Ringer solution

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT Ringer's Solution (RINGER'S SOLUTION)

Composition:

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

1 ml of solution contains: sodium chloride – 8.60 mg; potassium chloride – 0.30 mg; calcium chloride dihydrate – 0.33 mg;

Excipient: water for injections.

Ion composition of the medicinal product: sodium ion – 147.15 mmol/l; potassium ion – 4.0 mmol/l; calcium ion – 2.2 mmol/l; chloride ion – 155.6 mmol/l.

Pharmaceutical form. Infusion solution.

Main physico-chemical properties: clear, colorless liquid; theoretical osmolarity – 309 mosmol/l; pH 5.0–7.5.

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 an isotonic electrolyte solution (Na+, K+, Ca2+ and Cl-) with the same concentration as in blood plasma; therefore, its use does not lead to an increase in the concentration of these electrolytes in blood plasma when the dosage is observed.

Ringer's solution is a rehydration agent that exerts a detoxifying effect and normalizes the water and electrolyte composition of blood. When used as a means of replenishing circulating blood volume, due to its rapid exit from the vascular bed into the interstitial space, the effect lasts only 30–40 minutes (the solution is suitable only for short-term blood volume expansion).

Electrolytes Na+, K+, Ca2+ and Cl- are used to maintain or correct water-electrolyte homeostasis (including blood volume, osmotic balance, acid-base status, as well as specific ion properties).

Infusion of large amounts of chloride ions may cause bicarbonate ion loss, leading to acidosis.

Pharmacokinetics.

Since Ringer's solution is administered intravenously, its bioavailability is 100%.

Sodium and chloride are distributed mainly in the extracellular space, while potassium and calcium are distributed intracellularly.

The kidneys are the main regulators of water-electrolyte balance. Sodium and chloride are primarily excreted via the kidneys, as well as in small amounts through the skin and gastrointestinal tract. 90% of potassium is excreted in urine, 10% via the gastrointestinal tract. Calcium is excreted in approximately equal proportions via the kidneys and the gastrointestinal tract.

The pharmacokinetics of each component of the solution are not altered when administered simultaneously.

Clinical characteristics.

Indications.

• Correction of water-electrolyte imbalances in various pathological conditions, including hypochloremic alkalosis;
• replenishment of chloride in the body;
• short-term expansion of circulating blood volume;
• isotonic dehydration;
• hypotonic dehydration;
• solvent for compatible concentrated electrolyte solutions and medicinal products.

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 due to liver cirrhosis;
• concomitant use with cardiac glycosides.

Interaction with other medicinal products and other types of interactions.

Interaction due to the presence of sodium in the solution

Concomitant use of medicinal products such as steroids/corticosteroids, 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 due to the presence of potassium in the solution

Concomitant use with potassium-sparing diuretics (amiloride, spironolactone, triamterene, and similar agents), angiotensin-converting enzyme (ACE) inhibitors, and possibly angiotensin II receptor inhibitors, as well as with tacrolimus, cyclosporine, succinylcholine, and potassium-containing preparations, increases the risk of hyperkalemia. Elevated plasma potassium concentration may lead to potentially fatal hyperkalemia, especially in the presence of renal impairment.

Potassium administration may reduce the therapeutic effect of cardiac glycosides.

Corticosteroids and loop diuretics may increase renal potassium excretion.

Interaction due to the presence of calcium in the solution

Since calcium potentiates the effects of cardiac glycosides, concomitant use of this combination may lead to severe, including fatal, cardiac arrhythmias.

Concomitant use of calcium-containing preparations with thiazide diuretics or vitamin D may lead to hypercalcemia.

Concomitant use of calcium-containing solutions with bisphosphonates, fluorides, fluoroquinolones, and tetracyclines may reduce the bioavailability (decreased absorption) of the aforementioned agents.

Interaction with ceftriaxone

Do not administer Ringer's solution and ceftriaxone simultaneously, even if different infusion systems and different administration sites are used (see section "Special precautions").

Special precautions for use.

In patients with cardiac and/or pulmonary insufficiency, administration of large volumes of solution is possible only in exceptional cases and under medical supervision.

During prolonged infusion therapy, laboratory parameters should be monitored and the patient's clinical condition assessed every 6 hours (depending on the infusion rate) to monitor electrolyte concentrations and fluid-electrolyte balance.

Administration of intravenous solutions may cause fluid and/or solution overload, hyperhydration, congestion, and pulmonary edema. The risk of dilutional effects is inversely proportional to the electrolyte concentration. The risk of 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 administered with caution to 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.

Solutions containing sodium should be used cautiously in patients receiving corticosteroids or corticotropin.

Due to the presence of potassium, 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 as occurs in severe burns.

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

Since the preparation 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. Care should be taken during intravenous administration to prevent hemorrhage. Caution is required when administering 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 should be used for transfusion and infusion.

