Consumer medicine information

ClinOleic 20%

Olive oil; Soya oil

BRAND INFORMATION

Brand name

ClinOleic 20%

Active ingredient

Olive oil; Soya oil

Schedule

Unscheduled

 

Consumer medicine information (CMI) leaflet

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

What is in this leaflet

This leaflet answers some common questions about ClinOleic 20%. It does not contain all of the available information. All medicines have risks and benefits. Your doctor has weighed the risks of you using ClinOleic against the benefit they expect it will have for you.

It does not take the place of talking to your doctor or pharmacist.

If you have any concerns about being administered this medicine, ask your doctor or pharmacist.

What ClinOleic is used for

ClinOleic is a sterile fat emulsion containing soya oil and olive oil as active components. It is used as a source of energy and for correction of essential fatty acids deficiency, and is given as an infusion directly into your veins. ClinOleic is intended to provide you with nourishment (essential fatty acids) whilst you are unable to consume food by mouth.

Before you are given ClinOleic

ClinOleic should not be given to you if:

  • you have an allergy to any ingredient listed at the end of this leaflet;
  • you have had an allergic reaction to egg-yolk containing foodstuffs or soybean products. Some of the symptoms of an allergic reaction may include skin rash, peeling of the skin and swelling of the face, lips or tongue causing difficulty swallowing or shortness of breath;
  • you have one of the following conditions:
    - an abnormal level of lipids in the blood
    - uncontrolled diabetes, lactic acidosis
    - a blood or other infection
    - severe liver disease
    - blood clotting problems
    - kidney disease
    - heart attack
  • The expiry date printed on the pack has passed.

You must tell your doctor if you:

  • are fluid overloaded or overhydrated;
  • have diabetes;
  • have liver disease
  • are taking any prescription medicine
  • are taking any other medicines including nutritional supplements, purchased from your pharmacy, supermarket or health food stores, , in particular warfarin;
  • are pregnant;
  • are breastfeeding.

The doctor will regularly monitor your condition whilst on ClinOleic. Please ask your doctor about the benefits and risks of using this medicine.

Other precautions:

Paediatric (children) use:

ClinOleic must be used with caution in very small and premature infants, especially in the case of jaundice. The doctor will regularly monitor your child’s progress whilston ClinOleic. Please ask your doctor about the benefits and risks in these cases.

How ClinOleic is given

How much is given:

Your doctor will decide how much ClinOleic will be given to you, which depends on your need and condition.

How it is given:

ClinOleic will be given at a slow rate (drip) of injection by your health professional. Usually, you will need to stay in a health institution (hospital, nursing home, etc.) but in some cases at home, as it requires a special medical equipment to deliver the medicine into your circulation. A cannula (administration needle) is placed in a vein by your doctor or nurse.

The infusion is for single use and for one person only. Any unused portion must be discarded and not used later, either for you or anyone else.

ClinOleic may be given at the same time as other intravenous nutrition solutions such as glucose and amino acids.

Overdose

The doctor or nurse giving you the ClinOleic has had experience in the use of this sort of medicine, so it is unlikely that you will be given an overdose. However, in case of an overdose, the infusion will be discontinued and another treatment may be needed. You may experience some of the effects listed under “Side Effects” below.

While you are receiving ClinOleic

Discuss with your doctor your progress whilst receiving ClinOleic, especially if any complications occur during the first few days of therapy. Frequent clinical evaluation and laboratory tests may be required. As ClinOleic is normally given in a hospital, your nurse provider will take records of your progress and any unexpected reactions.

Side Effects

As with any medicines, some side effects may occur.

Undesirable side effect such as fever, itching, nausea, vomiting, diarrhoea, abdominal pain, back pain, muscle spasms, passing large amounts of urine, excessive thirst and having a dry mouth and skin, low blood pressure, hot flush, shortness of breath, yellowing of the skin and eyes, dark coloured urine, unusual weakness, rash, and generally feeling unwell.

Always tell your doctor or nurse if you have any unexpected effects during or after receiving ClinOleic and they worry you.

