Nutriflex lipid peri nova

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT NUTRIFLEX LIPID PERI NOVO

Composition:

Active substances: ready-to-use emulsion after mixing the contents of the chambers contains:

From the upper chamber (glucose solution)	in 1000 ml	in 1250 ml	in 1875 ml	in 2500 ml
Glucose monohydrate, equivalent to anhydrous glucose	70.40 g 64.00 g	88.00 g 80.00 g	132.0 g 120.0 g	176.0 g 160.0 g
Sodium dihydrogen phosphate dihydrate	0.936 g	1.170 g	1.755 g	2.340 g
Zinc acetate dihydrate	5.280 mg	6.600 mg	9.900 mg	13.20 mg
From the middle chamber (fat emulsion)	in 1000 ml	in 1250 ml	in 1875 ml	in 2500 ml
Refined soybean oil	20.00 g	25.00 g	37.50 g	50.00 g
Medium-chain triglycerides	20.00 g	25.00 g	37.50 g	50.00 g
From the lower chamber (amino acid solution)	in 1000 ml	in 1250 ml	in 1875 ml	in 2500 ml
Isoleucine	1.872 g	2.340 g	3.510 g	4.680 g
Leucine	2.504 g	3.130 g	4.695 g	6.260 g
Lysine hydrochloride, equivalent to lysine	2.272 g 1.818 g	2.840 g 2.273 g	4.260 g 3.410 g	5.680 g 4.546 g
Methionine	1.568 g	1.960 g	2.940 g	3.920 g
Phenylalanine	2.808 g	3.510 g	5.265 g	7.020 g
Threonine	1.456 g	1.820 g	2.730 g	3.640 g
Tryptophan	0.456 g	0.570 g	0.855 g	1.140 g
Valine	2.080 g	2.600 g	3.900 g	5.200 g
Arginine	2.160 g	2.700 g	4.050 g	5.400 g
Histidine hydrochloride monohydrate, equivalent to histidine	1.352 g 1.000 g	1.690 g 1.251 g	2.535 g 1.876 g	3.380 g 2.502 g
Alanine	3.880 g	4.850 g	7.275 g	9.700 g
Aspartic acid	1.200 g	1.500 g	2.250 g	3.000 g
Glutamic acid	2.800 g	3.500 g	5.250 g	7.000 g
Glycine	1.320 g	1.650 g	2.475 g	3.300 g
Proline	2.720 g	3.400 g	5.100 g	6.800 g
Serine	2.400 g	3.000 g	4.500 g	6.000 g
Sodium hydroxide	0.640 g	0.800 g	1.200 g	1.600 g
Sodium chloride	0.865 g	1.081 g	1.622 g	2.162 g
Sodium acetate trihydrate	0.435 g	0.544 g	0.816 g	1.088 g
Potassium acetate	2.354 g	2.943 g	4.415 g	5.886 g
Magnesium acetate tetrahydrate	0.515 g	0.644 g	0.966 g	1.288 g
Calcium chloride dihydrate	0.353 g	0.441 g	0.662 g	0.882 g

Electrolytes (mmol)	in 1000 ml	in 1250 ml	in 1875 ml	in 2500 ml
Sodium	40	50	75	100
Potassium	24	30	45	60
Magnesium	2.4	3.0	4.5	6.0
Calcium	2.4	3.0	4.5	6.0
Zinc	0.024	0.03	0.045	0.06
Chlorides	38	48	72	96
Acetates	32	40	60	80
Phosphates	6.0	7.5	11.25	15.0

	in 1000 ml	in 1250 ml	in 1875 ml	in 2500 ml
Amino acids	32 g	40 g	60 g	80 g
Nitrogen	4.6 g	5.7 g	8.6 g	11.4 g
Carbohydrates	64 g	80 g	120 g	160 g
Lipids	40 g	50 g	75 g	100 g

	in 1000 ml	in 1250 ml	in 1875 ml	in 2500 ml
Energy in the form of lipids [kJ (kcal)]	1590 (380)	1990 (475)	2985 (715)	3980 (950)
Energy in the form of carbohydrates [kJ (kcal)]	1075 (255)	1340 (320)	2010 (480)	2680 (640)
Energy in the form of amino acids [kJ (kcal)]	535 (130)	670 (160)	1005 (240)	1340 (320)
Non-protein energy [kJ (kcal)]	2665 (635)	3330 (795)	4995 (1195)	6660 (1590)
Total energy [kJ (kcal)]	3200 (765)	4000 (955)	6000 (1435)	8000 (1910)

