Consumer medicine information

SMOFlipid 20%

Soya oil; Medium chain triglycerides; Olive oil; Fish oil - rich in omega-3 acids

BRAND INFORMATION

Brand name

SMOFlipid

Active ingredient

Soya oil; Medium chain triglycerides; Olive oil; Fish oil - rich in omega-3 acids

Schedule

Unscheduled

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using SMOFlipid 20%.

SUMMARY CMI

SMOFlipid®

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using SMOFlipid?

SMOFlipid contains the active ingredients soya oil, medium chain triglycerides, olive oil and fish oil-rich in omega-3 fatty acids. SMOFlipid is a supplement to parenteral nutrition, which provides your body with nutrition by the intravenous route. It is usually given together with carbohydrates, amino acids and salts to provide an intravenous diet.

For more information, see Section 1. Why am I using SMOFlipid? in the full CMI.

2. What should I know before I use SMOFlipid?

Do not use if you have ever had an allergic reaction to fish, soy, eggs, peanuts or any of the ingredients listed at the end of the CMI. Tell your doctor if you have an inability to break down fats.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I use SMOFlipid? in the full CMI.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking anticoagulants (medicines for preventing blood clotting) or any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines may interfere with SMOFlipid and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use SMOFlipid?

The dose of SMOFlipid which you will require will be determined by your doctor or pharmacist. Your doctor will supervise your treatment with SMOFlipid.

More instructions can be found in Section 4. How do I use SMOFlipid? in the full CMI.

5. What should I know while using SMOFlipid?

Things you should do
  • Remind any doctor, dentist, pharmacist or nurse you visit that you are using SMOFlipid.
  • Call you doctor straightaway if you have signs and symptoms of allergic reactions. In case of an allergic reaction, the infusion should be stopped immediately, and appropriate measures need to be taken.
Things you should not do
  • Do not stop using this medicine without consulting your health care professional
  • Do not take any other medicines without first telling your health care professional
  • Do not give this medicine to anyone else, even if they have the same condition as you
Driving or using machines
  • The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.
Drinking alcohol
  • The effects of alcohol with SMOFlipid use were not studied. Your doctor will decide what you need to do.
Looking after your medicine
  • Store below 25°C. Do not freeze. Do not use after the expiry date stated on the label.

For more information, see Section 5. What should I know while using SMOFlipid? in the full CMI.

6. Are there any side effects?

Less serious side effects such as nausea, vomiting, headaches, and flatulence may occur. If you get any adverse effects, talk to your doctor or nurse.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

SMOFlipid®

Active ingredient(s): soya oil, medium chain triglycerides, olive oil and fish oil-rich in omega-3 fatty acids

Consumer Medicine Information (CMI)

This leaflet provides important information about using SMOFlipid. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using SMOFlipid.

Where to find information in this leaflet:

1. Why am I using SMOFlipid?
2. What should I know before I use SMOFlipid?
3. What if I am taking other medicines?
4. How do I use SMOFlipid?
5. What should I know while using SMOFlipid?
6. Are there any side effects?
7. Product details

1. Why am I using SMOFlipid?

SMOFlipid contains the active ingredients soya oil, medium chain triglycerides, olive oil and fish oil-rich in omega-3 fatty acids. SMOFlipid is used for supply of energy and essential fatty acids via intravenous route. When the intake of nutrients or food into the mouth or directly into the gut is not possible or not enough to supply the needs, then intravenous nutrients or food can be given. This is especially important for people under physical stress from illness or recent surgery.

2. WHAT SHOULD I KNOW BEFORE I USE SMOFLIPID?

Warnings

Do not use SMOFlipid if:

  • you are allergic to fish, soy, eggs, peanuts, or any of the ingredients listed at the end of this leaflet.
    Always check the ingredients to make sure you can use this medicine.
  • if you have one of the following conditions:
    - an abnormal level of lipids in the blood
    - severe liver failure
    - severe kidney failure (when dialysis facilities are not available)
    - severe blood coagulation disorders
    - not able to receive infusion therapy
    - unstable, e.g. acute shock, uncompensated diabetes mellitus, heart attack, stroke, metabolic acidosis.

Check with your doctor if you:

  • are at risk for having an abnormal level of lipid in the blood (severe sepsis, extremely low birth weight infant)
  • have any other medical conditions such as liver, kidney, pancreas or thyroid disorders or diabetes
  • are taking any other medicines including any that you buy without a prescription from your pharmacy, supermarket or health food shop. These medicines may affect the action of SMOFlipid or may affect how well SMOFlipid works.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

It is not known whether SMOFlipid will harm your unborn baby or affect your reproductive capacity.

