Potassium Chloride 0.3% Sodium Chloride 0.18% & Glucose 4%
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Potassium Chloride 0.3 %, Sodium Chloride 0.18 % and Glucose 4% Solution for Infusion - BP.
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
|
Potassium Chloride |
3.0 g/L | ||
|
Sodium Chloride: |
1.8 g/L | ||
|
Glucose monohydrate: |
44.0 g/L | ||
|
K+ |
Na+ |
Cl- | |
|
mmol/l |
40 |
31 |
71 |
|
mEq/l |
40 |
31 |
71 |
For excipients : see section 6.1.
3. PHARMACEUTICAL FORM
Solution for infusion.
Clear solution, free from visible particles
4. CLINICAL PARTICULARS
4.1. Therapeutic indications
Prevention and treatment of potassium, sodium and chloride depletion due to a loss of gastrointestinal fluid (vomiting, diarrhoea, surgical drainage, gastric suction, small intestinal bypass procedure, or small bowel fistula), a chronic abuse of laxative, malabsorption syndromes, mucus secreting villous adenoma of the small intestine, or renal salt-losing conditions (renal disorders, overuse of diuretics), particularly in cases (e.g. starvation) where a source of energy is required.
Posology
Adults, the Elderly and Children
The dosage depends on the age, weight, clinical and biological conditions of the patient and concomitant therapy.
Typical doses of potassium for the prevention of hypokalemia may be up to 50 mmoles daily and similar doses may be adequate in mild potassium deficiency. In severe acute hypokalemia, up to 20 mmoles of potassium in 500 ml over 2 to 3 hours under ECG control. Patients with renal impairment should receive lower doses.
The maximum recommended dose of potassium is 2 to 3 mmol/kg/24h. The rate should not exceed 10 to 40 mmol/h to avoid hyperkalaemia. For peripheral infusions, potassium concentration should be less than 60 mmol/l to avoid pain.
The maximum rate of glucose is about 500 to 800 mg/kg/h.
Paediatric Population
The infusion rate and volume depends on the age, weight, clinical and metabolic conditions of the patient, concomitant therapy and should be determined by the consulting physician experienced in paediatric intravenous fluid therapy (see Section 4.4).
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 central vein, be sure the catheter is not in the atrium or ventricle to avoid localised hyperkalaemia. Solutions containing potassium should be administered slowly.
Rate of administration
As administered intravenously, potassium should not be given faster than 10 to 40 mmol/h to avoid a dangerous hyperkalaemia.
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 contraindicated in patients presenting:
- Hyperchloremia and hyperkalaemia that are not related to the concentration effect associated to a volume depletion
- Severe renal insufficiency (with oliguria/anuria)
- Uncompensated heart failure and severe congestive heart failure
- Addison’s disease
- Fluid and sodium retention
- Acute ischemic stroke
- Head trauma (first 24 hours)
- Uncompensated diabetes
- Hyperosmolar coma
- Hyperglycaemia
- Hyperlactatemia
- Other known glucose intolerances (such as metabolic stress situations)
4.4 Special warnings and precautions for use
Potassium chloride 0.3%, Sodium chloride 0.18% and Glucose 4% is a slightly hypertonic solution. Once administered, the solution becomes hypotonic due to its low sodium content.
Potassium should be administered with considerable care to patients with cardiac disease or conditions predisposing to hyperkalaemia such as renal or adrenocortical insufficiency, acute dehydration, or extensive tissue destruction as occurs with severe burns. Regular monitoring of clinical status, serum electrolytes and ECG is advisable in patients receiving potassium therapy, particularly those with cardiac or renal impairment.
Sodium salts should be administered with caution to patients with hypertension, heart failure, peripheral or pulmonary oedema, impaired renal function, pre-eclampsia, or other conditions associated with sodium retention (see also Section 4.5 - Interactions with other medicinal products and other forms of interaction).
In diabetic patients, the amount of infused glucose has to be taken into account and insulin requirements may be modified.
During long term parenteral treatment, a convenient nutritive supply must be given to the patient.
Potassium chloride 0.3%, Sodium chloride 0.18% and Glucose 4% solution contains glucose derived from corn. It should be used with caution in patients with known corn allergies (see section 4.8).
Paediatric population
Plasma electrolyte concentrations should be closely monitored in the paediatric population as this population may have impaired ability to regulate fluids and electrolytes.
The infusion of hypotonic fluids together with the non-osmotic secretion of ADH may result in hyponatraemia. Hyponatraemia can lead to headache, nausea, seizures, lethargy, coma, cerebral oedema and death, therefore acute symptomatic hyponatraemic encephalopathy is considered a medical emergency.
Newborns - especially those born premature and with low birth weight - are at increased risk of developing hypo- or hyperglycemia and therefore need close monitoring during treatment with intravenous glucose solutions to ensure adequate glycaemic control in order to avoid potential long term adverse effects. Hypoglycaemia in the newborn can cause prolonged seizures, coma and brain damage. Hyperglycaemia has been associated with intraventricular haemorrhage, late onset bacterial and fungal infection, retinopathy of prematurity, necrotizing enterocolitis, bronchopulmonary dysplasia, prolonged length of hospital stay, and death.
