Oliclinomel N4-550 E (Emulsion) Instructions for Use

Marketing Authorization Holder

Baxter, S.A. (Belgium)

ATC Code

B05BA10 (Combined preparations for parenteral nutrition)

Dosage Form

Oliclinomel N4-550 E

Infusion emulsion: three-chamber containers 1 L 6 pcs, 1.5 L 4 pcs, or 2 L 4 pcs.

Dosage Form, Packaging, and Composition

Infusion emulsion (after mixing the contents of the 3 chambers).

I chamber – 5.5% amino acid solution with electrolytes – a transparent, colorless or light yellow liquid.

Excipients : acetic acid – q.s., water for injections – up to 1 L.

II chamber – 20% dextrose (glucose) solution with calcium chloride – a transparent, colorless or light yellow liquid.

Excipients : hydrochloric acid – q.s., water for injections – up to 1 L.

III chamber – 10% lipid emulsion – a homogeneous white or almost white liquid.

* Mixture of purified olive oil (80%) and soybean oil (20%).

Excipients : purified egg lecithin – 1.2 g, glycerol – 2.25 g, sodium oleate – 30 mg, sodium hydroxide – q.s., water for injections – up to 1 L.

After mixing the contents of the three sections, the resulting mixture is a white emulsion and contains

1 L (400 ml+400 ml+200 ml) – three-chamber containers (6) – cardboard boxes.
1.5 L (600 ml+600 ml+300 ml) – three-chamber containers (4) – cardboard boxes.
2 L (800 ml+800 ml+400 ml) – three-chamber containers (4) – cardboard boxes.

Clinical-Pharmacological Group

Drug for total parenteral nutrition – solution of amino acids, fats, carbohydrates, electrolytes

Pharmacotherapeutic Group

Parenteral nutrition agent

Pharmacological Action

The three-component mixture is intended to maintain protein and energy metabolism. L-amino acids serve as the source of organic nitrogen, while dextrose and fatty acids serve as the energy source. In addition, the mixture contains electrolytes.

The moderate content of essential fatty acids (EFA) in the mixture increases the content of higher EFA derivatives in the body, compensating for their deficiency.

Olive oil contains a significant amount of α-tocopherol, which, in combination with a small amount of polyunsaturated fatty acids (PUFA), increases the vitamin E content in the body and reduces lipid peroxidation.

Pharmacokinetics

The ingredients of the infusion emulsion (amino acids, electrolytes, dextrose, lipids) are metabolized and eliminated from the body in the same way as when they are administered separately.

The pharmacokinetic properties of intravenously administered amino acids mainly coincide with the properties of amino acids supplied through natural (enteral) nutrition (however, in the latter case, the amino acids obtained from dietary proteins pass through the liver before entering the systemic circulation).

The elimination rate of lipid emulsion particles depends on their size. Small lipid particles are eliminated more slowly, while they are broken down faster under the action of lipoprotein lipase.

The particle size of the lipid emulsion in the mixture approaches the size of chylomicrons, so they have a similar elimination rate.

Indications

• Parenteral nutrition in adults and children over 2 years of age in cases where enteral nutrition is impossible, insufficient, or contraindicated.

ICD codes

Dosage Regimen

IV via central or peripheral vein.

The dose of the drug and the duration of administration are determined by the need for parenteral nutrition in each specific patient depending on their condition.

Adults

The average requirement for organic nitrogen is 0.16-0.35 g/kg/day (approximately 1-2 g amino acids/kg/day).

Energy requirements vary depending on the patient’s condition and the intensity of catabolic processes. On average, they are 25-40 kcal/kg/day.

The maximum daily dose is 40 ml/kg body weight (equivalent to 0.88 g amino acids, 3.2 g dextrose and 0.8 g lipids per kg body weight), i.e., 2800 ml of infusion emulsion for a patient weighing 70 kg.

Children over 2 years of age

The average requirement for organic nitrogen is 0.35-0.45 g/kg/day (approximately 2-3 g amino acids/kg/day).

Energy requirements vary depending on age, patient’s condition and the intensity of catabolic processes. On average, they are 60-110 kcal/kg/day.

The dose depends on the amount of fluid administered and the daily protein requirement. In this case, the state of water metabolism should be taken into account.

The maximum daily dose is 100 ml/kg body weight (equivalent to 2.2 g amino acids, 8 g dextrose and 2 g lipids per kg body weight). As a rule, the dose should not exceed 3 g/kg/day of amino acids and/or 17 g/kg/day of dextrose and/or 3 g/kg/day of lipids except in special cases.

Maximum infusion rate: the infusion rate should not exceed 3 ml/kg/h, i.e., no more than 0.06 g amino acids, 0.24 g dextrose and 0.06 g lipids per 1 kg body weight/h.

