LIPOFLEX Emulsion

Contents of the leaflet

1. Package Leaflet: Information for the User
2. Lipoflex plus, infusion emulsion
3. Read the package leaflet carefully before using the medicine, as it contains important information for the patient.
   1. Package Leaflet Contents
4. What Lipoflex plus is and what it is used for
5. Important information before using Lipoflex plus
   1. When not to use Lipoflex plus
   2. Warnings and precautions
   3. Children
   4. Lipoflex plus and other medicines
   5. Pregnancy and breastfeeding
   6. Driving and using machines
   7. Lipoflex plus contains sodium
6. How to use Lipoflex plus
   1. Use in children
   2. Using more than the recommended dose of Lipoflex plus
7. Possible side effects
   1. The following side effects may be serious. If you experience any of the following side effects, tell your doctor immediately, who will stop the administration of the medicine:
   2. Other side effects include:
   3. Reporting side effects
8. How to store Lipoflex plus
9. Contents of the package and other information
   1. What Lipoflex plus contains
   2. What Lipoflex plus looks like and contents of the package
   3. Marketing authorization holder and manufacturer
   4. This medicine is authorized in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:
   5. Date of last revision of the package leaflet: 15.11.2023

Package Leaflet: Information for the User

Lipoflex plus, infusion emulsion

Read the package leaflet carefully before using the medicine, as it contains important information for the patient.

Important information for the patient.

• Keep this package leaflet, you may need to read it again.
• In case of any doubts, consult a doctor, pharmacist, or nurse.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm them, even if their symptoms are the same as yours.
• If the patient experiences any side effects, including any not listed in this package leaflet, they should inform their doctor, pharmacist, or nurse. See section 4.

Package Leaflet Contents

• 1. What Lipoflex plus is and what it is used for
• 2. Important information before using Lipoflex plus
• 3. How to use Lipoflex plus
• 4. Possible side effects
• 5. How to store Lipoflex plus
• 6. Contents of the package and other information

1. What Lipoflex plus is and what it is used for

Lipoflex plus contains fluids and substances, including amino acids, electrolytes, and fatty acids, which are necessary for growth or regeneration of the body. It also contains calories in the form of carbohydrates and fats.
This medicine is given to patients who are unable to eat normally. There are many situations where this may occur, such as after surgery, injury, or burns, or when the patient has difficulty absorbing food from the stomach or intestines.
This infusion emulsion can be administered to adults, adolescents, and children over 2 years of age.

2. Important information before using Lipoflex plus

When not to use Lipoflex plus

• If the patient is allergic to the active substances, egg protein, peanuts, or soy, or any of the other ingredients of this medicine (listed in section 6).
• The medicine must not be given to newborns, infants, and children under 2 years of age.

This medicine must not be used in the following cases:

• life-threatening circulatory disorders that occur during shock or collapse,
• heart attack or stroke,
• severe blood coagulation disorders, risk of bleeding (severe coagulopathy, exacerbation of bleeding disorder),
• blockage of blood vessels by blood clots or fat (embolism),
• severe liver failure,
• impairment of bile flow (intrahepatic cholestasis),
• severe kidney failure without renal replacement therapy,
• disorders of mineral salt composition in the body,
• fluid deficiency or excess water in the body,
• fluid in the lungs (pulmonary edema),
• severe heart failure,
• certain metabolic disorders, such as:
• excessive fat in the blood,
• inborn errors of amino acid metabolism,
• abnormally high blood sugar levels, which require administration of more than 6 units of insulin per hour,
• metabolic disorders occurring after surgical procedures or injuries,
• coma of unknown cause,
• insufficient oxygen supply to tissues,
• abnormally high levels of acids in the blood.

Warnings and precautions

Before starting treatment with Lipoflex plus, the patient should discuss it with their doctor, pharmacist, or nurse.
The patient should inform their doctor if they have:

• heart, liver, or kidney disorders,
• certain metabolic disorders, such as diabetes, abnormal fat levels in the blood, or disorders of water and electrolyte balance in the body or acid-base balance.

