ClinOleic

Refined olive oil, refined soy bean oil.

Refined olive oil and refined soya bean oil* 20.00 g.
Corresponding to a content of essential fatty acids 4.00 g.
Per 100 ml.
* Mixture of refined olive oil (approximately 80%) and refined soya bean oil (approximately 20%).
Energy content 2000 kcal/l (8.36 MJ/l).
Lipid content (olive and soya bean oil) 200 g/l.
Osmolarity 270 mOsm/l.
pH 6 - 8.
Density 0.986.
Phospholipids provide 47 milligrams or 1.5 mmol of phosphorus per 100 ml.
Excipients/Inactive Ingredients: Egg phosphatides, Glycerol, Sodium oleate, Sodium hydroxide, Water for injections.

ATC code: B05BA02.
PHARMACOLOGY: PHARMACODYNAMICS: The combination of olive and soybean oils allows a content of fatty acids in an approximate ratio of: Saturated fatty acids: 15% (SFA).
Mono-unsaturated fatty acids: 65% (MUFA).
Essential Poly-unsaturated fatty acids: 20% (EPUFA).
The moderate level of essential fatty acids (EFA) probably facilitates their utilisation, enables a correct status of EFA upper derivatives and corrects EFA deficiency.
In comparison with soybean oil: in preterm infants above 28 weeks of gestational age, treated for 7 days, the higher content in a tocopherol related to the presence of olive oil, results in an improved vitamin E status.
In children (8 per treatment group) under long-term parenteral nutrition, for 2 months, a better vitamin E/EPUFA ratio results in reduced lipid peroxidation. These properties have been verified for doses ranging from 1 to 3 g/kg/day. The high-energy content of the emulsion enables the administration of a large quantity of calories in a small volume.
PHARMACOKINETICS: Clearance rate of lipid emulsions is dependent on particle size: Small lipid droplet size tends to delay the clearance, while it improves lipolysis by lipoprotein lipase.
CLINOLEIC 20%, which has droplet size close to that of chylomicrons, has a similar elimination rate.
Toxicology: PRECLINICAL SAFETY DATA: Toxicological studies showed that the product is well tolerated.
Toxicity studies showed the usual modifications due to high intake of lipid emulsions: fat and pigments deposits in the liver, thrombocytopenia, and hypercholesterolemia.
A decrease of lipid peroxidation and improved vitamin E status has been experimentally showed for high intake of CLINOLEIC 20% compared to soybean emulsions.
One in vitro study performed on human cells, and one in vivo study performed in rats in comparison with soybean oil-based emulsions, have shown that CLINOLEIC 20%, emulsion for infusion, maintains lymphocyte proliferation, cell activation markers expression, and lL-2 release. The clinical relevance of these findings is unknown.

Indicated as a source of lipids for patients requiring parenteral nutrition. When oral or enteral nutrition is impossible, insufficient or contraindicated.

CLINOLEIC 20% contains 200 mg/ml of lipids.
Route of administration: Intravenous infusion: 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 osmolality 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 peripheral vein.
Dosage: IN ADULTS: The dosage is 1 g/kg/day to a maximum of 2 g lipids/kg/day. 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. Never exceed 0.15 g lipids/kg/hour (0.75 ml/kg/hour). (See Table 1.)

Click on icon to see table/diagram/image

IN CHILDREN: CLINOLEIC 20% should be administered as a continuous 24h/day infusion. It is recommended not to exceed a daily dose of 3g-lipids/kg b.w. (body weight) and an infusion rate of 0.15 g lipids/kg b.w./h.
Daily dose should be increased gradually during the first week of administration.
IN PREMATURE NEWBORNS AND LOW BIRTH WEIGHT INFANTS: The use of CLINOLEIC 20% is restricted to premature infants of 28 weeks of gestational age or more.
CLINOLEIC 20% should be administered as a continuous 24h/day infusion.
The initial daily dose should be 0.5-1.0g lipids/kg b.w. The dose may be increased by 0.5-1.0g lipids/kg b.w. every 24 hours up to a daily dose of 2.0 g lipids/kg b.w.
Usage in nutritive admixtures (with glucose and amino acids): Before administration to the patient, the compatibility of the components and stability of the admixture must be checked.
Admixing should be accompanied by gentle agitation during preparation under strict aseptic conditions.
"Breaking" or "oiling out" of the emulsion can be visibly identified by accumulation of yellowish droplets or particles in the admixture.
For intravenous infusion: When used in neonates and children below 2 years, the solution (in bags and administration sets) should be protected from light exposure after admixture through administration (Precautions and Instructions for Use/Handling and Disposal under Cautions for Usage).
It is recommended that after opening the bag, the contents should be used immediately, and should not be stored for a subsequent infusion.
The dosage depends on energy expenditure, the patient's clinical status, body weight, and ability to metabolize CLINOLEIC 20%, as well as additional energy given orally/enterally. Therefore, the dosage should be individualized and the bag size chosen accordingly.
The maximum daily dose of CLINOLEIC 20% should be based on individual total nutritional requirements and patient tolerance.
CLINOLEIC 20% can be administered via the central or peripheral route when infused alone as a complementary support to oral or enteral nutrition. When administered as an admixture (e.g., together with dextrose and/or amino acids) the route of administration should be chosen based on the final osmolarity of the infusate.
The administration flow rate must be adjusted taking into account the dose being administered, the daily volume intake, and the duration of the infusion (see OVERDOSAGE).
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.
Use of a final filter is recommended during administration of all parenteral nutrition solutions, where possible.

