Sterofundin iso

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT STEROFUNDIN ISO (STEROFUNDIN ISO)

Composition:

Active substances: sodium chloride; potassium chloride; magnesium chloride, hexahydrate; calcium chloride, dihydrate; sodium acetate, trihydrate; L-malic acid;

1000 ml of solution contain: sodium chloride 6.80 g; potassium chloride 0.30 g; magnesium chloride hexahydrate 0.20 g; calcium chloride dihydrate 0.37 g; sodium acetate trihydrate 3.27 g; L-malic acid 0.67 g;

Electrolyte concentrations: sodium – 145 mmol/l; potassium – 4 mmol/l; magnesium – 1 mmol/l; calcium – 2.5 mmol/l; chlorides – 127 mmol/l; acetates – 24 mmol/l; malates – 5 mmol/l;

Excipients: water for injections, sodium hydroxide.

Pharmaceutical form. Infusion solution.

Main physicochemical characteristics: clear, colorless solution, practically free from mechanical particles. Theoretical osmolarity 309 mOsm/l; pH 5.1 – 5.9.

Pharmacotherapeutic group. Plasma substitutes and perfusion solutions. Solutions for intravenous infusion. Solutions used for correction of electrolyte balance disorders. Electrolytes.

ATC code B05BB01.

Pharmacological properties.

Pharmacodynamics.

This medicinal product is an isotonic electrolyte solution in which electrolyte concentrations correspond to their plasma concentrations. It is used to correct extracellular fluid losses (i.e., losses of water and electrolytes in proportional amounts). The purpose of administering the solution is to restore and maintain normal osmotic conditions in both extracellular and intracellular spaces.

The anion composition of the drug represents a balanced combination of chlorides, acetates, and malates, which helps prevent the development of metabolic acidosis.

Pharmacokinetics.

Since Sterofundin ISO is administered intravenously, its bioavailability is 100%.

Sodium and chloride are distributed mainly in the extracellular space, whereas potassium, magnesium, and calcium are distributed predominantly intracellularly. The kidneys are the main route of elimination for sodium, potassium, magnesium, and chloride, although a small amount of electrolytes is lost through the skin and gastrointestinal tract. Calcium is excreted in urine and via intestinal secretion in approximately equal amounts.

During infusion of acetates and malates, their plasma levels rise until equilibrium levels are reached. After infusion is discontinued, anion concentrations rapidly decrease. Urinary excretion of acetates and malates increases during infusion; however, their metabolism in body tissues is so rapid that only negligible fractions are detected in urine.

Clinical characteristics.

Indications.

Replacement of extracellular fluid losses in isotonic dehydration associated with or threatened by acidosis.

Contraindications.

Hypersensitivity to any active or excipient ingredient of the medicinal product.

Hyperhydration.

Severe congestive heart failure.

Renal failure with oliguria or anuria.

Severe generalized edema.

Severe hyperkalemia.

Hypercalcemia.

Metabolic alkalosis.

Severe metabolic acidosis.

Interaction with other medicinal products and other forms of interaction.

Sodium, potassium, calcium, and magnesium are present in Sterofundin ISO at the same concentrations as in blood plasma. Therefore, administration of Sterofundin ISO according to the recommended indications and contraindications does not lead to increased plasma concentrations of these electrolytes. However, if plasma concentration of any electrolyte increases for other reasons, the following interactions should be considered.

Medicinal products causing sodium retention

The use of nonsteroidal anti-inflammatory drugs, corticosteroids/steroids, and carbenoxolone may lead to sodium and water retention (with edema and arterial hypertension).

Medicinal products interacting with potassium

Suxamethonium, ACE inhibitors, nonsteroidal anti-inflammatory drugs, potassium-sparing diuretics (amiloride, spironolactone, triamterene, alone or in combination), tacrolimus, and cyclosporine may increase plasma potassium concentration and lead to potentially fatal hyperkalemia, especially in the presence of renal insufficiency, which enhances the hyperkalemic effect and may result in cardiac arrhythmia.

Potassium administration may reduce the therapeutic effect of cardiac glycosides. ACTH, corticosteroids, and loop diuretics may increase renal potassium elimination.

Medicinal products interacting with calcium

The action of digitalis glycosides (cardiac glycosides) may be enhanced in hypercalcemia, leading to severe or fatal cardiac arrhythmia.

