Dianal pd4 with glucose 3.86 % m/v / 38.6 mg/ml

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT DIANEAL PD4 WITH GLUCOSE CONTENT 1.36% w/v / 13.6 mg/ml

DIANEAL PD4 WITH GLUCOSE CONTENT 2.27% w/v / 22.7 mg/ml
DIANEAL PD4 WITH GLUCOSE CONTENT 3.86% w/v / 38.6 mg/ml
(DIANEAL PD4 Glucose 1.36% w/v / 13.6 mg/ml)
(DIANEAL PD4 Glucose 2.27% w/v / 22.7 mg/ml)
(DIANEAL PD4 Glucose 3.86% w/v / 38.6 mg/ml)

Composition:

Active substances: glucose monohydrate; sodium chloride; calcium chloride dihydrate; magnesium chloride hexahydrate; sodium lactate;

1000 ml of solution contain:
glucose monohydrate 15 g or 25 g or 42.5 g (equivalent to anhydrous glucose 13.6 g or 22.7 g or 38.6 g),
sodium chloride 5.38 g,
calcium chloride dihydrate 0.184 g,
magnesium chloride hexahydrate 0.051 g,
sodium lactate 4.48 g;

Excipient: water for injections.

Pharmaceutical form. Solution for peritoneal dialysis.

Main physicochemical properties: clear solution.

Pharmacotherapeutic group. Agents for peritoneal dialysis. ATC code B05D B.

Pharmacological properties.

Pharmacodynamics.

Peritoneal dialysis in patients with renal insufficiency is a procedure designed to remove toxic substances produced during nitrogen metabolism that are normally excreted by the kidneys, as well as to maintain regulation of fluid, electrolyte, and acid-base balance.

This procedure is performed by introducing a peritoneal dialysis solution through a catheter into the peritoneal cavity. The movement of substances between the dialysis fluid and the patient's peritoneal capillaries occurs across the peritoneal membrane according to the principles of osmosis and diffusion. After remaining in the abdominal cavity for several hours, the solution becomes saturated with toxic substances and must be replaced.

Except for lactate, which serves as a bicarbonate precursor, the electrolyte concentrations in the solution are adjusted to match standardized plasma electrolyte concentrations. Nitrogenous waste products, present in high concentrations in the blood, pass through the peritoneal membrane into the dialysis fluid. Glucose creates a solution that is hyperosmolar relative to plasma, generating an osmotic gradient that promotes fluid removal from plasma into the dialysate, thereby compensating for the fluid overload observed in patients with chronic renal failure.

Pharmacokinetics.

When administered intraperitoneally, glucose is absorbed into the bloodstream and metabolized via normal physiological pathways.

Clinical characteristics.

Indications.

• Acute renal failure;
• chronic renal failure;
• pronounced fluid retention in the body;
• electrolyte imbalance;
• drug intoxication when other therapies are ineffective.

Dianil PD4 is particularly useful for controlling serum calcium and phosphate levels in patients with renal failure who are taking phosphate-binding agents containing calcium or magnesium.

Contraindications.

Dianil PD4 is contraindicated in the following cases:

• hypersensitivity to the active substances or to any of the excipients of the medicinal product;
• presence of severe lactic acidosis;
• irreversible mechanical defects that prevent effective peritoneal dialysis (hereinafter – PD) or increase the risk of infection;
• documented loss of peritoneal function or significant adhesions that negatively affect peritoneal function.

Interaction with other medicinal products and other forms of interaction.

No studies have been conducted on the interaction of Dianil PD4 with other medicinal products. During peritoneal dialysis, plasma concentrations of other dialyzable medicinal products may decrease.

Plasma levels of potassium, calcium, and magnesium should be carefully monitored in patients receiving cardiac glycosides due to the risk of digitalis intoxication. Potassium supplementation may be required.

Special precautions for use

Peritoneal dialysis should be performed with caution in patients with:

• Abdominal cavity disorders, including disruption of the peritoneal membrane and diaphragm due to surgical procedures, congenital malformations, or trauma (until recovery); with intra-abdominal tumors, infections of the abdominal wall, hernias, fecal fistulas, history of colostomy or ileostomy, frequent episodes of diverticulitis, inflammatory or ischemic bowel disease, polycystic kidneys (of large size), or other conditions that compromise the integrity of the abdominal wall, abdominal surface, or intraperitoneal cavity;
• Other conditions, including recently implanted aortic grafts and severe pulmonary disease.

Encapsulating peritoneal sclerosis (EPS) is considered a known rare complication of peritoneal dialysis. Cases of EPS have also been observed in patients treated with peritoneal dialysis solutions, including Dianeal PD4, as part of peritoneal dialysis therapy. Fatal outcomes of EPS during treatment with Dianeal PD4 have been reported infrequently.

