SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Potassium Chloride 0.3%w/v Glucose 5%w/v Solution for Infusion

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Active component	Per 500 ml	Per 1000 ml
Potassium chloride	15 g	3.0 g
	K+ 20 mmol	K+ 40 mmol
	Cl" 20 mmol	Cl" 40 mmol
Glucose	equivalent to 25.0 g	equivalent to 50.0 g
monohydrate	anhydrous glucose	anhydrous glucose
	139 mmol	278 mmol

Osmolality approx. 370 mOsm/kg H₂O.

For a full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Solution for infusion (Intravenous Infusion)

Colourless to faintly straw-coloured solution without visible particles in bags, individually overwrapped. pH 3.5 - 6.5

4 CLINICAL PARTICULARS

4.1    Therapeutic indications

For prevention and treatment of potassium depletion and/or hypokalaemia in cases where supply of water and carbohydrates is required due to restriction of intake of fluids and electrolytes by normal routes.

4.2    Posology and method of administration

For intravenous infusion under medical supervision.

Single use only.

The pathophysiological response to dehydration, to electrolyte loss and to potassium chloride and glucose infusion will vary with the age of the patient being treated and this should be taken into account during rehydration therapy.

The volume of solution needed to replenish deficits varies with hydration state, age, body weight, complementary treatment and clinical and biochemical status.

Doses may be expressed in terms of mEq or mmol of potassium, mass of potassium or mass of potassium salt:

1 g KCl = 525 mg of K+ or 13.4 mEq or 13.4 mmol of K+ and Cl^-1 mmol K+ = 39.1 mg K+

Posology

Adults:

500ml to 3000ml/24h

Paediatric population:

0 - 10kg body weight: 100ml/kg/24h

10 - 20kg body weight: 1000ml + (50ml/kg over 10kg)/24h

> 20kg body weight: 1500ml + (20ml/kg over 20kg)/24h

The infusion rate should not exceed the patient’s glucose oxidation capacities in order to avoid hyperglycaemia. Therefore the maximum dose ranges from 5mg/kg/min for adults to 10-18 mg/kg/min for babies and children depending on age and total body mass.

Posology for prevention and treatment ofpotassium depletion

Typical doses of potassium for the prevention of hypokalaemia and treatment of mild potassium deficiency may be up to 50mmoles per day. The recommended maximal dose of potassium is 2-3mmol/kg/24h.

When used for the treatment of hypokalaemia, the recommended dosage is 20 mmoles of potassium over 2 to 3 hours (i.e. 7-10 mmol/h) under ECG control.

Patients with renal impairment should receive lower doses.

Method of Administration

Route of administration

The administration is performed by intravenous route using sterile and non-pyrogenic equipment. Intravenous potassium should be administered in a large peripheral or central vein to diminish the risk of causing sclerosis. If infused through a central vein, to avoid localised hyperkalaemia the catheter must not be in the atrium or ventricle.

Rate of administration

The rate of administration of potassium containing solutions should not exceed 15 to 20 mmoles/h to avoid dangerous hyperkalaemia. Rapid infusion may be harmful. Infusion rates greater than 500ml over three hours should be controlled by infusion pump.

Monitoring

Adequate urine flow must be ensured and careful monitoring of plasma-potassium and other electrolyte concentrations is essential. Higher dosage or high speed infusion must be performed under ECG control. Repeated 500ml doses must be monitored by repeated plasma potassium levels.

4.3 Contraindications

Severe impairment of renal function or hyperkalaemia such as is associated with adrenal insufficiency. Hyperchloraemia, uncompensated cardiac failure, uncompensated diabetes, other known glucose intolerances (such as metabolic stress situations, thionine (Vit B1) deficiency), hyperosmolar coma, hyperglycaemia, hyperlactatemia. Conditions of water excess.

Administration of glucose-containing solutions may lead to hyperglycaemia. Infusion of solutions containing glucose are contraindicated after acute ischaemic strokes as hyperglycaemia has been implicated in increasing cerebral ischaemic brain damage and impairing recovery, and in the first

24hours following head trauma.

