Olimeel n4e

INSTRUCTION for medical use of the medicinal product Olimel N4E (Olimel N4E)

Composition:

Active substances: alanine; arginine; asparagine acid; glutamine acid; glycine; histidine; isoleucine; leucine; lysine acetate (equivalent to lysine); methionine; phenylalanine; proline; serine; threonine; tryptophan; tyrosine; valine; sodium acetate trihydrate; potassium chloride; magnesium chloride hexahydrate; sodium glycerophosphate hydrate; glucose monohydrate (equivalent to anhydrous glucose); calcium chloride dihydrate; refined olive oil; refined soybean oil.

1 three-chamber bag contains:

Composition of the emulsion after mixing the contents of 3 chambers:

The ratio of olive oil (approximately 80% by mass) to soybean oil (approximately 20% by mass) is calculated to achieve a content of essential fatty acids (linoleic acid plus α-linolenic acid) amounting to 20% of the total fatty acid content.

Nutritional properties of the emulsion after mixing the contents of 3 chambers:

a Includes calories from egg phospholipids for injection

b Includes phosphates from the lipid emulsion (egg phospholipids)

Pharmaceutical form. Emulsion for infusion.

Main physicochemical properties:

glucose solution with calcium and amino acid solution with electrolytes: clear, colourless or slightly yellow, practically free from particles;

lipid emulsion: homogeneous, milk-like liquid.

Pharmacotherapeutic group. Parenteral nutrition solutions. Combinations.

ATC code B05B A10.

Pharmacological properties.

Pharmacodynamics.

The nitrogen content (L-amino acid series) and caloric content (glucose and triglycerides) in Olimel N4E allow for maintaining an adequate nitrogen/calorie ratio.

The preparation also contains electrolytes.

The lipid (fat) emulsion contained in Olimel N4E consists of refined olive oil and refined soybean oil in an 80/20 ratio, with an approximate fatty acid distribution as follows:

• 15% saturated fatty acids (SFA);
• 65% monounsaturated fatty acids (MUFA);
• 20% polyunsaturated essential fatty acids (PUFA).

The phospholipid/triglyceride ratio is 0.06.

Olive oil contains significant amounts of alpha-tocopherol, which, in combination with moderate PUFA intake, contributes to improved vitamin E status and reduced lipid peroxidation.

The amino acid solution contains 17 L-amino acids (including 8 essential amino acids) necessary for protein synthesis.

Amino acids also serve as an energy source. Their oxidation leads to nitrogen excretion in the form of urea.

Amino acid profile:

• Essential amino acids / total amino acids − 44.8%;
• Essential amino acids (g) / total nitrogen (g) − 2.8;
• Branched-chain amino acids / total amino acids − 18.3%.

Glucose is the source of carbohydrates.

Pharmacokinetics.

The components of Olimel N4E (amino acids, electrolytes, glucose, and fats) are distributed, metabolized, and eliminated via the same pathways as when the individual components are administered separately.

Clinical characteristics.

Indications.

For parenteral nutrition in adults and children aged 2 years and older when oral or enteral nutrition is impossible, inadequate, or contraindicated.

Contraindications.

Age under 2 years.

Hypersensitivity to egg or soy proteins, peanuts, or corn/corn products (see section "Special precautions"), or to any of the active substances or excipients.

Inborn disorders of amino acid metabolism.

Severe hyperlipidemia or severe disturbances of fat metabolism characterized by hypertriglyceridemia.

Severe hyperglycemia.

Pathologically elevated plasma concentrations of sodium, potassium, magnesium, calcium, and/or phosphorus.

Interaction with other medicinal products and other types of interactions.

Interaction studies have not been conducted.

Olimel N4E must not be administered simultaneously with blood through the same infusion system due to the risk of pseudoagglutination.

The lipids contained in this emulsion may affect the results of certain laboratory tests (e.g., bilirubin, lactate dehydrogenase, oxygen saturation, hemoglobin levels) if blood samples are taken before clearance of lipids (typically cleared within 5–6 hours in the absence of repeated administration).