Check with your doctor if you are pregnant or intend to become pregnant.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

Use in Paediatrics

SMOFlipid should be given with caution to neonates and premature infants with hyperbilirubinaemia and pulmonary hypertension.

When used in neonates and children below 2 years, SMOFlipid should be protected from ambient light until administration is completed.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines may interfere with SMOFlipid and affect how it works.

Tell your doctor or pharmacist if you are taking anticoagulants (medicines for preventing blood clotting) such as heparin or any other medicines. Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect SMOFlipid.

4. How do I use SMOFlipid?

How much is given

  • The dose of SMOFlipid which you will require will be determined by your doctor or pharmacist. Your doctor will supervise your treatment with SMOFlipid.

How to use SMOFlipid

  • SMOFlipid will be given to as a continuous infusion into a vein. A cannula (administration needle) is placed in a vein by your health care professional. This is normally done in a health institution but in some cases at home. An electronic pump may be used to control the speed of the infusion of drip.
  • The infusion is for or single use in one person only.

If you forget to use SMOFlipid

This rarely happens as SMOFlipid is usually administered under the care of a trained health care professional in a hospital or clinic setting.

If you use too much SMOFlipid

This rarely happens as SMOFlipid is usually administered under the care of a trained professional in a hospital or clinic setting. However, if you are given SMOFlipid too quickly or too much, you may experience the following side effects: feeling sick (nausea and vomiting) or becoming flushed and sweaty. These effects usually reversed if the infusion is discontinued.

Your doctor has information on how to recognise and treat an overdose. Ask your doctor if you have any concerns.

If you think that you have used too much SMOFlipid, you may need urgent medical attention.

You should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while using SMOFlipid?

Things you should do

  • Remind any doctor, dentist, pharmacist or nurse you visit that you are using SMOFlipid.
  • Call your doctor straight away if you have signs and symptoms of allergic reactions. In case of an allergic reaction, the infusion should be stopped immediately, and appropriate measures need to be taken.
  • Discuss with your health care professional your progress, especially if any complications occur during therapy. Frequent clinical evaluations and laboratory tests maybe required.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how SMOFlipid affects you.

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

Drinking alcohol

Tell your doctor if you drink alcohol.

The effects of alcohol with SMOFlipid use were not studied. Your doctor will decide what you need to do.

Looking after your medicine

SMOFlipid is usually administered under the care of a health care professional in a hospital or clinic setting. Your doctor and hospital pharmacist are responsible for the correct storage, use and disposal of SMOFlipid. It is recommended that SMOFlipid be stored below 25°C in a cool dry place, protected from light and away from moisture or heat. The product should not be frozen.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or nurse if you have any further questions about side effects.

Less serious side effects

Less serious side effectsWhat to do
  • Nausea and vomiting
  • headaches
  • increased blood triglyceride or sugar level
Speak to your doctor if you have any of these less serious side effects and they worry you.

Tell your doctor or nurse if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What SMOFlipid contains

Active ingredients
(main ingredients)		soya oil 60 g/L
medium chain triglycerides 60 g/L
olive oil 50 g/L
fish oil-rich in omega-3 fatty acids 30 g/L
Other ingredients
(inactive ingredients)		egg lecithin
dl-alpha-tocopherol (Vitamin E)
glycerol
sodium hydroxide (pH adjustment)
sodium oleate
water for injections
Potential allergensFish, soy, peanut, egg

Do not take this medicine if you are allergic to any of these ingredients.

SMOFlipid does not contain any preservative. SMOFlipid does not contain gluten, lactose, sucrose, tartrazine or any other azo dyes.

Total energy: 8400 kJ (2000kcal) / 1000mL.

Osmolality: 380 mOsm/kg water

pH: approx. 8

SMOFlipid comes in different pack sizes and can be identified by AUST numbers:

10 or 20 x 100mL bags (Aust R 262963)

10 x 250mL bags (Aust R 262964)

12 x 500mL bags (Aust R 158359)

What SMOFlipid looks like

SMOFlipid is a milky white emulsion which is supplied in plastic bags packaged in a protective over wrap.

