Nutrinil pd4 with 1.1% amino acid content

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT NUTRINEAL PD4 WITH 1.1% AMINO ACIDS (NUTRINEAL PD4 WITH 1.1% AMINO ACIDS)

Composition:

Active substances: 1000 ml of solution contains L-tyrosine 0.3 g, L-tryptophan 0.27 g, L-phenylalanine 0.57 g, L-threonine 0.646 g, L-serine 0.51 g, L-proline 0.595 g, glycine 0.51 g, L-alanine 0.951 g, L-valine 1.393 g, L-methionine 0.85 g, L-isoleucine 0.85 g, L-leucine 1.02 g, L-lysine hydrochloride 0.955 g, L-histidine 0.714 g, L-arginine 1.071 g, calcium chloride dihydrate 0.184 g, magnesium chloride hexahydrate 0.051 g, sodium lactate 4.48 g, sodium chloride 5.38 g;

Excipients: hydrochloric acid concentrated, water for injections.

Pharmaceutical form. Solution for peritoneal dialysis.

Main physicochemical properties: clear, colorless to slightly yellowish solution, free from mechanical particles.

Pharmacotherapeutic group. Solutions for peritoneal dialysis.

ATC Code: B05DA.

Pharmacological properties.

Pharmacodynamics.

Nutrinil PD4 is a sterile, pyrogen-free solution for extrarenal elimination of metabolic waste products by prolonged ambulatory peritoneal dialysis.

The electrolyte concentration in the solution is similar to that of electrolytes in extracellular fluid under normal conditions (except for lactate).

The osmolarity of Nutrinil PD4 solution with 1.1% amino acid content is 365 mOsm/L.

Pharmacokinetics.

Nutrinil is administered into the patient's peritoneal cavity and then drained. The solution exerts its effect across the peritoneal membrane according to the principles of osmosis and diffusion; exchange (dialysis) occurs between the solution (dialysate) and the patient's blood plasma.

Electrolytes are metabolized via pathways typical for each ion.

70–80% of the administered amino acids are absorbed during the 6-hour dwell period in the peritoneal cavity.

The solution contains lactate, which is a biological precursor of bicarbonate.

Clinical characteristics.

Indications.

Treatment of patients with chronic renal insufficiency, including malnourished patients undergoing peritoneal dialysis.

Contraindications.

• Known hypersensitivity to amino acids of the drug or to any of the excipients;
• serum urea level exceeding 38 mmol/L;
• symptoms of uremia;
• metabolic acidosis;
• congenital defects of amino acid metabolism;
• hepatic insufficiency;
• severe hypokalemia;
• irreversible mechanical defects interfering with effective peritoneal dialysis or increasing the risk of infection;
• documented loss of peritoneal function or extensive adhesions preventing peritoneal function.

Special safety precautions.

The solution should be used immediately after addition of any drugs.

Before mixing medications, their compatibility must be verified, and the pH and salt content of the solution should be taken into account.

• Intraperitoneal administration requires the use of a special catheter and an appropriate infusion system connecting the solution container to the patient's catheter.
• Before home use, patients receive detailed instructions and training in performing peritoneal dialysis at a specialized training center.
• The drug must not be used if the container is damaged.
• The outer packaging should be removed only immediately before use.
• The solution must not be used if it is not clear.
• Any unused solution must be discarded.

Interaction with other medicinal products and other types of interactions.

Studies on the interaction of NUTRINIL with other drugs have not been conducted. The blood concentration of other medicinal products may decrease during dialysis.

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

Special precautions for use

Encapsulating peritoneal sclerosis (EPS) is considered a known rare complication of peritoneal dialysis. Cases of EPS have also been reported in patients using peritoneal dialysis solutions, including NUTRINYL.

In case of peritonitis, the choice and dosage of antibiotics should be based on results of tests identifying isolated microorganisms and their susceptibility, if possible. Prior to identification of microorganisms, treatment with broad-spectrum antibiotics may be necessary.

If any signs or symptoms suggestive of a hypersensitivity reaction occur, intraperitoneal administration of NUTRINYL should be discontinued immediately. Appropriate therapeutic measures should be initiated according to clinical indications.

Metabolic acidosis should be corrected prior to and during treatment with NUTRINYL.

The safety and efficacy of the drug in pediatric patients have not been established.

Significant losses of medications (including water-soluble vitamins) may occur during peritoneal dialysis. Replacement therapy should be administered when necessary.

Protein intake with food should be monitored.

Peritoneal dialysis should be performed with caution in patients with: 1) abdominal conditions, including abdominal wall defects, such as rupture of the peritoneal membrane and diaphragm due to surgical intervention, congenital anomalies or trauma after completion of treatment, intra-abdominal tumors, infection of the abdominal wall, hernia, fecal fistula, colostomy or ileostomy performed, frequent episodes of diverticulitis, inflammatory or ischemic bowel disease, large polycystic kidneys, or other conditions that may compromise the integrity of the abdominal wall, abdominal surface, or intraperitoneal cavity, and 2) other conditions, including implanted aortic graft and severe pulmonary disease.

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

To treat excessive infusion of peritoneal dialysis solution, fluid should be drained from the abdominal cavity.

Patients should be carefully monitored to avoid hyper- and hypovolemia. Fluid balance and body weight should be closely monitored.

Potassium is excluded from NUTRINYL due to the risk of developing hyperkalemia.

In situations with normal serum potassium levels or in the presence of hypokalemia, addition of potassium chloride (at a concentration up to 4 mEq/L) may be indicated to prevent severe hypokalemia. This should be done only after careful assessment of serum and total body potassium levels and under physician supervision.

