Lipidem

Package leaflet: Information for the patient

Lipidem, 200 mg/ml, emulsion for infusion
Medium-chain saturated triglycerides / purified soybean oil / omega-3 triglycerides
Please read carefully the entire leaflet before use, as it contains
important information for the patient.

• Keep this leaflet for future reference.
• If you have any questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If any adverse reactions occur in the patient, including any adverse reactions not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Contents of the leaflet

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

1. What Lipidem is and what it is used for

Lipidem is an oil-in-water emulsion. The oils contained in Lipidem provide a source of energy and
essential fatty acids necessary for body growth and recovery.
Lipidem is used to deliver fats to patients who require parenteral nutrition because they cannot
eat normally or when normal food intake is insufficient in their case.
Lipidem may be used in adults, preterm infants, full-term newborns, infants and young children, older children, and adolescents.

2. Important information before using Lipidem

DO NOT use Lipidem
if the patient has one or more of the following conditions:

• allergy to eggs, fish, peanuts or soy protein, or to any of the other components of this medicine (listed in section 6);
• abnormally high levels of fats in the blood (severe hyperlipidemia characterized by hypertriglyceridemia);
• disorders in which blood does not clot properly (severe coagulopathy);
• impaired bile flow (intrahepatic cholestasis);
• severe liver failure (severe impairment of liver function);
• severe kidney failure (severe impairment of kidney function) without access to kidney replacement therapy (hemofiltration or dialysis);
• blockage of blood vessels by blood clots or fat (acute thromboembolic event, fat embolism);
• abnormally high levels of acidic substances in the blood (acidosis).

Patients generally cannot receive intravenous nutritional therapy (parenteral nutrition)
if the patient has one or more of the following conditions:

• life-threatening circulatory disorders, such as those occurring in shock or collapse;
• acute phase of myocardial infarction (heart attack) or stroke;
• unstable metabolism, for example due to diabetes, severe systemic infection (sepsis) or coma of unknown origin;
• inadequate tissue oxygenation;
• disturbances in the body's electrolyte balance;
• fluid deficiency or excess water in the body;
• presence of fluid in the lungs (acute pulmonary edema);
• severe heart failure (decompensated heart failure).

Warnings and precautions

Monitoring

• During infusion, the doctor will monitor the level of fat (serum triglycerides) in the patient's blood. If the fat level becomes too high, the doctor may reduce or stop the infusion rate.
• While administering this solution, the doctor will also check the patient's fluid balance, electrolyte levels, and acid-base balance. Liver and kidney function, blood coagulation, and blood morphology will also be monitored.
• If the patient experiences any signs of an allergic reaction during administration of this medicine, such as fever, chills, rash or difficulty breathing, the doctor will immediately stop the infusion.

Additional precautions

• Before administering this medicine, the doctor will correct any existing disturbances in the patient's fluid and electrolyte levels and acid-base balance.
• In addition to Lipidem, the patient may also receive carbohydrate and amino acid solutions to prevent a metabolic condition in which blood pH becomes acidic (acidosis).
• To ensure complete parenteral nutrition, the patient will also receive carbohydrate and amino acid solutions. Nursing staff will also take appropriate measures to meet the body's requirements for fluids, electrolytes, vitamins, and trace elements.

Elderly patients
In certain conditions, the body's ability to properly metabolize fat may be impaired. The doctor will take into account that some of these conditions are often associated with advanced age, such as heart or kidney dysfunction.

Patients with heart or kidney dysfunction
If the patient has heart or kidney dysfunction, the doctor will exercise special caution when administering this medicine.

