Multimel n4-550e

Package leaflet: Information for the user

Multimel N4-550 E, infusion emulsion
Please read the entire leaflet carefully before use, as it contains important information
for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please consult your doctor or nurse.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or nurse immediately. See section 4.

Table of contents:

1. What Multimel N4-550 E is and what it is used for
2. Important information before administration of Multimel N4-550 E
3. How to administer Multimel N4-550 E
4. Possible side effects
5. How to store Multimel N4-550 E
6. Contents of the pack and other information

1. What Multimel N4-550 E is and what it is used for
Multimel N4-550 E is an infusion emulsion. It is packaged in a three-chamber bag.
The first chamber contains a glucose solution with calcium, the second chamber contains a fat emulsion, and the third chamber contains an amino acid solution with electrolytes.
Pharmacotherapeutic group: Parenteral nutrition fluids/mixtures.
Multimel N4-550 E is administered for intravenous nutrition in adults and children over 2 years of age when oral nutrition is not appropriate.
Multimel N4-550 E must be administered exclusively under medical supervision.

2. Important information before administration of Multimel N4-550 E

When not to use Multimel N4-550 E:

• In preterm infants, newborns, and children under 2 years of age;
• If the patient is allergic to eggs, soy, peanut proteins, corn/corn-containing products (see also section "Warnings and precautions" below), or to any of the other components of Multimel N4-550 E;
• If the administration of certain amino acids causes an abnormal reaction in the patient;
• If the patient has markedly elevated blood lipid levels (hyperlipidemia);
• If the patient has severe hyperglycemia (excessively high blood sugar levels);
• If the patient has abnormally high blood levels of any electrolyte (sodium, potassium, magnesium, calcium, and/or phosphorus).

In each case, the physician will decide on administration based on factors such as the patient's age, body weight, and clinical condition, taking into account laboratory test results.
Warnings and precautions
Before starting treatment with Multimel N4-550 E, discuss it with your doctor or nurse.
Too rapid administration of total parenteral nutrition solutions may result in death.
If unusual symptoms or signs of an allergic reaction occur, such as fever, chills, skin rash, breathing difficulties, excessive sweating, nausea, or headache, the infusion must be stopped immediately. The product contains soybean oil and egg phosphatides. Soy and egg proteins may cause hypersensitivity reactions. Cross-reactivity between soy and peanut proteins has been observed.
Multimel N4-550 E contains glucose derived from corn, which may cause hypersensitivity reactions if the patient is allergic to corn or corn-containing products (see section "When not to use Multimel N4-550 E" above).
Breathing difficulties may also indicate the formation of small particles blocking blood vessels in the lungs (pulmonary embolism). Inform your doctor or nurse immediately if you experience breathing difficulties. They will determine the appropriate course of action.
The antibiotic ceftriaxone must not be mixed or administered simultaneously with any calcium-containing solution given intravenously (including Multimel N4-550 E).
These drugs must not be administered simultaneously, even through separate infusion lines or different infusion sites.
However, Multimel N4-550 E and ceftriaxone may be administered sequentially if the infusion sets are changed or thoroughly flushed with physiological saline solution between infusions to prevent precipitation (formation of ceftriaxone-calcium salt particles).
Your doctor will monitor triglyceride levels (a type of fat in the blood).
Certain medications and diseases may increase the risk of infection or sepsis (presence of bacteria in the blood). The risk of infection or sepsis is particularly high after placement of a catheter (intravenous line) into the patient's vein. Your doctor will closely monitor the patient for signs of infection. Patients requiring parenteral nutrition (delivery of nutrients via a tube inserted into a vein) may be at increased risk of infection due to their clinical condition. Using strict aseptic technique (germ-free) during catheter placement, maintenance, and preparation of the nutritional solution may reduce the risk of infection.
Inform your doctor:

• About severe kidney disease. Also inform your doctor if the patient is undergoing dialysis (artificial kidney) or other blood purification methods;
• About severe liver disease;
• About blood coagulation disorders;
• About adrenal gland dysfunction (adrenal insufficiency). Adrenal glands are triangular-shaped glands located on top of the kidneys;
• About heart failure;
• About lung disease;
• About fluid retention in the body (overhydration);
• About insufficient body water (dehydration);
• About untreated high blood glucose levels (diabetes);
• About myocardial infarction or shock caused by sudden heart failure;
• About severe metabolic acidosis (excessively acidic blood);
• About systemic infection (sepsis);
• About coma.

