Olimel N12E emulsion for infusion: detailed information

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Olimel N12E infusion emulsion

Read the entire leaflet carefully before you are given this medicine, because it contains important information for you.

Keep this leaflet, as you may need to read it again.
If you have any questions, ask your doctor or nurse.
If you experience any adverse reactions, consult your doctor or nurse, even if they are adverse reactions not listed in this leaflet. See section 4.

Contents of the leaflet

What Olimel N12E is and what it is used for
What you need to know before you are given Olimel N12E
How Olimel N12E will be administered to you
Possible adverse effects
How to store Olimel N12E

6. Contents of the pack and other information

1. What Olimel N12E is and what it is used for

Olimel N12E is an infusion emulsion. It is supplied in a three-compartment bag.

One compartment contains a glucose solution with calcium, the second contains a lipid emulsion, and the third contains an amino acid solution with other electrolytes.

Olimel N12E is used to provide nutrition to adults and children over 2 years of age through a vein when normal oral feeding is not possible.

Olimel N12E should only be used under medical supervision.

2. What you need to know before Olimel N12E is administered to you

Olimel N12E must not be administered:

In premature neonates, infants, and children under two years of age
If you are allergic to egg proteins, soybean seeds, peanuts, corn/corn products (see also the section “Warnings and precautions” below), or to any of the other components of this medicine (listed in section 6).
If your body has difficulty utilizing certain amino acids.
If you have particularly high levels of fats in the blood
If you have hyperglycemia (too much sugar in the blood)
If you have abnormally high levels of any electrolyte (sodium, potassium, magnesium, calcium, and/or phosphorus) in the blood.

In all cases, your doctor will decide whether this medicine should be administered to you based on factors such as your age, weight, and clinical condition, along with the results of all tests performed.

Warnings and precautions

Consult your doctor or nurse before Olimel N12E is administered to you.

Administering total parenteral nutrition (TPN) solutions too rapidly may cause injury or death.

Infusion must be stopped immediately if any abnormal 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. Soybean and egg proteins may cause hypersensitivity reactions. Cross-allergic reactions between soybean seed proteins 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 products (see section “Olimel N12E must not be administered” above).

Difficulty in breathing could also be a sign that small particles have formed in the lungs and are blocking blood vessels (pulmonary vascular precipitates). If you experience any breathing difficulty, inform your doctor or nurse. They will decide on the appropriate action.

The antibiotic called ceftriaxone must not be mixed or administered simultaneously with solutions containing calcium (including Olimel N12E) given by intravenous infusion. Both medicines must not be administered together, even through different infusion lines or sites.

However, Olimel N12E and ceftriaxone may be administered sequentially one after the other if different infusion sites are used, or if infusion lines are replaced or thoroughly flushed with physiological saline solution between infusions to prevent precipitate formation (particles of ceftriaxone and calcium salt).

Certain medicines and diseases may increase the risk of developing infections or sepsis (bacteria in the blood). There is a risk of infection or sepsis, especially when a tube (intravenous catheter) is placed in the vein. Your doctor will closely monitor you for signs of infection. Patients requiring parenteral nutrition (administration of nutrients through a tube inserted into a vein) may be more prone to infections due to their medical condition. Using "aseptic techniques" (germ-free) when placing and maintaining the catheter and when preparing the nutritional formula (TPN) can reduce the risk of infection.

If you are severely malnourished and require intravenous feeding, your doctor should start treatment slowly. In addition, you will be monitored to prevent sudden changes in your fluid, vitamin, electrolyte, and mineral levels.

Metabolic disturbances and your body's water and salt balance must be corrected before starting the infusion. Your doctor will monitor your condition while this medicine is being administered and may adjust the dose or add other nutrients such as vitamins, electrolytes, and trace elements if deemed appropriate.

Cases of liver disorders have been reported in patients receiving intravenous nutritional therapy, including problems with bile excretion (cholestasis), fat storage (hepatic steatosis), fibrosis, which may possibly lead to liver failure, as well as cholecystitis and cholelithiasis. The cause of these disorders is believed to be multifactorial and may differ among 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 potential therapeutic and preventive measures.

