Composition, form of production and packaging
Emulsion for infusion (after mixing the contents of 3 chambers).
I chamber - 12.5% вЂ‹вЂ‹solution of amino acids.
L-alanine 20.7 g
L-arginine 11.5 g
glycine 10.3 g
L-Histidine 4.8 g
L-isoleucine 6 g
L-leucine 7.3 g
L-lysine (in the form of hydrochloride) 5.8 g (7.25) g
L-Methionine 4 g
L-phenylalanine 5.6 g
L-proline 6.8 g
L-serine 5 g
L-threonine 4.2 g
L-tryptophan 1.8 g
L-tyrosine 400 mg
L-valine 5.8 g
Auxiliary substances: acetic acid - qs pH, water d / u - up to 800 ml.
II chamber - 31.25% solution of dextrose.
dextrose (in the form of monohydrate) 250 g (275 g)
Auxiliary substances: hydrochloric acid - qs pH, water d / u - up to 800 ml.
III chamber - 15% lipid emulsion.
olive and soy beans oils mixture * 60g
Excipients: glycerol - 6.75 g, egg lecithin purified - 3.6 g, sodium oleate - 90 mg, sodium hydroxide qs pH, water d / u - up to 400 ml.
* - contains about 80% of refined olive oil and about 20% of refined soybean oil, which corresponds to the content of a mixture of linoleic and linolenic acids from 18.5 to 21.5% with respect to the total content of fatty acids.
After mixing the contents of the three sections, the mixture contains:
nitrogen (g) 16.5
amino acids (g) 100
dextrose (g) 250
lipids (g) 60
total calories (kcal) 2000
non-protein calories (kcal) 1600
carbohydrate calories (kcal) 1000
fat calories (kcal) 600
ratio non-protein calories / nitrogen (kcal / g N) 100
phosphate ** (mmol) 4.5
acetate (mmol) 85
chloride (mmol) 40
osmolarity (mOsm / l) 1230
** - due to lipid emulsion.
2 l (800 ml + 800 ml + 400 ml) - three-chamber containers (1) - plastic packaging.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2011.
The three-component mixture is designed to maintain protein and energy metabolism. The source of organic nitrogen is L-amino acids, dextrose and fatty acids serve as an energy source. The composition, which does not contain electrolytes, allows you to assign them individually, depending on the needs of the patient.
The amino acid solution contains 15 L-amino acids (including 8 essential amino acids) that, when administered iv, enter the systemic circulation (ie, completely bioavailable). Amino acids play both a structural and regulatory role in the body. They are required for the synthesis of proteins, and they are also a source of energy.Amino acids are metabolized in the liver, a small amount can be excreted by the kidneys unchanged. Nitrogen-containing decomposition products under the metabolism of amino acids are converted to urea and excreted from the body by the kidneys.
The source of carbon is dextrose. Dextrose (glucose), is involved in the metabolism of all cells of the body, and is the main source of energy. Glucose can accumulate in the body in the form of glycogen (mainly in the liver and skeletal muscles). Glucose is also able to convert to fatty acids and persist in the form of triglycerides in adipose tissue. The concentration of circulating glucose in the blood is regulated by the interaction of insulin hormones and glucagon, with the participation, to a lesser extent, of catecholamines, growth hormone and GCS hormones. Fatty acids (lipids) are an important source of energy. The human body can not synthesize omega-6 or omega-3-polyunsaturated fatty acids, so their presence in the diet is necessary. Fatty acids are also an important substrate for the construction of membranes, precursors of bioactive molecules (for example, prostaglandins), and regulate gene expression. Moderate content of essential fatty acids (EFA) in the mixture increases the content of higher EHF derivatives in the body, making up for their deficiency.
The olive oil included in the preparation contains a significant amount of alpha-tocopherol, which, in combination with a small amount of polyunsaturated essential fatty acids (PUFA), contributes to the production of vitamin E in the body and reduces lipid peroxidation. The nitrogen content (L-series amino acids) in the preparation and the energy substrates (dextrose and triglycerides) allow maintaining an adequate nitrogen / energy balance. Nitrogen and energy substrates are required for the normal functioning of all cells of the body and are important components in the synthesis of proteins, growth, healing of wounds, maintenance of immune and muscular system function, and also participate in a variety of other types of cellular activity.
