Israel - English - Ministry of Health
AME OF THE
emulsion for infusion
SmofKabiven consists of a three chamber bag system. Each bag contains the following partial volumes
depending on the four pack sizes.
Per 1000 ml
Amino acid solution with electrolytes
This corresponds to the following total compositions:
Per 1000 ml
Lysine (as acetate)
Calcium chloride (as dihydrate)
Sodium glycerophosphate (as hydrate)
Magnesium sulphate (as heptahydrate)
Sodium acetate (as trihydrate)
Zinc sulphate (as heptahydrate)
Glucose (as monohydrate)
Soya-bean oil, refined
Olive oil, refined
Fish oil, rich in omega-3-acids
Per 1000 ml
100 mmol 41 mmol
0.06 mmol 0.08 mmol
261 mmol 106 mmol
- Glucose (anhydrous)
- total (approx.)
- non protein (approx.)
approx. 1800 mosmol/kg water
approx. 1500 mosmol/l
pH (after mixing)
Contribution from both the lipid emulsion and the amino acid solution.
For a full list of excipients, see section 6.1.
Emulsion for infusion.
Glucose and amino acid solutions are clear and colourless to slightly yellow and free from particles. The lipid
emulsion is white and homogenous.
Parenteral nutrition for adult patients when oral or enteral nutrition is impossible, insufficient or contraindicated.
Posology and method of administration
The appearance of the product after mixing the 3 chambers is a white emulsion.
The patient’s ability to eliminate fat and metabolise nitrogen and glucose, and the nutritional requirements
should govern the dosage and infusion rate, see section 4.4.
The dose should be individualised with regard to the patient’s clinical condition and body weight (bw).
The nitrogen requirements for maintenance of body protein mass depend on the patient’s condition (e.g.
nutritional state and degree of catabolic stress or anabolism).
The requirements are 0.10-0.15 g nitrogen/kg bw/day (0.6-0.9 g amino acids/kg bw/day) in the normal
nutritional state or in conditions with mild catabolic stress. In patients with moderate to high metabolic stress
with or without malnutrition, the requirements are in the range of 0.15-0.25 g nitrogen/kg bw/day (0.9-1.6 g
amino acids/kg bw/day). In some very special conditions (e.g. burns or marked anabolism) the nitrogen need
may be even higher.
The dosage range of 13 ml – 31 ml SmofKabiven/kg bw/day corresponds to 0.10-0.25 g nitrogen/kg bw/day
(0.6-1.6 g amino acids/kg bw/day) and 14-35 kcal/kg bw/day of total energy (12-27 kcal/kg bw/day of non-
protein energy). This covers the need of the majority of the patients. In obese patients the dose should be
based on the estimated ideal weight.
The maximum infusion rate for glucose is 0.25 g/kg bw/h, for amino acid 0.1 g/kg bw/h, and for fat 0.15 g/kg
The infusion rate should not exceed 2.0 ml/kg bw/h (corresponding to 0.25 g glucose, 0.10 g amino acids, and
0.08 g fat/kg bw/h). The recommended infusion period is 14-24 hours.
Maximum daily dose
The maximum daily dose varies with the clinical condition of the patient and may even change from day to
day. The recommended maximum daily dose is 35 ml/kg bw/day.
The recommended maximum daily dose of 35 ml/kg bw/day will provide 0.28 g nitrogen/kg bw/day
(corresponding to 1.8 g amino acids/kg bw/day), 4.5 g glucose/kg bw/day, 1.33 g fat/kg bw/day and a total
energy of 39 kcal/kg bw/day (corresponding to 31 kcal/kg bw/day of non-protein energy).
Method of administration
Intravenous use, infusion into a central vein.
The four different package sizes of SmofKabiven are intended for patients with high, moderately increased or
basal nutritional requirements. To provide total parenteral nutrition, trace elements, vitamins and possibly
electrolytes (taking into account the electrolytes already present in SmofKabiven) should be added to
SmofKabiven according to the patients need.
SmofKabiven is not recommended for use in children, see section 4.4.
