Olimel n7e

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT Olimel N7E (Olimel N7E)

Composition:

Active substances: alanine; arginine; aspartic acid; glutamic 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, hydrated; glucose monohydrate (equivalent to anhydrous glucose); calcium chloride dihydrate; refined olive oil; refined soybean oil.

One three-chamber bag contains:

Components	Volume
	1000 ml	1500 ml	2000 ml
35 % glucose solution with calcium	400 ml	600 ml	800 ml
11.1 % amino acid solution with electrolytes	400 ml	600 ml	800 ml
20 % lipid emulsion	200 ml	300 ml	400 ml

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

Components	Quantity
	per 1 bag 1000 ml	per 1 bag 1500 ml	per 1 bag 2000 ml
Active substances:
Alanine	6.41 g	9.61 g	12.82 g
Arginine	4.34 g	6.51 g	8.68 g
Aspartic acid	1.28 g	1.92 g	2.56 g
Glutamic acid	2.21 g	3.32 g	4.42 g
Glycine	3.07 g	4.60 g	6.14 g
Histidine	2.64 g	3.97 g	5.29 g
Isoleucine	2.21 g	3.32 g	4.42 g
Leucine	3.07 g	4.60 g	6.14 g
Lysine acetate (equivalent to lysine)	4.88 g 3.48 g	7.31 g 5.23 g	9.75 g 6.97 g
Methionine	2.21 g	3.32 g	4.42 g
Phenylalanine	3.07 g	4.60 g	6.14 g
Proline	2.64 g	3.97 g	5.29 g
Serine	1.75 g	2.62 g	3.50 g
Threonine	2.21 g	3.32 g	4.42 g
Tryptophan	0.74 g	1.10 g	1.47 g
Tyrosine	0.11 g	0.17 g	0.22 g
Valine	2.83 g	4.25 g	5.66 g
Sodium acetate trihydrate	1.50 g	2.24 g	2.99 g
Potassium chloride	2.24 g	3.35 g	4.47 g
Magnesium chloride hexahydrate	0.81 g	1.22 g	1.62 g
Sodium glycerophosphate, hydrated	3.67 g	5.51 g	7.34 g
Glucose monohydrate (equivalent to anhydrous glucose)	154.00 g 140.00 g	231.00 g 210.00 g	308.00 g 280.00 g
Calcium chloride dihydrate	0.52 g	0.77 g	1.03 g
Refined olive oil and refined soybean oil	40.00 g	60.00 g	80.00 g
Excipients: injectable egg phospholipids, glycerol, sodium oleate, glacial acetic acid, hydrochloric acid, sodium hydroxide, water for injections.

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:

Indicators	Volume
	1000 ml	1500 ml	2000 ml
Nitrogen	7.0 g	10.5 g	14.0 g
Amino acids	44.3 g	66.4 g	88.6 g
Glucose	140.0 g	210.0 g	280.0 g
Lipids	40 g	60 g	80 g
Energy value:
Total energy (approximately)	1140 kcal	1710 kcal	2270 kcal
Non-protein energy (approximately)	960 kcal	1440 kcal	1920 kcal
Glucose energy	560 kcal	840 kcal	1120 kcal
Lipid energy (approximately)a	400 kcal	600 kcal	800 kcal
Non-protein energy/nitrogen ratio (approximately)	137 kcal/g	137 kcal/g	137 kcal/g
Glucose/lipid energy ratio (approximately)	58/42	58/42	58/42
Lipid/total energy ratio (approximately)	35 %	35 %	35 %
Electrolytes:
Sodium	35.0 mmol	52.5 mmol	70.0 mmol
Potassium	30.0 mmol	45.0 mmol	60.0 mmol
Magnesium	4.0 mmol	6.0 mmol	8.0 mmol
Calcium	3.5 mmol	5.3 mmol	7.0 mmol
Phosphatesb	15.0 mmol	22.5 mmol	30.0 mmol
Acetates	45 mmol	67 mmol	89 mmol
Chlorides	45 mmol	68 mmol	90 mmol
pH	6.4	6.4	6.4
Osmolarity	1360 mOsmol/l	1360 mOsmol/l	1360 mOsmol/l

a Includes calories from egg phospholipids for injection

b Includes phosphates from the lipid emulsion (egg phospholipids)

Pharmaceutical form. Infusion emulsion.

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 calories (glucose and triglycerides) in Olimel N7E allow for maintaining an adequate nitrogen/calorie ratio.

The preparation also contains electrolytes.

The lipid (fat) emulsion component of Olimel N7E consists of refined olive oil and refined soybean oil in an 80/20 ratio, with the following approximate fatty acid distribution:

• 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) required 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 carbohydrate source.

Pharmacokinetics.

