Smofkabiven central
Ukraine
Table of Contents
INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT SMOFKABIVEN CENTRAL
Composition:
"SmofKabiven Central" is supplied in a three-compartment container. Each compartment contains different solutions in varying volumes, depending on the container size.
| Container volume |
986 ml |
1477 ml |
1970 ml |
2463 ml |
| Chamber No. 1 Amino acid solution with electrolytes (Aminoven 10 % with electrolytes) |
500 ml |
750 ml |
1000 ml |
1250 ml |
| Chamber No. 2 Glucose 42 % |
298 ml |
446 ml |
595 ml |
744 ml |
| Chamber No. 3 Lipid emulsion (Smoflipid 20 %) |
188 ml |
281 ml |
375 ml |
469 ml |
Composition of the preparation after mixing the contents of the three chambers:
| Active substances |
986 ml |
1477 ml |
1970 ml |
2463 ml |
| Alanine |
7.0 g |
10.5 g |
14.0 g |
17.5 g |
| Arginine |
6.0 g |
9.0 g |
12.0 g |
15.0 g |
| Glycine |
5.5 g |
8.2 g |
11.0 g |
13.8 g |
| Histidine |
1.5 g |
2.2 g |
3.0 g |
3.7 g |
| Isoleucine |
2.5 g |
3.8 g |
5.0 g |
6.2 g |
| Leucine |
3.7 g |
5.6 g |
7.4 g |
9.4 g |
| Lysine (as lysine acetate) |
3.3 g |
5.0 g |
6.6 g |
8.4 g |
| Methionine |
2.2 g |
3.2 g |
4.3 g |
5.4 g |
| Phenylalanine |
2.6 g |
3.8 g |
5.1 g |
6.4 g |
| Proline |
5.6 g |
8.4 g |
11.2 g |
14.0 g |
| Serine |
3.2 g |
4.9 g |
6.5 g |
8.1 g |
| Taurine |
0.50 g |
0.75 g |
1.0 g |
1.2 g |
| Threonine |
2.2 g |
3.3 g |
4.4 g |
5.4 g |
| Tryptophan |
1.0 g |
1.5 g |
2.0 g |
2.5 g |
| Tyrosine |
0.20 g |
0.30 g |
0.40 g |
0.49 g |
| Valine |
3.1 g |
4.6 g |
6.2 g |
7.6 g |
| Calcium chloride (as calcium chloride dihydrate) |
0.28 g |
0.42 g |
0.56 g |
0.69 g |
| Sodium glycerophosphate (as sodium glycerophosphate hydrate) |
2.1 g |
3.1 g |
4.2 g |
5.2 g |
| Magnesium sulfate (as magnesium sulfate heptahydrate) |
0.60 g |
0.90 g |
1.2 g |
1.5 g |
| Potassium chloride |
2.2 g |
3.4 g |
4.5 g |
5.7 g |
| Sodium acetate (as sodium acetate trihydrate) |
1.7 g |
2.6 g |
3.4 g |
4.2 g |
| Zinc sulfate (as zinc sulfate heptahydrate) |
0.0065 g |
0.0097 g |
0.013 g |
0.016 g |
| Glucose (as glucose monohydrate) |
125 g |
187 g |
250 g |
313 g |
| Refined soybean oil |
11.3 g |
16.9 g |
22.5 g |
28.1 g |
| Medium-chain triglycerides |
11.3 g |
16.9 g |
22.5 g |
28.1 g |
| Refined olive oil |
9.4 g |
14.1 g |
18.8 g |
23.4 g |
| Fish oil, saturated omega-3 fatty acids |
5.6 g |
8.4 g |
11.3 g |
14.0 g |
What corresponds to:
| Amino acids |
50 g |
75 g |
100 g |
125 g |
| Nitrogen |
8 g |
12 g |
16 g |
20 g |
| Carbohydrates
|
125 g |
187 g |
250 g |
313 g |
| Fats |
38 g |
56 g |
75 g |
94 g |
| Electrolytes: |
||||
| Sodium |
40 mmol |
60 mmol |
80 mmol |
100 mmol |
| Potassium |
30 mmol |
45 mmol |
60 mmol |
74 mmol |
| Magnesium |
5.0 mmol |
7.5 mmol |
10 mmol |
12 mmol |
| Calcium |
2.5 mmol |
3.8 mmol |
5.0 mmol |
6.2 mmol |
| Phosphate |
12 mmol |
19 mmol |
25 mmol |
31 mmol |
| Zinc |
0.04 mmol |
0.06 mmol |
0.08 mmol |
0.1 mmol |
| Sulfate |
5.0 mmol |
7.5 mmol |
10 mmol |
13 mmol |
| Chloride |
35 mmol |
52 mmol |
70 mmol |
89 mmol |
| Acetate |
104 mmol |
157 mmol |
209 mmol |
261 mmol |
| Energy value: |
||||
|
1100 kcal 4.6 MJ |
1600 kcal 6.7 MJ |
2200 kcal 9.2 MJ |
2700 kcal 11.3 MJ |
|
900 kcal 3.8 MJ |
1300 kcal 5.4 MJ |
1800 kcal 7.5 MJ |
2200 kcal 9.2 MJ |