Fatal cases due to formation of ceftriaxone-calcium precipitates in the lungs and kidneys have been reported in premature infants and newborns up to 1 month of age. For patients of any age, ceftriaxone must not be mixed or administered simultaneously with any intravenous solutions containing calcium, even via separate infusion lines or at different infusion sites.

Ringer's solution contains insufficient concentrations of potassium or calcium for maintaining balance of these ions or correcting their deficiencies. Therefore, after treatment of dehydration, the intravenous infusion fluid should be replaced with a solution that ensures adequate balance of these ions.

Ringer's solution contains 147 mmol/L of sodium. Particular caution is recommended when administering to patients on a sodium-restricted diet.

Ringer's solution contains 4 mmol/L of potassium. Particular caution is recommended when administering to patients with impaired renal function or patients on a potassium-restricted diet.

In emergency situations where the solution is administered under pressure infusion, ensure prior to starting infusion that the container and infusion system are fully unobstructed.

Ringer's 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 medicinal products administered 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.

Caution should be exercised when using during pregnancy, especially in cases of eclampsia.

It is unknown whether this medicinal product passes into human milk. Since most drugs are excreted in human milk, Ringer's solution should be administered with caution to women who are breastfeeding.

Ability to affect reaction speed when driving or operating machinery.

Data are lacking due to the exclusive use of the medicinal product under hospital conditions.

Dosage and Administration

The solution is intended for intravenous use only.

The rate and duration of infusion, as well as the volume of infused solution, depend on the patient's clinical condition, body weight, age, type and degree of dehydration/hypovolemia, laboratory parameters, and concomitant use of other medicinal products.

Maximum daily dose

Up to 40 mL/kg body weight per day, corresponding to: 5.88 mmol of sodium /kg body weight and 0.16 mmol of potassium /kg body weight per day.

Maximum daily dose of electrolytes

The maximum daily dose of potassium is 2 mmol/kg/day.

The maximum daily dose of sodium ranges from 3 to 6 mmol/kg/day, depending on requirements.

Maximum infusion rate

The maximum infusion rate is 5 mL/kg body weight per hour.

The maximum drip infusion rate is approximately 1.7 drops/kg body weight per minute.

When Ringer's solution is used concomitantly with other intravenous medicinal products, their compatibility must be taken into account.

A dosage of 30 mL/kg body weight per day only meets the basic physiological electrolyte requirements of the body.

In the postoperative period and in patients in intensive care units, due to limited renal concentrating capacity and increased accumulation of metabolic end products, the dosage may be increased to approximately 40 mL/kg body weight per day.

The basal cation requirement is approximately 1.5–3.0 mmol sodium/kg/day and 0.8–1.0 mmol potassium/kg/day.

Children

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

Overdose

Overdose or too rapid administration of the solution may lead to fluid and sodium overload, with a risk of developing edema, especially in the presence of impaired renal sodium excretion. In such cases, hemodialysis may be required.

Excessive administration of the solution may result in electrolyte and acid-base imbalances (hypernatremia, hypercalcemia, hyperchloremia) and hyperhydration.

In case of overdose of a medicinal product administered concomitantly with Ringer's solution, appropriate therapy should be applied.

Treatment

Discontinuation of the medicinal product, use of diuretics with continuous monitoring of electrolyte balance, correction of electrolyte disturbances; in some cases, hemodialysis may be necessary. Treatment is symptomatic.

Adverse reactions.

Electrolyte imbalances (potassium, calcium, sodium, chloride), chloride-resistant acidosis, hyperhydration may occur; heart failure – in patients with cardiac diseases or pulmonary edema; tachycardia; hypersensitivity reactions, allergic reactions; reactions at the site of administration.

Adverse reactions may occur due to improper administration technique: febrile reactions, infections at the site of administration, pain or reactions at the site of administration, venous irritation, venous thrombosis or phlebitis extending from the site of administration, as well as extravasation.

Adverse reactions may occur as a result of adding additional medicinal products to the solution; the nature of the added substance/medicinal product determines the likelihood of the respective adverse reaction.

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

Reporting suspected adverse reactions.

Reporting of suspected adverse reactions after marketing authorization is important. It allows continuous monitoring of the benefit-risk ratio of the medicinal product. Healthcare professionals should report any suspected adverse reactions.

Shelf life. 2 years.

Storage conditions.

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

Incompatibilities.

Before using Ringer's solution, its compatibility with other medicinal products to be used concomitantly should be evaluated.

To minimize the risk of possible incompatibility arising from mixing this solution with other added medicinal products, the final infusion solution should be visually inspected for turbidity or precipitation immediately after mixing, before administration, and periodically during administration.

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. Medicinal products containing oxalates, phosphates, and carbonates/bicarbonates may precipitate when mixed with Ringer's solution.

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 or 400 ml in bottles; 250 ml or 500 ml in bags.

Prescription category. Prescription only.

Manufacturer. Limited liability company "Novofarm-Biosyntez".

Manufacturer's address and location of business activity.

38 Zhytomyrska Street, city of Zviahel, Zviahel district, Zhytomyr region, 11700, Ukraine.