Capd/pdca 4

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT CAPD/DPCA 4 (CAPD/DPCA 4)

Composition:

Active substances: 1 l of solution contains:

sodium chloride 5.786 g;

sodium (S)-lactate solution 7.85 g (equivalent to sodium (S)-lactate 3.925 g);

calcium chloride dihydrate 0.2573 g;

magnesium chloride hexahydrate 0.1017 g;

glucose monohydrate 25.0 g (equivalent to anhydrous glucose 22.73 g);

Na+ 134.0 mmol/l,

Ca++ 1.75 mmol/l,

Mg++ 0.5 mmol/l,

Cl- 103.5 mmol/l,

lactate 35.0 mmol/l;

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

Pharmaceutical form. Solution for peritoneal dialysis.

Main physicochemical properties: clear solution ranging from light yellow to yellow in color, free from visible particles, with a theoretical osmolarity of 401 mOsm/l.

Pharmacotherapeutic group.
Solutions for peritoneal dialysis. Hypertonic solutions. ATC code B05D B.

Pharmacological Properties

Pharmacodynamics

CAPD/DPCA 4 is an electrolyte solution containing glucose and a lactate buffer, intended for intraperitoneal administration in the treatment of end-stage chronic renal failure of various etiologies by continuous ambulatory peritoneal dialysis (CAPD).

The CAPD method involves the more or less constant presence of dialysis solution (usually 2 liters) in the peritoneal cavity, which is replaced with fresh solution 3 to 5 times daily.

The fundamental principle underlying any peritoneal dialysis technique is the use of the peritoneum as a semipermeable membrane, allowing exchange of solutes and water between blood and dialysis solution via diffusion and convection, according to their physicochemical properties.

The electrolyte composition of the solution is generally similar to physiological levels, although it has been adapted (e.g., potassium content) for use in patients with uremia, enabling renal replacement therapy through intraperitoneal exchange of solutes and fluids. During the dialysis procedure, substances normally excreted in urine—such as urea, creatinine, inorganic phosphates, uric acid, other dissolved solutes, and water—are removed from the body via the dialysate. It should be noted that medications taken by the patient may also be removed during dialysis; therefore, dose adjustments may be necessary.

Individual patient parameters (such as body size, body weight, laboratory parameters, residual kidney function, and ultrafiltration) should be used to determine the dose and combination of solutions with different osmolarities (glucose content), and concentrations of potassium, sodium, and calcium. The effectiveness of therapy should be regularly monitored based on these parameters.

Peritoneal dialysis solutions with high glucose content (2.3% or 4.25%) are used when the patient's body weight exceeds the desired dry weight. Fluid removal from the body increases proportionally with increasing glucose concentration in the peritoneal dialysis solution.

Pharmacokinetics

Uremic waste products such as urea, creatinine, and uric acid, inorganic phosphates, and electrolytes such as sodium, potassium, calcium, and magnesium are removed from the body via the dialysate through diffusion and convection.

Glucose in the dialysate, used as an osmotic agent in CAPD/DPCA 4, is slowly absorbed, thereby reducing the diffusion gradient between dialysate and extracellular fluid. Ultrafiltration is maximal at the beginning of the dwell time and peaks within 2–3 hours. Subsequently, absorption begins, leading to a progressive decline in ultrafiltration. Between 60% and 80% of glucose is absorbed from the dialysate.

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

Calcium exchange depends on glucose concentration in the dialysate, volume of drained dialysate, serum ionized calcium, and calcium concentration in the dialysis solution. The higher the glucose concentration, volume of drained dialysate, and serum ionized calcium, and the lower the calcium concentration in the dialysis solution, the greater the amount of calcium removed from the body into the dialysate.

Preclinical Safety Data

No toxicological preclinical studies with CAPD/DPCA 4 have been conducted. However, clinical studies with similar peritoneal dialysis solutions have not shown high toxicity.

Clinical characteristics.

Indications.

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

Contraindications.

For this specific solution.

