Kabiven central

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT KABIVEN CENTRAL (KABIVEN)

Composition:

Kabiven Central is supplied in a three-chamber container and is available in 4 different volumes. Each container, depending on its size, contains the following volumes of solutions:

Container volume	2566 ml	2053 ml	1540 ml	1026 ml
Chamber No. 1
Glucose (Glucose 19%)	1316 ml	1053 ml	790 ml	526 ml
Chamber No. 2
Amino acids and electrolytes (Vamin 18 Novum) Chamber No. 3	750 ml	600 ml	450 ml	300 ml
Lipid emulsion (Intralipid 20%)	500 ml	400 ml	300 ml	200 ml

Composition of the drug after mixing 3 chambers

Active substances	2566 ml	2053 ml	1540 ml	1026 ml
Purified soybean oil	100 g	80 g	60 g	40 g
Glucose monohydrate, equivalent to anhydrous glucose	275 g 250 g	220 g 200 g	165 g 150 g	110 g 100 g
Alanine	12.0 g	9.6 g	7.2 g	4.8 g
Arginine	8.5 g	6.8 g	5.1 g	3.4 g
Aspartic acid	2.6 g	2.0 g	1.5 g	1.0 g
Valine	5.5 g	4.4 g	3.3 g	2.2 g
Histidine	5.1 g	4.1 g	3.1 g	2.0 g
Glycine	5.9 g	4.7 g	3.6 g	2.4 g
Glutamic acid	4.2 g	3.4 g	2.5 g	1.7 g
Isoleucine	4.2 g	3.4 g	2.5 g	1.7 g
Leucine	5.9 g	4.7 g	3.6 g	2.4 g
Lysine hydrochloride, equivalent to lysine	8.5 g 6.8 g	6.8 g 5.4 g	5.1 g 4.1 g	3.4 g 2.7 g
Methionine	4.2 g	3.4 g	2.5 g	1.7 g
Proline	5.1 g	4.1 g	3.1 g	2.0 g
Serine	3.4 g	2.7 g	2.0 g	1.4 g
Tyrosine	0.17 g	0.14 g	0.10 g	0.07 g
Threonine	4.2 g	3.4 g	2.5 g	1.7 g
Tryptophan	1.4 g	1.1 g	0.86 g	0.57 g
Phenylalanine	5.9 g	4.7 g	3.6 g	2.4 g
Calcium chloride dihydrate, equivalent to calcium chloride	0.74 g 0.56 g	0.59 g 0.44 g	0.44 g 0.33 g	0.29 g 0.22 g
Sodium glycerophosphate	3.8 g	3.0 g	2.3 g	1.5 g
Magnesium sulfate heptahydrate, equivalent to magnesium sulfate	2.5 g 1.2 g	2.0 g 0.96 g	1.5 g 0.72 g	0.99 g 0.48 g
Potassium chloride	4.5 g	3.6 g	2.7 g	1.8 g
Sodium acetate trihydrate, equivalent to sodium acetate	6.1 g 3.7 g	4.9 g 2.9 g	3.7 g 2.2 g	2.5 g 1.5 g

What corresponds to: 2566 ml to 2053 ml to 1540 ml to 1026 ml

Amino acids	85 g	68 g	51 g	34 g
Nitrogen	13.5 g	10.8 g	8.1 g	5.4 g
Fats	100 g	80 g	60 g	40 g
Carbohydrates Anhydrous glucose	250 g	200 g	150 g	100 g

Nutritional value

Total	2300 kcal	1900 kcal	1400 kcal	900 kcal
Non-protein	2000 kcal	1600 kcal	1200 kcal	800 kcal

Electrolytes

Sodium	80 mmol	64 mmol	48 mmol	32 mmol
Potassium	60 mmol	48 mmol	36 mmol	24 mmol
Magnesium	10 mmol	8 mmol	6 mmol	4 mmol
Calcium	5 mmol	4 mmol	3 mmol	2 mmol
Phosphate	25 mmol	20 mmol	15 mmol	10 mmol
Sulfate	10 mmol	8 mmol	6 mmol	4 mmol
Chloride	116 mmol	93 mmol	70 mmol	46 mmol
Acetate	97 mmol	78 mmol	58 mmol	39 mmol

Osmolarity 1060 mOsmol/l

Osmolality 1230 mOsmol/kg water

pH 5.6;

Excipients: purified egg phospholipids, glycerol, sodium hydroxide, glacial acetic acid, water for injections.

