Balance 4.25% glucose 1.75 mmol/l calcium

INSTRUCTION for medical use of the medicinal product Balance 4.25% Glucose, 1.75 mmol/l Calcium (balance 4.25% Glucose, 1.75 mmol/l Calcium)

Composition:

Active substances: calcium chloride dihydrate; sodium chloride; sodium (S)-lactate solution (sodium (S)-lactate); magnesium chloride hexahydrate; glucose monohydrate (anhydrous glucose).

Before mixing

1 litre of acidic electrolyte solution based on glucose contains:

Calcium chloride dihydrate	0.5145 g
Sodium chloride	11.279 g
Magnesium chloride hexahydrate	0.2033 g
Glucose monohydrate (anhydrous glucose)	93.5 g (85.0 g)

1 litre of alkaline lactate solution contains:

sodium (S)-lactate solution 15.69 g

(sodium (S)-lactate 7.85 g)

After mixing

1 litre of neutral, ready-to-use solution contains:

Calcium chloride dihydrate	0.2573 g
Sodium chloride	5.640 g
Sodium (S)-lactate solution (sodium (S)-lactate)	7.85 g (3.925 g)
Magnesium chloride hexahydrate	0.1017 g
Glucose monohydrate (anhydrous glucose)	46.75 g (42.5 g)

Ca2+	1.75 mmol
Na+	134 mmol
Mg2+	0.5 mmol
Cl–	101.5 mmol
(S)-lactate	35 mmol
Gluc.	235.8 mmol

Excipients: water for injections, hydrochloric acid, sodium hydroxide, sodium hydrogencarbonate.

Dosage form. Solution for peritoneal dialysis.

Main physicochemical properties: a two-chamber bag containing a clear solution with a theoretical osmolarity of 511 mOsm/L and pH ≈ 7.0.

Pharmacotherapeutic group.

Solution for peritoneal dialysis, hypertonic solutions. ATC code B05D B.

Pharmacological Properties

Pharmacodynamics

The medicinal product "Balance 4.25% glucose 1.75 mmol/l calcium" is an electrolyte solution containing glucose and a lactate buffer, intended for intraperitoneal use in the treatment of end-stage renal failure of various etiologies by continuous ambulatory peritoneal dialysis (CAPD).

A characteristic feature of continuous ambulatory peritoneal dialysis (CAPD) is the presence of approximately 2 liters of dialysis solution in the peritoneal cavity, which is replaced with fresh solution 3 to 5 times daily.

The fundamental principle of any peritoneal dialysis method is the use of the peritoneum as a semipermeable membrane, enabling exchange of dissolved substances and water between blood and dialysis solution via diffusion and convection, according to their physicochemical properties.

The electrolyte profile of the solution is essentially similar to that of physiological serum, although it has been adapted (e.g., potassium content) for use in patients suffering from uraemia, to perform replacement therapy of renal function through exchange of peritoneal cavity contents and fluids.

Substances normally excreted in urine, such as urea, creatinine, inorganic phosphates, uric acid, other dissolved substances, and water, are removed from the body into the dialysis solution. Fluid balance can be maintained by using solutions with varying glucose concentrations, which influence fluid removal (ultrafiltration).

Secondary metabolic acidosis resulting from end-stage renal failure is compensated by the presence of lactate in the dialysis solution. Lactate is completely metabolized to bicarbonate.

Pharmacokinetics

Uremic substances (e.g., urea, creatinine, and uric acid), inorganic phosphates, and electrolytes such as sodium, potassium, calcium, and magnesium are removed from the body into the dialysis solution via diffusion and/or convection.

Glucose in the dialysate is used as an osmotic agent in the "Balance 4.25% glucose 1.75 mmol/l calcium" solution. It is slowly absorbed, reducing the diffusion gradient between the dialysis solution and extracellular fluid. Ultrafiltration is maximal at the beginning of the dwell time and reaches its peak after approximately 2–3 hours. Subsequently, progressive loss of ultrafiltrate occurs due to glucose absorption.