Osmolality [mOsm/kg]	950	950	950	950
Theoretical osmolarity [mOsm/L]	840	840	840	840
pH	5.0 – 6.0	5.0 – 6.0	5.0 – 6.0	5.0 – 6.0

Excipients: citric acid monohydrate; glycerol; egg lecithin; sodium oleate; α-tocopherol; water for injections.

Pharmaceutical form. Infusion emulsion.

Main physicochemical properties:

Amino acid chamber: clear solution, colorless to pale yellow, free from particles;

Glucose chamber: clear solution, colorless to pale yellow, free from particles;

Lipid emulsion chamber: white, milk-like emulsion.

Pharmacotherapeutic group. Solutions for parenteral nutrition. Combinations.

ATC code B05B A10.

Pharmacological properties.

Pharmacodynamics.

Mechanism of action

The goal of parenteral nutrition is to supply all necessary nutrients and energy for growth and/or tissue regeneration, as well as to maintain all bodily functions.

Amino acids are particularly important, as some of them are essential components for protein synthesis. Concurrent administration of energy sources (carbohydrates/lipids) is necessary to spare amino acids for tissue regeneration and anabolism, and to prevent their use as an energy source.

Glucose is widely metabolized in the body. Certain tissues and organs, such as the central nervous system, bone marrow, erythrocytes, and tubular epithelium, meet their energy requirements exclusively from glucose. In addition, glucose acts as a structural component of various cellular substances.

Due to their high energy density, lipids are an efficient source of energy. Long-chain triglycerides provide the body with essential fatty acids required for the synthesis of cellular components. For this purpose, long- and medium-chain triglycerides (soybean oil) are included in the lipid emulsion.

Medium-chain triglycerides are hydrolyzed, cleared from the bloodstream, and completely oxidized more rapidly than long-chain triglycerides. They serve as a preferred energy source, particularly in cases of impaired breakdown and/or utilization of long-chain triglycerides, for example, in lipoprotein lipase deficiency and/or deficiency of its cofactors.

Unsaturated fatty acids derived from the long-chain triglyceride fraction are primarily used for the prevention and treatment of essential fatty acid deficiency.

Preclinical studies with Nutriflex Lipid peri novo have not been conducted.

Toxic effects of nutrient mixtures used as replacement therapy at recommended doses are not expected.

Pharmacokinetics.

Absorption. Nutriflex Lipid peri novo is administered intravenously. Thus, all substrates are immediately incorporated into metabolism.

Distribution. The dose, infusion rate, metabolic status, and individual patient factors (degree of depletion) are decisive for achieving the maximum triglyceride concentration. When used according to recommended dosing, triglyceride concentration generally does not exceed 4.6 mmol/L (400 mg/dL).

Medium-chain fatty acids have low affinity for albumin. Animal experiments with pure medium-chain triglyceride emulsions have shown that medium-chain fatty acids may cross the blood-brain barrier in cases of overdose. No adverse reactions have been observed with the emulsion containing a mixture of medium- and long-chain triglycerides, as long-chain triglycerides inhibit the hydrolysis of medium-chain triglycerides. Therefore, toxic effects on the brain after administration of Nutriflex Lipid peri novo can be excluded.

Amino acids are components of a wide variety of proteins in different organs of the body. In addition, each amino acid is present in free form in blood and within cells.

Since glucose is water-soluble, it is distributed throughout the body via the bloodstream. Initially, the glucose solution distributes in the intravascular space and subsequently transfers into the intracellular space.

There are no available data on the passage of components/metabolites of Nutriflex Lipid peri novo across the placental barrier or into breast milk.

Biotransformation. Amino acids not involved in protein synthesis are metabolized via the pathways described below. The amino group is removed from the carbon skeleton by transamination. The carbon chain is either directly oxidized to CO₂ or used by the liver as a substrate for gluconeogenesis. The amino group is also metabolized in the liver to urea.