Pharmaceutical form. Emulsion for infusion.

Main physicochemical properties: mixture of the contents of three chambers – a homogeneous white emulsion.

Pharmacotherapeutic group. Solutions for parenteral nutrition. Combinations.

ATC code B05B A10.

Pharmacological Properties

Pharmacodynamics

The pharmacological properties of the medicinal product are determined by its composition.

Lipid emulsion (Intralipid 20%)

The lipid emulsion contained in Kabiven Central is a source of long-chain fatty acids (including essential ones), which are used in the body as an energy source and for building cellular membranes.

Intralipid, when administered at recommended doses, does not affect hemodynamics. No clinically significant deterioration in lung function has been observed when infusion rates are maintained within recommended limits. Elevated liver enzyme levels have been reported in a few patients. After discontinuation of parenteral nutrition, enzyme levels returned to baseline values. Similar changes may also occur during parenteral nutrition without lipid emulsion.

Amino acids and electrolytes (Vamin 18 Neofusum)

Amino acids are components of proteins in normal food. They are used in the body for protein synthesis and partially in gluconeogenesis processes. Infusion of amino acids leads to increased metabolic rate and, consequently, increased heat production in the body.

Glucose (Glucose 19%)

Glucose has the same pharmacodynamic properties as glucose involved in normal metabolism.

Pharmacokinetics

Lipid emulsion (Intralipid 20%)

Intralipid has biological properties similar to endogenous chylomicrons. Unlike chylomicrons, Intralipid does not contain cholesterol esters or apolipoproteins. The phospholipid content in Intralipid is significantly higher than in chylomicrons.

Intralipid is cleared from the bloodstream via the same pathway as chylomicrons. Exogenous lipid particles are primarily hydrolyzed in the blood and taken up by low-density lipoprotein receptors in the liver and peripheral tissues. The clearance rate depends on the composition of the lipid particles, the patient's clinical and nutritional status, and the infusion rate. The maximum clearance of Intralipid on an empty stomach is equivalent to 3.8±1.5 g of triglycerides/kg body weight per day. The clearance and oxidation rate of the lipid emulsion is accelerated in sepsis and after trauma, and conversely, slowed down in renal failure and hypertriglyceridemia.

Amino acids and electrolytes (Vamin 18 Neofusum)

The pharmacokinetic characteristics of amino acids and electrolytes administered intravenously are similar to those observed when they are ingested with food. However, dietary protein amino acids first enter the portal vein of the liver and only then enter systemic circulation, whereas intravenously administered amino acids enter directly into systemic circulation.

Glucose (Glucose 19%)

The pharmacokinetic characteristics of glucose administered by infusion are the same as those observed when glucose is ingested with normal food.

Clinical characteristics.

Indications.

Parenteral nutrition in adults and children aged 2 years and older when oral or enteral nutrition is impossible, inadequate, or contraindicated.

Contraindications.

Known hypersensitivity to egg, peanut, or soy 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 hemodialysis or hemofiltration.

Acute phase of shock.

Hyperglycemia requiring insulin administration at doses exceeding 6 units/hour.

Pathologically elevated plasma concentration of any of the electrolytes contained in the medicinal product.

General contraindications to infusion therapy (pulmonary edema, hyperhydration, cardiac insufficiency, hypotonic dehydration).

Hemophagocytic syndrome.

Unstable conditions (including post-traumatic state, uncompensated diabetes mellitus, acute stage of myocardial infarction, metabolic acidosis, severe sepsis, and hyperosmolar coma).

Children under 2 years of age.

Interaction with other medicinal products and other types of interactions.

Heparin, at clinically used doses, induces the release of lipoprotein lipase into the bloodstream, which may initially enhance lipolysis in plasma and subsequently reduce triglyceride clearance.

