Plasmoven®

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT Plasmoven® (Plasmoven)

Composition:

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

1 ml of solution contains sodium chloride 6.80 mg, potassium chloride 0.30 mg, calcium chloride dihydrate 0.37 mg, magnesium chloride hexahydrate 0.20 mg, sodium acetate trihydrate 3.27 mg, L-malic acid 0.67 mg;

Electrolyte concentrations: sodium — 145.0 mmol/L, potassium — 4.0 mmol/L, calcium — 2.5 mmol/L; magnesium — 1.0 mmol/L, chloride — 127.0 mmol/L; acetate — 24.0 mmol/L, malate — 5.0 mmol/L;

Excipients: sodium hydroxide, water for injections.

Pharmaceutical form. Infusion solution.

Main physicochemical properties: clear, colorless liquid. Theoretical osmolarity: 309 mOsm/L; pH: 5.1–5.9.

Pharmacotherapeutic group. Plasma substitutes and perfusion solutions. Solutions for intravenous administration. 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 the extracellular and intracellular compartments.

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

Pharmacokinetics.

Since Plasmaven® is administered intravenously, its bioavailability is 100%.

Sodium and chlorides are distributed mainly in the extracellular compartment, 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 enteric 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. Excretion of acetates and malates in urine 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 interstitial fluid losses in the case of isotonic dehydration with existing or threatened 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 Plasmoven® at the same concentrations as in blood plasma. Therefore, use of the medicinal product 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.

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

Medicinal products interacting with potassium.

Suxamethonium, angiotensin-converting enzyme (ACE) inhibitors, NSAIDs, 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 failure, which enhances the hyperkalemic effect and may result in cardiac arrhythmia.

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

Medicinal products interacting with calcium.

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

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

Medicinal products interacting with malate.

Alkalinization of urine following administration of bicarbonate precursors or bicarbonate increases renal clearance of acidic medicinal products.

The half-life of major medicinal products, especially sympathomimetics (e.g., ephedrine, pseudoephedrine) and stimulants (e.g., dexamphetamine sulfate, phenylpropanolamine 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").

Plasmoven® should be administered with particular caution and under continuous monitoring to patients with the following conditions:

• Hypernatraemia;
• Hyperchloraemia;
• Renal insufficiency;
• Coma of unknown origin;
• Concomitant treatment with digitalis preparations;
• Hyperkalaemia or conditions that may lead to hyperkalaemia, including Addison's disease, sickle cell anaemia;
• Hypertonic dehydration, arterial hypertension, impaired renal function, presence or risk of eclampsia, aldosteronism or other conditions, as well as concomitant treatment with drugs (e.g. corticoids/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 where sodium intake restriction is indicated, such as mild to moderate heart failure, peripheral oedema, generalized oedema, pulmonary oedema, pre-eclampsia or extracellular hyperhydration (for more severe conditions, see section "Contraindications");
• Conditions where calcium intake restriction is indicated, 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").

Solutions containing potassium salts should be administered with caution to patients with heart disease or conditions that may lead to hyperkalaemia, 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 performed simultaneously, 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 on the added substance approved by the respective manufacturer must be taken into account.

Solutions containing anions that are metabolized should be administered with caution to patients with respiratory disorders.

Clinical monitoring should include serum ionogram, fluid balance and pH.

During prolonged parenteral therapy, appropriate nutritional support should be provided to the patient.

Elderly patients.

Treatment of elderly patients, who more frequently suffer from heart failure and have impaired renal function, should be closely monitored, and the dose should be 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, plasma and urinary electrolyte concentrations is required.

In short-term volume replacement in cases of haemorrhage 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 system, applying aseptic technique. The system should be primed with the solution to prevent air entry.

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

Important information about excipients.

This medicinal product contains sodium. This should be taken into consideration if the patient is on a sodium-controlled diet.

Use during pregnancy or breastfeeding.

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

Plasmoven® should be used with caution in pregnant women with toxemia.

Ability to affect reaction speed when driving or operating machinery.

Plasmoven® has no effect or has a negligible effect on the ability to drive or operate machinery.

Administration and Dosage.

Dosage.

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

Adults.

Maximum daily dose. The infused volume should not exceed 40 mL/kg body weight per day (corresponding to 5.8 mmol sodium per 1 kg body weight and 0.16 mmol potassium per 1 kg body weight).

