Each 1000 mL of SMOFlipid contains refined soya bean oil 60 g, medium-chain triglycerides (MCT) 60 g, refined olive oil 50 g and fish oil (rich in omega-3-acids) 30 g. It also contains the following excipients: Glycerol, egg lecithin, all-rac-α-tocopherol, sodium hydroxide (for pH adjustment), sodium oleate and water for injections.
SMOFlipid has a total energy of 8.4 MJ/L (2000 kcal/L), pH value of approximately 8 and osmolality of approximately 380 mOsmol/kg.
Pharmacotherapeutic Group: Solutions for parenteral nutritions, fat emulsions. ATC Code: B05BA02.
Pharmacology: Pharmacodynamics: The fat emulsion has a particle size and biological properties similar to those of endogenous chylomicrons. The constituents of SMOFlipid (soya-bean oil, medium-chain triglycerides, olive oil and fish oil) have, except for their energy contents, their own pharmacodynamics properties.
Soya bean oil has a high content of essential fatty acids. The omega-6 fatty acid linoleic acid is the most abundant (approximately 55-60%). alpha-Linolenic acid, an omega-3 fatty acid, constitutes about 8%. This part of SMOFlipid provides the necessary amount of essential fatty acids.
Medium-chain fatty acids are rapidly oxidised and provide the body with a form of immediately available energy.
Olive oil mainly provides energy in the form of monounsaturated fatty acids, which are much less prone to peroxidation than the corresponding amount of polyunsaturated 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.
Two (2) studies providing home parenteral nutrition in patients in need of long-term nutrition support have been performed. The primary objective in both studies was to show safety. Efficacy was the secondary objective in 1 of the studies, which was done in paediatric patients. This study was stratified by age groups (1 month to <2 years and 2-11 years, respectively). Both studies showed that SMOFlipid has the same safety profile as the comparator (Intralipid 20%).
Efficacy in the paediatric study was measured by weight gain, height, body mass index, pre-albumin, retinol binding protein and fatty acid profile. There was no difference between the groups in any of the parameters except the fatty acid profile after 4 weeks treatment. The fatty acid profile in the SMOFlipid patients revealed an increase in omega-3 fatty acids in plasma lipoproteins and red blood cells phospholipids and hence, reflects the composition of the infused lipid emulsion.
Pharmacokinetics: The individual triglycerides have different clearance rate but SMOFlipid as a mixture is eliminated faster than long-chain triglycerides (LCT) with lower triglyceride levels during infusion. Olive oil has the slowest clearance rate of the components (somewhat slower than LCT) and medium-chain triglycerides (MCT) the fastest. Fish oil in a mixture with LCT has the same clearance rate as LCT alone.
Toxicology: Preclinical Safety Data: In preclinical studies, no other effects than those expected after high doses of lipids were observed based on single-dose and repeat-dose toxicity and genotoxicity studies performed with SMOFlipid emulsion. In a local tolerance study in rabbits, a slight, transient inflammation after intra-arterial, paravenous or SC administration was observed. After IM administration, a moderate, transient inflammation and tissue necrosis were seen in some animals.
In a test in guinea pigs (maximisation test), fish oil showed moderate dermal sensitisation. A systemic antigenicity test gave no indication of evidence of anaphylactic potential of fish oil.
Supply of energy and essential fatty acids and omega-3 fatty acids to patients, as part of a parenteral nutrition regimen, when oral or enteral nutrition is impossible, insufficient or contraindicated.
The patient's ability to eliminate the fat infused, should govern the dosage and infusion rate (see Precautions).
Adults: Standard Dose: 1-2 g fat/kg body weight/day, corresponding to 5-10 mL/kg body weight/day.
Recommended Infusion Rate: 0.125 g fat/kg body weight/hr, corresponding to SMOFlipid 0.63 mL/kg body weight/hr, and should not exceed 0.15 g fat/kg body weight/hr, corresponding to SMOFlipid 0.75 mL/kg body weight/hr.
Children: It is recommended not to exceed a daily dose of 3 g fat/kg body weight/day, corresponding to SMOFlipid 15 mL/kg body weight/day.
The daily dose should be increased gradually during the 1st week of administration.
The infusion rate should not exceed 0.15 g fat/kg body weight/hr.
Neonates and Infants: Initial Dose: 0.5-1 g fat/kg body weight/day followed by a successive increase by 0.5-1 g fat/kg body weight/day up to 3 g fat/kg body weight/day.
It is recommended not to exceed a daily dose of 3 g fat/kg body weight/day, corresponding to SMOFlipid 15 mL/kg body weight/day.
The rate of infusion should not exceed 0.125 g fat/kg body weight/hr. In premature and low birth weight neonates, SMOFlipid should be infused continuously over about 24 hrs.
Administration: IV infusion into a peripheral or central vein.
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 patients' clinical conditions eg, renal function impairment or infection.
Overdosage may lead to side effects (see Adverse Reactions). In these cases, the lipid infusion should be stopped, or if necessary, continued at a reduced dosage.
Hypersensitivity to fish-, egg-, soya- or peanut protein or to any of the active substances or excipients of SMOFlipid.
