Dextrose Monohydrate

5 WARNINGS AND PRECAUTIONS • Pulmonary Embolism due to Pulmonary Vascular Precipitates : If signs of pulmonary distress occur, stop the infusion and initiate a medical evaluation. ( 5.1 ) • Hyperglycemia or Hyperosmolar Hyperglycemic State : Monitor blood glucose and administer insulin as needed. ( 5.2 ) • Hypersensitivity Reactions : Monitor for signs and symptoms and discontinue infusion if reactions occur. ( 5.3 ) • Vein Damage and Thrombosis : Administer solutions containing more than 5% dextrose as the final concentration or solutions with an osmolarity of approximately 900 mOsm/L or greater through a central vein. ( 2.2 , 5.4 ) • Hyponatremia: Monitor serum sodium to minimize the risk of hypo- or hyperosmotic hyponatremia. ( 5.5 ) • Risk of Infection : Monitor for signs and symptoms and laboratory parameters. ( 5.6 ) • Refeeding Syndrome : Monitory laboratory parameters. ( 5.7 ) • Hepatobiliary Disorders : Monitor liver function parameters and ammonia levels. ( 5.8 ) • Aluminum Toxicity : Dextrose Injection contains aluminum that may be toxic. Adult patients with impaired renal function and preterm infants are at higher risk. Limit aluminum to less than 4 mcg/kg/day ( 5.9 , 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. ( 5.10 , 8.4 ) • Electrolyte Imbalance and Fluid Overload : Monitor daily fluid balance, blood electrolyte levels, correct as needed. ( 5.11 , 8.4 ) 5.1 Pulmonary Embolism due to Pulmonary Vascular Precipitates Pulmonary vascular precipitates causing pulmonary vascular emboli and pulmonary distress have been reported in patients receiving parenteral nutrition. In some cases, fatal outcomes due to pulmonary embolism have occurred. Patients, especially those with hypophosphatemia, may require the addition of phosphate. To prevent hypocalcemia, calcium supplementation should always accompany phosphate administration. Excessive addition of calcium and phosphate increases the risk of the formation of calcium phosphate precipitates. Precipitates have been reported even in the absence of phosphate salt in the solution. Precipitation following passage through an in-line filter and suspected in vivo precipitate formation has also been reported. If signs of pulmonary distress occur, stop the infusion and initiate a medical evaluation. In addition to inspection of the solution [see Dosage and Administration (2.1 , 2.2 )] , the infusion set and catheter should also periodically be checked for precipitates. 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 [see Warnings and Precautions (5.11) ] . 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. Insulin may be administered or adjusted to maintain optimal blood glucose levels during Dextrose Injection administration. 5.3 Hypersensitivity Reactions Hypersensitivity and infusion reactions including anaphylaxis have been reported with dextrose injection [see Adverse Reactions (6) ] . Stop infusion immediately and treat patient accordingly if signs or symptoms of a hypersensitivity reaction develop. Signs or symptoms may include: pruritis, bronchospasm, cyanosis, angioedema, hypotension, pyrexia, chills, and rash. 5.4 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 with an osmolarity of ≥ 900 mOsm/L through a central vein [see Dosage and Administration (2.2) ] . The infusion of hypertonic solutions into a peripheral vein may result in vein irritation, vein damage, and/or thrombosis. The primary complication of peripheral access is venous thrombophlebitis, which manifests as pain, erythema, tenderness or a palpable cord. Remove the catheter as soon as possible, if thrombophlebitis develops. 5.5 Hyponatremia Dextrose 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). Close clinical monitoring may be warranted. 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) ] . 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. 5.6 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. Infection and sepsis may also occur as a result of the use of intravenous catheters to administer parenteral nutrition. 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. 5.7 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 including Dextrose Injection. 5.8 Hepatobiliary Disorders Hepatobiliary disorders are known to develop in some patients without preexisting liver disease who receive parenteral nutrition, including cholecystitis, cholelithiasis, cholestasis, hepatic steatosis, fibrosis and cirrhosis, possibly leading to hepatic failure. The etiology of these disorders is thought to be multifactorial and may differ between patients. Monitor liver function parameters and ammonia levels. Patients developing signs of hepatobiliary disorders should be assessed early by a clinician knowledgeable in liver diseases in order to identify possible causative and contributory factors, and possible therapeutic and prophylactic interventions. 5.9 Aluminum Toxicity Dextrose Injection contains no more than 25 mcg/L of aluminum. However, with prolonged parenteral administration in patients with renal impairment, the aluminum contained in Dextrose Injection may reach toxic levels. Preterm infants are at greater risk because their kidneys are immature, and they require large amounts of concomitant calcium and phosphate solutions that contain aluminum. Patients with renal impairment, including preterm infants, who receive parenteral levels of aluminum at greater than 4 to 5 mcg/kg/day, accumulate aluminum at levels associated with central nervous system (CNS) and bone toxicity. Tissue loading may occur at even lower rates of administration of total parenteral nutrition products [see Use in Specific Populations (8.4) ] . 5.10 Risk of Parenteral Nutrition Associated Liver Disease Parenteral Nutrition Associated Liver Disease (PNALD) has been reported in patients who receive parenteral nutrition for extended periods of time, especially preterm infants, and can present as cholestasis or steatohepatitis. The exact etiology is not entirely clear and is likely multifactorial. If Dextrose Injection-treated patients develop abnormal liver function tests, consider discontinuation or dosage reduction. 5.11 Electrolyte Imbalance and Fluid Overload Electrolyte deficits, particularly in serum potassium and phosphate, may occur during prolonged use of concentrated dextrose solutions. Depending on the volume and rate of infusion, the intravenous administration of concentrated dextrose solutions can cause fluid and/or solute overloading resulting in dilution of serum electrolyte concentrations (including hypoosmotic hyponatremia), overhydration, congested states or pulmonary edema. The risk of dilutional states is inversely proportional to the electrolyte concentrations in the administered solution. The risk of solute overload causing congested states with peripheral and pulmonary edema is directly proportional to the electrolyte concentrations in the solution. Monitor blood electrolyte levels, glucose, acid-base balance, correct fluid and electrolyte imbalances, and administer essential vitamins and minerals as needed. Monitor daily fluid balance. Additional monitoring is recommended for patients with water and electrolyte disturbances that could be aggravated by increased glucose and/or free water load. Patients at increased risk for developing hyponatremic encephalopathy include pediatric patients; elderly patients, women, in particular premenopausal women; patients with hypoxemia; and patients with underlying CNS disease [see Use in Specific Populations (8.4 , 8.5 )].