If the patient is a child, the doctor will closely monitor fluid status and (or) blood parameters.
During treatment with Multimel and similar products, cases of fat overload syndrome have been reported. Reduced or limited ability of the body to eliminate the fats contained in Multimel N4-550 E may lead to "fat overload syndrome" (see section 4 — "Possible side effects").
Do not add any additional components to the bag without first verifying their compatibility. This could lead to particle formation or destabilization of the fat emulsion, potentially causing vascular occlusion.
If blood glucose levels rise excessively, the doctor should adjust the infusion rate of Multimel N4-550 E or administer insulin to the patient.
In cases of severe malnutrition requiring intravenous nutrient administration, parenteral nutrition should be initiated slowly and cautiously.
Before starting the infusion, any disturbances in water-electrolyte balance and metabolic abnormalities should be corrected. The doctor will monitor the patient during therapy and may adjust the dosage or, if appropriate, recommend additional nutrients such as vitamins, electrolytes, and trace elements.
During treatment, the doctor will perform clinical and laboratory tests to assess efficacy and continuously monitor safety. If the patient receives the medication for several weeks, blood tests will be performed regularly. These tests are particularly important in patients with certain conditions, such as liver failure, kidney failure, disorders in which amino acids cannot be properly metabolized, conditions causing excessively acidic blood, disorders with elevated fat and cholesterol levels, diabetes, anemia, or difficulties in controlling bleeding.
If pain, burning, stiffness, swelling, skin discoloration, or leakage at the infusion site occurs during infusion, inform your doctor or nurse immediately. Administration will be stopped immediately and resumed in another vein.
Children
If the patient is a child, particular care must be taken to ensure correct dosing. Additional supplementation with vitamins and trace elements may be required, depending on the dose and duration of administration. Due to children's increased susceptibility to infection, enhanced precautions must be taken.
Multimel N4-550 E and other medicines
Inform your doctor or nurse about all medicines currently or recently taken, as well as any medicines the patient plans to take.
Multimel N4-550 E must not be administered simultaneously with blood through the same infusion set.
Multimel N4-550 E contains calcium. It must not be administered together with the antibiotic ceftriaxone or through the same line, as particles may form. If the same infusion set is used to administer these drugs sequentially, it must be thoroughly flushed.
Olive oil and soybean oil present in Multimel N4-550 E contain vitamin K. This usually does not affect the action of anticoagulant drugs (blood thinners) such as coumarins. However, if the patient is taking anticoagulant medication, they should inform their doctor.
The fats in this emulsion may interfere with the results of certain laboratory tests if blood samples are taken before fat clearance (fats are typically cleared within approximately 5–6 hours after stopping infusion).
Multimel N4-550 E with electrolytes contains potassium. Particular caution is required in patients taking diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists (medications used for hypertension), or immunosuppressive drugs. These medications may increase blood potassium levels.
Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or plans to become pregnant, she should consult her doctor before using this medicine.

3. How to administer Multimel N4-550 E

Multimel N4-550 E may be administered only to adults and children above the age of 2 years.
It is an infusion emulsion given intravenously through a plastic tube into a vein in the arm or into a large vein in the patient's chest.
Treatment may be continued as long as necessary, depending on the patient's clinical condition.
Multimel N4-550 E is intended for single use only.

Dosage – Adults
The dosage is determined by the physician according to individual needs and the patient's clinical condition.
The maximum daily dose is 40 ml/kg body weight. For example: for a patient weighing 70 kg, the maximum daily dose should not exceed 2800 ml of infusion emulsion (40 ml of infusion emulsion multiplied by 70 kg).

Dosage – Children above 2 years of age
The dose and duration of treatment in children are determined by the physician. This depends on the child's age, body weight, height, clinical condition, daily fluid volume, energy requirements, and nitrogen requirements.

Overdose of Multimel N4-550 E
If the patient receives an excessive dose or the infusion is administered too rapidly, the amino acids contained in the product may contribute to increased blood acidity and increased fluid volume in the circulatory system. The glucose contained in the medicine may increase blood and urinary glucose levels, and the fats contained in the emulsion may increase blood triglyceride levels. Administration of an excessive volume of Multimel N4-550 E may cause nausea, vomiting, chills, chest pain, headache, irregular or rapid heartbeat, and electrolyte disturbances. In such a case, the infusion must be stopped immediately.