Patients with impaired fat metabolism
In certain conditions, the body's ability to properly metabolize fat may be limited, and blood fat levels may be too high. Therefore, it is important to inform the doctor:

• if the patient has diabetes;
• if the patient has pancreatitis;
• if the patient has liver or kidney dysfunction (kidney failure, liver failure);
• if the patient has thyroid dysfunction (hypothyroidism);
• if the patient has sepsis;
• if the patient has three or more of the following factors simultaneously: increased abdominal fat, reduced levels of "good cholesterol" (HDL-C), increased blood fat levels, high blood pressure, and elevated blood sugar levels (metabolic syndrome).
  In case of impaired ability to properly metabolize fat, the doctor will closely monitor the level of fat (serum triglycerides) in the patient's blood.

Children and adolescents
In infants at risk of jaundice, the doctor should monitor serum triglyceride and bilirubin levels. Daily fat doses may need to be adjusted.
During infusion, this solution must be protected from light used in phototherapy to minimize the formation of potentially harmful substances (triglyceride hydroperoxides).
When used in newborns and children under 2 years of age, the solution (in the bottle and administration set) must be protected from light until administration is complete. Exposure of Lipidem to light, particularly after addition of trace elements and/or vitamins, leads to the formation of peroxides and other degradation products, which can be minimized by protecting from light.

Lipidem with other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking, has recently taken, or plans to take.
Lipidem may interact with certain other medicines. Inform the doctor if the patient is taking or receiving medicines that prevent unwanted blood clotting, such as:

• heparin,
• coumarin derivatives, such as warfarin.
  Regular blood tests may be required to monitor blood clotting.

Pregnancy and breastfeeding

Pregnancy
This medicine will be given to pregnant women only if the doctor considers it absolutely necessary for treatment. There are no data on the use of Lipidem in pregnant women.

Breastfeeding
Breastfeeding is not recommended for mothers receiving parenteral nutrition.

Driving and operating machinery
This medicine will be administered under controlled conditions, i.e., in a hospital or under medical supervision, which generally excludes driving and operating machinery.

Lipidem contains sodium
This medicine contains 59.8 mg of sodium (the main component of table salt) in each 1,000 ml. This corresponds to 3% of the maximum recommended daily dietary sodium intake for adults.

3. How to use Lipidem

Dosage
The doctor will decide what dose is required for the patient and how long it should be administered.
Daily doses will be determined according to individual needs, age, and body weight of the patient. Doses are usually calculated based on "grams of fat per kilogram of body weight". Care will be taken to ensure that the doses used and infusion rates are appropriate for the individual patient, so as not to exceed the body's capacity to metabolize intravenously administered fat.

How Lipidem is administered
Lipidem is given as an intravenous infusion as part of a nutritional regimen. For this purpose, a tube (catheter) is inserted into a vein, through which the fat emulsion can be administered either alone or together with other fluids.

When used in newborns and children under 2 years of age, the solution (in the bottle and administration set) must be protected from light until administration is completed (see section 2).

Accidental overdose of Lipidem
If too much Lipidem is administered, the patient may develop excessively high levels of fat in the blood (hyperlipidemia), the blood may become too acidic (metabolic acidosis), or the patient may develop the so-called fat overload syndrome. Symptoms of fat overload syndrome are described in section 4, "Possible side effects".

If a patient receives too much Lipidem, the infusion will be stopped immediately. The infusion will not be resumed until the patient's condition has improved. The doctor may need to adjust the daily dose of fats. The doctor will decide whether additional treatment is necessary.

If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
The following adverse reactions may be serious. If any of the following occur in a patient,
contact a doctor immediately. The doctor will discontinue administration of this medicine:
Very rare: may occur in up to 1 in 10,000 people

• allergic reactions, for example skin reactions, shortness of breath, swelling of the lips, mouth and throat, difficulty breathing;
• breathing problems (dyspnoea);
• bluish discoloration of the skin (cyanosis).

Other adverse reactions include
Very rare: may occur in up to 1 in 10,000 people

• fat overload syndrome (see "Fat overload syndrome" below);
• increased tendency to form blood clots (hypercoagulability);
• abnormally high levels of fat in the blood (hyperlipidemia);
• abnormally high blood sugar levels (hyperglycaemia);
• high levels of acidic substances in the blood (metabolic acidosis);
• low or high blood pressure;
• drowsiness;
• nausea, vomiting, loss of appetite;
• headache;
• hot flushes;
• redness of the skin (flushing);
• fever;
• sweating;
• feeling cold, chills.

