Nutrineal PD 4 with 1.1% amino acids (Solution) Instructions for Use

Marketing Authorization Holder

Baxter Healthcare, S.A. (Ireland)

ATC Code

B05DB (Hypertonic solutions)

Dosage Form

Nutrineal PD 4 with 1.1% amino acids

Solution for peritoneal dialysis: containers 500, 1000, 1500, 2000, 2500, 3000 ml

Dosage Form, Packaging, and Composition

500 ml – plastic “Viaflex” containers (1) – polymer bags.
1 L – plastic “Viaflex” containers (1) – polymer bags.
1.5 L – plastic “Viaflex” containers (1) – polymer bags.
2 L – plastic “Viaflex” containers (1) – polymer bags.
2.5 L – plastic “Viaflex” containers (1) – polymer bags.
3 L – plastic “Viaflex” containers (1) – polymer bags.
2 L – plastic “Viaflex” containers (1) – polymer bags (5) – cardboard boxes.

Clinical-Pharmacological Group

Solution for peritoneal dialysis

Pharmacotherapeutic Group

Peritoneal dialysis solution

Pharmacological Action

A sterile, apyrogenic solution for peritoneal dialysis allows for the removal of toxic substances formed during the metabolism of nitrogen-containing compounds and normally excreted by the kidneys, as well as for maintaining adequate regulation of water, electrolyte, and acid-base balance. This procedure is performed by introducing the peritoneal dialysis solution into the abdominal cavity through a catheter. As a result of osmosis and diffusion through the peritoneum, an exchange of substances occurs between the peritoneal capillaries and the dialysis fluid. After a certain dwell time, the solution becomes saturated with toxic substances and must then be replaced. With the exception of lactate, which is a precursor to bicarbonate, the electrolyte concentrations in the solution are selected to normalize the patient’s plasma electrolyte concentrations. Nitrogen metabolism products, present in high concentrations in the blood, pass through the peritoneum into the dialysis solution.

The concentration of electrolytes in the fluid is equivalent to the electrolyte composition of normal extracellular fluid (with the exception of lactate).

Pharmacokinetics

Amino acids, electrolytes, buffer solution, and water introduced into the abdominal cavity are absorbed into the blood and metabolized in the usual way. Electrolytes are metabolized in a manner characteristic of each ion. From 70% to 80% of the administered amino acids are absorbed from the introduced solution into the blood within 4-6 hours of the solution’s dwell time in the abdominal cavity.

Indications

The drug is recommended for use as a non-glucose-based peritoneal dialysis solution (as part of a peritoneal dialysis procedure). In particular, it is intended for patients with malnutrition syndrome and albuminemia (serum albumin concentration less than 35 g/L) who are on peritoneal dialysis.

ICD codes

Dosage Regimen

For intraperitoneal administration only. Not for intravenous administration. This method of administration requires the use of a special catheter and an appropriate system that connects the container to the patient’s catheter.

Nutrineal PD4 with 1.1% amino acids should be administered at a rate comfortable for the patient. The volume of solution administered is determined by the attending physician.

The dosing regimen, frequency of use, volume of solution exchanged, dwell time of the solution in the abdominal cavity, and duration of treatment are prescribed and monitored by the attending physician.

If after 3 months of using the drug there is no positive dynamics in the patient’s clinical condition and such indicators as serum creatinine, urea, potassium concentration, hemoglobin level and red blood cell count, the treatment tactics should be reconsidered.

Before use, it is advisable to warm the solution in the outer bag to 37°C (98.6°F) to increase patient comfort during the peritoneal dialysis procedure. Only dry heat should be used for this purpose (e.g., a heating pad, heating plate). Do not heat the solution in water or a microwave oven, as this may cause patient discomfort or lead to damage.

Aseptic rules must be observed during the peritoneal dialysis procedure.

The outer protective bag should be removed immediately before use. Before use, the solution must be checked for clarity and the absence of foreign particles.

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

Any unused solution residue should be destroyed.

Patients on continuous ambulatory peritoneal dialysis at home must undergo training in specialized centers.

For single use only.

Adults and elderly patients

For patients with a body weight of 70 kg, one exchange of peritoneal solution per day of 2 or 2.5 L is recommended. For patients with lower body weight, the volume of solution administered may be reduced according to body weight.

In exceptional cases, a different administration regimen may be prescribed, but the dose should not exceed two administration cycles per day.