Components of the emulsion for infusions (amino acids, glucose, lipids) are distributed, metabolized and excreted from the body in the same way as when they are assigned separately. The pharmacokinetic properties of amino acids injected in / in basically coincide with the properties of amino acids supplied by natural (oral) nutrition (however, in this case the amino acids derived from food proteins pass through the liver before entering the systemic circulation).
The components of the dosage form are distributed to all cells of the body.
Amino acids, dextrose and triglycerides are metabolized in all cells of the body. Dextrose and triglycerides are metabolized to form carbon monoxide.
Nitrogen-containing degradation products are metabolized in the liver and excreted by the kidneys in the form of urea. Carbon dioxide is excreted in the lungs. The rate of elimination of lipid emulsion particles depends on their size. Small lipid particles are released more slowly, but they decompose faster under the action of lipoprotein lipase. The particle size of the lipid emulsion in the mixture of preparation Oliklinomel N8-800 approaches the size of chylomicrons, therefore they have the same elimination rate.
Pharmacokinetics in special clinical cases
Pharmacokinetics of the drug has not been studied in specific patient groups or in special conditions.
- parenteral nutrition in adults in cases where oral or enteral nutrition is impossible, insufficient or contraindicated.
Because of the high osmolarity, the drug is injected IV into the central vein. The drug is intended for single use only.
The drug is recommended to use immediately after opening the container.
Do not store the contents of the container for the next infusion.
The dose of the drug and the duration of application are determined by the need for parenteral nutrition in each individual patient, depending on its condition.
The rate of infusion should be calculated taking into account such parameters as: the required amount of the drug to be administered, the characteristics of the mixture after mixing, the daily infusion rate and its duration. Typically, the rate of administration should gradually increase during the first hour of infusion.
The average requirement for organic nitrogen in adults is 0.16 - 0.35 g / kg / day (approximately 1-2 g of amino acids / kg / day).
Energy needs vary depending on the patient's condition and intensity of catabolic processes. On average, this amount is 20-40 kcal / kg / day.
Mode of application
A. Opening of the package
- break the protective shell;
- after opening the containment, discard the container with oxygen-absorbing material (if available);
- Ensure the integrity of the container and partitions between the cameras.
Use only if the container is not damaged and the integrity of the partitions between the cameras is not broken (ie the contents of the three cameras were not mixed). In this case, solutions of amino acids and dextrose should be clear, colorless or light yellow, and the lipid emulsion is homogeneous white or almost white.
B. Mixing of solutions and emulsions
- make sure that the preparation has an ambient temperature at the time of destruction of the partitions between the chambers;
- place the container on a flat surface of the table and gently turn it from the top of the container (for which it is suspended) towards the connecting tubes, evenly distributing the pressure to all three chambers. Fold the container about half its length.
- continue folding the container until the partitions open for at least half of their length. Stir by turning the container at least 3 times.
B. Simultaneous administration of other nutrients
The composition of the drug includes microelements and vitamins in the usual concentration, however their level is insufficient to meet the needs of the body, so they should be added to the diet to prevent the development of a deficit condition.
Container capacities are sufficient to introduce additional nutrients (vitamins, electrolytes, trace elements). Additional nutrients (including vitamins) can be added to the finished mixture (after the destruction of the partitions between sections and three-fold mixing). Vitamins can also be added to the chamber with a dextrose solution before the contents of the sections are mixed (until the septa between the sections are broken and three times mixing).
After the introduction of additional nutrients, the osmolarity of the prepared solution should be calculated before the infusion begins.
Oliklinomel N8-800 can be supplemented with the following components:
- the stability of the emulsion is preserved by adding no more than 150 mmol of sodium, 150 mmol of potassium, 5.6 mmol of magnesium and 5.0 mmol of calcium per 1 liter of the final mixture.
- Organic phosphates: the stability of the emulsion is maintained by adding no more than 22 mmol per liter of the finished mixture.
Microelements and vitamins: the stability of the emulsion is preserved by adding doses not exceeding daily allowances (preparations of vitamins and microelements containing up to 1 mg of iron).
