4.1. Therapeutic indications

5% Glucose Intravenous Infusion Solution is indicated for:

• fluid replacement, administered alone or in regimens with electrolytes or additives known to be compatible with 5% glucose.

• medium for intravenous administration of medicinal products known to be compatible with 5% glucose.

4.2. Posology and method of administration

Fluid balance, serum glucose, serum sodium and other electrolytes may need to be monitored before and during administration, especially in patients with increased non-osmotic vasopressin release (syndrome of inappropriate antidiuretic hormone secretion, SIADH) and in patients comedicated with vasopressin agonist drugs due to the risk of hyponatraemia.

Monitoring of serum sodium is particularly important for physiologically hypotonic fluids. 5% Glucose Intravenous Infusion Solution may become extremely hypotonic after administration due to glucose metabolization in the body (see sections 4.4, 4.5 and 4.8).

To avoid dehydration in a healthy adult or in patients with no complicating factors such as fever or excessive fluid losses, daily fluid requirements are 1.5 to 2.5 litres. The volume of glucose solution needed to replenish deficits will vary with body weight, complementary treatment, severity of the clinical condition and hydration status of the patient, but in adults will usually lie between 2 and 10 litres. The pathophysiological response to dehydration, to electrolyte loss and to glucose infusion will vary with the age of the patient being treated and this should be taken into account during rehydration therapy. There is no recommended dose as this is a matter for clinical judgment and laboratory assessment in each case. The dose range is typically 500 – 3000ml in a 24 hour period and typical maximum rates are 800mg/kg/hr or 600ml/hr.

For intravenous infusion under medical supervision. Single use only.

4.3. Contraindications

Hyperglycaemia. Conditions of water excess.

4.4. Special warnings and precautions for use

The rate of infusion should be sufficiently slow to allow detection of osmotic diuresis Prior to and during infusion, serum and/or urinary electrolytes and glucose should be monitored to assess the nature and severity of fluid depletion and electrolyte imbalance. Close monitoring of patients with diabetes mellitus, and in patients with renal failure, is necessary during glucose infusion.

Glucose infusions are incompatible with blood for transfusion as haemolysis or clumping can occur; do not administer through the same infusion equipment as blood or blood components for transfusion (either before, during or after their administration)

Use with care in patients who have suffered an acute ischaemic stroke.

Glucose intravenous infusions are usually isotonic solutions. In the body, however, glucose containing fluids 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 hyponatraemia.

Hyponatraemia:

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.

4.5. Interaction with other medicinal products and other forms of interaction

Drugs leading to an increased vasopressin effect

The below listed drugs increase the vasopressin effect, leading to reduced renal electrolyte free water excretion and increase the risk of hospital acquired hyponatraemia following inappropriately balanced treatment with i.v. fluids (see sections 4.2, 4.4 and 4.8).

Drugs stimulating vasopressin release, e.g.:

• Chlorpropamide, clofibrate, carbamazepine, vincristine, selective serotonin reuptake inhibitors, 3.4-methylenedioxy-N-methamphetamine, ifosfamide, antipsychotics, narcotics Drugs potentiating vasopressin action, e.g.:

• Chlorpropamide, NSAIDs, cyclophosphamide Vasopressin analogues, e.g:

• Desmopressin, oxytocin, vasopressin, terlipressin

Other medicinal products increasing the risk of hyponatraemia also include diuretics in general and antiepileptics such as oxcarbazepine.

Check compatibility of medicinal products with 5% glucose before administration with the solution. See section 6.2 Incompatibilities.

4.6. Fertility, pregnancy and lactation

It is particularly important to avoid maternal hyperglycaemia during intravenous glucose infusion in the perinatal period in view of the possibility of inducing neonatal hypoglycaemia.

5% Glucose Intravenous Infusion Solution should be administrated with special caution for pregnant women during labour particularly if administered in combination with oxytocin due to the risk of hyponatraemia (see sections 4.4, 4.5 and 4.8).

4.7. Effects on ability to drive and use machines

Not relevant.

4.8. Undesirable effects

The frequency of adverse events listed below is defined using the following convention: very common (≥1/10); common (≥1/100 to < 1/10); uncommon (≥1/1,000 to < 1/100); rare (≥1/10,000 to < 1/1,000); very rare (< 1/10,000), not known (cannot be estimated from the available data).

Metabolism and nutrition disorders

Not known: fluid and electrolyte disturbances including hypokalaemia, hypomagnesaemia and hypophosphataemia, hyperglycaemia, glycosuria. Hypokalaemia may complicate glucose infusions, especially when combined with insulin in the treatment of diabetic ketoacidosis. Not known: Hospital Acquired Hyponatraemia*

General and administration site disorders

Not known: Irritation and discomfort at the site of infusion

Nervous system disorders

Not known: Hyponatraemic encephalopathy*

* Hospital acquired hyponatraemia may cause irreversible brain injury and death due to development of acute hyponatraemic encephalopathy (see sections 4.2 and 4.4).

In the event of adverse reaction stop infusion immediately

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system:

Yellow Card Scheme

Website: www.mhra.gov.uk/yellowcard

4.9. Overdose

Administration of excessive amounts of 5% glucose may result in fluid overload and water intoxication. Severe over-infusion is usually limited to infusion with higher concentrations of glucose solutions, which may cause plasma hyperosmolality and osmotic diuresis. Treatment is symptomatic.