Olimel

Package leaflet: Information for the user

OLIMEL

PERIPHERAL N4E, Infusion Emulsion
Please read this leaflet carefully before this medicine is administered to you because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or nurse. If you experience any side effects, including those not listed in this leaflet, inform your doctor or nurse. See section 4.

Contents of this leaflet:

1. What OLIMEL PERIPHERAL N4E infusion emulsion is and what it is used for
2. What you need to know before OLIMEL PERIPHERAL N4E infusion emulsion is administered to you
3. How to use OLIMEL PERIPHERAL N4E infusion emulsion
4. Possible side effects
5. How to store OLIMEL PERIPHERAL N4E infusion emulsion
6. Contents of the pack and other information

1. What OLIMEL PERIFERICO N4E infusion emulsion is and what it is used for

OLIMEL PERIFERICO N4E is an infusion emulsion. It is presented as a three-compartment bag.
One compartment contains a glucose solution with calcium, the second a lipid emulsion, and the third an amino acid solution with other electrolytes.
OLIMEL PERIFERICO N4E is used to provide nutrition to adults and children over two years of age through a tube inserted into a vein, when normal oral feeding is not suitable.
OLIMEL PERIFERICO N4E must be used exclusively under medical supervision.

2. What you need to know before OLIMEL PERIFERICO N4E emulsion for infusion is administered to you

OLIMEL PERIFERICO N4E, emulsion for infusion must not be used

• In premature neonates, infants, and children under 2 years of age
• If you are hypersensitive (allergic) to egg proteins, soybean seeds, peanuts, or corn/maize and corn-derived products (see also section "Warnings and precautions" below), or to any other excipient of this medicine (listed in section 6)
• If the administration of certain amino acids causes problems for your body
• If you have particularly high levels of fats in your blood
• If you have hyperglycemia (excessively high blood sugar)
• If you have abnormally high concentrations of any of the electrolytes (sodium, potassium, magnesium, calcium, and/or phosphorus) in your blood

In all cases, your doctor will decide whether you should receive this medicine based on factors such as age, weight, medical condition, and laboratory test results.

Warnings and precautions
Talk to your doctor or nurse before OLIMEL PERIFERICO N4E is administered to you.
If total parenteral nutrition solutions are administered too rapidly, this may cause injury or death.
Infusion must be stopped immediately if unusual signs or symptoms of an allergic reaction occur (such as sweating, fever, chills, headache, skin rash, or difficulty breathing). This medicine contains soybean oil and egg phospholipids. Soybeans and egg proteins may cause hypersensitivity reactions. Cross-allergic reactions between soy and peanut proteins have been observed.
OLIMEL Periferico N4E contains glucose derived from corn/maize, which may cause hypersensitivity reactions if you are allergic to corn/maize or corn-derived products (see section "OLIMEL PERIFERICO N4E, emulsion for infusion must not be used" above).
Difficulty in breathing may also be a sign of small particles forming and blocking blood vessels in the lungs (pulmonary vascular precipitates). If you experience breathing difficulties, inform your doctor or nurse, who will determine the necessary actions.
The antibiotic ceftriaxone must not be mixed or administered simultaneously with any calcium-containing solution (including OLIMEL PERIFERICO N4E) administered via intravenous infusion.
These medicines must not be administered together even through different infusion lines or different infusion sites.
However, you may receive OLIMEL PERIFERICO N4E and ceftriaxone sequentially, one after the other, provided different infusion sites are used or the infusion lines are replaced or thoroughly flushed with physiological saline between infusions to prevent the formation of precipitates (calcium-ceftriaxone salt particles).
Some medications and diseases may increase the risk of developing infection or sepsis (bacteria in the blood). There is a particular risk of infection or sepsis when a tube (intravenous catheter) is inserted into a vein. Your doctor will closely monitor you for signs of infection. Patients requiring parenteral nutrition (nutrition delivered through a tube placed in a vein) may have an increased risk of developing infections due to their underlying medical conditions. The use of aseptic techniques (germ-free) during catheter placement and maintenance, and during the preparation of the nutritional formula (total parenteral nutrition), can reduce this risk.
If you are severely malnourished and require intravenous nutrition, your doctor should start treatment slowly. Your doctor must also monitor you closely to prevent sudden changes in your fluid, vitamin, electrolyte, and mineral levels. Water and electrolyte imbalances and metabolic disturbances should be corrected before starting the infusion. Your doctor will monitor your condition during treatment and may adjust the dose or add additional nutrients such as vitamins, electrolytes, and trace elements if deemed appropriate.
Liver disorders, including impaired bile excretion (cholestasis), fat accumulation (hepatic steatosis), fibrosis—which may lead to liver failure—as well as cholecystitis and cholelithiasis, have been reported in patients receiving intravenous nutritional therapy. These disorders are believed to result from multiple factors and may vary between patients. If you experience symptoms such as nausea, vomiting, abdominal pain, or yellowing of the skin or eyes (jaundice), consult your doctor to identify possible causative and contributing factors and to determine appropriate therapeutic and preventive measures.
Your doctor must be informed if you have:

• Severe kidney problems. You must inform your doctor if you are on dialysis (artificial kidney) or undergoing another blood purification therapy;
• Severe liver problems;
• Coagulation disorders;
• Inadequate function of the adrenal glands (adrenal insufficiency), which are triangular-shaped glands located above the kidneys;
• Heart failure;
• Lung disease;
• Excess fluid in the body (overhydration);
• Insufficient fluid in the body (dehydration);
• Untreated high blood sugar levels (diabetes mellitus);
• Heart attack or stroke secondary to sudden heart failure;
• Severe metabolic acidosis (when blood is too acidic);
• Systemic infection (septicemia);
• Coma.

To assess the overall effectiveness and safety of administration, your doctor will perform clinical and laboratory tests while you are receiving this medicine. If you are to receive this medicine for several weeks, your blood will be monitored regularly.
Reduced ability of the body to eliminate the fats contained in this medicine may lead to a "fat overload syndrome" (see section 4 - Possible side effects).
If during infusion you experience pain, burning, swelling, or leakage at the infusion site, inform your doctor or nurse immediately. Administration will be stopped immediately and restarted in another vein.
If your blood sugar level becomes too high, your doctor will adjust the infusion rate of OLIMEL PERIFERICO N4E or administer a medicine to control blood sugar levels (insulin).
OLIMEL PERIFERICO N4E may be administered through a tube (catheter) into a vein in the arm or into a large central vein in the chest (central venous catheter).

Children and adolescents
If your child is under 18 years of age, special attention will be paid to ensuring the correct dosage. Extra precautions will also be taken due to children's increased susceptibility to infection. Vitamin and trace element supplementation is always required. Pediatric formulations must be used.

Other medicines and OLIMEL PERIFERICO N4E
Inform your doctor if you are currently taking or using, have recently taken or used, or might take or use any other medicines.
Concomitant administration of other medicines is generally not a contraindication. However, if you are taking any medicines, with or without prescription, inform your doctor in advance to verify compatibility.
Inform your doctor if you are taking or receiving any of the following:

• Insulin
• Heparin

OLIMEL PERIFERICO N4E must not be administered simultaneously with blood through the same infusion set.
OLIMEL PERIFERICO N4E contains calcium. It must not be administered together with the antibiotic ceftriaxone or through the same tubing, as particles may form. If the same device is used to administer these medicines sequentially, the device must be thoroughly flushed.
Due to the risk of precipitation, OLIMEL Periferico N4E must not be administered through the same infusion line or mixed with the antibiotic ampicillin or the antiepileptic fosphenytoin.
The olive and soybean oils in OLIMEL PERIFERICO N4E contain vitamin K. This vitamin generally does not affect blood-thinning medicines (anticoagulants) such as coumarin. However, inform your doctor if you are taking anticoagulant medicines.
The lipids in this emulsion may interfere with the results of certain laboratory tests if blood samples are taken before lipids have been cleared from your blood (which usually occurs after a 5- to 6-hour period without lipid infusion).
OLIMEL PERIFERICO N4E contains potassium. Exercise particular caution in patients taking diuretics, ACE inhibitors, angiotensin II receptor antagonists (medicines for hypertension), or immunosuppressants. These types of medicines may increase potassium levels in your blood.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor before this medicine is administered to you.
There is insufficient experience with the use of OLIMEL PERIFERICO N4E in pregnant or breastfeeding women. OLIMEL PERIFERICO N4E may be considered during pregnancy and breastfeeding if necessary. However, OLIMEL PERIFERICO N4E should only be administered to pregnant or breastfeeding women after careful evaluation.

Driving and using machines
Not applicable.

3. How to use OLIMEL PERIFERICO N4E, infusion emulsion

Dosage
OLIMEL PERIFERICO N4E must be administered only in adults and children over two years of age.
It is an infusion emulsion, to be administered through a tube (catheter) into a vein in the arm or a large vein in the chest.
OLIMEL PERIFERICO N4E must be at room temperature before use.
OLIMEL PERIFERICO N4E is for single use only.
The infusion of one bag usually lasts between 12 and 24 hours.

Dosage – Adults
Your doctor will determine an appropriate flow rate according to your individual needs and clinical condition.
The prescription may continue for as long as necessary, depending on your clinical status.

Dosage – Children over two years of age and adolescents
The doctor will decide the dose and duration of treatment, based on age, body weight, height, medical condition, and the body’s ability to metabolize and utilize the components of OLIMEL PERIFERICO N4E.

If you have been given more OLIMEL PERIFERICO N4E, infusion emulsion, than you should
If the administered dose is too high or the infusion rate is too fast, the amino acid content may cause the blood to become too acidic, and symptoms of hypervolemia (increased volume of circulating blood) may occur. Blood and urine glucose levels may rise, a hyperosmolar state (excessive blood viscosity) may develop, and the lipid content may increase triglyceride levels in your blood. Receiving the infusion too rapidly or an excessive volume of OLIMEL PERIFERICO N4E may cause nausea, vomiting, chills, headache, hot flushes, excessive sweating (hyperhidrosis), and electrolyte imbalances. In such cases, the infusion must be stopped immediately.
In severe cases, your doctor may temporarily perform renal dialysis to help your kidneys eliminate the excess product.
To prevent such events, your doctor will regularly monitor your condition and perform blood tests.
If you have any doubts about the use of this medicine, consult your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
If you notice any changes in how you feel during or after treatment, inform your doctor or nurse immediately.
The tests your doctor will perform while you are receiving this medicine help reduce the risks of side effects.
The infusion will be stopped immediately if any signs or symptoms of an allergic reaction occur, such as sweating, fever, chills, headache, skin rash, or breathing difficulties.

The following side effects have been reported with OLIMEL PERIFERICO N4E:

Frequency – Common: may affect up to 1 in 10 people

• Fast heart rate (tachycardia)
• Decreased appetite
• Increased blood fat levels (hypertriglyceridemia)
• Abdominal pain
• Diarrhea
• Nausea
• Increased blood pressure (hypertension)

Frequency – Not known: frequency cannot be estimated from the available data

• Hypersensitivity reactions including sweating, fever, chills, headache, skin rash (erythematous, papular, pustular, macular, generalized skin rash), itching, hot flushes, breathing difficulties
• Leakage of the infusion into surrounding tissue (extravasation), which may cause at the infusion site: pain, irritation, swelling/edema, redness (erythema)/warmth, tissue cell death (skin necrosis), or blisters/vesicles, inflammation, thickening or tightening of the skin
• Vomiting

With similar parenteral nutrition products, the following side effects have been reported:

Frequency – Very rare: may affect up to 1 in 10,000 people

• Reduced ability to clear lipids (lipid overload syndrome), associated with a sudden and sharp deterioration in the patient's clinical condition. The following symptoms of lipid overload syndrome are usually reversible after stopping the lipid emulsion infusion:
  1. Fever
  2. Reduction in red blood cells, which may make the skin pale and cause weakness or shortness of breath (anemia)
  3. Low white blood cell count, which may increase the risk of infection (leukopenia)
  4. Low platelet count, which may increase the risk of bruising and/or bleeding (thrombocytopenia)
  5. Blood clotting disorders that impair the blood's ability to clot
  6. High levels of fat in the blood (hyperlipidemia)
  7. Fatty infiltration of the liver (hepatomegaly)
  8. Worsening of liver function
  9. Central nervous system manifestations (e.g., coma)

Frequency – Not known: frequency cannot be estimated from the available data

• Allergic reactions
• Abnormal blood test results for liver function
• Problems with bile elimination (cholestasis)
• Enlargement of the liver (hepatomegaly)
• Liver disease associated with parenteral nutrition (see "Warnings and precautions" in section 2)
• Jaundice (icterus)
• Decreased platelet count (thrombocytopenia)
• Increased nitrogen levels in the blood (azotemia)
• Elevated liver enzymes
• Formation of small particles that may cause blockage of blood vessels in the lungs (pulmonary vascular precipitates), leading to pulmonary vascular embolism and breathing difficulties (respiratory distress)

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. You may also report side effects directly via the national reporting system at: https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store OLIMEL PERIFERICO N4E infusion emulsion

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the container and outer packaging (MM/YYYY). The expiry date refers to the last day of the month.
Do not freeze.
Store in the outer packaging.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What OLIMEL PERIFERICO N4E, emulsion for infusion contains
The active substances in each bag of the reconstituted emulsion are a solution of L-amino acids at
6.3% (equivalent to 6.3 g/100 mL) (alanine, arginine, glycine, histidine, isoleucine, leucine, lysine
(as lysine acetate), methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine,
aspartic acid, glutamic acid) with electrolytes (sodium, potassium, magnesium, phosphate, acetate,
chloride), a 15% lipid emulsion (equivalent to 15 g/100 mL) (purified olive oil and purified soybean
oil), and a 18.75% glucose solution (equivalent to 18.75 g/100 mL) (as monohydrate glucose) with calcium.
Other excipients are:
Compartment Compartment Compartment
Lipid emulsion Amino acid solution Glucose solution
Purified egg phospholipids, Glacial acetic acid (for Hydrochloric acid (for
glycerol, sodium oleate, sodium pH adjustment), pH adjustment),
hydroxide (for pH adjustment), water for injectable water for injectable
water for injectable preparations preparations
preparations
Appearance of OLIMEL PERIFERICO N4E, emulsion for infusion, and packaging contents
OLIMEL PERIFERICO N4E is an infusion emulsion supplied in a three-compartment bag. One compartment contains a lipid emulsion, another compartment contains an amino acid solution with electrolytes, and the third compartment contains a glucose solution with calcium. These compartments are separated by non-permanent membranes. Prior to administration, the contents of the compartments must be mixed by rolling the bag from top to bottom until the membranes open.
Appearance before reconstitution:
The amino acid and glucose solutions are clear, colourless or slightly yellow.
The lipid emulsion is homogeneous with a milky appearance.
Appearance after reconstitution: Homogeneous emulsion with a milky appearance.
The three-compartment bag is made of multilayer plastic. The material of the inner layer (in contact) of the bag is designed to be compatible with the authorized constituents and additives.
To prevent contact with atmospheric oxygen, the bag is packaged in an outer oxygen-barrier pouch containing an oxygen-absorbing sachet.
Packaging:
1,000 mL bag: 1 box containing 6 bags; 1 box containing 5 bags
1,500 mL bag: 1 box containing 4 bags; 1 box containing 5 bags
2,000 mL bag: 1 box containing 4 bags; 1 box containing 5 bags
2,500 mL bag: 1 box containing 2 bags
1 bag of 1,000 mL, 1,500 mL, 2,000 mL and 2,500 mL
Not all pack sizes may be marketed.
Marketing Authorization Holder
Baxter S.p.A.
Via Del Serafico 89
00142 Rome
Italy
Manufacturer:
Baxter S.A.,
Boulevard Rene Branquart, 80,
7860 Lessines –
Belgium
This medicinal product is authorized in the member states of the European Economic Community under the following names:
France, Portugal, Bulgaria, Romania, Czech Republic, Belgium, Spain, Slovak Republic, Luxembourg, Slovenia: PERIOLIMEL N4E
Estonia, Poland, Lithuania, Latvia, Greece, Cyprus: OLIMEL PERI N4E
Netherlands: Olimel Perifeer N4E
Austria: PeriOLIMEL 2,5 % mit Elektrolyten
Germany: Olimel Peri 2,5% E
Denmark, Iceland, Sweden, Norway, Finland: Olimel Perifer N4E
United Kingdom, Ireland, Malta: Triomel Peripheral 4g/L nitrogen 700 kcal/L with electrolytes
Hungary: PeriOlimel 4 g/L nitrogén elektrolitokkal emulziós infúzió
This leaflet was last approved on:

