2.1 Preparation Instructions Prior to Administration

Dextrose Injection is supplied as a pharmacy bulk package for admixing only and is not for direct intravenous infusion. Dextrose Injection is intended for use in the preparation of sterile, intravenous admixtures. Prior to administration, Dextrose Injection must be transferred to a separate PN container, diluted with other compatible intravenous fluids and used as an admixture in PN solutions.

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Do not remove from overpouch until ready to use.

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Tear protective overwrap at slit and remove solution container. Small amounts of moisture may be found on the solution container from water permeating from inside the container. The amount of permeated water is insufficient to affect the solution significantly. If larger amounts of water are found, the container should be checked for tears or leaks.

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Inspect Dextrose Injection prior to use. Opacity of the container may be observed due to moisture absorption during the sterilization process. This is normal and does not affect the solution quality or safety. The opacity will diminish gradually. Evaluate the following:

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If the outlet port protector is damaged, detached, or not present, discard container as solution path sterility may be impaired.

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Check for minute leaks by squeezing the inner container firmly. If leaks are found, discard solution as sterility may be impaired.

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Do not use unless solution is clear and container is intact.

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Because additives may be incompatible, evaluate all additions for compatibility and stability of the resulting preparation. Consult with a pharmacist, if available. If it is deemed advisable to introduce additives, use aseptic technique and mix thoroughly.

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Calcium and phosphate ratios must be considered. Excess addition of calcium and phosphate, especially in the form of mineral salts, may result in the formation of calcium phosphate precipitates [see Warnings and Precautions (5.1)].

Preparation for Admixing

1.

The Pharmacy Bulk Package is to be used only in a suitable work area such as a laminar flow hood (or an equivalent clean air compounding area).

2.

Suspend container from eyelet support.

3.

Remove plastic protector from outlet port at bottom of container.

4.

Attach solution transfer set. Refer to complete directions accompanying set.
Note: The closure shall be penetrated only one time with a suitable sterile transfer device or dispensing set which allows measured dispensing of the contents.

5.

The VIAFLEX plastic container should not be written on directly since ink migration has not been investigated. Affix accompanying label for date and time of entry notation.

6.

Once container closure has been penetrated, withdrawal of contents should be completed without delay. After initial entry, maintain contents at room temperature (25°C/77°F) and dispense within 4 hours.

2.2 Important Administration Instructions

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Dextrose Injection is for admixing use only and is not for direct intravenous infusion. Prior to administration, Dextrose Injection must be diluted with other compatible intravenous fluids and used as an admixture in PN solutions.

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To prevent air embolism, use a non-vented infusion set or close the vent on a vented set, avoid multiple connections, do not connect flexible containers in series, fully evacuate residual gas in the container prior to administration, do not pressurize the flexible container to increase flow rates, and if administration is controlled by a pumping device, turn off pump before the container runs dry.

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When Dextrose Injection is admixed, the choice of a central or peripheral venous route should depend on the osmolarity of the final infusate. Solutions with an osmolarity of 900 mOsm/L or greater must be infused through a central venous catheter [see Warnings and Precautions (5.4)].

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Prior to infusion, visually inspect the PN solution to ensure precipitates have not formed during the mixing or addition of additives. Discard container if precipitates are observed.

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If admixed or infused with lipid emulsion, do not use administration sets and lines that contain di-2-ethylhexyl phthalate (DEHP). Administration sets that contain polyvinyl chloride (PVC) components have DEHP as a plasticizer.

2.3 Dosing Instructions

Caution: Dextrose Injection is not for direct intravenous infusion. Prior to administration, Dextrose Injection must be diluted with other compatible intravenous fluids or used as an admixture in PN solutions.

Dextrose Injection is a part of the parenteral nutrition (PN) regimen which also includes amino acids, electrolytes, and possibly lipid emulsion. Protein, caloric, fluid and electrolyte requirements all need to be taken into consideration when determining individual patient dosage needs.