In certain severe cases, to assist the patient's kidneys in eliminating the excess drug, the physician may periodically initiate dialysis treatment.
To prevent such situations, the physician regularly monitors the patient's condition and checks blood parameters.

If you have any doubts regarding the use of the medicine, consult your physician.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
If you notice any changes in your condition during or after treatment, you should immediately inform your doctor or nurse.
Examinations performed by the physician during treatment aim to minimize the risk of adverse reactions.
If any unusual signs or symptoms of an allergic reaction occur, such as elevated body temperature, chills, skin rash, breathing difficulties, excessive sweating, nausea, or headache, the infusion should be stopped immediately.

The following adverse reactions have been reported during treatment with Multimel:

Uncommon (may affect up to 1 in 100 patients):

• Allergic reactions

Frequency: unknown (cannot be estimated from available data)

• Constriction of airways, wheezing and/or cough (bronchospasm as part of an allergic reaction)
• Tremor
• Diarrhea, nausea, vomiting
• Unnatural skin redness (flushing), excessive sweating
• Limb pain, muscle cramps
• Leakage of infusion into surrounding tissues (extravasation), which may cause swelling/edema at the infusion site, pain, irritation, phlebitis, redness/warmth, local tissue loss, tissue necrosis, or blistering
• Fever, chills, inflammatory state
• Thrombophlebitis (blood clot in a vein causing pain, swelling, and redness), when a hypertonic solution is administered by infusion
• Reduced or limited ability to clear fats contained in Multimel N4-550E may lead to "fat overload syndrome". This may result from overdosing, but may also occur early during infusion, even when the medicine is administered according to instructions. It is associated with a sudden clinical deterioration of the patient. It is characterized by high blood fat levels, fever, fatty infiltration of the liver (high fat content in the liver) and/or hepatomegaly. Anaemia (reduced number of red blood cells, which may result in pale skin, weakness, or shortness of breath), reduced number of white blood cells and platelets, coagulation disorders, and/or coma may also occur. This syndrome usually resolves after discontinuation of the fat emulsion infusion.

For similar medicines, the following adverse reactions have been reported:
Frequency unknown (cannot be estimated from available data)

• Formation of small particles, which may lead to blockage of blood vessels in the lungs (pulmonary vessel embolism), resulting in pulmonary embolism and breathing difficulties (respiratory failure)
• Decreased platelet count (reduction in blood cells responsible for clotting, leading to bleeding, such as nosebleeds)
• Difficulty in bile excretion (cholestasis), liver enlargement, jaundice (yellowing of the skin or whites of the eyes due to liver or blood disorders)
• Hypersensitivity
• Increased liver enzyme activity, increased blood fat levels (elevated triglyceride levels in blood), increased bilirubin levels in blood
• Increased nitrogen levels in blood (azotemia)

Cases of reduced white blood cell and platelet counts have been observed in children.

Reporting of adverse reactions
If any adverse reactions occur, including those not listed in this leaflet, you should inform your doctor or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181 C
PL 02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps to gather more information on the safety of the medicine.

5. How to store Multimel N4-550 E

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the container and outer packaging. The expiry date refers to the last day of the specified month.
Do not freeze.
Store in the protective packaging.
Keep in the outer cardboard carton to protect from light.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to properly dispose of medicines no longer in use. Such measures will help protect the environment.

6. Contents of the packaging and other information

What the medicine Multimel N4-550 E contains
Active substances in each bag of ready-to-use emulsion:

| Active substances | 1000 ml | 1500 ml | 2000 ml | 2500 ml | |------------------------|-------------|-------------|-------------|-------------| | Purified olive oil and
purified soybean oil* | 20.00 g | 30.00 g | 40.00 g | 50.00 g | | L-alanine | 4.56 g | 6.83 g | 9.11 g | 11.39 g | | L-arginine | 2.53 g | 3.80 g | 5.06 g | 6.33 g | | Glycine | 2.27 g | 3.40 g | 4.54 g | 5.67 g | | L-histidine | 1.06 g | 1.58 g | 2.11 g | 2.64 g | | L-isoleucine | 1.32 g | 1.98 g | 2.64 g | 3.30 g | | L-leucine | 1.61 g | 2.41 g | 3.22 g | 4.02 g | | L-lysine | 1.28 g | 1.91 g | 2.55 g | 3.19 g | | (equivalent to lysine hydrochloride) | (1.60 g) | (2.39 g) | (3.19 g) | (3.99 g) | | L-methionine | 0.88 g | 1.32 g | 1.76 g | 2.20 g | | L-phenylalanine | 1.23 g | 1.85 g | 2.46 g | 3.08 g | | L-proline | 1.50 g | 2.24 g | 2.99 g | 3.74 g | | L-serine | 1.10 g | 1.65 g | 2.20 g | 2.75 g | | L-threonine | 0.92 g | 1.39 g | 1.85 g | 2.31 g | | L-tryptophan | 0.40 g | 0.59 g | 0.79 g | 0.99 g | | L-tyrosine | 0.09 g | 0.13 g | 0.18 g | 0.22 g | | L-valine | 1.28 g | 1.91 g | 2.55 g | 3.19 g | | Sodium acetate trihydrate | 0.98 g | 1.47 g | 1.96 g | 2.45 g | | Sodium glycerophosphate pentahydrate | 2.14 g | 3.22 g | 4.29 g | 5.36 g | | Potassium chloride | 1.19 g | 1.79 g | 2.38 g | 2.98 g | | Magnesium chloride hexahydrate | 0.45 g | 0.67 g | 0.90 g | 1.12 g | | Glucose
(equivalent to monohydrated glucose) | 80.00 g | 120.00 g | 160.00 g | 200.00 g | | (88.00 g) | (132.00 g) | (176.00 g) | (220.00 g) | | Total energy value (kcal) | 610 | 910 | 1215 | 1520 | | Non-protein energy value (kcal) | 520 | 780 | 1040 | 1300 |

Other components: purified egg yolk phosphatides, glycerol, sodium oleate, sodium hydroxide, glacial acetic acid, hydrochloric acid, water for injections.

What Multimel N4-550 E looks like and contents of the pack
Multimel N4-550 E is an infusion emulsion supplied in a 3-compartment bag made of multilayer plastic. The inner (contact) layer of the bag consists of polymers (a mixture of polyolefin copolymers) compatible with the bag contents (amino acid solutions, glucose solutions, and lipid emulsions), permitted additives, and allows for the formation of peelable seals. The outer coating layer is made from EVA (ethylene vinyl acetate) and polyester copolymer.

Before mixing the contents of the three compartments, the first compartment contains a homogeneous milky-appearing liquid (lipid emulsion), while the other two compartments (containing amino acid solution with electrolytes and glucose solution with calcium) contain colorless or slightly yellow solutions, practically free from visible particles. After mixing, Multimel N4-550 E is an infusion emulsion appearing as a uniform milky-white liquid.

The bag is enclosed in an oxygen-protective overpouch containing an oxygen-absorbing sachet.

Pack sizes

• 1000 ml bag: 6 bags in a cardboard box
• 1500 ml bag: 4 bags in a cardboard box
• 2000 ml bag: 4 bags in a cardboard box
• 2500 ml bag: 2 bags in a cardboard box

Not all pack sizes may be marketed.

Marketing Authorization Holder:
For information about the medicine Multimel N4-550 E, please contact the representative of the Marketing Authorization Holder:
Baxter Polska Sp. z o.o.
ul. Kruczkowskiego 8
00-380 Warszawa
Poland

Manufacturer:
Baxter S.A.
Boulevard René Branquart 80
7860 Lessines
Belgium
 --------------------------------------------------------------------------------------------------------------

Information intended exclusively for healthcare professionals:

Multimel N4-550E, emulsion for infusion

1. QUALITATIVE AND QUANTITATIVE COMPOSITION

After mixing the contents of the 3 chambers, the mixture forms a homogeneous milky-appearing emulsion.
The ready-to-use emulsion after mixing contains the following ingredients in bags of different sizes:

** Including phosphates contained in the fat emulsion

2. DOSAGE AND ADMINISTRATION

Dosage must be determined according to the patient's energy expenditure, clinical condition, body weight, and ability to metabolize the components of Multimel N4-550 E, as well as any additional energy or protein components administered orally or enterally; therefore, the appropriate bag size should be selected accordingly.
Administration may be continued as long as clinically indicated.
The maximum daily dose must not be exceeded in adults or in children and adolescents. Due to the fixed composition of the multi-chamber bag, it may not be possible to meet all of the patient's nutritional requirements simultaneously. There may be clinical situations in which the patient requires different amounts of nutrients than those provided in the fixed composition of the bag.
As a general rule, doses exceeding 3 g amino acids/kg body weight/day and (or) 17 g glucose/kg body weight/day and (or) 3 g fats/kg body weight/day and (or) 100 ml fluid/kg body weight/day should not be administered, except in special cases.
Multimel is intended for single use only.
The recommended duration of infusion for parenteral nutrition is between 12 and 24 hours.

Dosage and infusion rate – Adults
The average nitrogen requirement ranges from 0.16 to 0.35 g/kg body weight/day (approximately 1 to 2 g amino acids/kg body weight/day).
Energy requirements vary depending on the patient's nutritional status and degree of catabolism. On average, energy needs range from 20 to 40 kcal/kg body weight/day.

Maximum daily dose:
For Multimel N4-550 E: The maximum daily dose is 40 ml/kg body weight (corresponding to 0.88 g amino acids, 3.2 g glucose, 0.8 g fats, 0.84 mmol sodium, and 0.64 mmol potassium/kg body weight), i.e., 2800 ml of infusion emulsion for a 70 kg patient.

Maximum infusion rate:
As a general rule, the infusion rate should not exceed 0.10 g amino acids/kg body weight/hour and (or) 0.25 g glucose/kg body weight/hour and (or) 0.15 g fats/kg body weight/hour, except in special cases.

For Multimel N4-550 E: As a general rule, the infusion rate should not exceed 3.0 ml/kg body weight/hour, i.e., 0.06 g amino acids, 0.24 g glucose, and 0.06 g fats/kg body weight/hour.

Dosage and infusion rate – Children over 2 years of age and adolescents
Studies in children and adolescents have not been conducted.
Dosage must be determined based on fluid intake and daily nitrogen requirements.
Administration should be adjusted according to the child's hydration status.
Daily requirements for fluids, nitrogen, and energy continuously decrease with age.
Guidelines for the maximum recommended hourly infusion rate and daily volume in children and adolescents are as follows:
Multimel N4-550 E:
Maximum daily dose:

Maximum speed per hour

Route of administration
Multimel N4-550 E should be administered intravenously via a central or peripheral vein.
The infusion rate should be adjusted according to the dose administered, the characteristics of the final mixture, the total volume scheduled for infusion over 24 hours, and the duration of the infusion.

3. SPECIAL WARNINGS AND PRECAUTIONS FOR USE

• Rapid administration of parenteral nutrition solutions, including Multimel N4-550 E, may result in serious or fatal complications.
• If symptoms or signs of an allergic reaction (such as sweating, fever, chills, headache, skin rash, dyspnea, or bronchospasm) occur, the infusion must be stopped immediately. The product contains soybean oil and egg phosphatides. Soy and egg proteins may cause hypersensitivity reactions. Cross-allergic reactions between soy proteins and peanuts have been observed.
• Multimel N4-550 E contains glucose derived from corn, which may cause hypersensitivity reactions in patients allergic to corn or corn-containing products.
• Severe disturbances in water and electrolyte balance, severe fluid overload, and severe metabolic disorders should be corrected before initiating infusion.
• Special clinical monitoring is required at the beginning of each intravenous infusion.
• Ceftriaxone must not be mixed or administered simultaneously with intravenous solutions containing calcium, even through different infusion lines or at different infusion sites. Ceftriaxone and calcium-containing solutions may be administered sequentially if different infusion sites are used or if infusion lines are replaced or thoroughly flushed with physiological saline solution between infusions to prevent precipitate formation. In patients requiring continuous infusion of parenteral nutrition solutions containing calcium, physicians may consider using an alternative antibacterial agent that does not carry a similar risk of precipitate formation. If ceftriaxone use is necessary in patients requiring continuous nutrition, parenteral nutrition solutions may be administered simultaneously, but through separate infusion lines at different infusion sites. Alternatively, the parenteral nutrition infusion may be temporarily interrupted during ceftriaxone infusion, taking into account the line-flushing principle between solutions (see section 4, “Interactions” and “Incompatibilities”).
• Pulmonary vascular precipitates leading to pulmonary embolism and respiratory failure have been reported in patients receiving parenteral nutrition. Fatal outcomes have occurred in some cases. Excessive addition of calcium and phosphate increases the risk of calcium phosphate precipitate formation (see section 4, “Incompatibilities”).

