OLIMEL N9 EMULSION FOR INFUSION

Introduction

Package Leaflet: Information for the User

Olimel N9 emulsion for infusion

Read all of this leaflet carefully before this medicine is administered to you, as it contains important information for you.

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

Contents of the package leaflet

1. What is Olimel N9 and what is it used for
2. What you need to know before you are given Olimel N9
3. How Olimel N9 will be given to you
4. Possible side effects
5. Storage of Olimel N9
6. Contents of the pack and further information

1. What is OLIMEL N9 and what is it used for

Olimel is an emulsion for infusion. It comes in a bag with 3 chambers.

One chamber contains a glucose solution, the second contains a lipid emulsion, and the third contains an amino acid solution.

Olimel is used to feed adults and children over 2 years of age through a tube in a vein when normal feeding by mouth is not possible.

Olimel should only be used under medical supervision.

2. What you need to know before you are given Olimel N9

Olimel N9 must not be given:

• To premature newborns, babies, and children under 2 years of age.
• If you are hypersensitive (allergic) to egg proteins, soybean proteins, peanut proteins, corn/maize products (see also the "Warnings and precautions" section below) or to any of the other components of this medicine (listed in section 6).
• If your body has problems using certain amino acids.
• If you have especially high levels of fat in your blood.
• If you have hyperglycemia (too much sugar in your blood).

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

Warnings and precautions

Talk to your doctor or nurse before you are given Olimel.

Too rapid administration of total parenteral nutrition (TPN) solutions can cause injury or death.

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

Olimel contains glucose derived from corn, which may cause hypersensitivity reactions if you are allergic to corn or corn products (see "Olimel N9 must not be given" section above).

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

Certain medicines and diseases can 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 a vein. Your doctor will monitor you closely for signs of infection.

Patients who require parenteral nutrition (administration of nutrients through a tube inserted into a vein) may be more prone to infections due to their medical condition. The use of "aseptic techniques" (without germs) when placing and maintaining the catheter and preparing the nutritional formula (TPN) can reduce the risk of infection.

If you are severely malnourished and need to receive feeding through a vein, your doctor will start treatment slowly. Additionally, you will be monitored to avoid sudden changes in your fluid, vitamin, electrolyte, and mineral levels.

Before starting the infusion, any metabolic disorders and water and salt balance in your body must be corrected. Your doctor will monitor your condition while you are given this medicine and may change the dose or add other nutrients, such as vitamins, electrolytes, and trace elements, if necessary.

There have been reports of liver disorders, including problems with bile elimination (cholestasis), fat storage (hepatic steatosis), fibrosis, which may lead to liver failure, as well as cholecystitis and cholelithiasis in patients receiving intravenous nutrition treatment. It is believed that the cause of these disorders is due to multiple factors and may differ between patients. If you experience symptoms such as nausea, vomiting, abdominal pain, yellowing of the skin or eyes, talk to your doctor to identify possible causative and contributing factors and possible therapeutic and preventive measures.

Your doctor should know if you have:

• any serious kidney problem. You should also inform your doctor if you are receiving dialysis treatment (artificial kidney) or if you have any other treatment to clean your blood.
• any serious liver problem.
• any blood coagulation problem.
• abnormal adrenal gland function (adrenal insufficiency). The adrenal glands are triangular in shape and are located above the kidneys.
• heart failure.
• lung disease.
• fluid accumulation in the body (hyperhydration).
• insufficient water in the body (dehydration).
• excess sugar in the blood (diabetes mellitus) without treatment for it.
• heart attack or shock due to sudden heart failure.
• severe metabolic acidosis (acidic blood).
• generalized infection (septicemia).
• coma.

To check the effectiveness and safety of administration, your doctor will perform laboratory and clinical tests while you are given this medicine. If you are given this medicine for several weeks, your blood will be analyzed regularly.

The decrease in the body's ability to eliminate the fats contained in this medicine may lead to a "fat overload syndrome" (see section 4 "Possible side effects").

If you notice pain, burning, or swelling at the infusion site or leakage of the infusion, inform your doctor or nurse. The administration will be stopped immediately and restarted in another vein.