Osmolality – approximately 1800 mOsmol/kg water.
Osmolarity – approximately 1500 mOsmol/L.
pH after mixing – approximately 5.6.
Excipients: glycerol, purified egg phospholipids, racemic mixture of α-tocopherols, sodium hydroxide, sodium oleate, glacial acetic acid, hydrochloric acid, water for injections.
Pharmaceutical form. Emulsion for infusion.
Main physicochemical properties. Amino acid solution with electrolytes (Aminoven 10% with electrolytes) – a clear, colorless or slightly yellow solution, free from particles. Glucose 42% – a clear, colorless solution, free from particles. Lipid emulsion (Smoflipid 20%) – a homogeneous white-colored solution. After mixing the contents of the three chambers, the preparation has the appearance of a white emulsion.
Pharmacotherapeutic group. Solutions for parenteral nutrition. Combinations.
ATC code B05B A10.
Pharmacological Properties
Pharmacodynamics
The lipid emulsion "SmofKabiven Central" consists of 20% Smoflipid, which is similar in particle size and biological properties to endogenous chylomicrons. The components of the lipid emulsion include soybean oil, medium-chain triglycerides, olive oil, and fish oil, which, in addition to their energy value, possess their own pharmacodynamic properties.
Soybean oil has a high content of essential fatty acids. The most prevalent is linoleic acid, belonging to the omega-6 fatty acid class, present in an amount of approximately 55–60%. The content of α-linolenic acid, belonging to the omega-3 fatty acid class, is approximately 8%. This component of "SmofKabiven Central" provides the necessary amount of essential fatty acids. Medium-chain fatty acids are rapidly oxidized and provide the body with readily available energy. Olive oil primarily supplies energy through monounsaturated fatty acids, which are significantly less susceptible to peroxidation than an equivalent amount of polyunsaturated fatty acids. Fish oil is characterized by a high content of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). DHA is an important structural component of cell membranes, while EPA serves as a precursor for eicosanoids such as prostaglandins, thromboxanes, and leukotrienes.
Amino acids contained in regular food are used for tissue protein synthesis, and any excess is directed toward various metabolic processes. Studies have demonstrated a thermogenic effect of amino acid infusions.
Glucose contained in the preparation participates in maintaining or restoring normal nutritional status and has no other pharmacodynamic effects.
Pharmacokinetics
Individual triglycerides in Smoflipid 20% have different clearance rates, but Smoflipid 20% as a mixture is eliminated faster than long-chain triglycerides (LCT). Olive oil has a slower component clearance (slightly lower than LCT), while medium-chain triglycerides are cleared more rapidly. Fish oil in a mixture with LCT has the same clearance as LCT alone.
The main pharmacokinetic properties of amino acids and electrolytes administered intravenously are essentially the same as those in regular food. However, dietary proteins initially enter the portal vein and then the systemic circulation, whereas administered amino acids and electrolytes reach the systemic circulation directly.