Your doctor should know if you have:

any serious kidney problems. You should also inform your doctor if you are receiving dialysis (artificial kidney) or any other type of blood-cleansing treatment
any serious liver problems
any blood clotting disorders
abnormal function of the adrenal glands (adrenal insufficiency). The adrenal glands are triangular-shaped and located above the kidneys
heart failure
lung disease
fluid accumulation in the body (hyperhydration)
insufficient body water (dehydration)
high blood sugar (diabetes mellitus) without treatment for it
heart attack or shock due to sudden heart failure
severe metabolic acidosis (blood too acidic)
generalized infection (septicemia)
coma

To monitor the effectiveness and safety of administration, your doctor will perform laboratory and clinical tests while you are receiving this medicine. If you receive this medicine for several weeks, your blood will be tested 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 the infusion you notice pain, burning, or swelling at the infusion site, or leakage from the infusion, inform your doctor or nurse immediately. Administration will be stopped immediately and restarted in another vein.

If your blood sugar levels become too high, your doctor will need to adjust the infusion rate of Olimel N12E or administer medication to control blood sugar concentration (insulin).

Olimel N12E can only be administered through a tube (catheter) connected to a large vein in your chest (central vein).

Children and adolescents

If your child is under 18 years of age, special attention must be paid to administering the correct dose. Additional precautions are necessary due to children's increased sensitivity to the risk of infection. Supplementation with vitamins and trace elements is always required. Pediatric formulations should be used.

Use of Olimel N12E with other medicines

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

Concomitant administration of other medicines is generally not a contraindication. If you are taking other prescription or over-the-counter medicines, you should consult your doctor in advance so they can check for compatibility.

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

insulin
heparin

Olimel N12E must not be administered simultaneously with blood through the same infusion line.

Olimel N12E contains calcium. It must not be administered together or through the same line as the antibiotic ceftriaxone, as particles may form. If the same device is used to administer these medicines sequentially, it 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 present in Olimel N12E contain vitamin K. This usually does not affect blood-thinning medicines (anticoagulants) such as coumarin. However, if you are taking anticoagulants, you must inform your doctor.

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

Olimel N12E contains potassium. Particular care is required in patients taking diuretics, ACE inhibitors, angiotensin II receptor antagonists (medicines for high blood pressure), or immunosuppressants. These classes of medicines may increase potassium levels in the blood.

Pregnancy and breastfeeding

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

There are no adequate experiences with the use of Olimel N12E in pregnant or breastfeeding women. Olimel N12E may be used during pregnancy and breastfeeding if necessary. Olimel N12E should only be administered to pregnant or breastfeeding women after careful consideration.

Fertility

Adequate data are not available.

Driving and using machines

Not applicable.

3. How Olimel N12E will be administered to you

Dosing

Olimel N12E should only be administered to adults and children over 2 years of age.

It is an infusion emulsion, meaning it is given through a tube (catheter) inserted into a vein in your chest.

Olimel N12E must be at room temperature before use.

Olimel N12E is for single use only.

Dosing – Adults

Your doctor will determine the infusion rate based on your individual needs and clinical condition.

Prescription may continue for as long as necessary, depending on your clinical status.

Dosing – Children over 2 years of age and adolescents

The doctor will decide the dose and duration of treatment based on age, weight, height, clinical condition, and the body's ability to metabolize and utilize the components of Olimel N12E.

If you have been given more Olimel N12E than you should have

If the administered dose is too high or the infusion is too fast, the amino acid content may cause your blood to become too acidic, and signs 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. Administering the infusion too rapidly or in excessive volume may cause nausea, vomiting, chills, headache, flushing, excessive sweating (hyperhidrosis), and electrolyte disturbances. In such cases, the infusion must be stopped immediately.

In severe cases, your doctor may need to perform temporary renal dialysis to help your kidneys eliminate the excess product.

To prevent such events, your doctor will regularly monitor your condition and assess your blood parameters.

If you have any further questions about the use of this product, ask your doctor.

In case of overdose or accidental ingestion, contact the Toxicology Information Service. Telephone 915.620.420.

4. Possible adverse effects

Like all medicines, this medicine may cause adverse effects, although not everyone experiences them. If you notice that you do not feel as usual, inform your doctor or nurse immediately.

The tests your doctor performs while you are receiving this medicine should minimize the risk of adverse effects.

