imbalance and Fluid Overload Electrolyte deficits, particularly serum potassium and phosphate, may occur during prolonged use of Dextrose Injection (5%). Depending on the administered volume and the infusion rate, Dextrose Injection (5%) can cause fluid overload, including pulmonary edema. Avoid Dextrose Injection (5%…

4 CONTRAINDICATIONS Dextrose Injection (5%) is contraindicated in patients with: • Clinically significant hyperglycemia [see Warnings and Precautions (5.2) ] . • Known hypersensitivity to dextrose [see Warnings and Precautions (5.3) ] . • Clinically significant hyperglycemia. ( 4 ) • Known hypersensitivity to dextrose. ( 4 )

7 DRUG INTERACTIONS Effects on Glycemic Control and Electrolyte Balance: Monitor blood glucose concentrations, fluid balance, serum electrolyte concentrations, and acid-base balance. Avoid use of Dextrose Injection in patients receiving drugs associated with hyponatremia. ( 7.1 ) 7.1 Drugs with Effects on Glycemic Control and Electrolyte Balance Dextrose Injection (5%) can affect glycemic control, vasopressin, and fluid and/or electrolyte balance [see Warnings and Precautions ( 5.1 , 5.2 , 5.5 , 5.6 )] . Monitor patients’ blood glucose concentrations, fluid balance, serum electrolyte concentrations, and acid-base balance. Concomitant administration of Dextrose Injection (5%) with drugs associated with hyponatremia may increase the risk of developing hyponatremia. Drugs associated with hyponatremia include diuretics and those that cause SIADH (e.g., selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), arginine vasopressin analogs, certain antiepileptic, psychotropic, and cytotoxic drugs). Avoid use of Dextrose Injection (5%) in patients receiving drugs associated with hyponatremia. If use cannot be avoided, closely monitor serum sodium concentrations during concomitant use [see Warnings and Precautions (5.5) ].

8.1 Pregnancy Risk Summary Dextrose Injection (5%) has been used for decades during labor and delivery. Although there are a few case reports that describe adverse effects of dextrose use in other stages of pregnancy, exposure during pregnancy in general is not expected to cause major birth defects, miscarriage, or adverse maternal or fetal outcomes. Animal reproduction studies have not been conducted with dextrose. The background risk of major birth defects and miscarriage for the indicated populations are 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.

6 ADVERSE REACTIONS The following clinically significant adverse reactions are also described elsewhere in the labeling: • Neonatal Hypoglycemia [see Warnings and Precautions (5.1) ] • Hyperglycemia and Hyperosmolar Hyperglycemic State [see Warnings and Precautions (5.2) ] • Hypersensitivity Reactions [see Warnings and Precautions (5.3) ] • Phlebitis and Thrombosis [see Warnings and Precautions (5.4) ] • Hyponatremia [see Warnings and Precautions (5.5) ] • Electrolyte Imbalance, Fluid Overload and Hypervolemia [see Warnings and Precautions (5.6) ] • Refeeding Syndrome [see Warnings and Precautions (5.7) ] The following adverse reactions associated with the use of Dextrose Injection (5%) were identified in clinical trials or postmarketing reports. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Administration site conditions: blister, erythema, extravasation, pain, phlebitis, vein damage, thrombosis Immune system disorders: anaphylaxis, angioedema, bronchospasm, chills, hypotension, pruritus, pyrexia, rash Cardiovascular disorders: cyanosis, volume overload The most common adverse reactions are hyperglycemia, hypersensitivity reactions, hyponatremia, infection (both systemic and at the injection site), vein thrombosis, phlebitis, and electrolyte imbalance. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Pfizer, Inc. at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.