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The following information is intended exclusively for physicians or healthcare professionals:
Pharmacotherapeutic category: Parenteral nutrition solutions/combinations
ATC Code: B05 BA10
A. QUALITATIVE AND QUANTITATIVE COMPOSITION
OLIMEL PERIFERICO N4E is supplied as a three-compartment bag.
Each bag contains a glucose solution with calcium, a lipid emulsion, and an amino acid solution with additional electrolytes:
Content per bag
1,000 mL 1,500 mL 2,000 mL 2,500 mL
Glucose solution 18.75%
400 mL 600 mL 800 mL 1,000 mL
(equivalent to 18.75 g/100 mL)
Amino acid solution 6.3%
400 mL 600 mL 800 mL 1,000 mL
(equivalent to 6.3 g/100 mL)
Lipid emulsion 15%
200 mL 300 mL 400 mL 500 mL
(equivalent to 15 g/100 mL)
Composition of the reconstituted emulsion after mixing the contents of the three compartments:
Active substances 1,000 mL 1,500 mL 2,000 mL 2,500 mL
Purified olive oil + purified
soybean oil 30.00 g 45.00 g 60.00 g 75.00 g
Alanine 3.66 g 5.50 g 7.33 g 9.16 g
Arginine 2.48 g 3.72 g 4.96 g 6.20 g
Aspartic acid 0.73 g 1.10 g 1.46 g 1.83 g
Glutamic acid 1.26 g 1.90 g 2.53 g 3.16 g
Glycine 1.76 g 2.63 g 3.51 g 4.39 g
Histidine 1.51 g 2.26 g 3.02 g 3.77 g
Isoleucine 1.26 g 1.90 g 2.53 g 3.16 g
Leucine 1.76 g 2.63 g 3.51 g 4.39 g
Lysine 1.99 g 2.99 g 3.98 g 4.98 g
(equivalent to lysine acetate) (2.81 g) (4.21 g) (5.62 g) (7.02 g)
Methionine 1.26 g 1.90 g 2.53 g 3.16 g
Phenylalanine 1.76 g 2.63 g 3.51 g 4.39 g
Proline 1.51 g 2.26 g 3.02 g 3.77 g
Serine 1.00 g 1.50 g 2.00 g 2.50 g
Threonine 1.26 g 1.90 g 2.53 g 3.16 g
Tryptophan 0.42 g 0.64 g 0.85 g 1.06 g
Tyrosine 0.06 g 0.10 g 0.13 g 0.16 g
Valine 1.62 g 2.43 g 3.24 g 4.05 g
Sodium acetate, trihydrate 1.16 g 1.73 g 2.31 g 2.89 g
Sodium glycerophosphate, hydrate 1.91 g 2.87 g 3.82 g 4.78 g
Potassium chloride 1.19 g 1.79 g 2.38 g 2.98 g
Magnesium chloride, hexahydrate 0.45 g 0.67 g 0.90 g 1.12 g
Calcium chloride, dihydrate 0.30 g 0.44 g 0.59 g 0.74 g
Glucose 75.00 g 112.50 g 150.00 g 187.50 g
(equivalent to monohydrate glucose) (82.50 g) (123.75 g) (165.00 g) (206.50 g)
Excipients are:
Compartment Compartment Compartment
Lipid emulsion Amino acid solution Glucose solution
Purified egg phospholipids, Glacial acetic acid (for Hydrochloric acid (for
glycerol, sodium oleate, sodium pH adjustment), pH adjustment),
hydroxide (for pH adjustment), water for injectable water for injectable
water for injectable preparations preparations
preparations
Nutritional content of the reconstituted emulsion for each bag size:

B. DOSAGE AND ADMINISTRATION
Dosage
OLIMEL PERIFERICO N4E is not recommended for children under 2 years of age due to its composition and inadequate volume (see sections 4.4, 5.1 and 5.2 of the SmPC).
Do not exceed the maximum daily dose indicated below. Because of the fixed composition of the multi-chamber bag, it may not be possible to simultaneously meet all of the patient's nutritional requirements. There may be clinical situations in which patients require variable amounts of nutrients compared to the fixed composition of the bag. In such cases, any adjustment of volume (dose) must take into account the resulting effect on the dosage of all other nutritional components in OLIMEL PERIFERICO N4E.

In adults:
The dosage depends on energy expenditure, clinical condition, body weight, and the patient's ability to metabolize the components of OLIMEL PERIFERICO N4E, as well as on additional energy or protein supplied orally/enterally; therefore, the bag size should be selected accordingly.
Average daily requirements are:

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

For OLIMEL PERIFERICO N4E, the maximum daily dose is defined by the fluid intake of 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 70 kg patient, this would be equivalent to 2800 mL of OLIMEL PERIFERICO N4E per day, providing 71 g of amino acids, 210 g glucose and 84 g lipids, resulting in 1680 non-protein kcal and 1960 total kcal.
Normally, the infusion rate should be gradually increased during the first hour, then adjusted according to the required dose, daily volumes to be administered, and duration of infusion.
For OLIMEL PERIFERICO N4E, the maximum infusion rate is 3.2 mL/kg/hour, corresponding to 0.08 g/kg/hour for amino acids, 0.24 g/kg/hour for glucose and 0.10 g/kg/hour for lipids.

In children over 2 years of age and adolescents:
No studies have been conducted in the pediatric population.
The dosage depends on energy expenditure, clinical condition, body weight, and the patient's ability to metabolize the components of OLIMEL PERIFERICO N4E, as well as on additional energy or protein supplied orally/enterally; therefore, the bag size should be selected accordingly.
Furthermore, daily requirements for fluids, nitrogen, and energy continuously decrease with age. Two age groups have been considered: ages 2 to 11 years, and ages 12 to 18 years.
In both age groups, magnesium concentration is the limiting factor for the daily dose. In the age group from 2 to 11 years, lipid concentration is the limiting factor for the hourly rate. In the age group from 12 to 18 years, glucose concentration is the limiting factor for the hourly rate. The resulting intakes are shown below.

a: Recommended values according to the 2018 ESPGHAN/ESPEN/ESPR Guidelines
Normally, the flow rate should be gradually increased during the first hour and
then adjusted considering the dose to be administered, the daily volume intake, and the duration of infusion.
In general, in young children it is recommended to start the infusion with a low daily dose,
gradually increasing it up to the maximum dosage (see above).
Method and duration of administration
For single use only.
It is recommended to use the bag content immediately after opening and not to store it for subsequent infusions.
After reconstitution, the mixture is homogeneous and has a milky appearance.
For instructions on the preparation and handling of the infusion emulsion, see section 6.6.
Due to its low osmolarity, OLIMEL PERIPHERAL N4E can be administered via peripheral or central vein.
The recommended infusion duration for a parenteral nutrition bag ranges between 12 and
24 hours.
Parenteral nutrition treatment may continue for as long as clinically required by the patient's condition.
C. INCOMPATIBILITIES
Do not add any other medicinal product or substances to any of the bag components or to the reconstituted emulsion without first verifying compatibility and stability of the resulting preparation (particularly lipid emulsion stability).
Incompatibilities may arise, for example, from excessive acidity (low pH) or unsuitable content of divalent cations (Ca and Mg), which may destabilize the lipid emulsion.
As with any other parenteral nutrition mixture, the calcium/phosphate ratio must be taken into account. Excessive addition of calcium and phosphate, particularly in the form of mineral salts, may lead to precipitation of calcium phosphate.
OLIMEL Peripheral N4E contains calcium ions which pose an additional risk of coagulation in blood or in anticoagulated or citrate-preserved blood components.
Ceftriaxone must not be mixed or administered concomitantly with intravenous solutions containing calcium, including OLIMEL Peripheral N4E, through the same infusion line (e.g., via a Y-connector) due to the risk of precipitation of ceftriaxone-calcium salt (see sections 4.4 and 4.5 of the SmPC). Ceftriaxone and calcium-containing solutions may be administered sequentially if different infusion sites are used or if the infusion lines are replaced or thoroughly flushed with physiological saline between infusions to prevent precipitate formation.
Due to the risk of precipitation, OLIMEL Peripheral N4E must not be administered through the same infusion line or mixed with the antibiotic ampicillin or the antiepileptic fosphenytoin.
Check compatibility with solutions administered simultaneously through the same administration set, catheter, or cannula.
Do not administer before, simultaneously with, or after blood transfusion through the same line due to the risk of pseudoagglutination.
D. SPECIAL PRECAUTIONS FOR DISPOSAL AND HANDLING
An overview of the various preparation stages for administration of OLIMEL Peripheral N4E is shown in Figure 1.
Opening
Remove the outer protective wrapper.
Discard the oxygen absorber bag.
Check the integrity of the bag and the non-permanent separation membranes. Use only if the bag is undamaged, the non-permanent separation membranes are intact (i.e., no mixing of the contents of the three compartments), the amino acid solution and glucose solution are clear, colorless or slightly yellow, practically free from visible particles, and the lipid emulsion is a homogeneous liquid with a milky appearance.
Mixing of solutions and emulsion
Ensure the product is at room temperature when breaking the non-permanent separation membranes.
Manually roll the bag upon itself, starting from the top (end with loop). The non-permanent separation membranes will disappear from the side adjacent to the openings.
Continue rolling the bag until the separation membranes are opened approximately halfway along their length.
Mix the bag by inverting it at least three times.
After reconstitution, the mixture is a homogeneous emulsion with a milky appearance.
Additions:
The bag has sufficient capacity to allow additions such as vitamins, electrolytes, and trace elements.
Any addition (including vitamins) should be made into the reconstituted mixture (after opening the non-permanent separation membranes and after mixing the contents of the three compartments).
Vitamins may also be added to the glucose compartment before reconstitution (before opening the non-permanent separation membranes and before mixing the three compartments).
When making additions to formulations containing electrolytes, consider the amount of electrolytes already present in the bag.
Additions must be performed by trained personnel under aseptic conditions.
OLIMEL PERIPHERAL N4E can be supplemented with electrolytes based on the following table:

Corresponding value for the addition of inorganic phosphate
Including the phosphate provided by the lipid emulsion
Trace elements and vitamins:
Stability has been demonstrated with commercially available preparations of vitamins and trace elements
(containing up to 1 mg of iron).
Compatibility of other additives is available upon request.
When adding substances, measure the final osmolarity of the mixture before administration via peripheral vein.
To perform an addition:

• The procedure must be carried out under aseptic conditions.
• Prepare the injection site of the bag.
• Pierce the injection site and inject the additives using an injection needle or a reconstitution device.
• Mix the contents of the bag and the added substances.

Preparation of the infusion
The procedure must be carried out under aseptic conditions.
Suspend the bag.
Remove the plastic cover from the administration port.
Firmly insert the spike of the infusion set into the administration port.

1 2 3

4 5 6
Administration
For single use only.
Administer the product only after breaking the non-permanent separation membranes between
the 3 compartments and mixing the contents of all 3 compartments.
Ensure that the final infusion emulsion shows no evidence of phase separation.
After opening the bag, the contents must be used immediately. Never store an opened bag for subsequent infusion.
Do not reconnect partially used bags.
Do not connect bags in series to avoid the risk of gas embolism due to gas contained in the primary bag.
Dispose of any unused product, generated waste, and all necessary devices.
Extravasation
The catheter site must be regularly checked for possible signs of extravasation.
In case of extravasation, administration must be stopped immediately, while maintaining the catheter or cannula in place for immediate patient treatment. If possible, perform aspiration through the inserted catheter or cannula to reduce the amount of fluid in the tissues before removing the catheter or cannula. If extravasation involves a limb, it should be elevated.
Depending on the extravasated product (including one or more products mixed with OLIMEL Periferico N4E, if applicable) and the extent or severity of a potential injury, appropriate specific measures should be taken. Treatment options may include non-pharmacological, pharmacological, and/or surgical interventions. In case of massive extravasation, consult a plastic surgeon within the first 72 hours.
The site of extravasation should be monitored at least every 4 hours during the first 24 hours, then once daily.
Infusion should not be restarted in the same peripheral or central vein.

• Package leaflet: Information for the user

OLIMEL

N7E, infusion emulsion
Please read this leaflet carefully before this medicine is administered to you, as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or nurse.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor or nurse. See section 4.

Contents of this leaflet:

1. What OLIMEL N7E infusion emulsion is and what it is used for
2. What you need to know before being administered OLIMEL N7E infusion emulsion
3. How to use OLIMEL N7E infusion emulsion
4. Possible side effects
5. How to store OLIMEL N7E infusion emulsion
6. Contents of the pack and other information

1. What OLIMEL N7E, infusion emulsion is and what it is used for

OLIMEL is an infusion emulsion. It is provided as a three-compartment bag.
One compartment contains a glucose solution with calcium, the second a lipid emulsion, and
the third an amino acid solution with other electrolytes.
OLIMEL is used to provide nutrition to adults and children over the age of two via a tube inserted into a vein, when normal oral feeding is not appropriate.
OLIMEL must be used only under medical supervision.

2. What you need to know before you are given OLIMEL N7E, infusion emulsion

OLIMEL N7E, infusion emulsion must not be used:

• In premature neonates, infants and children under 2 years of age
• If you are hypersensitive (allergic) to egg proteins, soybean seeds, peanuts or corn/maize-derived products (see also section "Warnings and precautions" below), or to any other excipient of this medicine (listed in section 6)
• If the use of certain amino acids causes problems for your body
• If you have particularly high levels of fats in your blood
• If you suffer from hyperglycaemia (too much sugar in the blood)
• If you have abnormally high concentrations of any of the electrolytes (sodium, potassium, magnesium, calcium and/or phosphorus) in your blood

In all cases, your doctor will decide whether you should receive this medicine based on factors such as age, weight and medical condition, together with the results of tests performed.

Warnings and precautions
Speak to your doctor or nurse before you are given OLIMEL N7E.
If total parenteral nutrition solutions are administered too rapidly, this may cause injury or death.
Infusion must be stopped immediately if you develop unusual signs or symptoms of an allergic reaction (such as sweating, fever, chills, headache, skin rashes or difficulty breathing). This medicine contains soybean oil and egg phospholipids. Soybeans and egg proteins may cause hypersensitivity reactions. Cross-allergic reactions between soy and peanut proteins have been observed.
OLIMEL N7E contains glucose derived from maize which may cause hypersensitivity reactions if you are allergic to maize or maize-derived products (see section "OLIMEL N7E, infusion emulsion must not be used" above).
Difficulty in breathing may also be a sign that small particles have formed, blocking blood vessels in the lungs (pulmonary vascular precipitates). If you experience difficulty breathing, inform your doctor or nurse, who will decide what actions to take.
The antibiotic called ceftriaxone must not be mixed or administered simultaneously with any calcium-containing solution (including OLIMEL N7E) being administered to you via intravenous infusion.
These medicines must not be administered even through different infusion lines or different infusion sites.
However, you may receive OLIMEL N7E and ceftriaxone sequentially, one after the other, provided different infusion sites are used or the infusion lines are replaced or thoroughly flushed with physiological saline between infusions to prevent formation of precipitates (calcium-ceftriaxone salt particles).
Some medicines and diseases may increase the risk of developing infection or sepsis (bacteria in the blood). There is a particular risk of infection or sepsis when a tube (central venous catheter) is inserted into a vein. Your doctor will closely monitor you for any signs of infection. Patients requiring parenteral nutrition (nutrition delivered through a tube placed in a vein) may have an increased risk of developing infections due to their underlying medical conditions. The use of aseptic (germ-free) techniques during catheter placement and maintenance, and during preparation of the nutritional formula (total parenteral nutrition), can reduce this risk.
If you are severely malnourished to the point of requiring intravenous nutrition, your doctor should start treatment slowly. Your doctor must also monitor you closely to prevent sudden changes in your fluid, vitamin, electrolyte and mineral levels. Water and electrolyte imbalances and metabolic disorders should be corrected before starting the infusion. Your doctor will monitor your condition while you are receiving this medicine and may adjust the dose or add further nutrients such as vitamins, electrolytes and trace elements if appropriate.
Liver disorders, including problems with bile elimination (cholestasis), fat accumulation (hepatic steatosis), fibrosis, which may lead to liver failure, as well as cholecystitis and cholelithiasis, have been reported in patients receiving intravenous nutritional therapy. The cause of these disorders is believed to be multifactorial and may vary between patients. If you experience symptoms such as nausea, vomiting, abdominal pain, or yellowing of the skin or eyes, consult your doctor to identify possible causative and contributing factors and appropriate therapeutic and preventive measures.

Your doctor must be informed if you have:

• Severe kidney problems. You must inform your doctor if you are on dialysis (artificial kidney) or undergoing another blood purification treatment
• Severe liver problems
• Blood clotting disorders
• Inadequate function of the adrenal glands (adrenal insufficiency), which are triangular-shaped glands located above the kidneys
• Heart failure
• Lung disease
• Fluid accumulation in the body (hyperhydration)
• Insufficient fluid in the body (dehydration)
• High blood sugar levels (untreated diabetes mellitus)
• Heart attack or stroke secondary to sudden heart failure
• Severe metabolic acidosis (when the blood is too acidic)
• Generalized infection (septicaemia)
• Coma

To assess the overall effectiveness and safety of administration, your doctor will perform clinical and laboratory tests while you are receiving this medicine. If you are to receive this medicine for several weeks, your blood will be monitored regularly.
Reduced ability of the body to clear the fats contained in this medicine may cause a "fat overload syndrome" (see section 4 - Possible side effects).
If during infusion you experience pain, burning or swelling at the infusion site or leakage of the infusion solution, inform your doctor or nurse. Administration will be stopped immediately and restarted in another vein.
If your blood sugar level becomes too high, your doctor will adjust the infusion rate of OLIMEL N7E or give you a medicine to control your blood sugar level (insulin).
OLIMEL N7E may only be administered via a catheter into a large vein in the chest (central vein).