During treatment with Lipoflex plus, the patient will be closely monitored to detect early signs of an allergic reaction (such as fever, chills, rash, or shortness of breath).
Additional monitoring and laboratory tests will be performed, including various blood sample analyses, to ensure that the patient's body is properly utilizing the administered nutrients.
Nursing staff may take action to ensure that the patient's body is receiving sufficient fluids and electrolytes. The patient may receive other nutritional components in addition to this medicine to fully meet the body's needs.

Children

This medicine must not be given to newborns, infants, and children under 2 years of age.

Lipoflex plus and other medicines

The patient should tell their doctor, pharmacist, or nurse about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take.
Lipoflex plus may interact with other medicines. The patient should inform their doctor, pharmacist, or nurse if they are taking or receiving any of the following medicines:

• insulin,
• heparin,
• medicines that prevent unwanted blood clotting, such as warfarin or other coumarin derivatives,
• diuretics,
• medicines used to treat high blood pressure (ACE inhibitors),
• medicines used to treat high blood pressure or heart disorders (angiotensin II receptor antagonists),
• medicines used in organ transplantation, such as cyclosporine and tacrolimus,
• medicines used to treat inflammation (corticosteroids),
• hormonal medicines that affect fluid balance (adrenocorticotropic hormone or ACTH).

Pregnancy and breastfeeding

If the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a child, they should consult their doctor or pharmacist before using this medicine. If the patient is pregnant, they will only receive this medicine if their doctor or pharmacist considers it absolutely necessary for their recovery. There is no available data on the use of Lipoflex plus in pregnant women.
Breastfeeding is not recommended for mothers receiving parenteral nutrition.

Driving and using machines

This medicine is usually administered to immobilized patients, e.g., in a hospital or clinic, which excludes driving and using machines. However, the medicine itself does not affect the ability to drive and use machines.

Lipoflex plus contains sodium

The medicine contains 1150 mg of sodium (the main component of common salt) per 1250 ml bag. This corresponds to 58% of the maximum recommended daily sodium intake in the diet for adults.
The maximum recommended daily dose of this medicinal product contains 2580 mg of sodium (the main component of common salt). This corresponds to 129% of the maximum recommended daily sodium intake in the diet for adults.
If one or more bags are taken per day for a long time, patients, especially those controlling their sodium intake, should consult their doctor or pharmacist.

3. How to use Lipoflex plus

The medicine is administered as an intravenous infusion (drip), i.e., through a small tube directly into a vein. The medicine is administered only into larger (central) veins.
The doctor or pharmacist will determine the dose and decide how long to use the medicine.

Use in children

This medicine must not be given to newborns, infants, and children under 2 years of age.
The doctor will decide how much of this medicine the child needs and how long they will need treatment with this medicine.

Using more than the recommended dose of Lipoflex plus

If too much of this medicine is administered, the patient may experience a so-called overload syndrome with the following symptoms:

• excess fluid in the body and electrolyte imbalance,
• fluid in the lungs (pulmonary edema),
• loss of amino acids in the urine and disturbed amino acid balance,
• vomiting, nausea,
• chills,
• high blood sugar levels,
• glucose in the urine,
• fluid deficiency,
• significantly higher than normal levels of blood components (hyperosmolality),
• disorder or loss of consciousness due to very high blood sugar levels,
• enlargement of the liver (hepatomegaly) with or without jaundice,
• enlargement of the spleen (splenomegaly),
• fat deposition in internal organs,
• abnormal liver function test results,
• decreased red blood cell count (anemia),
• decreased white blood cell count (leukopenia),
• decreased platelet count (thrombocytopenia),
• increased number of immature red blood cells (reticulocytosis),
• red blood cell breakdown (hemolysis),
• bleeding or tendency to bleed,
• blood coagulation disorders (expressed as changes in bleeding time, coagulation time, prothrombin time, etc.),
• fever
• high fat levels in the blood,
• loss of consciousness.

If any of the above symptoms occur, the infusion should be stopped immediately.
In case of any further doubts about using this medicine, consult a doctor or pharmacist.

4. Possible side effects

Like all medicines, Lipoflex plus can cause side effects, although not everybody gets them.

The following side effects may be serious. If you experience any of the following side effects, tell your doctor immediately, who will stop the administration of the medicine:

Rare (may affect up to 1 in 1000 people):

• allergic reactions, such as skin reactions, shortness of breath, swelling of the lips, mouth, and throat, difficulty breathing.