Insulin may also affect lipase activity; however, data on adverse effects of this factor on the therapeutic value of the product are lacking.

Vitamin K1, contained in soybean oil, is an antagonist of coumarin derivatives; therefore, careful monitoring of blood coagulation is recommended in patients receiving these agents.

There are no data on other clinically significant types of interactions.

Special precautions for use.

When using this medication, lipid elimination should be monitored. This is recommended to be done by measuring plasma triglyceride levels 5–6 hours after the last fat intake. The preparation contains soy proteins and egg phospholipids, which may cause allergic reactions. Cross-sensitivity reactions between soy proteins and peanuts are possible.

Plasma triglyceride concentration during infusion should not exceed 3 mmol/L.

The bag volume and quantitative composition must be carefully selected. Each container is intended for single use only.

The volume of administered preparation should be accurately calculated and adjusted according to the patient's fluid balance and nutritional status.

Significant disturbances in electrolyte and fluid balance (e.g., abnormally high or low serum electrolyte levels) should be corrected prior to initiating infusion.

Patients should be closely monitored at the beginning of infusion. Infusion should be discontinued if the patient's condition worsens. Since any central venous infusion carries an increased risk of infection, strict aseptic techniques must be followed during catheter insertion and handling to prevent infection.

Kabiven Central should be used with caution in patients with impaired lipid metabolism, as observed in renal insufficiency, uncompensated diabetes mellitus, pancreatitis, liver dysfunction, hypothyroidism (with hypertriglyceridemia), and sepsis. Administration of Kabiven Central to such patients should be performed under mandatory continuous monitoring of serum triglyceride concentration.

Plasma glucose and electrolyte concentrations, plasma osmolarity, fluid balance, acid-base status, and liver enzyme activity should be regularly monitored.

During prolonged lipid administration, blood cell counts and coagulation parameters should be monitored.

In patients with renal insufficiency, phosphate and potassium balance should be strictly monitored to prevent hyperphosphatemia and hyperkalemia.

The amount of additional electrolytes should be determined by regular monitoring of their concentrations, taking into account the patient's clinical condition.

This preparation does not contain vitamins or trace elements. Addition of trace elements and vitamins is possible. When adding vitamins, the same calculations as in pediatrics should be used.

Parenteral infusion should be administered with caution to patients with metabolic acidosis (e.g., lactic acidosis), as increased serum osmolarity may require rehydration. Kabiven Central should be used with caution in patients with a tendency toward electrolyte retention.

If any signs of allergic reactions occur, infusion should be stopped immediately.

The presence of lipids in the preparation may interfere with 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 bloodstream. In most patients, infused lipids are cleared within 5–6 hours.

Intravenous administration of amino acids may be associated with increased renal excretion of trace elements, especially zinc. Patients requiring prolonged parenteral nutrition may need additional trace element supplementation.

In malnourished patients, initiation of parenteral nutrition may cause fluid imbalance, potentially leading to pulmonary edema and congestive heart failure. Additionally, within 24–48 hours, plasma concentrations of potassium, phosphorus, magnesium, and water-soluble vitamins may decrease. Parenteral nutrition should be initiated slowly, with careful monitoring and appropriate correction of fluid, electrolyte, vitamin, and trace element levels.

Kabiven Central should not be administered through the same catheter simultaneously with blood or blood products.

Patients with hyperglycemia may require insulin administration.

Kabiven Central solutions have an osmolarity of 1060 mOsm/L and therefore are not intended for intravenous administration into peripheral veins in adults or children due to the risk of thrombophlebitis.

Use during pregnancy or breastfeeding.

Specific studies on the safety of the drug during pregnancy or breastfeeding have not been conducted. Before prescribing Kabiven Central to pregnant women or women who are breastfeeding, the physician must evaluate the risk-benefit ratio.

Ability to affect reaction speed when driving or operating machinery.

Not studied. The drug is intended for use only in hospital settings.

Method of Administration and Dosage

For intravenous infusion. Administration is permitted only into central veins.

Fat clearance capacity and glucose metabolism must be taken into account when determining dosage and infusion rate.

Dosage must be individually adjusted, as well as container size selected, based on the patient's condition, body weight, and nutritional requirements.