Who distributes SMOFlipid

Fresenius Kabi Australia Pty Limited
Level 2, 2 Woodland Way
Mount Kuring-gai NSW 2080
Australia

Telephone: 1300 361 004

This leaflet was prepared in March 2023.

Published by MIMS April 2024

BRAND INFORMATION

Brand name

SMOFlipid

Active ingredient

Soya oil; Medium chain triglycerides; Olive oil; Fish oil - rich in omega-3 acids

Schedule

Unscheduled

 

1 Name of Medicine

Fish oil - rich in omega-3 acids, medium chain triglycerides, olive oil, soya oil.

2 Qualitative and Quantitative Composition

SMOFlipid emulsion for infusion is a white homogenous emulsion.
Each 1000 mL contains: soya oil 60 g, medium chain triglycerides 60 g, olive oil 50 g, fish oil - rich in omega-3 acids 30 g.
Total energy: 8400 kJ (2000 kcal); pH: approx. 8; osmolality: 380 mOsm/kg water.

Excipients with known effect.

Egg lecithin.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

SMOFlipid is a white homogenous emulsion for infusion.

4 Clinical Particulars

4.1 Therapeutic Indications

Supply of energy and essential fatty acids to patients, as part of a parenteral nutrition regimen, when oral or enteral nutrition is impossible, insufficient or contraindicated.

4.2 Dose and Method of Administration

The patient's ability to eliminate the fat infused should govern the dosage and infusion rate (see Section 4.4 Special Warnings and Precautions for Use).

Adults.

The standard dose is 1.0-2.0 g fat/kg body weight (b.w)/day, corresponding to 5-10 mL/kg b.w/day.
The recommended infusion rate is 0.125 g fat/kg b.w/hour, corresponding to 0.63 mL SMOFlipid/kg b.w/hour, and should not exceed 0.15 g fat/kg b.w/hour, corresponding to 0.75 mL SMOFlipid/kg b.w/hour.

Neonates and infants.

The initial dose should be 0.5-1.0 g fat/kg b.w/day followed by a successive increase by 0.5-1.0 g fat/kg b.w/day up to 3.0 g fat/kg b.w/day.
It is recommended not to exceed a daily dose of 3 g fat/kg b.w/day, corresponding to 15 mL SMOFlipid/kg b.w/day.
The rate of infusion should not exceed 0.125 g fat/kg b.w/hour.
In premature and low birth weight neonates, SMOFlipid should be infused continuously over around 24 hours.

Children.

It is recommended not to exceed a daily dose of 2 g fat/kg b.w/day, corresponding to 10 mL SMOFlipid/kg b.w/day. With increased requirements in the youngest children a dose up to a maximum of 3 g fat/kg b.w/day can be considered.
The daily dose should be increased gradually during the first week of administration.
The infusion rate should not exceed 0.15 g fat/kg b.w/hour.

Administration.

Intravenous infusion into a peripheral or central vein.
When used in neonates and children below 2 years, the solution (in bags and administration sets) should be protected from light exposure until administration is completed (see Section 4.4; Section 6.3).

Instructions for use.

Use only if the emulsion is homogeneous.
When used in neonates and children below 2 years, protect from light exposure, until administration is completed. Exposure of SMOFlipid to ambient light, especially after admixture with trace elements and/or vitamins, generates peroxides and other degradation products that can be reduced by protection from light exposure (see Section 4.4; Section 6.3).

For inner bag.

The integrity indicator (Oxalert) should be inspected before removing the overpouch. If the indicator is black, oxygen has penetrated the overpouch and the product should be discarded (see Section 4.2 Dose and Method of Administration, Special handling instructions).
Inspect the emulsion visually for phase separation prior to administration. Ensure that the final emulsion for infusion does not show any evidence of phase separation. For single use only. Any unused emulsion should be discarded.

Additives.

SMOFlipid may be aseptically admixed with amino acid, glucose, and electrolyte solutions to produce "All-In-One" total parenteral nutrition (TPN) admixtures.
Additions should be made aseptically. Any mixture remaining after infusion must be discarded.

Compatibility.

Compatibility data are available with the named branded products Addaven, Aminoven 10%, Dipeptiven, Glycophos, Vamin 18EF, Vitalipid N Adult, Soluvit N and IV generics of glucose 20-50% solutions in defined amounts and IV generics of electrolytes in defined concentrations. When making electrolyte additions, the amounts already present in the bag should be taken into account to meet the clinical needs of the patient. Generated data supports additions according to Table 1.

Note.