In the event of peritonitis, antibiotic selection and dosing should be based on microbiological identification and susceptibility testing, whenever possible. Broad-spectrum antibiotics may be indicated prior to pathogen identification.

Glucose-containing solutions should be used with caution in patients diagnosed with corn allergy or allergy to products containing corn. Hypersensitivity reactions due to allergy to cornstarch may occur, including anaphylactic/anaphylactoid reactions. If any signs or symptoms of hypersensitivity occur, infusion of the solution should be stopped immediately and the solution drained from the peritoneal cavity. Appropriate therapeutic measures should be initiated according to clinical indications.

Lactate-based peritoneal dialysis solutions should not be administered to patients with diagnosed severe lactic acidosis (see section "Contraindications"). Patients at risk of lactic acidosis (e.g., severe hypotension or sepsis, which may be associated with acute renal failure, inherited metabolic disorders, or treatment with drugs such as metformin and nucleoside/nucleotide reverse transcriptase inhibitors) should be monitored before and during treatment with lactate-based peritoneal dialysis solutions.

Before initiating therapy, potential interactions between the dialysis solution and treatment for pre-existing conditions should be evaluated for each individual patient. Serum levels of potassium, calcium, and magnesium should be closely monitored in patients receiving cardiac glycosides.

Accurate records of fluid balance should be maintained and patient body weight should be carefully monitored to avoid hyper- or hypohydration, which may lead to serious complications, including congestive heart failure, reduced extracellular fluid volume, and shock.

Significant losses of protein, amino acids, and water-soluble vitamins may occur during peritoneal dialysis. Replacement therapy should be administered as needed.

In patients receiving solutions with low calcium content, calcium concentration should be monitored to prevent the development of hypocalcemia or worsening of hypercalcemia. In such cases, the physician should adjust the doses of phosphate binders and/or vitamin D analogs, and/or calcimimetics.

The use of 5 or 6 liters of solution per single exchange cycle is not recommended in continuous ambulatory peritoneal dialysis (CAPD) or automated peritoneal dialysis (APD) due to the risk of overfilling.

Excessive infusion of Dianeal PD4 solution into the peritoneal cavity may manifest as abdominal distension/pain and/or dyspnea.

To treat excessive infusion of Dianeal PD4 into the peritoneal cavity, the solution should be drained from the peritoneal cavity.

Incorrect sequence of clamp application or solution administration may result in air infusion into the peritoneal cavity, which may lead to abdominal pain and/or peritonitis.

Excessive use of Dianeal PD4 with high glucose content during peritoneal dialysis may cause significant dehydration.

Potassium is excluded from the composition of Dianeal PD4 due to the risk of hyperkalemia. In patients with normal serum potassium levels or hypokalemia, addition of potassium chloride (up to 4 mEq/L) may be indicated to prevent severe hypokalemia. This should be done only under medical supervision following careful assessment of serum potassium levels and total body potassium.

Serum electrolyte concentrations (particularly bicarbonate, potassium, magnesium, calcium, and phosphate), blood chemistry (including parathyroid hormone and lipid levels), and hematological parameters should be monitored periodically.

In diabetic patients, blood glucose levels should be monitored regularly during and after dialysis with glucose-containing solutions, and insulin dosage or other hyperglycemia treatment should be adjusted accordingly.

The product should be used immediately after removal from the outer packaging.

Use during pregnancy or breastfeeding

Pregnancy

Data on the use of Dianeal PD4 in pregnant women are limited. Reproductive toxicity studies in animals are insufficient.

Dianeal PD4 is not recommended for use in pregnant women or in women of reproductive potential who are not using contraception.

Breastfeeding

It is unknown whether metabolites of Dianeal PD4 are excreted in human breast milk. Risk to newborns/infants cannot be excluded.

The decision whether to discontinue breastfeeding or to discontinue/abstain from treatment with Dianeal PD4 should be made based on the benefit of breastfeeding to the child and the benefit of therapy to the woman.

Fertility

Clinical data on fertility are lacking.

Effect on ability to drive and use machines

Patients with end-stage renal disease undergoing peritoneal dialysis may experience adverse effects (e.g., malaise, hypovolemia) that could impair their ability to drive or operate machinery.

Method of Administration and Dosage.

Dosing.

The treatment regimen, frequency, exchange volume, dwell time in the peritoneal cavity, and duration of dialysis are determined by the physician.

Adults.

For CAPD, patients usually undergo 4 cycles per day (24 hours). For APD, 4–5 cycles are usually performed overnight and up to 2 cycles during the day. The volume of solution to be instilled depends on body size and is typically between 2 and 2.5 liters.

Children (neonates and children under 18 years of age).

The recommended dose is 800–1400 mL/m² per cycle. The maximum dose of 2000 mL must not be exceeded. For children under 2 years of age, the recommended instilled volume is 500–1000 mL/m².

As the patient's body weight approaches ideal dry body weight, it is recommended to reduce the glucose content in the Dianeal PD4 solution.

