Olimel N12 emulsion for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Olimel N12 emulsion for infusion

Read all of this 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 side effects, talk to your doctor or nurse, even if it is a side effect not listed in this leaflet. See section 4.

Contents of the leaflet

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

1. What Olimel N12 is and what it is used for

Olimel N12 is an infusion emulsion. It is supplied in a three-compartment bag.

One compartment contains a glucose solution, the second compartment contains a lipid emulsion, and the third compartment 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 possible.

Olimel N12 should only be used under medical supervision.

2. What you need to know before Olimel N12 is administered to you

Olimel N12 must not be administered:

• To premature neonates, infants, or 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 your blood.
• If you have hyperglycemia (excessively high blood sugar levels).

In all cases, your doctor will decide whether you should be given this medicine 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 N12 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 N12 contains glucose derived from corn, which may cause hypersensitivity reactions in individuals with allergy to corn or corn products (see section “Olimel N12 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 difficulties, inform your doctor or nurse. They will decide on the appropriate action.

Certain medications 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 an intravenous catheter is placed into a 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 inserting 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. Additionally, you will be monitored to prevent sudden changes in your fluid, vitamin, electrolyte, and mineral levels.

Before starting the infusion, metabolic disturbances and your body's water and salt balance should be corrected. 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 as appropriate.

Cases of liver disorders, including problems with bile excretion (cholestasis), fat accumulation in the liver (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 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 (jaundice), consult your doctor to identify possible causative and contributing factors and to consider potential therapeutic and preventive measures.

Your doctor should know if you have:

• Severe kidney problems. You should also inform your doctor if you are undergoing dialysis (artificial kidney) or any other type of blood-cleansing treatment.
• Severe liver problems.
• Blood clotting disorders.
• Abnormal function of the adrenal glands (adrenal insufficiency). The adrenal glands are triangular-shaped and located on top of the kidneys.
• Heart failure.
• Lung disease.
• Fluid accumulation in the body (hyperhydration).
• Insufficient body water (dehydration).
• High blood sugar levels (diabetes mellitus) without treatment.
• Heart attack or shock due to sudden heart failure.
• Severe metabolic acidosis (excessively acidic blood).
• Systemic infection (septicemia).
• Coma.

To monitor the effectiveness and safety of treatment, 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 infusion you experience pain, burning, swelling at the infusion site, or leakage of the infusion fluid, inform your doctor or nurse immediately. The infusion 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 N12 or administer medication to control blood sugar concentration (insulin).

Olimel N12 must only be administered through a catheter inserted into a large vein in your chest (central vein).

Children and adolescents

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

Use of Olimel N12 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 medicines.

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

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

• Insulin
• Heparin

Olimel N12 must not be administered simultaneously with blood through the same infusion line.

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 drug fosphenytoin.

The olive and soybean oils present in Olimel N12 contain vitamin K. This usually does not affect blood-thinning medications (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 5 to 6-hour period without lipid infusion).

Pregnancy and breastfeeding

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

There are no adequate experiences with the use of Olimel N12 in pregnant or breastfeeding women. Olimel N12 may be used during pregnancy and breastfeeding if necessary. However, Olimel N12 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 N12 will be administered to you

Dosing

Olimel N12 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) into a vein in your chest.

Olimel N12 must be at room temperature before use.

Olimel N12 is for single use only.

Dosing – Adults

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

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

Dosing – Children over two 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 N12.

If you have been given more Olimel N12 than you should have

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 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 lipid content may increase blood triglycerides. Administration of an excessively rapid infusion or an excessive volume of Olimel N12 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 will experience them. If you notice that you do not feel as usual, inform your doctor or nurse immediately.

The tests your doctor will perform while you are taking 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 – Frequent: may affect up to 1 in 10 people

• Increased heart rate (tachycardia).
• Decreased appetite.
• Increased blood fat levels (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 products for parenteral nutrition:

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 abrupt deterioration in the patient's medical condition. The following symptoms of lipid 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).
  • Coagulation disorders affecting the blood's ability to clot.
  • Elevated fat levels 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).
• Liver diseases 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, consult your doctor or nurse, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly via 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 N12

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 indicated month.

Do not freeze.

Store within 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 packaging. This helps protect the environment.

6. Contents of the pack and other information

Composition of Olimel N12

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), 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).