If any abnormal sign or symptom of an allergic reaction occurs, such as sweating, fever, chills, headache, skin rash, or difficulty breathing, the infusion must be stopped immediately.

The following adverse effects have been reported with Olimel:

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

Increased heart rate (tachycardia).
Decreased appetite.
Increased levels of fats in the blood (hypertriglyceridemia).
Abdominal pain.
Diarrhea.
Nausea.
High blood pressure (hypertension).

Frequency – Not known: cannot be estimated from available data

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

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

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

Reduced ability to eliminate lipids (fat overload syndrome), associated with a sudden and abrupt worsening of the patient's medical condition. The following symptoms of fat overload syndrome are usually reversible when the lipid emulsion infusion is stopped:
- Fever.
- Decrease in red blood cells, which may cause paleness of the skin and lead to weakness or difficulty breathing (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 affecting the blood's ability to clot.
- Elevated levels of fats in the blood (hyperlipidemia).
- Fat infiltration into the liver (hepatomegaly).
- Worsening of liver function.
- Central nervous system manifestations (e.g., coma).

Frequency – Not known: cannot be estimated from available data

Allergic reactions.
Abnormal blood tests for liver function.
Problems with bile elimination (cholestasis).
Enlargement of the liver (hepatomegaly).
Conditions associated with parenteral nutrition (see “Warnings and precautions” in section 2).
Jaundice.
Decrease in platelet count (thrombocytopenia).
Increased levels of nitrogen in the blood (azotemia).
Increased liver enzymes.
Formation of small particles that may lead to blockage of blood vessels in the lungs (pulmonary vascular precipitates), resulting in pulmonary vascular embolism and difficulty breathing (dyspnea).

Reporting of adverse effects:

If you experience any adverse effect, talk to your doctor or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Olimel N12E

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 following (MM/YYYY). The expiry date refers to the last day of the month indicated.

Do not freeze.

Store inside the overpouch.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to properly dispose of unused medicines and their containers. This will help protect the environment.

6. Contents of the pack and other information

Composition of Olimel N12E

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 of 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 of refined olive oil and refined soybean oil), and a 27.5% glucose solution (corresponding to 27.5 g/100 ml as glucose monohydrate) with calcium.

The other components are:

Lipid emulsion compartment	Amino acid solution compartment	Glucose solution compartment
Purified egg phospholipids, glycerol, sodium oleate, sodium hydroxide (for pH adjustment), water for injectable preparations	Glacial acetic acid (for pH adjustment), water for injectable preparations	Hydrochloric acid (for pH adjustment), water for injectable preparations

Appearance of Olimel N12E and contents of the pack

Olimel N12E is an infusion emulsion supplied in a 3-compartment bag. One compartment contains a lipid emulsion, another an amino acid solution with electrolytes, and the third a glucose solution with calcium. These compartments are separated by non-permanent seals. Prior to administration, the contents of the compartments must be mixed by rolling the bag over itself starting from the top of the bag until the seals are opened.

Appearance prior to reconstitution:

The amino acid and glucose solutions are transparent, colourless or slightly yellowish.
The lipid emulsion is homogeneous and has a milky appearance.

Appearance after reconstitution: Homogeneous milky emulsion.

The triple-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 authorised components and additives.

To avoid contact with oxygen from the air, the bag is packaged in an overpouch acting as an oxygen barrier, which contains an oxygen-absorbing sachet.

Pack sizes

650 ml bag: 1 cardboard box containing 10 bags
1000 ml bag: 1 cardboard box containing 6 bags
1500 ml bag: 1 cardboard box containing 4 bags
2000 ml bag: 1 cardboard box containing 4 bags

1 bag of 650 ml, 1000 ml, 1500 ml and 2000 ml

Only some pack sizes may be commercially available.