Glucose is metabolized to CO₂ and H₂O via well-known metabolic pathways. Some glucose is used for lipid synthesis.

After infusion, triglycerides are hydrolyzed to glycerol and fatty acids. Both compound groups participate in physiological processes of energy production, synthesis of biologically active molecules, gluconeogenesis, and re-synthesis of lipids.

Elimination. Only a small amount of amino acids is excreted unchanged in urine.

Excess glucose is excreted in urine only if the renal threshold for glucose is exceeded.

Both soybean oil triglycerides and medium-chain triglycerides are completely metabolized to CO₂ and H₂O. Only a small amount of lipids is lost through desquamation of skin cells and other epithelial membranes. Renal excretion does not occur.

Clinical characteristics.

Indications.

For providing energy, essential fatty acids, amino acids, electrolytes, and fluid during parenteral nutrition of patients with moderate or moderately severe catabolism when oral or enteral nutrition is impossible, inadequate, or contraindicated.

Nutriflex Lipid peri is indicated for adults, adolescents, and children aged 2 years and older.

Contraindications.

• Hypersensitivity to the active substances, egg, peanut or soy proteins, or to any other component of the medicinal product;
• congenital disorders of amino acid metabolism;
• hyperglycemia unresponsive to insulin doses up to 6 units insulin/hour;
• intrahepatic cholestasis;
• severe hepatic insufficiency;
• severe renal insufficiency in the absence of renal replacement therapy;
• hemorrhagic diathesis during an exacerbation period;
• acute thromboembolic events, lipid embolism;
• severe hypertriglyceridemia (≥ 1000 mg/dL, or 11.4 mmol/L);
• severe coagulopathy;
• acidosis.

Nutriflex Lipid peri must not be used in neonates, infants, and children under 2 years of age due to its composition.

General contraindications for parenteral nutrition:

• unstable circulatory condition with life-threatening risk (state of collapse or shock);
• acute phase of myocardial infarction and stroke;
• unstable metabolic state (e.g., severe post-aggression syndrome, coma of unknown origin);
• inadequate cellular oxygen supply;
• disturbances of electrolyte or fluid balance;
• acute pulmonary edema;
• decompensated heart failure.

Interaction with other medicinal products and other forms of interaction.

Solutions containing potassium should be used with caution in patients receiving medicinal products that increase serum potassium concentrations, such as potassium-sparing diuretics (triamterene, amiloride, spironolactone), ACE inhibitors (e.g., captopril, enalapril), angiotensin-II receptor antagonists (e.g., losartan, valsartan), cyclosporine, and tacrolimus.

Soy oil contains a natural amount of vitamin K1. This may influence the therapeutic effect of coumarin derivatives, which should be carefully monitored in patients receiving such agents.

The use of corticosteroids and adrenocorticotropic hormone is associated with sodium and fluid retention.

Some drugs, such as insulin, may interfere with the body's lipase system. However, this type of interaction has only limited clinical significance.

Heparin at clinical doses causes a temporary release of lipoprotein lipase into the bloodstream. This may initially lead to increased plasma lipolysis, followed by a temporary reduction in triglyceride clearance.

The product must not be administered simultaneously with blood using the same infusion set due to the risk of pseudoagglutination (see also section "Special precautions").

Special precautions for use.

In the event of any signs or symptoms of an anaphylactic reaction (such as fever, chills, rash, or dyspnea), the infusion must be stopped immediately.

Caution should be exercised in cases of increased serum osmolarity. Fluid, electrolyte, and acid-base imbalances should be corrected prior to initiating the infusion.

Too rapid infusion may lead to fluid overload, accompanied by abnormal electrolyte concentrations, hyperhydration, and pulmonary edema.

When administering Nutriflex Lipid peri, serum triglyceride concentrations should be monitored.

Depending on the patient's metabolic status, hypertriglyceridemia may occasionally occur. If plasma triglyceride concentration exceeds 4.6 mmol/L (400 mg/dL) during lipid administration, the infusion rate should be reduced. The infusion must be interrupted if plasma triglyceride concentration exceeds 11.4 mmol/L (1000 mg/dL), as such levels are associated with acute pancreatitis.

