Document: Glukosel solution for infusion ENG SmPC change

• Glukosel solution for infusion SmPC
• Glukosel solution for infusion ENG SmPC

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Summary of Product Characteristics

1.Name of the Medicinal Product

Glukosel solution for infusion

2.Qualitative and Quantitative Composition

1000 ml solution for infusion contains:

Glucose monohydrate (equivalent to glucose 100.0 g)	100.0 g) 110.0	110.0 g
Sodium chloride	2.34	g
Potassium chloride	1.87	g
Magnesium chloride hexahydrate	0.51	g
Sodium dihydrogen phosphate dihydrate	1.56	g
Zinc acetate dihydrate	16.5	mg

Electrolyte content:
Sodium	50	mmol/l
Potassium	25	mmol/l
Magnesium	2.5	mmol/l
Zinc	0.075	mmol/l
Chloride	70	mmol/l
Dihydrogen phosphate	10	mmol/l
Acetate	0.15	mmol/l

For a full list of excipients, see section 6.1.

3.Pharmaceutical Form

Solution for infusion.

Clear, colourless to slightly yellow aqueous solution.

Caloric value: 1680 kJ/l (400 kcal/l)

Osmolarity 710 mOsm/l

pH approx. 3.5

Acidity, titration (to pH 7) approx. 8 mmol/l

4.Clinical Particulars

4.1Therapeutic indications

Glukosel solution for infusion with electrolytes is indicated for caloric support by means of glucose and for electrolyte supply in parenteral nutrition. It may also be given postoperatively after elective surgery to meet the basal daily fluid, energy and electrolyte requirement.

It may be used as a supplement to enteral nutrition.

Note:

This solution is only one component of parenteral nutrition. Total parenteral nutrition also includes amino acids, vitamins, essential fatty acids and trace elements.

4.2Posology and method of administration

Posology

The dosage should be individually adjusted according to the patient’s age, body weight and clinical condition.

Recommended dosage in adults:

The maximum daily dose is 40 ml/kg, corresponding to 4 g of glucose/kg.

The maximum infusion rate is 2.5 ml/kg/hour corresponding to 0.25 g of glucose/kg per hour. The maximum drop rate is 0.8 drops/kg/minute. Thus, for a patient weighing 70 kg, the maximum infusion rate is approx. 175 ml/hour (corresponding maximum drop rate of 58 drops/min), resulting in a glucose intake of 17.5 g/hourand a potassium intake of 4.4 mmol/hour.

General limits for potassium and glucose intake

Only under very special circumstances such as severe hypokalaemia, potassium administration may exceed 20 mmol/hour, due to the risk of cardiac arrhythmias.

Glucose administration must not exceed 1 g/kg/hour, due to the risk of hyperglycemia and osmotic diuresis.

In the presence of metabolic disorders (e.g. postoperatively or after injuries, hypoxia, organ insufficiency), the oxidative metabolism of glucose may be impaired. In such situations, the glucose intake should be limited to 2–4 g/kg/day. The blood glucose level should not exceed 6.1 mmol/l (110 mg/100 ml).

To avoid post-infusion hypoglycaemia, the infusion rate should be gradually reduced during the final phase of the administration. See also section 4.4.

Paediatric population

Children over 2 years of age:

The recommended dosage schedule corresponds to that of adults (see dosage recommendations for adults above). Additional fluid and energy that may be required for paediatric patients should be administered in the form of glucose solutions or fat emulsions, as appropriate.

The given dosage recommendations are guiding data based on average requirements. The dosage should be individually adapted, according to age, development stage and illness. For calculation of dosage account must be taken of the hydration status of the paediatric patient.

Recommendations for zinc intake in children:

The recommended zinc intake is 50 micrograms per kg body weight per day. This should be taken into account when determining the daily dose of Glukoselfor children.

Care should be taken not to exceed a total maximum zinc dose of 5 mg per day in children weighing more than 25 kg.

In the case of increased zinc requirements (e.g. due to excessive cutaneous or digestive losses) higher doses may be necessary.

Children under 2 years of age:

On account of its compositionGlukoselshould not be used in children under 2 years of age because it does not properly meet the requirements of that age group.

Monitoring of the treatment

Fluid balance, electrolytes, glucose and osmolality should be checked regularly both in the blood and in the urine. In case of trauma, sepsis and relative insulin resistance, glucose levels should be monitored at frequent intervals, e.g. every 4–6 hours. It is advisable to monitor the zinc status routinely in patients receivingGlukosel.

Method of administration

Intravenous use. The solution can be infused into peripheral veins.

The solution should not be infused through the same infusion equipment as blood, see section 4.4.