Hypersensitivity to fish-, egg, soya- or peanut protein or to any of the active substances or excipients
Severe liver insufficiency
Severe blood coagulation disorders
Congenital errors of amino acid metabolism
Severe renal insufficiency without access to hemofiltration or dialysis
Pathologically elevated serum levels of any of the included electrolytes
General contraindications to infusion therapy: acute pulmonary oedema, hyperhydration, and
decompensated cardiac insufficiency
Unstable conditions (e.g. severe post-traumatic conditions, uncompensated diabetes mellitus, acute
myocardial infarction, stroke, embolism, metabolic acidosis, severe sepsis, hypotonic dehydration and
Special warnings and precautions for use
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. The concentration of triglycerides in serum
should not exceed 4 mmol/l during infusion. An overdose may lead to fat overload syndrome, see section 4.8.
SmofKabiven 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.
This medicinal product 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
To avoid risks associated with too rapid infusion rates, it is recommended to use a continuous and well-
controlled infusion, if possible by using a volumetric pump.
Disturbances of the electrolyte and fluid balance (e.g. abnormally high or low serum levels of the electrolytes)
should be corrected before starting the infusion.
SmofKabiven should be given with caution to patients with a tendency towards electrolyte retention. Special
clinical monitoring is required at the beginning of any intravenous infusion. Should any abnormal sign occur,
the infusion must be stopped.
Since an increased risk of infection is associated with the use of any central vein, strict aseptic precautions
should be taken to avoid any contamination during catheter insertion and manipulation.
Serum glucose, electrolytes and osmolarity as well as fluid balance, acid-base status and liver enzyme tests
should be monitored.
Blood cell count and coagulation should be monitored when fat is given for a longer period.
In patients with renal insufficiency, the phosphate and potassium intake should be carefully controlled to
prevent hyperphosphatemia and hyperkalaemia.
The amount of individual electrolytes to be added is governed by the clinical condition of the patient and by
frequent monitoring of serum levels.
Parenteral nutrition should be given with caution in lactic acidosis, insufficient cellular oxygen supply and
increased serum osmolarity.
Any sign or symptom of anaphylactic reaction (such as fever, shivering, rash or dyspnoea) should lead to
immediate interruption of the infusion.
The fat content of SmofKabiven may interfere with certain laboratory measurements (e.g. bilirubin, lactate
dehydrogenase, oxygen saturation, hemoglobin) if blood is sampled before fat has been adequately cleared
from the bloodstream. Fat is cleared after a fat-free interval of 5-6 hours in most patients.
Intravenous infusion of amino acids is accompanied by increased urinary excretion of the trace elements, in
particular copper and zinc. This should be considered in the dosing of trace elements, especially during long-
term intravenous nutrition. Amounts of zinc administered with SmofKabiven should be taken into account.
In malnourished patients, initiation of parenteral nutrition can precipitate fluid shifts resulting in pulmonary
oedema and congestive heart failure as well as a decrease in the serum concentration of potassium,
phosphorus, magnesium and water soluble vitamins. These changes can occur within 24 to 48 hours,
therefore careful and slow initiation of parenteral nutrition is recommended in this patient group, together with
close monitoring and appropriate adjustments of fluid, electrolytes, minerals and vitamins.
SmofKabiven should not be given simultaneously with blood in the same infusion set due to the risk of
In patients with hyperglycaemia, administration of exogenous insulin might be necessary.
Due to composition of the amino acid solution in SmofKabiven it is not suitable for the use in new-borns or
infants below 2 years of age. There is at present no clinical experience of the use of SmofKabiven in children
(age 2 years to 11 years).
Interaction with other medicinal products and other forms of interaction
Some medicinal products, like insulin, may interfere with the body’s lipase system. This kind of interaction
seems, however, to be of limited clinical importance.
Heparin given in clinical doses causes a transient release of lipoprotein lipase into the circulation. This may
result initially in increased plasma lipolysis followed by a transient decrease in triglyceride clearance.
Soya-bean oil has a natural content of vitamin K
. However, the concentration in SmofKabiven is so low that it
is not expected to significantly influence the coagulation process in patients treated with coumarin derivatives.