Patients with lipid metabolism disorders

Nutriflex Lipid peri should be administered with caution to patients with lipid metabolism disorders and elevated serum triglyceride levels, such as those with renal insufficiency, diabetes mellitus, pancreatitis, hepatic dysfunction, hypothyroidism (with hypertriglyceridemia), sepsis, or metabolic syndrome. When Nutriflex Lipid peri is administered to patients in these conditions, careful monitoring of serum triglyceride levels is mandatory to ensure adequate triglyceride clearance and maintenance of stable triglyceride levels below 11.4 mmol/L (1000 mg/dL).

In combined hyperlipidemia and metabolic syndrome, triglyceride levels are sensitive to glucose, lipids, and excessive food intake. Dose adjustment is required. Other sources of lipids and glucose, as well as medications interfering with their metabolism, should be evaluated and controlled.

The presence of hypertriglyceridemia 12 hours after lipid administration also indicates a lipid metabolism disorder.

Infusion should also be discontinued if blood glucose concentration exceeds 14 mmol/L (250 mg/dL) during administration.

Administration of Nutriflex Lipid peri, as with all carbohydrate-containing solutions, may lead to hyperglycemia. Blood glucose levels should be monitored regularly. In case of hyperglycemia, the infusion rate should be reduced or insulin administered. If the patient is simultaneously receiving other intravenous glucose solutions, the amount of additional glucose administered should be taken into account.

Re-feeding or initiation of nutrition in malnourished patients or those who have been poorly nourished may cause hypokalemia, hypophosphatemia, or hypomagnesemia. Adequate electrolyte supplementation must be provided according to deviations from normal values.

Monitoring of serum electrolyte concentrations, fluid balance, acid-base balance, blood count, coagulation status, and liver and kidney function is required.

Vitamins and trace elements should be administered according to individual needs.

Since Nutriflex Lipid peri contains zinc and magnesium, calcium, and phosphates, caution is advised when co-administered with other solutions containing these elements.

As with all intravenous solutions, especially those used for parenteral nutrition, strict adherence to aseptic techniques is essential during infusion of Nutriflex Lipid peri. The medicinal product should not be administered simultaneously with blood through the same administration set due to the risk of pseudoagglutination (see section "Interaction with other medicinal products and other forms of interaction").

Nutriflex Lipid peri is a complex formulation. Therefore, it is recommended not to add other solutions unless compatibility has been established (see section "Incompatibilities").

Additives may increase the overall osmolarity of the emulsion; this should be considered, particularly with peripheral administration, and the infusion site should be monitored.

Infusion into peripheral veins may cause thrombophlebitis. The infusion site should be examined daily for signs of thrombophlebitis.

Geriatric patients

The same dose as in adults is generally used; however, caution is required in patients with cardiac or renal insufficiency, which may be associated with advanced age.

Patients with diabetes mellitus, cardiac or renal insufficiency

As with all large-volume infusion solutions, Nutriflex Lipid peri should be administered with caution to patients with cardiac or renal insufficiency.

Experience with its use in patients with diabetes mellitus or renal insufficiency is limited.

This medicinal product contains 1150 mg of sodium in a 1250 mL bag, equivalent to 58% of the WHO recommended maximum daily intake of 2 g sodium for an adult.

The maximum daily dose of this medicinal product for a 70 kg adult is equivalent to 129% of the WHO recommended maximum daily sodium intake.

Nutriflex Lipid peri is considered a sodium-rich preparation. This should be particularly considered if the patient is on a low-salt diet.

Effect on laboratory test results

The presence of fat may interfere with certain laboratory tests (e.g., bilirubin, lactate dehydrogenase, oxygen saturation) if blood is drawn before fat has been sufficiently cleared from the circulation.

Use during pregnancy or breastfeeding

Pregnancy. Data on the effects of Nutriflex Lipid peri during pregnancy are limited. Animal studies are insufficient with respect to reproductive toxicity (see section "Pharmacodynamics"). Parenteral nutrition may be required during pregnancy. The physician must weigh the benefit-risk ratio before administering the product to pregnant women.