After 4 hours, the average ultrafiltrate volume is 100 ml for the 1.5% glucose solution, 400 ml for the 2.3% glucose solution, and 800 ml for the 4.25% glucose solution. During six hours of dialysis, 60 to 80% of the dialysate glucose is absorbed.

Lactate, used as a buffer agent, is almost completely absorbed within a 6-hour dwell. In patients with normal liver function, rapid metabolism of lactate is confirmed by normal levels of intermediate metabolites.

Calcium transfer depends on the glucose concentration in the dialysis solution, the volume of dialysate drained, and the serum ionized calcium level as well as the calcium concentration in the dialysis solution. The higher the glucose concentration, the volume of drained dialysate, and the serum calcium concentration, and the lower the calcium concentration in the dialysis solution, the greater the calcium removal from the patient’s body into the dialysate.

Clinical characteristics.

Indications.

End-stage (decompensated) chronic renal failure of various etiologies, requiring treatment with peritoneal dialysis.

Contraindications.

For use of this peritoneal dialysis solution

"Balance 4.25% glucose 1.75 mmol/L calcium" must not be used in patients with lactic acidosis, severe hypokalemia, severe hypercalcemia, hypovolemia, and arterial hypotension.

General contraindications for peritoneal dialysis

Peritoneal dialysis must not be used in the following cases:

• recent abdominal surgery or trauma, history of abdominal surgery leading to fibrous adhesions, severe abdominal burns, perforation of the peritoneum;

• extensive inflammatory skin lesions of the abdominal area (dermatitis);

• inflammatory bowel diseases (Crohn's disease, ulcerative colitis, diverticulitis);

• peritonitis;

• internal or external abdominal fistula;

• umbilical, inguinal, or other abdominal wall hernia;

• intra-abdominal tumors;

• ileus;

• lung diseases (including pneumonia);

• sepsis;

• severe hyperlipidemia;

• certain cases of uremia unresponsive to peritoneal dialysis;

• cachexia and significant weight loss, especially if adequate dietary protein intake cannot be ensured;

• physical or mental inability of the patient to undergo peritoneal dialysis treatment and comply with physician instructions.

If any of the above conditions develop during peritoneal dialysis treatment, the physician must make a decision regarding further management.

Interaction with other medicinal products and other forms of interaction.

Use of this peritoneal dialysis solution may reduce the efficacy of other medicinal products, as they may diffuse into the dialysate and be removed from the body along with it. In such cases, dose adjustment of these drugs may be required.

Significant reduction in serum potassium levels may increase the frequency of adverse reactions associated with digitalis. Potassium levels must be monitored particularly carefully when concomitant therapy with cardiac glycosides is administered (see section "Special precautions").

The use of diuretics may be beneficial in maintaining residual diuresis, but may simultaneously lead to disturbances in water and electrolyte balance.

For patients with diabetes mellitus, the daily dose of insulin or oral hypoglycemic agents must be adjusted to account for the increased glucose load.

Concomitant use of medicinal products containing calcium or vitamin D may lead to hypercalcemia.

The medicinal product "Balance 4.25% glucose 1.75 mmol/L calcium" may be mixed only with the following medicinal products due to the risk of incompatibility and contamination: heparin 1000 IU/L, insulin 20 IU/L, vancomycin 1000 mg/L, teicoplanin 400 mg/L, cefazolin 500 mg/L, ceftazidime 250 mg/L, gentamicin 8 mg/L. Medicinal products must be added under sterile conditions and only upon physician's prescription. After thorough mixing and inspection for clarity and absence of particulate matter, the peritoneal dialysis solution must be used immediately (do not store).

Special precautions for use.

Peritoneal dialysis solution must not be administered intravenously.

The solution "Balance 4.25% glucose 1.75 mmol/L calcium" may be used after careful assessment of risk versus benefit in the following cases:

• in hypercalcemia, for example due to administration of calcium-containing phosphate binders and/or vitamin D (consideration should be given to temporary or permanent replacement of the peritoneal dialysis solution with a similar one containing a lower calcium concentration);
• in electrolyte loss due to vomiting and/or diarrhea (in such cases, temporary replacement with a peritoneal dialysis solution containing potassium may be required);
• in patients receiving therapy with cardiac glycosides: continuous monitoring of serum potassium levels is mandatory (see section "Interaction with other medicinal products and other forms of interaction"). In case of severe hypokalemia, use of a dialysis solution containing potassium and dietary consultation may be necessary;
• in extensive polycystic kidney disease.