This table is intended to present compatibility. It is not a dosing guideline. Prior to admixture preparation, it is important to confirm the additive compatibility and the recommended mixing sequences.

Special handling instructions.

Infusion bag with Biofine 1 chamber primary bag.

1. The integrity indicator (Oxalert) A should be inspected before removing the overwrap. If the indicator is black the overwrap is damaged and the product should be discarded (see Figure 1).
2. Remove the overwrap by tearing at the notch and pulling down along the container (see Figure 2). The Oxalert sachet A and the oxygen absorber B should be disposed.
3. If additions are to be used, break off the tamper-evident arrow flag from the white additive port (see Figure 3). If no additives are to be used, see Figure 5.
4. Insert the needle horizontally through the centre of the septum of the additive port and inject the additives (with known compatibility). Mix thoroughly by inverting container several times (see Figure 4).
5. Use a non-vented infusion set or close the air vent on a vented set (see Figure 5). Follow the instructions for use for the infusion set.
6. Break off the tamper-evident arrow flag from the blue infusion port (see Figure 6).
7. Hold the base of the infusion port. Insert the spike through the infusion port, by rotating your wrist slightly until the spike is inserted (see Figure 7).
8. To hang the bag, invert and place hanger through the container notch (see Figure 8).

4.3 Contraindications

Hypersensitivity to fish, egg, soya or peanut protein, or to any of the active ingredients or excipients.
Severe hyperlipidaemia.
Severe liver insufficiency.
Severe blood coagulation disorders.
Severe renal insufficiency without access to hemofiltration or dialysis.
Acute shock.
General contraindications to infusion therapy: acute pulmonary oedema, hyperhydration, decompensated cardiac insufficiency.
Unstable conditions (e.g. severe post-traumatic conditions, uncompensated diabetes mellitus, acute myocardial infarction, stroke, embolism, metabolic acidosis and severe sepsis and hypotonic dehydration).

4.4 Special Warnings and Precautions for Use

The capacity to eliminate fat is individual and should therefore be monitored routinely by the clinician. This is in general done by checking the triglyceride levels. Special precaution should be taken in patients with a marked risk for hyperlipidaemia (e.g. patients with high lipid levels, severe sepsis and extremely low birth weight infants). The concentration of triglycerides in serum should in general not exceed 3 mmol/L during infusion. Reduction of the dosage or cessation of the lipid emulsion should be considered if serum or plasma triglyceride concentrations during or after infusion exceed 3 mmol/L. An overdose may lead to fat overload syndrome.
This medicinal product contains soya oil, fish oil and egg lecithin, which may rarely cause allergic reactions. Cross allergic reaction has been observed between soya-bean and peanut.
SMOFlipid should be given with caution in conditions of impaired lipid metabolism, which may occur in patients with renal failure, diabetes mellitus, pancreatitis, impaired liver function, hypothyroidism and sepsis.
Clinical data in patients with diabetes mellitus or renal failure are limited.
Administration of medium-chain fatty acids alone can result in metabolic acidosis. This risk is to a great extent reduced by the simultaneous infusion of the long chain fatty acids included in SMOFlipid. Concomitant administration of carbohydrates will further reduce this risk. Hence, simultaneous infusion of carbohydrate or a carbohydrate containing amino acid solution is recommended.
Any signs or symptoms of anaphylactic reaction (such as fever, shivering, rash or dyspnoea) should lead to immediate interruption of the infusion.

Fat overload syndrome.

Impaired capacity to eliminate triglycerides can lead to "fat overload syndrome" which may be caused by overdose. Possible signs of metabolic overload must be observed. The cause may be genetic (individually different metabolism) or the fat metabolism may be affected by ongoing or previous illnesses. This syndrome may also appear during severe hypertriglyceridaemia, even at the recommended infusion rate, and in association with a sudden change in the patient's clinical condition, such as renal function impairment or infection. The fat overload syndrome is characterised by hyperlipaemia, fever, fat infiltration, hepatomegaly with or without icterus, splenomegaly, anaemia, leukopaenia, thrombocytopenia, coagulation disorder, haemolysis and reticulocytosis, abnormal liver function tests and coma. The symptoms are usually reversible if the infusion of the fat emulsion is discontinued.
Should signs of a fat overload syndrome occur, the infusion of SMOFlipid should be discontinued.

Use in the elderly.

No data available.

Paediatric use.