Pregnancy and lactation
There are no data available on exposure of SmofKabiven in pregnant or breast-feeding women. There are no
studies available on reproductive toxicity in animals. Parenteral nutrition may become necessary during
pregnancy and lactation. SmofKabiven should only be given to pregnant and breast-feeding women after
Effects on ability to drive and use machines
≥ 1/100, <1/10
≥ 1/1000, <1/100
≥ 1/10000, <1/1000
Respiratory, thoracic and
Lack of appetite, nausea,
Metabolism and nutrition
Elevated plasma levels of
General disorders and
Slight increase in body
(e.g. anaphylactic or
skin rash, urticaria, flush,
headache), heat or cold
cyanosis, pain in the neck,
back, bones, chest and
Should these side-effects occur the infusion of SmofKabiven should be stopped or, if necessary, continued at
a reduced dosage.
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, such as 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 lipid emulsion is discontinued.
Excess of amino acid infusion
As with other amino acid solutions, the amino acid content in SmofKabiven may cause undesirable effects
when the recommended infusion rate is exceeded. These effects are nausea, vomiting, shivering and
sweating. Amino acid infusion may also cause a rise in body temperature. With an impaired renal function,
increased levels of nitrogen containing metabolites (e.g. creatinine, urea) may occur.
Excess of glucose infusion
If the glucose clearance capacity of the patient is exceeded, hyperglycaemia will develop.
See section 4.8 “Fat overload syndrome”, “Excess of amino acid infusion” and “Excess of glucose infusion”.
If symptoms of overdose of fat or amino acids occur, the infusion should be slowed down or discontinued.
There is no specific antidote for overdose. Emergency procedures should be general supportive measures,
with particular attention to respiratory and cardiovascular systems. Close biochemical monitoring would be
essential and specific abnormalities treated appropriately.
If hyperglycaemia occurs, it should be treated according to the clinical situation either by appropriate insulin
administration and/or adjustment of the infusion rate.
Additionally, overdose might cause fluid overload, electrolyte imbalances and hyperosmolality.
In some rare serious cases, haemodialysis, haemofiltration or haemo-diafiltration may be considered.
Pharmacotherapeutic group: Solutions for parenteral nutrition.
ATC code: B05BA10
The lipid emulsion of SmofKabiven is composed of Smoflipid and has a particle size and biological properties
similar to those of endogenous chylomicrons. The constituents of SmofKabiven; soya-bean oil, medium-chain
triglycerides, olive oil and fish oil have except for their energy contents, their own pharmacodynamic
Soya-bean oil has a high content of essential fatty acids. The omega-6 fatty acid linoleic acid is the most
abundant (approx. 55-60%). Alpha-linolenic acid, an omega-3 fatty acid, constitutes about 8 %. This part of
SmofKabiven 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
Olive oil mainly provides energy in the form of mono-unsaturated fatty acids, which are much less prone to
peroxidation than the corresponding amount of poly-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
prostaglandines, thromboxanes and leucotrienes.
Two 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
one of the studies, which was done in paediatric patients. This study was stratified by age groups (1 month -
<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.
Amino acids and electrolytes
The amino acids, constituents of protein in ordinary food, are utilised for tissue protein synthesis and any
surplus is channelled to a number of metabolic pathways. Studies have shown a thermogenic effect of amino
Glucose should have no pharmacodynamic effects apart from contributing to maintain or replete the normal
The individual triglycerides in Smoflipid have different clearance rate but Smoflipid as a mixture is eliminated
faster than long chain triglycerides (LCT). 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.
Amino acids and electrolytes
The principal pharmacokinetic properties of the infused amino acids and electrolytes are essentially the same
as for amino acids and electrolytes supplied by ordinary food. However, the amino acids of dietary protein first
enter the portal vein and then the systemic circulation, while intravenously infused amino acids reach the
systemic circulation directly.
The pharmacokinetic properties of infused glucose are essentially the same as those of glucose supplied by
Preclinical safety data
Preclinical safety studies with SmofKabiven have not been performed. However, preclinical data for Smoflipid
as well as amino acid and glucose solutions of various concentrations and sodium glycerophosphate reveal no
special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity and
genotoxicity. No teratogenic effects or other embryotoxic injuries could be observed in rabbits with amino acid
solutions and are not to be expected from fat emulsions and sodium glycerophosphate when giving at the
recommended doses as substitution therapy.Nutritional products (amino acid solutions, fat emulsions, and
sodium glycerophosphate) used in replacement therapy at physiological levels are not expected to be
embryotoxic, teratogenic, or to influence reproductive performance or fertility.