The components of Olimel N7E (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, soy, peanut, or corn/corn products (see section "Special precautions"), or to any of the active substances or excipients.

Inborn errors of amino acid metabolism.

Severe hyperlipidemia or severe disturbances in 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 forms of interaction.

Interaction studies have not been conducted.

Olymель N7E 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, blood hemoglobin levels) if blood samples are taken before clearance of lipids (typically cleared within 5–6 hours provided no repeated administration occurs).

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 Olymель N7E, through the same infusion system (e.g., via a Y-connector). However, ceftriaxone and calcium-containing solutions may be administered sequentially one after another, provided the infusion system is thoroughly flushed with a compatible fluid between infusions (see sections "Special precautions" and "Incompatibilities").

Olymель N7E contains vitamin K, naturally present in lipid emulsions. The amount of vitamin K in the recommended doses of Olymель N7E is considered not to affect coumarin derivatives.

Due to the potassium content in Olymель N7E, particular caution should be exercised 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 in clinical doses causes a transient release of lipoprotein lipase into the circulation. This may initially lead to enhanced plasma lipolysis followed by a temporary reduction 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 signs 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 and peanut proteins have been reported.

Olimel N7E 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 administered simultaneously 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 replaced or thoroughly flushed with physiological 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 precipitation risk. If ceftriaxone use is considered necessary in a patient also requiring continuous parenteral nutrition, TPN solutions and ceftriaxone may be administered simultaneously, but through different infusion systems connected at different sites. Alternatively, the TPN infusion may be interrupted during ceftriaxone administration, following recommendations for flushing the infusion system between administrations (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 resulted in death. Excessive addition of calcium and phosphate increases the risk of calcium phosphate precipitate formation (see section "Incompatibilities").

There have also been reports of possible 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, infusion should be stopped and medical evaluation initiated.

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

Catheter-related infection and sepsis are complications that may occur in patients receiving parenteral nutrition, especially with inadequate catheter care or due to immunosuppressive effects of disease or medications. Careful monitoring for signs of infection and laboratory results indicating 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 with 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 for any component of the drug is inaccurately assessed. Undesirable metabolic effects may result from insufficient or excessive intake of nutrients or from an inappropriate mixture composition relative to the individual patient's requirements.

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.

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

Depending on the extravasated drug (including any drug(s) mixed with Olimel N7E, if applicable) and the stage/extent of injury, 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 extravasation site should be observed at least every 4 hours during the first 24 hours, and then once daily.

Infusion into the same 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 neurologic disorders associated with hyperammonemia. Regular clinical and laboratory evaluations, 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, particularly those with hyperkalemia, due to the risk of developing or worsening metabolic acidosis and hyperazotemia if metabolic waste products are not adequately eliminated through extrarenal 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 or anemia. Complete blood count and coagulation parameters should be closely 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 monitoring is required;
• Diabetes mellitus. Glucose concentrations, glucosuria, ketonuria, and, if applicable, appropriate insulin dose adjustments should be monitored;
• Hyperlipidemia, due to the fat content of the infusion emulsion. Regular clinical and laboratory monitoring is 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 occur during parenteral nutrition in some patients. The etiology of these disorders is considered multifactorial and may vary among patients. Patients with abnormal laboratory parameters or other signs of hepatobiliary disorders should be evaluated by a physician specializing in such conditions to identify potential causative factors and implement necessary therapeutic and preventive measures.

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

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

In suspected fat metabolism disorders, serum triglyceride levels should be measured daily after a 5–6 hour fat-free period. In adults, serum should be clear within less than 6 hours after discontinuation of a fat-containing infusion. The next infusion should only be administered 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 fats contained in Olimel N7E may lead to fat overload syndrome, which may result from overdose; however, signs of this syndrome may also occur with administration according to instructions (see also section "Adverse reactions").

In case of hyperglycemia, the infusion rate of Olimel N7E should be adjusted and/or insulin administered.

Do NOT administer the product 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 requirements. Trace elements and vitamins should be added in adequate amounts to meet individual patient needs and prevent deficiency. See instructions for adding other substances to this product.

Olimel N7E 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, phosphorus, magnesium, or water-soluble vitamins. These changes may occur within 24–48 hours; therefore, parenteral nutrition should be initiated cautiously and gradually, with careful monitoring and appropriate correction of fluid, electrolyte, trace element, and vitamin levels.

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

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

Olimel N7E 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 doses, especially during prolonged intravenous nutrition.

Effect on laboratory tests

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

Special precautions for use in children

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

Olimel N7E is not suitable for use in children under 2 years of age because:

• Glucose intake is too low, resulting in a reduced glucose/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 2.6 mL/kg/hour for children aged 2 to 11 years and 1.7 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

Dosage selection for elderly patients should generally be cautious, taking into account the higher prevalence of decreased hepatic, renal, or cardiac function, and concomitant diseases or other medicinal therapies.

