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PHARMACOLOGICAL PROPERTIES 

Pharmacotherapeutic group “Electrolytes with Carbohydrates”, 

Sodium Chloride 0.18% w/v and Glucose 4.3% w/v is an isotonic and hyperosmolar solution of sodium chloride  and glucose. 

The pharmacodynamic properties of this solution are those of its components (glucose, sodium and chloride). Ions, such as sodium, circulate through the cell membrane, using various mechanisms of transport, among which  is the sodium pump (Na+/K+-ATPase). Sodium plays an important role in neurotransmission and cardiac  electrophysiology, and also in renal metabolism. 

Chloride is mainly an extracellular anion. Intracellular chloride is in high concentration in red blood cells and  gastric mucosa. Reabsorption of chloride follows reabsorption of sodium. 

Glucose is the principal source of energy in cellular metabolism. The glucose in this solution provides a caloric  intake of 200kcal/l. 

Pharmacokinetic properties 

The pharmacokinetic properties of this solution are those of its components (glucose, sodium and chloride). After injection of radiosodium (24Na), the half-life is 11 to 13 days for 99% of the injected Na and one year for  the remaining 1%. The distribution varies according to tissues: it is fast in muscles, liver, kidney, cartilage and  skin; it is slow in erythrocytes and neurones; it is very slow in the bone. Sodium is predominantly excreted by the  kidneys, but (as described earlier) there is extensive renal reabsorption. Small amounts of sodium are lost in the  faeces and sweat. 

The two main metabolic pathways of glucose are gluconeogenesis (energy storage) and glycogenolysis (energy  release). Glucose metabolism is regulated by insulin. 

Preclinical safety data 

Preclinical safety data of this solution for infusion in animals are not relevant since its constituents are  physiological components of animal and human plasma. 

Toxic effects are not to be expected under the condition of clinical application. 

The safety of potential additives should be considered separately. 

INDICATIONS 

– Treatment of sodium depletion, extracellular dehydration or hypovolaemia in cases where supply of water and  carbohydrates is required due to restriction of the intake of fluids and electrolytes by normal routes. 

METHOD OF ADMINISTRATION 

The choice of the specific sodium chloride and glucose concentration, dosage, volume, rate and duration of  administration depends on the age, weight, clinical condition of the patient and concomitant therapy. It should be  determined by a physician. For patients with electrolyte and glucose abnormalities and for paediatric patients,  consult a physician experienced in intravenous fluid therapy. Rapid correction of hyponatraemia and  hypernatraemia is potentially dangerous (risk of serious neurologic complications). 

Adults, older patients and adolescents (age 12 years and over):

The recommended dosage is: 500 ml to 3 L/24h 

Administration rate: 

The infusion rate is usually 40 ml/kg/24h and should not exceed the patient’s glucose oxidation capacities in order  to avoid hyperglycaemia. Therefore the maximum acute administration rate is 5 mg/kg/min. Paediatric population 

The dosage varies with weight: 

• 0-10 kg body weight: • 10-20 kg body weight: • > 20 kg body weight: 

100 ml / kg / 24 h 

1000 ml + (50 ml/ kg over 10 kg) / 24h 1500 ml + (20 ml/ kg over 20 kg) / 24h. 

The administration rate varies with weight: 

• 0-10 kg body weight: • 10-20 kg body weight: • > 20 kg body weight: 

6-8 ml/kg/h 4-6 ml/kg/h 2-4 ml/kg/h 

The infusion rate should not exceed the patient’s glucose oxidation capacities in order to avoid hyperglycaemia.  Therefore the maximum acute administration rate is 10-18 mg/kg/min depending on the total body mass. For all patients, a gradual increase of flow rate should be considered when starting administration of glucose  containing products. 

Method of administration 

The administration is performed by intravenous infusion. 

Sodium chloride 0.18% w/v and Glucose 4.3% w/v solution is isotonic and hyperosmolar, due to the glucose  content. It has an approximate osmolarity of 540 mOsmol/l. 

