Periolimel N4-E emulsion for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

PeriOlimel N4E emulsion for infusion

Read all of this leaflet carefully before you are given this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor or nurse.
• If you experience any side effects, talk to your doctor or nurse, even if it is a side effect not listed in this leaflet. See section 4.

Leaflet contents

1. What PeriOlimel N4E is and what it is used for

2. What you need to know before PeriOlimel N4E is administered to you

3. How PeriOlimel N4E will be administered to you

4. Possible side effects

5. How to store PeriOlimel N4E

6. Contents of the pack and other information

1. What PeriOlimel N4E is and what it is used for

PeriOlimel is an infusion emulsion. It is supplied as a three-compartment bag.

One compartment contains a glucose solution with calcium, the second contains a lipid emulsion, and the third contains an amino acid solution with other electrolytes.

PeriOlimel is used to provide nutrition to adults and children over two years of age via intravenous infusion when normal oral feeding is not possible.

PeriOlimel must only be used under medical supervision.

2. What you need to know before PERIOLIMEL N4E is administered to you

PERIOLIMEL N4E must not be administered:

• In premature neonates, infants, and children under two years of age
• If you are hypersensitive (allergic) to egg proteins, soybean seed proteins, peanuts, corn/corn products (see also section “Warnings and precautions” below), or to any of the other components of this medicine (listed in section 6).
• If your body has difficulty utilizing certain amino acids.
• If you have markedly elevated levels of fats in the blood.
• If you have hyperglycemia (excessively high blood sugar).
• If you have abnormally high levels of any electrolyte (sodium, potassium, magnesium, calcium, and/or phosphorus) in the blood.

In all cases, your doctor will decide whether this medicine should be administered to you based on factors such as your age, weight, clinical condition, and the results of all tests performed.

Warnings and precautions

Talk to your doctor or nurse before PERIOLIMEL is administered to you.

Administering total parenteral nutrition (TPN) solutions too rapidly may cause injury or death.

Infusion must be stopped immediately if any abnormal signs or symptoms of an allergic reaction occur (such as sweating, fever, chills, headache, skin rash, or difficulty breathing). This medicine contains soybean oil and egg phospholipids. Soybean and egg proteins may cause hypersensitivity reactions. Cross-allergic reactions between soybean seed proteins and peanut proteins have been observed.

Periolimel contains glucose derived from corn, which may cause hypersensitivity reactions in individuals allergic to corn or corn products (see section “Periolimel N4E must not be administered” above).

Difficulty in breathing may also be a sign that small particles have formed in the lungs, blocking blood vessels (pulmonary vascular precipitates). If you experience any breathing difficulty, inform your doctor or nurse. They will decide on the appropriate action.

The antibiotic called ceftriaxone must not be mixed or administered simultaneously with solutions containing calcium (including Periolimel) given by intravenous infusion.

These medicines must not be administered together, even through different infusion lines or infusion sites.

However, Periolimel and ceftriaxone may be administered sequentially, one after the other, 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 (formation of ceftriaxone-calcium salt particles).

Certain medications and diseases may increase the risk of developing infections or sepsis (bacteria in the blood). There is a risk of infection or sepsis, especially when a tube (intravenous catheter) is placed into a vein. Your doctor will closely monitor you for signs of infection.

Patients requiring parenteral nutrition (administration of nutrients through a tube inserted into a vein) may be more prone to infections due to their medical condition. The use of "aseptic techniques" (germ-free) when placing and maintaining the catheter and when preparing the nutritional formula (TPN) can reduce the risk of infection.

If you are severely malnourished and require intravenous feeding, your doctor should start treatment slowly. You will also be monitored to avoid sudden changes in fluid, vitamin, electrolyte, and mineral levels.

Before starting the infusion, any metabolic disorders and disturbances in your body's water and salt balance should be corrected. Your doctor will monitor your condition while you are receiving this medicine and may adjust the dose or add other nutrients such as vitamins, electrolytes, and trace elements as appropriate.