4.4 Special warnings and precautions for use

Potassium Chloride 0.3%w/v Glucose 5%w/v Solution for Infusion is a hypertonic solution, with an approximate osmolarity of 370mOsmol/kg H2O.

The solution must be administered with caution to patients with conditions associated with high potassium levels, cardio-pulmonary disease, oedema, acute dehydration, acute acidosis and cell destruction as in tissue trauma, burns, haemolysis, rhabdomyolysis, renal dysfunction, digitilisation or hepatic insufficiency.

Use with caution in diabetic patients: blood and urine glucose levels must be monitored and insulin requirements may be modified.

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).

Fluid replacement therapy should be administered with caution to very young and elderly patients who have reduced capacity to compensate for fluctuations in fluid and electrolyte balance.

Administration should be carried out under regular and careful surveillance. Regular monitoring of clinical status, plasma potassium, blood and urinary glucose level, serum and/or urinary electrolytes, plasma creatinine levels, BUN level, acid-base balance and ECG is essential in patients receiving potassium therapy, particularly those with cardiac or renal impairment. Plasma electrolyte concentrations should be carefully monitored especially in patients with pre-existing imbalances or conditions predisposing to hyperkalaemia, such as renal or adrenal insufficiency.

High volume infusion must be used under specific monitoring in patients with cardiac or pulmonary failure.

Adequate urine flow must be ensured and fluid balance should be monitored.

Administration of potassium chloride in glucose solutions may lower the level of serum potassium attained. Blood glucose concentration should be closely monitored during intracranial hypertension episodes.

If hyperglycaemia occurs, the rate of infusion should be adjusted or insulin administered.

During long-term treatment, a convenient nutritive treatment supply must be given to the patient.

4.5 Interaction with other medicinal products and other forms of interaction

Care should be taken in the concurrent use of drugs containing potassium, potassiumsparing diuretics such as spironolactone and triamterene, and drugs which have the potential for inducing hyperkalaemia, ACE inhibitors, angiotensin II receptor antagonists, tacrolimus and cyclosporine.

Check compatibility of medicinal products with the solution before admixture and administration.

4.6    Pregnancy and lactation

Administration of intravenous fluids to pregnant and lactating women requires special consideration of the consequences of possible unwanted effects in relation to the desired therapeutic objective.

It has been suggested that if used during labour the glucose load on the mother may lead to foetal hyperglycaemia, hyperinsulinaemia, and acidosis, with subsequent neonatal hypoglycaemia and jaundice. Others have found no evidence of such an effect.

Hyperkalaemic and hypokalaemic serum levels lead to impaired cardiac function of the maternal and foetal hearts. Therefore, maternal electrolyte levels must be controlled regularly. As long as the maternal electrolyte serum levels are kept within the physiological range, there are no potential concerns regarding administration of Potassium Chloride 0.3%w/v Glucose 5%w/v Solution for Infusion during pregnancy and lactation.

4.7    Effects on ability to drive and use machines

Not applicable

4.8    Undesirable effects

Prolonged intravenous infusion may lead to venous irritation and thrombophlebitis at the infusion site.

Adverse reactions may be associated with the technique of administration and include febrile response, infection at the site of injection, local pain or reaction, vein irritation, venous thrombosis or phlebitis extending from the site of injection, extravasation and hypervolemia.

Discontinue infusion if adverse reaction occurs.

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:

For United Kingdom Yellow Card Scheme

Website: www.mhra.gov .uk/yellowcard

For Ireland

HPRA Pharmacovigilance

Earlsfort Terrace IRL - Dublin 2 Tel: +353 1 6764971 Fax: +353 1 6762517 Website: www.hpra.ie E-mail: medsafetv@,hpra.ie

4.9 Overdose

Excessive or rapid administration of potassium-containing solutions may cause hyperkalaemia with hypotension, cardiac arrhythmias, heart block, ECG abnormalities and cardiac arrest, mental confusion, and neuromuscular dysfunction such as muscle weakness, paraesthesia of the extremities and paralysis.