Precipitation of ceftriaxone and calcium may occur if ceftriaxone is mixed with calcium-containing solutions in the same infusion system. Ceftriaxone must not be mixed or administered simultaneously with calcium-containing intravenous solutions, including Olimel N4E, through the same infusion system (e.g., via a Y-connector). However, ceftriaxone and calcium-containing solutions may be administered consecutively, provided the infusion system is thoroughly flushed with a compatible fluid between infusions (see sections "Special precautions" and "Incompatibilities").

Olimel N4E contains vitamin K, naturally present in lipid emulsions. The amount of vitamin K in the recommended doses of Olimel N4E is considered not to affect coumarin derivatives.

Due to the potassium content of Olimel N4E, special caution is required when administering the product to patients receiving potassium-sparing diuretics (e.g., amiloride, spironolactone, triamterene), angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, or immunosuppressants such as tacrolimus or cyclosporine, due to the risk of hyperkalemia.

Some medicinal products, such as insulin, may affect the body's lipase system. However, this type of interaction has limited clinical significance.

Heparin, administered at clinical doses, causes a transient release of lipoprotein lipase into the circulation. This may initially lead to enhanced plasma lipolysis followed by a transient decrease in triglyceride clearance.

Special precautions for use.

Too rapid administration of any solution for total parenteral nutrition (TPN) may lead to severe or fatal consequences.

Infusion should be stopped immediately if any symptoms of an allergic reaction occur (such as sweating, fever, chills, headache, skin rash, or dyspnea). This medicinal product contains soybean oil and egg phospholipids. Soy and egg proteins may cause hypersensitivity reactions. Cross-allergic reactions between soy proteins and peanuts have been observed.

Olimel N4E contains glucose derived from corn, which may cause hypersensitivity reactions in patients allergic to corn or corn products (see section "Contraindications").

Ceftriaxone must not be mixed or co-administered with any calcium-containing intravenous solutions, even if different infusion systems or different infusion sites are used. Ceftriaxone and calcium-containing solutions may be administered sequentially one after another, provided different infusion systems connected at different sites are used, or if the infusion system is changed or thoroughly flushed with saline solution between infusions to prevent precipitation. If a patient requires continuous infusion of calcium-containing solutions for total parenteral nutrition, healthcare professionals may consider using alternative antibacterial agents that do not carry the same risk of precipitation. If ceftriaxone administration is considered necessary for a patient also requiring continuous parenteral nutrition, TPN solutions and ceftriaxone may be administered simultaneously, but through separate infusion systems connected at different sites. Alternatively, the TPN infusion may be interrupted during ceftriaxone administration, following the recommended flushing procedure between infusions (see sections "Interaction with other medicinal products and other forms of interaction" and "Incompatibilities").

Cases of precipitate formation in pulmonary vessels leading to pulmonary embolism and respiratory distress have been reported in patients receiving parenteral nutrition. Some cases were fatal. Excessive addition of calcium and phosphate increases the risk of calcium phosphate precipitate formation (see section "Incompatibilities").

There have also been reports of potential precipitate formation in the bloodstream.

In addition to checking the solution, the infusion system and catheter should be periodically inspected for precipitate formation.

If signs of respiratory distress occur, the infusion should be stopped and medical evaluation initiated.

Other medicinal products or substances should not be added to any component of the bag or to the reconstituted emulsion unless their compatibility and stability in the resulting solution have been confirmed (including stability of the lipid emulsion).

Precipitate formation or destabilization of the lipid emulsion may lead to vascular occlusion (see sections "Method of administration and dosage" and "Incompatibilities").

Severe disturbances in fluid and electrolyte balance, severe fluid overload, and severe metabolic disorders must be corrected before initiating infusion.

Special clinical monitoring is required at the beginning of intravenous infusion.

Infection at the vascular access site and sepsis are complications that may occur in patients receiving parenteral nutrition, particularly due to inadequate catheter care or immunosuppressive effects of disease or medications. Careful monitoring of signs of infection and laboratory results for fever/chills, leukocytosis, technical complications related to the access device, and hyperglycemia may help detect infections early. Patients requiring parenteral nutrition are often predisposed to infectious complications due to malnutrition and/or underlying disease. The frequency of septic complications can be reduced by strict adherence to aseptic techniques during catheter insertion and maintenance, as well as by using aseptic preparation techniques for the parenteral nutrition mixture.