Cases of liver disorders have been reported in patients receiving intravenous nutritional therapy, including impaired bile excretion (cholestasis), fat accumulation in the liver (hepatic steatosis), fibrosis (which may lead to liver failure), as well as cholecystitis and cholelithiasis. The cause of these disorders is believed to be multifactorial and may vary between patients. If you experience symptoms such as nausea, vomiting, abdominal pain, or yellowing of the skin or eyes (jaundice), consult your doctor to identify possible causative and contributing factors, as well as potential therapeutic and preventive measures.

Your doctor should be informed if you have:

• Severe kidney problems. You should also inform your doctor if you are undergoing dialysis (artificial kidney) or any other blood-cleansing treatment
• Severe liver problems
• Blood clotting disorders
• Adrenal gland dysfunction (adrenal insufficiency). The adrenal glands are triangular-shaped and located above the kidneys
• Heart failure
• Lung disease
• Fluid accumulation in the body (hyperhydration)
• Insufficient body fluids (dehydration)
• High blood sugar levels (untreated diabetes mellitus)
• Heart attack or shock due to sudden heart failure
• Severe metabolic acidosis (excessively acidic blood)
• Systemic infection (septicemia)
• Coma

To monitor the effectiveness and safety of treatment, your doctor will perform laboratory and clinical tests while you are receiving this medicine. If you receive this medicine for several weeks, your blood will be tested regularly.

Reduced ability of the body to eliminate the fats contained in this medicine may lead to a "fat overload syndrome" (see section 4 “Possible side effects”).

If during the infusion you feel pain, burning, or swelling at the infusion site, or if leakage occurs, inform your doctor or nurse immediately. The infusion will be stopped immediately and restarted in another vein.

If your blood sugar levels become too high, your doctor will adjust the infusion rate of PERIOLIMEL or administer medication to control blood sugar concentration (insulin).

PERIOLIMEL may be administered through a tube (catheter) connected to a vein in your arm or a large vein in your chest (central vein).

Children and adolescents

If your child is under 18 years of age, special attention must be paid to administering the correct dose. Additional precautions are necessary due to children's increased susceptibility to infection risk. Supplementation with vitamins and trace elements is always required. Pediatric formulations should be used.

Use of PERIOLIMEL with other medicines

Tell your doctor if you are taking or using, have recently taken or used, or might need to take or use any other medicines.

Concurrent administration of other medicines is generally not a contraindication. However, if you are taking other prescription or over-the-counter medicines, you should consult your doctor in advance to ensure compatibility.

Inform your doctor if you are taking or receiving any of the following medicines:

• Insulin
• Heparin

PERIOLIMEL must not be administered simultaneously with blood through the same infusion line.

PERIOLIMEL contains calcium. It must not be administered together or through the same line as the antibiotic ceftriaxone, as particles may form. If the same device is used to administer these medicines sequentially, it must be thoroughly flushed.

Due to the risk of precipitation, PERIOLIMEL must not be administered through the same infusion line or mixed with the antibiotic ampicillin or the antiepileptic drug fosphenytoin.

The olive and soybean oils present in PERIOLIMEL contain vitamin K. This usually does not affect blood-thinning medications (anticoagulants) such as coumarin. However, if you are taking anticoagulants, you must inform your doctor.

The lipids contained in this emulsion may interfere with the results of certain laboratory tests if blood samples are taken before the lipids have been cleared from the bloodstream (typically cleared after a 5 to 6-hour lipid-free period).

PERIOLIMEL contains potassium. Caution is required in patients taking diuretics, ACE inhibitors, angiotensin II receptor antagonists (medications for high blood pressure), or immunosuppressants. These classes of drugs may increase blood potassium levels.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor before receiving this medicine.

There is insufficient experience with the use of PERIOLIMEL in pregnant or breastfeeding women. PERIOLIMEL may be used during pregnancy and breastfeeding if necessary. However, PERIOLIMEL should only be administered to pregnant or breastfeeding women after careful consideration.

Driving and using machines

Not applicable.

3. How PERIOLIMEL N4E will be administered to you

Dosing

PERIOLIMEL should only be administered to adults and children over two years of age.

It is an infusion emulsion, meaning it is administered through a tube (catheter) connected to a vein in your arm or a large vein (central vein).

PERIOLIMEL must be at room temperature before use.

PERIOLIMEL is for single use only.

Dosing – Adults

Your doctor will determine the infusion rate based on your individual needs and clinical condition.