Other side effects include:

Uncommon (may affect up to 1 in 100 people):

• nausea, vomiting, loss of appetite.

Rare (may affect up to 1 in 1000 people):

• increased blood coagulation,
• blue discoloration of the skin,
• shortness of breath,
• headache,
• hot flashes,
• redness of the skin (flushing),
• sweating,
• chills,
• feeling cold,
• increased body temperature,
• drowsiness,
• chest pain, back pain, bone and lumbar pain,
• decreased or increased blood pressure.

Very rare (may affect up to 1 in 10,000 people):

• abnormally high levels of fat or sugar in the blood,
• high levels of acidic substances in the blood,
• excessive fat levels may lead to a fat overload syndrome; see "Using more than the recommended dose of Lipoflex plus", section 3. Symptoms usually resolve after stopping the infusion.

Unknown (frequency cannot be estimated from available data)

• decreased white blood cell count (leukopenia),
• decreased platelet count (thrombocytopenia),
• bile flow disorders (cholestasis).

Reporting side effects

If you experience any side effects, including any not listed in this package leaflet, tell your doctor, pharmacist, or nurse.
Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocidal Products
Al. Jerozolimskie 181C, 02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder.
Reporting side effects will help to gather more information on the safety of this medicine.

5. How to store Lipoflex plus

Store the medicine out of sight and reach of children.
Do not store above 25°C.
Do not freeze. If the medicine is accidentally frozen, the bag should be discarded.
Store in the outer protective bag to protect from light.
Do not use this medicine after the expiry date stated on the label. The expiry date refers to the last day of the month stated.

6. Contents of the package and other information

What Lipoflex plus contains

The active substances in the ready-to-use mixture are:

Other ingredients are: citric acid monohydrate (for pH adjustment), egg lecithin for injection, glycerol, sodium oleate, all-rac-α-tocopherol, and water for injection.

What Lipoflex plus looks like and contents of the package

The ready-to-use product is an infusion emulsion, i.e., it is administered through a small tube into a vein.
Lipoflex plus is supplied in three-chamber bags containing:

• 1250 ml (500 ml amino acid solution + 250 ml fat emulsion + 500 ml glucose solution)
• 1875 ml (750 ml amino acid solution + 375 ml fat emulsion + 750 ml glucose solution)
• 2500 ml (1000 ml amino acid solution + 500 ml fat emulsion + 1000 ml glucose solution)

Figure A
Figure B
Figure A: The multi-chamber bag is packaged in a protective package. Between the bag and the protective package, an oxygen absorber and an oxygen level indicator are placed; the oxygen absorber pouch is made of a neutral material and contains iron hydroxide.
Figure B: The upper chamber contains a glucose solution, the middle chamber contains a fat emulsion, and the lower chamber contains an amino acid solution.
The glucose and amino acid solutions are clear and colorless or have a straw-colored tint. The fat emulsion is milky white.
The upper and middle chambers can be connected to the lower chamber by opening the internal welds (tear-off welds).
The bag is designed to allow mixing of amino acids, glucose, fats, and electrolytes in one chamber. Breaking the welds will cause sterile mixing of the contents and formation of an emulsion.
The product in different sizes is available in cardboard boxes containing five bags.
Not all package sizes may be marketed.

Marketing authorization holder and manufacturer

• B. Braun Melsungen AG Carl-Braun-Straße 1 Postal address34212 Melsungen, Germany 34209 Melsungen, Germany

Phone: +49-(0)-5661-71-0
Fax: +49-(0)-5661-71-4567

This medicine is authorized in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:

Austria
Nutriflex Lipid plus B.Braun Emulsion zur Infusion
Belgium
Nutriflex Lipid plus, 38 g/l Amino + 120 g/l G, emulsie voor infusie
Denmark
Lipoflex plus
Finland
Nutriflex Lipid 38/120/40 infuusioneste, emulsio
France
MEDNUTRIFLEX E, émulsion pour perfusion
Germany
NuTRIflex Lipid plus novo Emulsion zur Infusion
Iceland
Nutriflex Lipid 38/120 plus innrennslislyf, fleyti
Italy
LIPOFLEX AA38/G120 Emulsione per infusione
Luxembourg
NuTRIflex Lipid plus novo Emulsion zur Infusion
Netherlands
Nutriflex Lipid plus, 38 g/l Amino + 120 g/l G, emulsie voor infusie
Norway
Lipoflex plus infusjonsvæske, emulsjon
Poland
Lipoflex plus
Romania
NuTRIflex Lipid plus novo, emulsie perfuzabilă
Spain
Lipoflex plus emulsión para perfusión EFG
Sweden
Nutriflex Lipid 38/120/40 infusionsvätska, emulsion
United Kingdom (Northern Ireland) Lipoflex plus emulsion for infusion

Date of last revision of the package leaflet: 15.11.2023

______________________________________________________________________________
Information intended for healthcare professionals only:
No special requirements for disposal.
Before use, parenteral nutrition products should be inspected visually for damage, discoloration, or instability of the emulsion.
Do not use damaged bags. The outer and inner bag, as well as the welds between the chambers, should be intact. The product should only be used if the amino acid and glucose solutions are clear and colorless to straw-colored, and the fat emulsion is homogeneous in a milky white color. Do not use if the solutions contain solid particles.
After mixing the contents of the three chambers, do not use if the emulsion shows discoloration or signs of phase separation (oil droplets, oil layer). In case of emulsion discoloration or signs of phase separation, the infusion should be stopped immediately.
Before opening the protective package, check the oxygen indicator (see Figure A). Do not use if the oxygen indicator has changed color to pink. Use only if the oxygen indicator is yellow.
Preparing the mixed emulsion
Strictly follow aseptic handling procedures.
To open: tear the protective package, starting from the notches (Fig. 1).
Remove the bag from the protective package. Remove the protective package, oxygen indicator, and oxygen absorber.
Inspect the product bag for any signs of damage. Damaged bags should be discarded due to the lack of guarantee of their sterility.

Mixing the contents of the bag and adding additional substances
To open and mix the contents of the subsequent chambers, roll the bag with both hands, starting from the weld separating the upper chamber (glucose) and the lower chamber (amino acids) (Fig. 2).

After removing the aluminum cap (Fig. 3), compatible, water-soluble additional substances can be added to the clear aqueous solutions through the drug administration port (Fig. 4). Mix the contents thoroughly (Fig. 5) and inspect for any precipitates (Fig. 6). Only use a clear solution.

Then, continue rolling until the weld separating the middle chamber (fats) and the lower chamber is opened (Fig. 7). The mixture is a homogeneous, milky white emulsion of the oil-in-water type. After mixing the contents of all chambers, compatible additional substances can be added through the drug administration port (Fig. 4). Mix the contents thoroughly (Fig. 8) and inspect the mixture (Fig. 9).

Information on the compatibility of various additional substances (e.g., electrolytes, trace elements, vitamins) and the shelf life of such admixtures can be obtained upon request from the manufacturer.
Preparation for infusion
Before infusion, the emulsion should always be brought to room temperature.
Remove the aluminum foil (Fig. 10) from the infusion port and attach the infusion set (Fig. 11). Use infusion sets without an air vent or close the air vent when using sets with an air vent. Hang the bag on an infusion stand (Fig. 12) and administer the infusion using standard technique.

For single use only. After use, the container and any unused contents should be discarded.
Do not reconnect partially used containers.
If filters are used, they must be fat-permeable (pore size ≥ 1.2 µm).
Shelf life after removal of the protective package and mixing the contents of the bag
Chemical and physicochemical stability of the mixed amino acid, glucose, and fat emulsion has been demonstrated before use for 7 days at 2-8°C and for an additional 2 days at 25°C.
Shelf life after addition of compatible additional substances
From a microbiological point of view, the product should be used immediately after addition of additional substances. The user is responsible for the storage time and conditions before use if the product is not used immediately after addition of additional substances.
The emulsion should be used immediately after opening the container.
The recommended infusion time from a single bag for parenteral nutrition is 24 hours.
Do not mix this medicinal product with other medicinal products for which compatibility has not been established.
This medicinal product should not be administered simultaneously with blood through the same infusion set due to the risk of pseudoagglutination.