In rare circumstances, more serious side effects may occur such as chest pain, fast or slow heartbeat, or swelling of the face, lips or mouth causing breathing difficulties. If these occur, tell your health professional on duty immediately. These maybe symptoms of a serious allergic reaction. Your health professional will take appropriate action promptly, such as stopping the infusion.

Product Description

What ClinOleic looks like

It is a milky white emulsion filled in plastic bag or glass bottle packaged in a protective over wrap.

It is available in different sizes:

ClinOleic in sizes of 100mL, 125mL, 250mL, 500mL and 1000mL glass bottle,

ClinOleic in sizes of 100mL, 250mL, 350mL, 500mL and 1000mL plastic bag.

Ingredients

Active ingredients:

Mixture of refined olive oil (approximately 80%) and refined soya oil (approximately 20%), 200g of mixture/litre.

Other ingredients:

  • egg lecithin;
  • glycerol;
  • sodium oleate;
  • water for injections and
  • ascorbyl palmitate.

Storage

ClinOleic will be stored in the pharmacy or the hospital ward. It is recommended that the product be stored in a cool dry place, protected from light, where the temperature stays below 25°C.

Where can you get more information?

You can get more information from your doctor or pharmacist.

Name and Address of Sponsor

Baxter Healthcare Pty Ltd.
1 Baxter Drive
Old Toongabbie, NSW 2146

Australia

Australian Registration number:

ClinOleic 20% bottle AUST R 97538

ClinOleic 20% bag AUST R 97537

Date of preparation:

September 2014

ClinOleic and Baxter are trademarks of Baxter International Inc

Published by MIMS July 2017

BRAND INFORMATION

Brand name

ClinOleic 20%

Active ingredient

Olive oil; Soya oil

Schedule

Unscheduled

 

1 Name of Medicine

Olive oil and soya oil.

2 Qualitative and Quantitative Composition

ClinOleic is a sterile fat emulsion [containing a mixture of refined olive oil (approximately 80%) and refined soya oil (approximately 20%)] 200 g, egg lecithin (purified egg phospholipids) 12 g, glycerol 22.5 g, sodium oleate 0.3 g and water for injections to 1,000 mL (final pH between 6.0-8.0).
One of the active ingredients, soya oil, contains ascorbyl palmitate as an antioxidant (free radical scavenger), in the concentration of 0.15 mg/g of oil.

3 Pharmaceutical Form

ClinOleic is an emulsion for intravenous injection.
ClinOleic 20% is a milk-like homogeneous liquid.

4 Clinical Particulars

4.1 Therapeutic Indications

Parenteral nutrition when oral or enteral nutrition is impossible, insufficient or contraindicated.

4.2 Dose and Method of Administration

The dosage depends on energy expenditure, the patient's clinical status, bodyweight, and ability to metabolise ClinOleic 20%, as well as additional energy given orally/enterally. Therefore, the dosage should be individualised and the bag size chosen accordingly. The maximum daily dose of ClinOleic 20% should be based on individual total nutritional requirements and patient tolerance.

Dosage.

Note.

The percentage (%) of lipid in the ClinOleic 20% formulation is expressed in weight by volume (w/v). That is, 5 mL of ClinOleic 20% contains 1 g of lipid.

Adult.

The dosage is 1 to a maximum of 2 g lipids/kg/day.
Never exceed 0.15 g lipids/kg/hour (0.75 mL/kg/hour). (See Table 1.)

Children.

It is recommended not to exceed a daily dose of 3 g lipids/kg of bodyweight, and an infusion rate of 0.15 g lipids/kg of bodyweight/hour.
Daily dose should be increased gradually during the first week of administration.

Premature newborns and low birthweight infants.

The use of ClinOleic 20% is restricted to premature infants of 28 weeks gestational age or more.
The initial daily dose should be 0.5-1.0 g lipids/kg of bodyweight. The dose may be increased by 0.5-1.0 g lipids/kg of bodyweight every 24 hours up to a daily dose of 2.0 g lipids/kg of bodyweight.

Flow rate and duration.