Method of administration

A. Opening the package.

1. Tear the protective shell.

2. After opening the protective shell, discard the bag with the oxygen-absorbing substance (if present).

3. Check the integrity of the container and the partitions between the chambers.

4. Use only if the container is not damaged and the integrity of the partitions between the chambers is not compromised (i.e., the contents of the three chambers have not been mixed), and the amino acid and dextrose solutions should be clear, and the emulsion should be homogeneous.

B. Mixing the solutions and emulsion.

1. Ensure that the drug is at room temperature at the moment of breaking the partitions between the chambers.

2. Manually rotate the top of the container (by which it is suspended) around its axis.

3. The partitions will disappear from the side of the future inlet. Continue twisting the top until the partitions open for at least half their length. Mix by turning the container over (at least 3 times).

C. Preparation for infusion.

1. Aseptic conditions must be observed.

2. Hang the container.

3. Remove the plastic protector from the future outlet site.

4. Attach the infusion system to this site.

D. Simultaneous administration of other nutrients.

Any additional nutrients (including vitamins) can be added to the finished mixture.

Vitamins can also be added to the dextrose solution chamber before mixing the chamber contents.

Oliclinomel can be supplemented with the following components

• Electrolytes: emulsion stability is maintained when adding no more than 150 mmol sodium, 150 mmol potassium, 5.6 mmol magnesium and 5 mmol calcium /1 L of the finished mixture;
• Organic phosphates: emulsion stability is maintained when adding up to 15 mmol/1 container;
• Trace elements and vitamins: emulsion stability is maintained when adding doses not exceeding daily doses.

Addition of micronutrients should be performed under aseptic conditions by injecting the micronutrients through a special port.

1. Prepare the container port.

2. Puncture the port and inject the micronutrient solution.

3. Mix the added substances with the container contents.

E. Rules for drug administration.

If Oliclinomel was stored at low temperature, before use, ensure that the drug is warmed to room temperature.

The drug should be administered only after the integrity of the partitions between all three sections has been broken and their contents have been mixed.

Adverse Reactions

Possible side effects hyperthermia, sweating, tremor, nausea, headache, respiratory distress.

Also, a temporary increase in the concentration of biochemical markers of liver function (such as alkaline phosphatase, transaminases, bilirubin) was sometimes observed, especially with long-term use of parenteral nutrition (several weeks).

In rare cases, hepatomegaly and jaundice developed.

Reduced ability to eliminate lipids contained in Oliclinomel from the bloodstream can cause fat overload syndrome, which can be caused by overdose or occur at the beginning of the infusion, accompanied by a sudden deterioration in the patient’s condition. Fat overload syndrome is characterized by hyperlipidemia, fever, fatty infiltration of the liver, hepatomegaly, anemia, leukopenia, thrombocytopenia, coagulation disorders, and coma. These symptoms are reversible if the lipid emulsion infusion is stopped. Rare cases of thrombocytopenia in children receiving lipid emulsion infusions have also been reported.

The drug contains soybean oil, which can cause a severe allergic reaction (rarely).

The infusion should be stopped immediately as soon as any symptoms of an allergic reaction appear (such as fever, chills, skin rash, respiratory distress).

Contraindications

• Severe renal failure in the absence of the possibility of hemofiltration or dialysis;
• Severe hepatic failure;
• Congenital disorders of amino acid metabolism;
• Severe blood clotting disorders;
• Severe hyperlipidemia;
• Hyperglycemia;
• Electrolyte metabolism disorders, increased plasma concentration of one of the electrolytes included in the mixture;
• Lactic acidosis;
• Pulmonary edema, hyperhydration, decompensated heart failure and hypotonic dehydration;
• Unstable conditions (e.g., severe post-traumatic conditions, decompensated diabetes mellitus, acute phase of hypovolemic shock, acute phase of myocardial infarction, severe metabolic acidosis, severe sepsis, hyperosmolar coma);
• Children under 2 years of age;
• Hypersensitivity to the drug components.

With caution : in patients with increased plasma osmolality, adrenal insufficiency, heart failure and pulmonary pathology.

Use in Pregnancy and Lactation

Currently, there are no reliable data on the use of the drug in pregnant and lactating women.

In such cases, the physician must independently assess the risk-benefit ratio to make a decision.

Use in Hepatic Impairment

Contraindicated

• Severe hepatic failure.

Regular clinical and biochemical examination should be performed in the following cases

• In hepatic failure – due to the risk of occurrence or intensification of neurological disorders associated with hyperammonemia.

Use in Renal Impairment

Contraindicated

• Severe renal failure in the absence of the possibility of hemofiltration or dialysis.

Regular clinical and biochemical examination should be performed in the following cases

• In renal failure, especially if hyperkalemia is present; risk of occurrence or intensification of metabolic acidosis and hyperazotemia in the absence of the possibility of hemofiltration or dialysis.

Pediatric Use

Contraindicated in children under 2 years of age.

Children over 2 years of age

The average requirement for organic nitrogen is 0.35-0.45 g/kg/day (approximately 2-3 amino acids/kg/day).