Administration may continue for as long as necessary, depending on your clinical status.

Dosing – Children over two years of age and adolescents

The doctor will decide the dose and duration of treatment based on age, weight, height, clinical condition, and the body's ability to metabolize and utilize the components of PERIOLIMEL.

If you have been given more PERIOLIMEL N4E than you should have

If the dose administered is too high or the infusion is too rapid, the amino acid content may cause your blood to become too acidic, and signs of hypervolemia (increased volume of circulating blood) may occur. Blood and urine glucose levels may rise, a hyperosmolar syndrome (excessively viscous blood) may develop, and the lipid content may increase triglyceride levels in your blood. Administering the infusion too rapidly or in excessive volume may cause nausea, vomiting, chills, headache, flushing, excessive sweating (hyperhidrosis), and electrolyte disturbances. In such cases, the infusion must be stopped immediately.

In severe cases, your doctor may need to perform temporary renal dialysis to help your kidneys eliminate the excess product.

To prevent such events, your doctor will regularly monitor your condition and assess your blood parameters.

If you have any further questions about the use of this product, ask your doctor.

In case of overdose or accidental ingestion, contact the Toxicology Information Service. Telephone 915.620.420

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them. If you notice that you do not feel as you normally do, inform your doctor or nurse immediately.

The tests your doctor performs while you are receiving this medicine should help minimize the risk of adverse effects.

If any abnormal sign or symptom of an allergic reaction occurs, such as sweating, fever, chills, headache, skin rash, or difficulty breathing, the infusion must be stopped immediately.

The following adverse effects have been reported with PeriOlimel:

Frequency – Common: may affect up to 1 in 10 people

• Increased heart rate (tachycardia).
• Decreased appetite.
• Increased blood fat levels (hypertriglyceridemia).
• Abdominal pain.
• Diarrhea.
• Nausea.
• High blood pressure (hypertension).

Frequency – Not known: cannot be estimated from available data

• Hypersensitivity reactions including sweating, fever, chills, headache, skin rash (erythematous, papular, pustular, macular, generalized eruption), itching, flushing, breathing difficulties.
• Leakage of the infusion into surrounding tissue (extravasation) may cause pain at the infusion site, irritation, swelling/edema, redness (erythema)/warmth, death of tissue cells (skin necrosis), or blisters/vesicles, inflammation, thickening, or tightening of the skin.
• Vomiting.

The following adverse effects have been reported with other similar products for parenteral nutrition:

Frequency – Very rare: may affect up to 1 in 10,000 people

• Reduced ability to eliminate lipids (lipid overload syndrome), associated with a sudden and marked deterioration in the patient's medical condition. The following symptoms of lipid overload syndrome are usually reversible when the lipid emulsion infusion is stopped:
  • Fever.
  • Decreased red blood cells, which may cause paleness, weakness, or difficulty breathing (anemia).
  • Low white blood cell count, which may increase the risk of infection (leukopenia).
  • Low platelet count, which may increase the risk of bruising and/or bleeding (thrombocytopenia).
  • Coagulation disorders affecting the blood's ability to clot.
  • Elevated fat levels in the blood (hyperlipidemia).
  • Fat accumulation in the liver (hepatomegaly).
  • Worsening of liver function.
  • Central nervous system manifestations (e.g., coma).

Frequency – Not known: cannot be estimated from available data

• Allergic reactions.
• Problems with bile elimination (cholestasis).
• Abnormal blood tests for liver function.
• Increased liver size (hepatomegaly).
• Conditions associated with parenteral nutrition (see “Warnings and precautions” in section 2).
• Jaundice.
• Decreased platelet count (thrombocytopenia).
• Increased nitrogen levels in the blood (azotemia).
• Increased liver enzymes.
• Formation of small particles that may lead to blockage of blood vessels in the lungs (pulmonary vascular precipitates), resulting in pulmonary vascular embolism and difficulty breathing (dyspnea).

Reporting of adverse effects:

If you experience any adverse effect, consult your doctor or nurse, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicinal Products: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of PeriOlimel N4E

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 (MM/YYYY). The expiry date refers to the last day of the month indicated.

Do not freeze.

