Special Warning : אזהרת שימוש

4.4 Special warnings and precautions for use

Glucose-containing solutions for intravenous infusion are usually isotonic. In the body, however, glucose-containing solutions can become extremely physiologically hypotonic due to rapid glucose metabolization (see section 4.2).

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.


Hyponatremia:

Patients with non-osmotic vasopressin release (e.g., in acute illness, pain, postoperative stress, infections, burns and CNS diseases), patients with heart, liver and kidney diseases and patients exposed to vasopressin agonists (see section 4.5) are at particular risk of acute hyponatremia upon infusion of hypotonic solutions.

Acute hyponatremia can lead to acute hyponatremic encephalopathy (cerebral edema) characterized by headache, nausea, convulsions, lethargy and vomiting. Patients with cerebral edema are at particular risk of severe, irreversible and life-threatening brain damage.

Children, women of childbearing potential and patients with reduced cerebral compliance (e.g., meningitis, intracranial hemorrhage and brain contusion) are at particular risk of severe and life-threatening cerebral edema caused by acute hyponatremia.

Sodium retention, fluid overload and edema

Sodium chloride 0.33% and Glucose 5% Baxter should be used with particular caution, in: 
• Patients with conditions that may cause sodium retention, fluid overload and edema (central and peripheral), such as o Primary hyperaldosteronism,
o Secondary hyperaldosteronism associated with, for example,
- hypertension,
- congestive heart failure,
- hepatic disease (including cirrhosis),
- renal disease (including renal artery stenosis, nephrosclerosis) o Pre-eclampsia.
• Patients taking medicinal products that may increase the risk of sodium and fluid retention, such as corticosteroids

Hypopotassemia
Sodium chloride 0.33% and Glucose 5% Baxter may result in hypopotassemia. This medicinal product should be used with particular caution in patients with or at risk for hypopotassemia.
Close clinical monitoring may be warranted in, for example:
• persons with metabolic alkalosis
• persons with thyrotoxic periodic paralysis, administration of intravenous glucose has been associated with aggravation of hypopotassemia
• persons with increased gastrointestinal losses (for example, diarrhea, vomiting)
• prolonged low potassium diet
• persons with primary hyperaldosteronism
• patients treated with medicinal products that increase the risk of hypopotassemia (for example, diuretics, beta-2 agonists or insulin)

Hypo- and hyperosmolality, serum electrolytes and fluid imbalance

Depending on the volume and rate of infusion and depending on the patient’s underlying clinical condition and capability to metabolize glucose, administration of Sodium chloride 0.33% and Glucose 5% Baxter can cause:
• Hypo-osmolality
• Hyperosmolality, osmotic diuresis and dehydration
• Electrolyte disturbances such as o hyponatremia (see above),

o hypopotassemia (see above),
o hypophosphatemia,
o hypomagnesemia,
• Overhydration/hypervolemia and, for example, congested states, including central (e.g., pulmonary congestion) and peripheral edema.

Clinical evaluations and periodic laboratory determinations may be necessary to monitor changes in fluid balance, electrolyte concentrations and acid-base balance during prolonged parenteral therapy or whenever the condition of the patient or the rate of administration warrants such evaluation.

Hyperglycemia
Rapid administration of glucose solutions may produce substantial hyperglycemia and a hyperosmolar syndrome. In order to avoid hyperglycemia, the infusion rate should not exceed the patient’s ability to utilize glucose.

To reduce the risk of hyperglycemia-associated complications, the infusion rate must be adjusted and/or insulin administered if blood glucose levels exceed levels considered acceptable for the individual patient.