During peritoneal dialysis, loss of proteins, amino acids, and water-soluble vitamins occurs. To prevent their deficiency, an appropriate diet or nutritional supplements should be ensured.

During long-term peritoneal dialysis, transport characteristics of the peritoneal membrane may change, primarily indicated by lack of ultrafiltration. In severe cases, peritoneal dialysis should be discontinued and hemodialysis initiated.

The following parameters should be continuously monitored:

• body weight for early detection of hyperhydration and dehydration;
• serum levels of sodium, potassium, calcium, magnesium, phosphates, acid-base balance, blood gases, and blood proteins;
• concentrations of creatinine and urea;
• parathyroid hormone and other indicators of bone metabolism;
• blood glucose levels;
• residual kidney function for adaptation of peritoneal dialysis.

The volume and clarity of the drained solution should be monitored. Cloudiness of the fluid and/or abdominal pain indicate development of peritonitis.

Encapsulating peritoneal sclerosis is considered a known rare complication of peritoneal dialysis therapy, which may occasionally lead to fatal outcomes.

Elderly patients

Before prescribing peritoneal dialysis, consider the higher incidence of hernias in elderly patients.

Instructions for handling the medicinal product

The ready-to-use solution should be used immediately. If this is not possible, it must be used no later than 24 hours after mixing.

The plastic packaging may occasionally become damaged during transport or storage, which may lead to contamination and increased microbial growth in the dialysis solution. Therefore, the entire package must be carefully inspected for damage before connecting the bag and using the peritoneal dialysis solution. Pay attention to any damage, even minor, to connectors, body, seams, or corners of the bag to prevent contamination. Never use damaged bags or bags containing cloudy solution.

The peritoneal dialysis solution may be used only if it is clear and the container is undamaged.

The outer wrapper should be opened immediately before use. Do not use two-chamber solutions without mixing.

To reduce the risk of infection during dialysate exchange, sterile conditions must be maintained.

Preclinical studies on the toxicity of the solution "Balance 4.25% glucose 1.75 mmol/L calcium" have not been conducted. The electrolytes and glucose contained in the medicinal product are physiological components of human blood plasma. Therefore, no toxic effects are expected when following recommendations for indications, dosage, and use, taking into account contraindications.

Use during pregnancy or breastfeeding.

Pregnancy

Data on use of "Balance" solutions in pregnant women are limited. Data from animal studies are insufficient. The peritoneal dialysis solution should be used in pregnant women only after careful evaluation of the potential benefit versus possible risks to mother and fetus.

Breastfeeding

Components of the "Balance" solution are excreted in human milk. However, with adequate therapy, no adverse effects in the infant are expected. The necessity of temporary interruption of breastfeeding should be considered, taking into account the benefit of breastfeeding for the infant and the therapeutic benefit for the mother.

Fertility

There are no clinical data on the effect on fertility. However, during therapeutic use, no effect on fertility is expected.

Ability to affect reaction speed when driving or operating machinery.

"Balance 4.25% glucose 1.75 mmol/L calcium" has no or negligible effect on the ability to drive or operate machinery.

Method of Administration and Dosage

Dosage

This solution is intended exclusively for intraperitoneal administration.

The treatment regimen, frequency of exchanges, and dwell time are determined by the physician.

Continuous Ambulatory Peritoneal Dialysis (CAPD)

Adults

In the absence of other prescriptions, patients are usually prescribed 2000 mL of solution per exchange, four times daily. After the solution has remained in the peritoneal cavity for 2 to 10 hours, it is drained.

The dosage, volume of solution, and number of exchanges must be individually adjusted for each patient.

If pain occurs at the beginning of peritoneal dialysis, temporarily reduce the volume per exchange to 500–1500 mL.

If the patient has excess body weight or residual kidney function has been lost, the dialysis solution volume should be increased. For such patients, and for patients who tolerate large fill volumes well, the volume per exchange may be increased to 2500–3000 mL.