The pharmacokinetic properties of administered glucose are essentially the same as when supplied through regular food.
Clinical characteristics.
Indications.
Parenteral nutrition when oral or enteral nutrition is impossible, inadequate, or contraindicated.
Contraindications.
- Hypersensitivity to fish, egg, soy, or peanut proteins or to any component of the medicinal product.
- Severe hyperlipidemia.
- Severe hepatic insufficiency.
- Severe coagulation disorders.
- Inherited disorders of amino acid metabolism.
- Severe renal insufficiency in the absence of access to hemofiltration or dialysis.
- Acute phase of shock.
- Uncontrolled hyperglycemia.
- Pathologically elevated plasma levels of any of the electrolytes contained in the product.
- General contraindications to infusion therapy: acute pulmonary edema, hyperhydration, decompensated heart failure.
- Hemophagocytic syndrome.
- Unstable clinical condition (including severe post-traumatic state, uncompensated diabetes mellitus, acute myocardial infarction, stroke, embolism, metabolic acidosis, severe sepsis, hypotonic dehydration, and hyperosmolar coma).
- Pediatric use under 2 years of age.
Special precautions.
For single use only.
Do not use if the packaging is damaged. Use only if the amino acid solution and glucose solution are clear and colorless or light yellow, and the lipid emulsion is white and homogeneous. The contents of the three separate chambers must be mixed before use or before adding additives through the appropriate port. After opening the clamps, the container should be inverted several times to homogenize the mixture, which should not show phase separation.
Additives should be added under aseptic conditions.
Any unused solution should be discarded.
Interaction with other medicinal products and other forms of interaction.
Some medicinal products, such as insulin, may affect the body's lipase system.
However, this type of interaction has limited clinical significance.
Heparin, at clinical doses, causes a transient release of lipoprotein lipase into the circulation. This may lead to increased lipolysis in plasma and a temporary reduction in triglyceride clearance.
Soybean oil contains natural vitamin K1. However, its concentration in "SmofKabiven Central" is so low that its effect on blood coagulation in patients taking coumarin derivatives is negligible.
Special precautions for use.
The level of triglycerides should be monitored, and their concentration in blood plasma during infusion should not exceed 4 mmol/L. Overdosage may lead to the development of fat overload syndrome. "SmofKabiven I.V. Fat Emulsion" should be administered with caution in patients with lipid metabolism disorders, which may occur in patients with renal insufficiency, diabetes mellitus, pancreatitis, liver dysfunction, hypothyroidism, and sepsis.
The medicinal product contains soybean oil, fish oil, and egg phospholipids, which in rare cases may cause allergic reactions. Allergy to soy and peanuts may be cross-reactive.
To avoid risks associated with very rapid infusion, continuous and well-controlled infusions are recommended, preferably using a volumetric infusion pump.
Electrolyte and fluid imbalances (e.g., abnormally high or low serum electrolyte levels) should be corrected prior to the start of infusion.
"SmofKabiven I.V. Fat Emulsion" should be administered with caution to patients predisposed to electrolyte retention. Clinical parameters should be monitored before initiating any intravenous infusions. If any abnormal symptoms occur, the infusion should be stopped immediately.
Since any central venous infusion carries an increased risk of infection, strict adherence to aseptic techniques is essential during catheter insertion and handling to prevent infection.
Glucose levels, electrolytes, osmolarity, fluid balance, acid-base balance, and liver enzyme levels in blood plasma should be monitored.
During prolonged lipid administration, cellular blood composition and coagulation parameters should be monitored.
In patients with renal insufficiency, phosphate and potassium intake should be carefully monitored to prevent hyperphosphatemia and hyperkalemia.
The amount of additional electrolytes should be determined by regular monitoring of their plasma concentrations, taking into account the patient's clinical condition.
Parenteral nutrition should be administered with caution in patients with lactic acidosis, inadequate cellular oxygen supply, and increased plasma osmolarity.
If any symptoms of an anaphylactic reaction occur (e.g., fever, chills, rash, or dyspnea), the infusion must be stopped immediately.