ECG changes are important indicators of potassium toxicity, including tall, peaked T-waves, depression of S-T segment, disappearance of the P-wave, prolongation of the Q-T interval, and widening and slurring of the QRS complex.

Excessive administration of chloride salts may cause a loss of bicarbonate with an acidifying effect.

In the event of accidental over infusion, treatment should be discontinued.

Treatment depends on the individual clinical situation but involves administration of calcium to counteract the effects of hyperkalaemia on cardiac excitability, the use of agents such as insulin or sodium bicarbonate to promote cellular uptake of potassium, and enhanced potassium excretion with exchange resins or dialysis. Administration of excessive amounts of 5% glucose may result in hyperglycaemia. Treatment is symptomatic.

5    PHARMACOLOGICAL PROPERTIES

5.1    Pharmacodynamic properties

Pharmacotherapeutic group (ATC code): “electrolytes with carbohydrates” (B05BB02).

Potassium Chloride 0.3%w/v Glucose 5%w/v Solution for Infusion is a hypertonic solution, with an approximate osmolarity of 370 mOsmol/l.

The pharmacodynamic properties of this solution are those of its components (potassium, chloride and glucose). Potassium is predominantly an intracellular cation, primarily found in muscle; only about 2% is present in the extracellular fluid. It is essential for numerous metabolic and physiological processes including nerve conduction, muscle contraction, and acid-base regulation.

Chloride is mainly an extracellular anion. Intracellular chloride is in high concentration in red blood cells and gastric mucosa.

Glucose is the principal source of energy in cellular metabolism.

5.2 Pharmacokinetic properties

The pharmacokinetic properties of this solution are those of its components (potassium, chloride and glucose).

Intravenous administration of the solution provides an immediate supply of electrolytes and glucose to blood. Factors influencing potassium transfer between intracellular and extracellular fluid such as acid base disturbances can distort the relationship between plasma concentrations and total body stores. Potassium is excreted mainly by the kidneys; it is secreted in the distal tubules in exchange for sodium or hydrogen ions. The capacity of the kidneys to conserve potassium is poor and some urinary excretion of potassium continues even when there is severe depletion. Some potassium is excreted in the faeces and small amounts may also be excreted in sweat. The two main metabolic pathways of glucose are gluconeogenesis (energy storage) and glycogenolysis (energy release). Glucose metabolism is regulated by insulin.

5.3    Preclinical safety data

Preclinical safety data of Potassium Chloride 0.3%w/v Glucose 5%w/v Solution for Infusion in animals are not relevant since potassium chloride and glucose are physiological components of the body. Toxic effects are not to be expected if serum electrolytes are kept within    physiological range.

6    PHARMACEUTICAL    PARTICULARS

6.1    List of excipients

Water for Injections in bulk.

6.2 Incompatibilities

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

6.3    Shelf life

2 years

Use immediately on removal from overwrap.

6.4    Special precautions for storage

Do not store above 25^oC. Do not freeze. Store in the original outer container (overwrap) to prevent moisture loss to the air.

6.5    Nature and contents of container

Flexible Macoflex PVC bags containing 500ml or 1000ml solution, individually overwrapped in transparent polypropylene laminate.

Not all pack sizes may be marketed

6.6 Special precautions for disposal and other handling

Do not use unless the solution is clear and the container undamaged.

Discard any unused solution. For single use only.

The space between the bag and the overwrap is not guaranteed sterile.

Before use, remove the bag from the plastic overwrapping. Remove the twist-off protector of the infusion site and connect by clamping to the administration set.

Addition of medicinal products: Confirm additive compatibility before addition through the injection port. Clean the injection site using antiseptic solution. Carefully introduce the sterile needle into the sterile chamber in the injection site, attach the needle to the container with the medicinal product, introduce the needle through the second membrane into the bag and inject the medicine. Carefully withdraw the needle. Mix aseptically and thoroughly with the solution. Use immediately.

7 MARKETING AUTHORISATION HOLDER

MACO PHARMA (UK) LTD 8^th Floor - Regal House 70 London Road Twickenham Middlesex TW1 3QS United Kingdom