This information is intended for use by health professionals

1. Name of the medicinal product

Potassium Chloride 0.3% w/v & Sodium Chloride 0.9%w/v Solution for Infusion- BP

2. Qualitative and quantitative composition

Potassium Chloride

Sodium Chloride

3.00 g/L

9.00 g/L

mmol/l:

K+: 40

Na+: 154

Cl-: 194

For excipients: see 6.1

3. Pharmaceutical form

Solution for infusion.

Clear solution, free from visible particles.

4. Clinical particulars
4.1 Therapeutic indications

Potassium Chloride 0.3% & Sodium Chloride 0.9% Solution for Infusion is indicated for the prevention and treatment of potassium depletion and/or hypokalemia, in sodium chloride and water-losing conditions.

4.2 Posology and method of administration

Posology

Fluid balance, serum electrolytes and acid-base balance should 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 0.3% & Sodium Chloride 0.9% Solution for Infusion has a tonicity of 388 mOsm/l (approx.)

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 intravenous fluid therapy (see sections 4.4. and 4.8).

Adults, the Elderly and Children

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

- for sodium

1 g NaCl = 394 mg of Na+ or 17.1 mEq or 17.1 mmol of Na+ and Cl-

1 mmol Na+ = 23mg Na+

- for potassium

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+

General posology

The recommended dosage for treatment of isotonic fluid depletion (extracellular dehydration) by means of any intravenous solution is:

- for adults : 500 ml to 3Liters /24h

- for babies and children : 20 to 100 ml per 24 h and per kg of body weight, depending of the age and the total body mass.

Posology for prevention and treatment of potassium depletion

Typical dose of potassium for the prevention of hypokalemia may be up to 50 mmoles daily and similar doses may be adequate in mild potassium deficiency.

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

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

The maximum recommended administration rate should not exceed 15-20 mmol/h.

Patient with renal impairment should receive lower doses.

However, in any case, the dosage given under “general posology” should not be exceeded.

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 central vein, be sure the catheter is not in the atrium or ventricle to avoid localized hyperkalemia.

Solutions containing potassium should be administered slowly.

Rate of administration

As administered intravenously, potassium should not be given faster than 15 to 20 mmoles/h to avoid a dangerous hyperkalemia.

Monitoring

Adequate urine flow must be ensured and careful monitoring of plasma-potassium and other electrolyte concentrations is essential. High dosage or high speed infusion must be performed under ECG control.

4.3 Contraindications

The solution is contra-indicated in patients with:

- documented hyperkalemia, hyperchloremia or hypernatremia

- severe renal insufficiency (with oliguria/anuria)

- uncompensated cardiac failure

- Addison's disease

4.4 Special warnings and precautions for use

Potassium chloride 0.3% & Sodium chloride 0.9% solution is an hypertonic solution, see 4.2.

Administration should be carried out under regular and careful surveillance. Regular monitoring of clinical status, plasma electrolyte concentrations, plasma creatinine levels, BUN level, acid-base balance and ECG is essential in patients receiving potassium therapy, particularly those with cardiac or renal impairment.

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

Potassium salts should be administered with considerable care to patients with cardiac disease or conditions predisposing to hyperkalemia such as renal or adrenocortical insufficiency, acute dehydration, or extensive tissue destruction as occurs with severe burns. In patients under digitalis therapy, regular monitoring of the plasma potassium level is mandatory.

Sodium salts should be administered with caution to patients with hypertension, heart failure, peripheral or pulmonary edema, impaired renal function, pre-eclampsia, or other conditions associated with sodium retention (see also Section 4.5 – Interactions with other medicaments and other forms of interaction).

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, 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 (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

Solutions containing potassium should be used with caution in patients receiving drugs that increase plasma potassium concentrations (e.g. potassium-sparing diuretics, ACE inhibitors, Angiotensin II receptors antagonists, ciclosporin, tacrolimus and drugs that contain potassium).

Corticosteroids are associated with the retention of sodium and water, with edema and hypertension.

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, terlipressin

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

4.6 Pregnancy and lactation

Hyperkalemic and hypokalemic serum levels lead to impaired cardiac function of the maternal and foetal hearts. Therefore, the maternal electrolyte levels are to be controlled regularly.

Potassium chloride 0.3% & Sodium chloride 0.9% solution should be administrated with special caution for pregnant women during labour particularly as to serum-sodium if administered in combination with oxytocin (see section 4.4, 4.5 and 4.8).

If taken for the corresponding indications and at the therapeutic dosage, and with consideration of the special cautions above, administration of Potassium chloride 0.3% & Sodium chloride 0.9% solution would be possible during pregnancy and lactation.

4.7 Effects on ability to drive and use machines

Not applicable

4.8 Undesirable effects

Adverse reactions may be associated to the technique of administration including 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.

Adverse reactions associated to metabolism and nutrition disorders

- Hospital acquired hyponatraemia*

Adverse reactions associated nervous system disorders:

- 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).

In case of undesirable effect(s), the infusion must be discontinued.

4.9 Overdose

Excessive administration of potassium may lead to the development of hyperkalemia, especially in patients with renal impairment. Symptoms include paresthesia of the extremities, muscle weakness, paralysis, cardiac arrhythmias, heart block, cardiac arrest, and mental confusion. Treatment of hyperkalemia involves the administration of calcium, insulin or sodium bicarbonate, and exchange resins or dialysis.

Retention of excess sodium when there is a defective renal sodium excretion may result in pulmonary and peripheral edema.

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 and the patient should be observed for the appropriate signs and symptoms related to the drug administered. The relevant symptomatic and supportive measures should be provided as necessary.