The presence of lipids in the preparation may affect the results of certain laboratory tests (e.g., bilirubin concentration, lactate dehydrogenase activity, blood oxygen saturation, hemoglobin levels) if blood samples are taken before adequate clearance of lipids from the circulation. In most patients, lipids are cleared within 5–6 hours.
Intravenous administration of amino acids is associated with increased urinary excretion of trace elements, especially copper and zinc. This should be taken into account when adding trace elements, particularly during prolonged parenteral nutrition. The amount of zinc administered with "SmofKabiven I.V. Fat Emulsion" should be considered.
In patients with malnutrition, initiation of parenteral nutrition may cause fluid redistribution, potentially leading to pulmonary edema and congestive heart failure, as well as decreased plasma concentrations of potassium, phosphate, magnesium, and water-soluble vitamins. These effects may manifest within 24–48 hours; therefore, parenteral nutrition should be initiated cautiously and slowly in such patients, with careful monitoring and appropriate correction of fluid, electrolyte, trace element, and vitamin levels.
"SmofKabiven I.V. Fat Emulsion" should not be administered simultaneously with blood through the same infusion system due to the risk of pseudoagglutination.
Patients with hyperglycemia may require insulin administration.
Only medicinal products and nutritional additives whose compatibility with "SmofKabiven I.V. Fat Emulsion" has been documented should be added to the solution.
Use during pregnancy or breastfeeding.
There are no available data on the effects of "SmofKabiven I.V. Fat Emulsion" in pregnant or breastfeeding women; therefore, the benefit-risk ratio should be carefully evaluated before prescribing the product.
Ability to affect reaction speed when driving or operating machinery.
Not studied. The product is intended for hospital use only.
Administration and Dosage
Intravenous administration into a central vein.
When determining dosage and infusion rate, the patient's ability to metabolize fats, nitrogen, and glucose must be taken into account. The dose should be individually adjusted based on the patient's condition, body weight, nutritional and energy requirements, and additional oral/enteral nutrition.
Nitrogen requirements for maintaining body protein mass depend on the patient's condition (nutritional status, level of catabolic stress, and anabolism).
Adults
In patients with normal nutritional status or mild catabolic stress, nitrogen requirement is 0.10–0.15 g nitrogen/kg body weight/day (0.6–0.9 g amino acids/kg body weight/day). In patients with moderate to high metabolic stress, including malnutrition, the requirement is 0.15–0.25 g nitrogen/kg body weight/day (0.9–1.6 g amino acids/kg body weight/day). In certain special situations (e.g., burns or pronounced anabolism), nitrogen requirements may be even higher.
Dosing
A dose of 13–31 mL/kg body weight/day of "SmofKabiven central" corresponds to 0.10–0.25 g nitrogen/kg body weight/day (0.6–1.6 g amino acids/kg body weight/day) and provides 14–35 kcal/kg body weight/day total energy (12–27 kcal/kg body weight/day non-protein energy). This range meets the needs of most patients. For patients with excess body weight, dosing should be based on ideal body weight.
Infusion Rate
Maximum infusion rates are as follows: glucose – 0.25 g/kg body weight/hour, amino acids – 0.1 g/kg body weight/hour, lipids – 0.15 g/kg body weight/hour.
The infusion rate should not exceed 2 mL/kg body weight/hour (corresponding to 0.25 g glucose, 0.10 g amino acids, and 0.08 g lipids/kg body weight/hour). The recommended duration of infusion is 14–24 hours.
Maximum Daily Dose
The maximum daily dose depends on the patient's clinical condition and may vary. The recommended maximum daily dose is 35 mL/kg body weight/day, which provides 0.28 g nitrogen/kg body weight/day (equivalent to 1.8 g amino acids/kg body weight/day), 4.5 g glucose/kg body weight/day, 1.33 g lipids/kg body weight/day, and a total energy intake of 39 kcal/kg body weight/day (corresponding to 31 kcal/kg body weight/day of non-protein energy).