Rare: may occur in up to 1 in 1,000 people

• back, bone, chest or lower back pain.

Not known: frequency cannot be estimated from available data

• impaired bile flow (cholestasis);
• decreased number of white blood cells (leukopenia);
• decreased number of platelets (thrombocytopenia).

If any of these adverse reactions occur, the infusion will be stopped.
Fat overload syndrome:
If a patient receives too high a dose of Lipidem, the body may have difficulty using fat, leading to a condition known as fat overload syndrome. The body's ability to metabolize fat may change due to sudden changes in the patient's condition (e.g. due to impaired kidney function or infection). These symptoms are usually reversible after stopping the infusion. Fat overload syndrome is characterized by the following symptoms:

• high levels of fat in the blood (hyperlipidemia);
• fever;
• fat deposition in the liver and other organs (fatty infiltration);
• enlargement of the liver (hepatomegaly), which may sometimes be accompanied by jaundice (icterus);
• enlargement of the spleen (splenomegaly);
• decreased number of red blood cells (anaemia);
• decreased number of white blood cells (leukopenia);
• decreased number of platelets (thrombocytopenia);
• blood clotting disorders (coagulation disorders);
• breakdown of blood cells (haemolysis);
• increased number of immature red blood cells (reticulocytosis);
• abnormal liver function test results;
• loss of consciousness (coma).

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw
Tel.: + 48 22 49 21 301
Fax: + 48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store Lipidem

Keep the medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label and outer cardboard
packaging. The expiry date refers to the last day of the stated month.
After first opening, Lipidem must be used immediately.
Do not store above 25°C.
Keep the container in the outer packaging to protect from light.
Do not freeze. Products that have been frozen must be discarded.
Do not use this medicine if any of the following signs are observed:

• large oil droplets or two separate liquid layers,
• discoloration,
• container or closure damage.

When used in neonates and children under 2 years of age, the solution (in the bottle and administration set) must be protected from light until administration is completed (see section 2).

6. Contents of the pack and other information

What Lipidem contains

• The active substances in 1,000 ml of Lipidem are:
  Medium-chain triglycerides 100.0 g
  Refined, purified soybean oil 80.0 g
  Omega-3 triglycerides 20.0 g

This provides the following contents of essential fatty acids per litre:
Linoleic acid (omega-6) 38.4–46.4 g
Alpha-linolenic acid (omega-3) 4.0–8.8 g
Eicosapentaenoic acid and
docosahexaenoic acid (omega-3) 8.6–17.2 g
200 mg/ml (20%) corresponds to the total triglyceride content.
Energy value [kJ/l (kcal/l)] 7990 (1910)
Osmolality [mOsm/kg], approximately 410
Acidity or alkalinity (titration to pH 7.4) < 0.5
[mmol/l NaOH or HCl]
pH 6.0–8.5

• The other ingredients are glycerol, egg phospholipids for injection, all-rac-α-tocopherol, sodium oleate, sodium hydroxide (for pH adjustment) and water for injection.

What Lipidem looks like and contents of the pack
Lipidem is a milky white, sterile oil-in-water emulsion for infusion (for intravenous administration via drip).
It is supplied in glass bottles with rubber stoppers; pack sizes:
10 × 100 ml, 1 × 250 ml, 10 × 250 ml, 1 × 500 ml, 10 × 500 ml, 1 × 1,000 ml, 6 × 1,000 ml
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
B. Braun Melsungen AG
Carl-Braun-Straße 1
34212 Melsungen, Germany
Correspondence address
34209 Melsungen, Germany