CAPD/PD4 should not be used in patients with lactic acidosis, severe hypokalemia, or severe hypercalcemia.

Due to its fructose content, CAPD/PD4 is not recommended for patients with fructose intolerance (hereditary fructose intolerance). Hereditary fructose intolerance must be excluded before use in children and infants.

For peritoneal dialysis as a method.

Peritoneal dialysis should not be performed in the following cases:

• recent abdominal surgery or trauma, abdominal operations with history of fibrotic 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 fistulas;
• umbilical, inguinal, or other abdominal wall hernias;
• intra-abdominal tumors;
• ileus;
• lung diseases (particularly pneumonia);
• sepsis;
• severe hyperlipidemia;
• cases where uremia is unresponsive to peritoneal dialysis;
• cachexia and significant weight loss, especially if adequate protein intake cannot be achieved;
• physical or mental inability of the patient to follow physician instructions for performing peritoneal dialysis procedures.

If any of the above conditions develop during peritoneal dialysis treatment, the physician must decide on further management.

Special precautions.

Before using the peritoneal dialysis solution CAPD/PD4, it is mandatory to read the instructions for use of the "stay-safe" continuous ambulatory peritoneal dialysis system.

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 be removed from the body together with the dialysate; therefore, dose adjustments may be necessary.

Significant reduction in serum potassium levels may increase the frequency of dialysis-related adverse reactions. Serum potassium levels should be monitored particularly carefully during concomitant therapy with cardiac glycosides.

When prescribing medications containing calcium or vitamin D, the possibility of hypercalcemia should be considered.

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

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

Special precautions for use.

The peritoneal dialysis solution must not be administered intravenously.

The KAPD/DPCA 4 solution may be used only after careful assessment of the benefit-risk ratio in the following cases:

• in case of electrolyte loss due to vomiting and/or diarrhea (in such cases, temporary substitution with a peritoneal dialysis solution containing potassium may be required);
• in hypercalcemia, for example, caused by calcium-containing phosphate binders and/or vitamin D, consideration should be given to temporarily or permanently switching to a peritoneal dialysis solution with a lower calcium concentration;
• in patients receiving cardiac glycoside therapy: serum potassium levels must be monitored particularly carefully. In case of severe hypokalemia, use of a potassium-containing dialysis solution and consultation with a dietitian may be necessary.

Peritoneal dialysis solutions with high glucose content (2.3% or 4.25%) should be used with caution to prevent dehydration and reduce osmotic pressure.

During peritoneal dialysis, loss of proteins, amino acids, and water-soluble vitamins occurs. To prevent their deficiency, adequate dietary intake or supplementation with 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 fluid overload or dehydration;
• concentrations of sodium, potassium, calcium, magnesium, phosphates, acid-base balance, and blood proteins;
• creatinine and urea levels;
• blood glucose levels;
• parathyroid hormone and other markers of bone metabolism;
• residual kidney function, to adjust peritoneal dialysis treatment.

Adding other medicinal products to the peritoneal dialysis solution is not recommended, as there is a risk of contamination and incompatibility between the peritoneal dialysis solution and the medicinal product.

To minimize the risk of infection, any addition of medicinal products to the solution should be performed under aseptic conditions. After thorough mixing and inspection for clarity, the solution should be used immediately.

KAPD/DPCA 4 contains 22.73 g of glucose per 1000 ml of solution. Depending on dosage and the size of the package used, up to 57 g of glucose may be delivered into the body (KAPD/DPCA 4: 2500 ml in a "stay-safe" system). This should be taken into account in diabetic patients.

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

Use in elderly patients

Hernias are common in elderly patients and should be considered before initiating peritoneal dialysis.

Use during pregnancy or breastfeeding.

Pregnancy

There are no clinical data on the use of KAPD/DPCA 4 in pregnant women. No reproductive toxicity studies have been conducted in animals. KAPD/DPCA 4 is not recommended during pregnancy unless the woman's clinical condition requires treatment with KAPD/DPCA 4.