Marketing Authorization Holder

Baxter S.L.
Pouet de Camilo 2, 46394 Ribarroja del Turia (Valencia)

Manufacturer

Baxter S.A., Boulevard René Branquart, 80, 7860 Lessines, Belgium

This medicinal product is authorised in the European Economic Area member states under the following names:

Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Estonia, France, Greece, Italy, Latvia, Lithuania, Luxembourg, Netherlands, Romania, Slovenia, Slovakia, Spain:

Austria: <ZentroOLIMEL 7,6 % mit Elektrolyten>

Germany: <Olimel 7,6 % E>

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

Ireland, Malta, United Kingdom: <TRIOMEL 12 g/l nitrogen 950 kcal/l with electrolytes>

Hungary: <Olimel 12 g/l nitrogén elektrolitokkal emulziós infúzió>

Date of latest review of this summary April 2020

Detailed and up-to-date information on this medicinal product is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS) http://www.aemps.gob.es/

This information is intended for healthcare professionals only

A. Qualitative and quantitative composition

Olimel N12E is supplied as a bag with 3 compartments. Each bag contains a glucose solution with calcium, a lipid emulsion, and an amino acid solution with other electrolytes.

	Content per bag
	650 ml	1000 ml	1500 ml	2000 ml
27.5% glucose solution (equivalent to 27.5 g/100 ml)	173 ml	267 ml	400 ml	533 ml
14.2% amino acid solution (equivalent to 14.2 g/100 ml)	347 ml	533 ml	800 ml	1067 ml
17.5% lipid emulsion (equivalent to 17.5 g/100 ml)	130 ml	200 ml	300 ml	400 ml

After mixing the contents of the 3 compartments, the composition of the reconstituted emulsion is shown in the following table for each bag size.

Active Ingredients

650 ml

1000 ml

1500 ml

2000 ml

Refined olive oil + refined soybean oil^a

Alanine

Arginine

Aspartic acid

Glutamic acid

Glycine

Histidine

Isoleucine

Leucine

Lysine

(equivalent to lysine acetate)

Methionine

Phenylalanine

Proline

Serine

Threonine

Tryptophan

Tyrosine

Valine

Sodium acetate trihydrate

Sodium glycerophosphate hydrate

Potassium chloride

Magnesium chloride hexahydrate

Calcium chloride dihydrate

Glucose

(equivalent to glucose monohydrate)

22.75 g

7.14 g

4.84 g

1.43 g

2.46 g

3.42 g

2.94 g

2.46 g

3.42 g

3.88 g

(5.48 g)

2.46 g

3.42 g

2.94 g

1.95 g

2.46 g

0.82 g

0.13 g

3.16 g

0.97 g

2.39 g

1.45 g

0.53 g

0.34 g

47.67 g

(52.43 g)

35.00 g

10.99 g

7.44 g

2.20 g

3.79 g

5.26 g

4.53 g

3.79 g

5.26 g

5.97 g

(8.43 g)

3.79 g

5.26 g

4.53 g

3.00 g

3.79 g

1.26 g

0.20 g

4.86 g

1.50 g

3.67 g

2.24 g

0.81 g

0.52 g

73.33 g

(80.67 g)

52.50 g

16.48 g

11.16 g

3.30 g

5.69 g

7.90 g

6.79 g

5.69 g

7.90 g

8.96 g

(12.64 g)

5.69 g

7.90 g

6.79 g

4.50 g

5.69 g

1.90 g

0.30 g

7.29 g

2.24 g

5.51 g

3.35 g

1.22 g

0.77 g

110.00 g

(121.00 g)

70.00 g

21.97 g

14.88 g

4.39 g

7.58 g

10.53 g

9.06 g

7.58 g

10.53 g

11.95 g

(16.85 g)

7.58 g

10.53 g

9.06 g

5.99 g

7.58 g

2.53 g

0.39 g

9.72 g

2.99 g

7.34 g

4.47 g

1.62 g

1.03 g

146.67 g

(161.33 g)

(a) A mixture of refined olive oil (approximately 80%) and refined soybean oil (approximately 20%), corresponding to a ratio of essential fatty acids / total fatty acids of 20%.

