Dextrose

1 INDICATIONS AND USAGE Dextrose (50%) Injection is indicated for the treatment of insulin-induced hypoglycemia (e.g., hyperinsulinemia, insulin shock) in adults and pediatric patients 2 years of age and older. Dextrose Injection (50%) is indicated for the treatment of insulin-induced hypoglycemia (e.g., hyperinsulinemia, insulin shock) in adults and pediatric patients 2 years of age and older. ( 1 )

2 DOSAGE AND ADMINISTRATION • Only for intravenous infusion. Do not administer subcutaneously or intramuscularly. ( 2.1 ) • Adults and Pediatric Patients 12 Years of Age and Older o Administer into a central vein or large peripheral vein. o Recommended dosage is 10 to 25 grams (20 to 50 mL) administered once. Repeated doses may be administered as clinically appropriate. ( 2.2 ) • Pediatric Patients 2 to 11 Years of Age o Administer into a central vein. o Appropriate dosage depends on the age, weight, clinical and metabolic conditions of the patient, and concomitant therapy. ( 2.2 ) • Maximum rate of dextrose administration without producing hyperglycemia is 0.5 g/kg of body weight/hour. ( 2.2 ) • See full prescribing information for more information on preparation and administration instructions. ( 2.1 , 2.2 ) 2.1 Important Preparation and Administration Instructions • Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. Do not use Dextrose Injection (50%) if the solution is cloudy or the seal has been broken. • Obtain a blood glucose level prior to administering Dextrose Injection (50%). However, in an emergency, administer Dextrose Injection (50%) promptly without awaiting blood glucose test results. • Do not administer Dextrose Injection (50%) simultaneously with blood through the same infusion set because pseudoagglutination of red blood cells may occur. • Administer Dextrose Injection (50%) intravenously. Do not administer Dextrose Injection (50%) subcutaneously or intramuscularly. • Discard the unused portion. 2.2 Recommended Dosage and Administration Adults and Pediatric Patients 12 Years of Age and Older When possible, administer Dextrose Injection (50%) into a central vein or large peripheral vein because Dextrose Injection (50%) has an osmolarity greater than 900 mOsm/L and can cause venous irritation. The recommended dosage of Dextrose Injection (50%) is 10 to 25 grams (20 to 50 mL) of Dextrose Injection (50%), administered once via intravenous infusion. Repeated doses may be administered as clinically appropriate. Slowly infuse Dextrose Injection (50%) to reduce the risk of developing hyperglycemia and to minimize venous irritation [see Warnings and Precautions (5.1 , 5.3) ] . The maximum rate at which Dextrose Injection (50%) can be infused without producing hyperglycemia is 0.5 g/kg of body weight/hour. Pediatric Patients 2 to 11 Years of Age Administer Dextrose Injection (50%) into a central vein. Avoid administration of Dextrose Injection (50%) into a peripheral vein because Dextrose Injection (50%) has an osmolarity greater than 900 mOsm/L and can cause venous irritation [ Warnings and Precautions (5.3) ] . If central venous access cannot be obtained, consider using an alternative commercially available dextrose product with a lower concentration. The appropriate dosage of Dextrose Injection (50%) depends on the age, weight, clinical and metabolic conditions of the patient, and concomitant therapy. Slowly infuse Dextrose Injection (50%) to reduce the risk of developing hyperglycemia and to minimize venous irritation [see Warnings and Precautions (5.1 , 5.3 )] . The maximum rate at which Dextrose Injection (50%) can be infused without producing hyperglycemia is 0.5 g/kg of body weight/hour.