Nitrogen requirement for protein synthesis depends on the patient's condition (nutritional status and degree of catabolic stress). In patients with normal nutritional status, nitrogen requirement is 0.1–0.15 g nitrogen/kg body weight per day. For patients with moderate or severe catabolic syndrome, with or without malnutrition, nitrogen requirement is 0.15–0.3 g nitrogen/kg body weight per day (1–2 g amino acids/kg body weight per day). Administration of such amounts of amino acids also requires concomitant administration of 2–6 g glucose and 12 g fat per kg body weight.

Total energy requirement depends on the patient's condition and is approximately 25–35 kcal/kg body weight per day. For patients with excess body weight, dosage should be calculated based on ideal body weight.

Kabiven Central is available in containers of four different volumes, allowing its use in patients with high, medium, or low requirements for parenteral nutrition. When administering parenteral nutrition, supplementation with vitamins, essential electrolytes, or trace elements may be necessary.

Adults

19–38 mL Kabiven Central/kg body weight per day

(corresponding to 0.1–0.2 g nitrogen/kg body weight/day or 0.7–1.3 g amino acids/kg body weight per day; energetically equivalent to 25–35 kcal/kg body weight per day). For a 70 kg patient, this corresponds to 1330–2660 mL Kabiven Central per day.

Children aged 2 to 10 years

Infusion should be initiated at low doses:

12.5–25 mL Kabiven Central per kg body weight per day (corresponding to 0.49–0.98 g fat/kg body weight per day, 0.41–0.83 g amino acids/kg body weight per day, and 1.2–1.4 g glucose/kg body weight per day), increasing the dose by 10–15 mL/kg per day until reaching the maximum dose of Kabiven Central 40 mL/kg body weight per day.

Children aged 10 years and older

Dosage of Kabiven Central is the same as for adults.

Infusion Rate

Maximum glucose infusion rate – 0.25 g/kg body weight per hour.

Maximum amino acid infusion rate must not exceed 0.1 g/kg body weight per hour.

Maximum fat infusion rate – 0.15 g/kg body weight per hour.

The infusion rate must not exceed 2.6 mL/kg body weight per hour, corresponding to glucose, amino acids, and lipids doses of 0.25 g/kg body weight per hour, 0.09 g/kg body weight per hour, and 0.13 g/kg body weight per hour, respectively. The recommended duration of infusion is 12–24 hours.

Maximum Daily Dose

40 mL/kg body weight per day, equivalent to one bag (largest volume) for patients weighing 64 kg, providing 1.3 g amino acids/kg body weight per day (0.21 g nitrogen/kg body weight/day), and 31 kcal/kg body weight per day of non-protein energy (3.9 g glucose/kg body weight per day and 1.6 g lipids/kg body weight per day).

Instructions for Use of the Three-Chamber Bag

1. Remove the outer pouch by tearing it at the perforation and pulling along the bag.
2. Firmly grasp the side walls of the bag above the middle of the clamp separating chambers 1 and 2 with the thumbs and index fingers of both hands. Pull the bag walls apart and fully open the clamp.
3. Similarly, open the clamp between chambers 2 and 3. Mix the contents by inverting the bag several times.
4. If adding supplements (with known compatibility, e.g., vitamin or trace element preparations), disinfect the membrane of the injection port.
5. Place the bag on a flat surface; holding the base of the injection port, fully insert the needle through the center of the membrane and inject the supplement (with known compatibility). Before adding a second supplement, thoroughly mix the contents by inverting the bag several times.
6. Remove the cap from the infusion set needle by grasping the ring with thumb and index finger and pulling the ring upward. Use an infusion set without air vent or ensure air access is blocked on systems with air vent.
7. Place the bag on a flat surface. Holding the bag with the outlet port upward, fully insert the needle through the membrane, rotating and pushing as necessary. For secure fixation, the needle must be fully inserted.
8. Hang the bag on an IV stand and follow instructions for the infusion set and infusion pump.
9. Alternative method for opening clamps: place the bag on a flat surface and roll it from the handle side until the clamps open. Mix the contents by inverting the bag several times.