SMOFlipid should be given with caution to neonates and premature infants with hyperbilirubinaemia and cases with pulmonary hypertension. In neonates, particularly premature infants on long-term parenteral nutrition, blood platelet counts, liver function tests and serum triglycerides should be monitored.
Light exposure of solutions for intravenous parenteral nutrition, especially after admixture with trace elements and/or vitamins, may have adverse effects on clinical outcome in neonates, due to generation of peroxides and other degradation products. When used in neonates and children below 2 years, SMOFlipid should be protected from ambient light until administration is completed (see Section 4.2; Section 6.3).

Effects on laboratory tests.

Laboratory tests generally associated with monitoring of intravenous nutrition should be checked regularly. These include blood glucose levels, liver functions tests, acid/ base metabolism, fluid balance, full blood count and electrolytes.
As with all lipid emulsions, SMOFlipid may interfere with certain laboratory measurements (bilirubin, haemoglobin, lactate dehydrogenase, oxysaturation), if blood is sampled before fat has adequately been cleared from the bloodstream. In most patients, fat is cleared after a fat free period or interval of 5 to 6 hours.

4.5 Interactions with Other Medicines and Other Forms of Interactions

The addition of other medications or substances to SMOFlipid should generally be avoided unless compatibility is known (see Section 4.2 Dose and Method of Administration, Special handling instructions).
Heparin given in clinical doses causes a transient increase in lipoprotein lipase release into the circulation. This may initially result in increased plasma lipolysis, followed by a transient decrease in triglyceride clearance.
Soya oil has a natural content of vitamin K1. The content is however so low in SMOFlipid that it is not expected to significantly influence the coagulation process in patients treated with coumarin derivatives.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

The potential effects of SMOFlipid on fertility and general reproductive performance have not been determined in animal studies.
(Category B3)
There are no adequate and well-controlled studies in pregnant women with SMOFlipid or its individual components; therefore, the safety of SMOFlipid in pregnant women is not known.
No animal studies have been conducted with the combined lipid components of SMOFlipid to evaluate effects on reproduction. Embryotoxicity and increased incidences of fetal skeletal variations have been observed in rabbits that had received medium chain fatty acid containing lipids similar to SMOFlipid during the period of organogenesis. SMOFlipid should not be used during pregnancy unless the expected therapeutic benefit clearly outweighs the potential risk to the fetus.
 It is not known whether SMOFlipid can enter maternal milk. Therefore, SMOFlipid should be used during lactation only if clearly needed.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

Most common drug-related treatment-emergent adverse events (TEAEs) in SMOFlipid 20% and comparator pooled groups (i.e. those occurring in more than 2 patients of any pooled group) observed in 7 clinical trials are presented in Table 2.
Since SMOFlipid has been marketed, there was only 1 spontaneous report of an adverse drug reaction (a case of non-serious erythema) in a 75 year old female patient.
Should triglyceride levels during infusion of SMOFlipid rise above 3 mmol/L, the infusion should be stopped or, if necessary, continued at a reduced dosage.
SMOFlipid should always be a part of a complete parenteral nutritional treatment including amino acids and glucose. Nausea, vomiting and hyperglycaemia may sometimes be associated with parenteral nutrition.
Monitoring of triglycerides and blood glucose levels are recommended to avoid elevated levels, which may be harmful.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at https://www.tga.gov.au/reporting-problems.

4.9 Overdose

Overdose leading to fat overload syndrome may occur as a result of a too rapid infusion rate, or chronically at recommended rates of infusion in association with a change in the patient's clinical conditions e.g. renal function impairment or infection.
Overdosage may lead to side-effects (see Section 4.8 Adverse Effects (Undesirable Effects)). In these cases, the lipid infusion should be stopped or, if necessary, continued at a reduced dosage.
For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

The fat emulsion has a particle size and biological properties similar to those of endogenous chylomicrons. The constituents of SMOFlipid (soya oil, medium chain triglycerides, olive oil and fish oil) have their own pharmacodynamic properties in addition to their energy contents.
Soya oil has a high content of essential fatty acids. The omega-6 (ω6) fatty acid linoleic acid is the most abundant (approx. 55-60%). Alpha-linolenic acid, an omega-3 (ω3) fatty acid, constitutes about 8%. This part of SMOFlipid provides essential fatty acids.
Medium-chain fatty acids are rapidly oxidised.
Olive oil mainly provides energy in the form of mono-unsaturated fatty acids.
Fish oil is characterised by a high content of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). DHA is an important structural component of cell membranes, whereas EPA is a precursor of eicosanoids as prostaglandins, thromboxanes and leucotrienes.
Vitamin E protects unsaturated fatty acids against lipid peroxidation.

