Nutriflex 40/80 lipid (Emulsion) Instructions for Use

ATC Code

B05BA10 (Combined preparations for parenteral nutrition)

Clinical-Pharmacological Group

Drug for total parenteral nutrition – solution of amino acids, fats, carbohydrates, electrolytes

Pharmacotherapeutic Group

Parenteral nutrition agent

Pharmacological Action

The goal of parenteral nutrition is to supply the body with all the necessary nutrients for tissue growth and regeneration, as well as the energy required to maintain all body functions.

Amino acids are the most important, as some of them are essential for protein synthesis. The combined administration of energy sources (carbohydrates and lipids) is necessary to avoid the undesirable use of amino acids as an energy substrate.

Glucose is utilized by all tissues in the body. For some tissues and organs, such as the CNS, bone marrow, erythrocytes, and renal tubular epithelium, glucose is the only source of energy. Furthermore, glucose is a building material for various cellular structures.

Lipids have high energy value and are also a source of essential fatty acids for the synthesis of cellular structures and prostaglandins. For this purpose, the fat emulsion contains medium-chain and long-chain triglycerides (soybean oil).

Medium-chain triglycerides are hydrolyzed faster, eliminated from the bloodstream, and completely oxidized compared to long-chain triglycerides. They are the main energy substrate, especially when the process of metabolism and utilization of long-chain triglycerides is impaired, for example, in cases of lipoprotein lipase deficiency and/or lipoprotein lipase co-factor deficiency. Unsaturated fatty acids, which are part of long-chain triglycerides, are used in the body mainly for the prevention and treatment of essential fatty acid deficiency and only secondarily as a source of energy.

Pharmacokinetics

Absorption

Bioavailability: Since Nutriflex 40/80 lipid is administered intravenously, the bioavailability of all its components is 100%. Consequently, all substances become available for metabolism immediately.

The maximum individual concentration of triglycerides depends on the dose, infusion rate, metabolic state, and the patient’s condition (degree of exhaustion). When prescribed according to the instructions for use and adhering to the dose, the triglyceride concentration usually does not exceed 3 mmol/L.

Distribution

Amino acids are part of proteins in various body tissues. Furthermore, each amino acid is present in free form inside cells and in the extracellular space.

Since glucose is soluble in water, it is delivered by blood to all organs and tissues. Glucose first enters the intravascular space and then into the cell.

When the dosing recommendations for the drug are followed, medium-chain and long-chain fatty acids are almost completely bound to plasma albumin.

When the dose is adhered to, medium-chain and long-chain fatty acids do not cross the blood-brain barrier and, therefore, do not enter the cerebrospinal fluid.

Data on penetration through the placental barrier and into breast milk are not available.

Metabolism

Amino acids not used in protein synthesis are metabolized as follows. The amino group is cleaved from the carbon chain by transamination. The carbon chain is either oxidized to CO₂ or utilized as a substrate for gluconeogenesis in the liver. The amino group is also converted into urea in the liver. Glucose is metabolized to CO₂ and H₂O. Some glucose is converted into fat.

After administration, triglycerides are hydrolyzed to glycerol and fatty acids. Both components are used in energy-producing reactions, synthesis of biologically active molecules, gluconeogenesis, and resynthesis of lipids.

Excretion

A small amount of amino acids is excreted unchanged in the urine. Excess glucose is excreted in the urine only if the excretion threshold is reached. Both soybean oil triglycerides and medium-chain triglycerides are completely metabolized to CO₂ and H₂O. Small amounts of lipids are lost through the shedding of skin cells and other epithelial-lined membranes. Triglycerides are practically not excreted by the kidneys.

Indications

• Replenishment of energy, essential fatty acids, amino acids, electrolytes, and water requirements during parenteral nutrition in patients with standard and moderately increased metabolic needs, when normal food intake and enteral nutrition are impossible, insufficient, or contraindicated;
• Parenteral nutrition in patients with hyperglycemia or the threat of its development;
• Parenteral nutrition when infusion is only possible into peripheral veins (in outpatient settings, surgical departments, at home).

ICD codes

Dosage Regimen

Emulsion

Method of Administration

Intended for intravenous administration into peripheral and central veins.

The temperature of the administered emulsion should correspond to room temperature.

The configuration of the chambers of the Nutriflex 40/80 lipid preparation allows the fat emulsion to be added last, in order to preliminarily assess compatibility with other added medicinal products.

