Summary of medicine characteristics - GLUCOSE INTRAVENOUS INFUSION BP 30% W/V
1 NAME OF THE MEDICINAL PRODUCT
Glucose Intravenous Infusion BP 30% w/v
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
1000 ml of solution for infusion contain
Glucose monohydrate 330.0 g
(equivalent to glucose) (300.0 g)
For the full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Solution for infusion
Clear, colourless or slightly yellowish aqueous solution
Energy 5025 kJ/l = 1200 kcal/l
Theoretical osmolarity 1665 mOsm/l
Acidity (titration to pH 7.4) < 1 mmol/l
pH 3.5 – 5.5
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Administration of glucose for caloric support
Carbohydrate component in parenteral nutrition regimens
Therapy of hypoglycaemia
4.2 Posology and method of administration
Posology
The dosage of the solution depends on the patient’s individual glucose and fluid requirements.
Fluid balance, serum glucose, and other electrolytes may need to be monitored before and during administration, especially in patients with increased nonosmotic vasopressin release (syndrome of inappropriate antidiuretic hormone secretion, SIADH) and in patients co-medicated with vasopressin agonist drugs due to the risk of hyponatraemia.
Monitoring of serum sodium is particularly important for physiologically hypotonic fluids. Glucose Intravenous Infusion BP 30% w/v may become hypotonic after administration due to glucose metabolisation in the body (see sections 4.4. 4.5 and 4.8 Adults and adolescents from 15th year of life
The maximum daily dose is 20ml per kg body weight (BW) per day, corresponding to 6g of glucose per kg BW per day.
The maximum infusion rate is 0.83ml per kg BW per hour, corresponding to 0.25g of glucose per kg BW per hour.
Thus, for a patient weighing 70kg the maximum infusion rate is approximately 58ml per hour, resulting in a glucose intake of 17.5g per hour.
Children
10% glucose solution is recommended for hypoglycaemia in children.
Use of 30% glucose solution
If higher strength solutions are deemed essential, the dose and rate of delivery should be determines by specialist in paediatric medicine or other appropriate discipline (e.g. intensive care; Accident and Emergency; parenteral nutrition) and will depend on age weight, clinical and metabolic condition and concomitant therapy.
Monitoring
Careful monitoring is essential throughout treatment (see section 4.4 for details) and young children are particularly likely to develop hypoglycaemia if high glucose infusion rates are abruptly stopped (see below).
Elderly patients
Basically the same dosage as for adults applies, but caution should be exercised in patients suffering from further diseases such as cardiac insufficiency or renal insufficiency that increase in frequency with advancing age (see sections 4.3 and 4.4).
Patients with impaired glucose metabolism
If the oxidative metabolism of glucose is impaired (e.g. in the early postoperative or post-traumatic period or in the presence of hypoxia or organ failure), the dosage should be adjusted to keep the blood glucose level close to normal values. Close monitoring of blood glucose levels is recommended in order to prevent hyperglycaemia. Impaired oxidative metabolism of glucose may lead to metabolic acidosis.
Discontinuation of therapy
Sudden discontinuation of high glucose infusion rates can lead to profound hypoglycaemia due to the high serum insulin concentrations. This applies especially to children less than 2 years of age, patients with diabetes mellitus and other disease states associated with impaired glucose homeostasis. The glucose infusion should be tapered off over 30 – 60 minutes and as a precaution it is recommended that on the first day of abrupt discontinuation of parenteral nutrition every patient is monitored for hypoglycaemia for 30 minutes after the infusion is stopped.
Method of administration
For central intravenous infusion only.
This solution constitutes only one component of parenteral nutrition. In total parenteral nutrition, glucose infusions should always be combined with adequate supply of amino acids, lipids, electrolytes, vitamins and trace elements (see also section 4.4 – Parenteral nutrition).
In malnourished/depleted patients parenteral treatment should be instituted gradually (see section 4.4 – Parenteral nutrition).
4.3 Contraindications
Hyperglycaemia, not responding to insulin doses of up to 6 units insulin/hour
Delirium tremens if such patients are already dehydrated
Acute states of shock and collapse
Metabolic acidosis
Since the administration of glucose solutions is accompanied by the administration of free water, further contraindications may arise e.g.:
Hyperhydration
Pulmonary oedema
Acute congestive heart failure
4.4 Special warnings and precautions for use
General
Glucose Intravenous Infusion BP 30% w/v is a hypertonic solution. 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, 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 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.
Administration of glucose solutions is not recommended after acute ischaemic strokes as hyperglycaemia has been reported to worsen ischaemic brain damage and impair recovery.
Application of hyperosmolar glucose solutions in patients with damaged haematoencephalic barrier may lead to increase of intracranial/intraspinal pressure.
