Osmolife

INSTRUCTION for medical use of the medicinal product OSMOLIFE (OSMOLIFE)

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;

Excipients: sodium hydroxide, water for injections;

Electrolyte concentrations: sodium – 145 mmol/l; potassium – 4 mmol/l; magnesium – 1 mmol/l; calcium – 2.5 mmol/l; chloride – 127 mmol/l; acetate – 24 mmol/l; malate – 5 mmol/l.

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 administration. Solutions used for correction of electrolyte balance disorders. Electrolytes.

ATC code B05B B01.

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 compartments.

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

Pharmacokinetics

Since Osmylife is administered intravenously, its bioavailability is 100%.

Sodium and chloride are distributed primarily in the extracellular compartment, whereas potassium, magnesium, and calcium are distributed predominantly intracellularly. The kidneys represent 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 intraintestinal 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 decrease rapidly. Excretion of acetates and malates in urine increases during infusion; however, their metabolism in body tissues is so rapid that only minor fractions are detectable in urine.

Clinical Characteristics

Indications

Replacement of interstitial fluid losses in cases of isotonic dehydration when acidosis is present or threatened.

Contraindications

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

Hyperhydration.

Severe congestive heart failure.

Renal insufficiency 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 Osmodayf at the same concentrations as in blood plasma. Therefore, administration of Osmodayf 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 (NSAIDs), corticosteroids/steroids, and carbenoxolone may lead to sodium and water retention (with edema and arterial hypertension).

Medicinal products interacting with potassium

Suxamethonium, 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 cases of renal insufficiency, which enhances the hyperkalemic effect and may result in cardiac arrhythmia.

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

Medicinal products interacting with calcium

The effect of digitalis glycosides (cardiotonic digitalis agents) may be enhanced during 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 a bicarbonate precursor or bicarbonate increases renal clearance of acidic drugs.

The half-life of major medicinal products, especially sympathomimetics (e.g., ephedrine, pseudoephedrine) and stimulants (e.g., dexamfetamine sulfate, fenfluramine hydrochloride), is prolonged when solutions containing malate are administered simultaneously.

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").

Osmodayf should be administered with particular caution and 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, such as Addison's disease, sickle cell anaemia;
• 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 restriction of sodium intake, such as mild to moderate cardiac insufficiency, peripheral oedema, generalized oedema, pulmonary oedema, pre-eclampsia or extracellular hyperhydration (for more severe conditions, see section "Contraindications");
• conditions requiring restriction of calcium intake, such as sarcoidosis.

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

Potassium-containing solutions 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;
• when blood is being transfused simultaneously, this solution must not be administered through the same infusion system as blood components.

Use as a solvent

Caution! When using the medicinal product as a solvent, safety information regarding the added substance approved by the respective manufacturer should 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

Elderly patients, who more frequently suffer from cardiac insufficiency and impaired renal function, should be carefully monitored during treatment, 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 urine flow must be ensured, and careful monitoring of fluid balance, plasma and urine electrolyte concentrations is essential.

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

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 Osmodayf 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 parameters are carefully monitored.

Osmodayf should be used with caution in pregnant women with toxemia.

Osmodayf should be used with caution in pregnancy-induced hypertension (pre-eclampsia).

Effect on ability to drive and use machines

Osmodayf has no effect or has a negligible effect on the ability to drive 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) 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 need to 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 used, 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 sodium per 1 kg body weight per hour and 20 µmol 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.

Solvent

When using OsmaLyte 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.

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 or for short-term replenishment of intravascular volume, the above-mentioned doses may need to 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 1 kg body weight per hour and 20 µmol of potassium per 1 kg body weight per hour.

Elderly patients

The same doses as for adults are primarily used; however, attention should be paid to patients with 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 between 4 and 6 mmol/L/day for most cases, depending on the patient's condition and concomitant risk factors.

Method of administration

For intravenous infusion only.

Osmodil can be administered via peripheral veins (pH and theoretical osmolarity – see section "Pharmaceutical particulars").

All air must be removed from the infusion system before administration, as otherwise there is a risk of air embolism during infusion.

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

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

Children

The drug can be used in children from 28 days of age, as 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, especially in cases of impaired renal excretion of sodium. In such cases, additional hemodialysis may be required.

Excessive potassium administration may lead to hyperkalemia, particularly in patients with renal insufficiency. Symptoms include extremity 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 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 (disturbances in heart rhythm). In patients with concomitant hypocalcemia, increased muscle tone, muscle twitching, 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 contributing to its development, such as vitamin D. In cases of severe hypercalcemia, urgent treatment is required (e.g., loop diuretics, hemodialysis, calcitonin, bisphosphonates, or sodium edetate).

If overdose is related to medicinal products 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 examined for appropriate signs and symptoms related to the substance. Symptomatic and supportive measures should be taken as necessary.

Treatment

Immediately discontinue 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").

Adverse reactions are classified by system organ classes according to MedDRA and by frequency: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), frequency not known: cannot be estimated from the available data.

Immune system disorders

Frequency not known: isolated cases of hypersensitivity reactions such as urticaria have been reported after intravenous administration of magnesium salts.

Possible hyperhydration, pulmonary edema, and electrolyte disturbances.

Gastrointestinal disorders

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

General disorders and administration site conditions

Adverse reactions such as fever, injection site infection, local pain or reaction, venous irritation, venous thrombosis or phlebitis, injection site reactions, and extravasation may be caused by the route of administration.

Adverse reactions may also be related to medications added to the solution. The likelihood of this depends on the type of added drug.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after medicine authorization is important. It allows continuous monitoring of the benefit-risk balance of the medicine. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life. 2 years.

Shelf life after first opening of the bottle or vial

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

Storage conditions

Store in the original packaging at a temperature not exceeding 25 °C. Keep out of reach of children. Do not freeze.

Incompatibilities

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

Packaging

200 ml or 400 ml in bottles (vials).

Prescription status

Prescription only.

Manufacturer

JSC "Halychpharm".

Manufacturer's address and location of its business activities

6/8 Opryshkivska Street, Lviv, 79024, Ukraine