The administration flow rate must be adjusted taking into account the dose being administered, the daily volume intake, and the duration of the infusion. The recommended duration of infusion for a parenteral nutrition bag is between 12 and 24 hours, depending on the clinical situation. Treatment with parenteral nutrition may be continued for as long as is required by the patient's condition.

Adult.

The initial infusion rate must be slow and not exceed 0.1 g lipids or 0.5 mL (10 drops) per minute for 10 minutes, then gradually increased until reaching the required rate after half an hour.

Children.

ClinOleic 20% should be administered as a continuous 24 h/day infusion.
It is recommended not to exceed an infusion rate of 0.15 g lipids/kg of bodyweight/hour.
Daily dose should be increased gradually during the first week of administration.

Premature newborns and low birthweight infants.

ClinOleic 20% should be administered as a continuous 24 h/day infusion.

Route of administration.

Intravenous infusion only.

When used in premature newborns, low birth weight infants and children, the solution (in bags and administration sets) should be protected from light exposure after admixture through administration (see Section 4.4 Special Warnings and Precautions for Use).
When administered as part of a complete nutrition admixture (with glucose and amino acids), the central or peripheral venous route should be chosen depending on the osmolarity of the final admixture.
In rare cases, when infused alone as a complementary support to oral or enteral nutrition, ClinOleic 20% can be administered via central or peripheral vein.
When preparing an admixture that includes ClinOleic 20% (see Preparation for administration), the final osmolarity of the mixture should be measured before administration via a peripheral vein. If the mixture is hypertonic, it may cause irritation of the vein when administered into a peripheral vein.
ClinOleic 20% infusion does not contain an antimicrobial agent. To avoid the risk of microbial contamination, infusion should be commenced as soon as practicable after the preparation of an admixture. As with all parenteral administration, particularly infusions, strict aseptic technique should be used at all times. ClinOleic 20% intravenous infusion is for single use only in a single patient.

Method of preparation.

The order of mixing is critical to ensure compatibility and stability of admixtures containing ClinOleic 20%. Use aseptic technique all way through the compounding processes. Thorough mixing after the addition of each component is essential. ClinOleic 20% and other components of parenteral nutrition do not contain antimicrobial agents. Therefore, once mixed, the admixtures should be administered over a period not exceeding 24 hours.
ClinOleic 20% may be combined with other nutrients by adding the emulsion to a mixture of amino acids and glucose in fixed proportions.
Thus, for example, an extemporaneous formulation made of amino acid, Synthamin 9, with electrolytes (500 mL), glucose solution 10% (375 mL) and ClinOleic 20% (250 mL) could be prepared without the risk of instability. Some combinations of 3-in-1 total parenteral nutrition (TPN) admixtures are shown in Table 2.
The registration numbers for the amino acids are Synthamin 9 w/e (AUST R 19451), Synthamin 13 w/e (AUST R 19447) and Synthamin 17 w/e (AUST R 19449).
The order of admixing of the above components should be approached by minimising a sudden change in the negative charge of the emulsion. Firstly, mix the glucose infusion with the amino acid infusion. ClinOleic 20% emulsion can then be added into this admixture. Finally the electrolyte complements then trace elements can be added.
As the lipid emulsion is negatively charged, do not add electrolytes or trace elements directly into ClinOleic 20% emulsion as they destabilise the emulsion. The recommended sequence for adding electrolytes is monovalent, divalent and trivalent ions. Phosphate salts must always be added prior to calcium salts as discussed below.
The inclusion of calcium and phosphate ions in a TPN admixture requires special attention to a possible formation of calcium phosphate precipitate, which is affected by pH, temperature, calcium salt, sequence of calcium and phosphate addition to the admixtures and concentration of calcium and phosphate ions. The limits of these electrolytes should be less than or equal to 5.0 mmol/L for calcium and phosphates should not exceed a concentration of 30 mmol/L from all sources. At pH 7.0 and above, the addition of NaH2PO4 to calcium gluconate solution results in a precipitation of CaHPO4, that is, the equilibrium between [H2PO4]-1 and [HPO4]-2 is shifted to the [HPO4]-2 side.
At pH of 4.1, phosphate ions are predominantly in the form of monobasic phosphate, whilst at a higher pH it occurs in a form of dibasic phosphate ions. Taking into consideration that the glucose infusion has a pH in the range 3.2-6.5, and in order to minimise a formation of dibasic phosphate ions, the sodium monobasic phosphate should be added to the glucose infusion in the early stage of the compounding of a TPN admixture. Then, this admixture is added to the amino acid infusion, which has a buffer capacity and no charge effects at pH 5-6. This is followed by the addition of the lipid emulsion to the obtained admixture. Finally, calcium gluconate is added at the end of the TPN compounding process.
Separation of the product (gravity dispersion or 'creaming') may occur after the emulsion has been stored a period of time without agitation. It should only be necessary to invert the bottle or shake the bag 2 or 3 times before use. The product must not be used if the emulsion has a yellow appearance, or is seen to contain yellow droplets of oil. Do not use if shaking does not result in a uniform emulsion.

