Package Insert: Information for the User

SMOFlipid 200 mg/ml Infusion Emulsion

Soybean oil, Medium-Chain Triglycerides, Olive oil, Fish oil

Read this package insert carefully before starting to use this medication, as it contains important information for you.

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

1. What is SMOFlipid and how is it used

2. What you need to know before starting to take SMOFlipid

3. How to use SMOFlipid

4. Possible adverse effects

5. Storage of SMOFlipid

6. Contents of the package and additional information

SMOFlipid contains four different lipids (fats): soybean oil, medium-chain triglycerides, olive oil, and fish oil, which is rich in omega-3 fatty acids. The liquid is a mixture of fats and water, which is called a "lipid emulsion".

• it works by providing energy and fatty acids to the body
• it is introduced into the bloodstream through a catheter or infusion pump

A healthcare professional will administer SMOFlipid when other forms of nutrition are not suitable or have not been effective.

Do not use SMOFlipid

• if you are allergic to soybean oil, medium-chain triglycerides, olive oil, fish oil, or any of the other ingredients in this medication (listed in section 6)
• if you are allergic (hypersensitive) to other products that contain fish, egg, soy, or peanuts

• if you have severe high levels of fat in your blood (hyperlipemia)
• if you have severe kidney or liver problems
• if you have severe blood clotting disorders (coagulopathy)
• if you are in shock
• if you have fluid in your lungs (pulmonary edema), fluid overload (hyperhydration), or heart failure due to excess fluid in your body
• if you are in a unstable condition, for example, after severe injuries, acute myocardial infarction, cerebral hemorrhage, blood coagulation (thrombosis), metabolic acidosis (metabolic disorder resulting in elevated acid levels in the blood), or untreated diabetes, blood poisoning, and dehydration

Warnings and precautions

Consult your doctor or nurse before starting to use SMOFlipid ifyou have a problem with high levels of lipids in your blood due to your body not being able to use fats properly (altered lipid metabolism).

When used in newborns and children under 2 years, the solution (in bags and administration equipment) must be protected from exposure to light until the administration is completed. Exposure of SMOFlipid to ambient light, especially after mixing it with oligoelements or vitamins, generates peroxides and other degradation products that can be reduced if the product is protected from exposure to light.

Allergic reactions

If you have any allergic reaction while receiving SMOFlipid, it is necessary to stop it immediately. If you experience any of the following situations while receiving the infusion, inform your doctor or nurse immediately:

• fever (elevated temperature)
• shivering
• hives
• difficulty breathing

Children

Inform your doctor or nurse if this medication is being given to your newborn child and they have:

- too much bilirubin in the blood (hyperbilirubinemia)

- high blood pressure in their lungs (pulmonary hypertension)

If your newborn child is taking SMOFlipid for a long period of time, the doctor will perform blood tests to see how it is working.

Use of SMOFlipid with other medications:

Inform your doctor or pharmacist if you are using or have recently used other medications.

Specifically, inform your doctor if you are taking or have recently taken medications used to prevent blood clotting such as warfarin and heparin.

• SMOFlipid naturally contains vitamin K, which can affect warfarin. However, the content of vitamin K1in SMOFlipid is so low that such problems are very rare.
• Administered heparin at clinical doses can cause an initial increase in blood triglyceride levels due to the release of fatty acids from tissues into the bloodstream and therefore fewer fatty acids would be eliminated from your blood (decreased clearance of triglycerides).

Pregnancy and breastfeeding:

The safety of receiving SMOFlipid while pregnant or breastfeeding is unknown. If you need intravenous nutrition during pregnancy or breastfeeding, your doctor will only administer SMOFlipid after careful consideration.

If you are pregnant or breastfeeding, believe you may be pregnant, or intend to become pregnant, consult your doctor before using this medication.

Driving and operating machinery:

This is not relevant because the medication is administered in the hospital.

Smoflipid containssodium

This medication contains 5mmol (115mg) of sodium per 1000ml. Patients with a low-sodium diet should be aware of this.

SMOFlipid is administered into your bloodstream through an infusion set or a pump. Your doctor will decide your dose based on your body weight and your ability to use the infused fat amount.