Children

For children, the volume of solution per exchange should be prescribed according to age and body surface area (BSA).

The initial dose of solution per exchange should not exceed 600–800 mL/m² BSA, with 4 (sometimes 3 or 5) exchanges per day. The volume may be increased to 1000–1200 mL/m² BSA depending on tolerance, age, and residual renal function.

Automated Peritoneal Dialysis (APD)

When an automated device (Sleep•Safe cycler) is used for intermittent or continuous cyclic peritoneal dialysis, it is recommended to use larger-volume bags, allowing for more than one exchange of solution. Solution exchanges are performed according to the medical prescription stored in the cycler.

Adults

Patients typically spend 8–10 hours on the nighttime cycle. Fill volumes range from 1500 to 3000 mL, and the number of cycles varies from 3 to 10 per night. The total volume of fluid used is usually 10–18 L, but may range from 6 to 30 L. Cyclic therapy at night is usually combined with 1 or 2 daytime exchanges.

Children

The solution volume per exchange should be 800–1000 mL/m² BSA with 5–10 exchanges per night. It may be increased to 1400 mL/m² BSA depending on tolerance, age, and residual renal function.

No special dosage recommendations exist for elderly patients.

Peritoneal dialysis solutions with high glucose concentration (2.3% or 4.25%) are used when body weight exceeds the desired dry weight. Fluid removal from the body increases according to the glucose concentration in the peritoneal dialysis solution. These solutions should be used with caution to protect the peritoneal membrane, prevent dehydration, and maintain glucose load at the lowest possible level.

Peritoneal dialysis is a long-term therapy involving the regular use of individual solution bags.

“Balance 4.25% glucose 1.75 mmol/L calcium” contains 42.5 g of glucose in 1000 mL of solution.

Method and Duration of Procedure

Before performing peritoneal dialysis at home, the patient must undergo appropriate training, practice the technique, and achieve adequate proficiency. Training must be conducted by qualified personnel. Before discharging a patient for home peritoneal dialysis, the physician must ensure that the patient has mastered the procedure. In case of any problems or uncertainties, contact the physician.

Dialysis using the prescribed doses should be performed daily and continued as long as renal replacement therapy is considered necessary.

Continuous Ambulatory Peritoneal Dialysis (CAPD): Stay•Safe bag

The solution bag should be pre-warmed to body temperature. The prescribed dose is infused through the peritoneal catheter into the abdominal cavity over 5–20 minutes. According to the physician’s recommendations, the solution dose should remain in the abdominal cavity for 2–10 hours (dwell time), after which it is drained.

Automated Peritoneal Dialysis (APD): Sleep•Safe bag

To initiate the treatment procedure, insert the Sleep•Safe connectors of the system with the prescribed solution into the free ports of the cycler tray; they will then automatically connect to the Sleep•Safe cycler tubing sets. The cycler checks the barcodes on the solution bags and sounds an alarm if there is a discrepancy with the physician’s prescription stored in the cycler’s memory. After this verification, connect the system tubing to the patient’s catheter extension set to begin the procedure. The cycler automatically heats the Sleep•Safe solution to body temperature throughout the infusion into the peritoneal cavity. The dwell time and choice of glucose concentration are determined according to the medical prescription stored in the cycler’s memory (see the Sleep•Safe cycler user manual for details).

Depending on the required osmotic pressure, “Balance 4.25% glucose 1.75 mmol/L calcium” may be used sequentially with other peritoneal dialysis solutions with lower glucose content (i.e., lower osmolarity).

For single use only. Any unused solution should be discarded. No special requirements for disposal of the medicinal product.

Stay•Safe system for Continuous Ambulatory Peritoneal Dialysis (CAPD)

The solution bag is pre-warmed to body temperature. For bags with a volume up to 3000 mL, this should be done using an appropriate heater. The warming time for a 2000 mL bag starting at 22°C is approximately 120 minutes. Automatic temperature control is set at 39°C ± 1°C. More detailed information can be found in the heater’s user manual. Avoid using a microwave oven to prevent local overheating.