Cases of suspected precipitate formation in the bloodstream have also been reported.
In addition to visual inspection of the solution, the infusion set and catheter should be periodically checked for the presence of precipitates.
If symptoms of respiratory failure occur, the infusion should be stopped immediately and a medical evaluation initiated.

• Do not add other medicinal products or substances to any of the bag compartments or to the ready-to-use emulsion without prior verification of compatibility and stability of the resulting mixture (particularly the stability of the fat emulsion). Precipitate formation or fat emulsion destabilization may lead to vascular occlusion.

• Catheter-related infection and sepsis are potential complications in patients receiving parenteral nutrition, particularly in cases of inadequate catheter care or due to immunosuppressive effects of disease or medications. Close monitoring for signs, symptoms, and laboratory findings—such as fever/chills, leukocytosis, technical complications related to vascular access devices, and hyperglycemia—may aid in early detection of infection. Patients requiring parenteral nutrition are often predisposed to infectious complications due to malnutrition and/or underlying disease. The risk of septic complications can be reduced by strict adherence to aseptic techniques during catheter placement and maintenance, as well as during preparation of the nutritional product.

• During treatment, water and electrolyte balance, serum osmolality, serum triglyceride levels, acid-base balance, blood glucose concentration, liver and kidney function tests, coagulation parameters, and blood cell counts—including platelets—should be monitored regularly.

• If the amount of nutrients administered does not match the patient's requirements or if the metabolic capacity for any nutritional component is not accurately assessed, metabolic disturbances may occur. Adverse metabolic effects may result from excessive or inappropriate nutrient administration or from an inappropriate composition of additional components relative to the individual patient’s needs.

• Serum triglyceride levels and the body’s ability to clear fats should be systematically monitored.

• Serum triglyceride concentrations should not exceed 3 mmol/l during infusion. Measurements should be performed no sooner than 3 hours after the start of continuous infusion.

• In suspected fat metabolism disorders, daily measurement of serum triglyceride levels is recommended 5–6 hours after discontinuation of fat infusion. In adults, serum should clear within less than 6 hours after stopping the fat emulsion infusion. A subsequent infusion may only be started once serum triglyceride levels have returned to normal.

• The fat overload syndrome has been described during use of Multimel and similar products. Reduced or limited capacity to metabolize the fats in Multimel N4-550 E may lead to fat overload syndrome due to overdose; however, signs and symptoms of this syndrome may also appear even when the product is administered according to recommendations.

• In case of hyperglycemia, adjust the infusion rate of Multimel N4-550 E and/or administer insulin.

• Multimel N4-550 E may be administered via a peripheral vein, but thrombophlebitis may occur. The catheter insertion site should be inspected daily for local signs of phlebitis.

• When additional components are added, the final osmolality of the mixture should be measured before administration. The resulting mixture should be administered via central or peripheral vein depending on its final osmolality. If the final mixture is hypertonic, vein irritation may occur when administered via a peripheral vein.

• Although trace elements and vitamins are naturally present in the product, their quantities are insufficient to meet the body’s requirements. Therefore, supplementation is necessary to prevent deficiencies. Instructions for adding supplementary components should be followed carefully.

• Exercise caution when administering Multimel N4-550 E to patients with elevated osmolality, adrenal insufficiency, heart failure, or pulmonary disorders.

• Repletion of nutrients in severely malnourished patients may trigger a refeeding syndrome characterized by intracellular shifts of potassium, phosphate, and magnesium as anabolic processes begin to dominate. Thiamine deficiency and fluid retention may also occur. Careful monitoring and gradual increase in nutrient administration, avoiding overfeeding, may prevent these complications. This syndrome has been reported with similar products.

• Do not connect bags in series, to avoid air embolism caused by residual air in the first bag.