Use during pregnancy or breastfeeding.

Pregnancy

Clinical data on the use of Olimel N7E in pregnant women are lacking. Reproductive studies in animals have not been conducted. Given the route of administration and indications, Olimel N7E may be used during pregnancy if necessary. It should be prescribed to pregnant women only after careful evaluation.

Breastfeeding

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

Fertility

Adequate data are not available.

Ability to influence reaction rate when driving or operating machinery.

Not applicable.

Administration and Dosage

Dosage

Olimel N7E 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 a patient's nutritional requirements. There may be clinical situations where a patient requires nutrients in amounts different from those contained in the bag. Any adjustment in volume (dose) must take into account that such a change will affect the dosage of all other nutrients contained in Olimel N7E.

Adults

Dosage depends on the patient's energy expenditure, clinical condition, body weight, and ability to metabolize the components of Olimel N7E, as well as on any additional oral/enteral intake of calories or protein; 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 kcal expended.

The maximum daily dose of Olimel N7E is determined by total caloric intake – 40 kcal/kg in a volume of 35 mL/kg, corresponding to 1.5 g/kg amino acids, 4.9 g/kg glucose, 1.4 g/kg lipids, 1.2 mmol/kg sodium, and 1.1 mmol/kg potassium. For a patient weighing 70 kg, this equals 2450 mL of Olimel N7E per day, providing 108 g amino acids, 343 g glucose, and 98 g lipids (e.g., 2352 non-protein kcal and a total of 2793 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 N7E is 1.7 mL/kg/hour, corresponding to 0.08 g/kg/hour amino acids, 0.24 g/kg/hour glucose, and 0.07 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 N7E, as well as on any additional oral/enteral intake of calories or protein; therefore, the appropriate bag size should be selected accordingly.

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

Limiting factors for the use of Olimel N7E in both of the above age groups are the concentration of magnesium in the daily dose and the concentration of glucose in the hourly infusion dose. The resulting data are presented in Table 1.

Table 1

Component	From 2 to 11 years		From 12 to 18 years
	Recommended	Max. volume of Olimel N7E	Recommended	Max. volume of Olimel N7E
Maximum daily dose
Liquids (ml/kg/day)	60–120	25	50–80	25
Amino acids (g/kg/day)	1–2 (up to 2.5)	1.1	1–2	1.1
Glucose (g/kg/day)	1.4–8.6	3.5	0.7–5.8	3.5
Fats (g/kg/day)	0.5–3	1.0	0.5–2 (up to 3)	1.0
Total calories (kcal/kg/day)	30–75	28.5	20–55	28.5
Maximum hourly rate
Olimel N7E (ml/kg/hour)		2.6		1.7
Amino acids (g/kg/hour)	0.20	0.11	0.12	0.08
Glucose (g/kg/hour)	0.36	0.36	0.24	0.24
Fats (g/kg/hour)	0.13	0.10	0.13	0.07

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

Due to the high osmolarity of the product, Olimel N7E must be administered only through a 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.

Preparation of the product for infusion

Opening

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

Pull the top edge of the outer wrapper to remove the Olimel N7E bag. Remove the outer protective packaging. Discard the sachet containing the oxygen absorber.

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

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 non-permanent partitions.

Manually fold the bag starting from the top (from the end used for hanging). The non-permanent partitions will begin to rupture from the side near the port. 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 non-permanent partitions and mixing the contents of the 3 chambers).

Vitamins may also be added to the glucose chamber prior to reconstitution (before opening the non-permanent 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.

The addition must be performed by a qualified specialist under aseptic conditions.

The following electrolytes listed in Table 2 may be added to Olimel N7E.

Table 2

Per 1000 ml
Electrolytes	Included level	Maximum additional addition	Maximum total level
Sodium	35 mmol	115 mmol	150 mmol
Potassium	30 mmol	120 mmol	150 mmol
Magnesium	4.0 mmol	1.6 mmol	5.6 mmol
Calcium	3.5 mmol	1.5 (0.0a) mmol	5.0 (3.5a) mmol
Inorganic phosphate	0 mmol	3.0 mmol	3.0 mmol
Organic phosphate	15 mmolb	10 mmol	25 mmolb

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 trace element and vitamin preparations (containing up to 1 mg of iron).

If other substances are added to the product, the final osmolarity of the mixture must be checked prior to administration.

To perform additions:

• Aseptic technique must be followed.
• Prepare the injection site of the bag.
• Pierce the injection port and add the supplements using a syringe needle or a reconstitution device.
• Mix the contents of the bag with the added supplements.

Preparation of the infusion set

Aseptic technique must be followed.

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.

The product must be administered only after breaking the seals between the 3 chambers and mixing the contents of all 3 chambers.

