Ringer solution

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT Ringer's Solution (Solutio Ringeri)

Composition:

Active substances: sodium chloride, potassium chloride, calcium chloride dihydrate;

100 ml of solution contain sodium chloride 0.86 g, potassium chloride 0.03 g, calcium chloride dihydrate 0.0322 g;

Excipient: water for injections.

Molar composition, mmol per 1000 ml of product: Na+ – 147.15 mmol; K+ – 4.0 mmol;
Ca++ – 2.2 mmol; Cl- – 155.6 mmol.

Pharmaceutical form. Infusion solution.

Main physicochemical properties: clear, colorless liquid; theoretical osmolarity – 309 mosmol/L.

Pharmacotherapeutic group.
Solutions for intravenous administration. Solutions used for correction of electrolyte balance disorders.
ATC code B05B B01.

Pharmacological properties.

Pharmacodynamics.

Ringer's solution is a source of water and electrolytes. It may induce diuresis depending on the patient's condition.

Sodium – the principal cation of extracellular fluid, participates primarily in the control of water distribution, fluid balance, and osmotic pressure of body fluids. Sodium is also associated with chloride and bicarbonate in the regulation of acid-base balance of body fluids. Sodium plays an important role in neurotransmission and cardiac electrophysiology, as well as in renal metabolism.

Potassium – the principal intracellular cation, participates in carbohydrate utilization and protein synthesis, and is required for regulation of nerve conduction and muscle contraction, especially in the heart. Potassium is essential for many metabolic and physiological processes, including nerve conduction, muscle contractions, and acid-base balance. Normal plasma potassium concentration is approximately 3.5 to 5.0 mmol/L. Potassium is predominantly an intracellular cation, with the highest concentration found in muscle tissue; only about 2% of potassium is located in the extracellular fluid. Transport and retention of potassium ions within cells occurs against a concentration gradient via active transport mediated by the enzyme Na⁺/K⁺ ATPase.

Chloride – the main extracellular anion, closely associated with sodium metabolism.
Changes in the body's acid-base balance are reflected in changes in chloride ion concentration. Administration of large amounts of chloride ions may lead to a decrease in bicarbonate concentration, potentially resulting in acidosis.

Calcium – an important cation involved in the formation of bones and teeth (in the form of calcium phosphate and calcium carbonate). Approximately 99% of calcium is stored in bones, and only about 1% is present in tissues and body fluids. In its ionized form, calcium is essential for blood coagulation mechanisms, normal cardiac function, and regulation of neuromuscular excitability.

The pH of Ringer's infusion solution ranges from 4.5 to 7.0.

Pharmacokinetics.

The pharmacokinetic properties of this solution are determined by those of its components: sodium chloride, potassium chloride, and calcium chloride.

The volume and ionic composition of extracellular and intracellular fluid compartments are as follows:

Extracellular fluid – approximately 19 liters:
sodium – 142 mmol/L
potassium – 5 mmol/L
calcium – 2.5 mmol/L
chloride – 103 mmol/L

Intracellular fluid – approximately 23 liters:
sodium – 15 mmol/L
potassium – 150 mmol/L
calcium – 1 mmol/L
chloride – 1 mmol/L

Following administration of the radioactive isotope sodium-24 (²⁴Na), the half-life of the isotope is 11 to 13 days for 99% of the administered sodium. Isotope decay varies by tissue: it is rapid in muscle, liver, kidneys, cartilage, and skin, and very slow in erythrocytes, neurons, and bone. Sodium is primarily excreted by the kidneys. Small amounts of sodium are excreted in feces and sweat.

Factors affecting potassium shifts between intracellular and extracellular fluids, such as acid-base disturbances, may alter the relationship between plasma concentration and total body potassium. Potassium is mainly excreted by the kidneys. It is secreted in the distal tubules in exchange for sodium and hydrogen ions. The kidneys' ability to conserve potassium is limited; therefore, some potassium is excreted in urine even during significant potassium depletion. A certain amount of potassium is also eliminated in feces and, to a lesser extent, in sweat.

Plasma calcium concentration is regulated by parathyroid hormone, calcitonin, and vitamin D. Approximately 47% of plasma calcium exists in the ionized, physiologically active form, about 6% is complexed with anions such as phosphates or citrates, and approximately 30% is bound to proteins, primarily albumin. Changes in plasma albumin concentration—either increases (as in dehydration) or decreases (as seen in malignancies)—affect the proportion of ionized calcium. Thus, total plasma calcium concentration usually correlates with plasma albumin levels. Excess calcium is excreted by the kidneys, as well as in feces and bile. A small amount is excreted through the sweat glands of the skin and scalp. Calcium crosses the placenta and is excreted into breast milk.

Clinical characteristics.

Indications.