Preparation for administration.

Bottle. Before use check that the emulsion is homogeneous, and that the bottle is free of cracks or splinters.
The use of a final filter is recommended during administration of all parenteral nutrition solutions, where possible.
All opened bottles must be used immediately and not be stored for further use.
For single use only. Discard partly used bottle.
When used in premature newborns, low birth weight infants and children, protect from light exposure when admixtures include trace elements and/or vitamins, after admixture through administration. Exposure of ClinOleic 20% to ambient light after admixture generates peroxides and other degradation products that can be reduced by photoprotection (see Section 4.4 Special Warnings and Precautions for Use).
Bag. Store in protective overwrap.

Please note.

As lipid emulsions are oxygen sensitive, an oxygen indicator affixed to an oxygen absorber is added between the inner bag and the overwrap. The oxygen indicator shows whether oxygen has entered the packaging due to damage of the overwrap. The oxygen indicator should be inspected before removing the overwrap; compare it to the reference colour printed next to the OK symbol and depicted in the printed area of the indicator label. If oxygen enters the overwrap and is not absorbed by the oxygen absorber, the oxygen indicator changes colour. Do not use the product if the colour of the oxygen indicator does not correspond to the reference colour printed next to the OK symbol.
The oxygen indicator mixture may appear biphasic, as it is a suspension of a solid in a liquid. Once it is determined that the product is safe to use, the oxygen absorber/indicator should be discarded.
Do not use plastic containers in series connection. Such use could result in embolism due to residual air drawn from the primary container before administration of the fluid from the secondary container is completed.

a. To open.

Tear the protective overwrap; confirm the integrity of the bag; use only if the bag is not damaged and the emulsion is a homogenous liquid with a milky appearance.

b. Positioning the infusion.

Suspend the bag; remove the plastic protector from the administration outlet; firmly insert the infusion spike into the administration outlet.

c. Additions.

If it is necessary to introduce additives, verify the compatibility and mix thoroughly before administration to the patient. Additions must be performed under aseptic conditions. Never make any additions directly to the bag; additions are made into the injection site using a needle: prepare the injection site; puncture the injection site and inject; mix the contents of the bag and the additives (see Method of preparation).
All opened bags must be used immediately and not be stored for further use.
The use of a final filter is recommended during administration of all parenteral nutrition solutions, where possible.
For single use only.
Do not store partially used bags, discard partially used bags and destroy all accessory parts after use.
Do not reconnect partially used bags.
When used in premature newborns, low birth weight infants and children, protect from light exposure when admixtures include trace elements and/or vitamins, after admixture through administration. Exposure of ClinOleic 20% to ambient light after admixture generates peroxides and other degradation products that can be reduced by photoprotection (see Section 4.4 Special Warnings and Precautions for Use).

4.3 Contraindications

Known hypersensitivity to egg, soybean or peanut proteins or to any of the ingredients, including the lipid emulsion and/or excipients.
Severe hyperlipidaemia or severe disorders of lipid metabolism characterised by hypertriglyceridaemia and noncorrected metabolism disorders including lactic acidosis and uncompensated diabetes.
Severe sepsis.
Severe liver disease.
Blood coagulation disorders, thrombophlebitis.
Acute and chronic renal failure, in absence of specific studies, there is insufficient data to justify its use in acute/chronic renal failure.
Myocardial infarction.

