Ringer solution

INSTRUCTION for medical use of the medicinal product RINGER’S SOLUTION

Composition:

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

1 ml of solution contains sodium chloride 8.6 mg, potassium chloride 0.3 mg, calcium chloride dihydrate (calculated as calcium chloride) 0.24 mg;

Excipient: water for injections.

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, is primarily involved 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 the acid-base balance of body fluids.

Potassium, the principal intracellular cation, participates in carbohydrate utilization and protein synthesis, and is required for the regulation of nerve conduction and muscle contraction, especially in the heart.

Chloride, the main extracellular anion, is closely related to sodium metabolism. Changes in the body's acid-base balance are reflected in changes in chloride concentration. Infusion of large amounts of chloride ions may cause loss of bicarbonate ions, leading to acidosis. For this reason, Ringer's solution is buffered with lactate or acetate.

Calcium, an important cation, contributes to the formation of bones and teeth (in the form of calcium phosphate and calcium carbonate). In ionized form, calcium is required for the functional mechanism of blood coagulation, normal cardiac function, and regulation of neuromuscular excitability.

Pharmacokinetics.

Na+ and Cl− ions administered with Ringer's solution undergo the same pharmacokinetics as those ingested with food. They freely distribute throughout all organs, tissues, and interstitial spaces and are excreted via glomerular filtration in the kidneys. Substantial reabsorption of Na+ and Cl− ions occurs in the tubules, primarily in the loop of Henle and distal tubules, including blockade by loop and thiazide diuretics, respectively.

Potassium ions (K+) are freely filtered at the glomeruli but almost completely reabsorbed in the proximal tubules, with only 10% of filtered K+ ions being excreted. Secretion in the distal tubules and collecting ducts can significantly increase K+ elimination. The kidneys have a limited ability to retain K+ concentration. Therefore, when Na+ concentration in the distal tubules is high, K+ loss may be substantial, potentially leading to hypokalemia. This justifies the inclusion of K+ in Ringer's solution.

Calcium ion (Ca++) homeostasis is well regulated by hormones and rarely requires clinical intervention via intravenous infusion.

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 intervention and in the postoperative period.

Used for dilution of concentrated electrolyte solutions.

Contraindications.

• Extracellular hyperhydration or hypervolemia;
• hypertonic dehydration;
• hyperkalemia;
• hypernatremia;
• hypercalcemia;
• hyperchloremia;
• hypercoagulation;
• thrombophlebitis;
• metabolic alkalosis;
• severe renal failure (with oliguria/anuria);
• decompensated heart failure;
• severe arterial hypertension;
• generalized edema (including pulmonary edema, cerebral edema) and ascites caused by liver cirrhosis;
• concomitant use with digitalis glycosides.

Interaction with other medicinal products and other types of interactions.

Interaction due to the presence of sodium in the solution:

• corticosteroids and carbenoxolone, which cause sodium and water retention (with edema and arterial hypertension).

Possible increased sodium retention in the body when used concomitantly with the following medicinal products: nonsteroidal anti-inflammatory drugs, androgens, anabolic hormones, estrogens, corticotropin, mineralocorticoids, vasodilators or ganglion blockers.

Interaction due to the presence of potassium in the solution:

• potassium-sparing diuretics (e.g., amiloride, spironolactone, and triamterene, alone or in combination);
• angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor inhibitors;
• tacrolimus, cyclosporine.

When used with potassium-containing agents, the risk of developing hyperkalemia increases.

All these agents increase plasma potassium concentration and may lead to fatal hyperkalemia, especially in renal failure, which in turn potentiates hyperkalemia.

Succinylcholine and potassium, when used concomitantly, may cause significant hyperkalemia, thereby enhancing the negative effect on cardiac rhythm.

Interaction due to the presence of calcium in the solution:

• cardiac glycosides (cardiotonic glycosides), whose action is enhanced in the presence of calcium and may lead to serious or fatal cardiac arrhythmias;
• thiazide diuretics or vitamin D, which may lead to hypercalcemia when used concomitantly with calcium.

Solutions containing calcium, such as Ringer's solution, should not be used for reconstituting ceftriaxone or for further dilutions of intravenous solutions, as precipitation may occur.

Special precautions for use.

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

Administration of intravenous solutions may lead to fluid and/or solution overload, hyperhydration, congestion, and pulmonary edema. The risk of developing dilutional hyponatremia is inversely proportional to the electrolyte concentration. The risk of developing solution overload leading to congestion with peripheral edema and pulmonary edema is directly proportional to the electrolyte concentration.

Due to the presence of sodium ions, the solution should be used with caution in patients with arterial hypertension, renal and cardiovascular insufficiency, congestive heart failure (especially in the postoperative period), patients with preeclampsia, aldosteronism, elderly patients, and patients with clinical conditions associated with sodium retention and edema.

Sodium-containing solutions should be administered with caution to patients receiving corticosteroids or corticotropin.

Due to the potassium content, caution is required when administering the solution to patients with heart disease and clinical conditions associated with potassium retention, such as renal insufficiency or adrenocortical insufficiency, acute dehydration, or extensive tissue destruction occurring in severe burns.

In patients with impaired renal excretory function, administration of the solution may result in retention of sodium or potassium.

Calcium administration should be performed with consideration of ECG findings, especially in patients receiving cardiac glycosides (e.g., digoxin). Serum calcium levels do not always reflect tissue calcium levels.

The presence of calcium ions requires caution when co-administered with blood products due to the potential risk of coagulation.