5. Pharmacological properties
5.1 Pharmacodynamic properties

Pharmacotherapeutic group (ATC code): electrolytes “B05BB01”

Potassium Chloride 0.3% & Sodium Chloride 0.9% solution is an hypertonic solution of electrolytes, with an approximate osmolarity of 388 mOsm/l.

The pharmacodynamic properties of the solution are those of the sodium, potassium and chloride ions in maintaining the fluid and electrolyte balance.

Potassium is essential for numerous metabolic and physiological processes including nerve conduction, muscle contraction, and acid-base regulation. A normal concentration of potassium in plasma is about 3.5 to 5.0 mmoles per liter. Potassium is predominantly an intracellular cation. The passage of potassium into the cells and retention against the concentration gradient requires active transport via the Na+/K+ ATPase enzyme.

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 its 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.

5.2 Pharmacokinetic properties

The pharmacokinetic properties of Potassium Chloride 0.3% & Sodium Chloride 0.9% are those of the ions its composition includes (sodium, potassium 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 of 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 feces and small amounts may also be excreted in sweat.

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 neurons; it is very slow in the bone. Sodium is predominantly excreted by the kidney, but there is extensive renal reabsorption. Small amounts of sodium are lost in the feces and sweat.

5.3 Preclinical safety data

Preclinical safety data of Potassium Chloride 0.3% & Sodium Chloride 0.9% in animals are not relevant since electrolytes are physiological components of the body.

6. Pharmaceutical particulars
6.1 List of excipients

Water for Injections

6.2 Incompatibilities

As with all parenteral solutions, incompatibility of the additive medications with the solution must be assessed before addition.

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

It is the responsibility of the physician to judge the incompatibility of an additive medication with the Potassium Chloride 0.3% & Sodium Chloride 0.9% solution, by checking for eventual color change and/or eventual precipitate, insoluble complexes or crystals apparition. The Instructions for Use of the medication to be added must be consulted.

Before adding a drug, verify it is soluble and/or stable in water at the pH of the Potassium Chloride 0.3% & Sodium Chloride 0.9% solution (pH: 4.5 to 7.0).

Those additives known to be incompatible should not be used.

6.3 Shelf life

Shelf life as packaged: 3 years

In-use shelf life (Additives)

Chemical and physical stability of any additive medication at the pH of the Potassium Chloride 0.3% and Sodium Chloride 0.9% solution in the Viaflo container should be established prior to use. From a microbiological point of view, the diluted product must be used immediately unless dilution has taken place in controlled and validated aseptic conditions.

If not used immediately, in-use storage times and conditions are the responsibility of the user.

6.4 Special precautions for storage

No special precautions for storage

6.5 Nature and contents of container

The bags known as Viaflo are composed of polyolefin/polyamide co-extruded plastic (PL 2442). The bags are overwrapped with a protective plastic overpouch composed of polyamide/polypropylene.

The bag size is either 500 or 1000mL.

Outer carton contents :

- 20 bags of 500 ml

or - 10 bags of 1000ml.

6.6 Special precautions for disposal and other handling

Use only if the solution is clear, without visible particles and if the container is undamaged. Administer immediately following the insertion of infusion set.

Do not remove unit from overwrap until ready for use.

The inner bag maintains the sterility of the product.

Do not use plastic containers in series connections. Such use could result in air embolism due to residual air being drawn from the primary container before the administration of the fluid from the secondary container is completed.

The solution should be administered with sterile equipment using an aseptic technique. The equipment should be primed with the solution in order to prevent air entering the system.

Additives may be introduced before infusion or during infusion through the injection site. When additive is used, verify isotonicity prior to parenteral administration. Thorough and careful aseptic mixing of any additive is mandatory. Solutions containing additives should be used immediately and not stored.

Adding medication or using an incorrect administration technique might cause the appearance of fever reactions due to the possible introduction of pyrogens. In case of adverse reaction, infusion must be stopped immediately.

Discard after single use.

Discard any unused portion.

Do not reconnect partially used bags.

1. Opening

a. Remove the Viaflo container from the overpouch just before use.

b. Check for minute leaks by squeezing inner bag firmly. If leaks are found, discard solution, as sterility may be impaired.

c. Check the solution for limpidity and absence of foreign matters. If solution is not clear or contains foreign matters, discard the solution.

2. Preparation for administration

Use sterile material for preparation and administration.

a. Suspend container from eyelet support.

b. Remove plastic protector from outlet port at bottom of container:

- grip the small wing on the neck of the port with one hand,

- grip the large wing on the cap with the other hand and twist,

- the cap will pop off.

c. Use an aseptic method to set up the infusion.

d. Attach administration set. Refer to complete directions accompanying set for

connection, priming of the set and administration of the solution.

3. Techniques for injection of additive medications

Warning: Additives may be incompatible.

To add medication before administration

a. Disinfect medication site.

b. Using syringe with 19 to 22 gauge needle, puncture resealable medication port and inject.

c. Mix solution and medication thoroughly. For high-density medication such as potassium chloride, tap the ports gently while ports are upright and mix.

Caution: Do not store bags containing added medications.

To add medication during administration

a. Close clamp on the set.

b. Disinfect medication site.

c. Using syringe with 19 to 22 gauge needle, puncture resealable medication port and inject.

d. Remove container from IV pole and/or turn to an upright position.

e. Evacuate both ports by tapping gently while the container is in an upright position.

f. Mix solution and medication thoroughly.

g. Return container to in use position, re-open the clamp and continue administration

7. Marketing authorisation holder

Baxter Healthcare Ltd.,

Caxton Way,

Thetford,

Norfolk,

IP24 3SE

United Kingdom

8. Marketing authorisation number(s)

PL.0116/0337

9. Date of first authorisation/renewal of the authorisation

10th September 2001/ 19 March 2006

10. Date of revision of the text

Dec 2018