Breastfeeding. Components/metabolites of the medicinal product pass into breast milk; however, when used at therapeutic doses, no effect on neonates/infants who are breastfed is expected. However, women receiving parenteral nutrition are not recommended to breastfeed.

Fertility

There are no data on the effect on fertility when Nutriflex Lipid peri is administered.

Ability to influence reaction speed when driving or operating machinery

Nutriflex Lipid peri has no effect or a negligible effect on the ability to drive or operate machinery.

Method of Administration and Dosage

Dosage

Dosage must be adjusted according to individual patient requirements.

Nutriflex Lipid peri novo is recommended for continuous administration. Gradual increase in infusion rate to the desired level over the first 30 minutes helps prevent potential complications.

Patients aged 14 years and older, and adults

Maximum daily dose is 40 mL/kg body weight, corresponding to:

1.28 g amino acids/kg body weight per day;

2.56 g glucose/kg body weight per day;

1.6 g lipids/kg body weight per day.

Maximum infusion rate is 2.5 mL/kg body weight per hour, corresponding to:

0.08 g amino acids/kg body weight per hour;

0.16 g glucose/kg body weight per hour;

0.1 g lipids/kg body weight per hour.

For a patient weighing 70 kg, this corresponds to an infusion rate of 175 mL/hour. Thus, the amount of infused substrate is 5.6 g amino acids per hour, 11.2 g glucose per hour, and 7 g lipids per hour.

Children aged 2 to 13 years

The dosage recommendations provided are based on average requirements. Dosage should be individually adjusted according to age, stage of development, and type of disease. Hydration status of the child should be considered when calculating dosage.

It may be appropriate to initiate therapeutic nutrition in children at half the target dose. The dose should be gradually increased according to the individual's metabolic capacity until the maximum dose is reached.

Daily dose for children aged 2 to 4 years is 45 mL/kg body weight, corresponding to:

1.44 g amino acids/kg body weight per day;

2.88 g glucose/kg body weight per day;

1.8 g lipids/kg body weight per day.

Daily dose for children aged 5 to 13 years is 30 mL/kg body weight, corresponding to:

0.96 g amino acids/kg body weight per day;

1.92 g glucose/kg body weight per day;

1.2 g lipids/kg body weight per day.

Maximum infusion rate is 2.5 mL/kg body weight per hour, corresponding to:

0.08 g amino acids/kg body weight per hour;

0.16 g glucose/kg body weight per hour;

0.1 g lipids/kg body weight per hour.

Depending on the individual child's needs, Nutriflex Lipid peri novo may not fully meet total energy and fluid requirements. In such cases, additional carbohydrates, lipids, and fluids may be required, depending on the clinical situation.

Elderly patients

Metabolic rate and patterns in elderly patients may differ; therefore, careful monitoring is always advisable in this patient group.

Patients with renal/hepatic impairment

Dosage in patients with hepatic or renal impairment should be individually adjusted (see section "Special Warnings and Precautions for Use"). In special clinical conditions, such as parenteral nutrition during hemodialysis to compensate for nutrient losses associated with dialysis, a higher infusion rate may be required.

Treatment duration

Treatment duration for the recommended indications should not exceed 7 days. With prolonged use of Nutriflex Lipid peri novo, patients must receive adequate amounts of trace elements and vitamins.

Infusion duration from a single bag

Recommended duration of infusion from one bag of parenteral nutrition is a maximum of 24 hours.

Route of administration

Intravenous administration. For administration via peripheral or central veins.

Preparation of the mixed emulsion

Strict adherence to aseptic techniques is required.

Opening

Before opening the protective film of the pouch, check the color of the oxygen indicator. Do not use if the oxygen indicator has turned pink. Use only if the oxygen indicator is yellow.

Tear open the outer pouch along the perforation line.

Remove the bag from the outer pouch.

Dispose of the outer pouch, oxygen indicator, and oxygen absorber.

Visually inspect the primary bag for leaks. Discard any leaking bag, as sterility cannot be guaranteed.