Throughout the treatment period, monitoring of fluid and electrolyte balance, serum osmolarity, serum triglyceride levels, acid-base balance, blood glucose, liver and kidney function tests, coagulation tests, and complete blood count including platelet count is required.

Elevated liver enzymes and cholestasis have been reported during administration of similar medicinal products. If hepatic insufficiency is suspected, serum ammonia levels should be monitored.

Metabolic complications may develop if nutrient intake is not adapted to the patient's needs or if the metabolic capacity of any component of the drug is inaccurately assessed. Undesirable metabolic effects may result from insufficient or excessive administration of nutrients or from an inappropriate mixture composition relative to the individual patient's needs.

Administration of amino acid solutions may promote acute folate deficiency; therefore, daily folic acid supplementation is recommended.

Extravasation

The catheter insertion site should be regularly inspected for signs of extravasation.

In case of extravasation, infusion should be stopped immediately, leaving the inserted catheter or cannula in place for immediate treatment. If possible, aspiration through the inserted catheter/cannula should be performed to reduce the amount of fluid in the tissues before removing the catheter/cannula. If extravasation occurs in a limb, the limb should be elevated.

Depending on the extravasated drug (including any drug(s) mixed with Olimel N4E, if applicable) and the stage/severity of tissue damage, appropriate specific measures should be taken. Treatment may include non-pharmacological, pharmacological, and/or surgical interventions. In cases of significant extravasation, consultation with a plastic surgeon within the first 72 hours is recommended.

The site of extravasation should be monitored at least every 4 hours during the first 24 hours, and then once daily.

Infusion into the same peripheral or central vein should not be resumed.

Hepatic insufficiency

The product should be used with caution in patients with hepatic insufficiency due to the risk of developing or worsening neurological disorders associated with hyperammonemia. Regular clinical and laboratory examinations, including assessment of liver function, blood glucose, electrolytes, and triglycerides, are required.

Renal insufficiency

The product should be used with caution in patients with renal insufficiency, especially those with hyperkalemia, due to the risk of developing or worsening metabolic acidosis and hyperazotemia if metabolic waste products are not adequately eliminated via non-renal pathways. In such patients, fluid status, triglycerides, and electrolytes should be carefully monitored.

Blood

The product should be used with caution in patients with coagulation disorders and anemia. Complete blood count and coagulation parameters should be carefully monitored.

Endocrine and metabolic disorders

This product should be used with caution in patients with the following conditions:

• Metabolic acidosis; carbohydrate administration is not recommended in the presence of lactic acidosis. Regular clinical and laboratory examinations are required;
• Diabetes mellitus. Monitoring of glucose concentrations, glucosuria, ketonuria, and, if applicable, appropriate insulin dose adjustments are required;
• Hyperlipidemia caused by the fat content in the infusion emulsion. Regular clinical and laboratory examinations are required;
• Amino acid metabolism disorders.

Hepatobiliary disorders

Liver disorders, including cholestasis, steatosis, fibrosis, and cirrhosis, which may lead to hepatic insufficiency, as well as cholecystitis and cholelithiasis, are known to develop during parenteral nutrition in some patients. The etiology of these disorders is considered multifactorial and may vary among different patients. Patients with abnormal laboratory parameters or other signs of hepatobiliary disorders require consultation with a physician specialized in such disorders to identify potential causative factors and necessary therapeutic and preventive interventions.

Serum triglyceride concentrations and fat clearance capacity should be regularly monitored.

Serum triglyceride levels should not exceed 3 mmol/L during infusion.

If fat metabolism disorders are suspected, serum triglyceride levels should be measured daily after a 5–6 hour fat-free period. In adults, serum should become clear within less than 6 hours after discontinuation of lipid emulsion infusion. The next infusion should be administered only after serum triglyceride levels return to baseline.

Cases of fat overload syndrome have been reported with similar medicinal products. Impaired or limited ability to metabolize the fats contained in Olimel N4E may lead to fat overload syndrome, which may result from overdosing; however, signs of this syndrome may also occur even when the product is used according to instructions (see also section "Adverse reactions").