This medicinal product is authorised in the European Economic Area countries and in the United Kingdom (Northern Ireland) under the following names:
Austria: Lipidem
Czech Republic: Lipoplus 20%
Germany: Lipidem
Denmark: Lipidem
Spain: Lipoplus 20%
Finland: Lipoplus 200 mg/ml
France: Lipidem 200 mg/ml
United Kingdom
(Northern Ireland): Lipidem 200 mg/ml Emulsion for Infusion
Italy: Lipidem 200 mg/ml
Luxembourg: Lipidem
Norway: Lipidem
Portugal: Lipoplus
Sweden: Lipoplus
Slovakia: Lipoplus 20%
Poland: Lipidem

Information intended exclusively for medical professionals:

Administration method and special warnings regarding removal and handling of the medicinal product
Intravenous administration.
Fat emulsions are suitable for peripheral venous administration and may also be administered separately via peripheral veins as part of total parenteral nutrition.
When administering fat emulsions simultaneously with amino acid and carbohydrate solutions, the Y-type connector or bypass set should be placed as close to the patient as possible.
When used in neonates and children under 2 years of age, the solution (in the bottle and administration set) must be protected from light until the end of the infusion.
For single use only. The container and any unused portions of the product must be discarded. Do not connect partially used containers. Gently shake before use.
Use only undamaged containers containing a uniform, milky-white emulsion. The emulsion should be inspected before administration to detect phase separation or discoloration (presence of oil droplets or an oil layer).
Prior to infusion, the emulsion should be brought to room temperature naturally, i.e., the product must not be placed in any heating device (such as a heater or microwave oven).
If filters are used, they must be fat-permeable.
Before administering fat emulsion together with other solutions via a Y-connector or bypass set, compatibility of these fluids must be verified, especially when co-administered with carrier solutions containing other medicinal products. Particular caution is required when administering solutions containing divalent cations (e.g., calcium or magnesium) simultaneously.

Special precautions for disposal and preparation of the medicinal product for use
When used in neonates and children under 2 years of age, the solution (in the bottle and administration set) must be protected from light until the end of the infusion. Exposure of parenteral nutrition solutions to light, particularly after addition of trace elements and/or vitamins, may lead to formation of peroxides and other degradation products; this risk can be minimized by protecting the solution from light.

Duration of treatment
Due to limited clinical experience with long-term use of the medicinal product Lipidem, it should normally not be administered for longer than one week. If prolonged parenteral nutrition with fat emulsions is indicated, Lipidem may be administered for a longer duration provided that appropriate monitoring is performed.

Infusion rate
Infusion should be administered at the lowest possible rate. During the first 15 minutes, the infusion rate should be only 50% of the maximum recommended infusion rate.

Maximum infusion rate in adults
Up to 0.15 g lipids/kg body weight/hour.

Maximum infusion rate in preterm infants, full-term neonates, infants, and young children
Up to 0.15 g lipids/kg body weight/hour.

Maximum infusion rate in older children and adolescents
Up to 0.15 g lipids/kg body weight/hour.

Effect on laboratory test results
Lipids may interfere with certain laboratory tests (e.g., bilirubin, lactate dehydrogenase, oxygen saturation measurements) if blood samples are taken before lipids have been cleared from the circulation, which may take 4 to 6 hours.

Pharmaceutical incompatibilities
Do not mix this medicinal product with other medicinal products, as compatibility studies have not been conducted.

Shelf-life after addition of compatible substances
From a microbiological standpoint, the product should be used immediately after addition of other substances. If the product is not used immediately after addition of other substances, responsibility for storage duration and conditions lies with the user.

Complete information on this product is provided in the Summary of Product Characteristics for Lipidem.

Additional special warnings and precautions for use
Exposure of parenteral nutrition solutions to light, particularly after addition of trace elements and/or vitamins, may have undesirable effects on clinical response in neonates due to formation of peroxides and other degradation products. When used in neonates and children under 2 years of age, the medicinal product Lipidem must be protected from light until the end of the infusion.