Store inside the overpouch.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to properly dispose of unused medicines and their packaging. This will help protect the environment.

6. Contents of the container and other information

Composition of PERIOLIMEL N4E emulsion for infusion

The active ingredients in each bag of the reconstituted emulsion are a 6.3% L-amino acid solution (corresponding to 6.3 g/100 ml of alanine, arginine, glycine, histidine, isoleucine, leucine, lysine (as lysine acetate), methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine, aspartic acid, glutamic acid) with electrolytes (sodium, potassium, magnesium, phosphate, acetate, chloride), a 15% lipid emulsion (corresponding to 15 g/100 ml of refined olive oil and refined soybean oil), and a 18.75% glucose solution (corresponding to 18.75 g/100 ml as glucose monohydrate) with calcium.

The other components are:

Lipid emulsion compartment	Amino acid solution compartment	Glucose solution compartment
Purified egg phospholipids, glycerol, sodium oleate, sodium hydroxide (for pH adjustment), water for injections	Glacial acetic acid (for pH adjustment), water for injections	Hydrochloric acid (for pH adjustment), water for injections

Appearance of PERIOLIMEL N4E and contents of the packaging

PERIOLIMEL is a perfusion emulsion supplied in a 3-compartment bag. One compartment contains a lipid emulsion, another an amino acid solution with electrolytes, and the third a glucose solution with calcium. These compartments are separated by non-permanent seals. Prior to administration, the contents of the compartments must be mixed by rotating the bag from its top until the seals are opened.

Appearance prior to reconstitution:

• The amino acid and glucose solutions are transparent, colorless or slightly yellowish.
• The lipid emulsion is homogeneous and milky white.

Appearance after reconstitution: Homogeneous milky emulsion.

The triple-compartment bag is a multilayer plastic bag. The material of the inner layer (in contact) of the bag is designed to be compatible with the authorized components and additives.

To prevent contact with atmospheric oxygen, the bag is packaged in an overpouch acting as an oxygen barrier, which contains an oxygen-absorbing sachet.

Pack sizes

Bag of 1000 ml: 1 cardboard box containing 6 bags
Bag of 1500 ml: 1 cardboard box containing 4 bags
Bag of 2000 ml: 1 cardboard box containing 4 bags
Bag of 2500 ml: 1 cardboard box containing 2 bags

1 bag of 1000 ml, 1500 ml, 2000 ml, and 2500 ml

Only certain pack sizes may be marketed.

Marketing Authorization Holder

Baxter S.L.
Pouet de Camilo 2, 46394 Ribarroja del Turia (Valencia)

Manufacturer

Baxter S.A., Boulevard René Branquart, 80, 7860 Lessines, Belgium

This medicinal product is authorized in the Member States of the European Economic Area under the following names:

France, Portugal, Bulgaria, Romania, Czech Republic, Belgium, Spain, Slovak Republic, Luxembourg, Slovenia: PERIOLIMEL N4E

In some countries it is registered under different names as follows: Estonia, Poland, Lithuania, Latvia, Greece, Cyprus: Olimel Peri N4E

Netherlands: Olimel Perifeer N4E

Italy: Olimel Periferico N4E

Austria: PeriOLIMEL 2,5 % mit Elektrolyten

Germany: Olimel Peri 2,5% E

Denmark, Iceland, Sweden, Norway, Finland: Olimel Perifer N4E

United Kingdom, Ireland and Malta: Triomel Peripheral 4g/l nitrogen 700 kcal/l with electrolytes

Hungary: PeriOlimel 4 g/l nitrogén elektrolitokkal emulziós infúzió

Date of the most recent review of this summary: April 2020

Detailed and up-to-date information on this medicinal product is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS) http://www.aemps.gob.es/

This information is intended for healthcare professionals only

Pharmacotherapeutic group: parenteral nutrition solutions / combinations
ATC Code: B05 BA10

A. Qualitative and quantitative composition

PeriOlimel is supplied as a 3-compartment bag. Each bag contains a glucose solution with calcium, a lipid emulsion, and an amino acid solution with additional electrolytes.