In case of hyperglycemia, the infusion rate of Olimel N4E should be adjusted and/or insulin administered.

Thrombophlebitis may develop when administered via peripheral vein. The catheter insertion site should be checked daily for local signs of thrombophlebitis.

If other substances are added to the product, the final osmolarity of the mixture must be checked before administration. The resulting mixture should be administered via central or peripheral vein depending on its final osmolarity. If the final mixture is hypertonic, it may cause venous irritation when administered into a peripheral vein.

Despite the natural content of trace elements and vitamins, their levels in the product are insufficient to meet the body's needs. Adequate amounts of trace elements and vitamins should be added to meet individual patient requirements and prevent deficiency. See instructions for adding other substances to this product.

Olimel N4E should be used with caution in patients with increased osmolarity, adrenal insufficiency, cardiac insufficiency, or impaired lung function.

In patients with malnutrition, initiation of parenteral nutrition may cause fluid retention, leading to pulmonary edema and congestive heart failure, as well as decreased serum concentrations of potassium, phosphate, magnesium, or water-soluble vitamins. These changes may occur within 24–48 hours; therefore, parenteral nutrition should be initiated cautiously and slowly, with careful monitoring and appropriate correction of fluid, electrolyte, trace element, and vitamin levels.

Do not connect bags in series, to avoid potential air embolism caused by residual gas in the previous bag.

To prevent risks associated with excessively rapid infusion, continuous and controlled infusion techniques are recommended.

Olimel N4E should be administered with caution to patients predisposed to electrolyte accumulation.

Intravenous administration of amino acids increases urinary excretion of trace elements, particularly copper and zinc. This should be considered when determining trace element dosages, especially during prolonged intravenous nutrition.

Effect on laboratory tests

Lipids contained in this emulsion may interfere with certain laboratory tests (see section "Interaction with other medicinal products and other forms of interaction").

Special precautions when used in children

When administering the product to children aged 2 years and older, it is crucial to use a bag whose volume corresponds to the daily dosage.

Olimel N4E is not suitable for use in children under 2 years of age because:

• Glucose intake is too low, resulting in a reduced glucose-to-fat ratio;
• The absence of cysteine makes the amino acid profile inadequate;
• Calcium content is too low;
• Bag volumes are inappropriate.

Maximum infusion rates are 4.3 mL/kg/hour for children aged 2 to 11 years and 3.2 mL/kg/hour for children aged 12 to 18 years.

Vitamins and trace elements must always be added. Pediatric formulations should be used.

Elderly patients

Dose selection for elderly patients should generally be cautious. Consideration should be given to the higher frequency of decreased liver, kidney, or heart function, as well as concomitant diseases or other medicinal therapies.

Use during pregnancy or breastfeeding.

Pregnancy

There are no clinical data on the use of Olimel N4E in pregnant women. Reproductive studies in animals have not been conducted. Given the route of administration and the indications for Olimel N4E, the product may be used during pregnancy if necessary. It should be administered to pregnant women only after careful evaluation.

Breastfeeding

There is insufficient information on the passage of the product's components or its metabolites into human breast milk. Parenteral nutrition may be necessary during breastfeeding. It should be administered to nursing women only after careful evaluation.

Fertility

There are no adequate data.

Ability to affect reaction speed when driving or operating machinery.

Not applicable.

Method of Administration and Dosage

Dosage

Olimel N4E is contraindicated for use in children under 2 years of age due to its unsuitable composition and volume (see sections "Pharmacodynamics", "Pharmacokinetics", and "Special Warnings and Precautions for Use").

The maximum daily dose specified below should not be exceeded. Because of the fixed composition of the multi-chamber bag, it is not always possible to meet all of the patient's nutritional requirements. There may be clinical situations where the patient requires nutrients in amounts different from those contained in the bag. Any adjustment of volume (dose) must take into account that this will affect the dosage of all other nutrients present in Olimel N4E.

Adults

Dosage depends on the patient's energy expenditure, clinical condition, body weight, and ability to metabolize the components of Olimel N4E, as well as on the additional amount of calories or proteins administered orally/enterally; therefore, the appropriate bag size should be selected accordingly.