Individualize the dosage of Dextrose Injection based on the patient’s clinical condition (ability to adequately metabolize dextrose), body weight, nutritional and fluid requirements, as well as additional energy given orally or enterally to the patient. Vitamins and trace elements and other components (including amino acids, electrolytes, and lipid emulsion) can be added to the PN solution to meet nutrient needs and prevent deficiencies and complications from developing.

The administration rate should be governed, especially during the first few days of therapy, based on the patient’s tolerance to dextrose. Daily intake of amino acids and dextrose should be increased gradually to the maximum required dose as indicated by frequent determinations of blood glucose levels.

In many patients, provision of adequate calories in the form of hypertonic dextrose may require the administration of exogenous insulin to prevent hyperglycemia and glycosuria.

2.4 Discontinuation of Dextrose Injection

To reduce the risk of hypoglycemia, a gradual decrease in flow rate in the last hour of infusion should be considered [see Warnings and Precautions (5.2), Use in Specific Populations (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)].

7.1 Other Products that Affect Glycemic Control or Fluid and/or Electrolyte Balance

Dextrose Injection can affect glycemic control and fluid and/or electrolyte balance [see Warnings and Precautions (5.2, 5.5, 5.11)]. Monitor blood glucose concentrations, fluid balance, serum electrolyte concentrations and acid-base balance when using Dextrose Injection in patients treated with other substances that affect glycemic control, or fluid and/or electrolyte balance (such as diuretics and anti-epileptics).

8.1 Pregnancy

Risk Summary

Appropriate administration of Dextrose Injection 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. Malnutrition in pregnant women is associated with adverse maternal and fetal outcomes (see Clinical Considerations). Animal reproduction studies have not been conducted with injectable dextrose solutions.

The estimated background risk of major birth defects and miscarriage for the indicated population 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.

Clinical Considerations

Disease-Associated Maternal and/or Embryo/Fetal Risk

Severe malnutrition in pregnant women is associated with preterm delivery, low birth weight, intrauterine growth restriction, congenital malformations and perinatal mortality. Parenteral nutrition should be considered if a pregnant woman’s nutritional requirements cannot be fulfilled by oral or enteral intake.

8.2 Lactation

Risk Summary

There are no data on the presence of dextrose in human milk, the effects on a breastfed infant, or the effects on milk production. The lack of clinical data during lactation precludes a clear determination of the risk of Dextrose Injection to an infant during lactation; therefore, the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Dextrose Injection and any potential adverse effects on the breastfed infant from Dextrose Injection or from the underlying maternal condition.

8.4 Pediatric Use

The safety profile of Dextrose Injection in pediatric patients is similar to adults.

Neonates, especially premature infants with low birth weight, are at increased risk of developing hypo- or hyperglycemia and therefore need close monitoring during treatment with intravenous glucose infusions to ensure adequate glycemic control in order to avoid potential long-term adverse effects.

Plasma electrolyte concentrations should be closely monitored in pediatric patients who may have impaired ability to regulate fluids and electrolytes. In very low birth weight infants, excessive or rapid administration of Dextrose Injection may result in increased serum osmolality and risk of intracerebral hemorrhage.

Because of immature renal function, preterm infants receiving prolonged treatment with dextrose injection, may be at risk of aluminum toxicity [see Warnings and Precautions (5.9)]. Patients, including pediatric patients, may be at risk for Parenteral Nutrition Associated Liver Disease (PNALD) [see Warnings and Precautions (5.10)].

Children (including neonates and older children) are at increased risk of developing hyponatremia as well as for developing hyponatremic encephalopathy.

8.5 Geriatric Use

Clinical studies of Dextrose Injection did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Elderly patients are at increased risk of developing hyponatremia as well as for developing hyponatremic encephalopathy [see Warnings and Precautions (5.5)]. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

12.1 Mechanism of Action

Dextrose Injection is used to supplement nutrition by providing glucose parenterally. Dextrose is oxidized to carbon dioxide and water, yielding energy.