Mechanism of action.

No data available.

Clinical trials.

Nine studies examined the safety and tolerance of SMOFlipid with efficacy assessed in 4 studies. A total of 558 patients were assessed for safety and of these 282 received SMOFlipid (195 adults, and 87 paediatric patients including 72 preterm infants).

Adults.

Two hundred and forty-nine post-surgical adult patients received either SMOFlipid (n = 126) or an unregistered comparator containing 200 g/L soya oil (n = 123) for 5 days in a randomised, double blind study. SMOFlipid 20% or the comparator were administered at a rate of 1.5 g fat/kg b.w/day starting on the morning of Day 1 (the day after surgery) and continuing for 5 days. Patients also received amino acids and glucose as additional parenteral nutrition. Electrolytes, trace elements and vitamins were administered as required.
Elimination of SMOFlipid 20% was at least as rapid as the elimination of the soya oil product over the 5 days of infusion. Mean serum total cholesterol and phospholipid were comparable in the treatment groups at all time points. Patients given SMOFlipid were hospitalised for a mean of 15.7 days compared with 17.8 days for patients given the comparator. Mean length of stay in ICU was 4.7 days for SMOFlipid vs. 5.2 days for the comparator. In a subgroup of 19 patients given SMOFlipid and 14 given the comparator who were examined for differences in fatty acid profiles there were higher mean concentrations of the ω3 fatty acids EPA and DHA and a lower mean concentrations of the ω6 fatty acids, linoleic acid in plasma free fatty acids and in plasma, leukocyte and platelet phospholipids. The ω3/ω6 ratio increased in the SMOFlipid group compared to the comparator group. The mean concentration of the EPA derived LTB5 increased to a greater extent following SMOFlipid administration compared with the comparator. Mean concentrations of arachidonic acid-derived LTB4 increased following administration of Lipovenos and decreased following administration of SMOFlipid.

Children.

Twenty-eight infants and children aged from 5 months to 2 years and from 2 to 11.5 years with stable disease requiring parenteral nutrition for at least 4 weeks received SMOFlipid or Intralipid 20% in a randomised, double blind study. SMOFlipid or Intralipid were to be given as approx. 2 g fat/kg/day over 12-14 hours for 4-5 days per week with a recommended infusion rate of 0.125 g fat/kg/hour to a maximum of 0.15 g fat/kg/hour. Oral/ enteral intake was to be no more than 50% of caloric intake. Additional parenteral nutrition (amino acids and glucose) varied, dependent on patient total body weight.
Efficacy was a secondary objective in this study and was assessed by the fatty acid profile in plasma lipoproteins and RBC phospholipids and by body weight, height and body mass index. Changes from baseline in fatty acid concentrations in plasma lipoproteins or RBC phospholipids showed increase in EPA and DHA in patients given SMOFlipid compared with those given Intralipid. Small increases in weight, height and BMI were seen in both groups over the 4-week period.

Pre-term infants.

Two randomised, controlled, double blind studies were conducted in pre-term infants aged 0 to 9 days with a gestation age of < 34 weeks. Intralipid 20% was the comparator in both studies. In one study, patient's birth weight was from 1000 to 2500 g and in the other, birth weight was from 500 to 2000 g. Patients required parenteral nutrition including fat for at least 7 days. Oral/enteral intake of ≤ 30% of energy intake on Days 1-3 and ≤ 50% from Day 4 was permitted in both studies. In one study dosing commenced at 0.5 g fat/kg b.w/day on Day 1 and increased in steps of 0.5 g fat/kg b.w/day on Days 2, 3 and 4 and was given at 2.0 g fat/kg b.w/day from Days 4 to 14 with a maximum infusion rate of 0.125 g fat/kg/hour. In the other study dosing commenced at 1.0 g fat/kg birth weight/day on Days 1-3 then increased in 1.0 g fat/kg/birth weight/day on Days 4 and 5 and was then given at a dose of 3.5 g fat/kg birth weight/day from days 6 to 14 with a maximum infusion rate of 0.17 g fat/kg/hour. If actual body weight exceeded birth weight during treatment, dosing was to be adjusted according to actual body weight.
The primary efficacy measure in both studies was change in body weight during treatment. In one study 60 patients were enrolled with 30 receiving each treatment. Weight gain occurred in each group (mean of 5.01% for SMOFlipid vs. 5.1% for Intralipid 20%). There was considerable individual variation in weight gain in both groups. Higher ω3 fatty acid content was seen in patients given SMOFlipid compared with Intralipid. Plasma α-tocopherol was higher in patients given SMOFlipid compared with those given Intralipid 20%. There were no major differences in clinical outcomes in the 2 treatment groups. In the other study 84 patients were enrolled but 37% of the ITT population received incorrectly calculated treatment doses. No major differences were seen in triglyceride levels in the 2 study groups.

