Balance 1.5% glucose 1.75 mmol/l calcium

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT BALANCE 1.5% GLUCOSE 1.75 mmol/l CALCIUM (BALANCE 1.5% 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).

Prior to 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)	33.0 g (30.0 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)	16.5 g (15.0 g)

Ca2+	1.75 mmol
Na+	134 mmol
Mg2+	0.5 mmol
Cl–	101.5 mmol
(S)-lactate	35 mmol
Gluc.	83.2 mmol

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

Pharmaceutical form. Solution for peritoneal dialysis.

Main physicochemical properties: two-chamber bag containing a clear solution with a theoretical osmolarity of 358 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 1.5% 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 more or less constant presence of usually 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, allowing the 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 between the contents of the peritoneal cavity and fluid.

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 different 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 1.5% 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 approximately 2–3 hours after instillation. Subsequently, progressive loss of ultrafiltrate occurs during the absorption process.

After 4 hours, the volume of ultrafiltrate averages 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 practically completely absorbed within 6 hours of dwell time. In patients with normal liver function, rapid lactate metabolism is confirmed by normal levels of intermediate metabolites.

Calcium transfer depends on the glucose concentration in the dialysis solution, the volume of dialysate drained, serum ionized calcium, and calcium concentration in the dialysis solution. The higher the glucose concentration, the volume of drained dialysate, and 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 1.5% glucose 1.75 mmol/L calcium" must not be used in patients with lactic acidosis, severe hypokalemia, and severe hypercalcemia.

In general for peritoneal dialysis use

Peritoneal dialysis must not be used in the following cases:

• recent abdominal surgery or trauma, history of abdominal surgery with development of 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 hernias;
• intraperitoneal tumors;
• ileus;
• lung diseases (particularly pneumonia);
• sepsis;
• marked 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 treatment with peritoneal dialysis and to follow physician instructions.

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

Interaction with other medicinal products and other forms of interaction.

The use of this peritoneal dialysis solution may reduce the effectiveness of other medicinal products, as they may penetrate into the dialysate and be removed from the body along with it. In such cases, dose adjustment may be required.

A significant decrease 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 for use").

The use of diuretics may be beneficial for maintaining residual diuresis, but at the same time may lead to disturbances in water-electrolyte balance.

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

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

The medicinal product "Balance 1.5% 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 absence of turbidity and foreign particles, the peritoneal dialysis solution must be used immediately (do not store).

Special precautions for use.

The peritoneal dialysis solution must not be administered intravenously.

The "Balance 1.5% glucose 1.75 mmol/l calcium" solution may be used after careful assessment of the risk/benefit ratio 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 cardiac glycoside therapy: 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 potassium-containing dialysis solution 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, 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 monitored continuously:

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

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

The high incidence of hernias in elderly patients should be taken into account before initiating peritoneal dialysis.

Handling instructions

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

The plastic packaging may occasionally become damaged during transport or storage, which could lead to contamination and increased number of microorganisms in the dialysis solution. Therefore, the entire package must be carefully inspected for damage before connecting the bag and using the peritoneal dialysis solution. Any damage, even minor, to connectors, body, seams, or corners of the bag should be noted to prevent contamination. Do not 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 toxicity of the "Balance 1.5% glucose 1.75 mmol/l calcium" solution 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 the recommended indications, dosage, and administration instructions, taking into account contraindications.

Use during pregnancy or breastfeeding.

Pregnancy

Data on the 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 potential 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 temporarily discontinuing breastfeeding should be considered, taking into account the benefit of breastfeeding for the infant and the therapeutic benefit for the mother.

Reproductive function

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

Ability to affect reaction speed when driving or operating machinery.

"Balance 1.5% 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 use.

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 medical instructions, patients are typically prescribed 2000 mL of solution per exchange, four times daily. After a dwell time of 2 to 10 hours in the peritoneal cavity, the solution is drained.

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

If pain occurs at the initiation of peritoneal dialysis, the volume per exchange should be temporarily reduced to 500–1500 mL.

In patients with excess body weight or those who have lost residual kidney function, the dialysis solution volume should be increased. For such patients, as well as for those who tolerate large fill volumes well, the volume per exchange may be increased to 2500–3000 mL.

Children

For pediatric patients, the volume per exchange should be prescribed based on age and body surface area (BSA).