In the event of overdose, fat overload syndrome may result (see WARNINGS). Stop the infusion to allow lipids to clear from serum. The effects are usually reversible after the lipid infusion is stopped. If medically appropriate, further intervention may be indicated.

The use of CLINOLEIC 20% is contraindicated in the following populations/situations: Known hypersensitivity to egg or soybean proteins or to any of the ingredients, including the lipid emulsion and/or excipients.
Severe hyperlipidemia or severe disorders of lipid metabolism characterized by hypertriglyceridemia.
Non corrected metabolism disorders including lactic acidosis and uncompensated diabetes.
Severe sepsis.
Severe liver disease.
Blood coagulation disorders, thrombophlebitis.
Myocardial infarction.

Special clinical monitoring is required at the beginning of any intravenous infusion: The infusion must be stopped immediately if any signs or symptoms of an allergic reaction develop.
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 hyperglycemia, 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 hyperglycemia), and frequent checks of the access device for technical complications can help recognize early infections.
"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 OVERDOSAGE); 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 metabolize 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 characterized by findings such as fever, anemia, leukopenia, thrombocytopenia, coagulation disorders, hyperlipidemia, 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.
CLINOLEIC 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 characterized 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.
Do not make additions directly to the CLINOLEIC 20% bag.
If CLINOLEIC 20% is mixed with dextrose and/or amino acid solutions, the compatibility should be checked before administration (see INCOMPATIBILITIES and INSTRUCTIONS FOR USE/HANDLING AND DISPOSAL under Cautions for Usage). Formation of precipitates could result in vascular occlusion.
Plasma triglyceride levels and clearance should be monitored daily. The triglyceride concentration in serum under 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 phosphatases and total bilirubin should be checked at regular intervals, depending on the health status of the patient.
Electrolyte or metabolism disorders should be corrected before CLINOLEIC 20% administration.
Fat emulsions should be administered simultaneously with carbohydrates and amino acids to avoid occurrence of metabolic acidosis.
The blood sugar, the acid-base balance, electrolytes, and the blood count must be checked at regular intervals.
As for any parenteral infusion, particular attention should be given on water balance, especially in patients with acute oliguria or anuria.
As other lipid emulsions, CLINOLEIC 20% should be used in extremely premature and/or very low birth-weight infant under the close supervision of a neonatologist. There is clinical experience for CLINOLEIC 20% infusion time, up to 7 days in neonates and up to 2 months in children.
CLINOLEIC 20% should be administered with caution in case of neonatal hyperbilirubinemia (total serum bilirubin > 200 umol/l). Total bilirubin levels should be monitored closely.

To avoid air embolism due to possible residual gas contained in the primary bag, do not connect flexible bags in series.
Air embolism can result if residual gas in the bag is not fully evacuated prior to administration if the flexible bag is pressurized to increase flow rates.
Use of a vented intravenous administration set with the vent in the open position could result in air embolism.
Before starting the infusion, correct severe water and electrolyte equilibration disorders, severe fluid overload states, and severe metabolic disorders.
Fluid status should be closely monitored in patients with pulmonary edema or heart failure.
Monitor serum triglycerides, fluid and electrolyte status, serum osmolarity, blood glucose, liver and kidney function, and blood count, including platelets and coagulation parameters, throughout treatment.
Parenteral nutrition should be used with caution in patients with preexisting liver disease or liver insufficiency. Liver function parameters should be closely monitored in these patients.
Parenteral Nutrition Associated Liver Diseases (PNALD) 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 etiology of these disorders is thought to be multifactorial and may differ between patients. Patients developing abnormal laboratory parameters 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.
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 neonates and children below 2 years, CLINOLEIC 20% should be protected from ambient light after admixture until administration is complete (Dosage & Administration and Instructions for Use/Handling and Disposal under Cautions for Usage).
EFFECTS ON ABILITY TO DRIVE AND USE MACHINES: Not applicable.

