POTASSIUM CHLORIDE 0.15% SODIUM CHLORIDE 0.9% INTRAVENOUS IN - summary of medicine characteristics

1 NAME OF THE MEDICINAL PRODUCT

Potassium Chloride 0.15%w/v Sodium Chloride 0.9%w/v Solution for Infusion

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Osmolality approx. 322 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 prophylactic and replacement therapy requiring the use of sodium chloride and potassium.

4.2 Posology and method of administration

For intravenous infusion under medical supervision.

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

Posology for prevention and treatment of potassium depletion

Typical doses of potassium for the prevention of hypokalaemia and treatment of mild potassium deficiency may be up to 50mmoles per day. In severe hypokalaemia the recommended dosage is 20mmol potassium over 2 to 3 hours (i.e. 7–10 mmol/h) with ECG monitoring, but the dose and rate of administration are subject to clinical and laboratory assessment in each case.

The recommended maximal dose of potassium is 2–3mmol/kg/24h.

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.

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.

Fluid balance, serum electrolytes and acid-base balance may need to be monitored before and during administration, with particular attention to serum sodium 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 hospital acquired hyponatraemia (see sections 4.4, 4.5 and 4.8).

Monitoring of serum sodium is particularly important for hypotonic fluids.

Potassium Chloride 0.15%w/v Sodium Chloride 0.9%w/v Solution for Infusion tonicity: slightly hypertonic.

The infusion rate and volume depend on the age, weight, clinical condition (e.g. burns, surgery, head-injury, infections), and concomitant therapy should be determined by the consulting physician experienced in paediatric intravenous fluid therapy (see sections 4.4. and 4.8).

4.3 Contraindications

Hyperkalaemia such as is associated with severe renal insufficiency or adrenocortical insufficiency.

Hyperchloraemia. Patients with fluid and sodium retention, congestive heart failure, or severely impaired renal function.

4.4 Special warnings and precautions for use

Potassium Chloride 0.15%w/v Sodium Chloride 0.9%w/v Solution for Infusion is a hypertonic solution, with an approximate osmolarity of 322mOsm/l.

Potassium replacement must be used with caution to patients with conditions associated with high potassium levels including cardiac disease, oedema, renal dysfunction, hepatic insufficiency or digitilisation, acute dehydration, acute acidosis, extensive tissue destruction as occurs with tissue trauma and severe burns, haemolysis, rhabdomyolysis or hepatic insufficiency.

Sodium salts should be administered with caution to patients with hypertension.

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, 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.

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

High volume infusion must be used under specific monitoring in patients with cardiac or pulmonary failure, and in patients with non-osmotic vasopressin release (including SIADH), due to the risk of hospital-acquired hyponatraemia (see below).

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 (cerebral oedema) characterized by headache, nausea, seizures, lethargy and vomiting. Patients with cerebral 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, cerebral contusion and brain oedema) are at particular risk of the severe and life-threatening brain swelling caused by acute hyponatraemia.

4.5 Interaction with other medicinal products and other forms of interaction

Drugs leading to an increased vasopressin effect

The below listed drugs increase the vasopressin effect, leading to reduced renal electrolyte free water excretion and may 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 include:

Chlorpropamide, clofibrate, carbamazepine, vincristine, selective serotonin reuptake inhibitors, 3.4-methylenedioxy-N-methamphetamine, ifosfamide, antipsychotics, narcotics

Drugs potentiating vasopressin action include:

Chlorpropamide, NSAIDs, cyclophosphamide

Vasopressin analogues include:

Desmopressin, oxytocin, vasopressin, terlipressin

Other medicinal products increasing the risk of hyponatraemia also include diuretics in general and antiepileptics such as oxcarbazepine.

Care should be taken in the concurrent use of drugs containing potassium, potassium-sparing diuretics such as spironolactone and triamterene, and drugs which have the potential for inducing hyperkalaemia, ACE (angiotensin converting enzyme) inhibitors, angiotensin II receptor antagonists, tacrolimus and cyclosporine, as well as drugs which promote sodium retention such as corticosteroids.

Check compatibility of medicinal products with the solution before use.

4.6 Fertility, Pregnancy and lactation

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

Sodium salts should be administered with caution to patients with pre-eclampsia.

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 0.15%w/v Sodium Chloride 0.9%w/v Solution for Infusion during pregnancy and lactation.

Potassium Chloride 0.15%w/v Sodium Chloride 0.9%w/v Solution for Infusion should be administrated with special caution for pregnant women during labour particularly as to serum-sodium if administered in combination with oxytocin (see sections 4.4, 4.5 and 4.8).

4.7 Effects on ability to drive and use machines

Not applicable

4.8 Undesirable effects

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, extravasion and hypervolemia.

– Hospital acquired hyponatraemia*

– Acute hyponatraemic encephalopathy

Hospital acquired hyponatraemia may cause irreversible brain injury and death, due to development of acute hyponatraemic encephalopathy, frequency unknown (see sections 4.2. 4.4, 4.5).

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: medsafety@hpra­.ie

4.9 Overdose

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

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 and paralysis.

ECG changes are important indicators of potassium toxicity, including tall, peaked Twaves, 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 or rapid administration of sodium chloride solution may lead to fluid and electrolyte imbalances such as hypokalaemia, hypervolaemic haemodilution, sodium accumulation and hypernatraemia with resultant dehydration of organs particularly the brain, and oedema, also hypertension, tachycardia, oedema, anorexia and nausea. Excessive administration of chloride salts may cause a loss of bicarbonate with an acidifying effect.

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. Discontinue infusion if adverse reaction occurs.

5.1

Pharmacotherapeutic group (ATC code): “electrolytes” (B05BB01).

Potassium Chloride 0.15%w/v Sodium Chloride 0.9%w/v Solution for Infusion is a hypertonic solution, with an approximate osmolarity of 322 mOsmol/l.

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

Sodium is mainly an extracellular cation. Chloride is mainly an extracellular a­nion.

Intracellular chloride is in high concentration in red blood cells and gastric mucosa.

5.2 Pharmacokinetic properties

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

Intravenous administration of the solution provides an immediate supply of electrolytes 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.

5.3 Preclinical safety data

Preclinical safety data of Potassium Chloride 0.15%w/v Sodium Chloride 0.9%w/v

Solution for Infusion in animals are not relevant since potassium chloride and sodium chloride 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 25oC. 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

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 thoroughly with the solution.

Use immediately.

7 MARKETING AUTHORISATION HOLDER

CARELIDE UK LIMLITED

Brook house

3A Duffield Road

Little Eaton

Derbyshire

DE21 5DR

United Kingdom

8 MARKETING AUTHORISATION NUMBER(S)

PL 51515/0008