4.1. Therapeutic indications

– Energy supply;

– Vehicle solution for supplementary medication.

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 non-osmotic 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. 10% w/v Glucose Intravenous Infusion BP may become hypotonic after administration due to glucose metabolisation in the body (see sections 4.4. 4.5 and 4.8).

Vehicle solution for compatible medicinal products

The dose and infusion rate are determined by the characteristics of the added medicinal product. However, the maximum daily dose and the maximum infusion volume/rate specified in section 4.2 must not be exceeded.

Glucose for caloric support / component of parenteral nutrition

Maximum infusion rate

Adults and adolescents from 15th year of life

The maximum rate of 0.25 g of glucose per kg bodyweight per hour (4 mg glucose/kg/min) should not be exceeded in order to avoid exceeding the glucose oxidation capacity of the patient.

Paediatric population

Recommended parenteral glucose supply in (pre)term newborns in mg/kg per min (g/kg per day)

Day 1

mg/kg per min (g/kg per day)

Day 2 onwards

mg/kg per min (g/kg per day)

Preterm newborns

4-8 (5.8-11.5)

Target 8-10 (11.5-14.4)

Min 4 (5.8); max 12 (17.3)

Term newborns

2.5-5 (3.6-7.2)

Target 5-10 (7.2-14.4)

Min 2.5 (3.6); max 12 (17.3)

Recommended parenteral glucose supply in infants and children according to body weight and phase of illness (units are mg/kg/min (g/kg per day))

Acute Phase

Stable Phase

Recovery phase

28 d - 10 kg

2-4 (2.9-5.8)

4-6 (5.8-8.6)

6-10 (8.6-14)

11-30 kg

1.5-2.5 (2.2-3.6)

2-4 (2.8-5.8)

3-6 (4.3-8.6)

31-45 kg

1-1.5 (1.4-2.2)

1.5-3 (2.2-4.3)

3-4 (4.3-5.8)

>45 kg

0.5-1 (0.7-1.4)

1-2(1.4-2.9)

2-3 (2.9-4.3)

Acute phase = resuscitation phase when the patient requires vital organ support (sedation, mechanical ventilation, vasopressors, fluid resuscitation).

Stable phase = patient is stable on, or can be weaned, from this vital support.

Recovery phase = patient who is mobilizing.

Elderly patients

Basically, the same dosage as for adults applies, but caution should be exercised in patients suffering from further diseases like cardiac insufficiency or renal insufficiency that may frequently be associated with advanced age.

Patients with impaired glucose metabolism

If the oxidative metabolism of glucose is impaired (e.g. in the early post-operative 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.

Method of administration

Intravenous use. The solution can be infused via a large peripheral vein.

If 10 % w/v Glucose Intravenous Infusion is used as vehicle solution the possibility of peripheral infusion depends on the characteristics of the mixture prepared.

4.3. Contraindications

- Hypersensitivity to the active substance. See section 4.4 and 4.8 for corn allergies

- 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

Special Warnings

10% w/v Glucose Intravenous Infusion BP 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.

Due to the risk of developing a severe lactic acidosis and/or a Wernicke encephalopathy a preexisting thiamine (Vitamin B1) deficiency must be corrected before infusion of glucose containing solutions.

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.

Administration of glucose solutions is not recommended after acute ischaemic strokes as hyperglycaemia was 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 adequetely 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 acid-base 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.

Hypersensitivity reactions, including anaphylactic/anaphylactoid reactions, have been reported with Glucose solutions (see section 4.8). Solutions containing glucose should therefore be used with caution, if at all, in patients with known allergy to corn or corn products (see section 4.3).

The infusion must be stopped immediately if any signs or symptoms of a suspected hypersensitivity reaction develop. Appropriate therapeutic countermeasures must be instituted as clinically indicated.

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.

If signs of vein irritation, phlebitis or thrombophlebitis appear during peripheral venous infusion, change of the infusion site should be considered.

Please note: If this solution is used as vehicle solution, the safety information of the additive provided by the respective manufacturer have to be taken into account.

Paediatric population

Newborns, especially preterm neonates with low birth weight, are especially at risk of hyperglycaemia or hypoglycaemia. Close monitoring of the blood glucose level is mandatory to avoid longterm adverse events or fatal overdosage.

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.

Prescribers should refer to the information provided with the product concerned.

4.6. Fertility, pregnancy and lactation

Pregnancy

There are no or limited data from the use of glucose solutions 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 10% w/v Glucose Intravenous Infusion BP may be considered during pregnancy, if clinically needed.

Nevertheless, an intrapartum infusion of glucose solution may predispose the infant to an in-creased risk of hypoglycaemia at 2 h of age. Therefore, it is recommended that during intrapartum glucose administration the blood glucose levels of the mothers should be monitored closely and kept in physiological limits to prevent maternal and foetal hyperglycaemia and subsequent risk of neonatal hypoglycaemia.

10% w/v Glucose Intravenous Infusion BP 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 10% w/v Glucose Intravenous Infusion BP no effects on the breastfed newborns/infants are anticipated.

10% w/v Glucose Intravenous Infusion BP can be used during breast-feeding 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

Common

Uncommon

Rare

Very rare

Not known

(≥ 1/10)

(≥ 1/100 to < 1/10)

(≥ 1/1000 to < 1/100)

(≥ 1/10000 to < 1/1000)

(< 1/10000)

(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*

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

Neurological disorders:

Not known: Hyponatraemic encephalopathy

– Hypokalemia may be related to insulin therapy. In addition, hypokalaemia, hypomagnesaemia and hypophosphataemia may be caused by refeeding with glucose especially in malnourished patients.

– Abrupt discontinuation and/or insulin application may cause rebound hypoglycemia, especially in patients with glucose tolerance disorders.

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

Symptoms of glucose overdose

Excessive glucose infusions can cause hyperglycaemia, glucosuria, hyperosmolar dehydration and in extreme case overdose can lead to hyperglycaemic-hyperosmolar coma.

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.

Further symptoms of overdose may arise depending on the nature of the additive.

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.