Children and adolescents
If your child is under 18 years of age, particular attention will be paid to ensuring the correct dosage. Additional precautions will also be taken due to children's increased susceptibility to the risk of infection. Vitamin and trace element supplementation is always required. Paediatric formulations must be used.

Other medicines and OLIMEL N7E
Inform your doctor if you are taking or using, have recently taken or used, or might take or use any other medicines.
Concurrent administration of other medicines is generally not a contraindication. If you are taking other medicines, with or without a prescription, inform your doctor in advance to verify compatibility.
Inform your doctor if you are taking or receiving any of the following:

• Insulin
• Heparin

OLIMEL N7E must not be administered simultaneously with blood through the same infusion set.
OLIMEL N7E contains calcium. It must not be administered together with the antibiotic ceftriaxone or through the same tubing, as particles may form. If the same device is used to administer these medicines sequentially, the device must be thoroughly flushed.
Due to the risk of precipitation, OLIMEL N7E must not be administered through the same infusion line or mixed with the antibiotic ampicillin or the antiepileptic fosphenytoin.
The olive and soybean oils in OLIMEL N7E contain vitamin K. This vitamin generally does not affect blood-thinning medicines (anticoagulants) such as coumarin. However, inform your doctor if you are taking anticoagulant medicines.
The lipids contained in this emulsion may interfere with the results of certain laboratory tests if the blood sample is taken before lipids have been cleared from your blood (which usually occurs after a period of 5 to 6 hours without infusion).
OLIMEL N7E contains potassium. Exercise particular caution in patients taking diuretics, ACE inhibitors, angiotensin II receptor antagonists (medicines for the treatment of hypertension) or immunosuppressants. These types of medicines may increase potassium levels in the blood.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding, consult your doctor before you are given this medicine.
There is insufficient experience with the use of OLIMEL N7E in pregnant or breastfeeding women.
OLIMEL N7E may be considered during pregnancy and breastfeeding if necessary. OLIMEL N7E should only be administered to pregnant or breastfeeding women after careful evaluation.

Driving and using machines
Not applicable

3. How to use OLIMEL N7E, infusion emulsion

Dosage
OLIMEL must be administered only in adults and children over two years of age.
It is an infusion emulsion, to be administered through a tube (catheter) inserted into a vein in the chest.
OLIMEL must be at room temperature before use.
OLIMEL N7E is for single use only.
The infusion of one bag usually lasts from 12 to 24 hours.

Dosage – adults
Your doctor will determine an appropriate flow rate according to your needs and clinical condition.
The treatment may continue for as long as required, depending on your clinical status.

Dosage – children over two years of age and adolescents
Your doctor will decide the dose and duration of treatment. This will depend on age, body weight, height, medical condition, and the body's ability to metabolize and utilize the components of OLIMEL N7E.

If you have been given more OLIMEL N7E, infusion emulsion, than you should have received
If the dose administered is too high or the infusion is too rapid, the amino acid content may cause your blood to become too acidic, and symptoms of hypervolemia (increased volume of circulating blood) may occur. Blood and urine glucose levels may rise, a hyperosmolar syndrome (excessive blood viscosity) may develop, and lipid content may increase triglyceride levels in your blood. Receiving the infusion too rapidly or an excessive volume of OLIMEL N7E may cause nausea, vomiting, chills, headache, hot flushes, excessive sweating (hyperhidrosis), and electrolyte imbalances. In such cases, the infusion must be stopped immediately.
In severe cases, your doctor may temporarily perform renal dialysis to help your kidneys eliminate the excess product.
To prevent such events, your doctor will regularly monitor your condition and perform blood tests.
If you have any doubts about the use of this product, consult your doctor.

4. POSSIBLE SIDE EFFECTS

Like all medicines, this medicine can cause side effects, although not everyone experiences them. If you notice any changes in how you feel during or after treatment, inform your doctor or nurse promptly.
The tests your doctor performs while you are receiving this medicine help reduce the risks of side effects.
The infusion will be stopped immediately if signs or symptoms of an allergic reaction occur, such as sweating, fever, chills, headache, skin rash, or breathing difficulties.

The following side effects have been reported with OLIMEL N7E:

Frequency – Common: may affect up to 1 in 10 people

• Fast heart rate (tachycardia)
• Decreased appetite
• Increased blood fat levels (hypertriglyceridemia)
• Abdominal pain
• Diarrhea
• Nausea
• Increased blood pressure (hypertension)

Frequency – Not known: frequency cannot be estimated from the available data

• Hypersensitivity reactions including sweating, fever, chills, headache, skin rash (erythematous, papular, pustular, macular, generalized skin eruption), itching, hot flushes, breathing difficulties
• Leakage of the infusion into surrounding tissue (extravasation), which may cause at the infusion site: pain, irritation, swelling/edema, redness (erythema)/warmth, tissue cell death (skin necrosis), or blisters/vesicles, inflammation, thickening or tightening of the skin
• Vomiting

The following side effects have been reported with similar parenteral nutrition products:

Frequency – Very rare: may affect up to 1 in 10,000 people

• Reduced ability to clear lipids (fat overload syndrome), associated with a sudden and sharp worsening of the patient's medical condition. The following symptoms of fat overload syndrome are usually reversible after stopping the lipid emulsion infusion:
  • Fever
  • Reduction in red blood cells, which may make the skin appear pale and cause weakness or shortness of breath (anemia)
  • Low white blood cell count, which may increase the risk of infection (leucopenia)
  • Low platelet count, which may increase the risk of bruising and/or bleeding (thrombocytopenia)
  • Blood clotting disorders that impair the blood's ability to clot
  • High levels of fat in the blood (hyperlipidemia)
  • Fatty infiltration of the liver (hepatomegaly)
  • Worsening of liver function
  • Central nervous system manifestations (e.g., coma)

Frequency – Not known: frequency cannot be estimated from the available data

• Allergic reactions
• Abnormal blood test results for liver function
• Problems with bile elimination (cholestasis)
• Enlargement of the liver (hepatomegaly)
• Liver disease associated with parenteral nutrition (see "Warnings and precautions" in section 2)
• Jaundice (icterus)
• Decreased platelet count (thrombocytopenia)
• Increased nitrogen levels in the blood (azotemia)
• Elevated liver enzymes
• Formation of small particles that may cause blockage of blood vessels in the lungs (pulmonary vascular precipitates), leading to pulmonary vascular embolism and breathing difficulties (respiratory distress)

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please inform your doctor or pharmacist. You may also report side effects directly via the national reporting system at:
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store OLIMEL N7E infusion emulsion

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the container and outer packaging (MM/YYYY). The expiry date refers to the last day of the month.
Do not freeze.
Store in the outer packaging.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What OLIMEL N7E, infusion emulsion contains
The active substances in each bag of the reconstituted emulsion are: a 11.1% solution of L-amino acids
(corresponding to 11.1 g/100 mL) (alanine, arginine, glycine, histidine, isoleucine, leucine, lysine
(as lysine acetate), methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine,
aspartic acid, glutamic acid), with electrolytes (sodium, potassium, magnesium, phosphate, acetate,
chloride); a 20% lipid emulsion (corresponding to 20 g/100 mL) (purified olive oil and purified soybean
oil); and a 35% glucose solution (corresponding to 35 g/100 mL) (as glucose monohydrate) with calcium.
The excipients are:
Compartment Compartment Compartment
Lipid emulsion Amino acid solution Glucose solution

1. , 2. Glacial acetic acid 3. Hydrochloric acid glycerol, sodium oleate, (for pH sodium hydroxide (for adjustment) (for pH adjustment) water for water for preparations water for preparations preparations for injections injections injections 4. Appearance of OLIMEL N7E, infusion emulsion and contents of the packaging

OLIMEL N7E is an infusion emulsion supplied in a three-compartment bag. One compartment contains a lipid emulsion, another compartment contains an amino acid solution with electrolytes, and the third compartment contains a glucose solution with calcium. These compartments are separated by non-permanent membranes. Before administration, the contents of the compartments must be mixed by rolling the bag upon itself from the top until the membranes open.
Appearance before reconstitution:
The amino acid and glucose solutions are clear, colorless or slightly yellow, and transparent.
The lipid emulsion is homogeneous with a milky appearance.
Appearance after reconstitution: homogeneous emulsion with a milky appearance.
The three-compartment bag is a multilayer plastic bag. The material of the inner layer (in contact) of the bag is designed to be compatible with the authorized constituents and additives.
To prevent contact with atmospheric oxygen, the bag is packaged in an outer oxygen-barrier pouch containing an oxygen-absorbing sachet.
Packaging:
1,000 mL bag: 1 box containing 6 bags; 1 box containing 5 bags
1,500 mL bag: 1 box containing 4 bags; 1 box containing 5 bags
2,000 mL bag: 1 box containing 4 bags; 1 box containing 5 bags
1 bag of 1,000 mL, 1,500 mL and 2,000 mL
Not all pack sizes may be marketed.
Marketing Authorization Holder
Baxter S.p.A.
Via Del Serafico 89
00142 Rome
Italy
Manufacturer:
Baxter S.A.,
Boulevard Rene Branquart, 80,
7860 Lessines
Belgium
This medicinal product is authorized in the European Economic Community member states under the following names:
France, Portugal, Estonia, Poland, Lithuania, Bulgaria, Romania, Latvia, Czech Republic, Belgium, Spain, Slovakia, Netherlands, Luxembourg, Slovenia, Italy, Denmark, Iceland, Sweden, Norway, Finland, Greece, Cyprus: OLIMEL N7E
Austria: ZentroOLIMEL 4,4 % mit Elektrolyten >
Germany: Olimel 4,4% E
United Kingdom, Ireland, Malta: Triomel 7g/L nitrogen 1140 kcal/L with electrolytes
Hungary: Olimel 7 g/L nitrogén elektrolitokkal emulziós infúzió
This summary of product characteristics was last approved on:

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The following information is intended exclusively for physicians or healthcare professionals:
Pharmacotherapeutic category: Parenteral nutrition solutions/combinations
ATC code: B05 BA10
A. QUALITATIVE AND QUANTITATIVE COMPOSITION
OLIMEL N7E is supplied as a three-compartment bag.
Each bag contains a glucose solution with calcium, a lipid emulsion, and an amino acid solution with additional electrolytes:
Contents per bag
1,000 mL 1,500 mL 2,000 mL
35% glucose solution 400 mL 600 mL 800 mL
(corresponding to 35 g/100 mL)
11.1% amino acid solution 400 mL 600 mL 800 mL
(corresponding to 11.1 g/100 mL)
20% lipid emulsion 200 mL 300 mL 400 mL
(corresponding to 20 g/100 mL)
Composition of the reconstituted emulsion after mixing the contents of the three compartments:
Active substances 1,000 mL 1,500 mL 2,000 mL
Purified olive oil + purified soybean oil 40.00 g 60.00 g 80.00 g
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 3.48 g 5.23 g 6.97 g
(equivalent to lysine acetate) (4.88 g) (7.31 g) (9.75 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
Sodium glycerophosphate, hydrate 3.67 g 5.51 g 7.34 g
Potassium chloride 2.24 g 3.35 g 4.47 g
Magnesium chloride, hexahydrate 0.81 g 1.22 g 1.62 g
Calcium chloride, dihydrate 0.52 g 0.77 g 1.03 g
Glucose 140.00 g 210.00 g 280.00 g
(equivalent to glucose monohydrate) (154.00 g) (231.00 g) (308.00 g)
A mixture of purified olive oil (approximately 80%) and purified soybean oil (approximately 20%), corresponding to a ratio of essential fatty acids to total fatty acids of 20%.
The excipients are:
Compartment Compartment Compartment
Lipid emulsion Amino acid solution Glucose solution
Purified egg phospholipids, Glacial acetic acid (for pH Hydrochloric acid (for pH
glycerol, sodium oleate, adjustment), sodium hydroxide adjustment), water for
water for preparations for (for pH adjustment), water for preparations for injections
injections preparations for injections
Nutritional intake of the reconstituted emulsion for each bag size:

Contains calories from purified egg phospholipids
Contains phosphate supplied by the lipid emulsion

B. DOSAGE AND ADMINISTRATION

Dosage

The use of OLIMEL N7E is not recommended in children under 2 years of age due to its composition and volume being unsuitable (see sections 4.4, 5.1 and 5.2 of the SmPC).

Do not exceed the maximum daily dose indicated below. Because of the fixed composition of the multi-chamber bag, it may not be possible to meet all of the patient's nutritional requirements simultaneously. Clinical situations may arise where patients require variable amounts of nutrients compared to the composition of the fixed-bag formulation. In such cases, any adjustment in volume (dose) must take into account the resulting effect on the dosage of all other nutritional components in OLIMEL N7E.

In adults:

The dosage depends on energy expenditure, clinical condition, body weight, and the patient's ability to metabolize the components of OLIMEL N7E, as well as on additional energy or protein provided orally/enterally; therefore, the appropriate bag size should be selected accordingly.

Average daily requirements are:

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

For OLIMEL N7E, the maximum daily dose is defined by the total caloric intake: 40 kcal provided 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 70 kg patient, this would be equivalent to 2450 mL of OLIMEL N7E per day, providing 108 g amino acids, 343 g glucose, and 98 g lipids (i.e., 2352 non-protein kcal and 2793 total kcal).

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

For OLIMEL N7E, the maximum infusion rate 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.

In children over 2 years of age and adolescents:

No studies have been conducted in the pediatric population.

Dosage depends on energy expenditure, clinical condition, body weight, and the patient's ability to metabolize the components of OLIMEL N7E, as well as on additional energy or protein provided orally/enterally; therefore, the appropriate bag size should be selected accordingly.

Furthermore, daily requirements for fluids, nitrogen, and energy progressively decrease with age. Two age groups have been considered: ages 2 to 11 years, and ages 12 to 18 years.

For OLIMEL N7E, in both age groups, magnesium concentration limits the maximum daily dose. For both age groups, glucose concentration limits the maximum hourly infusion rate. The resulting nutrient intakes are shown below:

a: Recommended values according to ESPGHAN/ESPEN/ESPR 2018 Guidelines
Normally, the flow rate should be gradually increased during the first hour and then
adjusted considering the dose to be administered, the daily volume intake, and the duration of infusion.
In general, in young children it is recommended to start infusion with a low daily dose,
and gradually increase it up to the maximum dosage (see above).

Mode and duration of administration
For single use only.
It is recommended to use the contents immediately after opening the bag and not to
store it for subsequent infusion.
After reconstitution, the mixture is homogeneous and has a milky appearance.
For instructions on the preparation and handling of the infusion emulsion, see section 6.6.
Due to its high osmolarity, OLIMEL N7E must be administered only through a central vein.
The recommended infusion duration for a parenteral nutrition bag is between 12 and
24 hours.
Parenteral nutrition treatment may continue for as long as clinically required.

C. INCOMPATIBILITIES
Do not add any other medicinal product or substances to any of the bag components or to the reconstituted emulsion without first verifying the compatibility and stability of the resulting preparation (in particular, the stability of the lipid emulsion).
Incompatibilities may arise, for example, from excessive acidity (low pH) or unsuitable content of bivalent cations (Ca and Mg), which may destabilize the lipid emulsion.
As with any other parenteral nutrition mixture, the calcium/phosphate ratio must be taken into consideration. Excessive addition of calcium and phosphate, particularly in the form of mineral salts, may lead to precipitation of calcium phosphate.
OLIMEL N7E contains calcium ions, which pose an additional risk of coagulation in blood or in anticoagulated or citrate-preserved blood components.
Ceftriaxone must not be mixed or administered concomitantly with intravenous solutions containing calcium, including OLIMEL N7E, through the same infusion line (e.g., via a Y-connector) due to the risk of precipitation of ceftriaxone-calcium salt (see sections 4.4 and 4.5 of the SmPC). Ceftriaxone and calcium-containing solutions may be administered sequentially if different infusion sites are used or if the infusion lines are replaced or thoroughly flushed with physiological saline between infusions to prevent precipitate formation.
Due to the risk of precipitation, OLIMEL N7E must not be administered through the same infusion line or mixed with the antibiotic ampicillin or the antiepileptic fosphenytoin.
Check compatibility with solutions administered simultaneously through the same administration set, catheter, or cannula.
Do not administer before, simultaneously, or after a blood transfusion via the same line due to the risk of pseudoagglutination.