1. Preparation of the solution.

Check the appearance of the warmed solution bag (label, expiry date, clarity of solution, absence of damage to the bag, film, and integrity of the seal). Place the bag on a solid surface. Open the outer protective bag and the disinfection cap packaging. Wash hands using an antimicrobial soap. Twist the bag lying on the foil of the outer packaging at one of the side corners until the central seal opens. The solutions from the two chambers will then mix automatically. Then twist the bag from the upper edge of the chamber containing the ready solution until the seal forming the lower triangle is fully opened. Ensure all seals are fully open. Confirm that the solution is clear and the bag is not leaking.

1. Preparation for bag exchange.

Secure the bag in the upper ring of the infusion stand, unroll the solution bag tubing, and place the DISC in the organizer. Then unroll the drainage bag tubing and secure the drainage bag in the lower ring of the infusion stand. Place the catheter connector into one of the two organizer openings. Place the new disinfection cap into the other free opening of the organizer. Disinfect hands, then remove the protective cap from the DISC. Connect the catheter connector to the DISC.

1. Drainage.

Open the catheter extension clamp. The drainage procedure has started.

In switch position «●»

1. Rinsing.

After completion of the drainage procedure, rinse the tubing by draining a small amount of fresh solution into the drainage bag (approximately for 5 seconds).

In switch position «●●»

1. Infusion.

The infusion procedure starts after setting the control switch to position «○ ●»

1. Safety measures.

Close the catheter extension by inserting the PIN into the catheter connector.

In switch position «●●●●»

1. Disconnection.

Remove the protective cap from the new disinfection cap and screw it onto the old cap. Disconnect the catheter connector from the DISC, then screw the catheter connector onto the new disinfection cap.

1. Closing the DISC.

Close the DISC with the open end of the previously used protective cap, which remains in the right organizer opening.

1. Check the drained dialysate for clarity and weight. If the drained solution is clear, it should be discarded.

Sleep•Safe system for Automated Peritoneal Dialysis (APD)

(for system Sleep•Safe setup instructions, refer to its user manual):

3000 mL Sleep•Safe system:

1. Preparation of the solution: see Stay•Safe system.
2. Unroll the bag tubing.
3. Remove the protective cap.
4. Insert the bag connector into a free port of the Sleep•Safe cycler tray.
5. The bag is ready for use with the Sleep•Safe system.

5000 mL Sleep•Safe system:

1. Preparation of the solution.

Check the appearance of the solution bag (label, expiry date, clarity of solution, absence of damage to the bag, film, and integrity of the seal). Place the bag on a solid surface. Open the outer wrapping of the bag. Wash hands using an antimicrobial soap. Unroll the central seal and the bag connector. Twist the bag lying on the wrapping, starting from the end opposite the diagonally placed connector, until the central seal opens. Continue twisting until the seal on the small chamber opens. Ensure all seals are fully open. Confirm that the solution is clear and the bag is not leaking.

1. Unroll the bag tubing.
2. Remove the protective cap.
3. Insert the bag connector into a free port of the Sleep•Safe cycler tray.
4. The bag is ready for use with the Sleep•Safe system.

Overdose.

No incidents related to overdose have been reported.

Excess dialysis solution introduced into the peritoneal cavity can be easily drained into the drainage bag. However, if bag exchanges are performed too frequently, dehydration and/or electrolyte imbalances may develop, requiring immediate medical intervention. If an exchange has been missed, contact the physician or the appropriate dialysis center.

Incorrect dosing may lead to hyper- or dehydration and electrolyte imbalances.

The most likely consequence of overdose is dehydration.

Insufficient dosage, interruption, or discontinuation of treatment may lead to life-threatening hyperhydration with peripheral edema and cardiac decompensation and/or other uremic symptoms that may be life-threatening.

Management should follow generally accepted standards of emergency and intensive care. The patient may require immediate hemodialysis.

Adverse reactions.

The medicinal product "Balance 4.25% glucose 1.75 mmol/l calcium" is an electrolyte solution whose composition is similar to that of blood. In addition, the solution has a neutral pH, comparable to the physiological pH value.

Possible adverse reactions may result either directly from peritoneal dialysis as a procedure, or may be caused by this specific solution.