4.3Contraindications

Contraindications related to the product or to parenteral nutrition in general:

• Hyperglycaemia not responding to insulin doses of up to 6 units insulin/hour

• Decompensated diabetes mellitus, diabetic coma

• Untreated diabetes insipidus

• Anuria in absence of renal replacement therapy

• Intracranial or intraspinal haemorrhage

• Delirium tremens if the patient is already dehydrated

• Pathologically high serum electrolyte concentrations, particularly potassium (hyperkalaemia)

• Unstable circulatory status that is life-threatening (collapse and shock)

• Cellular hypoxia

• Metabolic acidosis

• Hypersensitivity to the active substances or to any of the excipients listed in section 6.1

4.4Special warnings and precautions for use

Administration of glucose solutions is not recommended after an acute ischaemic stroke, since hyperglycaemia has been reported to worsen the ischaemic brain damage and impair recovery.

Solutions containing glucose should be used with caution in patients with manifest or known subclinical diabetes mellitus or carbohydrate intolerance due to any reason.

This solution should be used with caution in patients with hypervolemia, renal insufficiency with a tendency to hyperkalaemia and impending or manifest cardiac decompensation.

In patients with cardiac insufficiency, the infused volume and infusion rate should be adjusted very carefully according to the patient's circulatory status, mainly his cardiac output, to avoid fluid and circulatory overload.

Electrolyte and fluid imbalances, such as hypotonic dehydration and hyponatraemia, should be corrected by adequate supply of fluid and electrolytes prior to parenteral nutrition.

This solution should only be administered with caution to patients with increased serum osmolarity.

Unstable metabolism (e.g. postoperatively or after injuries, hypoxia, organ insufficiency) impairs the oxidative metabolism of glucose and may lead to metabolic acidosis. See also section 4.2.

Hyperglycaemia should be adequately monitored and treated with insulin. Administration of insulin causes additional transfer of potassium into the cells and may thus cause or increase hypokalaemia.

Severe hypoglycemia may follow abrupt discontinuation of high-rate glucose infusion because of the associated high serum insulin concentrations. This concerns particularly children under 2 years of age, patients with diabetes mellitus and other disorders with impaired glucose homeostasis. In obvious cases, the glucose infusion should be tapered off within the last 30–60 minutes of the infusion. It is recommended as a precaution that each individual patient be monitored for 30 minutes for hypoglycemia on the first day of abrupt discontinuation of parenteral nutrition.

Clinical monitoring should include blood glucose, serum electrolytes, fluid and acid-base balance in general. Frequency of the laboratory tests and decision on which tests are necessary depend on the general status of the patient, the prevailing metabolic status and the dose administered. Also the total volume and amount of glucose administered should be monitored.

Refeeding of malnourished patients may cause particularly hypokalaemia, hypophosphataemia and hypomagnesaemia. Adequate electrolyte supplement according to the deviations from normal values is necessary.

This solution should not be administered to patients with hyponatraemia or hypokalaemia without additional supplementation of these electrolytes and careful monitoring of the serum electrolyte concentrations. Particular care must be taken to ensure adequate supply of potassium.

Vitamins should be supplied as necessary. Vitamin B, especially thiamine, is necessary for the glucose metabolism.

In general, this solution is not suitable for supply of water and electrolytes over longer periods without additional supplementation of electrolyte solutions in accordance with the complete infusion regimen. Infusion of this solution alone over an extended period may provoke an electrolyte and water imbalance, depending on the kidney function.

Paediatric population

Due to the individual needs of paediatric patients, Glukosel may not cover sufficiently the total energy requirements. In such cases carbohydrates and/or lipids must be provided in addition, as appropriate.

Glucose infusions should not be administered through the same infusion line concomitantly with, prior to or after administration of blood because of the risk of haemolysis and pseudoagglutination.

4.5Interaction with other medicinal products and other forms of interaction

In patients receiving treatment with cardiac glycosides, abrupt discontinuation of administration of potassium may provoke toxic effects from cardiac glycosides.

Potassium-sparing diuretics may lead to hyperkalaemia. Therefore, careful monitoring of serum potassium levels is required during and after administration of Glukosel solution for infusion.

4.6Fertility, pregnancy and lactation

For Glukosel solution for infusion no controlled clinical data on exposed pregnancies are available. Also, no animal studies with this glucose/electrolyte combination are available. However, there are no known risks with the treatment with the active substances in this product during pregnancy or lactation when the treatment is carried out as indicated, with careful monitoring of blood glucose levels, serum electrolytes, fluid and acid-base balance.

4.7Effects on ability to drive and use machines

This solution has no influence on the ability to drive and use machines.

4.8Undesirable effects

Common (≥ 1/100 to < 1/10): Thrombophlebitis in peripheral veins

Factors contributing to thrombophlebitis include infusion time, infusion rate, solution’s pH and osmolality, the venous catheter and vascular irritability of the individual patient.

The following undesirable effects that are not directly related to the product but to the administration conditions, underlying disorders or other concomitant treatment, may occur:

• Hypokalemia may be associated with insulin therapy. In addition, hypokalaemia, hypomagnesaemia and hypophosphataemia may be caused by refeeding with glucose particularly in malnourished patients.

• Abrupt discontinuation and/or administration of insulin may cause rebound hypoglycemia, particularly in patients with disturbances in the glucose tolerance.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation 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 listed in [To be completed nationally].