Energy requirements vary depending on age, patient’s condition and the intensity of catabolic processes. On average, they are 60-110 kcal/kg/day.

The dose depends on the amount of fluid administered and the daily protein requirement. In this case, the state of water metabolism should be taken into account.

Contraindicated in children under 2 years of age.

Special instructions for use in pediatrics

When selecting the dose, one should be guided by the child’s age, protein and energy requirements, as well as the disease. If necessary, proteins and/or energy components (carbohydrates, lipids) should be added enterally.

For parenteral nutrition in children over 2 years of age, it is advisable to select the container volume according to the daily dose.

Addition of vitamins and trace elements in doses always used in pediatrics is required.

The maximum daily dose is 100 ml/kg body weight (equivalent to 2.2 g amino acids, 8 g dextrose and 2 g lipids per kg body weight). As a rule, the dose should not exceed 3 g/kg/day of amino acids and/or 17 g/kg/day of dextrose and/or 3 g/kg/day of lipids except in special cases.

Maximum infusion rate: the infusion rate should not exceed 3 ml/kg/h, i.e., no more than 0.06 g amino acids, 0.24 g dextrose and 0.06 g lipids per 1 kg body weight/h.

Special Precautions

Correction of water and electrolyte balance disorders, as well as metabolic disorders, must be performed before starting the infusion.

Since the drug does not contain vitamins and trace elements, when adding them, the doses of these substances (depending on the need) should be determined before the start of the infusion and the osmolality of the resulting solution should be calculated. Use the drug only if the container is not damaged and the integrity of the partitions between the sections is not compromised (i.e., the contents of the three sections have not been mixed), and the amino acid and glucose solutions should be clear, and the emulsion should be homogeneous.

Throughout the course of treatment, monitoring of water and electrolyte balance, plasma osmolality, acid-base status, blood glucose and liver function tests is necessary.

The concentration of triglycerides in plasma and the ability to remove lipids from the bloodstream should be regularly assessed.

The serum triglyceride concentration during infusion should not exceed 3 mmol/L. Their concentration should be measured no earlier than 3 hours after the start of the infusion.

If lipid metabolism disorders are suspected, it is recommended to repeat the same tests 5-6 hours after stopping the emulsion administration. In adults, serum clearance (lipid elimination) should occur within less than 6 hours after stopping the lipid emulsion infusion. The next infusion should be carried out only after the plasma triglyceride concentration has normalized.

Regular clinical and biochemical examination should be performed in the following cases

• In hepatic failure – due to the risk of occurrence or intensification of neurological disorders associated with hyperammonemia;
• In renal failure, especially if hyperkalemia is present; risk of occurrence or intensification of metabolic acidosis and hyperazotemia in the absence of the possibility of hemofiltration or dialysis;
• Diabetes mellitus: control of glucose concentration, glucosuria, ketonuria and, if possible, correction of insulin dose;
• Blood clotting disorders;
• Anemia;
• Hyperlipidemia (since lipids are present in the emulsion).

With long-term use (several weeks), blood tests and clotting factors should be monitored more carefully.

Special instructions for use in pediatrics

When selecting the dose, one should be guided by the child’s age, protein and energy requirements, as well as the disease. If necessary, proteins and/or energy components (carbohydrates, lipids) should be added enterally.

For parenteral nutrition in children over 2 years of age, it is advisable to select the container volume according to the daily dose.

Addition of vitamins and trace elements in doses always used in pediatrics is required.

Overdose

Symptoms: hypervolemia, acidosis, nausea, vomiting, tremors, electrolyte imbalance in case of overdose and/or at an infusion rate exceeding the recommended one. Administration of excessive doses of dextrose may lead to hyperglycemia, glucosuria, and hyperosmolar syndrome.

Treatment: in such cases, the infusion should be stopped immediately. A reduced ability to eliminate lipids from the bloodstream may cause fat overload syndrome, all manifestations of which are reversible after discontinuation of the drug.

In severe cases, hemodialysis, hemofiltration, or hemodiafiltration may be required.

Drug Interactions

The infusion emulsion should not be administered simultaneously with blood products through the same catheter due to the risk of pseudoagglutination.

If blood sampling is performed before lipids are eliminated from the plasma (usually 5-6 hours after stopping the emulsion infusion), the lipids contained in the emulsion may affect the results of some laboratory tests; for example, they may alter bilirubin, LDH, oxygen saturation, and hemoglobin readings.

Storage Conditions

The drug should be stored out of the reach of children at a temperature between 2°C (35.6°F) and 25°C (77°F). Do not freeze.

Shelf Life

Shelf life – 2 years.

After mixing, the emulsion is stable for 7 days from 2°C (35.6°F) to 8°C (46.4°F) with subsequent storage for up to 48 hours at a temperature not exceeding 25°C (77°F). Do not use after the expiration date printed on the carton.

Dispensing Status

For hospital use only.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.