Thiazide diuretics and vitamin D may cause hypercalcemia. Calcium complexes render tetracycline antibiotics inactive.

Medicinal products interacting with malate

Alkalinization of urine following administration of bicarbonate precursors or bicarbonate leads to increased renal clearance of acidic drugs.

The elimination half-life of certain medicinal products, particularly sympathomimetics (e.g., ephedrine, pseudoephedrine) and stimulants (e.g., dexamphetamine sulfate, fenfluramine hydrochloride), is prolonged when solutions containing malate are administered concomitantly.

Special precautions for use.

Large volume infusions may be administered to patients with mild to moderate cardiac or respiratory insufficiency under careful monitoring (for more severe conditions, see section "Contraindications").

Sterofundin ISO should be administered with extreme caution and under continuous monitoring to patients with the following conditions:

• Hypernatremia;
• Hyperchloremia;
• Renal insufficiency;
• Coma of unknown origin;
• Concomitant treatment with digitalis preparations;
• Hyperkalemia or conditions that may lead to hyperkalemia, such as Addison's disease, sickle cell anemia;
• Hypertonic dehydration, arterial hypertension, impaired renal function, existing or impending eclampsia, hyperaldosteronism, or other conditions or concomitant treatment with drugs (e.g. corticosteroids/steroids) associated with sodium retention and drugs that increase serum potassium levels (see also section "Interaction with other medicinal products and other forms of interaction");
• Conditions requiring sodium restriction, such as mild to moderate heart failure, peripheral edema, generalized edema, pulmonary edema, pre-eclampsia, or extracellular hyperhydration (for more severe conditions, see section "Contraindications");
• Conditions requiring calcium restriction, such as sarcoidosis.

Patients receiving cardiac glycosides should use potassium- and calcium-containing solutions with caution (see section "Interaction with other medicinal products and other forms of interaction").

Potassium-containing solutions should be administered cautiously to patients with heart disease or conditions that may lead to hyperkalemia, such as renal or adrenocortical insufficiency, acute dehydration, or extensive tissue destruction in severe burns.

Due to the presence of calcium:

• Caution should be exercised during intravenous administration to avoid extravasation and local irritation by calcium salts;
• If blood transfusion is simultaneously required, this solution must not be administered through the same infusion system as blood components.

Use as a solvent

Please note: When using the medicinal product as a solvent, safety information regarding the added substance approved by the respective manufacturer should be taken into account.

Anion-containing solutions that are metabolized should be administered cautiously to patients with respiratory disorders.

Clinical monitoring should include serum electrolyte panel, fluid balance, and pH.

For prolonged parenteral therapy, patients should receive appropriate nutritional support.

Elderly patients

Elderly patients, who more frequently suffer from heart failure and impaired renal function, should be carefully monitored and dosage adjusted to avoid cardiac and renal complications caused by fluid overload.

Children

Intravenous therapy should be carefully monitored in children as well, due to possible disturbances in the ability to regulate fluids and electrolytes. Adequate urinary output must be ensured. Careful monitoring of fluid balance and plasma and urine electrolyte concentrations is essential.

In short-term volume replacement due to hemorrhage or trauma, volume overload due to overdosage should always be avoided.

For intravenous use only.

For single use only. Any unused solution should be discarded.

Only a clear, practically particle-free solution should be used.

The solution should be administered using a sterile infusion system under aseptic technique. The system should be primed with the solution to prevent air from entering.

When using the solution in plastic bags, the protective overwrap should be removed immediately before use.

Use during pregnancy or breastfeeding.

There are no data on the use of Sterofundin ISO in pregnant women or women who are breastfeeding. Within the recommended indications, no risk is expected if the volume of infused solution, electrolyte levels, and acid-base balance are carefully monitored.

Sterofundin ISO should be used with caution in pregnant women with toxemia.

Effect on ability to drive and use machines.

Sterofundin ISO has no effect or has a negligible effect on the ability to drive a vehicle or operate machinery.

Administration and Dosage

The dose should be determined according to the actual need for replenishment of water and electrolyte levels.

Adults

Maximum Daily Dose

The volume of infused solution should not exceed 40 ml/kg body weight per day (corresponding to 5.8 mmol of sodium per 1 kg body weight and 0.16 mmol of potassium per 1 kg body weight).