4.9Overdose

Symptoms

Overdose or an excessive infusion rate may give rise to disturbances in the electrolyte balance (e.g. hypokalaemia or hyperkalaemia, disturbances in the acid-base balance), hyperglycaemia, serum hyperosmolarity up to hyperglycaemic/hyperosmotic coma, glucosuria and increased diuresis. A massive overdose of glucose may also lead to increased lipogenesis resulting in hepatic steatosis.

Treatment

Dose and/or the infusion rate should be reduced or administration of the infusion should be completely discontinued. Renal excretion should be increased to reduce excessive serum substrate concentrations. Fluid, electrolyte and acid-base balance disturbances should be corrected. Administration of insulin may be necessary to correct hyperglycaemia.

5.Pharmacological Properties

5.1Pharmacodynamic properties

Pharmacotherapeutic group: Solutions affecting the electrolyte balance; ATC code: B05BB02

Glukosel is a physiologically balanced parenteral nutrition solution with an all-round electrolyte composition. The glucose content in 1,000 ml of Glukosel corresponds to about half of the glucose requirement after elective surgery. As a rule, 1,000–2,500 ml is administered to meet the basic energy requirement. For total parenteral nutrition (TPN), up to 40 ml/kg is given to patients weighing 70 kg. The remaining amount is given as lipid emulsion. Normally, adults can utilise up to 0.5 g of glucose per kg bodyweight (BW) and hour.

The amount of electrolytes in the solution is the basis for nutrition programmes. Special emphasis has been placed on intracellular electrolytes potassium, magnesium and phosphate. For individual adaptation, more electrolytes should be supplied, preferably in the form of a supplemental infusion concentrate.

To ensure satisfactory exploitation of glucose, potassium, magnesium and phosphate must be administered. Phosphate requirement is about 20 mmol per day, although 30–40 mmol may be given per day to patients suffering from severe loss and receiving high glucose/insulin doses. It is particularly important that phosphate be administered to ensure normal erythrocyte function, energy metabolism and neuromuscular function. Potassium, magnesium and phosphate supply is a prerequisite for normal tissue formation. Zinc is necessary during short periods (1–2 weeks) of parenteral nutrition to ensure optimal exploitation of nitrogen and tissue regeneration. In patients on postoperative parenteral nutrition or with an intestinal disorder and after intestinal surgery, zinc requirement is increased with increased urine output in conjunction with infusion therapy and through intestinal loss. Zinc replacement requirement is also increased by blood loss and tissue formation.

5.2Pharmacokinetic properties

Distribution

During infusion, glucose is first distributed to the intravascular space and is then taken up into the intracellular space.

Biotransformation

In glycolysis, glucose is metabolised to pyruvate or lactate. Lactate can be partially reintroduced into the glucose metabolism (Cori cycle). In aerobic conditions, pyruvate is completely oxidised to carbonic acid and water. The end products of the complete oxidation of glucose are eliminated via the lungs (carbon dioxide) and the kidneys (water).

Elimination

In healthy persons, practically no glucose is excreted renally. In pathological metabolic conditions (e.g. diabetes mellitus, post-operative or post-traumatic disturbances in the exploitation of glucose) associated with hyperglycaemia, glucose is also excreted via the kidneys (glucosuria) as the maximum tubular re-absorption capacity is exceeded.

5.3Preclinical safety data

There are no preclinical data of relevance to the prescriber that are not already included in the other sections of this Summary of Product Characteristics.

6.Pharmaceutical Particulars

Hydrochloric acid, water for injections

6.1Incompatibilities

Only solutions and medicinal products known to be compatible with the product may be mixed.

Because of the risk for pseudoagglutination, this solution should not be administered through the same infusion line with blood. For the same reason, erythrocyte concentrates must not be suspended in this solution.

6.2Shelf life

Shelf life of unopened container: 3 years.

Shelf life after the first opening the container

The product should be administered immediately after connecting the container to the administration line.

Shelf life after reconstitution / dilution

Administration should be started immediately after the reconstitution of the product.

6.3Special precautions for storage

No special requirements.

For storage conditions after reconstitution, dilution and first opening of the medicinal product, see section 6.3

6.4Nature and contents of container

Polyethylene bottle (Ecoflac Plus).

Pack size: 10 x 1000 ml

6.5Special precautions for disposal and other handling

The solution is supplied in containers for single use. Any unused product or waste material should be disposed of in accordance with local requirements.

Only clear solutions in undamaged containers should be used.

7.MARKETING AUTHORISATION HOLDER

B. Braun Melsungen AG
Carl-Braun-Strasse 1

34212 Melsungen, Germany

Postal address
B. Braun Melsungen AG
34209 Melsungen, Germany.

8.MARKETING AUTHORISATION NUMBER(S)

[To be completed nationally]

9.DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: [To be completed nationally]

Date of latest renewal: [To be completed nationally]

10.Date of Revision of the Text

20 February 2015