Special Warning : אזהרת שימוש

4.4 Special warnings and precautions for use

Dextrose (glucose) intravenous infusions are usually isotonic solutions. In the body, however, dextrose (glucose) containing fluids can become extremely physiologically hypotonic due to rapid dextrose (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 dextrose (glucose), intravenous administration of dextrose (glucose) can cause electrolyte disturbances, most importantly hypo- or hyperosmotic hyponatraemia.

Hyponatraemia
The infusion of solutions with sodium concentrations <0.9% may result in hyponatraemia. Close clinical monitoring maybe warranted.

Patients with non-osmotic vasopressin release (e.g., in acute illness, pain, post- operative 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 hyponatraemia upon infusion of hypotonic fluids.

Acute hyponatraemia can lead to acute hyponatraemic encephalopathy (brain oedema) characterized by headache, nausea, seizures, lethargy and vomiting.
Patients with brain oedema are at particular risk of severe, irreversible and life- threatening brain injury.

Children, women in the fertile age and patients with reduced cerebral compliance (e.g., meningitis, intracranial bleeding, and cerebral contusion) are at particular risk of the severe and life-threatening brain swelling caused by acute hyponatraemia.

Sodium retention, fluid overload and oedema

Dextrose 4.3 % w/v and sodium chloride 0.18 % w/v solution should be used with particular caution, in:
• Patients with conditions that may cause sodium retention, fluid overload and oedema (central and peripheral), such as o Primary hyperaldosteronism,
o Secondary hyperaldosteronism associated with, for example,
- hypertension,
- congestive heart failure,
- liver disease (including cirrhosis),
- renal disease (including renal artery stenosis, nephrosclerosis) o Pre-eclampsia.
• Patients taking medications that may increase the risk of sodium and fluid retention, such as corticosteroids.

Hypokalaemia

The infusion of dextrose 4.3 % w/v and sodium chloride 0.18 % w/v solution may result in hypokalaemia. This medicine should be used with particular caution in patients with or at risk for hypokalemia. Close clinical monitoring may be warranted in, for example:
• persons with metabolic alkalosis
• persons with thyrotoxic periodic paralysis, administration of intravenous dextrose (glucose) has been associated in aggravating hypokalaemia • persons with increased gastrointestinal losses (e.g., diarrhea, vomiting) • prolonged low potassium diet
• persons with primary hyperaldosteronism
• patients treated with medications that increase the risk of hypokalaemia (e.g., diuretics, beta-2 agonist, or insulin).

Hypo- and hyperosmolality, serum electrolytes and water imbalance 
Depending on the volume and rate of infusion and depending on a patient's underlying clinical condition and capability to metabolize dextrose (glucose), intravenous administration of dextrose 4.3 % w/v and sodium chloride 0.18 % w/v solution can cause:
•   Hypo-osmolality
•   Hyperosmolality, osmotic diuresis and dehydration
•   Electrolyte disturbances such as
- hyponatraemia (see above),
- hypokalaemia (see above),
- hypophosphataemia,
- hypomagnesaemia,
•   Overhydration/hypervolaemia and, for example, congested states, including central (e.g., pulmonary congestion) and peripheral oedema.

Clinical evaluation 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.

Hyperglycaemia

Rapid administration of dextrose (glucose) solutions may produce substantial hyperglycaemia and a hyperosmolar syndrome. In order to avoid hyperglycaemia the infusion rate should not exceed the patient's ability to utilize dextrose (glucose).

To reduce the risk of hyperglycaemia-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 dextrose (glucose) should be administered with caution in patients with, for example:
• impaired glucose tolerance (such as in diabetes mellitus, renal impairment, or in the presence of sepsis, trauma or shock),
• severe malnutrition (risk of precipitating a refeeding syndrome, see below), • thiamine deficiency, e.g., 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 dextrose (glucose) and/or free water load.

Other groups of patients in whom Dextrose 4.3 % w/v and sodium chloride 0.18 % w/v solution should be used with caution include:
• patients with ischemic stroke. Hyperglycaemia has been implicated in increasing cerebral ischemic brain damage and impairing recovery after acute ischemic strokes.
• patients with severe traumatic brain injury (in particular during the first 24 hours following the trauma). Early hyperglycaemia has been associated with poor outcomes in patients with severe traumatic brain injury.
• Newborns (see Paediatric glycaemia-related issues).

Prolonged intravenous administration of dextrose (glucose) and associated hyperglycaemia may result in decreased rates of glucose-stimulated insulin secretion.

Hypersensitivity Reactions

•   Hypersensitivity/infusion reactions, including anaphylaxis, have been reported (see section 4.8).
•   Stop the infusion immediately if signs or symptoms of hypersensitivity/infusion reactions develop. Appropriate therapeutic counter measures must be instituted as clinically indicated.
•   Solutions containing dextrose (glucose) should be used with caution in patients with known allergy to corn or corn products.

Refeeding syndrome

Refeeding severely under nourished 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. Careful monitoring and slowly increasing nutrient intake while avoiding overfeeding can prevent these complications.

Severe renal impairment

Dextrose 4.3 % w/v and sodium chloride 0.18 % w/v solution should be administered with particular caution to patients at risk of (severe) renal impairment. In such patients, administration may result in sodium retention and/or fluid overload.

Paediatric use

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 paediatric intravenous fluid therapy.

Paediatric Population

Intravenous fluid therapy should be closely monitored in the paediatric populations as they may have impaired ability to regulate fluids and electrolytes. Adequate urine flow must be ensured and careful monitoring of fluid balance, plasma and urinary electrolyte concentrations are essential.

Paediatric glycaemia-related issues

Newborns, especially those born premature and with low birth weight, are at increased risk of developing hypo- or hyperglycaemia. Close monitoring during treatment with intravenous dextrose (glucose) solutions is needed to ensure adequate glycaemic control, in order to avoid potential long term adverse effects.

Hypoglycaemia in the newborn can cause, e.g.,
• prolonged seizures,
• coma and
• cerebral injury.

Hyperglycaemia has been associated with
• cerebral injury, including intraventricular haemorrhage,
• late onset bacterial and fungal infection,
• retinopathy of prematurity,
• necrotizing enterocolitis,
• increased oxygen requirements,
• prolonged length of hospital stay and
• death.
Paediatric hyponatraemia-related issues
•    Children (including neonates and older children) are at increased risk of developing hyponatraemia as well as for developing hyponatraemic encephalopathy.
•    The infusion of hypotonic fluids together with the non-osmotic secretion of ADH may result in hyponatraemia.
•    Hyponatraemia can lead to headache, nausea, seizures, lethargy, coma, cerebral edema and death; therefore, acute symptomatic hyponatraemic encephalopathy is considered a medical emergency.
•    Plasma electrolyte concentrations should be closely monitored in the paediatric population.
•    Rapid correction of hyponatraemia is potentially dangerous (risk of serious neurologic complications). Dosage, rate, and duration of administration should be determined by a physician experienced in paediatric intravenous fluid therapy.

Blood

Dextrose 4.3 % w/v and sodium chloride 0.18 % w/v solution should not be administered simultaneously with blood through the same administration set because of the possibility of pseudo agglutination or haemolysis.

Geriatric use

When selecting the type of infusion and the volume/rate of infusion for a geriatric patient, consider that geriatric patients are generally more likely to have cardiac, renal, hepatic, and other diseases or concomitant drug therapy.

Effects on Driving

4.7 Effects on Ability to Drive and Use Machines

There is no information on the effects of dextrose 4.3 % w/v and sodium chloride 0.18 % w/v solution on the ability to operate an automobile or other heavy machinery.