Additional fluid losses (e.g., due to fever, diarrhea, vomiting, etc.) should be compensated according to the volume and composition of the lost fluid. In cases of dehydration, the dose of 40 ml/kg body weight per day may be exceeded.

The dose should be calculated based on the severity of dehydration and the patient's clinical condition.

In the treatment of acute fluid deficit, particularly severe or life-threatening hypovolemic shock, higher doses may be administered, for example, via rapid infusion (under pressure).

Maximum Infusion Rate

The infusion rate of the medicinal product should not exceed 100 ml/hour.

In the treatment of dehydration, the maximum infusion rate is 5 ml/kg body weight per hour, corresponding to 0.7 mmol of sodium per 1 kg body weight per hour and 20 micromol of potassium per 1 kg body weight per hour.

For short-term replenishment of intravascular volume, the maximum infusion rate depends on the patient's clinical condition.

In life-threatening situations, 500 ml of the preparation may be rapidly administered manually under pressure.

Solvent

When Sterofundin ISO is used as a solvent, the dosage and infusion rate are primarily determined based on the characteristics and dosing regimen of the drug being dissolved.

Paediatric Population

The dose is prescribed by a physician. The dose depends on the patient's age, body weight, laboratory parameters, clinical condition, and concomitant therapy.

Maximum Daily Dose

The following daily doses should not be exceeded.

Age	Dose (ml/kg body weight per day)
from 28 days of life	160
from 2 months	150
1–2 years	120
3–5 years	100
6–12 years	80
13–18 years	70

Additional fluid losses (e.g., due to fever, diarrhea, vomiting, etc.) should be compensated according to the volume and composition of the lost fluid.

In case of dehydration or for short-term replenishment of intravascular volume, the above-mentioned doses may be increased.

The dose should be calculated based on the severity of dehydration and the patient's clinical condition.

Infusion rate

Maximum infusion rate

Body weight	ml/hour
0–10 kg	4 ml/kg body weight/hour
10–20 kg	40 ml/hour + 2 ml/kg body weight/hour above 10 kg
>20 kg	60 ml/hour + 1 ml/kg body weight/hour above 20 kg

In the treatment of dehydration, the maximum infusion rate is 5 ml/kg body weight/hour, corresponding to 0.7 mmol of sodium per 1 kg of body weight per hour and 20 micromol of potassium per 1 kg of body weight per hour.

Elderly patients

In general, the same doses as for adults are used; however, attention should be paid to conditions such as heart failure or renal failure, which may be associated with advanced age (see section "Special precautions for use").

Patients with chronic hyponatremia

To prevent the development of osmotic demyelination syndrome, the increase in serum sodium concentration should not exceed 9 mmol/L/day. As a general recommendation, correction should be 4 to 6 mmol/L/day in most cases, depending on the patient's condition and concomitant risk factors.

Method of administration

For intravenous infusion only.

**Sterofundin ISO may be administered into peripheral veins (regarding pH and theoretical osmolarity, see section "**Physicochemical properties").

When administering under rapid infusion under pressure from a plastic container and infusion system, all air must be removed prior to infusion, as otherwise there is a risk of air embolism during infusion.

Monitoring of fluid balance, plasma electrolyte concentrations, and pH is required during administration.

Sterofundin ISO may be administered as long as there are indications for fluid replacement.

Children

The medicinal product can be used in children from 28 days of age, when indicated.

Overdose

Excessive or too rapid administration of the solution may lead to water or sodium overload, resulting in increased skin turgor, venous congestion, and development of edema, particularly in cases of impaired renal excretion of sodium. In such cases, additional hemodialysis may be required.

Excessive potassium administration may lead to hyperkalemia, especially in patients with renal failure. Symptoms include paresthesia of extremities, muscle weakness, paralysis, cardiac arrhythmia, heart block, cardiac arrest, and confusion. Treatment of hyperkalemia includes administration of calcium, insulin (with glucose), sodium bicarbonate, ion-exchange resins, or dialysis.

Excessive parenteral administration of magnesium salts leads to hypermagnesemia. Important signs include loss of deep tendon reflexes and respiratory depression, both resulting from neuromuscular blockade. Other symptoms of hypermagnesemia may include nausea, vomiting, skin flushing, thirst, arterial hypotension due to peripheral vasodilation, dizziness, confusion, muscle weakness, bradycardia, coma, and cardiac arrest.