It should be noted that the recommended daily protein intake is approximately 1.2 g/kg for an adult patient. A 2-liter container contains 22 g of amino acids, which is equivalent to 0.3 g/kg/day (approximately 25% of the daily protein intake) for patients with a body weight of 70 kg.

Children and adolescents

The efficacy and safety of the drug in clinical studies in pediatric patients have not yet been studied. In this regard, for this category of patients, it is necessary to compare the expected clinical benefit of using the drug and the risk of adverse reactions.

One cycle of solution administration per day is recommended. For children over 2 years of age, the recommended solution volume is from 800 to 1400 ml/m² per cycle, with a maximum volume of 2000 ml/m² if well tolerated. For children under 2 years of age, a volume from 200 to 1000 ml/m² is recommended.

With caution

• In patients with uncompensated metabolic acidosis, severe hepatic insufficiency, or hyperammonemia. It is necessary to control metabolic acidosis before prescribing Nutrineal PD4 with 1.1% amino acids and during treatment;
• In patients with pathology of the abdominal organs and peritoneum, including rupture of the peritoneum and diaphragm associated with surgical intervention, incomplete healing of defects arising from developmental anomalies or trauma, abdominal tumors, inflammatory diseases of the abdominal wall, hernias, rectal fistulas or colostomy, massive polycystic kidney lesions or other conditions associated with impaired integrity of the abdominal wall, peritoneal surface, or intra-abdominal cavity;
• In patients with other pathological conditions, including correction of an aortic defect with a graft or severe lung diseases;
• In patients taking cardiac glycosides. It is necessary to carefully monitor the concentration of potassium, calcium, and magnesium in the blood plasma.

In patients with diabetes mellitus, it is necessary to monitor blood glucose concentrations and adjust the doses of insulin or other drugs used for hyperglycemia accordingly.

If symptoms of hypersensitivity are suspected, the use of Nutrineal PD4 with 1.1% amino acids should be discontinued immediately. Appropriate therapy should be prescribed.

Adverse Reactions

The adverse events presented in this section are assumed to be related to the drug Nutrineal PD4 with 1.1% amino acids, or to the procedure of peritoneal dialysis.

Adverse events noted in clinical studies

The adverse events listed below were observed in clinical studies in >5% of patients receiving Nutrineal.

Adverse events are included in this table if the frequency of occurrence of events was higher than in the control group by 2% or more.

The frequency of adverse reactions for the medicinal product was assessed using the following scale: very common (≥1/10), common (≥1/100 – < 1/10), uncommon (≥ 1/1000 – < 1/100), rare (≥ 1/10,000 – < 1/1000) and very rare (< 1/10,000).

* The term “nausea or vomiting” does not correspond to the terminology of the MedDRA Medical Dictionary for Regulatory Activities 11.0. This term was retained to reflect the information presented in the source.

Adverse events noted in the post-marketing period

The following adverse events have been reported during the post-marketing period.

Infections and infestations bacterial peritonitis.

Immune system disorders hypersensitivity reactions, angioedema.

Metabolism and nutrition disorders anorexia.

Gastrointestinal disorders abdominal pain, peritonitis, cloudiness of peritoneal fluid, abdominal discomfort.

Skin and subcutaneous tissue disorders pruritus.

General disorders and administration site conditions catheter insertion related disorders, pyrexia, malaise.

Laboratory and instrumental data: abnormal peritoneal fluid analysis.

Contraindications

• Serum urea level exceeds 38 mmol/L;
• Uremia;
• Metabolic acidosis;
• Congenital defects of amino acid metabolism;
• Hepatic insufficiency;
• Severe hypokalemia;
• Hypersensitivity to the components of the drug.

Use in Pregnancy and Lactation

There are no data on the safety of using Nutrineal PD4 with 1.1% amino acids during pregnancy and breastfeeding.

Prescription of the drug during pregnancy and breastfeeding is possible only if the intended benefit to the mother outweighs the potential risk to the fetus or child.

Pediatric Use

The efficacy and safety of the drug in clinical studies in pediatric patients have not yet been studied. In this regard, for this category of patients, it is necessary to compare the expected clinical benefit of using the drug and the risk of adverse reactions.

One cycle of solution administration per day is recommended. For children over 2 years of age, the recommended solution volume is from 800 to 1400 ml/m² per cycle, with a maximum volume of 2000 ml/m² if well tolerated. For children under 2 years of age, a volume from 200 to 1000 ml/m² is recommended.