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 N12 and contents of the pack

Olimel N12 is an infusion emulsion supplied in a 3-compartment bag. One compartment contains a lipid emulsion, another an amino acid solution, and the third a glucose solution. These compartments are separated by non-permanent seals. Prior to administration, the contents of the compartments must be mixed by rolling the bag upon itself starting from the top of the bag until the seals open.

Appearance before reconstitution:

• The amino acid and glucose solutions are clear, 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 atmospheric oxygen, 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 Authorisation 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, Czech Republic, France, Greece, Italy, Luxembourg, Netherlands, Slovenia, Spain:

Austria: <ZentroOLIMEL 7,6 %>

Germany: <Olimel 7,6 %>

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

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

Date of the most recent review of this leaflet: April 2020

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

This information is intended for healthcare professionals only

A. Qualitative and quantitative composition

Olimel N12 is supplied as a 3-compartment bag.

Each bag contains a glucose solution, a lipid emulsion, and an amino acid solution.

	Content per bag
	650 ml	1000 ml	1500 ml	2000 ml
27.5% glucose solution (corresponding to 27.5 g/100 ml)	173 ml	267 ml	400 ml	533 ml
14.2% amino acid solution (corresponding to 14.2 g/100 ml)	347 ml	533 ml	800 ml	1,067 ml
17.5% lipid emulsion (corresponding 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 oila Alanine Arginine Aspartic acid Glutamic acid Glycine Histidine Isoleucine Leucine Lysine (equivalent to lysine acetate) Methionine Phenylalanine Proline Serine Threonine Tryptophan Tyrosine Valine 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 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 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 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 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	Glucose solution compartment
Purified egg phospholipids, glycerol, sodium oleate, sodium hydroxide (for pH adjustment), water for injections	Glacial acetic acid (for pH adjustment), water for injections	Hydrochloric acid (for pH adjustment), water for injections

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:
Total calories approx.	620 kcal	950 kcal	1420 kcal	1900 kcal
Non-protein calories	420 kcal	640 kcal	960 kcal	1280 kcal
Calories from glucose	190 kcal	290 kcal	430 kcal	580 kcal
Calories from lipids (a)	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:
Phosphate (b)	1.7 mmol	2.6 mmol	3.9 mmol	5.2 mmol
Acetate	35 mmol	54 mmol	80 mmol	107 mmol
pH	6.4	6.4	6.4	6.4
Approximate osmolarity	1130 mOsm/L	1130 mOsm/L	1130 mOsm/L	1130 mOsm/L

a Includes calories from purified egg phospholipids

b Includes phosphate provided by the lipid emulsion

B. Posology and method of administration

Posology

The use of Olimel N12 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 of the patient's nutrient 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 N12. In these situations, healthcare professionals may consider adjusting the volume (dose) of Olimel N12 to meet these increased requirements.

In adults

The dose depends on the patient's energy expenditure, clinical status, body weight, and ability to metabolize the components of Olimel N12, as well as on any 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 N12, 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 correspond to 1820 ml of Olimel N12 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 N12, 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 be equivalent to 2310 ml of Olimel N12 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 N12, the maximum daily dose is defined by amino acid intake, 33 ml/kg of ideal body weight, 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 be equivalent to 2310 ml of Olimel N12 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 and then adjusted according to the prescribed dose, daily volume intake, and duration of infusion.

For Olimel N12, the maximum infusion rate is 1.3 ml/kg/hour (except for intradialytic parenteral nutrition [IDPN], see below), 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.

Patients receiving intradialytic parenteral nutrition (IDPN): IDPN is intended for non-acute malnourished patients. The selection of the appropriate Olimel formulation and volume for use in IDPN should be guided by the gap between estimated spontaneous intakes (e.g., through dietary interview) and recommended intakes. In addition, metabolic tolerance must be taken into account.

For OLIMEL N12, in patients receiving IDPN, the maximum hourly infusion rate is 2.7 ml/kg/hour, corresponding to 0.2 g/kg/hour of amino acids, 0.2 g/kg/hour of glucose, and 0.09 g/kg/hour of lipids administered over 4 hours.

In children over 2 years of age and adolescents

Studies have not been conducted in the pediatric population.

The dose depends on the patient's energy expenditure, clinical status, body weight, and ability to metabolize the components of Olimel N12, as well as on any additional energy and protein administered orally or enterally. Therefore, the appropriate bag size should be selected.