Excessive administration of chlorides may cause bicarbonate loss, leading to acidosis.

Excessive use of compounds metabolized to bicarbonate anion, such as acetates and malates, may lead to metabolic alkalosis, particularly in patients with impaired renal function. Symptoms may include mood changes, fatigue, dyspnea, muscle weakness, and cardiac arrhythmia (disturbance of heart rhythm). In patients with concomitant hypocalcemia, increased muscle tone, muscle contractions, and tetany may develop. Treatment of metabolic alkalosis associated with elevated bicarbonate levels primarily involves appropriate correction of fluid and electrolyte balance.

Excessive administration of calcium salts may lead to hypercalcemia. Symptoms of hypercalcemia may include anorexia, nausea, vomiting, constipation, abdominal pain, muscle weakness, mental disturbances, polydipsia, polyuria, nephrocalcinosis, kidney stone formation, and in severe cases, cardiac arrhythmia and coma. Very rapid intravenous administration of calcium salts may also cause numerous symptoms of hypercalcemia, as well as a chalky taste in the mouth, hot flashes, and peripheral vasodilation. Mild asymptomatic hypercalcemia usually resolves after discontinuation of calcium and other agents promoting its development, such as vitamin D. In cases of severe hypercalcemia, urgent treatment is required (e.g., loop diuretics, hemodialysis, calcitonin, bisphosphonates, sodium edetate).

If overdose is related to medications added to the solution, signs and symptoms of their excessive administration will also depend on the nature of the added substances. In case of accidental overdose, treatment should be discontinued and the patient should be examined for appropriate signs and symptoms related to the added substance. Symptomatic and supportive measures should be taken as necessary.

Treatment

Immediately stop the infusion. Further treatment depends on the nature and severity of symptoms and may include administration of diuretics with frequent monitoring of electrolyte balance, and correction of electrolyte and acid-base imbalances.

Treatment of hyperkalemia includes administration of calcium, insulin (with glucose), sodium bicarbonate, ion-exchange resins, or dialysis.

Adverse Reactions.

Symptoms of overdose may occur (see section "Overdose").

Hypersensitivity reactions, including urticaria.

Hyperhydration, pulmonary edema, and electrolyte disturbances are possible.

Although oral administration of magnesium salts stimulates peristalsis, after intravenous administration of magnesium sulfate, paralytic ileus has been reported in rare cases.

Adverse reactions may be related to the administration technique, including febrile response, infections at the injection site, local pain or local reactions, venous irritation, thrombosis or thrombophlebitis extending from the injection site, and extravasation. Adverse reactions may also be associated with medications added to the solution; the nature of the added substances will determine the type of any additional adverse effects.

Shelf life.

Shelf life when stored in polyethylene containers is 3 years; in plastic bags it is 2 years.

Shelf life after first opening of the container

From a microbiological point of view, the medicinal product should be used immediately after opening. If the solution is not administered immediately, the person using this medicinal product is responsible for ensuring appropriate storage prior to use, which generally should not exceed 24 hours at a temperature of 2–8 °C, unless the solution has been reconstituted/diluted under controlled and validated aseptic conditions.

Storage conditions.

Store out of reach and sight of children, at a temperature not exceeding 25 °C. Do not freeze.

Incompatibilities.

Mixing this medicinal product with medications containing carbonates, phosphates, sulfates, or tartrates may result in precipitate formation.

Packaging.

Polyethylene container: 250 ml, 500 ml, or 1000 ml in packs of 10; 10 containers per cardboard box.

Plastic bag: 250 ml, 500 ml, or 1000 ml in packs of 10; 10 bags per cardboard box.

Prescription status.

Prescription only.

Manufacturer.

B. Braun Melsungen AG / B. Braun Melsungen AG.

B. Braun Medical S.A. / B. Braun Medical S.A.

B. Braun Medical S.A. / B. Braun Medical S.A.

Manufacturer's address and place of business.

Am Schwerzelshof 1, 34212 Melsungen, Germany / Am Schwerzelshof 1, 34212 Melsungen, Germany;

Carretera de Terrassa 121, 08191 Rubi (Barcelona), Spain / Carretera de Terrassa 121, 08191 Rubi (Barcelona), Spain.

Route de Sorge 9, 1023 Crissier, Switzerland / Route de Sorge 9, 1023 Crissier, Switzerland.