POTASSIUM CHLORIDE 0.3% & SODIUM CHLORIDE 0.9% SOLN FOR INFU - summary of medicine characteristics

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     3.00 g/l

Sodium Chloride       9.00 g/l

mmol/l:                K+: 40 Na+:   154    Cl-: 194

For excipients: see 6.1.

3 PHARMACEUTICAL FORM

4.   CLINICAL PARTICULARS

4.2 Posology and method of administration

Posology

Adults, the Elderly, Adolescents and Children

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 comedicated 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.

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

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.

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

Method 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 hyperkalaemia.

The osmolarity of a final admixed infusion solution must be taken into account when peripheral administration is considered.

Hyperosmolar solutions may cause venous irritation and phlebitis. Thus, clinically significant hyperosmolar solutions are recommended to be administered through a large central vein, for rapid dilution of the hyperosmolar solution.

Additional electrolyte supplementation may be indicated according to the clinical needs of the patient. When introducing additives to Potassium chloride 0.30% w/v & Sodium Chloride 0.9% w/v solution for infusion, the instructions for use of the medication to be added and other relevant literature must be consulted (see also Special precautions for disposal and other handling, section 6.6).

Risk of air embolism

Do not connect flexible plastic containers in series in order to avoid air embolism due to possible residual air contained in the primary container.

Pressurizing intravenous solutions contained in flexible plastic containers to increase flow rates can result in air embolism if the residual air in the container is not fully evacuated prior to administration.

Use of a vented intravenous administration set with the vent in the open position could result in air embolism. Vented intravenous administration sets with the vent in the open position should not be used with flexible plastic containers.

Rate of administration

Solutions containing potassium should be administered slowly. As administered intravenously, to avoid a dangerous hyperkalemia potassium should not be given faster than 15 to 20 mmoles/h. Rapid correction of hyponatremia and hypernatremia is potentially dangerous (risk of serious neurologic complications) (see also Special Warnings and precautions for Use; section 4.4).

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 Potassium chloride 0.3% w/w & Sodium Chloride 0.9% w/v solution for infusion is contra-indicated in patients with: –      known hypersensitivity to the product

– documented hyperkalaemia, hyperchloraemia or hypernatraemia

– severe renal insufficiency (with oliguria/anuria)

– uncompensated cardiac failure

– Addision’s disease

4.4 Special warnings and precautions for use

Potassium chloride 0.3% w/v & Sodium chloride 0.9% w/v solution for infusion is a hypertonic solution.

Hypersensitivity reactions:

– Hypersensitivi­ty/infusion reactions, including anaphylaxis, have been reported with other products containing potassium chloride and sodium chloride.

– Stop the infusion immediately if signs or symptoms of hypersensitivi­ty/infusion reactions develop. Appropriate therapeutic countermeasures must be instituted as clinically indicated.

Risk of serum electrolytes and water imbalance

Depending on the volume and rate of infusion and depending on a patient’s under­lying clinical condition, intravenous administration of Potassium Chloride 0.3% w/v & Sodium Chloride 0.9% w/v Solution for infusion can cause:

> electrolyte disturbances such as

– Hypernatremia,

– Hyponatremia (see use in patients at risk for sodium imbalance).

> acid-base imbalance.

> overhydration/hy­pervolemia and, for example, congested states, including central (e.g., pulmonary congestion) and peripheral edema.

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.

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-,

potassium sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, or the immunosuppressants cyclosporine and tacrolimus.

Administration of potassium in patients treated with such agents is associated with an increased risk of severe and potentially fatal hyperkalemia, in particular in the presence of other risk factors for hyperkalemia.

Potassium Chloride 0.3% w/v & Sodium chloride 0.9% w/v Solution for infusion should be used with particular caution in patients on concomitant medications that may increase the risk of sodium and fluid retention, such as corticosteroids.

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 Fertility, pregnancy and lactation

There are no adequate data from the use of Potassium Chloride 0.3% & Sodium Chloride 0.9% Solution for infusion in pregnant or lactating women.

Physicians should carefully consider the potential risks and benefits for each specific patient before administering Potassium Chloride 0.3% & Sodium Chloride 0.9% Solution for infusion.

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).

4.7 Effects on ability to drive and use machines

There is no information on the effects of Potassium Chloride 0.3% w/v & Sodium chloride 0.9% w/v solution for infusion on the ability to operate automobile or other heavy machinery.

4.8 Undesirable effects

The following adverse reactions have been reported spontaneously during Post-Marketing use of the product. The frequencies cannot be estimated due to the nature of the data.

1Hospital acquired hyponatraemia may cause irreversible brain injury and death due to the development of acute hyponatraemic encephalopathy, frequency unknown (see sections 4.2, 4.4, 4.5).

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.

Other adverse reactions reported with other potassium chloride and sodium chloride formulations include:

hypersensitivity, hyperkalemia, acidosis hyperchloremic and cardiac arrest as a manifestation of rapid intravenous administration and/or of hyperkalemia.

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

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. Health care professionals are asked to report any suspected adverse reactions via:

Yellow Card Scheme

Website: www.mhra.gov.uk/yellowcard

4.9 Overdose

Excessive administration of Potassium Chloride 0.3% w/v & Sodium Chloride 0.9% w/v Solution for Infusion can cause:

> hyperkalemia, manifestations of hyperkalemia may include:

disturbance in cardiac conduction and arrhythmias, including bradycardia, heart block, asystole, ventricular tachycardia, ventricular fibrillation.

hypotension,

muscle weakness up to and including muscular and respiratory paralysis, paresthesia of extremities,

gastrointestinal symptoms (ileus, nausea, vomiting, abdominal pain)

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

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

> See also section 4.3, 4.4 and 4.8

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

The effect of an overdose may require immediate medical attention and treatment.

Treatment of hyperkalaemia involves the administration of calcium, insulin or sodium bicarbonate, and exchange resins or dialysis.

Interventions include discontinuation of Potassium chloride 0.3% w/v & Sodium Chloride 0.9% w/v Solution for infusion administration, dose reduction and other measures as indicated for the specific clinical constellation.

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 litre. 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 that 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 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.

After injection of radiosodium (24Na), the half-life is 11 to 13 days for 99% of the injected Na and 1 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 faeces 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 colour change and/or eventual precipitate, insoluble complexes or the appearance of crystals. The Instructions for Use of the medication to be added must be consulted.

Before adding a drug, verify that 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)

The 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.

All packs may not be marketed.

6.6 Special precautions for disposal and other handling

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not administer unless the solution is clear and the seal is intact.

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.

After addition, if there is a discoloration and/or the appearance of precipitates, insoluble complexes or crystals, do not use.

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

PL 00116/0337

9. DATE OF FIRST AUTHORISATION/RE­NEWAL OF AUTHORISATION

10th September 2001