The frequency of adverse reactions has been defined as follows:

very common	(≥ 1/10)
common	(≥ 1/100 to < 1/10)
uncommon	(≥ 1/1000 to < 1/100)
rare	(≥ 1/10000 to < 1/1000)
very rare	(< 1/10000)
not known	(cannot be estimated from the available data).

Potential adverse reactions associated with the peritoneal dialysis solution

Metabolism and nutrition disorders:
Frequent — hyperglycemia, hyperlipidemia, weight gain due to prolonged glucose absorption from the peritoneal dialysis solution.

Cardiac disorders:
Uncommon — tachycardia, arterial hypotension/hypertension.

Respiratory, thoracic and mediastinal disorders:
Uncommon — dyspnea.

Renal and urinary disorders:
Very common — electrolyte imbalance, e.g. hypokalemia; frequent — hypercalcemia in combination with increased calcium absorption, for example when calcium-containing phosphate binders are administered.

General disorders:
Uncommon — dizziness, edema, fluid imbalance indicated by rapid weight loss (dehydration) or weight gain (hyperhydration). Severe dehydration may occur when using solutions with high glucose concentration.

Potential adverse reactions of the treatment method

Infections and infestations:
Very common — peritonitis, indicated by clouding of the drained dialysate (later, abdominal pain, fever, and general malaise may develop; in very rare cases, sepsis). The patient must seek immediate medical attention. The bag containing the cloudy dialysate should be sealed with a sterile cap and submitted for microbiological testing and leukocyte count in blood. Skin infection at the catheter exit site and tunnel infection along the catheter tract (in case of exit-site or tunnel infections, prompt medical consultation is required); very rare — sepsis.

Respiratory, thoracic and mediastinal disorders:
Frequent — shoulder pain; frequency not known — dyspnea caused by elevation of the diaphragm.

Gastrointestinal disorders:
Very common — hernias; frequent — abdominal distension and sensation of fullness; uncommon — diarrhea, constipation; frequency not known — encapsulating peritoneal sclerosis.

General disorders and catheter site reactions:
Very common — redness, swelling, discharge, crusts, and pain at the catheter exit site; frequent — complications related to the dialysis solution infusion and drainage procedures; frequency not known — general weakness.

Reporting suspected adverse reactions

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

Shelf life.

The product in the original retail packaging — 2 years.

The ready-to-use solution without addition of other medicinal products: chemical and physical stability remains for 24 hours after opening the package, stored at 20 °C.

Storage conditions.

Store at a temperature not below 4 °C. Keep out of the reach of children.

Incompatibilities.

The medicinal product should be used only under medical supervision to avoid risks of incompatibility and contamination.

The medicinal product must not be mixed with other medicinal products except those specified in the section "Interaction with other medicinal products and other forms of interaction".

Packaging.

2000 ml or 2500 ml in a dual-chamber stay•safe bag system; 4 bags per cardboard box with a Ukrainian-language sticker or labeling in Ukrainian and other languages;

3000 ml in a dual-chamber sleep•safe bag system; 4 bags per cardboard box with a Ukrainian-language sticker or labeling in Ukrainian and other languages;

5000 ml in a dual-chamber sleep•safe bag system; 2 bags per cardboard box with a Ukrainian-language sticker or labeling in Ukrainian and other languages.

Prescription status.

Prescription only.

Manufacturer.

Fresenius Medical Care Deutschland GmbH / Fresenius Medical Care Deutschland GmbH

Manufacturer's address.

Frankfurter Strasse 6-8, 66606 St. Wendel, Germany / Frankfurter Strasse 6-8, 66606 St. Wendel, Germany

Marketing authorization holder.

Fresenius Medical Care Deutschland GmbH / Fresenius Medical Care Deutschland GmbH

Address of the marketing authorization holder.

Else-Kroener-Str. 1, 61352 Bad Homburg v.d.H., Germany / Else-Kroener-Str. 1, 61352 Bad Homburg v.d.H., Germany

Address of the representative of the marketing authorization holder.

LLC "Fresenius Medical Care Ukraine", 9 Boryspylska St., Kyiv, 02099, Ukraine