The addition of micronutrients should be performed by a specialist in aseptic conditions by injecting micronutrients through a special port:
- prepare the container port;
- pierce the port and inject the solution of micronutrients with an injection needle or a special device for administration;
- Mix the added substances with the contents of the container.
Rules of drug administration
Aseptic conditions must be met.
If Oliklinomel N8-800 was stored at a low temperature, before using it, make sure that the preparation has an ambient temperature. Enter the drug should be only after the integrity of the partitions between all three sections is broken and their contents are carefully swept. Make sure that the final emulsion is not divided into phases.The drug is intended for single use only. The drug is recommended to use immediately after opening the container. Do not store the contents of the container for the next infusion. Do not combine containers with each other. Such actions can lead to the development of air embolism due to the ingress of residual air from the primary container.
- hang the container;
- remove the plastic fuse from the place of the future outlet;
- tightly insert the needle of the infusion system into the outlet. Unused product or waste and all disposable equipment must be disposed of properly.
The undesirable reactions that may be associated with the use of Oliklinomel N8-800 or occur when the drug is administered are listed below.
Undesirable reactions according to clinical studies
Three clinical trials were conducted with regard to Oliklinomel N8-800 for assessing the ease of use, safety and effectiveness of correction of nutritional deficiencies.The combination of data (64 patients) obtained in three studies revealed the following undesirable reactions associated with the use of the drug:
System-Organ Class Preferred Term Frequency / Ratio *
Disturbances from the immune system Hypersensitivity 2:64
Disturbances from the nervous system Headache 1: 64
Disorders from the gastrointestinal tract Diarrhea 1: 64
Disorders from the kidneys and urinary tracts Azotemia 1: 64
General disorders and disorders at the site of injection Chills 1: 64
Bruising at the site of injection 4:64
Edema at the site of injection 6:64
Pain at the injection site 2:64
Bubbles at the injection site 1: 64
Laboratory and instrumental data Increase in the level of liver enzymes 6:64
Increase in the level of gamma-glutamyltransferase 4:64
Increase in triglyceride level in plasma 2:64
Increase in alkaline phosphatase in plasma 1:64
* The study involved 64 patients who received Oliklinomel. Given the limited number of patients, estimates of the incidence of adverse reactions are provided for informational purposes only.
Undesirable reactions according to post-marketing research data:
From the nervous system: tremor.
On the part of the digestive system: abdominal pain, vomiting, nausea.
From the liver and bile ducts: increased levels of liver enzymes, hepatitis, cholestasis, jaundice, increased bilirubin in the blood.
From the skin and subcutaneous tissues: erythema, excessive sweating (hyperhidrosis).
From the osteomuscular and connective tissue: musculoskeletal pain, back pain, chest pain, pain in the extremities, muscle spasm.
General disorders and disorders at the site of administration: phlebitis at the site of insertion of the catheter, edema at the site of introduction, localized edema, peripheral edema, fever, fever, hyperthermia, anxiety, inflammation.
Laboratory, instrumental and other data: hyperglycemia, increased blood glucose levels.
If any of the side effects indicated in the manual are aggravated or you notice any other side effects not listed in the instructions, inform your doctor.
- congenital disorders of the metabolism of amino acids that make up the drug;
- severe hyperlipidemia or severe lipid metabolism, characterized by hypertriglyceridemia;
- severe hyperglycemia;
- severe renal failure in the absence of the possibility of hemofiltration or dialysis;
severe hepatic impairment;
- severe bleeding disorders;
- lactic acidosis;
- Hyperhydration, decompensated heart failure and hypotonic dehydration;
- unstable conditions (for example, severe post-traumatic conditions, decompensated diabetes mellitus, acute shock phase, acute phase of myocardial infarction, severe metabolic acidosis, severe sepsis, hyperosmolar coma);
- Hypersensitivity to egg or soy protein, amino acids, components of the container or to any of the active or auxiliary substances of the drug.
With caution in patients with pulmonary edema or heart failure. The balance of the liquid should be carefully monitored; In patients with renal failure, the water-electrolyte balance should be closely monitored.