4.4 Special Warnings and Precautions for Use

Special clinical monitoring is required at the beginning of any intravenous infusion. Should any abnormalities occur, the infusion must be stopped.

Allergic reactions.

The infusion must be stopped immediately if any signs or symptoms of an allergic reaction develop.

Infections.

Patients who require parenteral nutrition are often predisposed to infectious complications due to malnutrition and/or their underlying disease state.
Infection and sepsis may occur as a result of the use of intravenous catheters to administer parenteral formulations, or poor maintenance of catheters and contaminated solutions.
Immunosuppression and other factors such as hyperglycaemia, malnutrition and/or their underlying disease state may predispose patients to infectious complications.
The occurrence of septic complications can be decreased with heightened emphasis on aseptic technique in catheter placement and maintenance, as well as aseptic technique in the preparation of the nutritional formula.
Careful monitoring of signs, symptoms, and laboratory test results (including fever, chills, leukocytosis, and hyperglycaemia), and frequent checks of the access device for technical complications can help recognise early infections.

Fat overload syndrome.

Fat overload syndrome has been reported with similar products. This may be caused by inappropriate administration (e.g. overdose and/or infusion rate higher than recommended, see Section 4.9 Overdose); however, the signs and symptoms of this syndrome may also occur when the product is administered according to instructions. The reduced or limited ability to metabolise the lipids contained in ClinOleic 20% accompanied by prolonged plasma clearance may result in a fat overload syndrome. This syndrome is associated with a sudden deterioration in the patient's clinical condition and is characterised by findings such as fever, anaemia, leukopaenia, thrombocytopaenia, coagulation disorders, hyperlipidaemia, liver fatty infiltration (hepatomegaly), deteriorating liver function and central nervous system manifestations (e.g. coma). The syndrome is usually reversible when the infusion of the lipid emulsion is stopped.

Refeeding syndrome.

ClinOleic 20% is administered as part of a parenteral nutrition regimen. Refeeding severely undernourished patients with parenteral nutrition may result in the refeeding syndrome. The syndrome is characterised by the intracellular shift of potassium, phosphorus and magnesium as the patient becomes anabolic. Thiamine deficiency and fluid retention may also develop. Careful monitoring and slowly increasing nutrient intakes, while avoiding overfeeding, can prevent these complications.
Fat emulsions should be administered simultaneously with carbohydrates and amino acids to avoid metabolic acidosis.
Never make additions directly to the ClinOleic 20% bag. If ClinOleic 20% is mixed with glucose and/or amino acid solutions, the compatibility should be checked before administration (see Section 4.2 Dose and Method of Administration). Formation of precipitates could result in vascular occlusion.
To avoid air embolism due to possible residual gas contained in the primary bag, do not connect flexible bags in series (see Section 4.2 Dose and Method of Administration). Air embolism can result if residual gas in the bag is not fully evacuated prior to administration if the flexible bag is pressurised to increase flow rates. Use of a vented intravenous administration set with the vent in the open position could result in air embolism.

Use with caution in the following circumstances.

Fat metabolism may be disturbed in uncompensated diabetes. The use of ClinOleic in patients with diabetes mellitus has not been investigated. If ClinOleic is administered the elimination of fat should be monitored daily.

Check the following before/during treatment.

Water/fluid balance and overload states, electrolytic or metabolic disorders should be corrected before administration of ClinOleic 20%.
Plasma triglyceride levels and clearance should be monitored daily. The triglyceride concentration in serum during infusion should not exceed 3 mmol/L. Infusion should only be started when serum triglyceride levels have returned to baseline level.
During short-term or long-term intravenous nutrition, alkaline phosphatase and total bilirubin should be checked at regular intervals, depending on the health status of the patient.
Monitor serum triglycerides, fluid and electrolyte status, acid/base balance, serum osmolarity, blood glucose, liver and kidney function, and blood count, including platelet and coagulation parameters, throughout treatment.
Fluid status should be closely monitored in patients with pulmonary oedema or heart failure.

Use in hepatic impairment.