Severe hyperlipidemia, liver insufficiency, blood coagulation disorders, renal insufficiency without access to hemofiltration or dialysis; acute shock; general contraindications to infusion therapy: Acute pulmonary oedema, hyperhydration, decompensated cardiac insufficiency; unstable conditions (eg, severe posttraumatic conditions, uncompensated diabetes mellitus, acute myocardial infarction, stroke, embolism, metabolic acidosis and severe sepsis and hypotonic dehydration).
The capacity to eliminate fat is individual and should therefore be monitored according to the routines of the clinician. This is in general done by checking the triglyceride levels. Special caution should be taken in patients with a marked risk for hyperlipidemia (eg, patients with high lipid dosage, 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 (see Adverse Reactions).
SMOFlipid contains soya bean oil, fish oil and egg phospholipids, 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 eliminated by the simultaneous infusion of the long chain fatty acids included in SMOFlipid. Concomitant administration of carbohydrates will further eliminate this risk. Hence, simultaneous infusion of carbohydrate or a carbohydrate-containing amino acid solution is recommended. Laboratory test generally associated with monitoring of IV nutrition should be checked regularly. These include blood glucose levels, liver function tests, acid-base metabolism, fluid balance, full blood count and electrolytes.
Any sign or symptom of anaphylactic reaction (eg, fever, shivering, rash or dyspnoea) should lead to immediate interruption of the infusion.
SMOFlipid should be given with caution to neonates and premature neonates with hyperbilirubinemia and cases with pulmonary hypertension. In neonates, particularly premature neonates on long-term parenteral nutrition, blood platelet counts, liver function tests and serum triglycerides should be monitored.
High levels of lipids in plasma may interfere with some laboratory blood tests eg, haemoglobin.
The addition of other medicaments or substances to SMOFlipid should generally be avoided unless compatibility is known (see Incompatibilities under Interactions and Cautions for Usage).
Effects on the Ability to Drive or Operate Machinery: Not relevant.
Use in pregnancy & lactation: There are no data available on exposure of SMOFlipid in pregnant or breastfeeding women. There are no studies available on reproductive toxicity in animals. Parenteral nutrition may become necessary during pregnancy and lactation. SMOFlipid should only be given to pregnant and breastfeeding women after careful consideration.
There are no data available on exposure of SMOFlipid in pregnant or breastfeeding women. There are no studies available on reproductive toxicity in animals. Parenteral nutrition may become necessary during pregnancy and lactation. SMOFlipid should only be given to pregnant and breastfeeding women after careful consideration.
The following undesirable effects were observed during the administration of the fat emulsions. The following convention has been used for the classification of frequency: Common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10,000 to <1/1000) and very rare (<1/10,000).
Respiratory, Thoracic and Mediastinal Disorders:
Uncommon: Lack of appetite, nausea, vomiting.
Rare: Hypotension, hypertension.
General Disorders and Administration Site Conditions:
Common: Slight increase in body temperature. Uncommon: Chills. Rare: Hypersensitivity reactions (eg, anaphylactic or anaphylactoid reactions, skin rash, urticaria, flush, headache), heat or cold sensation, paleness, cyanosis, pain in the neck, back, bones, chest and loins.
Reproductive System and Breast Disorders:
Very Rare: Priapism.
Should these undesirable effects occur or should the triglyceride level during infusion rise >3 mmol/L, the infusion of SMOFlipid 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 hyperglycemia are symptoms related to conditions indicating parenteral nutrition and may sometimes be associated with parenteral nutrition.
Monitoring of triglycerides and blood glucose levels are recommended to avoid elevated levels, which may be harmful.
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 hypertriglyceridemia, even at the recommended infusion rate, and in association with a sudden change in the patient's clinical condition eg, renal function impairment or infection. The fat overload syndrome is characterised by hyperlipemia, fever, fat infiltration, hepatomegaly with or without icterus, splenomegaly, anemia, leukopenia, thrombocytopenia, coagulation disorder, hemolysis 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.
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 bean oil has a natural content of vitamin K1. The content is however low in SMOFlipid that it is not expected to significantly influence the coagulation process in patients treated with coumarin derivatives.
Incompatibilities: SMOFlipid must not be mixed with other medicinal products except those mentioned in Cautions for Usage.
Special Precautions for Disposal and Handling: Use only if the emulsion is homogeneous. For Excel 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.
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.
SMOFlipid is 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.
Compatibility for different additives and the storage time of the different admixtures will be available upon request.
Additions should be made aseptically. Any mixture remaining after infusion must be discarded.
Do not store above 25°C. Do not freeze.
Storage 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 >24 hrs at 2-8°C, unless additions have taken place in controlled and validated aseptic conditions.
Shelf-Life: 2 years.
Shelf-Life After First Opening the Container: Chemical and physical in-use stability has been demonstrated for 24 hrs 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 hrs at 2-8°C.
B05BA02 - fat emulsions ; Belongs to the class of solutions for parenteral nutrition used in I.V. solutions.
Emulsion for infusion (white homogenous) 100 mL.