In addition, 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 N12, in the 2 to 11-year age group, the amino acid concentration is the limiting factor for both daily dose and hourly rate. In the 12 to 18-year age group, the amino acid concentration is the limiting factor for both daily dose and hourly rate. The resulting intakes are as follows:

Constituent	From 2 to 11 years	From 12 to 18 years
Recommendeda	Olimel N12Vol. Max	Recommendeda	Olimel N12Vol. Max
Maximum daily dose
Fluid (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 N12 (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 according to the 2018 ESPGHAN/ESPEN/ESPR Guidelines

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

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, it is recommended to use its contents immediately and not to save them 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 Technical Data Sheet.

Due to its high osmolarity, Olimel N12 must only be administered through a central vein.

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

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

C. Incompatibilities

No other medicinal product should be added to any of the components of the bag or to the reconstituted emulsion without first confirming the compatibility and stability of the resulting preparation (particularly 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, calcium and phosphate ratios must be taken into account. Excessive addition of calcium and phosphate, especially 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 ampicillin or fosphenytoin.

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

It must not be administered before, simultaneously, or after blood through the same equipment 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 N12.

To open

Remove the protective overpouch.

Discard the oxygen-absorbing sachet.

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 yet 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 onto 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.

Olimel N12 formulation may be supplemented with electrolytes, inorganic/organic phosphate, and commercially available multivitamin preparations (such as Cernevit) and multiple trace element products (such as Nutrytel). The maximum total levels for additions listed in the table below have been established based on stability data and should not be considered as dosage recommendations. The addition must be determined based on the patient's clinical needs and must not exceed nutritional guidelines. Electrolytes already present in the bag must be considered 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 N12 (for pediatric patients)

	Level included	Maximum addition	Total maximum level
Sodium	0 mmol	150 mmol	150 mmol
Potassium	0 mmol	150 mmol	150 mmol
Magnesium	0 mmol	5.6 mmol	5.6 mmol
Calcium	0 mmol	5.0 mmol	5.0 mmol
Inorganic phosphate	0 mmol	10 mmol Pi + 12 mmol Po or 22 mmol Po b	10 mmol Pi + 15 mmol Po or 25 mmol Po a,b 25/15 mmol a,b
Organic phosphate	3 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 (lyophilisate)
Selenium	60 µg per bag
Zinc	3 mg per bag

• 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 the 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: 1 vial 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 N12 (for adult patients)

	Level included	Maximum addition	Total maximum level
Sodium	0 mmol	150 mmol	150 mmol
Potassium	0 mmol	150 mmol	150 mmol
Magnesium	0 mmol	5.6 mmol	5.6 mmol
Calcium	0 mmol	5.0 mmol	5.0 mmol
Inorganic phosphate	0 mmol	10 mmol Pi + 12 mmol Po or 22 mmol Po b	10 mmol Pi + 15 mmol Po or 25 mmol Po ,a,b
Organic phosphate	3 mmol a
Other supplements (trace elements, vitamins, selenium and zinc)c
Trace elements – Nutryelt 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

• 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 for the 1L bags. The addition of vitamins is per liter of emulsion.

• Nutryelt (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 retinol 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:

• It 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 additives.

Validity period after reconstitution:

Chemical and physical stability in use has been demonstrated for 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 conditions and duration of storage in use after reconstitution and before administration are the responsibility of the user and normally should not exceed 24 hours between 2 °C and 8 °C, unless reconstitution was performed under controlled and validated aseptic conditions.

Validity period after addition of supplements

For certain mixtures, chemical and physical stability in use has been demonstrated for 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 conditions and duration of storage in use after mixing and before administration are the responsibility of the user and normally should not exceed 24 hours between 2 °C and 8 °C, unless the addition of supplements was performed under controlled and validated aseptic conditions.

Perfusion preparation

Must be carried out under aseptic conditions.

Hang the bag.

Remove the plastic protector from the administration outlet.

Firmly insert the tip of the infusion set into the administration outlet.

Table 1: Preparation steps for administration of Olimel N12

1.		2.		3.
Break from the top to open the overpouch.	Remove the front part of the overpouch to access the Olimel N12 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. Firmly roll up the top of the bag 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 outlet. 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 stored 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 to allow immediate treatment of the patient. 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 any products mixed with Olimel N12).

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

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

Infusion must not be resumed in the same central vein.