Used in hypovolemia and extracellular dehydration due to prolonged vomiting, diarrhea, extensive burns, frostbite, peritonitis, severe infectious diseases, shock conditions, collapse; during surgical interventions and in the postoperative period. It is used for dilution of concentrated electrolyte solutions.

Contraindications.

• Extracellular hyperhydration or hypervolemia;
• Hypertonic dehydration;
• Hypernatremia;
• Hyperkalemia;
• Hypercalcemia;
• Hyperchloremia;
• Hypercoagulation;
• Thrombophlebitis;
• Metabolic alkalosis;
• Severe renal failure (with oliguria/anuria);
• Decompensated heart failure;
• Severe arterial hypertension;
• Generalized edema (including pulmonary and cerebral edema) and ascites caused by liver cirrhosis;
• Concomitant use with cardiac glycosides.

Interaction with other medicinal products and other types of interactions.

Interaction related to sodium ions.

Concomitant use of medicinal products such as steroids/corticoids, including androgens, estrogens, anabolic hormones, corticotropin, mineralocorticoids, and carbenoxolone, may be accompanied by edema and hypertension caused by sodium and water retention in the body.

Interaction related to potassium ions.

Concomitant use with potassium-sparing diuretics (amiloride, spironolactone, triamterene and similar), ACE inhibitors and possibly angiotensin II receptor blockers, as well as with tacrolimus, cyclosporine, and potassium-containing preparations increases the risk of hyperkalemia development. Increased plasma potassium concentration may lead to potentially fatal hyperkalemia, especially in case of renal insufficiency.

Interaction related to calcium ions.

Since calcium enhances the effect of cardiac glycosides, concomitant use of such a combination may lead to severe, including fatal, cardiac arrhythmias. Concomitant use of calcium preparations with thiazide diuretics or vitamin D may lead to hypercalcemia.

Special precautions for use

During prolonged parenteral therapy, laboratory parameters should be monitored and clinical assessment of the patient's condition performed to control electrolyte concentrations and water-electrolyte balance every 6 hours (depending on the infusion rate). Administration of large volumes of the drug to patients with cardiac or pulmonary insufficiency requires monitoring of the functional status of these organs.

Administration of Ringer's solution may lead to fluid overload and/or overload with dissolved substances, which may cause decreased plasma electrolyte concentrations, hyperhydration, congestion, and pulmonary edema. The risk of developing a dilutional state is inversely proportional to the electrolyte concentration in the solution. Conversely, the risk of overload with dissolved substances leading to peripheral and pulmonary edema is directly proportional to the electrolyte concentration in the solution.

Since the drug contains sodium, it should be administered with caution to patients with hypertension, heart failure, renal insufficiency, preeclampsia, hyperaldosteronism, peripheral edema, or pulmonary edema, as well as to patients receiving certain medications (e.g., steroids/corticoids), due to the potential for sodium retention in the body.

Since the drug contains potassium, administration requires caution in patients with cardiac diseases or pathological conditions that may lead to hyperkalemia: severe renal insufficiency or severe adrenal insufficiency, acute dehydration, or extensive tissue damage (e.g., in severe burns), due to the potential for potassium retention in the body.

Since the drug contains calcium, administration should be performed under ECG monitoring, especially in patients receiving cardiac glycosides. Serum calcium concentration does not always reflect tissue calcium levels. Caution should be exercised during intravenous administration to prevent hemorrhage. The drug should be administered with caution to patients with impaired renal function or diseases associated with increased vitamin D levels, such as sarcoidosis. When Ringer's solution is administered simultaneously with blood products, coagulation may occur; therefore, if such concomitant use is necessary, separate infusion systems for blood transfusion and solution infusion should be used.

Ringer's infusion solution contains insufficient amounts of potassium and calcium ions to maintain their blood levels or correct deficiencies. Therefore, if electrolyte balance correction is required after restoration of circulating fluid volume (dehydration correction), appropriate potassium- and calcium-containing preparations should be used. During prolonged parenteral treatment, the patient should receive nutrients via an appropriate route (e.g., enteral or parenteral nutrition).

This solution is intended for intravenous use with sterile equipment. It is recommended to replace the intravenous administration set at least every 24 hours.

The solution should be used only if it is clear and the container is intact and sealed.

The physician should also consider the potential for adverse reactions to drugs administered concomitantly with Ringer's solution.

If an adverse reaction occurs, the infusion should be discontinued, the patient's condition assessed, and appropriate therapeutic measures initiated.

Use during pregnancy or breastfeeding

Studies on the use of Ringer's solution in pregnant women have not been conducted.

It is not known whether this drug is excreted in human milk. Since most drugs are excreted in human milk, Ringer's solution should be administered with caution during lactation.

Ability to affect reaction speed when driving or operating machinery

Data are unavailable due to the exclusive use of the drug under hospital conditions.

Administration and Dosage.