Intravenous glucose should be administered with caution in patients with, for example:
• impaired glucose tolerance (such as in diabetes mellitus, renal failure or in the presence of sepsis, trauma or shock),
• severe malnutrition (risk of precipitating a refeeding syndrome, see below),
• thiamine deficiency, for example, in patients with chronic alcoholism (risk of severe lactic acidosis due to impaired oxidative metabolism of pyruvate),
• water and electrolyte disturbances that could be aggravated by increased glucose and/or free water load

Other groups of patients in whom Sodium chloride 0.33% and Glucose 5% Baxter should be used with caution include:
• patients with ischemic stroke. Hyperglycemia has been implicated in increasing cerebral ischemic brain damage and impairing recovery after ischemic strokes.
• patients with severe traumatic brain injury (in particular during the first 24 hours following the trauma). Early hyperglycemia has been associated with poor outcomes in patients with severe traumatic brain injury.
• Newborns (See Pediatric glycemia-related complications).

Prolonged intravenous administration of glucose and associated hyperglycemia may result in decreased rates of glucose-stimulated insulin secretion.

Hypersensitivity reactions
• Hypersensitivity/infusion reactions, including anaphylaxis/anaphylactoid reactions, have been reported with glucose solutions (see section 4.8).
• The infusion must be stopped immediately if any signs or symptoms of a suspected hypersensitivity reaction develop, and appropriate therapeutic measures must be instituted as clinically indicated.
Solutions containing glucose should be used with caution in patients with known allergy to corn or corn products (see section 4.3).


Refeeding syndrome

Refeeding severely undernourished patients may result in a refeeding syndrome that is characterized by a shift of potassium, phosphorus and magnesium intracellularly as the patient becomes anabolic. Thiamine deficiency and fluid retention may also develop. Careful monitoring and slowly increasing nutrient intake while avoiding overfeeding can prevent these complications.

Severe renal failure
Sodium chloride 0.33% and Glucose 5% Baxter should be administered with particular caution to patients at risk of severe renal failure. In such patients, administration of the solution may result in sodium retention and fluid overload.

Pediatric population

Pediatric glycemia-related complications
The infusion rate and volume depend on the age, weight, clinical and metabolic conditions of the patient, concomitant therapy, and should be determined by a physician experienced in pediatric therapy with solutions for intravenous infusion.

• Newborns, especially those born premature and with low birth weight, are at increased risk of developing hypoglycemia or hyperglycemia, and therefore, they need close monitoring during treatment with intravenous glucose solutions to ensure adequate glycemic control, in order to avoid potential long-term adverse effects.
• Hypoglycemia in the newborn can cause, e.g.: o prolonged convulsions,
o coma and o brain damage.
• Hyperglycemia has been associated with: o brain injury, including intraventricular hemorrhage,
o late-onset bacterial and fungal infection,
o retinopathy of prematurity,
o necrotizing enterocolitis,
o increased oxygen requirements,
o prolonged length of hospital stay and o death.

Pediatric hyponatremia-related complications

• Children (including newborns and older children) are at increased risk of developing hypo- osmotic hyponatremia as well as for developing hyponatremic encephalopathy.
• The infusion of hypotonic fluids together with the non-osmotic secretion of ADH may result in hyponatremia.
• Hyponatremia can lead to headache, nausea, convulsions, lethargy, coma, cerebral edema and death; therefore, acute symptomatic hyponatremic encephalopathy is considered a medical emergency.
• In the pediatric population, plasma electrolyte concentrations should be closely monitored.
• Rapid correction of hyponatremia is potentially dangerous (risk of serious neurologic complications). The dosage, frequency and duration of administration should be determined by a physician experienced in pediatric therapy with solutions for intravenous infusion.


Blood

Sodium chloride 0.33% and Glucose 5% Baxter should not be administered simultaneously with blood through the same infusion set, because hemolysis and clot formation can occur.

Geriatric use

When selecting the type of infusion solution and the volume and rate of infusion for a geriatric patient, it must be taken into account that such patients are generally more likely to have cardiac, renal, hepatic and other diseases or concomitant therapies.

Effects on Driving

4.7 Effects on ability to drive and use machines

There is no information on the effects of Sodium chloride 0.33% and Glucose 5% Baxter on the ability to drive or use heavy machinery.