The use of ClinOleic in patients with chronic liver disease without systemic failure has not been evaluated. If parenteral nutrition is to be used in patients with pre-existing liver disease or insufficiency, liver function parameters as well as liver condition should be closely followed when using ClinOleic. Hetapobiliary disorders including cholestasis, hepatic steatosis, fibrosis and cirrhosis, possibly leading to hepatic failure, as well as cholecystitis and cholelithiasis are known to develop in some patients on parenteral nutrition. The aetiology of these disorders is thought to be multifactorial and may differ between patients. Patients developing abnormal laboratory parameters (see Section 4.4 Special Warnings and Precautions for Use, Effects on laboratory tests) or other signs of hepatobiliary disorders should be assessed early by a clinician knowledgeable in liver diseases in order to identify possible causative and contributory factors, and possible therapeutic and prophylactic interventions.
See Section 4.3 Contraindications.

Use in renal impairment.

See Section 4.3 Contraindications.

Use in the elderly.

No data available.

Paediatric use.

Extremely premature and/or very low birthweight infants receiving ClinOleic 20% should be under the close supervision of a neonatologist. Clinical experience exists for administration of ClinOleic 20% for up to 7 days in neonates and up to 2 months in children.
ClinOleic 20% should be administered with caution in the case of neonatal hyperbilirubinaemia (total serum bilirubin > 200 micromol/L). Total bilirubin levels should be monitored closely.
Light exposure of solutions for intravenous parenteral nutrition, 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 premature newborns, low birth weight infants and children, ClinOleic 20% should be protected from ambient light after admixture until administration is complete (see Section 4.2 Dose and Method of Administration).
Serious adverse reactions including acute respiratory distress and metabolic acidosis have been reported in neonates and infants after rapid infusion of intravenous lipid emulsions.

Effects on laboratory tests.

The lipids contained in ClinOleic 20% may interfere with the results of certain laboratory tests (e.g. bilirubin, lactate dehydrogenase, oxygen saturation, haemoglobin) if the blood sample is taken before the lipids are eliminated. Administered lipids are generally eliminated from the bloodstream after a period of 5 to 6 hours following discontinuation of administration.

4.5 Interactions with Other Medicines and Other Forms of Interactions

No interaction studies have been performed with ClinOleic 20%.
Olive and soybean oils have a natural content of vitamin K1 that may counteract the anticoagulant activity of coumarin derivatives, including warfarin.

Compatibility with other drugs and nutrients.

Complete information about incompatibilities is not available.
Electrolytes or medication should not be added directly to the lipid emulsion.
If it is necessary to introduce additives to a solution containing ClinOleic 20%, first verify the compatibility and then mix thoroughly before administration to the patient.
The compatibility of drugs intended for administration by the Y-site of an infusion containing ClinOleic 20% must first be established.
ClinOleic 20% may be included as a component of parenteral nutrition admixtures incorporating carbohydrates and amino acids where compatibility and stability have been established before administration to the patient. Admixing should be accompanied by gentle agitation during preparation under strict aseptic conditions. The addition of polyvalent electrolytes to an admixture requires thorough review of the interaction of calcium and phosphate. This review should be made before compounding is initiated, due to the possible interaction between the calcium and the phosphate.
In the case of Synthamin amino acid solutions with electrolytes, the limits of these electrolytes should be less than or equal to 5.0 mmol/L for calcium, and phosphates should not exceed a concentration of 30 mmol/L from all sources.
Absolute solubility of calcium/phosphate in parenteral admixtures is dependent upon many factors, including the concentration of amino acids in the admixture. Reference should be made to calcium/phosphate solubility curves (appropriate to the amino acid in use), published by the amino acid solution manufacturers, to determine the solubility limits before admixing commences.
'Breaking' or 'oiling out' of the emulsion can be visibly identified by accumulation of yellowish droplets or particles in the admixture.

Compatibility with containers and administration sets.