If your blood sugar levels rise too high, your doctor will adjust the rate of Olimel administration or provide medication to control blood sugar levels (insulin).

Olimel 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 will be paid to administering the correct dose. Additional precautions will also be taken due to the increased sensitivity of children to the risk of infection. Supplementation with vitamins and trace elements is always necessary. Pediatric formulations should be used.

Use of Olimel with other medicines

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

Simultaneous absorption of other medicines is generally not a contraindication. If you are taking other medicines, obtained with or without a prescription, you should consult your doctor beforehand to check if they are compatible.

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

• insulin.
• heparin.

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

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

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

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

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 is no sufficient experience with the use of Olimel in pregnant or breastfeeding women. Olimel may be used during pregnancy and breastfeeding if necessary. Olimel should only be administered to pregnant or breastfeeding women after careful consideration.

Driving and using machines

Not applicable.

3. How Olimel N9 will be given to you

Dose

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

This is an emulsion for infusion, i.e., for administration through a tube (catheter) into a large vein in your chest.

Olimel should be at room temperature before use.

Olimel is for single use only.

Dose – Adults

Your doctor will determine an infusion rate based on your needs and medical condition.

Administration can continue for as long as necessary, depending on your medical condition.

Dose – Children over 2 years and adolescents

The doctor will decide on the dose and the duration of administration based on age, weight, height, medical condition, and the body's ability to break down and use the ingredients of OLIMEL.

If you have been given too much Olimel N9

If the dose administered is too high or the infusion is too rapid, the amino acid content can make your blood too acidic, and signs of hypervolemia (increased blood volume) may occur. Your blood and urine glucose levels may increase, and a hyperosmolar syndrome (excessive blood viscosity) may develop, and the lipid content may increase your blood triglycerides. Administration of an infusion that is too rapid or a volume that is too high can cause nausea, vomiting, chills, headache, fever, sweating, and electrolyte disturbances. In this case, the infusion should be stopped immediately.

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

To avoid these cases, your doctor will regularly monitor your condition and analyze 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, consult the Toxicology Information Service. Telephone 915.620.420

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. If you notice that you do not feel as you did before, tell your doctor or nurse immediately.

The tests that your doctor will perform while you are taking this medicine should minimize the risk of side effects.

If any abnormal signs or symptoms of an allergic reaction (such as sweating, fever, chills, headache, skin rash, or difficulty breathing) develop, the infusion must be stopped immediately.

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 fat levels in the blood (hypertriglyceridemia).
• Abdominal pain.
• Diarrhea.
• Nausea.
• High blood pressure (hypertension).

Frequency - Unknown: cannot be estimated from the available data

• Hypersensitivity reactions, including sweating, fever, chills, headache, skin rash (erythematous, papular, pustular, macular, generalized rash), itching, flushing, difficulty breathing.
• Infusion site reactions, including pain, irritation, swelling/edema, redness (erythema)/heat, skin necrosis, or blisters/vesicles, inflammation, thickening, or constriction of the skin.
• Vomiting.

The following side 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 eliminate 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 when the lipid emulsion infusion is stopped:
• • Fever.
  • Decreased red blood cells, which can cause pale skin and weakness or difficulty breathing (anemia).
  • Low white blood cell count, which can increase the risk of infection (leucopenia).
  • Low platelet count, which can increase the risk of bruising and/or bleeding (thrombocytopenia).
  • Coagulation disorders affecting 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 symptoms (e.g., coma).

Frequency - Unknown: cannot be estimated from the available data

• Allergic reactions.
• Bile elimination problems (cholestasis).
• Abnormal liver function blood tests.
• Increased liver size (hepatomegaly).
• Diseases associated with parenteral nutrition (see "Warnings and precautions" in section 2).
• Jaundice.
• Decreased platelet count (thrombocytopenia).
• Increased blood nitrogen levels (azotemia).
• Increased liver enzymes.
• Formation of small particles that can lead to blockage of blood vessels in the lungs (pulmonary vascular precipitates), resulting in pulmonary vascular embolism and difficulty breathing (respiratory distress).

Reporting of side effects:

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

5. Storage of Olimel N9

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the packaging and outer packaging (MM/YYYY). The expiry date is the last day of the month stated.