Average daily requirements for patients are:

• 0.16 to 0.35 g nitrogen/kg body weight (1 to 2 g amino acids/kg), depending on the patient's nutritional status and degree of catabolic stress;
• 20 to 40 kcal/kg;
• 20 to 40 mL fluid/kg or 1 to 1.5 mL per kilocalorie expended.

The maximum daily dose of Olimel N4E is determined by total fluid intake – 40 mL/kg, corresponding to 1 g/kg amino acids, 3 g/kg glucose, 1.2 g/kg lipids, 0.8 mmol/kg sodium, and 0.6 mmol/kg potassium. For a patient weighing 70 kg, this equals 2800 mL of Olimel N4E per day, providing 71 g of amino acids, 210 g of glucose, and 84 g of lipids (e.g., 1680 non-protein kcal and a total of 1960 kcal).

The infusion rate should usually be gradually increased during the first hour, then adjusted according to the dose administered, total daily volume, and duration of infusion.

The maximum infusion rate of Olimel N4E is 3.2 mL/kg/hour, equivalent to 0.08 g/kg/hour amino acids, 0.24 g/kg/hour glucose, and 0.10 g/kg/hour lipids.

Children aged 2 years and older

Clinical studies in pediatric patients have not been conducted.

Dosage depends on the patient's energy expenditure, clinical condition, body weight, and ability to metabolize the components of Olimel N4E, as well as on the additional amount of calories or proteins administered orally/enterally; therefore, the appropriate bag size should be selected accordingly.

In addition, daily requirements for fluid, nitrogen, and calories continuously increase with age. Two pediatric age groups are considered: 2 to 11 years and 12 to 18 years.

The limiting factor for the use of Olimel N4E in both of these age groups is the magnesium concentration in the daily dose. In the age group 2 to 11 years, the limiting factor is also the lipid concentration in the hourly dose. In the age group 12 to 18 years, the limiting factor is the glucose concentration in the hourly dose. The resulting recommendations are shown in Table 1.

Table 1

a Recommended values according to the 2018 guidelines of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN)/European Society for Clinical Nutrition and Metabolism (ESPEN)/European Society for Research in Paediatrics (ESRP).

Usually, the infusion rate should be gradually increased during the first hour and then adjusted according to the administered dose, daily intake volume, and duration of infusion.

In general, it is recommended to start infusion in younger children with a low daily dose and gradually increase it to the maximum dosing level (see above).

Method and duration of administration

For single use only.

It is recommended to use the contents immediately after opening the bag and not to reuse for subsequent infusions.

After reconstitution, the mixture should appear homogeneous and milk-like.

Instructions for preparation and administration of the infusion emulsion are provided below.

Due to the low osmolarity of Olimel N4E, it may be administered via peripheral or central vein.

The recommended duration of infusion using a parenteral nutrition bag is 12–24 hours.

Parenteral nutrition treatment may be continued as long as clinically indicated by the patient's condition.

Preparation of the medicinal product for infusion

Opening

Tear the outer wrapper at the top to open the system.

Pull the upper edge of the outer wrapper to release the Olimel N4E bag. Remove the outer protective packaging. Discard the sachet containing the oxygen absorber.

Check the integrity of the bag and the temporary partitions. Use only undamaged bags with intact temporary partitions (i.e., with unmixed contents of the 3 chambers), clear and colorless or slightly yellow solutions of amino acids and glucose, and a homogeneous milk-like lipid emulsion practically free from visible particles.

Place the bag on a clean, horizontal surface in front of you.

Mixing of solutions and emulsion

Ensure the product has reached room temperature before breaking the temporary partitions.

Manually fold the bag starting from the top (from the end used for hanging). The temporary partitions will begin to rupture from the side near the opening. Continue folding the bag until the partitions are opened along approximately half of their length.

Mix the contents by inverting the bag at least 3 times.

After reconstitution, the mixture should appear as a homogeneous, milk-like emulsion.

Addition of other substances

The bag capacity allows for the addition of substances such as vitamins, electrolytes, and trace elements.

Any medicinal products (including vitamins) may be added to the reconstituted mixture (after opening the temporary partitions and mixing the contents of the 3 chambers).