Children aged 2 to 11 years
Dosing
A dose of up to 35 mL/kg body weight/day should be regularly adjusted according to the changing nutritional needs of pediatric patients, which vary more than in adults.
Infusion Rate
The recommended maximum infusion rate is 2.4 mL/kg body weight/hour (corresponding to 0.12 g amino acids/kg/hour, 0.30 g glucose/kg/hour, and 0.09 g lipids/kg/hour). At this maximum recommended infusion rate, the product should be administered over no more than 14 hours 30 minutes, except in exceptional cases and under close monitoring.
The recommended infusion duration is 12–24 hours.
Maximum Daily Dose
The maximum daily dose depends on the patient's clinical condition and may vary from day to day. The recommended maximum daily dose is 35 mL/kg body weight/day, providing 0.28 g nitrogen/kg body weight/day (equivalent to 1.8 g amino acids/kg body weight/day), 4.5 g glucose/kg body weight/day, 1.33 g lipids/kg body weight/day, and a total energy content of 39 kcal/kg body weight/day (corresponding to 31 kcal/kg body weight/day of non-protein energy).
Adolescents aged 12–16/18 years
SmofKabiven central should be administered to adolescents as in adults.
Four different package sizes of SmofKabiven central are intended for patients with high, moderately increased, and normal nutritional requirements. To ensure complete parenteral nutrition according to individual patient needs, trace elements, vitamins, and electrolytes may be added to SmofKabiven central (taking into account the electrolytes already present in SmofKabiven central).
Instructions for Use of the Three-Chamber Container "Biofin"
- Perforation on the outer plastic bag
- Handle
- Hanging hole for container
- Partition
- Blind port (not used)
- Inlet port (for additives)
- Outlet port (for infusion system)
- Antioxidant (in the outer plastic bag)
- Removal of the outer plastic bag
Holding the container horizontally, remove the outer plastic bag by tearing it at the perforation and pulling along the edge. Discard together with the antioxidant.
- Mixing
Place the three-chamber container on a flat surface. Twist the container tightly, starting from the corner near the handle diagonally toward the blind port.
Then, holding the twisted portion with the right hand while maintaining constant internal pressure with the left hand, press on the container until the vertical partitions open.
Open the vertical partitions using the pressure built up inside the container. The horizontal partition does not need to be opened; the contents of the chambers mix easily after only the vertical partitions are opened.
Mix the chamber contents by turning the container 2–3 times.
Note: The vertical partitions can be opened without removing the outer bag, after which the outer bag can be removed.
- Connecting the Infusion System
If additives are required, break off the cap with the arrow from the white-colored port immediately before administration. While holding the inlet port, insert the needle through the center of the membrane and inject the additive (with known compatibility). The port membrane is sterile. After adding another component, thoroughly mix the solution by turning the container several times.
Break off the cap from the blue-colored port with the arrow immediately before inserting the needle. Holding the bag with the inlet port facing upward, insert the needle through the center of the membrane, rotating and pushing it through if necessary. Use an air-free infusion system or block air entry in systems that allow air access.
- Hanging on the Infusion Stand
Hang the container on the stand using the hanging hole.
Children
Due to the composition of the amino acid solution in SmofKabiven central, the product is not suitable for use in newborns and children under 2 years of age.
Overdose
Fat Overload Syndrome
Impaired ability to eliminate triglycerides may lead to fat overload syndrome. Causes include fat overdose, genetic factors (individual metabolic peculiarities), pre-existing or concurrent diseases, or sudden changes in the patient's clinical condition (e.g., renal failure or infection). This syndrome may also occur during severe hypertriglyceridemia, even at the recommended infusion rate. Fat overload syndrome, arising from the above causes, is characterized by hyperlipidemia, fever, fat infiltration, hepatomegaly with or without jaundice, splenomegaly, anemia, leukopenia, thrombocytopenia, coagulation disorders, hemolysis, reticulocytosis, liver dysfunction, and coma. Symptoms are usually reversible if lipid emulsion infusion is discontinued.