The solution is intended for intravenous use only.

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

The usual dose for adults is up to 1–2 L per day; the maximum dose depends on the patient's fluid and electrolyte balance, cardiovascular status, and renal function.

The infusion rate for adults is 60–80 drops/min or as a bolus infusion.

The administration of the solution should be based on the calculated maintenance or replacement fluid requirements for each individual patient.

Before administration, parenteral preparations should be visually inspected for the presence of particles and discoloration.

Children.

Studies on the use of Ringer's solution in children have not been conducted.

Overdose.

Administration of an excessive amount of solution may lead to disturbances in fluid and electrolyte balance (hypervolemia).

Overdose or excessively rapid administration of water and sodium may result in edema, particularly in cases of impaired renal sodium excretion.

Treatment of hypervolemia. At the first signs of hypervolemia, administration of the drug must be discontinued and hemodialysis initiated.

Excessive potassium administration may lead to hyperkalemia, especially in patients with renal insufficiency. Symptoms include paresthesia of extremities, muscle weakness, paralysis, cardiac arrhythmias, heart block, cardiac arrest, and confusion.

Treatment of hyperkalemia. At the first signs, administration of the drug must be discontinued, and calcium, insulin (with glucose), and sodium bicarbonate should be administered. Ion-exchange resins or hemodialysis are also effective.

Excessive administration of calcium salts may lead to hypercalcemia. Symptoms of hypercalcemia may include loss of appetite, nausea, vomiting, constipation, abdominal pain, muscle weakness, psychiatric disturbances, polydipsia, polyuria, nephrocalcinosis, kidney stones, and, in severe cases, cardiac arrhythmias and coma. In cases of too rapid intravenous administration of calcium salts, numerous symptoms of hypercalcemia may occur, as well as hot flashes and peripheral vasodilation.

Treatment of hypercalcemia. At the first signs of hypercalcemia, administration of the drug must be discontinued. Mild, asymptomatic hypercalcemia usually resolves after discontinuation of calcium and other agents promoting its development, such as vitamin D. In cases of severe manifestations, emergency treatment is required, aimed at enhancing diuresis (e.g., use of loop diuretics), hemodialysis, calcitonin, bisphosphonates, or sodium edetate.

Excessive administration of chlorides may lead to bicarbonate loss, resulting in acidosis.

Treatment. If necessary, appropriate symptomatic and supportive measures should be taken.

Adverse reactions.

Possible electrolyte imbalances (potassium, calcium, sodium, chlorides), chloride acidosis, and hyperhydration.

If adverse reactions occur, administration of the solution should be discontinued, the patient's condition assessed, and appropriate medical support provided.

The following adverse reactions were frequently observed during administration of Ringer's solution:

• Hyperhydration, cardiac failure in patients with heart disorders, pulmonary edema;
• Electrolyte imbalances.

Adverse reactions may be related to the administration technique, including phlebitis, infections, pain or reactions at the injection site, venous irritation, venous thrombosis or phlebitis extending from the injection site, and hemorrhage. Adverse reactions may also be associated with medicinal products added to the solution, which will determine the likelihood of any additional undesirable effects. If any adverse effects occur, administration of the solution must be discontinued.

In case of any adverse events, adverse reactions, or lack of therapeutic effect, please notify State Enterprise "Farmatreyd" at: Sambirska St., 85, Drohobych, Lviv region, Ukraine, 82111; tel.: /03244/ 2-40-27, 3-80-71; fax: /03244/ 3-99-94; mobile phone: +38-099-729-37-89; E-mail: [email protected], [email protected]

Shelf life. 2 years.

Storage conditions.

Store at a temperature not exceeding 25 °C. Do not freeze.

Keep out of reach of children.

Incompatibilities.

Other medicinal products may be added to Ringer's solution only if they are soluble and stable in it and have a similar pH (see section "Pharmacological properties").

Calcium salts are known to be incompatible with a wide range of medicinal products, as they may form complexes leading to precipitate formation. Listed below are medicinal products known to be incompatible with Ringer's solution and therefore should not be mixed (the list is not exhaustive):

• Amphotericin B;
• Cortisone;
• Erythromycin lactobionate;
• Ethamivan;
• Ethyl alcohol;
• Sodium thiopental;
• Disodium edetate;

Packaging.

200 ml, 250 ml, 400 ml or 500 ml in polyvinyl chloride containers.

Prescription status.

Prescription only.

Manufacturer.

Subsidiary enterprise "Farmatreyd".

Manufacturer's address and place of business.

Sambirska St., 85, Drohobych, Lviv region, Ukraine, 82111.

Marketing Authorization Holder.

Subsidiary enterprise "Farmatreyd".

Address of the Marketing Authorization Holder.

Sambirska St., 85, Drohobych, Lviv region, Ukraine, 82111.