warnings and cautions
5 WARNINGS AND PRECAUTIONS • Hypersensitivity Reactions : Monitor for signs and symptoms and discontinue infusion if reactions occur. ( 5.1 ) • Hyperglycemia or Hyperosmolar Hyperglycemic State : Monitor blood glucose and administer insulin as needed. ( 5.2 , 8.4 ) • Hyponatremia, Hypokalemia, Hypernatremia and Hyperchloremia : Avoid in patients with or at risk for hypo-/hypernatremia and hypokalemia. If use cannot be avoided, monitor serum sodium and potassium concentrations. ( 5.3 , 5.4 , 5.5 , 8.4 ) • Fluid Overload : Avoid in patients with or at risk for fluid and/or solute overloading. If use cannot be avoided, monitor daily fluid balance and electrolyte, concentrations and acid-base balance, as needed and especially during prolonged use. ( 5.6 ) • Refeeding Syndrome : Monitor severely undernourished patients and slowly increase nutrient intake. ( 5.7 ) 5.1 Hypersensitivity Reactions Hypersensitivity and infusion reactions, including anaphylaxis, have been reported with Dextrose and Sodium Chloride Injection [see Adverse Reactions (6) ]. Stop the infusion immediately if signs or symptoms of a hypersensitivity or infusion reaction develops [see Contraindications (4) ]. Appropriate therapeutic countermeasures must be instituted as clinically indicated. 5.2 Hyperglycemia and Hyperosmolar Hyperglycemic State The use of dextrose infusions 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. 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 Dextrose and Sodium Chloride Injection. Insulin may be administered or adjusted to maintain optimal blood glucose concentrations. 5.3 Hyponatremia Dextrose and Sodium Chloride Injection is a hypertonic solution [see Description, Table 1 (11) ]. 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. Depending on the tonicity of the solution, the volume and rate of infusion, and depending on a patient’s underlying clinical condition and capability to metabolize glucose, intravenous administration of glucose can cause electrolyte disturbances, most importantly hypo- or hyperosmotic hyponatremia. The risk for hyponatremia is increased, in pediatric patients, elderly patients, postoperative patients, those with psychogenic polydipsia and in patients treated with medications that increase the risk of hyponatremia (such as certain diuretic, antiepileptic and psychotropic medications) [see Drug Interactions (7.1) ]. Acute 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. Patients at increased risk for developing complications of hyponatremia, such as hyponatremic encephalopathy include pediatric patients; women, in particular, premenopausal women; patients with hypoxemia; and in patients with underlying central nervous system disease [see Use in Specific Populations (8.4 , 8.5 )]. Avoid Dextrose and Sodium Chloride Injection in patients with or at risk for hyponatremia. If use cannot be avoided, monitor serum sodium concentrations. Rapid correction of hyponatremia is potentially dangerous with risk of serious neurologic complications such as osmotic demyelination syndrome with risk of seizures and cerebral edema. To avoid complications, monitor serum sodium and chloride concentrations, fluid status, acid-base balance, and signs of neurologic complications. High volume infusion must be used with close monitoring in patients with cardiac or pulmonary failure, and in patients with non-osmotic vasopressin release (including SIADH), due to the risk of hospital-acquired hyponatremia. 5.4 Hypokalemia Excessive administration of Dextrose and Sodium Chloride Injection may result in significant hypokalemia. Hypokalemic periodic paralysis, metabolic alkalosis, increased gastrointestinal losses (e.g. diarrhea, vomiting), prolonged low potassium diet, or primary hyperaldosteronism may increase the risk of hypokalemia. Avoid the administration of Dextrose and Sodium Chloride Injection in patients with or at risk of hypokalemia or taking medications that may increase the risk. If use cannot be avoided, monitor serum potassium levels. 5.5 Hypernatremia and Hyperchloremia Electrolyte imbalances such as hypernatremia and hyperchloremia, leading to metabolic acidosis may occur with solutions containing 0.9% sodium chloride. Conditions that may increase the risk of hypernatremia, fluid overload and edema (central and peripheral), include patients with pre-eclampsia, primary hyperaldosteronism and secondary hyperaldosteronism associated with, for example, hypertension, congestive heart failure, severe renal impairment, liver disease (including cirrhosis), and renal disease (including renal artery stenosis, nephrosclerosis). Medications such as corticosteroids or corticotropin, may increase the risk of sodium and fluid retention. Avoid in patients with or at risk for hypernatremia. If use cannot be avoided, monitor serum sodium concentrations. Rapid correction of hypernatremia is potentially dangerous with risk of serious neurologic complications. Excessively rapid correction of hypernatremia is also associated with a risk for serious neurologic complications such as osmotic demyelination syndrome (ODS) with risk of seizures and cerebral edema. 5.6 Fluid Overload Depending on the volume and rate of infusion, the patient’s underlying clinical condition and capability to metabolize dextrose, intravenous administration of Dextrose and Sodium Chloride Injection can cause fluid and/or solute overloading resulting in dilution of serum electrolyte concentrations, overhydration, congested states or pulmonary edema. Avoid Dextrose and Sodium Chloride Injection 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. 5.7 Refeeding Syndrome Refeeding severely undernourished patients may result in the refeeding syndrome that is characterized by the shift of potassium, phosphorus, and magnesium intracellularly as the patient becomes anabolic. Thiamine deficiency and fluid retention may also develop. To prevent these complications, monitor severely undernourished patients and slowly increasing nutrient intake.