Excessive Amino Acid Administration
If the infusion rate is exceeded, as with other amino acid solutions, administration of SmofKabiven central may cause nausea, vomiting, chills, sweating, and elevated body temperature. In patients with impaired renal function, increased levels of nitrogen-containing metabolites (e.g., creatinine, urea) may occur.
Excessive Glucose Administration
If the glucose infusion rate exceeds its clearance, hyperglycemia may develop in patients.
If symptoms of fat or amino acid overdose occur, the infusion rate should be reduced or administration discontinued. There are no specific antidotes for overdose. Supportive care should be provided, with special attention to respiratory and cardiovascular function. Close monitoring of biochemical parameters is essential, and specific abnormalities should be treated accordingly.
In case of hyperglycemia, treatment should be based on the clinical situation—either insulin administration or adjustment of the infusion rate. Additionally, overdose may lead to hypervolemia, electrolyte imbalance, and hyperosmolarity. In some severe cases, hemodialysis, hemofiltration, or hemodiafiltration may be indicated.
Adverse Reactions
The following classification is used to assess the frequency of adverse effects: very common: ≥ 1/10; common: ≥ 1/100 and < 1/10; uncommon: ≥ 1/1,000 and < 1/100; rare: ≥ 1/10,000 and < 1/1,000; very rare: < 1/10,000; frequency not known (cannot be estimated from available data).
Cardiac disorders.
Rare: tachycardia.
Respiratory, thoracic and mediastinal disorders.
Rare: dyspnoea.
Gastrointestinal disorders.
Uncommon: loss of appetite, nausea, vomiting.
Metabolism and nutrition disorders.
Uncommon: increased levels of liver enzymes in blood plasma.
Vascular disorders.
Rare: hypotension, hypertension.
General disorders and administration site conditions.
Common: slight increase in body temperature.
Uncommon: chills, dizziness, headache.
Rare: hypersensitivity reactions (e.g. anaphylactic or anaphylactoid reactions, skin rash, urticaria, facial flushing, headache), sensation of cold or warmth, pallor, cyanosis, pain in the neck, back, bones, chest, or lower back.
If any of these adverse reactions occur, administration of "SmofKabiven Central" should be stopped or, if necessary, the dose should be reduced and administration continued.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients, as well as their legal representatives, should report any suspected adverse reactions and lack of efficacy via the Automated Information System for Pharmacovigilance at: https://aisf.dec.gov.ua.
Shelf life
Shelf life of the medicinal product in the outer plastic bag: 2 years.
Shelf life after mixing.
Chemical and physical stability after opening and mixing of the three chambers is maintained for 36 hours at 25 °C. From a microbiological standpoint, the product should be used immediately. If immediate use is not possible, storage is the responsibility of the user. Generally, storage time should not exceed 24 hours at 2–8 °C.
Shelf life after mixing with additives.
From a microbiological standpoint, the product should be used immediately. If immediate use is not possible, storage is the responsibility of the user. Generally, storage time should not exceed 24 hours at 2–8 °C.
Storage conditions.
Store in a light-protected, child-resistant place at a temperature not exceeding 25 °C. Do not freeze.
Incompatibilities.
Only medical and nutritional additives whose compatibility with "SmofKabiven Central" has been documented may be added to the product.
Packaging.
986 ml, 1477 ml, 1970 ml, 2463 ml in a three-chamber plastic container "Biofin", together with an antioxidant, placed in an outer plastic bag.
986 ml, 1477 ml, 1970 ml in a three-chamber plastic container "Biofin", together with an antioxidant, placed in an outer plastic bag, pack of 4 in a cardboard box.
2463 ml in a three-chamber plastic container "Biofin", together with an antioxidant, placed in an outer plastic bag, pack of 3 in a cardboard box.
Prescription status.
For hospital use only.
Manufacturer.
Fresenius Kabi AB.
Manufacturer's address.
Rapsagatan 7, Uppsala, 754 50, Sweden.
Marketing Authorization Holder.
Fresenius Kabi Deutschland GmbH.
Address of Marketing Authorization Holder.
Else-Kröner-Straße 1, 61352 Bad Homburg, Germany.