The initial dose 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 using an automated device (Sleep•Safe cycler) for intermittent or continuous cycling peritoneal dialysis, larger-volume bags are recommended to allow for multiple solution exchanges. Solution exchanges are performed according to the medical prescription stored in the cycler.

Adults

Patients typically undergo an 8–10 hour nighttime cycle. Fill volumes range from 1500 to 3000 mL, with 3 to 10 cycles per night. The total volume used is usually 10–18 L, but may range from 6 to 30 L. Cyclic therapy at night is generally combined with 1 or 2 daytime exchanges.

Children

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

There are no specific dosage recommendations for elderly patients.

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

"Balance 1.5% glucose 1.75 mmol/L calcium" contains 15 g of glucose per 1000 mL of solution.

Method and Duration of Procedure

Before performing peritoneal dialysis at home, the patient must receive 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, the patient should consult their physician.

Dialysis using the prescribed doses should be performed daily and continued as long as renal replacement therapy is deemed 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 remains in the peritoneal cavity for 2–10 hours (dwell time), after which it is drained.

Automated Peritoneal Dialysis (APD): Sleep•Safe bag

To initiate treatment, insert the Sleep•Safe system connectors 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 solution bag barcodes and alerts if there is a mismatch with the prescription stored in its 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 period. The dwell time and glucose concentration selection are determined according to the medical prescription stored in the cycler’s memory (see Sleep•Safe cycler user manual for details).

Depending on the required osmotic pressure, "Balance 1.5% glucose 1.75 mmol/L calcium" may be used sequentially with other peritoneal dialysis solutions with higher glucose content (i.e., higher 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 up to 3000 mL in volume, this should be done using an appropriate heater. The warming time for a 2000 mL bag starting at 22°C is approximately 120 minutes. The automatic temperature control is set at 39°C ± 1°C. For more detailed information, refer to the heater’s user manual. Avoid using a microwave oven to prevent local overheating.

1. Solution preparation

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

2. Bag exchange preparation

   Secure the bag in the upper ring of the infusion stand, unroll the solution bag tubing, and place the DISC into 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.

3. Drainage

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

   In switch position «●»

4. Rinsing

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

   In switch position «●●»

5. Infusion

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

6. Safety measures

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

   In switch position «●●●●»

7. 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.

8. Closing the DISC

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

9. 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 setup instructions, refer to the Sleep•Safe user manual):

3000 mL Sleep•Safe system:

1. Solution preparation: 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. Solution preparation

   Inspect the appearance of the solution bag (label, expiry date, clarity of solution, absence of bag damage, film integrity, and seal integrity). Place the bag on a solid surface. Open the outer wrapping of the bag. Wash hands using an antimicrobial cleansing agent. Unroll the central seal and 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.

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.

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 imbalance may develop, requiring immediate medical intervention. If an exchange has been missed, the patient should contact their 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 standard emergency care and intensive therapy protocols. The patient may require immediate hemodialysis.

Adverse reactions.

The medicinal product "Balance 1.5% 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 be a direct consequence of peritoneal dialysis as a method, or may be caused by this specific solution.

The frequency of adverse reactions is 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 peritoneal dialysis solution

Metabolism and nutrition disorders:
Frequent — hyperglycemia, hyperlipidemia, weight gain due to prolonged absorption of glucose 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, e.g. when using calcium-containing phosphate binders.

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, or, very rarely, sepsis). The patient must seek immediate medical attention. The bag containing the cloudy dialysate should be capped 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 insertion/exit site reactions:
Very common — redness, swelling, discharge, crusts, and pain at the catheter exit site; frequent — complications related to dialysis solution infusion and drainage procedures; frequency not known — general malaise.

Reporting of suspected adverse reactions

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

Shelf life.

The medicinal 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 packaging, stored at 20 °C.

Storage conditions.

Store at temperature not below 4 °C. Keep out of 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 bag system stay•safe; 4 bags per cardboard box with a Ukrainian-language sticker or labeling in Ukrainian and other languages;

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

5000 ml in a dual-chamber bag system sleep•safe; 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 and place of business.

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 Marketing Authorization Holder's Representative.

LLC "Fresenius Medical Care Ukraine", 9 Borispilska Street, Kyiv, 02099, Ukraine