D. SPECIAL PRECAUTIONS FOR DISPOSAL AND HANDLING
An overview of the various steps in preparing OLIMEL N7E for administration is shown in Figure 1.

Opening
Remove the outer protective wrapper.
Discard the oxygen absorber bag.
Check the integrity of the bag and the non-permanent separation membranes. Use only if the bag is undamaged, the non-permanent separation membranes are intact (i.e., no mixing of the contents of the three compartments has occurred), the amino acid solution and glucose solution are clear, colorless or slightly yellow, and practically free from visible particles, and the lipid emulsion is a homogeneous liquid with a milky appearance.

Mixing of solutions and emulsion
Ensure the product is at room temperature when breaking the non-permanent separation membranes.
Manually roll the bag onto itself starting from the top (end with loop). The non-permanent separation membranes will disappear from the side adjacent to the openings.
Continue rolling the bag until the separation membranes are opened for approximately half of their length.
Mix the bag by inverting it at least three times.
After reconstitution, the mixture is a homogeneous emulsion with a milky appearance.

Additions:
The bag has sufficient capacity to allow additions such as vitamins, electrolytes, and trace elements.
Any addition (including vitamins) should be made to the reconstituted mixture (after opening the non-permanent separation membranes and after mixing the contents of the three compartments).
Vitamins may also be added to the glucose compartment before the mixture is reconstituted (before opening the non-permanent separation membranes and before mixing the three compartments).
When making additions to formulations containing electrolytes, the amount of electrolytes already present in the bag must be taken into account.
All additions must be performed by trained personnel under aseptic conditions.
OLIMEL N7E can be supplemented with electrolytes based on the following table:

Equivalent value corresponding to the addition of inorganic phosphate
Including the phosphate provided by the lipid emulsion
Trace elements and vitamins:
Stability has been demonstrated with commercially available preparations of vitamins and trace elements
(containing up to a maximum of 1 mg of iron).
Compatibility of other additives is available upon request.
When performing additions, measure the final osmolarity of the mixture before administration via peripheral vein.
To perform an addition:

• The procedure must be carried out under aseptic conditions.
• Prepare the injection site of the bag.
• Pierce the injection site and inject the additives using an injection needle or a reconstitution device.
• Mix the contents of the bag and the added components.

Preparation of the infusion
The procedure must be carried out under aseptic conditions.
Suspend the bag.
Remove the plastic protective cover from the administration port.
Firmly insert the spike of the infusion set into the administration port.

Administration
For single use only.
Administer the product only after breaking the non-permanent separation membranes between
the 3 compartments and mixing the contents of all 3 compartments.
Ensure that the final infusion emulsion shows no evidence of phase separation.
After opening the bag, the contents must be used immediately. Never store an opened bag for subsequent infusion.
Do not reconnect partially used bags.
Do not connect bags in series to avoid the risk of gas embolism due to gas contained in the primary bag.
Dispose of any unused product, waste materials, and all necessary devices.

Extravasation
The catheter site must be regularly checked for possible signs of extravasation.
In case of extravasation, administration must be immediately stopped while maintaining the catheter or cannula in place for immediate patient management. If possible, perform aspiration through the inserted catheter or cannula to reduce the amount of fluid present in the tissues before removing the catheter or cannula.
Depending on the extravasated product (including one or more products mixed with OLIMEL N7E, if applicable) and the extent or severity of a potential injury, appropriate specific measures should be taken. Treatment options may include non-pharmacological, pharmacological, and/or surgical interventions. In case of major extravasation, consult a plastic surgeon within the first 72 hours.
The site of extravasation should be monitored at least every 4 hours during the first 24 hours, then once daily.
Infusion should not be restarted in the same central vein.

Package leaflet: Information for the user

OLIMEL

N9E infusion emulsion
Please read this leaflet carefully before this medicine is administered to you, as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, consult your doctor or nurse.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor or nurse. See section 4.

Contents of this leaflet:

1. What OLIMEL N9E infusion emulsion is and what it is used for
2. What you need to know before OLIMEL N9E infusion emulsion is administered to you
3. How to use OLIMEL N9E infusion emulsion
4. Possible side effects
5. How to store OLIMEL N9E infusion emulsion
6. Contents of the pack and other information
7. (Note: Section numbers appear incorrectly listed in the original)

1. What OLIMEL N9E infusion emulsion is and what it is used for

OLIMEL N9E is an infusion emulsion. It is presented as a three-compartment bag.
One compartment contains a glucose solution with calcium, the second a lipid emulsion, and
the third an amino acid solution with other electrolytes.
OLIMEL N9E is used to provide nutrition to adults and children over the age of two via
a tube inserted into a vein, when normal oral feeding is not appropriate.
OLIMEL N9E must be used exclusively under medical supervision.

2. What you should know before OLIMEL N9E emulsion for infusion is administered to you

OLIMEL N9E emulsion for infusion must not be used in the following cases:

• In premature infants, infants and children under 2 years of age
• If you are hypersensitive (allergic) to egg proteins, soybean seeds, peanuts, or corn/corn-derived products (see also section "Warnings and precautions" below), or to any other excipient of this medicine (listed in section 6)
• If the use of certain amino acids causes problems for your body
• If you have particularly high levels of fats in your blood
• If you suffer from hyperglycaemia (too much sugar in the blood)
• If you have abnormally high concentrations of any of the electrolytes (sodium, potassium, magnesium, calcium and/or phosphorus) in your blood

In all cases, your doctor will decide whether you should receive this medicine based on factors such as your age, weight and medical condition, together with the results of laboratory tests.

Warnings and precautions

Talk to your doctor or nurse before OLIMEL N9E is administered to you.

If total parenteral nutrition solutions are administered too rapidly, this may cause injury or death.

Infusion must be stopped immediately if signs or symptoms of an allergic reaction occur (such as sweating, fever, chills, headache, skin rash or difficulty breathing). This medicine contains soybean oil and egg phospholipids. Soybeans and egg proteins may cause hypersensitivity reactions. Cross-allergic reactions between soy and peanut proteins have been observed.

OLIMEL N9E contains glucose derived from corn which may cause hypersensitivity reactions if you are allergic to corn or corn-derived products (see section "OLIMEL N9E emulsion for infusion must not be used" above).

Difficulty in breathing may also be a sign that small particles have formed, blocking blood vessels in the lungs (pulmonary vascular precipitates). If you experience difficulty breathing, inform your doctor or nurse, who will decide on the necessary actions.

The antibiotic ceftriaxone must not be mixed or administered simultaneously with any calcium-containing solution (including OLIMEL N9E) administered via intravenous infusion.

These medicines must not be administered together even through separate infusion lines or at different infusion sites.

However, you may receive OLIMEL N9E and ceftriaxone sequentially, one after the other, provided different infusion sites are used or the infusion lines are replaced or thoroughly flushed with physiological saline between infusions to prevent formation of precipitates (calcium-ceftriaxone salt particles).

Some medicines and medical conditions may increase the risk of developing infection or sepsis (bacteria in the blood). There is a particular risk of infection or sepsis when a tube (intravenous catheter) is inserted into a vein. Your doctor will closely monitor you for any signs of infection. Patients requiring parenteral nutrition (nutrition delivered through a tube placed in a vein) may have an increased risk of developing infections due to their underlying medical conditions. The use of aseptic techniques (germ-free) during catheter placement and maintenance, as well as during preparation of the nutritional formula (total parenteral nutrition), can reduce this risk.

If you are severely malnourished to the point of requiring intravenous nutrition, your doctor should start treatment slowly. Your doctor must also monitor you closely to prevent sudden changes in your fluid, vitamin, electrolyte and mineral levels. Water and electrolyte imbalances and metabolic disorders should be corrected before starting the infusion. Your doctor will monitor your condition while you are receiving this medicine and may adjust the dose or add additional nutrients such as vitamins, electrolytes and trace elements if deemed appropriate.

Liver disorders, including impaired bile excretion (cholestasis), fat accumulation (hepatic steatosis), fibrosis, which may lead to liver failure, as well as cholecystitis and cholelithiasis, have been reported in patients receiving intravenous nutritional therapy. These disorders are believed to result from multiple factors and may vary between patients. If you experience symptoms such as nausea, vomiting, abdominal pain or yellowing of the skin or eyes (jaundice), consult your doctor to identify possible causative and contributing factors and appropriate therapeutic or preventive measures.

You must inform your doctor if you have:

• Severe kidney problems. You must inform your doctor if you are on dialysis (artificial kidney) or receiving another blood purification treatment
• Severe liver problems
• Blood clotting disorders
• Inadequate function of the adrenal glands (adrenal insufficiency), which are triangular-shaped glands located above the kidneys
• Heart failure
• Lung disease
• Fluid accumulation in the body (overhydration)
• Insufficient fluid in the body (dehydration)
• High blood sugar levels (untreated diabetes mellitus)
• Heart attack or stroke secondary to sudden cardiac failure
• Severe metabolic acidosis (when the blood is too acidic)
• Generalized infection (septicaemia)
• Coma

To monitor the overall effectiveness and safety of treatment, your doctor will perform clinical and laboratory tests while you are receiving this medicine. If you are to receive this medicine for several weeks, your blood will be monitored regularly.

Reduced ability of the body to clear the fats contained in this medicine may lead to a "fat overload syndrome" (see section 4 - Possible side effects).

If during infusion you experience pain, burning or swelling at the infusion site, or leakage of the infusion solution, inform your doctor or nurse immediately. Administration will be stopped immediately and restarted in another vein.

If your blood sugar level becomes too high, your doctor will adjust the infusion rate of OLIMEL N9E or administer a medicine to control your blood sugar level (insulin).

OLIMEL N9E may be administered via a tube (catheter) into a large vein in the chest (central vein).

Children and adolescents

If your child is under 18 years of age, particular attention will be paid to ensuring the correct dosage. Additional precautions will also be taken due to children's increased susceptibility to infection risk. Vitamin and trace element supplementation is always required. Paediatric formulations must be used.

Other medicines and OLIMEL N9E

Inform your doctor if you are taking, have recently taken or might take any other medicines.

Concomitant administration of other medicines is generally not a contraindication. However, if you are taking other medicines, whether prescribed or over-the-counter, inform your doctor in advance to verify compatibility.

Inform your doctor if you are taking or receiving any of the following:

• Insulin
• Heparin

OLIMEL N9E must not be administered simultaneously with blood through the same infusion set. OLIMEL N9E contains calcium. It must not be administered together with the antibiotic ceftriaxone or through the same tubing, as particles may form. If the same device is used to administer these medicines sequentially, the device must be thoroughly flushed.

Due to the risk of precipitation, OLIMEL N9E must not be administered through the same infusion line or mixed with the antibiotic ampicillin or the antiepileptic fosphenytoin.

The olive and soybean oils in OLIMEL N9E contain vitamin K. This vitamin generally does not affect blood-thinning medicines (anticoagulants) such as coumarin. However, inform your doctor if you are taking anticoagulant medicines.

The lipids contained in this emulsion may interfere with the results of certain laboratory tests if blood samples are taken before lipids have been cleared from your blood (which usually occurs after a period of 5 to 6 hours without infusion).

OLIMEL N9E contains potassium. Exercise particular caution in patients taking diuretics, ACE inhibitors, angiotensin II receptor antagonists (medicines for the treatment of hypertension) or immunosuppressants. These types of medicines may increase potassium levels in the blood.

Pregnancy and breastfeeding

If you are pregnant, suspect you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor before this medicine is administered to you.

There is insufficient experience with the use of OLIMEL N9E in pregnant or breastfeeding women. OLIMEL N9E may be considered during pregnancy and breastfeeding if necessary. However, OLIMEL N9E should be administered to pregnant or breastfeeding women only after careful evaluation.

Driving and using machines

Not applicable

3. How to use OLIMEL N9E infusion emulsion

Dosage
OLIMEL N9E must be administered only in adults and children over two years of age.
It is an infusion emulsion, to be administered through a tube (catheter) into a vein in the chest.
OLIMEL N9E must be at room temperature before use.
OLIMEL N9E is for single use only.
The infusion of one bag usually lasts between 12 and 24 hours.

Dosage – adults
Your doctor will determine an appropriate flow rate according to your needs and clinical condition.
The treatment may continue for as long as necessary, depending on your clinical status.

Dosage – children over two years of age and adolescents
Your doctor will decide the dose and duration of treatment. This will depend on age, weight, height, medical condition, and the body's ability to metabolize and utilize the components of OLIMEL N9E.

If you have been given more OLIMEL N9E infusion emulsion than you should have
If the dose administered is too high or the infusion rate is too fast, the amino acid content may make your blood too acidic, and symptoms of hypervolemia (increased volume of circulating blood) may occur. Blood and urine glucose levels may rise, a hyperosmolar syndrome (excessive blood viscosity) may develop, and the lipid content may increase triglyceride levels in your blood. Receiving an infusion too rapidly or an excessive volume of OLIMEL N9E may cause nausea, vomiting, chills, headache, hot flushes, excessive sweating (hyperhidrosis), and electrolyte imbalances. In such cases, the infusion must be stopped immediately.
In severe cases, your doctor may temporarily initiate renal dialysis to help your kidneys eliminate the excess product.
To prevent such events, your doctor will regularly monitor your condition and perform blood tests.

5. If you have any questions about the use of OLIMEL N9E, consult your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
If you notice any changes in how you feel during or after treatment, inform your doctor or nurse immediately.
The tests your doctor will carry out while you are receiving this medicine help reduce the risk of side effects.
The infusion will be stopped immediately if signs or symptoms of an allergic reaction occur, such as sweating, fever, chills, headache, rash, or difficulty breathing.

The following side effects have been reported with OLIMEL N9E:

Frequency - Common: may affect up to 1 in 10 people

• Fast heart rate (tachycardia)
• Decreased appetite
• Increased blood fat levels (hypertriglyceridemia)
• Abdominal pain
• Diarrhea
• Nausea
• Increased blood pressure (hypertension)

Frequency - Not known: frequency cannot be estimated from the available data

• Hypersensitivity reactions including sweating, fever, chills, headache, skin rash (erythematous, papular, pustular, macular, generalized rash), itching, hot flushes, breathing difficulties
• Leakage of the infusion into surrounding tissue (extravasation), which may cause pain, irritation, swelling/edema, redness (erythema)/heat, tissue cell death (skin necrosis), or blisters/vesicles, inflammation, thickening or tightening of the skin at the infusion site
• Vomiting

With similar parenteral nutrition products, the following side effects have been reported:

Frequency - Very rare: may affect up to 1 in 10,000 people

• Reduced ability to clear lipids (lipid overload syndrome), associated with a sudden and sharp worsening of the patient's clinical condition. The following symptoms of lipid overload syndrome are usually reversible after stopping the lipid emulsion infusion:
  • Fever
  • Reduced red blood cells, which may make the skin pale and cause weakness or breathlessness (anaemia)
  • Low white blood cell count, which may increase the risk of infection (leucopenia)
  • Low platelet count, which may increase the risk of bruising and/or bleeding (thrombocytopenia)
  • Blood clotting disorders that impair the blood's ability to clot
  • High levels of fat in the blood (hyperlipidaemia)
  • Fatty infiltration of the liver (hepatomegaly)
  • Worsening of liver function
  • Central nervous system manifestations (e.g., coma)

Frequency - Not known: frequency cannot be estimated from the available data

• Allergic reactions
• Abnormal blood test results for liver function
• Problems with bile elimination (cholestasis)
• Enlargement of the liver (hepatomegaly)
• Liver disease associated with parenteral nutrition (see "Warnings and precautions" in section 2)
• Jaundice (icterus)
• Decreased platelet count (thrombocytopenia)
• Increased nitrogen levels in the blood (azotaemia)
• Elevated liver enzymes
• Formation of small particles that may cause blockage of blood vessels in the lungs (pulmonary vascular precipitates), leading to pulmonary vascular embolism and breathing difficulties (respiratory distress)

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please inform your doctor or pharmacist. You can also report side effects directly via the national reporting system at:
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store OLIMEL N9E infusion emulsion

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the container and outer packaging (MM/YYYY). The expiry date refers to the last day of the month.
Do not freeze.
Store in the outer packaging.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Package contents and other information

What OLIMEL N9E, infusion emulsion contains
The active substances in each bag of the reconstituted emulsion are a solution of L-amino acids at
14.2% (equivalent to 14.2 g/100 mL) (alanine, arginine, glycine, histidine, isoleucine, leucine, lysine
(as lysine acetate), methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine,
aspartic acid, glutamic acid) with electrolytes (sodium, potassium, magnesium, phosphate, acetate,
chloride), a 20% lipid emulsion (equivalent to 20 g/100 mL) (purified olive oil and purified soybean
oil), and a 27.5% glucose solution (equivalent to 27.5 g/100 mL) (as monohydrate glucose) with calcium.
Excipients:
Compartment Compartment Compartment
Lipid emulsion Amino acid solution Glucose solution
Purified egg phospholipids, Glacial acetic acid (for Hydrochloric acid (for
glycerol, sodium oleate, sodium pH adjustment), pH adjustment),
hydroxide (for pH adjustment), water for injection water for injection
water for injection

Appearance of OLIMEL N9E, infusion emulsion and contents of the packaging
OLIMEL N9E is an infusion emulsion supplied in a three-compartment bag. One compartment contains a lipid emulsion, another compartment contains an amino acid solution with electrolytes, and the third compartment contains a glucose solution with calcium. These compartments are separated by non-permanent membranes. Before administration, the contents of the compartments must be mixed by rolling the bag on itself from the top until the membranes open.
Appearance before reconstitution:
The amino acid and glucose solutions are clear, colourless or slightly yellow, and transparent.
The lipid emulsion is homogeneous with a milky appearance.
Appearance after reconstitution: Homogeneous emulsion with a milky appearance.
The three-compartment bag is a multilayer plastic bag. The material of the inner layer (in contact) of the bag is designed to be compatible with the constituents and authorised additives.
To prevent contact with atmospheric oxygen, the bag is packaged in an outer oxygen-barrier pouch containing an oxygen-absorbing sachet.