Mixing Technique for Container Chamber Contents

If it is necessary to add other medicinal products to the Nutriflex 40/80 lipid preparation, use the following technique:

1. Remove the secondary plastic bag from the container, unfold it, and place the container on a hard, flat surface (on a table);
2. Pressing with both hands on the upper left chamber of the container (containing the glucose solution with electrolytes), break the partition separating it from the lower chamber (containing the amino acid solution with electrolytes);
3. If necessary, add electrolytes, trace elements, and other compatible medicinal products (including water-soluble vitamins) through the additional port with a red protective cap;
4. Pressing with both hands on the upper right chamber of the container (containing the fat emulsion), break the partition separating it from the lower chamber;
5. If necessary, add fat-soluble vitamins through the additional port with a red protective cap;
6. Gently mix the contents of all container chambers.

If there is no need to add other medicinal products to the Nutriflex 40/80 lipid preparation, use the following technique:

1. Remove the secondary plastic bag from the container, unfold it, and place the container on a hard, flat surface (on a table);
2. Pressing with both hands on the two upper chambers of the container, break the partitions separating them from the lower chamber;
3. Gently mix the contents of all container chambers.

For Conducting Infusion After Mixing the Container Chamber Contents

• After transferring the emulsion to the lower chamber, fold the container along the midline separating the empty upper chambers from the lower one;
• Hang the container on the infusion stand using the special ring in the center of the container;
• Remove the white protective cap from the infusion port, connect the system for intravenous infusion, and begin the infusion at the rate specified in this instruction for use.

Doses

Selected according to individual needs.

Children aged 14 years and older and adults

The maximum daily dose is 40 ml/kg body weight, which corresponds to

• 1.28 g amino acids/kg body weight/day,
• 2.56 g glucose/kg body weight/day,
• 1.6 g fat/kg body weight/day.

Children aged 2 to 14 years

These recommendations are based on average requirements. The dose should be individually adapted depending on age, stage of development, and severity of the disease. When calculating the dose, the degree of hydration of pediatric patients must be taken into account.

For children, it may be necessary to start therapeutic nutrition with half the calculated dose. The dose should be increased to the maximum gradually, in accordance with the individual metabolic capabilities of the body.

For children aged 2 to 5 years, the daily dose is 45 ml/kg body weight, which corresponds to

• 1.44 g amino acids/kg body weight/day,
• 2.88 g glucose/kg body weight/day,
• 1.8 g fat/kg body weight/day.

For children aged 5 to 14 years, the daily dose is 30 ml/kg body weight, which corresponds to

• 0.96 g amino acids/kg body weight/day,
• 1.92 g glucose/kg body weight/day,
• 1.20 g fat/kg body weight/day.

Due to the age characteristics of children, Nutriflex 40/80 lipid may not fully meet the energy requirement. In such cases, a glucose solution or fat emulsion can be added to the parenteral nutrition program as needed.

Infusion Rate

Long-term administration of the Nutriflex 40/80 lipid preparation is recommended. A stepwise increase in the infusion rate over the first 30 minutes reduces the frequency of possible complications.

The maximum infusion rate is 2.5 ml/kg body weight/hour, which corresponds to

• 0.08 g amino acids/kg body weight/hour,
• 0.16 g glucose/kg body weight/hour,
• 0.1 g fat/kg body weight/hour.

For a patient weighing 70 kg, the maximum infusion rate would be 175 ml/hour. In this case, the amino acid infusion rate would be 5.6 g/hour, glucose – 11.2 g/hour, fats – 7.0 g/hour.

Elderly patients

Doses do not differ from those recommended for other adult patients. However, metabolism can vary significantly in old age, so careful monitoring of this patient group is necessary.

Patients with renal and/or hepatic impairment

Doses are selected individually.

Duration of Use

Administration of the Nutriflex 40/80 lipid preparation is not recommended for more than seven days.

Adverse Reactions

Adverse reactions are listed below by system organ class and frequency of occurrence. Most adverse reactions associated with the use of this drug occur rarely (>1/10000 – <1/1000).

The following classification of adverse reactions by frequency is used:

Very common (>1/10), common (>1/100, <1/10), uncommon (>1/1000, <1/100), rare (>1/10000, <1/1000), very rare (<1/10000)

Blood and lymphatic system disorders rare – hypercoagulation.

Immune system disorders rare – allergic reactions (e.g., anaphylactic reactions, skin rash, laryngeal edema, oral and facial edema).

Metabolism and nutrition disorders very rare – hyperlipidemia, hyperglycemia, metabolic acidosis.

The frequency of these adverse reactions depends on the dose and may be higher in case of lipid overdose.

Nervous system disorders rare – drowsiness.

Vascular disorders rare – increase or decrease in blood pressure, “flushing”.

Respiratory, thoracic and mediastinal disorders: rare – dyspnea, cyanosis of the skin.

Gastrointestinal disorders uncommon – nausea, vomiting, loss of appetite.

General disorders and administration site conditions common – after several days of using the drug, vein irritation, phlebitis or thrombophlebitis may develop; rare – headache, increased body temperature, sweating, feeling of cold, chills, back pain, bone pain, chest pain and lumbar pain; very rare – fat overload syndrome.