There are no adequate data from the use of CLINOLEIC 20% in pregnant or lactating women. Physicians should carefully consider the potential risks and benefits for each specific patient before prescribing CLINOLEIC 20%.

Allergic reactions (hypersensitivity to egg and soybean protein) may occur rarely. At the beginning of the infusion, any of the following abnormal signs (sweating, shivering, cephalgia, dyspnea) should be cause for immediate discontinuation of the infusion.
Adverse Reactions from Clinical Trials: See Table 2.

Click on icon to see table/diagram/image

Post-marketing Adverse Reactions: The following additional adverse reactions have been reported in the postmarketing experience, listed by MedDRA System Organ Class (SOC), then by Preferred Term (PT) in order of severity.
GASTROINTESTINAL DISORDERS: Diarrhea.
SKIN AND SUBCUTANEOUS TISSUE DISORDERS: Pruritus.
IMMUNE SYSTEM DISORDERS: Hypersensitivity with the manifestations of rash and dyspnea.
INVESTIGATIONS: International normalized ratio decreased.
Class/Other Reactions: Blood and lymphatic system disorders: Thrombocytopenia.
Hepatobiliary disorders: Parenteral Nutrition associated liver disease (including Hepatic failure, Hepatic cirrhosis, Hepatic fibrosis, Cholestasis, Hepatic steatosis, Cholecystitis, Cholelithiasis).
Injury, poisoning and procedural complications: Fat overload syndrome.

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.
The lipids contained in this emulsion may interfere with the results of certain laboratory tests if the blood sample is taken before the lipids are eliminated.
Complete information about incompatibilities is not available.
Never add medication or electrolytes directly to the lipid emulsion. If it is necessary to introduce additives, verify the compatibility and mix thoroughly before administration to the patient. The compatibility with solutions administered simultaneously via a common and section must be ensured.

INCOMPATIBILITIES: Complete information about incompatibilities is not available.
Do not add medication or electrolytes directly to the lipid emulsion. If it is necessary to introduce additives, verify the compatibility and mix thoroughly before administration to the patient.
INSTRUCTIONS FOR USE/HANDLING AND DISPOSAL: BOTTLE: Before opening the protective overwrap, check the color of the oxygen indicator affixed to the oxygen absorber. Compare it to the reference color printed next to the OK symbol and depicted in the printed area of the indicator label. Do not use the product if the color of the oxygen indicator does not correspond to the reference color printed next to the OK symbol.
All opened bottles must be used immediately and not be stored for further use.
For single use only. Discard partly use bottle.
BAG: To open: Remove the protective overwrap. Discard the oxygen absorber/indicator.
Confirm the integrity of the bag.
Use only if the bag is not damaged and if the emulsion is a homogeneous liquid with a milky appearance.
Once the bag is opened, use immediately. Discard partially used containers.
Positioning the infusion: Suspend the bag.
Remove the plastic protector from the administration outlet.
Firmly insert the infusion spike into the administration outlet.
Additions: Do not make any additions directly to the bag.
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. These 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.
Administration: For single use only.
Do not store partially used bags and destroy all accessory parts after use.
Do not re-connect partially used bags.
Do not connect a bag in series in order to avoid the possibility of air embolism due to gas contained in the first bag.
Any unused product or waste material and all necessary disposable devices must be discarded.
When used in neonates and children below 2 years, 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 (Precautions).
When administered as a component of parenteral nutrition, the compatibility of the components and stability of the admixture must be checked before administration to the patient. Admixing should be accompanied by gentle agitation during preparation under strict aseptic conditions.
When preparing an admixture that includes CLINOLEIC 20%, the final osmolarity of the mixture should be measured before administration via a peripheral vein.
If the final mixture is hypertonic, it may cause irritation of the vein when administered into a peripheral vein.

Do not store above 25°C.
Do not freeze.
Keep the container in the outer carton.
Store in protective overwrap.
SHELF-LIFE: 18 months in glass bottle or in plastic bag in its overwrap.

Parenteral Nutritional Products

B05BA02 - fat emulsions ; Belongs to the class of solutions for parenteral nutrition used in I.V. solutions.

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