Dextrose and Electrolyte No. 48

INDICATIONS AND USAGE 5% Dextrose and Electrolyte No. 48 Injection (Multiple Electrolytes and Dextrose Injection, Type 1, USP) is indicated as a source of water, electrolytes, and calories or as an alkalinizing agent.

DOSAGE AND ADMINISTRATION Important Administration Instructions • 5% Dextrose and Electrolyte No. 48 Injection (Multiple Electrolytes and Dextrose Injection, Type 1, USP) is intended for intravenous administration using sterile equipment. • Do not connect flexible plastic containers in series in order to avoid air embolism due to possible residual air contained in the primary container. • 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. • Do not pressurize intravenous solutions contained in flexible plastic containers to increase flow rates in order to avoid air embolism due to incomplete evacuation of residual air in the container. • Prior to infusion, visually inspect the solution for particulate matter and discoloration. The solution should be clear and there should be no precipitates. Do not administer unless solution is clear, and container is undamaged. • Do not administer 5% Dextrose and Electrolyte No. 48 Injection (Multiple Electrolytes and Dextrose Injection, Type 1, USP) simultaneously with blood through the same administration set because of the possibility of pseudoagglutination or hemolysis. Dosing Information The choice of product, dosage, volume, rate, and duration of administration is dependent upon the age, weight and clinical condition of the patient and concomitant therapy, and administration should be determined by a physician experienced in intravenous fluid therapy. Introduction of Additives 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, in the informed judgment of the physician, it is deemed advisable to introduce additives, use aseptic technique. Mix thoroughly when additives have been introduced. After addition, if there is a discoloration and/or the appearance of precipitates, insoluble complexes or crystals, do not use. Do not store solutions containing additives. Discard any unused portion.

CONTRAINDICATIONS 5% Dextrose and Electrolyte No. 48 Injection (Multiple Electrolytes and Dextrose Injection, Type 1, USP) is contraindicated in patients • with a known hypersensitivity to the product (see WARNINGS ) • with clinically significant hyperglycemia (see WARNINGS )