If adverse reactions occur, the infusion should be stopped or, if necessary, continued at a lower dose.

Upon re-administration, especially at the beginning of the infusion, careful monitoring of the patient’s condition is required. Plasma triglycerides should be monitored with increased frequency.

Additional information on some adverse reactions

Nausea, vomiting, lack of appetite, and hyperglycemia are symptoms that are the basis for prescribing parenteral nutrition or are often present in patients for whom parenteral nutrition is indicated.

Fat overload syndrome

An impaired ability to utilize triglycerides, which can be caused by overdose, may lead to “fat overload syndrome”. Monitoring should be performed to detect symptoms of metabolic overload early. Fat overload syndrome may be of genetic etiology (individual differences in metabolism), furthermore, existing or past diseases can affect fat metabolism. This syndrome can also develop against the background of severe hypertriglyceridemia, even when adhering to the recommended infusion rate, as well as against the background of the development of severe complications such as renal failure or infection. Fat overload syndrome is characterized by hyperlipidemia, fever, fatty infiltration, hepatomegaly (with or without jaundice), splenomegaly, abdominal pain, anemia, leukopenia, thrombocytopenia, coagulation disorders, hemolysis and reticulocytosis, abnormal liver function tests, and coma. The symptoms are reversible and usually disappear after the infusion is stopped. If signs of fat overload syndrome appear, the administration of Nutriflex 40/80 lipid must be stopped immediately.

Contraindications

The drug must not be prescribed under the following conditions

• Congenital disorders of amino acid metabolism;
• Disorders of fat metabolism;
• Pathologically high concentration of plasma electrolytes;
• Unstable metabolism (e.g., severe post-aggression syndrome, decompensated hyperglycemia in diabetes mellitus, metabolic acidosis, coma of unknown etiology);
• Severe hyperglycemia, not correctable with insulin doses up to 6 units/hour;
• Intrahepatic cholestasis;
• Severe hepatic failure;
• Severe renal failure in the absence of renal replacement therapy;
• Progressive hemorrhagic diathesis;
• Acute phase of myocardial infarction and stroke;
• Acute cases of thromboembolism, fat embolisms;
• Children under 2 years of age;
• Identified hypersensitivity to egg white or soybean protein, nut oil, or any of the components of the drug.

General contraindications for parenteral nutrition

• Unstable, life-threatening circulatory disorder (collapse and shock);
• Severe tissue hypoxia;
• States of hyperhydration;
• Disturbances of water-electrolyte balance;
• Acute pulmonary edema;
• Decompensated heart failure.

With caution

Caution should be exercised with increased serum osmolality. Given the possible risk of volume overload when using Nutriflex 40/80 lipid, caution should be exercised in patients with impaired heart or kidney function.

The drug should be administered with caution to patients with impaired fat metabolism (e.g., in renal failure, diabetes mellitus, pancreatitis, impaired liver function, hypothyroidism with hypertriglyceridemia, and sepsis). In these conditions, monitoring of serum triglyceride concentration is mandatory.

Use in Pregnancy and Lactation

Pregnancy

No studies have been conducted to assess the effect of Nutriflex 40/80 lipid on the embryo or fetus. Prescribing the drug during pregnancy is possible if the potential benefit to the mother outweighs the potential risk to the fetus.

Breastfeeding period

Generally, breastfeeding during parenteral nutrition is not recommended.

Use in Hepatic Impairment

The drug should be administered with caution to patients with impaired liver function.

Use in Renal Impairment

Given the possible risk of volume overload when using Nutriflex 40/80 lipid, caution should be exercised in patients with impaired kidney function.

Pediatric Use

Contraindicated in children under 2 years of age.

Geriatric Use

Doses do not differ from those recommended for other adult patients. However, metabolism can vary significantly in old age, so careful monitoring of this patient group is necessary.

Special Precautions

If anaphylactic reactions, such as fever, convulsions, rash, or dyspnea, occur, the infusion should be stopped immediately.

Disturbances in water-electrolyte balance or acid-base status, e.g., hyperhydration, hyperkalemia, acidosis, should be corrected before starting the infusion.

Too rapid administration can lead to fluid overload with disturbance of plasma electrolyte balance, hyperhydration, and pulmonary edema.

When administering Nutriflex 40/80 lipid, plasma triglyceride concentration must be monitored.

In patients suspected of having impaired fat metabolism, there should be no hyperlipidemia when prescribing the drug. Administration of fats in hyperlipidemia is contraindicated. Hypertriglyceridemia 12 hours after drug administration indicates impaired fat metabolism.