Phthalate plasticisers are extracted from PVC bags and administration sets by intravenous fat emulsions. PVC bags and administration sets should not be used for delivery of ClinOleic 20% or of solutions containing ClinOleic 20%. Bags made from ethyl vinyl acetate (EVA) and administration sets made from nonplasticised materials are recommended.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Tests for effects on fertility have not been conducted with ClinOleic 20%.
The safety of administration of ClinOleic 20% during pregnancy has not been established. No reproductive toxicity studies with ClinOleic 20% have been carried out in animals, and its use in pregnancy is not recommended.
 The safety of administration of ClinOleic 20% during lactation has not been established. Therefore, ClinOleic 20% 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)

During administration of parenteral nutrition fat emulsions, two types of adverse reactions can occur:

Immediate reactions.

At the beginning of the infusion, any of the following abnormal signs evoking a hypersensitivity reaction should be cause for immediate discontinuation of the infusion: sweating, shivering, cephalgia, dyspnoea.

Delayed reactions.

During long-term parenteral nutrition of fat emulsions, the following adverse reactions have been observed.

Hepatobiliary disorders.

Increase of alkaline phosphatase, bilirubin and transaminases (ALT, AST); hepatomegaly; icterus.

Blood and lymphatic system disorders.

Thrombocytopenia.
Of the clinical trials performed with ClinOleic 20%, a summary of the serious adverse events (SAE) are summarised in Table 3. Over a period from November 1995 to November 2003, sixteen (16) SAE's were reported in clinical studies. Of the 16 AE's, seven (7) were not related, one (1) possibly related and one (1) unlikely related to the product administration. The total number of units used during this period was 1,325,117.
To date, two (2) spontaneous adverse events were reported.
In addition to the adverse reactions noted above, the following adverse reactions have been reported in clinical trials.

Blood and lymphatic system disorders.

Leukopaenia.

Metabolism and nutrition disorders.

Hyperglycaemia, diabetes mellitus inadequate control, hypoproteinaemia, hyperlipidaemia (including hypertriglyceridaemia).

Vascular disorders.

Mean arterial pressure decreased, circulatory collapse, hypotension, hot flush.

Respiratory, thoracic, and mediastinal disorders.

Dyspnoea.

Gastrointestinal disorders.

Vomiting, nausea, abdominal pain, abdominal distension, epigastric discomfort.

Hepatobiliary disorders.

Cholestasis, hepatic function abnormal, cytolytic hepatitis.

Musculoskeletal and connective tissue and bone disorders.

Muscle spasms, back pain.

General disorders and administration site conditions.

Pyrexia, asthenia, malaise.

Investigations.

Blood bilirubin increased, bilirubin conjugated increased, hepatic enzyme increased, liver function test abnormal, pancreatic enzyme increased, blood triglycerides increased.

Post-marketing adverse effects.

The following additional adverse reactions have been reported in the postmarketing experience.

Gastrointestinal disorders.

Diarrhoea.

Skin and subcutaneous tissue disorders.

Pruritus.

Investigations.

International normalised ratio decreased.

Immune system disorders.

Hypersensitivity with the manifestations of rash and dyspnoea.

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 www.tga.gov.au/reporting-problems.

4.9 Overdose

In case of overdose (an abnormal rise in triglyceride levels during infusion of fat) where any of the following reactions occur, fat infusion should be stopped to allow lipids to clear from serum, or if necessary, continue the infusion at a reduced dosage: general symptoms such as fever or evocating an haemodynamic instability, emesis, algia, liver function abnormalities, hepato or splenomegalia, haemostasis disorders, hyperlipidaemia, hypersensitivity, and fat overload syndrome. In neonates and infants, an overdose and/or increased infusion rate may cause serious adverse events such as metabolic acidosis and respiratory distress. The effects are usually reversible after the lipid infusion is stopped. If medically appropriate, further intervention may be indicated (see Section 4.4 Special Warnings and Precautions for Use).
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

ClinOleic 20% provides a moderate proportion of essential fatty acids (EFA), which probably facilitates their utilisation. The combination of olive and soya oils allows a content of fatty acids in an approximate ratio of:
saturated fatty acids: 15% (SFA);
monounsaturated fatty acids: 65% (MUFA);
essential polyunsaturated fatty acids: 20% (EPUFA).
For patients requiring complete parenteral nutrition, complementary carbohydrates, amino acids, electrolytes, vitamins, and trace elements supplements are required.
ClinOleic 20% is a source of energy; the high energy content of the emulsion enables the administration of a large quantity of calories in a small volume. ClinOleic 20% also contains glycerol for isotonicity. Egg lecithin supplies phosphorus and choline.