PREGNANCY AND LACTATION
At present, there are no reliable data on the use of the drug in pregnant and lactating women.
In such cases, the doctor for the decision should assess the risk ratio for the fetus / child and the benefits to the mother when using the drug.
APPLICATION FOR FUNCTIONS OF THE LIVER
Contraindicated in severe renal failure in the absence of the possibility of hemofiltration or dialysis.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Contraindicated in severe hepatic insufficiency.
APPLICATION FOR CHILDREN
Contraindicated in children.
Do not administer the drug through the peripheral vein.
Infusion should be discontinued immediately as soon as any symptoms of an allergic reaction appear (such as fever, tremor, skin rash, respiratory failure).
Excessive addition of calcium and phosphorus can lead to the formation of calcium phosphorus precipitates, which can lead to vascular occlusion.
When intravenous catheters are used for parenteral nutrition, infections and sepsis can occur with insufficient catheter care, due to the immunosuppressive effect of the disease, drugs and parenteral dosage forms. Angiogenic sepsis is a complication that can occur in patients receiving parenteral nutrition.
A thorough assessment of the symptoms and laboratory indicators in the dynamics for the appearance of fever / chills, leukocytosis, technical complications from the access device and hyperglycemia may allow one to recognize the infection at an early stage. Patients who require parenteral nutrition are often predisposed to infectious complications due to a lack of nutrients and / or due to a condition caused by the underlying disease. The frequency of septic complications can be reduced by strictly observing the rules of asepsis during the placement of the catheter, during the care of it, and also by monitoring the sterility of the drug itself for parenteral nutrition.
Reduced ability to eliminate blood lipids contained in Oliklinomel N8-800 can cause fat overload syndrome, which is the result of overdose or occurs at the beginning of infusions, and is accompanied by a sudden deterioration in the patient's condition. The "fat-congestion syndrome" is characterized by hyperlipidemia, fever, fatty liver infiltration, impaired liver function, anemia, leukopenia, thrombocytopenia, coagulation disorders and coma and may require hospitalization of the patient. All these symptoms are reversible if the lipid emulsion is suspended.
Renewal of nutrition in severely malnourished patients can lead to the development of the syndrome of renewed feeding, which is characterized by intracellular increase in potassium, phosphorus and magnesium levels, due to increased anabolic processes. Also, thiamine deficiency and fluid retention may develop. Prevention of the development of such complications is carried out through careful and regular monitoring and a gradual increase in the intake of nutrients, avoiding excessive nutrition. The appearance of this syndrome is described against the background of the use of similar Oliklinomel N8-800 drugs.
Do not combine containers with each other. Such actions can lead to the development of air embolism due to the ingress of residual air from the primary container.
Use the drug only if the container is not damaged and the integrity of the partitions between the chambers is not broken (ie, the contents of the three chambers were not mixed), while the amino acid and dextrose solutions should be clear, colorless or light yellow in color, and the lipid emulsion is homogeneous, white or almost white. The drug is intended for single use only.
The drug is recommended to use immediately after opening the container. Do not store the contents of the container for the next infusion.
When Oliklinomel preparations are used, the appearance of extravasation is described. Electrolytes, trace elements, vitamins and other medications can be added, if necessary, to one of three chambers or into a triple mixture. Before the addition, it is necessary to check the compatibility of the administered drugs and the components of the mixture, as well as the stability of the final solution obtained after the addition of the above components. With the introduction of additional substances should determine their dose (depending on the need) and calculate the osmolality of the resulting solution before the infusion. During the whole course of treatment is necessary to monitor the water-electrolyte balance, plasma osmolarity, triglyceride levels in plasma, the acid-base balance, blood glucose, liver and kidney functions and in the number of blood cells, including the number of platelets and the parameters of blood coagulation . The concentration of serum triglycerides during infusion should not exceed 3 mmol / l. Their concentration should be measured no earlier than 3 hours after the start of infusion. When applying formulations described Oliklinomel elevation of liver enzymes and the appearance of cholestasis.
Metabolic complications may arise if the administration of nutrients is not adapted to the needs of the patient or the metabolic capacity of any component of the diet is not defined precisely. Metabolic undesirable effects may arise upon administration of inadequate or excessive amount of a preparation or composition of the final mixture was inadequate to meet the specific needs of the patient.