Vitamins may also be added to the glucose chamber prior to reconstitution (before opening the temporary partitions and mixing the contents of the 3 chambers).

When adding electrolytes to the product, the amount of electrolytes already present in the bag should be taken into account.

Addition must be performed by a qualified specialist under aseptic conditions.

The following electrolytes listed in Table 2 may be added to Olimel N4E.

Table 2

a Values corresponding to the addition of inorganic phosphate.

b Phosphate contained in the lipid emulsion has been taken into account.

Trace elements and vitamins: stability has been demonstrated when using commercially available vitamin and trace element preparations (containing up to 1 mg of iron).

If other substances are added to the preparation, the final osmolarity of the mixture must be checked before administration into a peripheral vein.

To perform additions:

• Aseptic technique must be observed.
• Prepare the injection port of the bag.
• Pierce the injection port and add additives using a syringe needle or a reconstitution device.
• Mix the contents of the bag and the additives.

Preparation of the infusion set

Aseptic technique must be observed.

Hang the bag.

Remove the plastic protective cap from the entry port.

Firmly insert the needle of the infusion set into the entry port.

Precautions for use

For single use only.

Administer the preparation only after breaking the seals between the 3 chambers and mixing the contents of all 3 chambers.

The final ready-to-use infusion emulsion should be inspected visually for signs of phase separation.

After opening, the contents of the bag must be used immediately. An opened bag must not be stored for subsequent infusions. Do not connect partially used bags.

Do not connect bags in series, in order to avoid the risk of air embolism due to residual air from the previous bag.

Any unused medicinal product or waste material, as well as all devices used during administration, must be disposed of in accordance with current regulations.

Children

The preparation may be administered to children aged 2 years and older, according to the instructions provided in the section "Dosage and administration".

Overdose

In case of incorrect administration (overdose and/or exceeding the recommended infusion rate), signs of hypervolemia and acidosis may occur.

Too rapid infusion or administration of an inappropriately large volume of the preparation may cause nausea, vomiting, chills, headache, hot flushes, hyperhidrosis, and electrolyte imbalances. In such cases, infusion must be stopped immediately.

If the glucose infusion rate exceeds the clearance capacity, hyperglycemia, glucosuria, and hyperosmolar syndrome may develop.

Reduced or limited ability to metabolize fats may lead to fat overload syndrome. The effects are usually reversible and resolve after discontinuation of fat infusion (see also section "Adverse reactions").

In severe cases, hemodialysis, hemofiltration, or hemodiafiltration may be indicated.

Adverse reactions

Potential adverse effects may occur as a result of improper use (e.g., overdose, excessively rapid infusion rate) (see sections "Special precautions" and "Overdose").

At the beginning of infusion, any of the listed pathological signs (sweating, elevated body temperature, tremor, headache, skin rash, dyspnea) should be considered a reason for immediate discontinuation of the infusion.

The adverse drug reactions listed in Table 3 were observed during administration of Olimel N9-840 in a randomized, double-blind, active-controlled study evaluating efficacy and safety. Twenty-eight patients with various medical conditions (e.g., postoperative fasting, severe malnutrition, inadequate or impossible enteral nutrition) participated in the study and received treatment; patients in the Olimel study group received up to 40 mL/kg/day of the product for 5 days.

Based on combined data from clinical trials and post-marketing experience, the following adverse reactions related to the use of Olimel have been identified.

Table 3

a The frequency of reactions is defined as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), rare (≥ 1/10,000 to < 1/1000), very rare (< 1/10,000), or frequency not known (cannot be estimated based on available data).

b Adverse drug reactions reported during post-marketing use of Olimel.

Adverse drug reactions typical of the class of drugs, described in other sources in connection with parenteral nutrition products, and for which the frequency is unknown:

• Blood and lymphatic system disorders: thrombocytopenia.
• Hepatobiliary and biliary tract disorders: cholestasis, hepatomegaly, jaundice.
• Immune system disorders: hypersensitivity.
• Injuries, poisonings, and procedural complications: parenteral nutrition-associated liver disease (see section "Special precautions for use").
• Investigations: increased blood alkaline phosphatase, increased transaminase levels, increased blood bilirubin, increased liver enzymes.
• Renal and urinary disorders: azotemia.
• Vascular disorders: precipitates in pulmonary vessels (pulmonary embolism and respiratory distress) (see section "Special precautions for use").