Additional fluid losses (e.g., due to fever, diarrhea, vomiting) 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 are permitted, for example, via rapid infusion (under pressure).

Maximum infusion rate. The infusion rate of the medicinal product should not exceed 100 mL per hour.

When treating dehydration, the maximum infusion rate is 5 mL/kg body weight per hour, corresponding to 0.7 mmol sodium per 1 kg body weight per hour and 20 µmol potassium per 1 kg body weight per hour.

For short-term restoration of intravascular volume, the maximum infusion rate depends on the clinical situation.

In life-threatening situations, 500 mL of the medicinal product may be rapidly administered manually under pressure.

Solvent. When Plasmoven® is used as a solvent, dosage and infusion rate are primarily determined based on the characteristics and dosing regimen of the dissolved agent.

Pediatric population.

Dosage is determined by the 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:

Additional fluid losses (e.g., due to fever, diarrhea, vomiting) 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 indicated 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:

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 kg body weight per hour and 20 μmol of potassium per kg body weight per hour.

Elderly patients.

The same doses as for adults are generally used, but attention should be paid to patients with conditions such as cardiac or renal insufficiency, which may be associated with advanced age (see section "Special precautions").

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.

Route of administration.

For intravenous infusion only.

Plasmoven® may be administered into peripheral veins (regarding pH and theoretical osmolarity, see section "Pharmaceutical particulars").

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

During administration, fluid balance, plasma electrolyte concentrations, and pH should be monitored.

Plasmoven® may be administered as long as there are indications for fluid replacement.

Do not insert needle(s) into non-designated areas of the plastic bottle—only into sterile ports!

For infusion therapy, follow this procedure:

1. Remove the protective plastic cap with tamper-evident seal (if present).
2. Remove protective closure(s) No. 1 as shown in Fig. 1 and Fig. 2 (manufacturer may use different types and materials for protective closures).
3. Remove the needle cap and insert the needle into any of the designated ports No. 2 of the infusion bottle (see Fig. 1 and Fig. 2).
4. The other sterile port may be used either for adding other medicinal products into the infusion bottle (No. 4, see Fig. 3) or, in case of insufficient flow rate, for a venting needle (No. 4, see Fig. 3).
5. Hang the solution bottle using the special ring No. 3 located at the bottom of the bottle (see Fig. 3).

Children.

The medicinal product may be used in children aged 28 days and older 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 patients with 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 insufficiency. Symptoms include limb paresthesia, 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 manifestations of 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 (disturbances in heart rhythm). In patients with concomitant hypocalcemia, muscle hypertonia, muscle twitching, and tetany may develop. Treatment of bicarbonate-related metabolic alkalosis 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 flushes, and peripheral vasodilation. Mild, asymptomatic hypercalcemia usually resolves after discontinuation of calcium and other medicinal products that may contribute to its development, such as vitamin D. In cases of severe hypercalcemia, emergency treatment is required (e.g., loop diuretics, hemodialysis, calcitonin, bisphosphonates, or trisodium edetate).

If overdose is related to medicinal products added to the solution, signs and symptoms of overdose will also depend on the nature of the added substances. In case of accidental overdose, treatment should be discontinued immediately, and the patient should be examined for relevant signs and symptoms associated with the added medicinal product. If necessary, appropriate symptomatic and supportive measures should be taken.

Treatment.

Immediately stop the infusion. Subsequent 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.

Side effects.

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 rarely.

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

Reporting of suspected adverse reactions.

Reporting of suspected adverse reactions after marketing authorization of the medicinal product is of great importance. It allows ongoing monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients, as well as their legal representatives, are encouraged to report all suspected adverse reactions and/or lack of efficacy of the medicinal product via the Automated Information System for Pharmacovigilance at the following link: https://aisf.dec.gov.ua.

Shelf life. 3 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C. Do not freeze.

Keep out of reach of children.

Incompatibilities.

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

Packaging.

500 ml in a bottle.

Prescription status. Prescription only.

Manufacturer. JSC "Pharmaceutical Company "Darnytsia".

Manufacturer's address and location of its business activities.

13, Boryspilska Street, Kyiv, 02093, Ukraine.