Dianeal PD4, 3.86% glucose solution, is a highly osmotic fluid; its independent use may lead to dehydration (see section "Special Warnings and Precautions for Use").

To prevent the risk of severe dehydration and hypovolemia and to minimize protein loss, it is recommended to select a peritoneal dialysis solution with the lowest osmolarity sufficient to remove the required amount of fluid during each session.

Method of Administration

Precautions to be taken before preparation or administration of the medicinal product.

The peritoneal dialysis solution is intended only for intraperitoneal administration. Not for intravenous use.

Warming the solution to 37°C reduces patient discomfort. However, this procedure should only be performed using dry heat (e.g., a heating pad or warming plate). Solutions must not be heated in water due to the increased risk of contamination. To avoid potential damage to the bag and patient injury or discomfort, solutions must not be heated in a microwave oven.

The entire procedure must be performed under strict aseptic conditions.

Administration must not be performed if the solution is discolored, cloudy, contains particulate matter, if the container shows signs of leakage, or if the seals preventing contact of the solution with the external environment are damaged.

The drained fluid should be examined for the presence of fibrin and cloudiness, which may indicate peritonitis.

For single use only.

Potassium Addition

Potassium is excluded from the composition of Dianeal PD4 because dialysis may be performed to correct hyperkalemia. Potassium chloride (at concentrations up to 4 mEq/L) may be added when serum potassium levels are normal or in cases of hypokalemia to prevent severe hypokalemia. This should only be done under medical supervision following careful assessment of serum potassium levels.

Children.

Administer to children according to the recommendations in the section "Method of Administration and Dosage."

Overdose.

There is a possibility of overdose, which may manifest as hypervolemia, hypovolemia, electrolyte imbalance, or (in diabetic patients) hyperglycemia.

Excessive use of Dianeal PD4, 3.86% glucose solution, during peritoneal dialysis may cause significant patient dehydration.

Treatment of Overdose

Hypervolemia can be treated by using hypertonic peritoneal dialysis solutions and fluid restriction.

Hypovolemia can be treated by restoring fluid losses orally or intravenously, depending on the degree of dehydration.

Electrolyte imbalances should be treated according to the specific type of disturbance identified by blood analysis. The most likely imbalance, hypokalemia, can be treated by oral potassium supplementation or by adding potassium chloride to the peritoneal dialysis solution as prescribed by the physician.

Hyperglycemia (in diabetic patients) should be managed by adjusting insulin dosage or oral antidiabetic medications according to the treatment regimen prescribed by the physician.

Adverse reactions.

The adverse reactions listed below have been reported following the marketing of the medicinal product.

The adverse effects of the medicinal product are listed according to the recommended frequency categories: very common – > 10%, common – > 1% and < 10%; uncommon – > 0.1% and < 1%; very rare – < 0.01%; frequency not known (cannot be estimated from available data).

Other side effects associated with peritoneal dialysis procedure: fungal peritonitis, bacterial peritonitis, catheter-related infection, catheter-related complications.

Shelf life. 2 years.

Do not use the solution remaining in the bag after completion of the procedure.

Storage conditions.

Store at a temperature not exceeding 25 °C, in a place inaccessible to children. Do not freeze.

Incompatibility.

Formal drug interaction studies have not been conducted.

Compatibility should be checked when using additives. The resulting mixture should be used immediately.

Packaging.

2000 ml of solution in a single polyvinyl chloride (PVC) PL 146-3 plastic bag equipped with an injection port and connector, or in a “Twin Bag” system equipped with an injection port and a drain empty plastic bag integrated via two lines and a Y-connector, all contained in a transparent plastic pouch; 5 sets per cardboard box;

2500 ml of solution in a single polyvinyl chloride (PVC) PL 146-3 plastic bag equipped with an injection port and connector, or in a “Twin Bag” system equipped with an injection port and a drain empty plastic bag integrated via two lines and a Y-connector, all contained in a transparent plastic pouch; 4 sets per cardboard box;

3000 ml of solution in a single polyvinyl chloride (PVC) PL 146-3 plastic bag equipped with an injection port and connector, or in a “Twin Bag” system equipped with an injection port and a drain empty plastic bag integrated via two lines and a Y-connector, all contained in a transparent plastic pouch; 3 sets per cardboard box;

5000 ml of solution in a single polyvinyl chloride (PVC) PL 146-3 plastic bag equipped with an injection port and connector, contained in a transparent plastic pouch; 2 sets per cardboard box.

Prescription status. Prescription only.

Manufacturer.

Vantive Manufacturing Limited / Vantive Manufacturing Limited

Manufacturer's address and site of manufacturing activity.

Moneen Road, Castlebar, Co. Mayo, F23 XR63, Ireland. / Moneen Road, Castlebar, Co. Mayo, F23 XR63, Ireland.