Packaging:
1,000 mL bag: 1 box containing 6 bags; 1 box containing 5 bags
1,500 mL bag: 1 box containing 4 bags; 1 box containing 5 bags
2,000 mL bag: 1 box containing 4 bags; 1 box containing 5 bags
1 bag of 1,000 mL, 1,500 mL and 2,000 mL
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Baxter S.p.A.
Via Del Serafico 89
00142 Rome
Italy

Manufacturer:
Baxter S.A.,
Boulevard Rene Branquart, 80
7860 Lessines
Belgium

This medicinal product is authorised in the European Economic Area member states under the
following names:
France, Portugal, Estonia, Poland, Lithuania, Bulgaria, Romania, Latvia, Czech Republic, Belgium,
Spain, Slovak Republic, Netherlands, Luxembourg, Slovenia, Italy, Denmark, Iceland, Sweden,
Norway, Finland, Greece, Cyprus: OLIMEL N9E
Austria: ZentroOLIMEL 5,7 % mit Elektrolyten
Germany: Olimel 5,7% E
United Kingdom, Ireland, Malta: Triomel 9g/L nitrogen 1070 kcal/L with electrolytes
Hungary: Olimel 9 g/L nitrogén elektrolitokkal emulziós infúzió

This patient information leaflet was last approved on:

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The following information is intended exclusively for physicians or healthcare professionals:
Pharmacotherapeutic category: Parenteral nutrition solutions/combinations
ATC code: B05BA10

A. QUALITATIVE AND QUANTITATIVE COMPOSITION
OLIMEL N9E is supplied as a three-compartment bag.
Each bag contains a glucose solution with calcium, a lipid emulsion, and an amino acid solution with additional electrolytes:

Contents per bag
1,000 mL 1,500 mL 2,000 mL
Glucose solution 27.5% 400 mL 600 mL 800 mL
(equivalent to 27.5 g/100 mL)
Amino acid solution 14.2% 400 mL 600 mL 800 mL
(equivalent to 14.2 g/100 mL)
Lipid emulsion 20% 200 mL 300 mL 400 mL
(equivalent to 20 g/100 mL)

Composition of the reconstituted emulsion after mixing the contents of the three compartments:

Active substances 1,000 mL 1,500 mL 2,000 mL
Purified olive oil + purified soybean oil 40.00 g 60.00 g 80.00 g
Alanine 8.24 g 12.36 g 16.48 g
Arginine 5.58 g 8.37 g 11.16 g
Aspartic acid 1.65 g 2.47 g 3.30 g
Glutamic acid 2.84 g 4.27 g 5.69 g
Glycine 3.95 g 5.92 g 7.90 g
Histidine 3.40 g 5.09 g 6.79 g
Isoleucine 2.84 g 4.27 g 5.69 g
Leucine 3.95 g 5.92 g 7.90 g
Lysine 4.48 g 6.72 g 8.96 g
(as lysine acetate) (6.32 g) (9.48 g) (12.64 g)
Methionine 2.84 g 4.27 g 5.69 g
Phenylalanine 3.95 g 5.92 g 7.90 g
Proline 3.40 g 5.09 g 6.79 g
Serine 2.25 g 3.37 g 4.50 g
Threonine 2.84 g 4.27 g 5.69 g
Tryptophan 0.95 g 1.42 g 1.90 g
Tyrosine 0.15 g 0.22 g 0.30 g
Valine 3.64 g 5.47 g 7.29 g
Sodium acetate, trihydrate 1.50 g 2.24 g 2.99 g
Sodium glycerophosphate, hydrate 3.67 g 5.51 g 7.34 g
Potassium chloride 2.24 g 3.35 g 4.47 g
Magnesium chloride, hexahydrate 0.81 g 1.22 g 1.62 g
Calcium chloride, dihydrate 0.52 g 0.77 g 1.03 g
Glucose 110.00 g 165.00 g 220.00 g
(as monohydrate glucose) (121.00 g) (181.50 g) (242.00 g)
A mixture of purified olive oil (approximately 80%) and purified soybean oil (approximately 20%),
corresponding to a ratio of essential fatty acids to total fatty acids of 20%.

Excipients:
Compartment Compartment Compartment
Lipid emulsion Amino acid solution Glucose solution
Purified egg phospholipids, Glacial acetic acid (for Hydrochloric acid (for
glycerol, sodium oleate, sodium pH adjustment), pH adjustment),
hydroxide (for pH adjustment), water for injection water for injection
water for injection

Nutritional content of the reconstituted emulsion for each bag size:

Includes calories from purified egg phospholipids
Includes phosphate supplied by the lipid emulsion
B. DOSAGE AND ADMINISTRATION
Dosage
The use of OLIMEL N9E is not recommended in children under 2 years of age due to its composition and volume being unsuitable (see sections 4.4, 5.1 and 5.2 of the SmPC).
Do not exceed the maximum daily dose indicated below. Due to the fixed composition of the multi-chamber bag, it may not be possible to simultaneously meet all of the patient's nutritional requirements. There may be clinical situations in which patients require different amounts of nutrients compared to the composition of the fixed-bag formulation. In such cases, any adjustment of volume (dose) must take into account the resulting effect on the dosage of all other nutrients in OLIMEL N9E. For example, pediatric patients may have a phosphate requirement exceeding 0.2 mmol/kg/day. In these circumstances, healthcare professionals may consider adjusting the volume (dose) of OLIMEL N9E to meet this increased requirement.

In adults:
The dosage depends on energy expenditure, clinical condition, body weight, and the patient's ability to metabolize the components of OLIMEL N9E, as well as on additional energy or protein provided orally/enterally; therefore, the appropriate bag size should be selected accordingly.
Average daily requirements are:

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

For OLIMEL N9E, the maximum daily dose is defined by the amino acid intake of 35 mL/kg, corresponding to 2.0 g/kg amino acids, 3.9 g/kg glucose, 1.4 g/kg lipids, 1.2 mmol/kg sodium, and 1.1 mmol/kg potassium. For a 70 kg patient, this would be equivalent to 2,450 mL of OLIMEL N9E per day, resulting in an intake of 140 g amino acids, 270 g glucose, and 98 g lipids (i.e., 2,058 kcal non-protein energy and 2,622 kcal total energy).
Normally, the infusion rate should be gradually increased during the first hour, then adjusted according to the required dose, daily volume, and duration of infusion.
For OLIMEL N9E, the maximum infusion rate is 1.8 mL/kg/hour, corresponding to 0.10 g/kg/hour amino acids, 0.19 g/kg/hour glucose, and 0.07 g/kg/hour lipids.

In children over 2 years of age
No studies have been conducted in the pediatric population.
Dosage depends on energy expenditure, clinical condition, body weight, and the patient's ability to metabolize the components of OLIMEL N9E, as well as on additional energy or protein provided orally/enterally; therefore, the appropriate bag size should be selected accordingly.
Furthermore, daily requirements for fluids, nitrogen, and energy continuously decrease with age.
Two age groups have been considered: 2 to 11 years, and 12 to 18 years.
For OLIMEL N9E in the 2- to 11-year age group, the limiting factors are the phosphate concentration for the daily dose (0.2 mmol/kg/day) and the lipid concentration for the hourly rate. In the 12- to 18-year age group, the limiting factors are the phosphate concentration for the daily dose (0.2 mmol/kg/day) and the amino acid concentration for the hourly rate. The resulting nutrient intakes are shown below:

a: Recommended values according to ESPGHAN/ESPEN 2005 Guidelines
Normally, the flow rate should be gradually increased during the first hour and then
adjusted according to the dose to be administered, daily volume intake, and duration of infusion.
In general, in young children it is recommended to start infusion with a low daily dose,
gradually increasing it up to the maximum dosage (see above).

Administration method and duration
For single use only.
It is recommended to use the contents immediately after opening the bag and not to
store it for subsequent infusions.
After reconstitution, the mixture is homogeneous and has a milky appearance.
For instructions on the preparation and handling of the infusion emulsion, see section 6.6.
Due to its high osmolarity, OLIMEL N9E must be administered only through a central vein.
The recommended infusion duration for a parenteral nutrition bag is between 12 and 24 hours.
Parenteral nutrition treatment may continue for as long as clinically indicated by the patient's condition.

C. INCOMPATIBILITIES
Do not add other medicinal products or substances to any of the bag components or to the reconstituted emulsion without first verifying compatibility and stability of the resulting preparation (particularly lipid emulsion stability).
Incompatibilities may arise, for example, from excessive acidity (low pH) or inappropriate content of bivalent cations (Ca and Mg), which may destabilize the lipid emulsion.
As with any other parenteral nutrition mixture, the calcium/phosphate ratio must be considered. Excessive addition of calcium and phosphate, particularly in the form of mineral salts, may lead to precipitation of calcium phosphate.
OLIMEL N9E contains calcium ions, which pose an additional risk of coagulation in blood or in anticoagulated or citrate-preserved blood components.
Ceftriaxone must not be mixed or administered concomitantly with intravenous solutions containing calcium, including OLIMEL N9E, through the same infusion line (e.g., via a Y-connector) due to the risk of precipitation of ceftriaxone-calcium salt (see sections 4.4 and 4.5 of the SmPC). Ceftriaxone and calcium-containing solutions may be administered sequentially if separate infusion lines at different sites are used, or if the infusion lines are replaced or thoroughly flushed with physiological saline between infusions to prevent precipitate formation.
Due to the risk of precipitation, OLIMEL N9E must not be administered through the same infusion line or mixed with the antibiotic ampicillin or the antiepileptic fosphenytoin.
Check compatibility with solutions administered simultaneously through the same infusion set, catheter, or cannula.
Do not administer before, during, or after blood transfusion through the same line due to the risk of pseudoagglutination.

D. SPECIAL PRECAUTIONS FOR DISPOSAL AND HANDLING
An overview of the various steps in preparing OLIMEL N9E for administration is shown in Figure 1.

Opening
Remove the outer protective wrapper.
Discard the oxygen absorber bag.
Check the integrity of the bag and the non-permanent separation membranes. Use only if the bag is undamaged, the non-permanent separation membranes are intact (i.e., no mixing of the contents of the three compartments has occurred), the amino acid solution and glucose solution are clear, colorless or slightly yellow, and practically free of visible particles, and the lipid emulsion is a homogeneous liquid with a milky appearance.

Mixing of solutions and emulsion
Ensure the product is at room temperature when breaking the non-permanent separation membranes.
Manually roll the bag from the top (end with loop). The non-permanent separation membranes will disappear from the side adjacent to the openings.
Continue rolling the bag until the separation membranes are opened along approximately half their length.
Mix the bag by inverting it at least three times.
After reconstitution, the mixture is a homogeneous emulsion with a milky appearance.

Additions:
The bag has sufficient capacity to allow additions such as vitamins, electrolytes, and trace elements.
Any addition (including vitamins) should be made to the reconstituted mixture (after opening the non-permanent separation membranes and after mixing the contents of the three compartments).
Vitamins may also be added to the glucose compartment before reconstitution (before opening the non-permanent separation membranes and before mixing the three compartments).
When making additions to formulations containing electrolytes, consider the amount of electrolytes already present in the bag.
All additions must be performed by trained personnel under aseptic conditions.
OLIMEL N9E can be supplemented with electrolytes based on the following table:

Corresponding value for the addition of inorganic phosphate
Including phosphate provided by the lipid emulsion
Trace elements and vitamins:
Stability has been demonstrated with commercially available preparations of vitamins and trace elements
(containing up to a maximum of 1 mg of iron).
Compatibility data for other additives are available upon request.
When making additions, measure the final osmolarity of the mixture before administration via peripheral vein.
To make an addition:

• Work under aseptic conditions.
• Prepare the injection site of the bag.
• Pierce the injection site and inject additives using an injection needle or reconstitution device.
• Mix the contents of the bag and the added components thoroughly.

Preparation of the infusion
The procedure must be carried out under aseptic conditions.
Suspend the bag.
Remove the plastic protective cover from the administration port.
Firmly insert the spike of the infusion set into the administration port.

Administration
For single use only.
Administer the product only after breaking the non-permanent separation membranes between
the three compartments and mixing the contents of all three compartments.
Ensure that the final infusion emulsion shows no evidence of phase separation.
After opening the bag, the contents must be used immediately. Never store an opened bag for subsequent infusion.
Do not reconnect partially used bags.
Do not connect bags in series, to avoid the risk of gas embolism due to gas contained in the primary bag.
Dispose of any unused product, waste materials, and all necessary devices.

Extravasation
The catheter site must be checked regularly for possible signs of extravasation.
In case of extravasation, administration must be stopped immediately, while leaving the catheter or cannula in place to allow immediate treatment of the patient. If possible, perform aspiration through the inserted catheter or cannula to reduce the amount of fluid in the tissues before removing the catheter or cannula.
Depending on the extravasated product (including one or more products mixed with OLIMEL N9E, if applicable) and the extent or severity of a potential injury, appropriate specific measures should be taken. Treatment options may include non-pharmacological, pharmacological, and/or surgical interventions. In case of major extravasation, seek consultation with a plastic surgeon within the first 72 hours.
The site of extravasation should be monitored at least every 4 hours during the first 24 hours, then once daily.
Infusion should not be restarted in the same central vein.

Package leaflet: Information for the user

OLIMEL

N12E infusion emulsion
Please read this leaflet carefully before this medicine is administered to you, as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or nurse.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor or nurse. See section 4.

Contents of this leaflet:

1. What OLIMEL N12E is and what it is used for
2. What you need to know before OLIMEL N12E infusion emulsion is administered to you
3. How to use OLIMEL N12E infusion emulsion
4. Possible side effects
5. How to store OLIMEL N12E infusion emulsion
6. Contents of the pack and other information

1. What OLIMEL N12E infusion emulsion is and what it is used for

OLIMEL N12E is an infusion emulsion. It is supplied as a three-compartment bag.
One compartment contains a glucose solution with calcium, the second a lipid emulsion, and
the third an amino acid solution with other electrolytes.
OLIMEL N12E is used to provide nutrition to adults and children over the age of two via
a tube inserted into a vein, when normal oral feeding is not suitable.
OLIMEL N12E must only be used under medical supervision.

2. What you need to know before OLIMEL N12E infusion emulsion is administered to you

OLIMEL N12E infusion emulsion must not be used

• In premature neonates, infants and children under 2 years of age
• If you are allergic to egg proteins, soybean seeds, peanuts, or maize/corn-derived products (see also section "Warnings and precautions" below), or to any other excipient of this medicine (listed in section 6).
• If the use of certain amino acids causes problems for your body.
• If you have particularly high levels of fats in the blood.
• If you suffer from hyperglycemia (excess sugar in the blood).
• If you have abnormally high concentrations of any of the electrolytes (sodium, potassium, magnesium, calcium and/or phosphorus) in the blood.

In all cases, your doctor will decide whether you should receive this medicine based on factors such as age, weight, and medical condition, together with the results of tests performed.

Warnings and precautions

Talk to your doctor or nurse before OLIMEL N12E is administered to you.

If total parenteral nutrition solutions are administered too rapidly, this may cause injury or death.

Infusion must be stopped immediately if unusual signs or symptoms of allergic reaction occur (such as sweating, fever, chills, headache, skin rash, or difficulty breathing). This medicine contains soybean oil and egg phospholipids. Soybeans and egg proteins may cause hypersensitivity reactions. Cross-allergic reactions between soybean and peanut proteins have been observed.

OLIMEL N12E contains glucose derived from corn, which may cause hypersensitivity reactions if you are allergic to corn or corn-derived products (see section “OLIMEL N12E infusion emulsion must not be used” above).

Difficulty in breathing may also be a sign that small particles have formed, blocking blood vessels in the lungs (pulmonary vascular precipitates). If you experience difficulty breathing, inform your doctor or nurse, who will decide which actions to take.