In order to avoid potentially fatal over infusion of intravenous fluids to the neonate, special attention needs to be paid to the method of administration. When using a syringe pump to administer intravenous fluids or medicines to neonates, a bag of fluid should not be left connected to the syringe.
When using an infusion pump all clamps on the intravenous administration set must be closed before removing the administration set from the pump, or switching the pump off. This is required regardless of whether the administration set has an antifree flow device.
The intravenous infusion device and administration equipment must be frequently monitored.
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 serum potassium concentrations (potassiumsparing diuretics, ACE inhibitors, ciclosporin, and drugs that contains potassium such as potassium salts of penicillin).
Corticosteroids are associated with the retention of sodium and water, with edema and hypertension.
Glucose should not be administered through the same infusion equipment as whole blood as hemolysis and clumping can occur.
It has been suggested that if used during labour, the glucose load on the mother may lead to fetal hyperglycemia, hyperinsulinemia, and acidosis, with subsequent neonatal hypoglycemia and jaundice. Others have found no evidence of such an effect.
There is no other data reported in the literature on special warnings or precautions regarding the use of Potassium Chloride 0.3 %, Sodium Chloride
0.18 % & Glucose 4% Solution in case of pregnancy or lactation.
4.7. Effects on ability to drive and use machines
Not relevant.
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 hypervolaemia.
Anaphylactic reaction, hypersensitivity, and chills have also been reported.1 Hyponatremia has also been reported.2
1Reported for similar solutions containing dextrose.
2Reported for similar solutions containing low sodium chloride (<0.9%).
Table 1
Tabulated list of adverse reactions
|
System Organ Class |
Symptoms (LLT terms MedDRA) |
Frequency |
|
Immune system disorders |
Allergic reaction Anaphylactic reaction** Hypersensitivity** |
Not known (*) |
|
Metabolism and nutrition disorders |
Hypervolaemia, Hyponatremia | |
|
Skin and subcutaneous tissue disorders |
Sweating | |
|
General disorders and administration site conditions |
Chills**, Shivering Febrile reaction, Fever |
Infection at site of injection
__Thrombophlebitis__
(*) cannot be estimated from the available data
(**)Potential manifestation in patients with allergy to corn, see section 4.4 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 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 overdose, treatment should be discontinued and the patient should be observed for the appropriate signs and symptoms related to the drug administered.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Electrolytes with Carbohydrates ATC code: B05BB02.
Potassium Chloride 0.3%, Sodium Chloride 0.18% and Glucose 4% is a hypertonic solution. Once administered, the solution becomes hypotonic due to its low sodium content.
The pharmacodynamic properties of this solution are those of its components (glucose, sodium, potassium, and chloride) in maintaining fluid, electrolyte and energy 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 action. 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.
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 (glucose, sodium, potassium, and chloride).
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 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 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 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 kidney, 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.
5.3. Preclinical safety data
The preclinical safety assessment of Potassium Chloride 0.3%, Sodium Chloride 0.18% and Glucose 4% solution for infusion in animals is not
relevant as electrolytes and glucose are physiological constituents of the body and are covered by appropriate pharmacopoeial references.
6. PHARMACEUTICAL PARTICULARS
6.1. List of excipients
Water for Injections
6.2. Incompatibilities
As with all parenteral solutions, before adding medications, compatibility of these additives with the solution in Viaflo container must be assessed.
It is the responsibility of the physician to judge the incompatibility of an additive medication with the Potassium Chloride 0.3%, Sodium Chloride 0.18% and Glucose 4% solution by checking for eventual colour 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 stable in water at the pH of Potassium Chloride
0.3%, Sodium Chloride 0.18% and Glucose 4%.
When a compatible medication is added to this formulation, the solution must be administered immediately, unless dilution has taken place in controlled and validated aseptic conditions.
As a guidance, the following medications are incompatible with the Potassium Chloride 0.3%, Sodium Chloride 0.18% and Glucose 4% solution (nonexhaustive listing) :
-Amphotericin B -Dobutamine
Glucose should not be administered through the same infusion equipment as whole blood as hemolysis and clumping can occur.
Those additives known to be incompatible should not be used.
6.3. Shelf life
Shelf life as packaged :
500 and 1000mL containers : 3 years In-use shelf-life (Additives)
Chemical and physical stability of any additive medication at the pH of the Potassium Chloride 0.3%, Sodium Chloride 0.18% and Glucose 4% 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 pouch composed of polyamide/polypropylene
Bag sizes : 500 and 1000 mL.
Outer carton contents : - 20 bags of 500 ml or - 10 bags of 1000 ml.
6.6 Special precautions for disposal
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.
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. The inner bag maintains the sterility of the product.
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 administration or during administration through the resealable medication port.
When additive is used, verify tonicity prior to parenteral administration. Thorough and careful aseptic mixing of any additive is mandatory. Solutions containing additives should be used immediately after preparation, unless preparation has taken place in controlled and validated aseptic conditions.
Adding other medication or using an incorrect administration technique might cause the appearance of fever reactions due to the possible introduction of pyrogens. In case of an 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.
Warning: Additives may be incompatible
To add medicinal product 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 medicinal product 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 00116/0341
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
25 April 2002
10 DATE OF REVISION OF THE TEXT
30/10/2013