WARNINGS Hypersensitivity Reactions Hypersensitivity and infusion reactions have been reported with 5% Dextrose and Electrolyte No. 48 Injection (Multiple Electrolytes and Dextrose Injection, Type 1, USP). See ADVERSE REACTIONS . Stop the infusion immediately if signs or symptoms of a hypersensitivity reaction develop, such as tachycardia, chest pain, dyspnea and flushing. Institute appropriate therapeutic countermeasures as clinically indicated. Electrolyte Imbalances Fluid Overload Depending on the volume and rate of infusion, the intravenous administration of 5% Dextrose and Electrolyte No. 48 Injection (Multiple Electrolytes and Dextrose Injection, Type 1, USP) can cause electrolyte disturbances such as overhydration and congested states, including pulmonary congestion and edema. Avoid 5% Dextrose and Electrolyte No. 48 Injection (Multiple Electrolytes and Dextrose Injection, Type 1, USP) in patients with or at risk for fluid and/or solute overloading. If use cannot be avoided, monitor fluid balance, electrolyte concentrations, and acid base balance, as needed and especially during prolonged use. Hyponatremia 5% Dextrose and Electrolyte No. 48 Injection (Multiple Electrolytes and Dextrose Injection, Type 1, USP) may cause hyponatremia. 5% Dextrose and Electrolyte No. 48 Injection (Multiple Electrolytes and Dextrose Injection, Type 1, USP) is a hypertonic solution. In the body, however, glucose containing fluids can become extremely physiologically hypotonic due to rapid glucose metabolization. Monitoring of serum sodium is particularly important for hypotonic fluids. Hyponatremia can lead to acute hyponatremic encephalopathy characterized by headache, nausea, seizures, lethargy, and vomiting. Patients with brain edema are at particular risk of severe, irreversible and life-threatening brain injury. The risk of hospital-acquired hyponatremia is increased in patients with cardiac or pulmonary failure, and in patients with non-osmotic vasopressin release (including SIADH) treated with high volume of physiologically hypotonic 5% Dextrose and Electrolyte No. 48 Injection (Multiple Electrolytes and Dextrose Injection, Type 1, USP). Avoid 5% Dextrose and Electrolyte No. 48 Injection (Multiple Electrolytes and Dextrose Injection, Type 1, USP) in hypervolemic or overhydrated patients. If use cannot be avoided, monitor serum sodium concentrations. Hyperglycemia and Hyperosmolar Hyperglycemic State Administration of solutions containing dextrose and lactate in patients with impaired glucose tolerance or diabetes mellitus may worsen hyperglycemia (see PRECAUTIONS , Pediatric Use ). 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. Patients with underlying central nervous system disease and renal impairment who receive dextrose infusions, may be at greater risk of developing hyperosmolar hyperglycemic state. Monitor blood glucose concentrations and treat hyperglycemia to maintain concentrations within normal limits while administering 5% Dextrose and Electrolyte No. 48 Injection (Multiple Electrolytes and Dextrose Injection, Type 1, USP). Insulin may be administered or adjusted to maintain optimal blood glucose concentrations. Hypernatremia Hypernatremia may occur with 5% Dextrose and Electrolyte No. 48 Injection (Multiple Electrolytes and Dextrose Injection, Type 1, USP). Conditions that may increase the risk of hypernatremia, fluid overload and edema (central and peripheral), include patients with: primary hyperaldosteronism; secondary hyperaldosteronism associated with, for example, hypertension, congestive heart failure, liver disease (including cirrhosis), renal disease (including renal artery stenosis, nephrosclerosis); and pre-eclampsia. Certain medications, such as corticosteroids or corticotropin, may also increase risk of sodium and fluid retention, see PRECAUTIONS . Avoid 5% Dextrose and Electrolyte No. 48 Injection (Multiple Electrolytes and Dextrose Injection, Type 1, USP) in patients with, or at risk for, hypernatremia. If use cannot be avoided, monitor serum sodium concentrations. Hypermagnesemia Avoid solutions containing magnesium, including 5% Dextrose and Electrolyte No. 48 Injection (Multiple Electrolytes and Dextrose Injection, Type 1, USP) in patients with or predisposed to hypermagnesemia, including patients with severe renal impairment and those patients receiving magnesium therapy (e.g., treatment of eclampsia and myasthenia gravis). 5% Dextrose and Electrolyte No. 48 Injection (Multiple Electrolytes and Dextrose Injection, Type 1, USP) is not indicated for the treatment of hypomagnesemia. Acidosis 5% Dextrose and Electrolyte No. 48 Injection (Multiple Electrolytes and Dextrose Injection, Type 1, USP) is not for use for the treatment of lactic acidosis or severe metabolic acidosis in patients with severe liver and/or renal impairment. Alkalosis Excess administration of 5% Dextrose and Electrolyte No. 48 Injection (Multiple Electrolytes and Dextrose Injection, Type 1, USP) can result in metabolic alkalosis. Avoid 5% Dextrose and Electrolyte No. 48 Injection (Multiple Electrolytes Injection, Type 1, USP) in patients with alkalosis or at risk for alkalosis. 5% Dextrose and Electrolyte No. 48 Injection (Multiple Electrolytes and Dextrose Injection, Type 1, USP) is not indicated for the treatment of hypochloremic hypokalemic alkalosis. Avoid use in patients with hypochloremic hypokalemic alkalosis. Hypocalcemia 5% Dextrose and Electrolyte No. 48 Injection (Multiple Electrolytes and Dextrose Injection, Type 1, USP) contains no calcium, and an increase in plasma pH due to its alkalinizing effect may lower the concentration of ionized (not-protein bound) calcium. Avoid 5% Dextrose and Electrolyte No. 48 Injection (Multiple Electrolytes and Dextrose Injection, Type 1, USP) in patients with hypocalcemia. Hyperkalemia Potassium-containing solutions, including 5% Dextrose and Electrolyte No. 48 Injection (Multiple Electrolytes and Dextrose Injection, Type 1, USP) may increase the risk of hyperkalemia. Patient’s at increased risk of developing hyperkalemia include those: • With conditions predisposing to hyperkalemia and/or associated with increased sensitivity to potassium, such as patients with severe renal impairment, acute dehydration, extensive tissue injury or burns, certain cardiac disorders such as congestive heart failure. • Treated concurrently or recently with agents or products that cause or increase the risk of hyperkalemia (see PRECAUTIONS ). Avoid 5% Dextrose and Electrolyte No. 48 Injection (Multiple Electrolytes and Dextrose Injection, Type 1, USP) in patients with, or at risk for hyperkalemia. If use cannot be avoided, monitor serum potassium concentrations. Hyperphosphatemia 5% Dextrose and Electrolyte No. 48 Injection (Multiple Electrolytes and Dextrose Injection, Type 1, USP) may increase the risk of hyperphosphatemia. Avoid use in patients with hyperphosphatemia or conditions predisposing to hyperphosphatemia, such as patients with severe renal or adrenal impairment.