The antibiotic called ceftriaxone must not be mixed or administered simultaneously with any calcium-containing solution (including OLIMEL N12E) administered via intravenous infusion.

These medicines must not be administered together even through different infusion lines or at different infusion sites.

However, you may receive OLIMEL N12E and ceftriaxone sequentially, one after the other, provided different infusion sites and lines are used, or if the infusion lines are replaced or thoroughly flushed with physiological saline between infusions to prevent formation of precipitates (calcium-ceftriaxone salt particles).

Some medicines and diseases may increase the risk of developing infection or sepsis (bacteria in the blood). There is a particular risk of infection or sepsis when a tube (intravenous catheter) is inserted into a vein. Your doctor will closely monitor you for signs of infection. Patients requiring parenteral nutrition (nutrition through a tube placed in a vein) may have an increased risk of developing infections due to their underlying medical conditions. The use of aseptic techniques (germ-free) during catheter placement and maintenance, and during preparation of the nutritional formula (total parenteral nutrition), can reduce this risk.

If you are severely malnourished to the point of requiring intravenous nutrition, your doctor should start treatment slowly. Your doctor should also monitor you closely to prevent sudden changes in your fluid, vitamin, electrolyte, and mineral levels. Water and electrolyte imbalances and metabolic disorders should be corrected before starting the infusion. Your doctor will monitor your condition while you receive this medicine and may adjust the dose or add further nutrients such as vitamins, electrolytes, and trace elements if deemed appropriate.

Liver disorders, including problems with bile elimination (cholestasis), fat accumulation (hepatic steatosis), fibrosis—which could lead to liver failure—as well as cholecystitis and cholelithiasis, have been reported in patients receiving intravenous nutritional therapy. These disorders are believed to have multiple causes and may vary between patients. If you experience symptoms such as nausea, vomiting, abdominal pain, or yellowing of the skin or eyes, consult your doctor to identify possible causative and contributing factors and appropriate therapeutic and preventive measures.

Your doctor must be informed if you have:

• Severe kidney problems. You must inform your doctor if you are on dialysis (artificial kidney) or receiving another blood purification treatment;
• Severe liver problems;
• Blood clotting disorders;
• Inadequate function of the adrenal glands (adrenal insufficiency), which are triangular-shaped glands located above the kidneys;
• Heart failure;
• Lung disease;
• Fluid accumulation in the body (hyperhydration);
• Insufficient fluid in the body (dehydration);
• Untreated high blood sugar levels (diabetes mellitus);
• Heart attack or cardiogenic shock secondary to sudden heart failure;
• Severe metabolic acidosis (when blood is too acidic);
• Generalized infection (septicemia);
• Coma.

To verify the overall effectiveness and safety of administration, your doctor will perform clinical and laboratory tests while you receive this medicine. If you are to receive this medicine for several weeks, your blood will be monitored regularly.

Reduced ability of the body to clear the fats contained in this medicine may lead to a “fat overload syndrome” (see section 4 – Possible side effects).

If during infusion you experience pain, burning, or swelling at the infusion site, or leakage of the infused solution, inform your doctor or nurse. Administration will be stopped immediately and restarted in another vein.

If your blood sugar level becomes too high, your doctor will adjust the infusion rate of OLIMEL N12E or give you a medicine to control blood sugar levels (insulin).

OLIMEL N12E may be administered through a tube (catheter) inserted into a large vein in the chest (central vein).

Children and adolescents

If your child is under 18 years of age, particular attention will be paid to providing the correct dosage. Additional precautions will also be taken due to children's increased sensitivity to the risk of infection. Vitamin and trace element supplementation is always required. Pediatric formulations should be used.

Other medicines and OLIMEL N12E

Inform your doctor if you are taking or using, have recently taken or used, or might take or use any other medicines.

Concomitant administration of other medicines is generally not a contraindication. If you are taking other medicines, with or without prescription, inform your doctor in advance to verify compatibility.

Inform your doctor if you are taking or receiving any of the following:

• Insulin
• Heparin

OLIMEL N12E must not be administered simultaneously with blood through the same infusion set.

OLIMEL N12E contains calcium. It must not be administered together with the antibiotic ceftriaxone or through the same tubing, as particles may form. If the same device is used to administer these medicines sequentially, the device must be thoroughly flushed.

Due to the risk of precipitation, OLIMEL N12E must not be administered through the same infusion line or mixed with the antibiotic ampicillin or the antiepileptic fosphenytoin.

The olive and soybean oils in OLIMEL N12E contain vitamin K. This vitamin generally does not affect blood-thinning medicines (anticoagulants) such as coumarin. However, inform your doctor if you are taking anticoagulant medicines.

The lipids contained in this emulsion may interfere with the results of certain laboratory tests if the blood sample is taken before lipids have been cleared from your blood (which usually occurs after a period of 5 to 6 hours without infusion).

OLIMEL N12E contains potassium. Exercise particular caution in patients taking diuretics, ACE inhibitors, angiotensin II receptor antagonists (medicines for treatment of hypertension), or immunosuppressants. These types of medicines may increase potassium levels in the blood.

Pregnancy and breastfeeding

If you are pregnant, suspect you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor before taking this medicine.

There are no adequate experiences regarding the use of OLIMEL N12E in pregnant or breastfeeding women.

OLIMEL N12E may be considered during pregnancy and breastfeeding if necessary. OLIMEL N12E should be administered to pregnant or breastfeeding women only after careful assessment.

Fertility

Adequate data are not available.

Driving and using machines

Not relevant.

3. How to use OLIMEL N12E infusion emulsion

Dosage
OLIMEL N12E must only be administered to adults and children over two years of age.
It is an infusion emulsion, to be given through a tube (catheter) inserted into a vein in the chest.
OLIMEL N12E must be at room temperature before use.
OLIMEL N12E is for single use only.
Infusion of one bag usually lasts between 12 and 24 hours.

Dosage – Adults
Your doctor will determine an appropriate flow rate according to your individual needs and clinical condition.
Treatment may continue for as long as clinically necessary, depending on your condition.

Dosage – Children over two years of age and adolescents
Your doctor will decide the dose and duration of treatment. This will depend on age, weight, height, medical condition, and the body's ability to metabolize and utilize the components of OLIMEL N12E.

If you have been given more OLIMEL N12E infusion emulsion than you should have
If the dose administered is too high or the infusion is too fast, the amino acid content may make your blood too acidic, and symptoms of hypervolemia (increased volume of circulating blood) may occur. Blood and urine glucose levels may rise, a hyperosmolar syndrome (excessive blood viscosity) may develop, and the lipid content may increase triglyceride levels in your blood. Receiving the infusion too rapidly or an excessive volume of OLIMEL N12E may cause nausea, vomiting, chills, headache, hot flushes, excessive sweating (hyperhidrosis), and electrolyte imbalances. In such cases, the infusion must be stopped immediately.
In severe cases, your doctor may temporarily initiate renal dialysis to help your kidneys eliminate the excess product.

To prevent such events, your doctor will regularly monitor your condition and perform blood tests.

If you have any doubts about the use of OLIMEL N12E, consult your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
If you notice any changes in how you feel during or after treatment, inform your doctor or nurse immediately.
The tests your doctor will perform while you are receiving this medicine help reduce the risks of side effects.
The infusion must be stopped immediately if any unusual signs or symptoms of an allergic reaction occur, such as sweating, fever, chills, headache, skin rash, or difficulty breathing.

The following side effects have been reported with OLIMEL:

Frequency - Common: may affect up to 1 in 10 people

• Fast heart rate (tachycardia)
• Decreased appetite
• Increased blood fat levels (hypertriglyceridemia)
• Abdominal pain
• Diarrhea
• Nausea
• Increased blood pressure (hypertension)

Frequency - Not known: frequency cannot be estimated from the available data

• Hypersensitivity reactions including sweating, fever, chills, headache, skin rash (erythematous, papular, pustular, macular, generalized rash), itching, hot flushes, breathing difficulties
• Leakage of the infusion into surrounding tissue (extravasation), which may cause at the infusion site: pain, irritation, swelling/edema, redness (erythema)/warmth, tissue cell death (skin necrosis), or blisters/vesicles, inflammation, thickening or tightening of the skin
• Vomiting

With similar parenteral nutrition products, the following side effects have been reported:

Frequency - Very rare: may affect up to 1 in 10,000 people

• Reduced ability to clear lipids (fat overload syndrome), associated with a sudden and severe worsening of the patient's medical condition. The following symptoms of fat overload syndrome are usually reversible after stopping the lipid emulsion infusion:
  • Fever
  • Reduction in red blood cells, which may cause pale skin, weakness, or shortness of breath (anemia)
  • Low white blood cell count, which may increase the risk of infection (leukopenia)
  • Low platelet count, which may increase the risk of bruising and/or bleeding (thrombocytopenia)
  • Blood clotting disorders impairing the blood's ability to clot
  • High levels of fat in the blood (hyperlipidemia)
  • Fatty infiltration of the liver (hepatomegaly)
• Worsening of liver function
• Central nervous system manifestations (e.g., coma)

Frequency - Not known: frequency cannot be estimated from the available data

• Allergic reactions
• Abnormal blood test results for liver function
• Problems with bile elimination (cholestasis)
• Enlargement of the liver (hepatomegaly)
• Liver disease associated with parenteral nutrition (see "Warnings and precautions" in section 2)
• Jaundice (icterus)
• Reduction in platelet count (thrombocytopenia)
• Increased nitrogen levels in the blood (azotemia)
• Elevated liver enzymes
• Formation of small particles that may cause blockage of blood vessels in the lungs (pulmonary vascular precipitates), potentially leading to pulmonary embolism and breathing difficulties (respiratory distress)

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at:
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store OLIMEL N12E infusion emulsion

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the container and outer packaging (MM/YYYY). The expiry date refers to the last day of that month.
Do not freeze.
Store in the outer packaging.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What OLIMEL N12E, infusion emulsion contains
The active substances in each bag of the reconstituted emulsion are a 14.2% solution of L-amino acids
(corresponding to 14.2 g/100 mL) (alanine, arginine, glycine, histidine, isoleucine, leucine, lysine
(as lysine acetate), methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine,
aspartic acid, glutamic acid) with electrolytes (sodium, potassium, magnesium, phosphate, acetate,
chloride), a 17.5% lipid emulsion (corresponding to 17.5 g/100 mL) (purified olive oil and purified soybean oil), and a 27.5% glucose solution (corresponding to 27.5 g/100 mL) (as glucose monohydrate) with calcium.
The other excipients are:
Compartment Compartment Compartment
Lipid emulsion Amino acid solution Glucose and
and electrolytes calcium solution
Purified egg phospholipids, Glacial acetic acid (for pH Hydrochloric acid (for pH
glycerol, sodium oleate, adjustment), water for adjustment), water for
sodium hydroxide (for pH preparations for injectable preparations for
adjustment), water for preparations injectable injectable
preparations
Appearance of OLIMEL N12E, infusion emulsion and contents of the packaging
OLIMEL N12E is an infusion emulsion supplied in a three-compartment bag. One compartment contains a lipid emulsion, another compartment contains an amino acid solution with electrolytes, and the third compartment contains a glucose solution with calcium. These compartments are separated by non-permanent membranes. Before administration, the contents of the compartments must be mixed by rolling the bag on itself from the top until the membranes open.
Appearance before reconstitution:
The amino acid and glucose solutions are clear, colorless or slightly yellow.
The lipid emulsion is homogeneous with a milky appearance.
Appearance after reconstitution: Homogeneous emulsion with a milky appearance.
The three-compartment bag is made of multilayer plastic. The material of the inner layer (in contact) of the bag is designed to be compatible with the components and authorized additives.
To prevent contact with atmospheric oxygen, the bag is packaged in an outer oxygen-barrier pouch containing an oxygen-absorbing sachet.
Packaging:
650 mL bag: 1 box containing 10 bags; 1 box containing 5 bags
1,000 mL bag: 1 box containing 6 bags; 1 box containing 5 bags
1,500 mL bag: 1 box containing 4 bags; 1 box containing 5 bags
2,000 mL bag: 1 box containing 4 bags; 1 box containing 5 bags
1 bag of 650 mL, 1,000 mL, 1,500 mL, and 2,000 mL
Not all pack sizes may be marketed.
Marketing Authorization Holder
Baxter S.p.A.
Via Del Serafico 89
00142 Rome
Italy
Manufacturer:
Baxter S.A.,
Boulevard Rene Branquart, 80
7860 Lessines
Belgium
This medicinal product is authorized in the European Economic Community member states under the following names:
Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Estonia, France, Greece, Italy, Latvia, Lithuania,
Luxemburg, The Netherlands, Romania, Slovenia, Slovakia, Spain:

Austria:
< ZentroOLIMEL 7.6 % with Electrolytes>
Germany:
< Olimel 7.6 % E >
Denmark, Iceland, Sweden, Norway, Finland, Poland, Portugal:

Ireland, Malta, The United Kingdom:
< TRIOMEL 12 g/l nitrogen 950 kcal/l with electrolytes>
Hungary:
< Olimel 12 g/l nitrogén elektrolitokkal emulziós infúzió

---

The following information is intended exclusively for physicians or healthcare professionals:
A. QUALITATIVE AND QUANTITATIVE COMPOSITION
OLIMEL N12E is supplied as a three-compartment bag.
Each bag contains a glucose solution with calcium, a lipid emulsion, and an amino acid solution with other electrolytes:

Composition of the reconstituted emulsion after mixing the contents of the three compartments:

The excipients are:
Compartment Compartment Compartment
Lipid emulsion Amino acid solution Glucose and calcium
and electrolytes solution
Purified egg phospholipids, Glacial acetic acid (for Hydrochloric acid (for
glycerol, sodium oleate, sodium pH adjustment), water for pH adjustment), water for
hydroxide (for pH adjustment), preparations for injectable preparations for injectable
water for preparations for injectable use
injectable use
Nutritional content of the reconstituted emulsion for each bag size:

B. DOSAGE AND ADMINISTRATION
Dosage
The use of OLIMEL N12E is not recommended in children under 2 years of age due to the composition and volume being unsuitable (see sections 4.4, 5.1 and 5.2 of the SmPC).
Do not exceed the maximum daily dose indicated below. Due to the fixed composition of the multi-chamber bag, it may not be possible to simultaneously meet all the patient's nutritional requirements. There may be clinical situations where patients require varying amounts of nutrients compared to the fixed composition of the bag. In such cases, any adjustment in volume (dose) must take into account the resulting effect on the dosage of all other nutrients in OLIMEL N12E. In these circumstances, healthcare professionals may consider adjusting the volume (dose) of OLIMEL N12E to meet such increased requirements.

In adults:
The dosage depends on energy expenditure, clinical condition, body weight, and the patient's ability to metabolize the components of OLIMEL N12E, as well as any additional energy or protein provided orally/enterally; therefore, the bag size should be selected accordingly.
Average daily requirements are:

• 0.16–0.35 g nitrogen/kg body weight (1–2 g amino acids/kg), depending on the patient's nutritional status and degree of catabolic stress. Special populations may require up to 0.4 g nitrogen/kg body weight (2.5 g amino acids/kg).
• 20–40 kcal/kg,
• 20–40 mL fluids/kg or 1–1.5 mL per kcal expended.

For OLIMEL N12E, the maximum daily dose is defined by the amino acid intake, 26 mL/kg, corresponding to 2.0 g/kg amino acids, 1.9 g/kg glucose, and 0.9 g/kg lipids. For a 70 kg patient, this would be equivalent to 1,820 mL of OLIMEL N12E per day, resulting in an intake of 138 g amino acids, 133 g glucose, and 64 g lipids (i.e., 1,171 non-protein kcal and 1,723 total kcal).

In continuous renal replacement therapy (CRRT): For OLIMEL N12E, the maximum daily dose is defined by amino acid intake, 33 mL/kg, corresponding to 2.5 g/kg amino acids, 2.4 g/kg glucose, and 1.2 g/kg lipids. For a 70 kg patient, this would equate to 2,310 mL of OLIMEL N12E per day, resulting in an intake of 175 g amino acids, 169 g glucose, and 81 g lipids (i.e., 1,486 non-protein kcal and 2,187 total kcal).

In patients with morbid obesity: Dosage should be calculated based on ideal body weight (IBW). For OLIMEL N12E, the maximum daily dose is defined by amino acid intake, 33 mL/kg IBW, corresponding to 2.5 g/kg amino acids, 2.4 g/kg glucose, and 1.2 g/kg lipids. For a 70 kg patient, this would equate to 2,310 mL of OLIMEL N12E per day, resulting in an intake of 175 g amino acids, 169 g glucose, and 81 g lipids (i.e., 1,486 non-protein kcal and 2,187 total kcal).

Normally, the infusion rate should be gradually increased during the first hour, then adjusted according to the required dose, daily volumes to be administered, and duration of infusion.
For OLIMEL N12E, the maximum infusion rate is 1.3 mL/kg/hour, corresponding to 0.10 g/kg/hour of amino acids, 0.10 g/kg/hour of glucose, and 0.05 g/kg/hour of lipids.