CONTRAINICATIONS 

The solution is contraindicated in patients presenting with: 

• Known hypersensitivity to the product 
• Extracellular hyperhydration or hypervolaemia 
• Fluid and sodium retention 
• Severe renal insufficiency (with oliguria/anuria) 
• Uncompensated cardiac failure 
• Hypernatraemia or hyperchloraemia 
• General oedema and ascitic cirrhosis 

Clinically significant hyperglycaemia. The solution is also contraindicated in case of uncompensated diabetes,  other known glucose intolerances (such as metabolic stress situations), hyperosmolar coma or hyperlactataemia. 

WARNINGS & PRECAUTIONS  

Hypokalemia 

The infusion of Sodium chloride 0.9% w/v and Glucose 4.3% w/v solution may result in hypokalaemia. Close  clinical monitoring may be warranted in patients with or at risk for hypokalaemia, for example: • Persons with metabolic alkalosis 

• Persons with thyrotoxic periodic paralysis. Administration of intravenous 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 agonists or insulin) Sodium retention, fluid overload and oedema 

Sodium chloride 0.9% w/v and Glucose 4.3% w/v solution should be used with particular caution in • Patients with metabolic acidosis 

• Patients at risk of Hypernatraemia, Hyperchloraemia, Hypervolaemia 
• Patients with conditions that may cause sodium retention, fluid overload and oedema (central and peripheral), such as;  
• Primary hyperaldosteronism, 
• Secondary hyperaldosteronism associated with, for example, 
• hypertension,
• congestive heart failure, 
• liver disease (including cirrhosis), 
• renal disease (including renal artery stenosis, nephrosclerosis) 
• Pre-eclampsia. 

Patients taking medications that may increase the risk of sodium and fluid retention, such as corticosteroids Hyperosmolality, serum electrolytes and water imbalance 

Depending on the volume, rate of infusion, the patient’s underlying clinical condition and capability to metabolize  glucose, administration of Sodium chloride 0.9% w/v and Glucose 4.3% w/v solution can cause: • Hyperosmolality, osmotic diuresis and dehydration 

• Electrolyte disturbances such as 
• hyponatraemia  
• hypokalaemia  
• hypophosphataemia, 
• hypomagnesaemia, 
• Acid-base imbalance 
• Overhydration/hypervolaemia and, for example, congested states, including central (e.g. pulmonary congestion) and peripheral oedema. 
• An increase in serum glucose concentration is associated with an increase in serum osmolality. Osmotic diuresis associated with hyperglycaemia can result in or contribute to the development of dehydration and in electrolyte losses. 

Sodium imbalance 

Sodium chloride 0.9% w/v and Glucose 4.3% w/v solution should be used with particular caution in patients with;  or at risk for hyponatraemia, for example: 

• Children 
• Elderly patients 
• Women 
• Postoperatively 
• Persons with psychogenic polydipsia 

Hyponatraemia can lead to headache, nausea, seizures, lethargy, coma, cerebral oedema, and death. Acute  symptomatic hyponatraemic encephalopathy is considered a medical emergency. 

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 glucose solutions may produce substantial hyperglycaemia and hyperosmolar syndrome.  In order to avoid hyperglycaemia the infusion rate should not exceed the patient’s ability to utilize 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 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. 
• 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 glucose and/or free water load Other groups of patients in whom Sodium chloride 0.9% w/v and Glucose 4.3% 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 glucose and associated hyperglycaemia may result in decreased rates of  glucose-stimulated insulin secretion. 

Hypersensitivity Reactions 

• Hypersensitivity/infusion reactions, including anaphylaxis, have been reported. 
• Stop the infusion immediately if signs or symptoms of hypersensitivity/infusion reactions develop. Appropriate therapeutic countermeasures must be instituted as clinically indicated. 