To open the compartments and mix their contents sequentially, twist the bag with both hands, starting from the seal separating the upper compartment (glucose) and the lower compartment (amino acids). Then continue applying pressure to open the seal between the middle compartment (lipids) and the lower compartment.

Addition of additives

After mixing the contents of all compartments and removing the aluminum seal, compatible additives may be added through the medication port.

Information on compatibility of various additives (e.g., electrolytes, trace elements, vitamins) and the corresponding shelf life of such additives can be provided by the manufacturer upon request.

Thoroughly mix the bag contents and visually inspect the mixture. There should be no signs of emulsion phase separation.

The mixture forms a milky-white, homogeneous "oil-in-water" emulsion.

Preparation for infusion

Before infusion, the emulsion should always be brought to room temperature.

Remove the protective aluminum foil from the infusion port and connect the infusion set.

Use an infusion set without a venting valve, or close the venting port if using a set with a venting valve.

Hang the infusion bag on a stand and administer infusion according to standard procedures.

For single use only.

The bag and any unused portions of the medication must be discarded after use.

Do not reconnect a bag containing partially used medication.

If filters are used, they must be lipid-permeable (pore size ≥ 1.2 µm).

Parenteral nutrition preparations should be visually inspected before use for packaging damage, color change, and emulsion instability.

Do not use damaged bags. The outer pouch film, primary bag, and seals between compartments must be intact. Use only if the amino acid and glucose solutions are clear and colorless to pale straw-colored, and the lipid emulsion is white and milky. Do not use if the solutions contain particulate matter.

After mixing the three compartments, do not use the medicinal product if the emulsion has changed color or shows signs of phase separation (oil droplets, oil layer). In case of color change or phase separation, discontinue infusion immediately.

Before opening the protective pouch film, check the color of the oxygen indicator. Do not use if the oxygen indicator has turned pink. Use only if the oxygen indicator is yellow.

No special requirements for disposal.

Children

Nutriflex Lipid peri novo is contraindicated in newborns, infants, and children under 2 years of age (see section "Contraindications").

Overdose

Symptoms of fluid and electrolyte overdose

Hyperhydration, electrolyte imbalance, and pulmonary edema.

Symptoms of amino acid overdose

Renal excretion of amino acids leading to amino acid imbalance, nausea, vomiting, and tremor.

Symptoms of glucose overdose

Hyperglycemia, glucosuria, dehydration, hyperosmolarity, hyperglycemic-hyperosmolar coma.

Symptoms of lipid overdose

Described in the section "Adverse Reactions."

Treatment

In case of overdose, immediate discontinuation of infusion is indicated. Further therapeutic measures depend on the specific symptoms and their severity. If re-initiation of infusion is necessary after symptom resolution, it is recommended to gradually increase the infusion rate with frequent monitoring.

Adverse Reactions

Even with correct use, adherence to safety rules and instructions for use, adverse reactions may still occur. Below is a list of systemic reactions that may be associated with the use of the medicinal product Nutriflex Lipid peri novo.

Adverse reactions are listed according to their frequency of occurrence:

Very common (≥ 1/10);

Common (≥ 1/100 to < 1/10);

Uncommon (≥ 1/1,000 to < 1/100);

Rare (≥ 1/10,000 to < 1/1,000);

Very rare (< 1/10,000);

Not known (frequency cannot be estimated from available data).

Blood and lymphatic system disorders

Rare: hypercoagulation

Not known: leukopenia, thrombocytopenia

Immune system disorders

Rare: allergic reactions (including anaphylactic reactions, skin rashes, angioedema of larynx, oral cavity, and face)

Metabolism and nutrition disorders

Uncommon: loss of appetite

Very rare: hyperlipidemia, hyperglycemia, metabolic acidosis. The frequency of these adverse reactions is dose-dependent and may increase in cases of absolute or relative lipid overdose.