When used in newborns and children under 2 years old, the solution (in the bags and administration equipment) must be protected from light exposure until the end of administration (see section 2).

For doctors and healthcare professionals, consult “Administration Method” at the end of the leaflet for more details on the dose and administration.

If you take more SMOFlipid than you should

If you receive a dose that is too high, there will be a risk that the amount of fat you receive will be greater than what your body can absorb. This is called “fat overload syndrome”. For more information, see section 4, Possible Adverse Effects.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately, or call the Toxicology Information Service, phone 91 562 04 20 (indicating the medication and the amount ingested)

Like all medications, this medication may produce adverse effects, although not all people may experience them.

Fatty Liver Syndrome.

This may occur when your body has trouble using fats due to an excess of SMOflipid. It may also occur due to a sudden change in your condition (such as kidney problems or infection). Fatty liver syndrome is characterized by high levels in the blood (hyperlipidemias), fever, excessive fat in your tissues (steatosis), and disorders in various organs of the body and coma. All symptoms will normally disappear when treatment is stopped.

Frequent(may affect up to 1 in 10 patients)

• mild increase in body temperature

Occasional(may affect up to 1 in 100 patients)

• shaking
• loss of appetite
• nausea
• vomiting

Rare(may affect up to 1 in 1000 patients)

• allergic reactions (e.g. elevated temperature, inflammation, decreased blood pressure, skin rash, redness, headache)
• sensation of cold or heat
• pallor
• blue discoloration of the skin and mucous membranes (due to a reduction in oxygen content in the blood)
• pain in the neck, back, bones, chest, and lower back
• elevated or decreased blood pressure
• difficulty breathing

Very Rare(may affect up to 1 in 10,000 patients)

• prolonged and convulsive erection in men

Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is an adverse effect that does not appear in this prospectus. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use:www.notificaRAM.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medication.

Keep out of sight and reach of children.

Do not store at a temperature above25ºC. Do not freeze.

Do not use SMOFlipid after the expiration date that appears on the label after CAD. The expiration date is the last day of the month indicated.

Do not use SMOFlipid if you notice that the container is damaged. Use only if the solution is white and homogeneous. For single use only. Unused product must be eliminated. Do not reuse.

Ask your pharmacist how to dispose of the containers and medications you do not need. In this way, you will help protect the environment.

When used in newborns and children under 2 years, the solution (in bags and administration equipment) must be protected from exposure to light until the administration is completed (see section 2).

Composition of SMOFlipid:

The active principles are:

Soybean oil, refined60 mg/ml

Medium-chain triglycerides60 mg/ml

Refined olive oil50 mg/ml

Fish oil, rich in omega-3 fatty acids30 mg/ml

The other components are: Glycerol, egg lecithin, dl-?-tocoferol (vitamin E), water for injection, sodium hydroxide (to adjust the pH), sodium oleate

Appearance of the product and contents of the container:

SMOFlipid is a white and homogeneous emulsion and is available in glass bottles or plastic bags

Glass bottlePlastic bag

100 ml100 ml

10x100 ml10x100 ml, 20 x100 ml

250 ml250 ml

10x250 ml10x250 ml

500 ml500 ml

10x500 ml10x500 ml

1000 ml

6x1000 ml

Only some sizes of packaging may be commercially available.

Marketing authorization holder and manufacturer:

Marketing authorization holder

Fresenius Kabi AB

751 74 Uppsala

Sweden

Local representative

Fresenius Kabi España S.A.U

Marina 16-18 08005 (Barcelona)

Spain

Manufacturer

Fresenius Kabi AB, SE-751 74 Uppsala, Sweden (plastic bags)

Fresenius Kabi Austria GmbH, A-8055 Graz, Austria (glass bottles)

For more information about this medicinal product, please contact the local representative of the marketing authorization holder:

This medicinal product is authorized in the Member States of the European Economic Area under the following names:

Austria, Belgium, Finland, France, Germany, Iceland, Ireland, Italy, Netherlands, Norway, Slovenia, Sweden, United Kingdom: SMOFlipid 200 mg/ml