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

In diabetic patients, blood glucose levels should be monitored regularly, and insulin dosage or other hyperglycemia treatment should be adjusted accordingly.

The amino acid component of NUTRINYL is converted into metabolic nitrogenous waste products such as urea. If dialysis is inadequate, the additional metabolic waste generated by NUTRINYL administration may lead to uremic symptoms such as anorexia and vomiting. These symptoms can be managed by reducing the number of NUTRINYL exchanges, discontinuing NUTRINYL administration, or increasing dialysis dose using a non-amino acid-based dialysis solution.

In patients with secondary hyperparathyroidism, the benefits and risks of using a low-calcium dialysis solution should be carefully considered, as it may exacerbate hyperparathyroidism.

Use during pregnancy or breastfeeding

There are no data on the use of the drug during pregnancy or breastfeeding, nor are there animal studies available. The use of the drug during pregnancy and breastfeeding is not recommended except when its use is considered absolutely necessary.

Ability to influence the speed of reactions while driving or operating machinery

Adverse effects that may affect the ability to drive or operate machinery (e.g., malaise, hypovolemia) may occur in patients with end-stage renal disease undergoing peritoneal dialysis.

Method of Administration and Dosage

NUTRINIL is intended for intraperitoneal administration only. Intravenous administration is not permitted.

Peritoneal dialysis solutions should be warmed in their outer protective packaging to 37°C to improve patient comfort. However, only dry heat sources (e.g., a heating pad or warming plate) should be used for this purpose. Solutions must not be heated in water due to the increased risk of contamination. Microwave heating is not recommended due to potential damage to the solution container, which may cause harm or discomfort to the patient.

The entire peritoneal dialysis procedure must be performed under strict aseptic conditions.

Administration should not be performed if the solution has changed color, become cloudy, contains particulate matter, shows signs of leakage, or if the seals are damaged.

Drained fluid should be inspected for the presence of fibrin or cloudiness, which may indicate peritonitis.

For single use only.

Dosing.

The method and frequency of treatment, exchange volume, dwell time in the peritoneal cavity, and duration of dialysis are prescribed and monitored by a physician.

Treatment should be re-evaluated after 3 months if there is no clinical or biochemical improvement in the patient's condition.

Adults: One daily peritoneal dialysis exchange using a single 2 L or 2.5 L bag is the recommended dose for a patient with a body weight of 70 kg. For smaller patients, the fill volume may need to be reduced according to body size. In exceptional cases, an alternative dose may be indicated; however, the dose should not exceed two exchanges per day. Note that the recommended daily protein intake is 1.2 g/kg body weight or more for adult dialysis patients. A 2.0 L bag of NUTRINIL contains 22 g of amino acids, corresponding to 0.30 g/kg body weight/24 hours (approximately 25% of daily protein requirement) for a 70 kg adult dialysis patient.

Elderly patients: Dose adjustment is not required.

Children.

The safety and efficacy of the drug in children have not been established. When using NUTRINIL, the recommended dose is one daily exchange of peritoneal dialysis solution.

The clinical benefits of NUTRINIL should be weighed against the risk of adverse effects in this patient population.

The recommended volume for pediatric patients aged >2 years is 800–1400 mL/m², with a maximum of 2000 mL, depending on tolerability. For children under 2 years of age, a volume of 200–1000 mL/m² is recommended.

Overdose.

There is a potential risk of overdose, which may lead to hypervolemia and electrolyte imbalance.

Treatment of overdose:

• Hypervolemia can be managed by using hypertonic peritoneal dialysis solutions and restricting fluid intake.
• Electrolyte imbalances should be treated according to the specific imbalance identified by blood analysis. The most likely imbalance, hypokalemia, can be corrected by oral potassium supplementation or by adding potassium chloride to the peritoneal dialysis solution as directed by a physician.

Adverse reactions.

This section lists adverse effects considered to be associated with the drug NUTRINIL or with the procedure of peritoneal dialysis.

Undesirable events observed in patients receiving NUTRINIL in clinical studies and during the post-marketing period are listed below.

The frequency of adverse reactions is classified as follows: very common (> 1/10), common (> 1/100 and < 1/10), uncommon (> 1/1000 and < 1/100), rare (> 1/10,000 and < 1/1000), very rare (< 1/10,000).

* The terms “nausea” or “vomiting” are not present in MedDRA 11.0. This term was retained to reflect the source data available.

Other adverse events associated with peritoneal dialysis procedure: catheter insertion site infection, catheter-related complications, hypocalcemia, and bacterial peritonitis.

Shelf life.

2 years.

Do not use the medicinal product after the expiry date stated on the container.

Storage conditions.

Store at temperatures not exceeding 30 °C in a place inaccessible to children.

Protect from light. Do not freeze.

Do not use if the solution is not clear or if the container is damaged.

Any unused portion should be discarded.

Incompatibilities.

Heparin and insulin preparations showed no signs of incompatibility with the NUTRINIL solution. NUTRINIL PD4 in PVC containers should not be mixed with other medicinal products except those specified in the section “Special precautions for disposal and handling”.

Packaging.

2 L of solution in a plastic bag equipped with an injection port and connector, placed in an individual pouch. 5 units in a cardboard box.

2 L of solution in a plastic bag equipped with an injection port, connected via two lines and a Y-connector to an empty plastic drainage bag, all placed in an individual pouch. 5 units in a cardboard box.

Prescription status.

Prescription only.

Manufacturer.

Vantive Manufacturing Limited

Vantive Manufacturing Limited

Address.

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

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