Note: Separate administration of components from individual chambers of Kabiven Central is technically impossible (except for Intralipid). Administration of individual components may be performed using separate pharmaceutical forms: glucose solution, Vamin, and Intralipid.

Children

May be used in children aged 2 years and older (see section "Method of Administration and Dosage").

Overdose

Impaired fat clearance may lead to development of fat overload syndrome (see section "Adverse Reactions").

Nausea, vomiting, and increased sweating may occur if the recommended amino acid infusion rate is exceeded.

Additionally, overdose may result in disturbances of fluid and electrolyte balance, hyperglycemia, and hyperosmolarity.

If symptoms of overdose occur, the infusion rate should be reduced or administration stopped completely.

In severe cases of overdose, hemodialysis, hemofiltration, or hemodiafiltration should be performed.

Adverse Reactions

The following classification is used to assess the frequency of adverse reactions: very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1000, < 1/100), rare (≥ 1/10,000, < 1/1000), very rare (< 1/10,000), frequency not known (cannot be estimated from the available data).

Blood and lymphatic system.

Very rare: haemolysis, reticulocytosis.

Immune system.

Very rare: allergic reactions (e.g. anaphylactic reactions, skin rash, urticaria).

Nervous system.

Uncommon: headache.

Vascular system.

Very rare: hypotension, hypertension.

Respiratory system.

Very rare: tachypnoea.

Gastrointestinal system.

Uncommon: gastrointestinal disorders (abdominal pain, vomiting, nausea).

Reproductive system.

Very rare: priapism.

General disorders.

Common: increased body temperature.

Uncommon: chills, fatigue.

Investigations.

Uncommon: increased levels of liver enzymes in plasma.

Thrombophlebitis of peripheral veins may occur during infusion of the preparation, as with the administration of any other hypertonic infusion solution.

Fat overload syndrome.

Impaired ability to eliminate fats (Intralipid, fat emulsion contained in the preparation) may lead to the development of fat overload syndrome. This may be due to overdose, but may also occur at the recommended infusion rate if the patient's clinical condition deteriorates rapidly and severe renal or hepatic failure develops.

Fat overload syndrome is characterized by hyperlipidaemia, fever, hepatomegaly, splenomegaly, anaemia, leucopenia, thrombocytopenia, coagulopathy and coma. If this syndrome occurs, infusion must be discontinued.

Reporting of suspected adverse reactions.

It is important to report suspected adverse reactions after administration of the medicinal product. This allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are requested to report any suspected adverse reactions via the national reporting system.

Shelf life.

2 years in the outer container.

Do not use after the expiry date stated on the packaging. After opening the seals and mixing the three solutions, compatible additives may be added through the inlet port.

After opening the seals, the chemical and physical stability of the mixed contents of the three chambers is maintained for 24 hours at 25 °C.

To ensure microbiological safety, the mixture should be used immediately after preparation. If the mixture is not used immediately, under conditions of aseptic addition of additives, the emulsion mixture may be stored for up to 6 days at 2–8 °C, after which the mixture must be used within 24 hours.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C.

Do not freeze.

Incompatibilities.

Addition of any medicinal products or other solutions to Kabiven Central is possible only if their compatibility has been clinically proven and documented.

Packaging.

Three-chamber container "Biofine" with a volume of 1026 ml or 1540 ml, or 2053 ml, or 2566 ml (chamber 1 – 526 ml or 790 ml, or 1053 ml, or 1316 ml of 19% glucose solution; chamber 2 – 300 ml or 450 ml, or 600 ml, or 750 ml of Vamin 18 Nutridex; chamber 3 – 200 ml or 300 ml, or 400 ml, or 500 ml of Intralipid 20%), together with an antioxidant, contained in an outer plastic bag.

Prescription status.

Prescription only.

Manufacturer.

Fresenius Kabi AB, Sweden.

Manufacturer's name and address of the place of business.

Rapsvägen 7, Uppsala, 754 50, Sweden

Marketing Authorisation Holder.

Fresenius Kabi Deutschland GmbH.

Address of the Marketing Authorisation Holder and/or its representative.

Else-Kröner-Strasse 1, 61352 Bad Homburg, Germany