The excipients are:

Lipid emulsion compartment	Amino acid solution compartment with electrolytes	Glucose solution compartment with calcium
Purified egg phospholipids, glycerol, sodium oleate, sodium hydroxide (for pH adjustment), water for injectable preparations	Glacial acetic acid (for pH adjustment), water for injectable preparations	Hydrochloric acid (for pH adjustment), water for injectable preparations

The reconstituted emulsion provides the following nutritional contributions for each bag size:

	650 ml	1000 ml	1500 ml	2000 ml
Lipids	22.8 g	35.0 g	52.5 g	70.0 g
Amino Acids	49.4 g	75.9 g	113.9 g	151.9 g
Nitrogen	7.8 g	12.0 g	18.0 g	24.0 g
Glucose	47.7 g	73.3 g	110.0 g	146.7 g
Energy:
Approximate total calories	620 kcal	950 kcal	1420 kcal	1900 kcal
Non-protein calories	420 kcal	640 kcal	960 kcal	1280 kcal
Glucose calories	190 kcal	290 kcal	430 kcal	580 kcal
Lipid calories (b)	230 kcal	350 kcal	520 kcal	700 kcal

Non-protein calories / nitrogen ratio	53 kcal/g	53 kcal/g	53 kcal/g	53 kcal/g
Glucose calories / lipid calories ratio	45/55	45/55	45/55	45/55
Lipid calories / total calories	37%	37%	37%	37%
Electrolytes:
Sodium	22.8 mmol	35.0 mmol	52.5 mmol	70.0 mmol
Potassium	19.5 mmol	30.0 mmol	45.0 mmol	60.0 mmol
Magnesium	2.6 mmol	4.0 mmol	6.0 mmol	8.0 mmol
Calcium	2.3 mmol	3.5 mmol	5.3 mmol	7.0 mmol
Phosphate (c)	9.5 mmol	15.0 mmol	21.9 mmol	29.2 mmol
Acetate	46 mmol	70 mmol	105 mmol	140 mmol
Chloride	30 mmol	45 mmol	68 mmol	90 mmol
pH	6.4	6.4	6.4	6.4
Approximate osmolarity	1270 mOsm/L	1270 mOsm/L	1270 mOsm/L	1270 mOsm/L

b Includes calories from purified egg phospholipids

c Includes phosphate provided by the lipid emulsion

B. Dosage and method of administration

Dosage

The use of Olimel N12E is not recommended in children under 2 years of age, as neither the composition nor the volume are appropriate (see sections 4.4, 5.1 and 5.2 of the Summary of Product Characteristics).

The maximum daily dose mentioned below must not be exceeded. 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 in which the patient requires nutrient amounts differing from the bag's composition. In such cases, healthcare professionals should consider the impact of any volume (dose) adjustment and the resulting effect on the dosing of the other nutrients in Olimel N12E. In these situations, healthcare professionals may consider adjusting the volume (dose) of Olimel N12E to meet these increased requirements.

In adults

The dose depends on the patient's energy expenditure, clinical condition, body weight, and ability to metabolize the components of Olimel N12E, as well as on additional energy or protein administered orally or enterally. Therefore, the appropriate bag size should be selected.

Average daily requirements are:

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

For Olimel N12E, the maximum daily dose is defined by amino acid intake: 26 ml/kg, corresponding to 2.0 g/kg of amino acids, 1.9 g/kg of glucose, and 0.9 g/kg of lipids. For a 70 kg patient, this would equate to 1820 ml of Olimel N12E per day, providing 138 g of amino acids, 133 g of glucose, and 64 g of lipids (i.e., 1171 non-protein kcal and 1723 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 of amino acids, 2.4 g/kg of glucose, and 1.2 g/kg of lipids. For a 70 kg patient, this would equate to 2310 ml of Olimel N12E per day, resulting in an intake of 175 g of amino acids, 169 g of glucose, and 81 g of lipids (i.e., 1486 non-protein kcal and 2187 total kcal).

Patients with morbid obesity: the dose should be calculated based on ideal body weight. For Olimel N12E, the maximum daily dose is defined by amino acid intake: 33 ml/kg of ideal body weight corresponds to 2.5 g/kg of amino acids, 2.4 g/kg of glucose, and 1.2 g/kg of lipids. For a 70 kg patient, this would equate to 2310 ml of Olimel N12E per day, resulting in an intake of 175 g of amino acids, 169 g of glucose, and 81 g of lipids (i.e., 1486 non-protein kcal and 2187 total kcal).

Normally, the infusion rate should be gradually increased during the first hour, then adjusted according to the dose being administered, daily volume intake, 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

Studies have not been conducted in the pediatric population.