Nervous system disorders

Rare: headache, somnolence

Vascular disorders

Rare: arterial hypertension or hypotension, hot flushes

Respiratory system disorders

Rare: dyspnea, cyanosis

Gastrointestinal disorders

Uncommon: nausea, vomiting

Hepatobiliary disorders

Not known: cholestasis

Skin and subcutaneous tissue disorders

Rare: erythema, sweating

Musculoskeletal and connective tissue disorders

Rare: back, bone, shoulder, and lumbar pain

General disorders and administration site conditions

Rare: increased body temperature, feeling of cold, chills

Very rare: fat overload syndrome (further details below)

Common: after several days, venous irritation, phlebitis, or thrombophlebitis may occur

If signs of venous irritation, phlebitis, or thrombophlebitis occur, consider changing the infusion site.

Infusion should be discontinued if these adverse reactions occur.

If serum triglyceride levels rise to 11.4 mmol/L (1000 mg/dL) during infusion, the infusion must be stopped. Infusion may continue at lower doses when levels are above 4.6 mmol/L (400 mg/dL) (see section "Special precautions for use").

If the infusion is restarted, close monitoring of the patient is required, especially at the beginning, with frequent measurement of serum triglyceride concentrations.

Information on specific adverse reactions

Nausea, vomiting, and loss of appetite are symptoms commonly associated with conditions requiring parenteral nutrition, but they may also be related to parenteral nutrition itself.

Fat Overload Syndrome

Reduced ability to eliminate triglycerides may lead to fat overload syndrome, which may be caused by overdose. Possible signs of metabolic overload should be observed. Causes may include genetic disorders (individual metabolic differences), and existing or previous diseases may also affect fat metabolism. This syndrome may also occur in severe hypertriglyceridemia, even when the recommended infusion rate is followed, and in association with sudden changes in the patient's clinical condition, such as renal dysfunction or infection. Fat overload syndrome is characterized by hyperlipidemia, fever, fatty infiltration, hepatomegaly with or without jaundice, splenomegaly, anemia, leukopenia, thrombocytopenia, coagulation disorders, hemolysis, reticulocytosis, abnormal liver function tests, and coma. These symptoms are usually reversible after discontinuation of the fat emulsion infusion.

If symptoms of fat overload syndrome occur, administration of Nutriflex Lipid peri novo must be stopped immediately.

Reporting suspected adverse reactions

Reporting suspected adverse reactions after medicinal product authorization is of great importance. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy through the Automated Information System for Pharmacovigilance at the following link: https://aisf.dec.gov.ua.

Shelf life

Unopened bag: 2 years.

After first opening (puncturing the infusion port): the emulsion should be used immediately after first opening of the packaging.

After removal of the protective film from the outer pouch and after mixing the contents of the chambers: chemical and physical stability of the mixture of amino acids, glucose, and fat has been demonstrated for 7 days at 2–8 °C and an additional 2 days at 25 °C.

After addition of compatible additives: from a microbiological standpoint, the medicinal product should be administered immediately after addition of compatible additives. If not administered immediately, responsibility for storage time and conditions prior to use lies with the user.

Storage conditions

Store at temperatures not exceeding 25 °C. Do not freeze. If the bag contents accidentally freeze, the product should be discarded.

Store the bag in its outer packaging, protected from light and out of reach of children.

Incompatibilities

Nutriflex Lipid peri novo must not be mixed with other medicinal products whose compatibility has not been documented (see section "Instructions for use and dosage").

Nutriflex Lipid peri novo must not be administered simultaneously with blood products (see sections "Special precautions for use" and "Interaction with other medicinal products and other forms of interaction").

Packaging

1250 ml (500 ml amino acid solution + 250 ml lipid emulsion + 500 ml glucose solution) in a flexible multi-chamber bag made of multilayer foil; 5 bags per cardboard box.

1875 ml (750 ml amino acid solution + 375 ml lipid emulsion + 750 ml glucose solution) in a flexible multi-chamber bag made of multilayer foil; 5 bags per cardboard box.

2500 ml (1000 ml amino acid solution + 500 ml lipid emulsion + 1000 ml glucose solution) in a flexible multi-chamber bag made of multilayer foil; 5 bags per cardboard box.

Prescription status: Prescription only.

Manufacturer

B. Braun Melsungen AG / B. Braun Melsungen AG.

Manufacturer's location and address of place of business

Am Schwerzelshof 1, 34212 Melsungen, Germany / Am Schwerzelshof 1, 34212 Melsungen, Germany.