Breastfeeding

It is unknown whether active substances/metabolites of KAPD/DPCA 4 pass into breast milk. Breastfeeding is not recommended in women undergoing peritoneal dialysis.

Reproductive function

There are no data on the effect of KAPD/DPCA 4 on reproductive function.

Effect on ability to drive or operate machinery.

KAPD/DPCA 4 has no or negligible effect on the ability to drive or operate machinery.

Method of Administration and Dosage

The CAPD/DPCA 4 solution is intended exclusively for intraperitoneal use.

The method of peritoneal dialysis, frequency, and duration of exchanges are determined by the physician.

Continuous Ambulatory Peritoneal Dialysis (CAPD)

Adults

In the absence of other prescriptions, 2000 mL of solution per exchange is administered four times daily. After the dwell time in the abdominal cavity (2 to 10 hours), the solution is drained.

Dosage, volume of solution, and number of exchanges are individually adjusted for each patient.

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

If the patient has excess body weight or residual kidney function has been lost, the volume per exchange should be increased. For such patients and for patients who tolerate large 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 the child's age and body surface area (BSA).

The initial dose per exchange should not exceed 600–800 mL/m² BSA, administered four times daily (sometimes three or five times). The volume per exchange may be increased to 1000–1200 mL/m² BSA depending on tolerance, the child's age, and residual kidney function.

Elderly Patients

No special dosage recommendations are available for elderly patients.

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

Method and Duration of the 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-based peritoneal dialysis, the physician must ensure that the patient has mastered the procedure. In case of any problems or uncertainties, consult a physician.

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

Continuous Ambulatory Peritoneal Dialysis (CAPD): "Stay-Safe" System

The solution must be prewarmed to body temperature. The required dose is infused through the peritoneal catheter into the abdominal cavity over 5–20 minutes. According to the physician's recommendations, the solution should remain in the abdominal cavity for 2–10 hours (equilibration time), after which it is drained.

Depending on the required osmotic pressure, CAPD/DPCA 4 may be used sequentially with other peritoneal dialysis solutions with higher or lower glucose content (i.e., higher or lower osmolarity).

For single use only. Any unused solution remnants must be discarded. There are no special requirements for disposal of the medicinal product.

Instructions for Using the Continuous Ambulatory Peritoneal Dialysis "Stay-Safe" System

The "Stay-Safe" system is a double-bag system consisting of a solution bag made of non-PVC multilayer polyolefin film, a tubing set also made of polyolefins, a system connector (DISC, polypropylene), a drainage bag, and an outer bag also made of multilayer polyolefin film.

The solution should be prewarmed 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 volume from an initial temperature of 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 operating instructions. Microwave heating is not recommended due to the risk of local overheating.

1. Inspect the solution bag (labeling, expiration date, ensure the solution is clear) – open the outer protective bag and the disinfection cap packaging.
2. Wash hands using an antimicrobial cleansing agent.
3. Place the DISC into the organizer (hang the solution bag on the upper ring of the infusion stand – unroll the "solution bag-DISC" tubing – place the DISC into the organizer – then place the drainage bag into the lower ring of the infusion stand).
4. Place the catheter extension set into one of the two organizer openings. Place a new disinfection cap into the other free opening of the organizer.
5. Disinfect hands and then remove the protective cap from the DISC.
6. Connect the catheter extension set to the DISC.
7. Open the catheter extension set clamp – switch position "●" – drainage procedure begins.
8. After completion of drainage: Flushing – switch position "●●" – flush with fresh dialysate into the drainage bag (approximately for 5 seconds).
9. Filling – switch position "○●●" – connection between the solution bag and the catheter.
10. Safety step – switch position "●●●●" – automatic closure of the catheter extension set by inserting the PIN.
11. Disconnection – remove the protective cap from the new disinfection cap and screw it onto the old cap. Unscrew the catheter extension set from the DISC and screw it onto the new disinfection cap.
12. Close the DISC with the open end of the protective cap (which remains in the right opening of the organizer).
13. Check the used dialysate for clarity and volume. If the drained solution is clear, it should be discarded.