Furthermore, daily requirements for fluid, nitrogen, and energy continuously decrease with age. Two age groups are considered: one between 2 and 11 years, and another from 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 dose. 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 dose. In this age group, the amino acid concentration is the limiting factor for the hourly rate. The resulting intakes are as follows:

Constituent	From 2 to 11 years	From 12 to 18 years
Recommended^a	Olimel N12E Vol. Max	Recommended^a	Olimel N12E Vol. Max
Maximum daily dose
Liquid (ml/kg/day)	60 – 120	33	50 – 80	26
Amino acids (g/kg/day)	1 – 2 (up to 2.5)	2.5	1 – 2	2
Glucose (g/kg/day)	1.4 – 8.6	2.4	0.7 – 5.8	1.9
Lipids (g/kg/day)	0.5 – 3	1.2	0.5 – 2 (up to 3)	0.9
Total energy (kcal/kg/day)	30 – 75	31.4	20 – 55	24.7
Maximum infusion rate per hour
Olimel N12E (ml/kg/h)		2.6		1.6
Amino acids (g/kg/h)	0.20	0.20	0.12	0.12
Glucose (g/kg/h)	0.36	0.19	0.24	0.12
Lipids (g/kg/h)	0.13	0.09	0.13	0.06

a: Recommended values in the 2018 ESPGHAN/ESPEN/ESPR Guidelines

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

In general, for young children, it is recommended to start infusion with a reduced daily dose and gradually increase it to the maximum dose (see previous section).

The maximum infusion rate is 2.6 ml/kg/hour for children aged 2 to 11 years and 1.6 ml/kg/hour for children aged 12 to 18 years.

Method and duration of administration

For single use only.

Once the bag has been opened, the contents should be used immediately and must not be stored for subsequent infusions.

The appearance of the mixture after reconstitution is a homogeneous emulsion resembling milk.

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 only be administered via a central vein.

The recommended duration for the infusion of one bag of parenteral nutrition ranges between 12 and 24 hours.

Parenteral nutrition treatment may continue for as long as required by the patient's clinical condition.

C. Incompatibilities

No other medicinal product should be added to any of the bag components or to the reconstituted emulsion without first confirming the compatibility and stability of the resulting preparation (specifically, the stability of the lipid emulsion).

Incompatibilities may occur, for example, due to excessive acidity (low pH) or inappropriate content of divalent cations (Ca²⁺ and Mg²⁺), which may destabilize the lipid emulsion.

As with any parenteral nutrition mixture, the proportions of calcium and phosphate must be taken into account. Excessive addition of calcium and phosphate, especially in the form of mineral salts, may lead to the formation of calcium phosphate precipitates.

Olimel N12E contains calcium ions, which poses an additional risk of coagulation in anticoagulated/ citrate-preserved blood or its components.

Ceftriaxone must not be mixed or administered together with intravenous solutions containing calcium, including Olimel N12E, through the same infusion line (e.g., Y-connector) due to the risk of precipitation of ceftriaxone-calcium salt (see sections 4.4 and 4.5 of the Summary of Product Characteristics). Ceftriaxone and calcium-containing solutions may be administered sequentially one after the other if different infusion sites are used, or if the infusion lines are replaced or thoroughly flushed with physiological saline solution 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 ampicillin or fosphenytoin.

Check compatibility with solutions administered simultaneously through the same administration set, catheter, or cannula.

Olimel N12E must not be administered before, simultaneously, or after blood through the same administration set due to the risk of pseudoagglutination.

D. Special precautions for disposal and other handling

Table 1 provides an overview of the preparation steps for administering Olimel N12E.

To open

Remove the protective overpouch.

Discard the sachet containing the oxygen absorber.

Check the integrity of the bag and the non-permanent seals. Use only if the bag is undamaged, the non-permanent seals are intact (i.e., the contents of the three compartments have not mixed), the amino acid solution and glucose solution are clear, colorless or slightly yellowish, practically free from visible particles, and the lipid emulsion is a homogeneous milky-appearing liquid.

Mixing of solutions and emulsion

Ensure the product is at room temperature when breaking the non-permanent seals.

Manually roll the bag upon itself, starting from the top of the bag (hanger end). The non-permanent seals will disappear from the side near the inlets. Continue rolling until the seals open approximately halfway along their length.

Mix the bag by inverting it at least three times.