Liver dysfunction
Exercise caution when administering the product to patients with liver dysfunction, as there is a risk of developing or worsening neurological disorders associated with hyperammonemia. Regular clinical and laboratory monitoring, particularly of liver function parameters, blood glucose, electrolytes, and triglycerides, is required.

Renal dysfunction
Exercise caution when administering the product to patients with renal dysfunction, especially in the presence of hyperkalemia, due to the risk of developing or worsening metabolic acidosis and hyperazotemia if renal excretion of metabolic by-products is not supplemented. In these patients, fluid and electrolyte status and triglyceride levels should be closely monitored.

Hematology
Exercise caution when administering the product to patients with coagulation disorders or anemia. Blood morphology and coagulation parameters should be carefully monitored.

Endocrinology and metabolism
Exercise caution when administering the product to patients with:

• Metabolic acidosis. Administration of bicarbonates is not recommended in lactic acidosis. Regular clinical and laboratory monitoring is required.
• Diabetes mellitus. Blood and urine glucose concentrations and ketonuria should be monitored, and insulin dosage adjusted as needed.
• Hyperlipidemia due to fat-containing infusion emulsions. Regular clinical and laboratory monitoring is required.
• Disorders of amino acid metabolism.

Extravasation
The catheter insertion site should be regularly inspected for signs of extravasation. If extravasation occurs, infusion should be stopped immediately, while maintaining the catheter or cannula in place to allow immediate initiation of treatment. If possible, aspiration through the catheter/cannula should be performed to reduce the volume of fluid in the tissues before removal. If the affected area is a limb, the limb should be elevated.
Depending on the product extravasated (including any product mixed with Multimel N4-550 E, if applicable) and the extent of injury, appropriate measures should be taken. Management options may include non-pharmacological, pharmacological, and/or surgical interventions. In case of worsening of the affected area (persistent pain, necrosis, ulceration, suspected compartment syndrome), surgical consultation should be sought immediately.
The extravasation site should be monitored at least every 4 hours during the first 24 hours, then once daily.
Infusion should not be resumed in the same peripheral or central vein.

Special warnings for treatment in children and adolescents
When administering to children over 2 years of age, it is important to use a bag with a volume corresponding to the daily dose.
Supplementation with vitamins and trace elements is always required. Products with compositions adapted to the pediatric age group should be used.

4. PRACTICAL INFORMATION ON PREPARATION FOR USE AND DISPOSAL OF THE MEDICINAL PRODUCT

Multimel N4-550 E should only be used if:

• The bag is undamaged.
• The seals are intact.
• The amino acid and glucose solutions are clear, colorless or slightly yellow, and practically free of visible particles.
• The fat emulsion is a homogeneous, milky-appearing liquid.

Before use, bring Multimel N4-550 E to room temperature.
Administer only after breaking the seals between the three compartments and mixing the contents of all three compartments, as shown below.
Ensure that the final infusion emulsion shows no signs of phase separation.

1. 2. 3.

Remove the protective packaging from the top. Remove the front part of the protective packaging to expose the bag Multimel N4-550 E. Place the bag on a flat, horizontal, clean surface with the handle facing toward you. Discard the protective packaging and the oxygen-absorbing sachet.

4. 5. 6.

Lift the bag by the handle to remove fluid from the upper part of the bag. Roll the bag firmly downward with both hands, starting from the top, until the seals are broken (approximately halfway along their length). Mix the contents of the bag by rotating it at least three times. Ensure that the mixture is homogeneous and that no phase separation occurs. Hang the bag. Remove the plastic cover from the infusion port. Firmly insert the spike of the infusion set into the port.

Once the bag is opened, the contents should be used immediately. Do not store an opened bag for subsequent infusions.
Do not reconnect partially used bags.
Do not connect bags in series, to avoid air embolism caused by residual gas in the first bag.
For single use only. Any unused product or waste, including the entire infusion set, must be discarded.
Do not store partially used bags; dispose of all components of the set after use.

Additional components
Do not add other medicinal products or substances to any of the bag compartments or to the final emulsion without prior verification of compatibility and stability of the resulting mixture (especially fat emulsion stability).
Multimel N4-550 E may be used without additional components or, if needed, after adding electrolytes, trace elements, or vitamins.
The bag capacity allows for the addition of supplementary components such as vitamins, electrolytes, and trace elements. All additional components (including vitamins) may be added to the final emulsion (after breaking the seals and mixing the contents of the three compartments).
Vitamins may also be added to the glucose compartment before preparing the final emulsion (before breaking the seals and mixing the solutions and emulsion).
When additional components are added, the final osmolality of the mixture should be measured before administration via a peripheral vein.