In children over 2 years of age and adolescents:
No studies have been conducted in the pediatric population.
Dosage depends on energy expenditure, clinical condition, body weight, and the patient's ability to metabolize the components of OLIMEL N12E, as well as any additional energy or protein provided orally/enterally; therefore, the bag size should be selected accordingly.
Furthermore, daily requirements for fluids, nitrogen, and energy continuously decrease with age. Two age groups have been considered: 2 to 11 years and 12 to 18 years.
For OLIMEL N12E in the 2 to 11-year age group, the concentrations of amino acids and magnesium are the limiting factors for the daily dosage. In this age group, the amino acid concentration is the limiting factor for the hourly rate.
In the 12 to 18-year age group, the concentrations of amino acids and magnesium are the limiting factors for the daily dosage. In this age group, the amino acid concentration is the limiting factor for the hourly rate. The resulting intakes are shown below:

Normally, the flow rate should be gradually increased during the first hour and then adjusted according to the dose to be administered, the daily volume requirement, and the duration of infusion.
In general, in young children it is recommended to start the infusion with a low daily dose, gradually increasing it to the maximum dosage (see above).
The maximum infusion rate is 2.6 ml/kg/hour in children aged between 2 and 11 years and 1.6 ml/kg/hour in children aged between 12 and 18 years.

Mode and duration of administration
For single use only.
It is recommended to use the contents immediately after opening the bag and not to store it for subsequent infusions.
After reconstitution, the mixture is homogeneous and has a milky appearance.
For instructions on the preparation and handling of the infusion emulsion, see section 6.6 of the Summary of Product Characteristics.
Due to its high osmolarity, OLIMEL N12E must be administered only through a central vein.
The recommended infusion duration for a parenteral nutrition bag is between 12 and 24 hours.
Parenteral nutrition treatment may continue for as long as required by the patient's clinical condition.

C. INCOMPATIBILITIES
Do not add any other medicinal product or substances to any of the bag components or to the reconstituted emulsion without first verifying compatibility and stability of the resulting preparation (particularly the stability of the lipid emulsion).
Incompatibilities may arise, for example, from excessive acidity (low pH) or unsuitable content of bivalent cations (Ca and Mg), which may destabilize the lipid emulsion.
As with any other parenteral nutrition mixture, the calcium/phosphate ratio must be considered. Excessive addition of calcium and phosphate, particularly in the form of mineral salts, may lead to precipitation of calcium phosphate.
OLIMEL N12E contains calcium ions, which pose an additional risk of coagulation in blood or in anticoagulated or citrate-preserved blood components.
Ceftriaxone must not be mixed or administered concomitantly with intravenous solutions containing calcium, including OLIMEL N12E, through the same infusion line (e.g., via a Y-connector) due to the risk of precipitation of ceftriaxone-calcium salt (see sections 4.4 and 4.5 of the SmPC). Ceftriaxone and calcium-containing solutions may be administered sequentially if different infusion sites are used, or if the infusion lines are replaced or thoroughly flushed with physiological saline between infusions to prevent precipitate formation.
Due to the risk of precipitation, OLIMEL N12E must not be administered through the same infusion line or mixed with the antibiotic ampicillin or the antiepileptic fosphenytoin.
Check compatibility with solutions administered simultaneously through the same infusion set, catheter, or cannula.
Do not administer before, simultaneously with, or immediately after a blood transfusion via the same line, due to the risk of pseudoagglutination.

D. SPECIAL PRECAUTIONS FOR DISPOSAL AND HANDLING
An overview of the various steps in preparing OLIMEL N12E for administration is shown in Figure 1.

Opening
Remove the outer protective envelope.
Discard the oxygen absorber bag.
Check the integrity of the bag and the non-permanent separation membranes. Use only if the bag is undamaged, the non-permanent separation membranes are intact (i.e., no mixing of the contents of the three compartments has occurred), the amino acid solution and glucose solution are clear, colourless or slightly yellow, and practically free from visible particles, and the lipid emulsion is a homogeneous liquid with a milky appearance.

Mixing of solutions and emulsion
Ensure the product is at room temperature when breaking the non-permanent separation membranes.
Manually roll the bag from top to bottom (end with loop). The non-permanent separation membranes will disappear from the side adjacent to the openings.
Continue rolling the bag until the separation membranes are opened approximately halfway along their length.
Mix the bag by inverting it at least three times.
After reconstitution, the mixture is a homogeneous emulsion with a milky appearance.

Additions:
The bag has sufficient capacity to allow additions such as vitamins, electrolytes, and trace elements.
Any addition (including vitamins) should be made into the reconstituted mixture (after opening the non-permanent separation membranes and after mixing the contents of the three compartments).
Vitamins may also be added to the glucose compartment before the mixture is reconstituted (before opening the non-permanent separation membranes and before mixing the three compartments).
All additions must be performed by trained personnel under aseptic conditions.
The OLIMEL N12E formulation can be supplemented with electrolytes, inorganic/organic phosphate, and commercially available multi-vitamin (e.g., Cernevit) and multi-trace element (e.g., Nutryelt) preparations. The maximum total additive levels listed in the table below have been established based on stability data and should not be interpreted as dosage recommendations. Supplementation should be based on the patient's clinical needs and must not exceed nutritional guidelines. The electrolytes already present in the bag should be taken into account when determining the total maximum levels.
Compatibility may vary between products from different sources, and healthcare professionals are advised to perform appropriate checks when mixing OLIMEL N12E with other parenteral solutions.

To perform an addition:

• Work under aseptic conditions.
• Prepare the injection site of the bag.
• Puncture the injection site and inject additives using an injection needle or a reconstitution device.
• Mix the contents of the bag and the added substances.

Stability after reconstitution:
Chemical and physical stability during use has been demonstrated for 7 days at 2°C - 8°C, followed by 48 hours at a temperature not exceeding 30°C.
From a microbiological standpoint, the product should be used immediately. If not used immediately, the times and conditions of storage during use and prior to use are the responsibility of the user and normally should not exceed 24 hours at 2-8°C, unless reconstitution was carried out under controlled and validated aseptic conditions.

Stability after addition of supplements:
For specific mixtures, chemical and physical stability during use has been demonstrated for 7 days at 2°C - 8°C, followed by 48 hours at a temperature not exceeding 30°C.
From a microbiological standpoint, any mixture should be used immediately. Otherwise, the times and conditions of storage during use after mixing and prior to use are the responsibility of the user and normally should not exceed 24 hours at 2°C - 8°C, unless the addition of supplements was carried out under controlled and validated aseptic conditions.

Preparation of infusion
The procedure must be performed under aseptic conditions.
Suspend the bag.
Remove the plastic protector from the administration port.
Firmly insert the spike of the infusion set into the administration port.

Figure 1. Administration procedure for OLIMEL

Administration
For single use only.
Administer the product only after breaking the non-permanent separating membranes between the 3 compartments and mixing the contents of the 3 compartments.
Ensure that the final emulsion for infusion shows no evidence of phase separation.
After opening the bag, the contents must be used immediately. Never store an opened bag for subsequent infusion.
Do not reconnect partially used bags.
Do not connect bags in series, to avoid the risk of gas embolism due to gas contained in the main bag.
Dispose of any unused product, any waste material, and all necessary devices.

Extravasation
The catheter site should be regularly checked for possible signs of extravasation.
In case of extravasation, administration must be immediately stopped while maintaining the catheter or cannula in place for immediate patient treatment. If possible, perform aspiration through the inserted catheter or cannula to reduce the amount of fluid present in the tissues before removing the catheter or cannula.
Depending on the extravasated product (including one or more products mixed with OLIMEL N12E, if applicable) and the extent or severity of a potential injury, appropriate specific measures should be taken. Treatment options may include non-pharmacological, pharmacological, and/or surgical interventions. In case of major extravasation, consult a plastic surgeon within the first 72 hours.
The extravasation site should be monitored at least every 4 hours during the first 24 hours, then once daily.
Infusion should not be restarted in the same central vein.

Package leaflet: Information for the user

OLIMEL

N12 infusion emulsion
Please read this leaflet carefully before you are given this medicine, as it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, consult your doctor or nurse.
• If you experience any side effects, including those not listed in this leaflet, consult your doctor or nurse. See section 4.

Contents of this leaflet:

1. What OLIMEL N12 is and what it is used for
2. What you need to know before you are given OLIMEL N12 infusion emulsion
3. How to use OLIMEL N12 infusion emulsion
4. Possible side effects
5. How to store OLIMEL N12 infusion emulsion
6. Contents of the pack and other information

1. What OLIMEL N12 infusion emulsion is and what it is used for

OLIMEL N12 is an infusion emulsion. It is supplied as a three-compartment bag.
One compartment contains a glucose solution, the second contains a lipid emulsion, and the third
contains an amino acid solution.
OLIMEL N12 is used to provide nutrition to adults and children over two years of age through
a tube inserted into a vein, when normal oral feeding is not suitable.
OLIMEL N12 must be used exclusively under medical supervision.

2. What you need to know before OLIMEL N12 infusion emulsion is administered to you

OLIMEL N12 infusion emulsion must not be used

• In premature neonates, infants and children under 2 years of age
• If you are allergic to egg proteins, soybean seeds, peanuts, or maize/corn or corn-derived products (see also section "Warnings and precautions" below), or to any other excipient of this medicine (listed in section 6)
• If the use of certain amino acids causes problems in your body
• If you have particularly high levels of fats in your blood
• If you suffer from hyperglycemia (excessively high blood sugar)

In all cases, your doctor will decide whether you should receive this medicine based on factors such as age, weight, medical condition, and test results.

Warnings and precautions

Talk to your doctor or nurse before OLIMEL N12 is administered to you.

If total parenteral nutrition solutions are administered too rapidly, this may cause injury or death.

The infusion must be stopped immediately if signs or symptoms of an allergic reaction occur (such as sweating, fever, chills, headache, skin rash, or difficulty breathing). This medicine contains soybean oil and egg phospholipids. Soybeans and egg proteins may cause hypersensitivity reactions. Cross-allergic reactions between soy and peanut proteins have been observed.

OLIMEL N12 contains glucose derived from corn, which may cause hypersensitivity reactions if you are allergic to corn or corn-derived products (see section "OLIMEL N12 infusion emulsion must not be used" above).

Difficulty in breathing may also be a sign of small particles forming and blocking blood vessels in the lungs (pulmonary vascular precipitates). If you experience breathing difficulties, inform your doctor or nurse, who will decide on the necessary actions.

Some medicines and medical conditions may increase the risk of developing infection or sepsis (bacteria in the blood). There is a particular risk of infection or sepsis when a tube (intravenous catheter) is inserted into a vein. Your doctor will closely monitor you for any signs of infection. Patients requiring parenteral nutrition (nutrition delivered through a vein) may have an increased risk of infections due to their underlying medical conditions. Using aseptic techniques (germ-free) during catheter insertion and maintenance, and during the preparation of the nutritional formula (total parenteral nutrition), can reduce this risk.

If you are severely malnourished and require intravenous nutritional support, your doctor should start treatment slowly. Your doctor should also monitor you closely to prevent sudden changes in your fluid, vitamin, electrolyte, and mineral levels. Water and electrolyte imbalances and metabolic disorders should be corrected before starting the infusion. Your doctor will monitor your condition during treatment and may adjust the dose or add additional nutrients such as vitamins, electrolytes, and trace elements as appropriate.

Liver disorders, including impaired bile elimination (cholestasis), fat accumulation (hepatic steatosis), fibrosis—which may lead to liver failure—as well as cholecystitis and cholelithiasis, have been reported in patients receiving intravenous nutritional therapy. These disorders are believed to result from multiple factors and may vary between patients. If you experience symptoms such as nausea, vomiting, abdominal pain, or yellowing of the skin or eyes (jaundice), consult your doctor to identify possible causative and contributing factors and to consider appropriate therapeutic and preventive measures.

You must inform your doctor if you have:

• Severe kidney problems. You must inform your doctor if you are on dialysis (artificial kidney) or undergoing another blood purification treatment
• Severe liver problems
• Blood clotting disorders
• Inadequate function of the adrenal glands (adrenal insufficiency), which are triangular-shaped glands located above the kidneys
• Heart failure
• Lung disease
• Fluid accumulation in the body (overhydration)
• Insufficient body fluids (dehydration)
• High blood sugar levels (untreated diabetes mellitus)
• Heart attack or cardiogenic shock due to sudden heart failure
• Severe metabolic acidosis (when blood is too acidic)
• Systemic infection (septicemia)
• Coma

To assess the overall effectiveness and safety of administration, your doctor will perform clinical and laboratory tests while you are receiving this medicine. If you are to receive this medicine for several weeks, your blood will be monitored regularly.

Reduced ability of the body to clear the fats contained in this medicine may lead to a "fat overload syndrome" (see section 4 - Possible side effects).

If during infusion you experience pain, burning, swelling at the infusion site, or leakage of the infusion solution, inform your doctor or nurse immediately. Administration will be stopped immediately and restarted in another vein.

If your blood sugar level becomes too high, your doctor will adjust the infusion rate of OLIMEL N12 or administer a medicine to control blood sugar levels (insulin).

OLIMEL N12 may be administered through a tube (catheter) inserted into a large vein in the chest (central vein).

Children and adolescents

If your child is under 18 years of age, special attention will be paid to ensuring the correct dosage. Additional precautions will also be taken due to children's increased susceptibility to infection risk. Vitamin and trace element supplementation is always required. Pediatric formulations must be used.

Other medicines and OLIMEL N12

Inform your doctor if you are currently taking or using, have recently taken or used, or might take or use any other medicines.

Concurrent administration of other medicines is generally not a contraindication. However, if you are taking any other medicines, whether prescription or over-the-counter, inform your doctor in advance to verify compatibility.

Inform your doctor if you are taking or receiving any of the following:

• Insulin
• Heparin

OLIMEL N12 must not be administered simultaneously with blood through the same infusion set.

Due to the risk of precipitation, OLIMEL N12 must not be administered through the same infusion line or mixed with the antibiotic ampicillin or the antiepileptic fosphenytoin.

The olive and soybean oils in OLIMEL N12 contain vitamin K. This vitamin generally does not affect blood-thinning medicines (anticoagulants) such as coumarin. However, inform your doctor if you are taking anticoagulant medicines.

The lipids contained in this emulsion may interfere with the results of certain laboratory tests if the blood sample is taken before lipids have been cleared from your blood (which usually occurs after a 5- to 6-hour period without infusion).

Pregnancy and breastfeeding

If you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding, consult your doctor before taking this medicine.

There is insufficient experience regarding the use of OLIMEL N12 in pregnant or breastfeeding women.

OLIMEL N12 may be considered during pregnancy and breastfeeding if necessary. However, OLIMEL N12 should only be administered to pregnant or breastfeeding women after careful assessment.

Fertility

Adequate data are not available.

Driving and using machines

Not applicable.

3. How to use OLIMEL N12 infusion emulsion

Dosage
OLIMEL N12 must be administered only in adults and children over two years of age.
It is an infusion emulsion, to be administered through a tube (catheter) inserted into a vein in the chest.
OLIMEL N12 must be at room temperature before use.
OLIMEL N12 is for single use only.
The infusion of one bag usually lasts between 12 and 24 hours.

Dosage – Adults
Your doctor will determine an appropriate flow rate according to your individual needs and clinical condition.
The treatment may continue for as long as clinically necessary, depending on your condition.

Dosage – Children over two years of age and adolescents
Your doctor will decide the dose and duration of treatment. This will depend on age, body weight, height, medical condition, and the body's ability to metabolize and utilize the components of OLIMEL N12.

If you have been given more OLIMEL N12 infusion emulsion than you should have received
If the administered dose is too high or the infusion is too fast, the amino acid content may make your blood too acidic, and symptoms of hypervolemia (increased volume of circulating blood) may occur. Blood and urine glucose levels may rise, a hyperosmolar syndrome (excessively viscous blood) may develop, and the lipid content may increase triglyceride levels in your blood. Receiving the infusion too rapidly or an excessive volume of OLIMEL N12 may cause nausea, vomiting, chills, headache, hot flushes, excessive sweating (hyperhidrosis), and electrolyte imbalances. In such cases, the infusion must be stopped immediately.
In severe cases, your doctor may temporarily perform renal dialysis to help your kidneys eliminate the excess product.
To prevent such events, your doctor will regularly monitor your condition and perform blood tests.
If you have any doubts about the use of OLIMEL N12, consult your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
If you notice any changes in how you feel during or after treatment, inform your doctor or nurse immediately.
The tests your doctor performs while you are receiving this medicine help reduce the risks of side effects.
The infusion must be stopped immediately if any signs or symptoms of an allergic reaction occur, such as sweating, fever, chills, headache, skin rash, or difficulty breathing.