The plastic bag may be damaged during transport or storage, which could lead to contamination of the dialysis solution and an increase in microbial count. Therefore, the entire package must be carefully inspected for damage before connecting and using the peritoneal dialysis solution. Any damage, even minor, to the connections, housing, seams, or corners of the bag must be noted to prevent contamination.

Damaged bags or bags containing cloudy solution must never be used! If in doubt, consult a physician regarding the use of this solution.

The peritoneal dialysis solution may only be used if the bag and seal are undamaged.

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

The outer packaging should be opened immediately before use.

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

Children

For children, the volume of solution per exchange should be prescribed according to the child's age and body surface area.

Overdose

No incidents related to overdose have been reported.

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

Incorrect dosing may lead to hyperhydration 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.

Standard emergency care and intensive therapy protocols should be applied. The patient may require immediate hemodialysis.

Side effects.

Possible side effects may be due to peritoneal dialysis as a method or may be caused by this specific solution.

The frequency of side effects is defined as follows:

Potential adverse reactions associated with this specific solution

Metabolism and nutrition disorders:

• increased blood sugar (common);
• weight gain due to prolonged glucose exposure from peritoneal dialysis solution (common);
• hyperlipidemia or worsening of pre-existing hyperlipidemia (common).

Cardiac disorders:

• hypotension (uncommon);
• tachycardia (uncommon);
• hypertension (uncommon).

Respiratory, thoracic and mediastinal disorders:

• dyspnea (uncommon).

Renal and urinary disorders:

• electrolyte imbalance, e.g. hypokalemia (very common);
• hypercalcemia in combination with increased calcium absorption (common), e.g. when calcium-containing phosphate binders are administered.

General disorders and administration site conditions:

• dizziness (uncommon);
• edema (uncommon);
• fluid imbalance (uncommon), indicated by rapid weight loss (dehydration) or weight gain (hyperhydration). Severe dehydration may occur with the use of high-glucose concentration solutions.

Potential adverse reactions of peritoneal dialysis as a treatment method

Infections and infestations:

• peritonitis (very common), indicated by cloudy effluent dialysate. Abdominal pain, fever, and malaise may subsequently develop, or in very rare cases, sepsis. In such cases, the patient must seek immediate medical attention. The bag containing the drained cloudy dialysate should be capped with a sterile cap and submitted for microbiological testing and blood leukocyte level determination;
• skin infections and tunnel infections (very common), indicated by redness, swelling, exudate, crusts, and pain at the catheter exit site.

In case of skin infection, prompt consultation with the treating physician is required.

Respiratory, thoracic and mediastinal disorders:

• dyspnea due to diaphragmatic elevation (frequency not known).

Gastrointestinal disorders:

• hernias (very common);
• abdominal distension and sensation of fullness (common);
• diarrhea (uncommon);
• constipation (uncommon).

Injury, poisoning and procedural complications:

• problems with inflow and outflow of dialysis solution (common);
• shoulder pain (common).

Reporting of adverse reactions

It is very important to report adverse reactions occurring after the use of a medicinal product. This allows continuous monitoring of the benefit-risk balance of the medicinal product.

Healthcare professionals are requested to report any adverse reactions occurring during the use of this medicinal product.

Shelf life. 2 years.

Storage conditions

Store at temperatures not exceeding 25°C. Do not freeze.

Packaging

2000 mL or 2500 mL in a double-bag "stay-safe" system; 4 bags per cardboard box labeled in Ukrainian and other languages.

Prescription category. Prescription only.

Manufacturer

Fresenius Medical Care Deutschland GmbH / Fresenius Medical Care Deutschland GmbH.

Manufacturer's address

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

Marketing authorization holder

Fresenius Medical Care Deutschland GmbH / Fresenius Medical Care Deutschland GmbH.

Address of marketing authorization holder

Else-Kröner-Strasse 1, 61352 Bad Homburg v.d.H., Germany.