The following may be added to Multimel N4-550 E:

• Electrolytes: consider the amount of electrolytes already present in the bag; stability has been demonstrated for mixtures containing up to 150 mmol sodium, 150 mmol potassium, 5.6 mmol magnesium, and 5 mmol calcium per liter of the three-component mixture.
• Organic phosphates: stability has been demonstrated for mixtures with up to 15 mmol of added phosphate per bag.

Trace elements and vitamins: stability has been demonstrated after adding commercially available vitamin and trace element products (containing up to 1 mg of iron). Compatibility with other additional components is available upon request.
Additional components must be added by qualified personnel under aseptic conditions.
Additional components are introduced through the injection site using a needle:

• Prepare the injection site.
• Insert the needle into the injection site and inject.
• Mix the bag contents thoroughly.

When additional components are added, the final osmolality of the mixture should be measured before administration. The resulting mixture should be administered via central or peripheral vein depending on its final osmolality. If the final mixture is hypertonic, vein irritation may occur when administered via a peripheral vein.

Interactions with other medicinal products
No interaction studies have been conducted with Multimel.
Multimel N4-550 E contains vitamin K, naturally present in fat emulsions. The amount of vitamin K in the recommended doses of Multimel N4-550 E should not affect the action of coumarin derivatives.
Ceftriaxone must not be mixed or administered simultaneously with intravenous solutions containing calcium, including Multimel N4-550 E, through the same infusion line due to the risk of precipitation of ceftriaxone-calcium salts.
Ceftriaxone and calcium-containing solutions may be administered sequentially if different infusion sites are used or if infusion lines are replaced or thoroughly flushed with physiological saline solution between infusions to prevent precipitate formation.
Due to the potassium content of Multimel N4-550 E, particular caution is required when administering it to patients treated with potassium-sparing diuretics (e.g., amiloride, spironolactone, triamterene), angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, or immunosuppressive agents (tacrolimus and cyclosporine) due to the risk of hyperkalemia.
The fats in this emulsion may interfere with results of certain laboratory tests (e.g., bilirubin, lactate dehydrogenase, oxygen saturation, hematocrit) if blood samples are drawn before fat clearance (fats are usually eliminated within approximately 5–6 hours after discontinuation of infusion).

Pharmaceutical incompatibilities
This infusion emulsion must not be administered simultaneously with blood through the same infusion set.
Multimel N4-550 E contains calcium ions, which pose an additional risk of coagulation and precipitate formation in anticoagulated/citrate-preserved blood or blood components.
Incompatibility may also result from excessive acidity (low pH) or inappropriate content of divalent cations (Ca and Mg), which may adversely affect fat emulsion stability.
As with all parenteral nutrition mixtures, calcium and phosphate contents should be considered. Excessive addition of calcium or phosphate, especially in the form of mineral salts, may lead to calcium phosphate precipitate formation.
Compatibility of the product with solutions administered simultaneously through the same infusion set, catheter, or cannula should be verified.
Ceftriaxone must not be mixed or administered simultaneously with intravenous solutions containing calcium, including Multimel N4-550 E, through the same infusion line (e.g., Y-connector) due to the risk of precipitation of ceftriaxone-calcium salts (see section “Interactions”).

5. EXPIRY DATE

2 years, if the protective packaging is undamaged.
It is recommended that the product be used promptly after breaking the seals between the three compartments. However, the final emulsion has been shown to remain stable for up to 7 days at +2°C to +8°C and for an additional 48 hours at temperatures not exceeding +25°C.
After addition of supplementary components (electrolytes, trace elements, vitamins), the final emulsion of Multimel N4-550 E (see previous section) maintains chemical and physical stability for 7 days at +2°C to +8°C and for an additional 48 hours at temperatures below 25°C. From a microbiological standpoint, any ready-to-use mixture containing supplementary components should be used immediately. Otherwise, the responsibility for storage conditions and duration prior to use lies with the user. However, such mixtures should not be stored for longer than 24 hours at 2–8°C unless the addition of supplementary components was performed under controlled and validated aseptic conditions.