Depending on the patient’s metabolic state, transient hypertriglyceridemia or an increase in plasma glucose concentration may develop. If the plasma triglyceride concentration during lipid administration exceeds 3 mmol/L, it is recommended to reduce the infusion rate. If the plasma triglyceride concentration remains above 3 mmol/L, administration should be suspended until lipid concentrations normalize.

When blood glucose concentration increases above 14 mmol/L (250 mg/dL), a dose reduction or discontinuation of the infusion is necessary.

Similar to other medicinal products containing carbohydrates, the administration of Nutriflex 40/80 lipid may lead to hyperglycemia. Blood glucose concentration must be monitored. If hyperglycemia develops, the infusion rate should be reduced or insulin should be prescribed.

Intravenous administration of amino acids is accompanied by an increased excretion of trace elements in the urine, especially copper and zinc. This should be taken into account when prescribing trace elements, particularly during long-term parenteral nutrition.

Resumption or initiation of parenteral nutrition in debilitated patients or patients who have not received adequate nutrition may cause hypokalemia, hypophosphatemia, and hypomagnesemia. Adequate administration of electrolytes according to deviations from normal values is necessary.

Monitoring of plasma electrolyte concentrations, fluid balance, acid-base status, blood urea nitrogen, and, with prolonged administration; cellular composition, blood coagulation system, and liver function is necessary. The type and frequency of laboratory tests depend on the patient’s overall condition.

The drug should not be administered through the same transfusion systems simultaneously with, before, or after blood administration due to the risk of pseudoagglutination.

Replenishment of electrolytes, vitamins, and trace elements may be required.

The fat content in the drug may reduce the accuracy of laboratory tests (e.g., bilirubin, lactate dehydrogenase, oxygen saturation) if blood samples are taken during or immediately after the end of the drug infusion.

The infusion of Nutriflex 40/80 lipid, like all drugs for intravenous administration, must be carried out under aseptic conditions.

Nutriflex 40/80 lipid is a drug of complex composition. Therefore, it is not recommended to add other solutions to it without specific indications.

The emulsion must be used immediately after mixing, or it can be stored at a temperature of 2-8°C (35.6-46.4°F) for 4 days, and additionally for 48 hours (including infusion time) at a temperature of 25°C (77°F).

If filters are used during drug administration, they must be fat-permeable.

The drug must not be used after accidental freezing.

Use only intact packages in which the amino acid and glucose solutions are clear. Do not use packages where there is obvious phase separation (fat droplets) in the fat emulsion chamber.

Mix before use.

Single-use container. Discard any unused volumes of the drug.

Effect on the Ability to Drive and Operate Machinery

The drug does not affect the ability to drive vehicles, operate machinery, or engage in other potentially hazardous activities requiring increased concentration and speed of psychomotor reactions.

Overdose

When the drug is prescribed correctly, overdose is not observed.

Symptoms of volume overload or electrolyte overdose hypertonic hyperhydration, electrolyte balance disorders, pulmonary edema.

Symptoms of amino acid overdose: renal loss of amino acids with the development of amino acid imbalance, nausea, vomiting, tremor.

Symptoms of glucose overdose hyperglycemia, glucosuria, dehydration, serum hyperosmolarity, hyperglycemic or hyperosmolar coma.

Symptoms of lipid overdose lipid overdose may lead to the development of fat overload syndrome.

Therapy

If symptoms of overdose appear, administration of the drug must be discontinued. Further therapy is selected individually depending on the severity of the symptoms. The infusion may be resumed later at a lower rate with constant monitoring. The concentration of triglycerides in the blood plasma during infusion should not exceed 3 mmol/L.

Drug Interactions

Solutions containing potassium should be administered with caution to patients who are receiving medicinal products that increase serum potassium concentration, such as potassium-sparing diuretics, ACE inhibitors, cyclosporine, and tacrolimus. Soybean oil contains vitamin K₁, which may interfere with the therapeutic effect of indirect anticoagulants – coumarin derivatives. Therefore, the therapeutic effect of indirect anticoagulants – coumarin derivatives should be carefully monitored.

Corticosteroids and corticotropin cause sodium and fluid retention in the body. Some drugs, such as insulin, may interact with the body’s lipolytic enzymes. However, these interactions have little clinical significance.

Administration of heparin in therapeutic doses leads to increased lipolysis in plasma, which in turn may lead to a decrease in triglyceride clearance.

Nutriflex 40/80 lipid contains zinc and magnesium, which must be taken into account when prescribing other drugs containing these trace elements.

Nutriflex 40/80 lipid is a drug of complex composition. Therefore, it is not recommended to add other solutions to it without prior compatibility testing, as otherwise the stability of the emulsion cannot be guaranteed.

Storage Conditions

Store at a temperature not exceeding 25°C (77°F) in a light-protected place. Do not freeze. Keep out of the reach of children.

Shelf Life

Shelf life – 2 years.

Dispensing Status

For hospital use.

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.