Drug Interactions Other Products that Affect Fluid and/or Electrolyte Balance Administration of 5% Dextrose and Electrolyte No. 48 Injection (Multiple Electrolytes and Dextrose Injection, Type 1, USP) to patients treated concomitantly with drugs associated with sodium and fluid retention may increase the risk of hypernatremia and volume overload. Avoid use of 5% Dextrose and Electrolyte No. 48 Injection (Multiple Electrolytes and Dextrose Injection, Type 1, USP) in patients receiving such products, such as corticosteroids or corticotropin. If use cannot be avoided, monitor serum electrolytes, fluid balance and acid-base balance. Other Drugs that Increase the Risk of Hyponatremia Administration of 5% Dextrose and Electrolyte No. 48 Injection (Multiple Electrolytes and Dextrose Injection, Type 1, USP) in patients treated concomitantly with medications associated with hyponatremia may increase the risk of developing hyponatremia. Avoid use of 5% Dextrose and Electrolyte No. 48 Injection (Multiple Electrolytes and Dextrose Injection, Type 1, USP) in patients receiving products, such as diuretics, and certain antiepileptic and psychotropic medications. Drugs that increase the vasopressin effect reduce renal electrolyte free water excretion and may also increase the risk of hyponatremia following treatment with intravenous fluids. If use cannot be avoided, monitor serum sodium concentrations. Other Products that Increase the Risk of Hyperkalemia Because of its potassium content, avoid use of 5% Dextrose and Electrolyte No. 48 Injection (Multiple Electrolytes and Dextrose Injection, Type 1, USP) in patients receiving products that can cause hyperkalemia or increase the risk of hyperkalemia, such as potassium sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, or the immunosuppressants tacrolimus and cyclosporine. If use cannot be avoided, monitor serum potassium concentrations. Lithium Renal clearance of lithium may be increased during administration of 5% Dextrose and Electrolyte No. 48 Injection (Multiple Electrolytes and Dextrose Injection, Type 1, USP). Monitor serum lithium concentrations during concomitant use. Drugs with pH Dependent Renal Elimination Due to its alkalinizing effect (formation of bicarbonate), 5% Dextrose and Electrolyte No. 48 Injection (Multiple Electrolytes and Dextrose Injection, Type 1, USP) may interfere with the elimination of drugs with pH dependent renal elimination. Renal clearance of acidic drugs may be increased. Renal clearance of alkaline drugs may be decreased.

ADVERSE REACTIONS Post-marketing Adverse Reactions The following adverse reactions associated with the use of 5% Dextrose and Electrolyte No. 48 Injection (Multiple Electrolytes and Dextrose Injection, Type 1, USP) were identified in clinical trials or post marketing reports. Because post marketing 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: Hypersensitivity and Infusion Reactions: palpitations, feeling abnormal, piloerection, edema peripheral, hypotension, dyspnea, wheezing, urticaria, cold sweet, tachycardia, chest pain, chest discomfort, respiratory rate increased, flushing, hyperemia, asthenia, pyrexia, chills. General Disorders and Administration Site Conditions : infusion site pain, burning sensation, febrile response, infection at the site of injection, venous thrombosis or phlebitis extending from site of injection, extravasation and hypervolemia. Metabolism and nutrition disorders : hyperkalemia, hyperglycemia, hyponatremia. Nervous System Disorders : hyponatremic encephalopathy. 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. Overdose Excessive administration of 5% Dextrose and Electrolyte No. 48 Injection (Multiple Electrolytes and Dextrose Injection, Type 1, USP) can cause: • fluid overload with a risk of edema (peripheral and/or pulmonary), particularly when renal sodium excretion is impaired. • hyperglycemia, hyperosmolarity, and osmotic diuresis, dehydration and electrolyte loss. • hypernatremia and hyperkalemia, especially in patients with severe renal impairment. • hypermagnesemia. • metabolic alkalosis with or without hypokalemia and decreased ionized serum calcium and magnesium concentrations. • Hyperphosphatemia, hypocalcemia, and hypomagnesemia. See WARNINGS When assessing an overdose, any additives in the solution must also be considered. The effects of an overdose may require immediate medical attention and treatment. Interventions include discontinuation of 5% Dextrose and Electrolyte No. 48 Injection (Multiple Electrolytes and Dextrose Injection, Type 1, USP), dose reduction, and other measures as indicated for the specific clinical constellation (e.g., monitoring of fluid balance, electrolyte concentrations and acid base balance).

Pregnancy Teratogenic Effects Animal reproduction studies have not been conducted with 5% Dextrose and Electrolyte No. 48 Injection (Multiple Electrolytes and Dextrose Injection, Type 1, USP). Intrapartum maternal intravenous infusion of glucose-containing solutions may result in fetal insulin production, with an associated risk of fetal hyperglycemia and metabolic acidosis as well as rebound hypoglycemia in the neonate. 5% Dextrose and Electrolyte No. 48 Injection (Multiple Electrolytes and Dextrose Injection, Type 1, USP) should be given to a pregnant woman by health care providers only after careful consider of the potential risk and benefits for each specific patient.