Geriatric Use

Adults and elderly patients

For patients with a body weight of 70 kg, one exchange of peritoneal solution per day of 2 or 2.5 L is recommended. For patients with lower body weight, the volume of solution administered may be reduced according to body weight.

In exceptional cases, a different administration regimen may be prescribed, but the dose should not exceed two administration cycles per day.

It should be noted that the recommended daily protein intake is approximately 1.2 g/kg for an adult patient. A 2-liter container contains 22 g of amino acids, which is equivalent to 0.3 g/kg/day (approximately 25% of the daily protein intake) for patients with a body weight of 70 kg.

Special Precautions

Encapsulating peritoneal sclerosis (EPS) is a rare complication of dialysis therapy. EPS has been observed in patients using peritoneal dialysis solutions.

In case of peritonitis development, the choice and dose of antibiotics should, if possible, be based on the results of identification and sensitivity testing of the isolated microorganism(s). Until the microorganism(s) is identified, broad-spectrum antibiotics may be prescribed.

Nutrineal PD4 with 1.1% amino acids is for intraperitoneal administration only. Not intended for intravenous use.

Do not use if the solution has changed color, become cloudy, contains foreign inclusions, shows signs of leakage, or if the packaging integrity is compromised.

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

Protein, amino acids, water-soluble vitamins, and substances may be removed during the peritoneal dialysis procedure, which may require replacement therapy.

In patients taking cardiac glycosides, it is necessary to carefully monitor the concentration of potassium, calcium, and magnesium in the blood plasma.

Introduction of an excessive amount of peritoneal dialysis solution into the abdominal cavity may be accompanied by abdominal distension, abdominal pain, and/or dyspnea.

Measures in case of administration of an excessive volume of peritoneal dialysis solution involve draining the solution from the abdominal cavity. To avoid hyperhydration and dehydration, careful monitoring of the patient’s condition is necessary. The balance of fluid intake and output should be monitored, and the patient’s body weight should be monitored.

Potassium is not included in the composition of the Nutrineal PD4 with 1.1% amino acids solution due to the risk of hyperkalemia. If the patient has a normal serum potassium concentration or hypokalemia, additional potassium chloride (up to 4 mEq/L) may be administered to prevent the development of severe hypokalemia. Before prescribing, the serum potassium concentration should be determined. Treatment is prescribed only under the supervision of the attending physician.

Periodically, it is necessary to monitor serum electrolyte concentrations (in particular, bicarbonate, potassium, magnesium, calcium, and phosphate); perform blood biochemical tests (including parathyroid hormone concentration) and hematological parameters.

In patients with diabetes mellitus, it is necessary to monitor blood glucose concentration and adjust the doses of insulin or other drugs used for hyperglycemia accordingly.

Some of the amino acids from the Nutrineal PD4 with 1.1% amino acids solution are metabolized into nitrogen-containing metabolic products, such as urea. With incomplete peritoneal dialysis, nitrogen-containing metabolic products from the solution can accumulate, leading to symptoms of uremia, such as anorexia or vomiting. Symptoms are relieved by discontinuing the solution or increasing the proportion of the amino acid-free solution.

Effect on ability to drive vehicles and operate machinery

During peritoneal dialysis in patients with end-stage renal disease (ESRD), adverse effects may occur that may affect the ability to drive vehicles and operate machinery.

Overdose

Consequences of a possible overdose may include hypervolemia and electrolyte imbalance.

Treatment of overdose

Treatment of hypervolemia may involve the administration of hypertonic peritoneal dialysis solutions and fluid restriction. Electrolyte imbalances require specific treatment for each individual case, confirmed by blood analysis. Hypokalemia, which is the most likely disorder, can be treated with oral potassium or by adding potassium chloride to the peritoneal dialysis solution as prescribed by the attending physician.

Drug Interactions

Studies on the interaction of Nutrineal PD4 with 1.1% amino acids with other medicinal products have not been conducted.

Concentrations of other drugs in the blood may decrease during dialysis.

Incompatibility

If possible, consult a specialist competent in peritoneal dialysis issues. Aseptic rules must be followed if, based on a written recommendation from a specialist, the introduction of additional substances into the solution is deemed appropriate.

When using additives, it is necessary to check compatibility; the mixed solution with additives should be used immediately.

Storage Conditions

Store at a temperature from 0°C (32°F) to 30°C (86°F) in a light-protected place. Do not freeze. Keep out of reach of children.

Shelf Life

The shelf life is 2 years.

Do not use after the expiration date.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.