The following side effects have been reported with OLIMEL:

Frequency – Common: may affect up to 1 in 10 people

• Fast heart rate (tachycardia)
• Decreased appetite
• Increased levels of fat in the blood (hypertriglyceridemia)
• Abdominal pain
• Diarrhea
• Nausea
• Increased blood pressure (hypertension)

Frequency – Not known: frequency cannot be estimated from the available data

• Hypersensitivity reactions including sweating, fever, chills, headache, skin rash (erythematous, papular, pustular, macular, generalized skin rash), itching, hot flushes, breathing difficulties
• Leakage of the infusion into surrounding tissue (extravasation), which may cause at the infusion site: pain, irritation, swelling/edema, redness (erythema)/warmth, death of tissue cells (skin necrosis), or blisters/vesicles, inflammation, thickening or tightening of the skin
• Vomiting

The following side effects have been reported with similar parenteral nutrition products:

Frequency – Very rare: may affect up to 1 in 10,000 people

• Reduced ability to clear lipids (fat overload syndrome), associated with a sudden and severe worsening of the patient's medical condition. The following symptoms of fat overload syndrome are usually reversible after stopping the lipid emulsion infusion:
  • Fever
  • Reduction in red blood cells, which may cause pale skin, weakness, or shortness of breath (anaemia)
  • Low white blood cell count, which may increase the risk of infection (leucopenia)
  • Low platelet count, which may increase the risk of bruising and/or bleeding (thrombocytopenia)
  • Blood clotting disorders, impairing the blood’s ability to clot
  • High levels of fat in the blood (hyperlipidaemia)
  • Fatty infiltration of the liver (hepatomegaly)
  • Worsening of liver function
  • Central nervous system manifestations (e.g., coma)

Frequency – Not known: frequency cannot be estimated from the available data

• Allergic reactions
• Abnormal blood test results for liver function
• Problems with bile elimination (cholestasis)
• Enlargement of the liver (hepatomegaly)
• Liver disease associated with parenteral nutrition (see "Warnings and precautions" in section 2)
• Jaundice (jaundice)
• Decreased platelet count (thrombocytopenia)
• Increased levels of nitrogen in the blood (azotaemia)
• Elevated liver enzymes
• Formation of small particles that may cause blockage of blood vessels in the lungs (pulmonary vascular precipitates), leading to pulmonary vascular embolism and breathing difficulties (respiratory distress)

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at:
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store OLIMEL N12 emulsion for infusion

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the container and outer packaging (MM/YYYY). The expiry date refers to the last day of that month.
Do not freeze.
Store in the outer packaging.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer used. This will help protect the environment.

6. Package contents and other information

What OLIMEL N12, infusion emulsion contains
The active substances in each bag of the reconstituted emulsion are a solution of L-amino acids at
14.2% (equivalent to 14.2 g/100 mL) (alanine, arginine, glycine, histidine, isoleucine, leucine, lysine
(as lysine acetate), methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine,
aspartic acid, glutamic acid), a lipid emulsion at 17.5% (equivalent to 17.5 g/100 mL) (purified olive oil and purified soybean oil), and a glucose solution at 27.5% (equivalent to 27.5 g/100 mL) (as glucose monohydrate).
Other excipients:
Compartiment Compartiment Compartiment
Lipid emulsion Amino acid solution Glucose solution
Purified egg phospholipids, Glacial acetic acid (for pH Hydrochloric acid (for pH
glycerol, sodium oleate, adjustment), adjustment),
sodium hydroxide (for pH Water for injections
adjustment), water for Water for injections
injections

Appearance of OLIMEL N12, infusion emulsion and contents of the packaging
OLIMEL N12 is an infusion emulsion supplied in a three-compartment bag. One compartment contains a lipid emulsion, another compartment an amino acid solution, and the third compartment a glucose solution. These compartments are separated by non-permanent membranes. Prior to administration, the contents of the compartments must be mixed by rolling the bag on itself from top to bottom until the membranes open.
Appearance before reconstitution:
The amino acid and glucose solutions are clear, colorless or slightly yellow.
The lipid emulsion is homogeneous with a milky appearance.
Appearance after reconstitution: Homogeneous emulsion with a milky appearance.
The three-compartment bag is made of multilayer plastic. The material of the inner layer (in contact) of the bag is designed to be compatible with the authorized constituents and additives.
To prevent contact with atmospheric oxygen, the bag is packaged in an outer oxygen-barrier pouch containing an oxygen-absorbing sachet.
Packaging:
650 mL bag: 1 box containing 10 bags; 1 box containing 5 bags
1,000 mL bag: 1 box containing 6 bags
1,500 mL bag: 1 box containing 4 bags
2,000 mL bag: 1 box containing 4 bags
1 bag of 650 mL, 1,000 mL, 1,500 mL and 2,000 mL
Not all pack sizes may be marketed.
Marketing Authorization Holder
Baxter S.p.A.
Via Del Serafico 89
00142 Rome
Italy
Manufacturer:
Baxter S.A.,
Boulevard Rene Branquart, 80
7860 Lessines
Belgium
This medicinal product is authorized in the European Economic Community member states under the following names:
Belgium, Czech Republic, France, Greece, Italy, Luxembourg, The Netherlands, Slovenia, Spain:

Austria:

Germany:

Denmark, Iceland, Sweden, Norway, Finland, Portugal:

Ireland, Malta, The United Kingdom:
< TRIOMEL 12 g/l nitrogen 950 kcal

---

The following information is intended exclusively for physicians or healthcare professionals:
A. QUALITATIVE AND QUANTITATIVE COMPOSITION
OLIMEL N12 is supplied as a three-compartment bag.
Each bag contains a glucose solution, a lipid emulsion, and an amino acid solution:

Composition of the reconstituted emulsion after mixing the contents of the three compartments:

The excipients are:
Compartment Compartment Compartment
Lipid emulsion Amino acid solution Glucose solution
Purified egg phospholipids, Glacial acetic acid (for Hydrochloric acid (for
glycerol, sodium oleate, sodium pH adjustment), pH adjustment),
hydroxide (for pH adjustment), water for injectable water for injectable
water for injectable preparations preparations
preparations
Nutritional contribution of the reconstituted emulsion for each bag size:

B. DOSAGE AND ADMINISTRATION
Dosage
The use of OLIMEL N12 is not recommended in children under 2 years of age due to its composition and volume being unsuitable (see sections 4.4, 5.1 and 5.2 of the SmPC).
Do not exceed the maximum daily dose indicated below. Because of the fixed composition of the multi-chamber bag, it may not be possible to simultaneously meet all the patient's nutritional requirements. There may be clinical situations in which patients require variable amounts of nutrients compared to the fixed composition of the bag. In such cases, any adjustment of volume (dose) must take into account the resulting effect on the dosage of all other nutrients in OLIMEL N12. In these circumstances, healthcare providers may consider adjusting the volume (dose) of OLIMEL N12 to meet increased requirements.

In adults:
Dosage depends on energy expenditure, clinical condition, body weight, and the patient's ability to metabolize the components of OLIMEL N12, as well as on additional energy or protein provided orally/enterally; therefore, the appropriate bag size should be selected accordingly.
Average daily requirements are:

• 0.16–0.35 g nitrogen/kg body weight (1–2 g amino acids/kg), depending on the patient's nutritional status and degree of catabolic stress. Special populations may require up to 0.4 g nitrogen/kg body weight (2.5 g amino acids/kg).
• 20–40 kcal/kg,
• 20–40 mL fluids/kg or 1–1.5 mL per kcal expended.

For OLIMEL N12, the maximum daily dose is defined by amino acid intake: 26 mL/kg, corresponding to 2.0 g/kg amino acids, 1.9 g/kg glucose, and 0.9 g/kg lipids. For a 70 kg patient, this would be equivalent to 1820 mL of OLIMEL N12 per day, resulting in an intake of 138 g amino acids, 133 g glucose, and 64 g lipids (i.e., 1,171 non-protein kcal and 1,723 total kcal).

In continuous renal replacement therapy (CRRT): For OLIMEL N12, the maximum daily dose is defined by amino acid intake: 33 mL/kg, corresponding to 2.5 g/kg amino acids, 2.4 g/kg glucose, and 1.2 g/kg lipids. For a 70 kg patient, this would correspond to 2,310 mL of OLIMEL N12 per day, resulting in an intake of 175 g amino acids, 169 g glucose, and 81 g lipids (i.e., 1,486 non-protein kcal and 2,187 total kcal).

In patients with morbid obesity: Dosage should be calculated based on ideal body weight (IBW). For OLIMEL N12, the maximum daily dose is defined by amino acid intake: 33 mL/kg IBW, corresponding to 2.5 g/kg amino acids, 2.4 g/kg glucose, and 1.2 g/kg lipids. For a 70 kg patient, this would correspond to 2,310 mL of OLIMEL N12 per day, resulting in an intake of 175 g amino acids, 169 g glucose, and 81 g lipids (i.e., 1,486 non-protein kcal and 2,187 total kcal).

Normally, the infusion rate should be gradually increased during the first hour, then adjusted according to the required dose, daily volume to be administered, and duration of infusion.
For OLIMEL N12, the maximum infusion rate is 1.3 mL/kg/hour, except for patients receiving intradialytic parenteral nutrition (IDPN), corresponding to 0.10 g/kg/hour amino acids, 0.10 g/kg/hour glucose, and 0.05 g/kg/hour lipids.

Patients receiving intradialytic parenteral nutrition (IDPN): Intradialytic parenteral nutrition is intended for patients with non-acute malnutrition. The choice of appropriate Olimel formulation and volume for IDPN should be guided by the gap between spontaneous intake (as estimated, for example, by dietary interview) and recommended intake. In addition, metabolic tolerance must be taken into consideration. For OLIMEL N12, in IDPN patients, the maximum hourly infusion rate is 2.7 mL/kg/hour, corresponding to 0.2 g/kg/hour amino acids, 0.2 g/kg/hour glucose, and 0.09 g/kg/hour lipids administered over more than 4 hours.

In children over 2 years of age and adolescents
No studies have been conducted in the pediatric population.
Dosage depends on energy expenditure, clinical condition, body weight, and the patient's ability to metabolize the components of OLIMEL N12, as well as on additional energy or protein provided orally/enterally; therefore, the appropriate bag size should be selected accordingly.
Furthermore, daily requirements for fluids, nitrogen, and energy continuously decrease with age. Two age groups have been considered: 2 to 11 years and 12 to 18 years.
For Olimel N12, in the 2- to 11-year age group, the amino acid concentration is the limiting factor for both daily dosage and hourly infusion rate.
In the 12- to 18-year age group, the amino acid concentration is the limiting factor for both daily dosage and hourly infusion rate.
The resulting intakes are shown below:

The infusion flow rate should normally be gradually increased during the first hour, then adjusted according to the dose to be administered, daily volume requirements, and duration of infusion.
In general, for young children, it is recommended to start infusion with a low daily dose, gradually increasing it to the maximum dosage (see above).
The maximum infusion rate is 2.6 ml/kg/hour in children aged 2 to 11 years and 1.6 ml/kg/hour in children aged 12 to 18 years.

Mode and duration of administration
For single use only.
The contents of the bag should be used immediately after opening, and must not be stored for subsequent infusions.
After reconstitution, the mixture is homogeneous and has a milky appearance.
For instructions on the preparation and handling of the infusion emulsion, see section 6.6 of the Summary of Product Characteristics.
Due to its high osmolarity, OLIMEL N12 must be administered only through a central vein.
The recommended duration of infusion for a parenteral nutrition bag is between 12 and 24 hours.
Parenteral nutrition treatment may continue for as long as clinically indicated by the patient's condition.

C. INCOMPATIBILITIES
Do not add any other medicinal product or substance to any of the bag components or to the reconstituted emulsion without first verifying compatibility and stability of the resulting preparation (particularly the stability of the lipid emulsion).
Incompatibilities may arise, for example, from excessive acidity (low pH) or inappropriate content of bivalent cations (Ca and Mg), which may destabilize the lipid emulsion.
As with any other parenteral nutrition mixture, the calcium/phosphate ratio must be considered. Excessive addition of calcium and phosphate, particularly in the form of mineral salts, may lead to precipitation of calcium phosphate.
Due to the risk of precipitation, OLIMEL N12 must not be administered through the same infusion line or mixed with the antibiotic ampicillin or the anticonvulsant fosphenytoin.
Check compatibility with solutions administered simultaneously through the same infusion set, catheter, or cannula.
Do not administer before, during, or after blood transfusion through the same line, due to the risk of pseudoagglutination.

D. SPECIAL PRECAUTIONS FOR DISPOSAL AND HANDLING
An overview of the various steps in preparing OLIMEL N12 for administration is shown in Figure 1.

Opening
Remove the outer protective wrapper.
Discard the oxygen absorber bag.
Check the integrity of the bag and the non-permanent separation membranes. Use only if the bag is undamaged, the non-permanent separation membranes are intact (i.e., no mixing of the contents of the three compartments has occurred), the amino acid solution and glucose solution are clear, colorless or slightly yellow, and practically free from visible particles, and the lipid emulsion is a homogeneous liquid with a milky appearance.

Mixing of solutions and emulsion
Ensure the product is at room temperature when breaking the non-permanent separation membranes.
Manually roll the bag onto itself, starting from the top (end with loop). The non-permanent separation membranes will disappear from the side adjacent to the openings.
Continue rolling the bag until the separation membranes are opened along approximately half their length.
Mix the bag by inverting it at least three times.
After reconstitution, the mixture is a homogeneous emulsion with a milky appearance.

Additions:
The bag has sufficient capacity to allow additions such as vitamins, electrolytes, and trace elements.
Any addition (including vitamins) should be made to the reconstituted mixture (after opening the non-permanent separation membranes and after mixing the contents of the three compartments).
Vitamins may also be added to the glucose compartment before reconstitution (before opening the non-permanent separation membranes and before mixing the three compartments).
All additions must be performed by trained personnel under aseptic conditions.
OLIMEL N12 formulation may be supplemented with electrolytes, inorganic/organic phosphate, and commercially available multi-vitamin (e.g., Cernevit) and multi-trace element (e.g., Nutryelt) preparations. The maximum total levels of additives listed in the table below have been established based on stability data and should not be interpreted as dosage recommendations. Supplementation must be based on the patient's clinical needs and must not exceed nutritional guidelines. The electrolytes already present in the bag should be taken into account when reaching the maximum total levels.
Compatibility may vary between products from different sources, and healthcare professionals are advised to perform appropriate checks when mixing OLIMEL N12 with other parenteral solutions.

To perform an addition:

• Operate under aseptic conditions.
• Prepare the injection site of the bag.
• Pierce the injection site and inject additives using an injection needle or a reconstitution device.
• Mix the contents of the bag and the added substances.

Stability after reconstitution:
Chemical and physical in-use stability has been demonstrated for 7 days at 2°C - 8°C, followed by 48 hours at a temperature not exceeding 30°C.
From a microbiological standpoint, the product should be used immediately. If not used immediately, the storage times and conditions during use prior to administration are the responsibility of the user and should normally not exceed 24 hours at 2-8°C, unless reconstitution was carried out under controlled and validated aseptic conditions.

Stability after addition of supplements:
For specific mixtures, chemical and physical in-use stability has been demonstrated for 7 days at 2°C - 8°C, followed by 48 hours at a temperature not exceeding 30°C.
From a microbiological standpoint, any mixture should be used immediately. Otherwise, the times and conditions of storage during use after mixing and prior to administration are the responsibility of the user and should normally not exceed 24 hours at 2°C - 8°C, unless the addition of supplements was performed under controlled and validated aseptic conditions.

Preparation of the infusion
The procedure must be carried out under aseptic conditions.
Suspend the bag.
Remove the plastic protector from the administration port.
Firmly insert the spike of the infusion set into the administration port.

Figure 1. Procedure for administration of OLIMEL

Administration
For single use only.
Administer the product only after breaking the non-permanent separating membranes between the 3 compartments and mixing the contents of all 3 compartments.
Ensure that the final emulsion for infusion shows no evidence of phase separation.
After opening the bag, the contents must be used immediately. Never store an opened bag for subsequent infusion.
Do not reconnect partially used bags.
Do not connect bags in series, to avoid the risk of gas embolism due to gas contained in the primary bag.
Dispose of any unused product, waste materials, and all necessary devices.

Extravasation
The catheter site should be regularly checked for possible signs of extravasation.
In case of extravasation, administration must be stopped immediately, while maintaining the catheter or cannula in place to allow immediate patient treatment. If possible, perform aspiration through the inserted catheter or cannula to reduce the amount of fluid present in the tissues before removing the catheter or cannula.
Depending on the extravasated product (including one or more products mixed with OLIMEL N12, if applicable) and the extent or severity of a potential injury, appropriate specific measures should be taken. Treatment options may include non-pharmacological, pharmacological, and/or surgical interventions. In case of extensive extravasation, consult a plastic surgeon within the first 72 hours.
The site of extravasation should be monitored at least every 4 hours during the first 24 hours, then once daily.
Infusion should not be restarted in the same central vein.