Cyprus, Czech Republic, Estonia, Greece, Hungary, Latvia, Lithuania, Luxembourg, Spain: SMOFlipid 20%

Denmark, Poland, Portugal, Slovakia: SMOFlipid

Last update of the summary of product characteristics: February 2020

For detailed and updated information about this medicinal product, please visit the website of the Spanish Agency of Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/

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This information is intended solely for healthcare professionals:

Warnings and Precautions

The serum triglyceride concentration should not exceed 3 mmol/l during infusion. A overdose may cause a fat overload syndrome. Special caution should be exercised in patients with a marked risk of hyperlipidemias (e.g. patients receiving high doses of lipids, severe sepsis and very low birth weight infants).

The administration of medium-chain fatty acids alone may result in a metabolic acidosis. This risk is largely eliminated by the simultaneous infusion of long-chain fatty acids included in SMOFlipid. In addition, the simultaneous administration of carbohydrates will also eliminate this risk. Therefore, it is recommended to infuse a solution of carbohydrates or carbohydrates with amino acids simultaneously. Regular laboratory tests associated with the monitoring of parenteral nutrition should be checked. These include blood glucose levels, liver function tests, acid-base metabolism, fluid balance, complete blood count and electrolytes.

Any sign or symptom of anaphylactic reaction (such as fever, tremor, urticaria or dyspnea) should be followed by an immediate interruption of the infusion.

SMOFlipid should be administered with caution in neonates and premature infants with hyperbilirubinemia and in cases of pulmonary hypertension. In neonates, particularly in premature infants with long-term parenteral nutrition, platelet counts, liver function tests and serum triglycerides should be monitored.

SMOFlipid contains up to 5 mmol of sodium per 1000 ml. This should be taken into account in patients following a low-sodium diet.

Generally, the addition of other medications or substances to SMOFlipid should be avoided unless compatibility is known.

Administration

Intravenous infusion in a peripheral or central vein.

Instructions for use and handling

Use only if the emulsion is homogeneous. For the infusion bag: The Oxalert indicator should be inspected before removing the overbag. If the indicator is black, oxygen has penetrated the overbag and the product should be discarded.Check the emulsion visually for any signs of phase separation before administration. Ensure that the final infusion emulsion does not show any signs of phase separation. For single use only. Any remaining mixture should be discarded.

Admixtures:SMOFlipid can be mixed aseptically with amino acids, glucose and electrolyte solutions to produce Total Parenteral Nutrition (TPN) "All-In-one" mixtures. On request, compatibility data and storage times for different mixtures are available. Additives should be added aseptically. Any remaining mixture after infusion should be discarded.

Do not store above25ºC. Do not freeze

Stability after mixing

In the event of mixing SMOFlipid with other products, the mixture should be used immediately from a microbiological point of view. If the mixtures are not used immediately, the time once the container is opened and the storage conditions are the responsibility of the user and should not normally be greater than 24 hours at 2 –8ºC, unless the additions have been made in controlled and validated aseptic conditions.

Instructions for Use for the Infusion Bag Exclusively

Instructions for use:SMOFlipid 200 mg/ml emulsion for infusion

Infusion bags Fresenius Kabi

1. Inspect the Oxalert indicator A before removing the overbag. If the indicator is black, oxygen has penetrated the overbag and the product should be discarded.

1. Remove the overbag by tearing along the perforation and discard the Oxalert overbag and the oxygen absorber B.

1. If additives are required, break the white addition port by the arrow mark (A). If no additives are required, proceed to step 5.

1. Insert the needle horizontally through the center of the addition port membrane and inject the additives (of known compatibility). Use syringes with needles of caliber 18- 23 and a maximum length of 40 mm.

1. Use a perfusion equipment without air entry or close the air entry of the perfusion equipment. Follow the instructions for use of the perfusion equipment. Use a cannula with the specified diameter in ISO 8536-4, 5,6 +/ - 0.1 mm.

1. Break the blue infusion port by the arrow mark.

1. Hold the base of the infusion port. Insert the cannula through the infusion port by a slight rotation of the wrist until the cannula is fully inserted.

Hang the bag on the hanger by the perforation and start the infusion