Clinical trials.

ClinOleic has been used in a number of small clinical trials generally using Intralipid as a comparative agent. The numbers enrolled in these trials were small and they are not suitable for data pooling or meta-analysis or for demonstrating noninferiority to the comparator. The studies were of variable duration. The studies usually measured fatty acid composition of plasma lipid fractions. Of the population studied, 32% of the adults were aged over 65 years old.
The 2 pivotal studies enrolled 59 infants and children aged under 11 years old.
Study CT 2402/P14/93/F (Ricour study), double blind, randomised, parallel group, measured the level of fatty acids in plasma phospholipids (primary efficacy variable) and compared the long-term efficacy and safety of ClinOleic 20% (n = 9) to Intralipid 20% (n = 9) in children and infants who needed prolonged parenteral nutrition (PN) at home or hospital. Seventeen patients aged from 1 to 9 years old were exposed for 2 months and 1 patient was exposed for 1 month.
The results of the study are shown in Table 4.
Study CT 2402/P15/94/G (Koletzko study), double blind, randomised, parallel group, compared the efficacy and safety of ClinOleic 20% (n = 22) to Intralipid 20% (n = 20) in premature infants requiring lipid based total parenteral nutrition (TPN) for 7 days. Forty two premature infants aged, gestational age 28 to 36 weeks ± 6 days, were exposed.
The results are shown in Table 5.
Tolerability of the emulsions in the treatment and control groups was similar.

5.2 Pharmacokinetic Properties

In ClinOleic 20%, most of the lipid particle sizes are in the range of chylomicrons (0.08 - 0.6 micrometre) with the mean diameter of less than 0.45 micrometre. However, it may contain a small fraction (up to 2.5%) of particles having a diameter of more than 1 micrometre.

5.3 Preclinical Safety Data

Genotoxicity.

Tests for mutagenicity have not been conducted with ClinOleic 20%.

Carcinogenicity.

Tests for carcinogenicity have not been conducted with ClinOleic 20%.

6 Pharmaceutical Particulars

6.1 List of Excipients

See Section 2 Qualitative and Quantitative Composition.

6.2 Incompatibilities

See Section 4.5 Interactions with Other Medicines and Other Forms of Interactions.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C.
Do not freeze.
Protect from light.

6.5 Nature and Contents of Container

ClinOleic 20% bottle: AUST R 97538.
ClinOleic 20% bag: AUST R 97537.
ClinOleic 20% can be packaged in glass bottle (type II), or in bag container. This bag is a multi-layer plastic bag (EP-SEBS/EVA/EVA2/PCCE) packaged in an oxygen barrier over wrap.
The product is available in the following sizes:

In bottle.

100 mL in bottle - Package sizes: 24 or 10 units. 125 mL in bottle - Package sizes: 10 or 24 units. 250 mL in bottle - Package sizes: 10 or 12 units. 500 mL in bottle - Package sizes: 10 or 12 units. 1000 mL in bottle - Package size: 6 units.

In bag.

100 mL in bag: Box of 10 or 24 units. 250 mL in bag: Box of 10 or 20 units. 350 mL in bag: Box of 10 or 12 units. 500 mL in bag: Box of 10 or 12 units. 1000 mL in bag: Box of 6 units.
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.

6.7 Physicochemical Properties

ClinOleic 20% is an isotonic emulsion. It has an osmolality of approximately 345 mOsmL/kg water and energy content of 8.360 MJ (2,000 kcal)/L. The relative density of ClinOleic 20% is in the range of 0.983 - 0.989.

Refined olive oil.

Chemical structure.

No data available.

CAS number.

8001-25-0.

Refined soya oil.

Chemical structure.

No data available.

CAS number.

8001-22-7.

7 Medicine Schedule (Poisons Standard)

Not scheduled.

Summary Table of Changes