Glucose infusions should not be started before existing fluid and electrolyte deficiencies like hypotonic dehydration, hyponatraemia and hypokalaemia have adequately been corrected.
This solution should be used with caution in patients with
– Hypervolaemia
– Renal insufficiency
– Cardiac insufficiency
– Increased serum osmolarity
– Known subclinical diabetes mellitus or carbohydrate intolerance for any reason.
Unstable metabolism (e.g. postoperatively or after injuries, hypoxia, organ insufficiencies) impairs oxidative metabolism of glucose and may lead to metabolic acidosis.
States of hyperglycaemia should be adequately monitored and treated with insulin. The application of insulin causes additional shifts of potassium into the cells and may therefore cause or increase hypokalaemia.
Sudden discontinuation of high glucose infusion rates can lead to profound hypoglycaemia due to the accompanying high serum insulin concentrations. This applies especially to children less than 2 years of age, patients with diabetes mellitus and patients with other disease states associated with impaired glucose homeostasis. In obvious cases, the glucose infusion should be tapered off within the last 30 – 60 minutes of the infusion. As a precaution it is recommended that each individual patient be monitored for 30 minutes for hypoglycaemia on the first day of abrupt discontinuation of parenteral nutrition.
Clinical monitoring should include blood glucose, serum electrolytes, fluid and acidbase balance in general. A focus should be put on the sodium level as glucose solutions provide free water to the body and may therefore cause or worsen hyponatraemia. Frequency and kind of laboratory testing depend on the overall condition of the patient, the prevailing metabolic situation, the administered dose and the duration of treatment. Also monitor total volume and amount of glucose administered.
Parenteral nutrition in malnourished or depleted patients with full doses and full infusion rates from the very beginning and without adequate supplementation of potassium, magnesium and phosphate may lead to the refeeding syndrome, characterized by hypokalaemia, hypophosphataemia and hypomagnesaemia. Clinical manifestations may develop within a few days of starting parenteral nutrition. In such patients, infusion regimens should be built up gradually. Adequate supplementation of electrolytes according to deviations from normal values is necessary.
Special attention should be paid to hypokalaemia. Then, supplementation of potassium is mandatory.
Electrolytes and vitamins must be supplied as necessary. Vitamin B, especially thiamine, is needed for glucose metabolism.
Glucose infusions should not be administered through the same infusion equipment, simultaneously before, or after administration of blood, because of the possibility of pseudo-agglutination.
It should be noted that this solution constitutes only one component of parenteral nutrition. In total parenteral nutrition, glucose infusions should always be combined with an adequate supply of amino acids, lipids, electrolytes, vitamins and trace elements.
Paediatric population
For treatment of hypoglycaemia in children, use of 10% glucose solution is recommended.
Children in the 1st and 2nd year of life are especially at risk for rebound hypoglycaemia after abrupt discontinuation of high infusion rates, see above.
4.5 Interaction with other medicinal products and other forms of interaction
Interactions with medicinal products with an influence on glucose metabolism should be considered.
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.
4.6 Fertility, pregnancy and lactation
Pregnancy
There are no or limited data (less than 300 pregnancy outcomes) from the use of glucose monohydrate in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3).
The use of Glucose Intravenous Infusion BP 30% w/v may be considered during pregnancy, if clinically needed.
Glucose Intravenous Infusion BP 30% w/v 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 section 4.4, 4.5 and 4.8).
Careful monitoring of blood glucose is necessary.
Breast-feeding
Glucose/metabolites are excreted in human milk, but at therapeutic doses of Glucose Intravenous Infusion BP 30% w/v no effects on the breast-fed newborns/infants are anticipated. Glucose Intravenous Infusion BP 30% w/v can be used during breastfeeding as indicated.
Fertility
No special precautions.
4.7 Effects on ability to drive and use machines
The solution has no or negligible influence on the ability to drive and use machines.
4.8 Undesirable effects
General
Undesirable effects are listed according to their frequencies as follows:
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)
General disorders and administration site conditions:
Not known: Local reactions at the site of administration, including local pain, vein irritation, thrombophlebitis or tissue necrosis in case of extravasation.
Metabolism and nutrition disorders:
Not known: Hospital Acquired Hyponatraemia
Nervous system disorders:
Not known: Hyponatraemic encephalopathy
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 Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
4.9 Overdose
4.9 OverdoseSymptoms
Symptoms of glucose overdose
Excessive glucose infusions can cause hyperglycaemia, glucosuria, hyperosmolar dehydration and in extreme case overdose can lead up to hyperglycaemic-hyperosmolar coma. In cases of gross overdosing lipogenesis resulting in hepatic steatosis is possible.