5.2 Pharmacokinetic Properties

The individual triglycerides have different clearance rates.
Pharmacokinetic parameters of triglycerides following administration of SMOFlipid 20% at a dose of 0.125 g fat/kg/hour for 6 hours to 12 healthy adult volunteers are presented in Table 3.

5.3 Preclinical Safety Data

Genotoxicity.

SMOFlipid was not mutagenic or clastogenic in a battery of genotoxicity studies, including the Ames bacterial mutagenicity assay, a mammalian mutagenicity assay, a chromosome aberration assay in human peripheral lymphocytes, and an in vivo rat micronucleus assay.

Carcinogenicity.

No carcinogenicity studies have been conducted with the combined components of SMOFlipid.

6 Pharmaceutical Particulars

6.1 List of Excipients

Glycerol 25 g; egg lecithin 12 g; dl-alpha-tocopherol 163-225 mg; sodium hydroxide pH approx. 8; sodium oleate 300 mg; water for injections Q.S to 1000 mL.

6.2 Incompatibilities

SMOFlipid may only be mixed with other medicinal products for which compatibility has been documented. For compatibility information, please see Section 4.2 Dose and Method of Administration.

6.3 Shelf Life

Approved shelf life as packaged for sale.

24 months.

Shelf life after first opening the container.

Chemical and physical in-use stability has been demonstrated for 24 hours at 25°C. From a microbiological point of view the emulsion should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2-8°C.
When used in neonates and children below 2 years, the solution (in bags and administration sets) should be protected from light exposure until administration is completed (see Section 4.2; Section 4.4).

Shelf life after mixing.

If additions are made to SMOFlipid, the admixtures should be used immediately from a microbiological point of view. If admixtures are not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2-8°C.
When used in neonates and children below 2 years, the solution (in bags and administration sets) should be protected from light exposure until administration is completed (see Section 4.2; Section 4.4).

6.4 Special Precautions for Storage

Store below 25°C. Do not freeze.

6.5 Nature and Contents of Container

The container consists of an inner bag (primary package) with an overpouch. An oxygen absorber and an integrity indicator (Oxalert) are placed between the inner bag and the overpouch. The Biofine inner bag is made of a multilayer polymer film.
The Biofine inner bag consists of a poly (propylene-co-ethylene) copolymer and thermoplastic elastomers (SEBS and SIS).
The oxygen barrier overpouch consists of polyethylene terephthalate and polyolefin or polyethylene terephthalate, polyolefin and ethylene-vinyl alcohol copolymer (EVOH).
The oxygen absorber consists of iron powder in a polymer sachet.
The integrity indicator consists of oxygen sensitive solution in a polymer sachet.
The overpouch, the oxygen absorber and the integrity indicator should be discarded after opening of the overpouch. The integrity indicator (Oxalert) will react with free oxygen and change colour from clear to black in case of damage in the overpouch.

Pack sizes*.

10 x 100 mL, 20 x 100 mL AUST R 262963.
10 x 250 mL AUST R 262964.
12 x 500 mL AUST R 158359.
* Not all pack sizes may be marketed.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

Other handling.

When used in neonates and children below 2 years, protect from light exposure, until administration is completed. Exposure of SMOFlipid to ambient light, especially after admixture with trace elements and/or vitamins, generates peroxides and other degradation products that can be reduced by protection from light exposure (see Section 4.2; Section 4.4; Section 6.3).

6.7 Physicochemical Properties

CAS number.

Fish oil - rich in omega-3 acids: 8016-13-5.
Medium chain triglycerides: 73398-61-5 and 65381-09-1.
Olive oil: 8001-25-0.
Soya oil: 8001-22-7.

7 Medicine Schedule (Poisons Standard)

Australia: Not Scheduled.

Summary Table of Changes