Do not freeze.

Store in the overbag.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Container Content and Additional Information

Composition ofOlimel N9

The active principles of each bag of the reconstituted emulsion are a 14.2% L-amino acid solution (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, and glutamic acid), a 20% lipid emulsion (corresponding to 20 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:

Appearance ofOlimel N9and Container Content

Olimel is an emulsion for perfusion conditioned 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. Before administration, the content of the compartments must be mixed by rotating the bag from top to bottom until the seals are open.

Appearance before reconstitution:

• The amino acid and glucose solutions are transparent, colorless, or slightly yellowish.
• The lipid emulsion is homogeneous and milky white.

Appearance after reconstitution: Homogeneous milky emulsion.

The tricompartmental bag is a multilayer plastic bag. The material of the inner layer (contact) of the bag is designed to be compatible with the authorized components and additives

To avoid contact with air oxygen, the bag is packaged in an outer bag that acts as an oxygen barrier, which contains a sachet with an oxygen absorber.

Container Sizes

1000 ml bag: 1 cardboard box with 6 bags

1500 ml bag: 1 cardboard box with 4 bags

2000 ml bag: 1 cardboard box with 4 bags

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

Only some container sizes may be marketed.

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 authorized in the Member States of the European Economic Area under the following names:

France, Portugal, Estonia, Poland, Lithuania, Bulgaria, Romania, Latvia, Czech Republic, Belgium, Spain, Slovak Republic, Netherlands, Luxembourg, Slovenia, Italy, Greece, Cyprus: OLIMEL N9

In some countries, it is registered under different names as described below:

Austria: ZentroOLIMEL 5,7 %

Germany: Olimel 5,7%

Denmark, Iceland, Sweden, Norway, Finland: Olimel N9

United Kingdom, Ireland, Malta: Triomel 9g/l nitrogen 1070 kcal/l

Hungary: Olimel 9 g/l nitrogen emulsion for infusion

Date of the last revision of this leafletApril 2020.

Detailed and updated 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 only for healthcare professionals

Pharmacotherapeutic group: solutions for parenteral nutrition / combinations

ATC Code: B05 BA10.

• Qualitative and quantitative composition

Olimel is presented in the form of a 3-compartment bag. Each bag contains a glucose solution, a lipid emulsion, and an amino acid solution

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

(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:

The reconstituted emulsion provides the following for each bag size:

a Includes calories from purified egg phospholipids

b Includes phosphate provided by the lipid emulsion

• Dosage and administration

Dosage

The use of Olimel is not recommended in children under 2 years of age, as neither the composition nor the volume is suitable (see sections 4.4, 5.1, and 5.2 of the Technical Sheet).

The maximum daily dose mentioned below should not be exceeded. Due to the invariant composition of the multicompartimental bag, the ability to simultaneously meet all the patient's nutritional needs may not be possible. There may be clinical situations in which the patient requires amounts of nutrients that vary from the composition of the bag. In this situation, the impact of any volume adjustment (dose) and the resulting effect on the dosing of the rest of Olimel's nutrients should be considered.

In adults

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

The average daily needs are:

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

For Olimel, the maximum daily dose is defined by the intake of amino acids, 35 ml/kg, corresponding to 2.0 g/kg of amino acids, 3.9 g/kg of glucose, 1.4 g/kg of lipids. For a 70 kg patient, this would be equivalent to 2456 ml of Olimel per day, which would provide 140 g of amino acids, 270 g of glucose, and 98 g of lipids, i.e., 2063 non-protein kcal and 2628 total kcal.

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

For Olimel, the maximum infusion rate is 1.8 ml/kg/hour (except in NPID, see below), corresponding to 0.10 g/kg/hour of amino acids, 0.19 g/kg/hour of glucose, and 0.07 g/kg/hour of lipids.

In patients with intradialytic parenteral nutrition (NPID): NPID is intended for non-acute malnourished patients. The selection of the appropriate Olimel formulation and volume for use in NPID should be guided by the gap between estimated spontaneous intakes (e.g., through dietary interview) and recommended intakes. Additionally, metabolic tolerance should be taken into account. For OLIMEL N9, in patients with NPID, the maximum infusion rate per hour when administered during 4 hours is 3.6 ml/kg/hour, corresponding to 0.2 g/kg/hour of amino acids, 0.40 g/kg/hour of glucose, and 0.14 g/kg/hour of lipids.