Symptoms of fluid overdose
Fluid overdose may result in hyperhydration with increased skin tension, venous congestion, oedema – possibly also lung or brain oedema -, dilution of serum electrolytes, electrolyte imbalances, notably hyponatraemia and hypokalaemia (see section 4.4), and acid-base imbalances.
Clinical symptoms of water intoxication may occur like nausea, vomiting and spasms.
Treatment
The primary therapeutic measure is dose reduction or cessation of infusion, depending on the severity of the symptoms. Disorders of the carbohydrate and electrolyte metabolism are treated by insulin administration and appropriate electrolyte substitution, respectively.
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Solutions for parenteral nutrition, carbohydrates
ATC code: B05B A03
Pharmacodynamic effects
Glucose is metabolized ubiquitously as the natural substrate of the cells of the body. Under physiological conditions glucose is the most important energy-supplying carbohydrate with a caloric value of approx. 16.7 kJ/g or 4 kcal/g. In adults, the normal concentration of glucose in blood is reported to be 70 – 100 mg/dl or 3.9 to 5.6 mmol/l (fasting).
5.2
Absorption
Since the solution is administered intravenously, its bioavailability is 100%.
Distribution
After infusion glucose is first distributed in the intravascular space andthen is taken up into the intracellular space.
Biotransformation
In glycolysis, glucose is metabolized to pyruvate. Under aerobic conditions pyruvate is completely oxidized to carbon dioxide and water. In case of hypoxia pyruvate is converted to lactate. Lactate can be partially re-introduced into the glucose metabolism (Cori cycle).
Glucose utilisation disturbances (glucose intolerance) can occur under conditions of pathological metabolism. These mainly include diabetes mellitus and states of metabolic stress (e.g. intra-, and postoperatively, severe disease, injury), hormonally mediated depression of glucose tolerance, which can even lead to hyperglycaemia without exogenous supply of the substrate. Hyperglycaemia can – depending on its severity – lead to osmotically mediated renal fluid losses with consecutive hypertonic dehydration, to hyperosmotic disorders up to and including hyperosmotic coma.
Metabolism of glucose and electrolytes are closely related to each other. Insulin facilitates potassium influx into cells. Phosphate and magnesium are involved in the enzymatic reactions associated with glucose utilization. Potassium, phosphate and magnesium requirements may therefore increase following glucose administration and may therefore have to be monitored and supplemented according to individual needs. Especially cardiac and neurological functions may be impaired without supplementation.
Elimination
The final products of the complete oxidation of glucose are eliminated via the lungs (carbon dioxide) and the kidneys (water).
Practically no glucose is excreted renally by healthy persons. In pathological metabolic conditions associated with hyperglycaemia (e.g. diabetes mellitus, postaggression metabolism), glucose is also excreted via the kidneys (glucosuria) when the maximum tubular re-absorption capacity is exceeded (at blood glucose levels higher than 160–180 mg/dl or 8.8–9.9 mmol/l).
5.3 Preclinical safety data
5.3 Preclinical safety dataNon-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction and development.
6.1 List of excipients
Water for injections
Hydrochloric acid (for pH adjustment)
6.2 Incompatibilities
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
Erythrocyte concentrates must not be suspended in glucose solutions because of the risk of pseudo-agglutination. See also section 4.4.
6.3
Unopened
3 years
After first opening the container
Not applicable, see section 6.6.
After reconstitution or dilution
From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C, unless admixing has taken place in controlled and validated aseptic conditions.
Observe the directions given by the manufacturer of the respective additive or drug to be diluted.
6.4 Special precautions for storage
This medicinal product does not require any special storage conditions.
For storage conditions after dilution of the medicinal product, see section 6.3.
6.5 Nature and contents of container
Bottles of colourless low-density polyethylene
contents: 500ml
available in packs of: 10 × 500ml
6.6 Special precautions for disposal
6.6 Special precautions for disposalAny unused medicinal product or waste material should be disposed of in accordance with local requirements.
Containers are for single use only. Discard containers and any unused content after use.
Do not re-connect partially used containers.
Only to be used if the solution is clear and colourless or slightly yellowish and if the bottle and its closure are undamaged.
Administration should commence immediately after connecting the container to the giving set or infusion equipment.
Before addition of an additive or preparing a nutrient mixture, physical and chemical compatibility must be confirmed. Because glucose solutions have an acidic pH, incompatibilities can occur on mixing with other medicinal products. Information on compatibility can be requested from the manufacturer of the added drug.
When adding additives observe usual precautions of asepsis strictly
7 MARKETING AUTHORISATION HOLDER
B. Braun Melsungen AG
Carl-Braun-Strasse 1
D-34212 Melsungen, Germany
Postal address:
34209 Melsungen, Germany
Telephone: +49 5661 71 0
Telefax: +49 5661 71 4567