The appearance after reconstitution is a homogeneous emulsion resembling milk.

Additions

The bag has sufficient capacity to allow the addition of vitamins, electrolytes, and trace elements.

Any additions (including vitamins) must be made to the reconstituted mixture (after breaking the non-permanent seals and mixing the contents of the three compartments).

Vitamins may also be added to the glucose compartment before reconstituting the mixture (before breaking the non-permanent seals and mixing the contents of the three compartments).

All additions must be performed by qualified personnel under aseptic conditions.

The formulation of Olimel N12E may be supplemented with electrolytes, inorganic/organic phosphate, and commercially available multivitamin preparations (such as Cernevit) and multiple trace element products (such as Nutryelt). The maximum total levels for additions listed in the table below have been demonstrated based on stability data and should not be considered dose recommendations. Additions should be based on the patient's clinical needs and must not exceed nutritional guidelines. The electrolytes already present in the bag must be taken into account when reaching the total maximum level.

Compatibility may vary between products from different sources; therefore, healthcare professionals are advised to perform appropriate checks when mixing Olimel N12 with other parenteral solutions.

Possible supplements for 1000 ml of Olimel N12E (for pediatric patients)

	Level included	Maximum addition	Total maximum level
Sodium	35 mmol	115 mmol	150 mmol
Potassium	30 mmol	120 mmol	150 mmol
Magnesium	4.0 mmol	1.6 mmol	5.6 mmol
Calcium	3.5 mmol	1.5 mmol	5.0 mmol
Inorganic phosphate	0 mmol	10 mmol Pi or 10 mmol Po b	10 mmol Pi + 15 mmol Po or 25 mmol Po a,b
Organic phosphate	15 mmol a
Other supplements (trace elements, vitamins, selenium and zinc)c
Trace elements – Junyelt d	1 vial per bag (10 ml concentrated solution)
Vitamins e	1 vial (lyophilized)
Selenium	60 µg per bag
Zinc	3 mg per bag

Includes phosphate provided by the lipid emulsion.
Pi inorganic phosphate; Po organic phosphate
For all formats, the trace elements, vitamins, selenium, and zinc supplements may be the same as those used for 1L bags.
Junyelt (Composition per vial: Zinc 15.30 µmol; Copper 3.15 µmol; Manganese 0.091 µmol; Iodine 0.079 µmol; Selenium 0.253 µmol)
Multivitamins from 1 vial in combination (Composition per vial: Vit. B1 (thiamine) 2.5 mg, Vit. B2 (riboflavin) 3.6 mg, Vit. B6 (pyridoxine) 4.00 mg, Vit. B5 (pantothenic acid) 15.0 mg, Vit. C (ascorbic acid) 100 mg, Vit. B8 (biotin) 0.06 mg, Vit. B9 (folic acid) 0.4 mg, Vit. B12 (cyanocobalamin) 0.005 mg, Vit. PP (nicotinamide) 40 mg) and 1 multivitamin vial (Composition per vial: Vit. A (as retinol palmitate) 2300 IU, Vit. D (as ergocalciferol) 400 IU, Vit. E (alpha-tocopherol) 6.4 mg, Vit. K (phytomenadione) 200 µg)

Possible supplements for 1000 ml of Olimel N12E (for adult patients)

	Included level	Maximum addition	Total maximum level
Sodium	35 mmol	115 mmol	150 mmol
Potassium	30 mmol	120 mmol	150 mmol
Magnesium	4.0 mmol	1.6 mmol	5.6 mmol
Calcium	3.5 mmol	1.5 mmol	5.0 mmol
Inorganic phosphate	0 mmol	10 mmol Pi or 10 mmol Po b	10 mmol Pi + 15 mmol Po or 25 mmol Po a,b
Organic phosphate	15 mmol a
Other supplements (trace elements, vitamins, selenium and zinc)c
Trace elements – Nutryel® d	2 vials per bag (10 ml concentrated solution)
Vitamins – Cernevit® e	1 vial (5 ml lyophilized)
Selenium	500 µg per bag
Zinc	20 mg per bag