In children over 2 years and adolescents

No studies have been conducted in the pediatric population.

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

Additionally, the daily needs for fluid, nitrogen, and energy decrease continuously with age: Two age groups are considered, one between 2 and 11 years, and another between 12 and 18 years

For Olimel N9, in both age groups, the amino acid concentration is the limiting factor for the daily dose. In the 2 to 11-year-old group, the glucose concentration is the limiting factor for the hourly rate. In the 12 to 18-year-old group, the amino acid concentration is the limiting factor for the hourly rate. The resulting intakes are as follows:

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

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

In general, in the case of small children, it is recommended to start the infusion with a reduced daily dose and gradually increase it to the maximum dose (see previous point).

Form and duration of administration

For single use.

Once the bag is opened, it is recommended to use its contents immediately and not store it for subsequent infusions.

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

To obtain instructions on the preparation and handling of the emulsion for infusion, see section 6.6 of the Technical Sheet.

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

The recommended duration of infusion of a parenteral nutrition bag is between 12 and 24 hours.

Treatment with parenteral nutrition may continue for as long as the patient's clinical condition requires.

• Incompatibilities

No other medication or drug 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 (in particular the stability of the lipid emulsion).

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

Due to the risk of precipitation, Olimel should not be administered through the same infusion line or mixed with ampicillin or fosphenytoin.

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

It should not be administered before, simultaneously, or after blood through the same equipment due to the risk of pseudoagglutination.

• Special precautions for elimination and other handling

In Table 1, an overview of the preparation steps for the administration of Olimel is provided.

To open

Remove the protective overbag.

Discard the packet with the oxygen absorber.

Confirm the integrity of the bag and the non-permanent seals. Use it only if the bag is not damaged, the non-permanent seals are intact (i.e., the contents of the three compartments have not been mixed), if the amino acid solution and the glucose solution are transparent, colorless, or slightly yellowish, practically free of visible particles, and if the lipid emulsion is a homogeneous liquid with a milky appearance.

Mixing of solutions and emulsion

Ensure that the product is at room temperature when the non-permanent seals are broken.

Manually roll the bag over itself, starting from the top of the bag (hanger end). The non-permanent seals will disappear from the side close to the entrances. Continue rolling until the seals open approximately halfway.

Mix the bag by inverting it at least 3 times.

The appearance after reconstitution is a homogeneous emulsion similar to milk.

Additions

The bag has sufficient capacity for vitamins, electrolytes, and trace elements to be added.

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

Vitamins can 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).

When making additions to formulations containing electrolytes, the amount of electrolytes already present in the bag must be taken into account.

Additions must be carried out by qualified personnel under aseptic conditions.

Olimel can be supplemented with electrolytes according to the following table:

a Value corresponding to the addition of inorganic phosphate

b 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 1 mg of iron).

Compatibility with other additives can be consulted upon request.

When making additions, the final osmolarity of the mixture should be measured before administering it through a peripheral vein.

To make an addition:

• It must be carried out under aseptic conditions.
• Prepare the injection point of the bag.
• Puncture the injection point and inject the additives using a syringe or a reconstitution device.
• Mix the contents of the bag and the additives.

Preparation for infusion

It 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 equipment into the administration outlet.

Table1: Preparation stepsfor the administration ofOlimel

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. The opened bag should never be stored for subsequent infusion. Do not reconnect a partially used bag.

Do not connect bags in series to avoid gas embolism resulting from the gas present in the first bag.

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

Extravasation

The catheter area should be regularly inspected to identify signs of extravasation.

If extravasation occurs, administration should be stopped immediately, keeping the cannula or catheter inserted in place for immediate patient treatment. If possible, aspiration should be performed through the inserted cannula/catheter to reduce the amount of liquid 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).

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

The extravasation area should be inspected at least every 4 hours during the first 24 hours and then once a day.

Infusion should not be resumed in the same central vein.