Solutions containing glucose should be used with caution in patients with known allergy to corn or corn products

Refeeding syndrome 

Refeeding severely undernourished 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 

Sodium chloride 0.9% w/v and Glucose 4.3% 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 depends 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 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 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 hemorrhage, 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. 

• Hyponatraemia can lead to headache, nausea, seizures, lethargy, coma, cerebral oedema 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 

Sodium chloride 0.9% w/v and Glucose 4.3% 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 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. 

SIDE EFFECTS  

Frequencies cannot be estimated from the available data, as all listed adverse reactions are based on spontaneous  reporting. 

System Organ Class	Adverse reactions  (Preferred terms)	Frequency
Immune system disorders	anaphylactic reaction, *  hypersensitivity*	Not known
Metabolism and nutrition disorders	hypernatraemia,  hyperglycaemia,	Not known
Vascular disorders	phlebitis	Not known
Skin and subcutaneous tissue disorders	rash, pruritus	Not known
General disorders and administration site conditions	injection site reactions including: pyrexia  chills  infusion site pain  infusion site vesicles	Not known

 

Other adverse reactions reported with isotonic saline and glucose infusions include: 

• Hyponatraemia, which may be symptomatic 
• Hyperchloraemic acidosis

OVERDOSEAGE 

Excess administration of Sodium chloride 0.9% w/v and Glucose 4.3% w/v solution can cause: • Hyperglycaemia, adverse effects on water and electrolyte balance and corresponding complications. For  example, severe hyperglycaemia and severe dilutional hyponatraemia and their complications, can be fatal. • Hyponatraemia (which can lead to CNS manifestations, including seizures, coma, cerebral oedema and death). • Hypernatraemia especially in patients with renal impairment. 

• Fluid overload (which can lead to central and/or peripheral oedema). 

A clinically significant overdose of Sodium chloride 0.9% w/v and Glucose 4.3% w/v solution may, therefore,  constitute a medical emergency 

When assessing an overdose, any additives in the solution must also be considered. 

Interventions include discontinuation of Sodium chloride 0.9% w/v and Glucose 4.3% w/v solution  administration, dose reduction, administration of insulin and other measures as indicated for the specific clinical  constellation. 

DRUG INTERACTIONS 

Both the glycaemic and effects on water and electrolyte balance should be taken into account when administering  Sodium chloride 0.9% w/v and Glucose 4.3% w/v solution to patients treated with other substances that affect  glycaemic control, or fluid and/or electrolyte balance. 

Caution is advised in patients treated with 

• Lithium. Renal sodium and lithium clearance may be increased during administration and can result in decreased lithium levels. 
• Corticosteroids, which are associated with the retention of sodium and water (with oedema and hypertension). • Diuretics, beta-2 agonists or insulin, whom increase the risk of hypokalemia 

As guidance, the following medications are incompatible with the Sodium Chloride 0.9 % w/v & Glucose 4.3%  w/v solution (non-exhaustive listing): 

– Ampicillin sodium 

– Mitomycin 

– Amphotericin B 

– Erythromycin lactobionate 

Those additives known to be incompatible should not be used. 

Because of the presence of glucose, Sodium chloride 0.9% w/v and Glucose 4.3% w/v solution should not be  administered simultaneously with blood through the same administration set because of the possibility of  pseudoagglutination or haemolysis 

PREGNANCY AND LACTATION 

Pregnancy 

Intrapartum maternal intravenous glucose infusion may result in foetal hyperglycaemia and metabolic acidosis as  well as rebound neonatal hypoglycaemia due to foetal insulin production. 

Lactation 

Sodium chloride 0.9% w/v and Glucose 4.3% w/v solution can be used during breast-feeding. The potential risks and benefits for each specific patient should be carefully considered before administration. 

RECOMMENDED STORAGE 

Store in a cool place protected from light. Do not freeze. The overlap is a protective barrier. Do not remove the  container from overwrap until ready to use. Do not use if overwrap has been previously opened or damaged.