Includes phosphate provided by the lipid emulsion.
Pi inorganic phosphate; Po organic phosphate
For all formats, trace elements, vitamins, selenium, and zinc supplements may be the same as those used for 1L bags. Vitamin addition is per liter of emulsion.
(Composition per vial: Zinc 153 µmol; Copper 4.7 µmol; Manganese 1.0 µmol; Fluoride 50 µmol; Iodine 1.0 µmol; Selenium 0.9 µmol; Molybdenum 0.21 µmol; Chromium 0.19 µmol; Iron 18 µmol)
Cernevit (Composition per vial: Vit. A (as retinyl palmitate) 3500 IU, Vit. D3 (cholecalciferol) 220 IU, Vit. E (alpha-tocopherol) 11.2 IU, Vit. C (ascorbic acid) 125 mg, Vit. B1 (thiamine) 3.51 mg, Vit. B2 (riboflavin) 4.14 mg, Vit. B6 (pyridoxine) 4.53 mg, Vit. B12 (cyanocobalamin) 6 µg, Vit. B9 (folic acid) 414 µg, Vit. B5 (pantothenic acid) 17.25 mg, Vit. B8 (biotin) 69 µg, Vit. PP (nicotinamide) 46 mg)

To perform an addition:

Must be carried out under aseptic conditions.
Prepare the injection site on the bag.
Pierce the injection site and inject additives using an injection needle or reconstitution device.
Mix the contents of the bag and the additives thoroughly.

Stability period after reconstitution:

Chemical and physical stability has been demonstrated for up to 7 days (between 2 °C and 8 °C), followed by 48 hours at a temperature not exceeding 30 °C.

From a microbiological standpoint, after reconstitution, the product should be used immediately. If not used immediately, the in-use storage conditions and duration after reconstitution and prior to use are the responsibility of the user and normally should not exceed 24 hours at 2 °C to 8 °C, unless reconstitution was performed under controlled and validated aseptic conditions.

Stability period after addition of supplements:

For certain mixtures, chemical and physical stability has been demonstrated for up to 7 days (between 2 °C and 8 °C), followed by 48 hours at a temperature not exceeding 30 °C.

From a microbiological standpoint, any mixture should be used immediately. If not used immediately, the in-use storage conditions and duration after mixing and prior to use are the responsibility of the user and normally should not exceed 24 hours at 2 °C to 8 °C, unless the addition of supplements was performed under controlled and validated aseptic conditions.

Infusion preparation

Must be carried out under aseptic conditions.

Hang the bag.

Remove the plastic protector from the administration outlet.

Firmly insert the administration set spike into the administration outlet.

Table 1: Preparation steps for administration of Olimel N12E

1.		2.	3.
Break from the top to open the overpouch.	Remove the front part of the overpouch to access the Olimel N12E bag. Discard the overpouch and the oxygen sachet.	Place the bag on a clean, flat surface with the handle facing toward you.

4.		5.	6.
Lift the hanger area to remove the solution from the top of the bag. Roll up the top of the bag tightly until the seals are fully open (approximately halfway).	Mix the contents by inverting the bag at least three times.	Hang the bag. Rotate the protector to remove it from the administration port. Securely connect the spike connector.

Administration

For single use only.

Administer the product only after the non-permanent seals between the three compartments have been broken and the contents of the three compartments have been mixed.

Ensure that the final emulsion for infusion shows no phase separation.

After opening the bag, the contents must be used immediately. An opened bag must never be saved for subsequent infusion. Do not reconnect a partially used bag.

Do not connect bags in series to avoid the risk of gas embolism due to residual gas in the first bag.

All unused medicinal product, materials that have come into contact with it, and all necessary devices must be discarded.

Extravasation

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

If extravasation occurs, administration must be stopped immediately, while maintaining the cannula or catheter in place for immediate patient treatment. If possible, aspiration should be performed through the inserted cannula/catheter to reduce the amount of fluid present in the tissues before removing the cannula/catheter.

Specific measures should be taken depending on the stage or extent of any injury caused by the extravasated product (including the product(s) mixed with Olimel N12E).

Treatment options may include pharmacological, non-pharmacological, and/or surgical interventions. In case of significant extravasation, a plastic surgeon should be consulted within the first 72 hours.

The extravasation site should be inspected at least every 4 hours during the first 24 hours, and thereafter once daily.

Infusion must not be resumed in the same central vein.