In a test on guinea pigs (maximisation test) fish oil emulsion showed moderate dermal sensitisation. A
systemic antigenicity test gave no indication of evidence of anaphylactic potential of fish oil.
In a local tolerance study in rabbits with Smoflipid a slight, transient inflammation after intra-arterial,
paravenous or subcutaneous administration was observed. After intra-muscular administration a moderate
transient inflammation and tissue necrosis were seen in some animals.
List of excipients
Purified egg phospholipids
Sodium hydroxide (pH adjuster)
Acetic acid, glacial (pH adjuster)
Hydrochloric acid (pH adjuster)
Water for injections
SmofKabiven may only be mixed with other medicinal products for which compatibility has been documented.
Shelf life of the medicinal product as packaged for sale : 2 years
Shelf life after mixing
Chemical and physical in-use stability of the mixed three chamber bag has been demonstrated for 36 hours at
C. From a microbiological point of view the product 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
Shelf life after mixing with additives
From a microbiological point of view, the product should be used immediately when additions have been
made. If not used immediately, the in-use storage time and conditions prior to use are the responsibility of the
user and should normally not be longer than 24 hours at 2-8
Special precautions for storage
Do not store above 25°C. Do not freeze. Store in overpouch.
Shelf life after mixing: See section 6.3.
Shelf life after mixing with additives: See section 6.3.
Nature and contents of container
The container consists of a multichamber inner bag and an overpouch. The inner bag is separated into three
chambers by peelable seals. An oxygen absorber is placed between the inner bag and the overpouch. The
inner bag is made of a multilayer polymer film, alternatively Excel or Biofine. The Excel innerbag film consists
of three layers. The inner layer consists of poly (propylene/ethylene) copolymer and
styrene/ethylene/butylene/styrene thermoplastic elastomer (SEBS). The middle layer consists of SEBS and
the outer layer consists of copolyester-ether. The infusion port is equipped with a polyolefine cap. The
additive port is equipped with a synthetic polyisoprene (latex-free) stopper.
The Biofine inner bag film consists of poly(propylene-co-ethylene), synthetic rubber poly[styrene-block-
(butylene-co-ethylene)] (SEBS) and synthetic rubber poly(styrene-block-isoprene) (SIS). The infusion and
additive ports are made of polypropylene and synthetic rubber poly[styrene-block-(butylene-co-ethylene)]
(SEBS) equipped with synthetic polyisoprene (latex-free) stoppers. The blind port, which is only used during
manufacturing, is made of polypropylene equipped with a synthetic polyisoprene (latex-free) stopper.
1 x 986 ml, 4 x 986 ml
1 x1477 ml, 4 x 1477 ml
1 x 1970 ml, 2 x 1970 ml (Excel), 4 x 1970 ml (Biofine)
1 x 2463 ml, 2 x 2463 ml (Excel), 3 x 2463 ml (Biofine)
Not all pack sizes may be marketed.
Special precaution for disposal
Instructions for use
Do not use if package is damaged. Use only if the amino acid and glucose solutions are clear and colourless
or slightly yellow and the lipid emulsion is white and homogenous. The contents of the three separate
chambers have to be mixed before use, and before any additions are made via the additive port.
After separation of the peelable seals the bag should be inverted on a number of occasions to ensure a
homogenous mixture, which does not show any evidence of phase separation.
Only medicinal or nutrition solutions for which compatibility has been documented may be added to
SmofKabiven. Compatibility for different additives and the storage time of the different admixtures will be
available upon request.
Addition should be made aseptically.
For single use only. Any mixture remaining after infusion must be discarded.
7 Manufacturer: Fresenius Kabi AB, Uppsala, Sweden.
8 Registration holder: Cure Medical & Technical supply Ltd, Hashiloach 6, P.O.B. 3340, Petach Tikva.
The format of this leaflet was determined by the Ministry of Health and its
content was checked and approved in June 2013.