The final infused emulsion must be inspected to ensure there are no 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 use partially administered bags.

Bags must not be connected in series (piggybacked), in order to avoid possible air embolism caused by residual gas from the previous bag.

Any unused product or waste material, as well as all devices used during administration, must be disposed of according to current regulations.

Children.

The product may be used in children aged 2 years and older, as specified in the section "Dosage and administration".

Overdose.

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

Infusing too rapidly or administering an inappropriately large volume of the product 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 impaired ability to metabolize lipids may lead to fat overload syndrome, the effects of which are usually reversible and resolve after discontinuation of lipid 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, too high 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 as a reason for immediate discontinuation of the infusion.

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

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

Table 3

System Organ Class	Preferred MedDRA Term	Frequencya
Immune system disorders	Hypersensitivity reactions, including hyperhidrosis, pyrexia, chills, headache, skin rashes (erythematous, papular, pustular, macular, generalized), pruritus, hot flushes, dyspnea	Frequency not knownb
Cardiac disorders	Tachycardia	Commona
Metabolism and nutrition disorders	Decreased appetite	Commona
	Hypertriglyceridemia	Commona
Gastrointestinal disorders	Abdominal pain	Commona
	Diarrhea	Commona
	Nausea	Commona
	Vomiting	Frequency not knownb
Vascular disorders	Arterial hypertension	Commona
General disorders and administration site conditions	Extravasation, which may lead to symptoms at infusion site: pain, irritation, swelling/edema, redness/localized increased temperature, skin necrosis, blistering/vesiculation, inflammation, induration, skin hardening	Frequency not knownb

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 not known (cannot be estimated from the 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 disorders: cholestasis, hepatomegaly, jaundice.
• Immune system disorders: hypersensitivity.
• Injuries, poisonings and procedural complications: parenteral nutrition-associated liver disease (see section "Special precautions").
• Investigations: increased blood alkaline phosphatase, increased transaminase levels, increased blood bilirubin level, increased liver enzymes.
• Renal and urinary disorders: azotemia.
• Vascular disorders: precipitates in pulmonary vessels (pulmonary embolism and respiratory distress) (see section "Special precautions").

Fat overload syndrome (very rare)

Cases of fat overload syndrome have been reported with the use of similar medicinal products. This syndrome may be caused by improper administration (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. Impaired or limited ability to metabolize fats contained in Olimel N7E is associated with prolonged plasma clearance, which may lead to the development of 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), worsening liver function, and central nervous system manifestations (e.g., coma). The syndrome usually resolves after discontinuation of the fat emulsion infusion.

Reporting of suspected adverse reactions

Reporting of suspected adverse reactions after marketing authorization of the medicinal product is important. It allows continued 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 via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life.

2 years.

It is recommended to use the product immediately after opening the non-permanent partitions between the 3 chambers of the bag. However, after mixing the contents of the three chambers, the emulsion can be stored for up to 7 days at a temperature of 2 to 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 first confirming their compatibility and the stability of the resulting solution (including the 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-phosphate ratio must be considered. Excessive addition of calcium and phosphate, especially in the form of mineral salts, may lead to the formation of calcium phosphate precipitates.

Olimel N7E contains calcium ions, which pose an additional risk of precipitated coagulation in citrate anticoagulated/preserved blood or blood components.

Ceftriaxone must not be mixed or administered simultaneously with calcium-containing intravenous solutions, including Olimel N7E, through the same infusion system (e.g., via a Y-connector) due to the risk of precipitation of calcium ceftriaxone salt (see sections "Interaction with other medicinal products and other types of interactions" and "Special precautions").

Due to the risk of precipitate formation, Olimel N7E must not be administered through the same infusion system or mixed with ampicillin or fosphenytoin.

Compatibility of the product 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 (35% glucose solution with calcium – 400 ml; 11.1% amino acid solution with electrolytes – 400 ml; 20% lipid emulsion – 200 ml) in a triple-chamber plastic bag in a protective overwrap containing an oxygen absorber; 6 bags per cardboard box.

1500 ml (35% glucose solution with calcium – 600 ml; 11.1% amino acid solution with electrolytes – 600 ml; 20% lipid emulsion – 300 ml) in a triple-chamber plastic bag in a protective overwrap containing an oxygen absorber; 4 bags per cardboard box.

2000 ml (35% glucose solution with calcium – 800 ml; 11.1% amino acid solution with electrolytes – 800 ml; 20% lipid emulsion – 400 ml) in a triple-chamber plastic bag in a protective overwrap containing an oxygen absorber; 4 bags per cardboard box.

Prescription status.

By prescription only.

Manufacturer.

Baxter S.A. / Baxter SA.

Manufacturer's address and place of business.

Boulevard Rene Branquart 80, Lessines, 7860, Belgium.