5 WARNINGS AND PRECAUTIONS • Hyperglycemia or Hyperosmolar Syndrome : Monitor blood and urine glucose; administer insulin as needed. ( 5.1 ) • Hypersensitivity Reactions : Monitor for signs and symptoms and discontinue infusion immediately if reaction occurs. ( 5.2 ) • Phlebitis and Thrombosis : Remove catheter as soon as possible if thrombophlebitis develops. ( 2.1 , 5.3 ) • Electrolyte Imbalance and Fluid Overload : Monitor changes in fluid balance, electrolyte concentrations, and acid-base balance during administration. ( 5.4 ) • Hyponatremia : Monitor serum sodium and chloride concentrations, fluid status, acid-base balance, and neurologic status. ( 5.5 ) • Potential Aluminum Toxicity for Patients with Immature or Impaired Renal Function : Prolonged administration of Dextrose Injection (50%) may lead to toxic levels of aluminum in pediatric patients with immature renal function or renal impairment, and in adults with renal impairment. ( 5.6 ) 5.1 Hyperglycemia and Hyperosmolar Hyperglycemic State Significant hyperglycemia and hyperosmolar hyperglycemic state may result from too rapid administration of Dextrose Injection (50%). Symptoms of hyperosmolar hyperglycemic state include mental confusion and loss of consciousness . To minimize these risks, slowly infuse Dextrose Injection (50%) and monitor blood and urine glucose during treatment with Dextrose Injection (50%). If Dextrose Injection (50%) is abruptly discontinued, patients should receive 5% or 10% dextrose injection to avoid rebound hypoglycemia. 5.2 Hypersensitivity Reactions Hypersensitivity reactions, including anaphylaxis, have been reported with Dextrose Injection (50%) administration [see Adverse Reactions (6) ] . Stop administration of Dextrose Injection (50%) immediately if signs or symptoms of a hypersensitivity reaction develop. Initiate appropriate treatment as clinically indicated. 5.3 Phlebitis and Thrombosis Dextrose Injection (50%) is hypertonic (has an osmolarity greater than 900 mOsm/L) and may cause phlebitis and thrombosis at the site of injection. If thrombophlebitis occurs, remove the catheter as soon as possible. Administer Dextrose Injection (50%) via slow intravenous infusion into a central vein (when possible) to reduce the risk of phlebitis and thrombosis. Ensure that the needle is well within the lumen of the vein and that extravasation does not occur. If thrombosis occurs, stop administration of Dextrose Injection (50%) and initiate corrective measures. Avoid administration of Dextrose Injection (50%) into a peripheral vein in pediatric patients 2 to 11 years old. If central venous access cannot be obtained in these pediatric patients, consider using an alternative commercially available dextrose product with a lower concentration. Do not administer Dextrose Injection (50%) subcutaneously or intramuscularly. 5.4 Electrolyte Imbalance and Fluid Overload Electrolyte deficits, particularly serum potassium and phosphate, may occur during prolonged use of Dextrose Injection (50%). Depending on the administered volume and the infusion rate, administration of Dextrose Injection (50%) can cause fluid overload including pulmonary edema. Avoid Dextrose Injection (50%) in patients at risk for fluid and/or solute overload. If use cannot be avoided in these patients, monitor fluid balance, electrolyte concentrations, and acid base balance, especially during prolonged use. Additional monitoring is recommended for patients with water and electrolyte disturbances that could be aggravated by increased glucose, insulin administration, and/or free water load. 5.5 Hyponatremia Dextrose Injection (50%) 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 pediatric patients, geriatric patients, patients treated with diuretics, and patients with cardiac or pulmonary failure or with the syndrome of inappropr…

4 CONTRAINDICATIONS Dextrose Injection (50%) is contraindicated in patients with: • Intracranial or intraspinal hemorrhage because Dextrose Injection (50%) can worsen cerebral edema by causing a fluid shift across the blood-brain barrier. • Severe dehydration because of the potential to worsen the patient’s hyperosmolar state. • Alcohol withdrawal because of the potential to precipitate Wernicke encephalopathy (WE) or cardiomyopathy in thiamine-deficient patients. • Known hypersensitivity to dextrose [see Warnings and Precautions (5.2) ] . • Intracranial or intraspinal hemorrhage. ( 4 ) • Severe dehydration. ( 4 ) • Alcohol withdrawal. ( 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 (50%) can affect glycemic control, vasopressin, and fluid and/or electrolyte balance [see Warnings and Precautions (5.1 , 5.4 , 5.5) ] . Monitor patients’ blood glucose concentrations, fluid balance, serum electrolyte concentrations, and acid-base balance. Concomitant administration of Dextrose Injection (50%) 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 (50%) 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 Appropriate administration of Dextrose Injection (50%) during pregnancy is not expected to cause adverse developmental outcomes, including congenital malformations. However, maternal hyperglycemia secondary to infusion of glucose-containing products at the time of delivery has been associated with adverse neonatal outcomes such as neonatal hypoglycemia. Animal reproduction studies have not been conducted with dextrose. The background risk of major birth defects and miscarriage in patients with insulin-induced hypoglycemia (e.g., hyperinsulinemia, insulin shock) 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.

6 ADVERSE REACTIONS The following clinically significant adverse reactions are also described elsewhere in the labeling: • Hyperglycemia and Hyperosmolar Syndrome [see Warnings and Precautions (5.1) ] • Hypersensitivity Reactions [see Warnings and Precautions (5.2) ] • Phlebitis and Thrombosis [see Warnings and Precautions (5.3) ] • Electrolyte Imbalance and Fluid Overload [see Warnings and Precautions (5.4) ] • Hyponatremia [see Warnings and Precautions (5.5) ] The following adverse reactions associated with the use of Dextrose Injection 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 always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Administration site conditions: blister, extravasation, phlebitis, erythema, pain, vein damage, thrombosis Immune system disorders: anaphylaxis, angioedema, bronchospasm, chills, hypotension, pruritis, 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.