The concentration of triglycerides in the plasma and the body's ability to eliminate the lipids must be assessed on a regular basis. If found signs of lipid metabolism, clinically advisable to monitor the concentration of triglycerides in the plasma.
In case of hyperglycemia infusion rate should be adjusted Oliklinomel N8-800 and / or assign insulin. Correction of violations of water and electrolyte balance, as well as metabolic disorders should be done before the infusion.
When applying formulations described Oliklinomel occurrence of azotemia. Furthermore, it should conduct regular clinical and laboratory tests in the following cases:
- for violations of amino acid metabolism;
- with hepatic failure - because of the risk of the appearance or strengthening of neurological disorders associated with hyperammonemia;
- with renal insufficiency, especially if there is hyperkalemia; risk of appearance or enhancement of metabolic acidosis and hyperazotemia in the absence of the possibility of haemofiltration or dialysis;
- metabolic acidosis: the introduction of carbohydrates is not recommended in the presence of lactic acidosis;
- diabetes mellitus: control of glucose concentration, glucosuria, ketonuria and, if possible, correction of insulin dose;
- coagulation disorders;
- Hyperlipidemia (because in the emulsion there are lipids).
With prolonged use (several weeks) should be carefully monitored blood counts and coagulation.
Impact on the ability to drive vehicles and manage mechanisms
Symptoms: in case of incorrect use of the drug (overdose, wrong route of administration and / or exceeding the recommended rate of administration) can be signs hypervolemia and acidosis. Extremely rapid injection solutions for total parenteral nutrition including Oliklinomel N8-800, may lead to severe and fatal consequences.
Perhaps the development of hyperglycemia, glucosuria, and hyperosmolar syndrome, if the rate of introduction of dextrose exceeds its clearance. In the case of overdosage and / or in excess of the recommended rate of administration may occur: nausea, vomiting, fever, electrolyte imbalance. In such situations, the infusion should be discontinued immediately.
Treatment: In severe cases may require hemodialysis, hemofiltration or hemodiafiltration.
Reduced ability to eliminate the lipids from the blood stream may cause fat overload syndrome, existence which are usually reversible after cessation of drug administration.
Studies on the interaction was conducted with other drugs.
Emulsion for infusion should not be administered concurrently with blood products through the same catheter because of the possibility psevdoagglyutinatsii. If the blood sampling was performed before the lipids were eliminated from the plasma (usually 5-6 hours after the emulsion was stopped), the lipids contained in the emulsion may affect the results of some laboratory tests, for example, they can change the bilirubin, lactate dehydrogenase, oxygen saturation, hemoglobin.
Soybean oil is a natural source of vitamin K, which can neutralize the anticoagulant activity of coumarin (or coumarin derivatives including warfarin).
Electrolytes, minerals, vitamins and other medicines may be added if necessary. Before adding a compatibility check of input drugs and components of the mixture (e.g., a lipid emulsion destabilization can cause hyperacidity or inappropriate amount of bivalent cations - Ca 2+ and Mg 2+ ).
Excessive addition of iron to the drug may lead to destabilization of the lipid emulsion. Iron should not be added to the drug if the stability of the drug is not confirmed.
TERMS OF RELEASE FROM PHARMACY
TERMS AND CONDITIONS OF STORAGE
Store at a temperature of from 2 В° to 25 В° C. Do not freeze. Keep three-chamber container in a carton in order to protect from light. Keep out of the reach of children.Shelf life - 2 years.
Do not use after the expiration date printed on the package. It is recommended to introduce the drug immediately after mixing the contents of the three chambers.After mixing, the emulsion is stable for 7 days when stored at a temperature of from 2 В° to 8 В° C and then stored up to 48 hours at a temperature of not higher than 25 В° C. In case of introduction of additives to the finished mixture, from the microbiological point of view to use the emulsion immediately justified. If it is impossible immediate use emulsion may be stored at a temperature of from 2 В° to 8 В° C for up to 24 hours. Any introduction of additives must be made in the respective aseptic conditions.