Fat overload syndrome (very rare)

Cases of fat overload syndrome have been reported with the use of similar medicinal products. This syndrome may result from improper use (e.g., overdose and/or exceeding the recommended infusion rate; see section "Overdose"); however, symptoms of this syndrome may also appear at the beginning of infusion administered according to instructions. Reduced or limited ability to metabolize fats contained in Olimel N4E may lead to prolonged plasma clearance, potentially resulting in fat overload syndrome. This syndrome is associated with a sudden deterioration in the patient's clinical condition and is characterized by symptoms such as fever, anemia, leukopenia, thrombocytopenia, coagulation disorders, hyperlipidemia, fatty infiltration of the liver (hepatomegaly), impaired liver function, and central nervous system manifestations (e.g., coma). The syndrome usually resolves after discontinuation of the fat emulsion infusion.

Reporting suspected adverse reactions

Reporting of suspected adverse reactions after medicinal product registration is important. It allows ongoing monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals, pharmacists, patients, and their legal representatives should report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life.

2 years.

The product should preferably be used immediately after opening the non-permanent partitions between the three chambers of the bag. However, after mixing the contents of the three chambers, the emulsion may be stored for up to 7 days at 2–8 °C, followed by storage for up to 48 hours at a temperature not exceeding 25 °C.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C. Do not freeze. Keep out of reach of children.

Incompatibilities.

Do not add other medicinal products or substances to any of the bag chambers or to the reconstituted emulsion without prior confirmation of their compatibility and stability of the resulting solution (including stability of the fat emulsion).

Incompatibility may be caused, for example, by excessive acidity (low pH) or inappropriate levels of divalent cations (Ca²⁺ and Mg²⁺), which may destabilize the fat emulsion.

As with any other parenteral nutrition mixture, the calcium-to-phosphate ratio must be considered. Excessive addition of calcium and phosphate, especially in the form of mineral salts, may lead to precipitation of calcium phosphate.

Olimel N4E contains calcium ions, which pose an additional risk of precipitated coagulation in citrate anticoagulated/conserved blood or blood components.

Ceftriaxone must not be mixed or administered simultaneously with calcium-containing intravenous solutions, including Olimel N4E, via the same infusion system (e.g., through a Y-connector) due to the risk of precipitation of calcium ceftriaxone salt (see sections "Interaction with other medicinal products and other forms of interaction" and "Special precautions for use").

Due to the risk of precipitate formation, Olimel N4E must not be administered through the same infusion system or mixed with ampicillin or fosphenytoin.

Compatibility with solutions administered simultaneously through the same infusion system, catheter, or cannula should be verified.

Do not administer the product before, simultaneously with, or immediately after blood transfusion through the same equipment due to the risk of pseudoagglutination.

Packaging.

1000 ml (18.75% glucose solution with calcium – 400 ml; 6.3% amino acid solution with electrolytes – 400 ml; 15% lipid emulsion – 200 ml) in a three-chamber plastic bag in an oxygen-absorbing protective overwrap; 6 bags per cardboard box.

1500 ml (18.75% glucose solution with calcium – 600 ml; 6.3% amino acid solution with electrolytes – 600 ml; 15% lipid emulsion – 300 ml) in a three-chamber plastic bag in an oxygen-absorbing protective overwrap; 4 bags per cardboard box.

2000 ml (18.75% glucose solution with calcium – 800 ml; 6.3% amino acid solution with electrolytes – 800 ml; 15% lipid emulsion – 400 ml) in a three-chamber plastic bag in an oxygen-absorbing protective overwrap; 4 bags per cardboard box.

Prescription status.

Prescription only.

Manufacturer.

Baxter S.A. / Baxter SA.

Manufacturer's address and location of manufacturing site.

Boulevard Rene Branquart 80, Lessines, 7860, Belgium / Boulevard Rene Branquart 80, Lessines, 7860, Belgium.