Calcium should be administered parenterally to patients receiving cardiac glycosides with particular caution.

Due to the presence of calcium in this solution:

• Extravasation should be avoided during intravenous infusion;
• The solution should be used with caution in patients with impaired renal function or diseases associated with elevated vitamin D concentrations, such as sarcoidosis;
• In case of concomitant (i.e., simultaneous) transfusion, the solution must not be administered through the same infusion set/system due to the risk of coagulation.

Fatal reactions due to formation of ceftriaxone-calcium precipitates in the lungs and kidneys have been reported in premature infants and neonates under 1 month of age. Ceftriaxone must not be mixed or co-administered with calcium-containing solutions in any patient group, neither through separate infusion lines nor at different infusion sites.

In any case, for adult patients, ceftriaxone and calcium-containing solutions may be used sequentially if different infusion sites are used, if the infusion set is replaced, or if the infusion lines are flushed with saline between infusions. Sequential administration of ceftriaxone and calcium-containing solutions should be avoided in cases of hypovolemia.

Ringer's solution contains insufficient concentrations of potassium and calcium to maintain balance of these ions or correct their deficiencies. Therefore, after treatment of dehydration, the intravenous infusion fluid should be replaced with a solution providing balanced replacement of these ions. During prolonged parenteral therapy, the patient should receive nutritional support via an appropriate route.

Ringer's solution contains 147.2 mmol/L of sodium. Particular caution is recommended when administering this solution to patients on a sodium-controlled diet.

Ringer's solution contains 4.02 mmol/L of potassium. Caution should be exercised when administering to patients with impaired renal function and to those on a potassium-controlled diet.

This solution is intended for intravenous use with sterile equipment. It is recommended to change 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 possibility of adverse reactions to drugs used concomitantly with Ringer's Solution.

If an adverse reaction occurs, 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 unknown whether this medicinal product is excreted in human breast milk. Since most drugs are excreted in human breast milk, Ringer's Solution should be administered with caution to nursing women.

Ability to affect reaction rate while driving or operating machinery.

Information not available.

Method of Administration and Dosage

The solution is intended for intravenous use only.

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

The usual adult dose is up to 1–2 liters 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 rapid infusion.

The solution should be administered according to the calculated maintenance or replacement fluid requirements for each individual patient.

Parenteral preparations should be visually inspected for particulate matter and discoloration prior to use.

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, hypernatremia, hypercalcemia, hyperchloremia) and acid-base equilibrium. Treatment is symptomatic.

Overdose or too rapid infusion of this solution may result in water and sodium overload, with a risk of edema, especially in the presence of impaired renal sodium excretion. In such cases, hemodialysis may be necessary.

Excessive potassium administration may lead to hyperkalemia, particularly in patients with impaired renal function. Symptoms may include: limb paresthesia, muscle weakness, paralysis, cardiac arrhythmias, heart block, cardiac arrest, and confusion.

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

Excessive administration of calcium salts may cause hypercalcemia. Symptoms of hypercalcemia may include anorexia, nausea, vomiting, constipation, abdominal pain, muscle weakness, mental disturbances, polydipsia, polyuria, nephrocalcinosis, kidney stones, and, in severe cases, cardiac arrhythmias and coma. Too rapid intravenous administration of calcium salts may also cause numerous symptoms of hypercalcemia, as well as an unusual taste in the mouth (chalk-like taste), flushing, 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 manifestations, emergency treatment is required (e.g., loop diuretics, hemodialysis, calcitonin, bisphosphonates, or trisodium edetate).

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

When overdose is caused by the addition of substances/medicinal products to the solution, the symptoms of excessive infusion will also depend on the properties of these added agents.

In case of accidental overdose, infusion should be discontinued and the patient should be monitored for symptoms related to the infused additive. Appropriate symptomatic and supportive measures should be applied as necessary.

Side effects.

Electrolyte disturbances (potassium, calcium, sodium, chloride), chloride acidosis, hyperhydration, site reactions, tachycardia, hypersensitivity reactions, allergic reactions, or anaphylaxis/anaphylactoid symptoms may occur.

The following side effects were frequently observed during administration of Ringer's Solution:

• hyperhydration, heart failure in patients with cardiac disorders, pulmonary edema;
• electrolyte imbalance.

Side effects 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, hemorrhage (extravasation). Side effects may also be associated with the medicinal product added to the solution, which will determine the likelihood of any additional adverse effects.

If side effects occur, the infusion should be discontinued, the patient's condition assessed, and appropriate supportive measures provided.

Shelf life. 2 years.

Storage conditions.

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

Incompatibilities.

Before using Ringer's Solution, its compatibility with other concurrently used medicinal products should be evaluated. To reduce the risk of potential incompatibility arising from mixing this solution with other added medicinal products, the final infusion solution must be inspected immediately after mixing, before administration, and periodically during administration for turbidity or precipitation.

Other medicinal products may be added to Ringer's Solution only if they are soluble and stable in it and have a similar pH.

Ringer's Solution is incompatible with ceftriaxone (see section "Special precautions for use").

Calcium salts are known to be incompatible with a wide range of medicinal products. 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;
• ethimivan;
• ethyl alcohol;
• sodium thiopental;
• disodium edetate.

Packaging.

200 ml, 400 ml in glass bottles.

Prescription status. Prescription only.

Manufacturer. LLC "Yuria-Pharm".

Manufacturer's address and location of business activity.

108, Kobzarska Street, Cherkasy, Cherkasy region, 18030, Ukraine. Tel.: (044) 281-01-01.