	Content per bag
	1000 ml	1500 ml	2000 ml	2500 ml
18.75% glucose solution (equivalent to 18.75 g/100 ml)	400 ml	600 ml	800 ml	1000 ml
6.3% amino acid solution (equivalent to 6.3 g/100 ml)	400 ml	600 ml	800 ml	1000 ml
15% lipid emulsion (equivalent to 15 g/100 ml)	200 ml	300 ml	400 ml	500 ml

After mixing the contents of the 3 compartments, the composition of the reconstituted emulsion is indicated in the following table for each bag size.

Active Ingredients	1000 ml	1500 ml	2000 ml	2500 ml
Refined olive oil + refined soybean oila Alanine Arginine Aspartic acid Glutamic acid Glycine Histidine Isoleucine Leucine Lysine (equivalent to lysine acetate) Methionine Phenylalanine Proline Serine Threonine Tryptophan Tyrosine Valine Sodium acetate trihydrate Sodium glycerophosphate hydrate Potassium chloride Magnesium chloride hexahydrate Calcium chloride dihydrate Glucose (equivalent to glucose monohydrate)	30.00 g 3.66 g 2.48 g 0.73 g 1.26 g 1.76 g 1.51 g 1.26 g 1.76 g 1.99 g (2.81 g) 1.26 g 1.76 g 1.51 g 1.00 g 1.26 g 0.42 g 0.06 g 1.62 g 1.16 g 1.91 g 1.19 g 0.45 g 0.30 g 75.00 g (82.50 g)	45.00 g 5.50 g 3.72 g 1.10 g 1.90 g 2.63 g 2.26 g 1.90 g 2.63 g 2.99 g (4.21 g) 1.90 g 2.63 g 2.26 g 1.50 g 1.90 g 0.64 g 0.10 g 2.43 g 1.73 g 2.87 g 1.79 g 0.67 g 0.44 g 112.50 g (123.75 g)	60.00 g 7.33 g 4.96 g 1.46 g 2.53 g 3.51 g 3.02 g 2.53 g 3.51 g 3.98 g (5.62 g) 2.53 g 3.51 g 3.02 g 2.00 g 2.53 g 0.85 g 0.13 g 3.24 g 2.31 g 3.82 g 2.38 g 0.90 g 0.59 g 150.00 g (165.00 g)	75.00 g 9.16 g 6.20 g 1.83 g 3.16 g 4.39 g 3.77 g 3.16 g 4.39 g 4.98 g (7.02 g) 3.16 g 4.39 g 3.77 g 2.50 g 3.16 g 1.06 g 0.16 g 4.05 g 2.89 g 4.78 g 2.98 g 1.12 g 0.74 g 187.50 g (206.25 g)

(a) A mixture of refined olive oil (approximately 80%) and refined soybean oil (approximately 20%), corresponding to a ratio of essential fatty acids / total fatty acids of 20%.

The excipients are:

Lipid emulsion compartment	Compartment of amino acid solution with electrolytes	Compartment of glucose solution with calcium
Purified egg phospholipids, glycerol, sodium oleate, sodium hydroxide (for pH adjustment), water for injections	Glacial acetic acid (for pH adjustment), water for injections	Hydrochloric acid (for pH adjustment), water for injections

The reconstituted emulsion provides the following for each bag size:

	1000 ml	1500 ml	2000 ml	2500 ml
Lipids	30 g	45 g	60 g	75 g
Amino Acids	25.3 g	38.0 g	50.6 g	63.3 g
Nitrogen	4.0 g	6.0 g	8.0 g	10.0 g
Glucose	75.0 g	112.5 g	150.0 g	187.5 g
Energy:
Approximate total calories	700 kcal	1050 kcal	1400 kcal	1750 kcal
Non-protein calories	600 kcal	900 kcal	1200 kcal	1500 kcal
Calories from glucose	300 kcal	450 kcal	600 kcal	750 kcal
Calories from lipids(a)	300 kcal	450 kcal	600 kcal	750 kcal
Non-protein calories / nitrogen ratio	150 kcal/g	150 kcal/g	150 kcal/g	150 kcal/g
Glucose calories / lipid calories ratio	50/50	50/50	50/50	50/50
Lipid calories / total calories	43%	43%	43%	43%
Electrolytes:
Sodium	21.0 mmol	31.5 mmol	42.0 mmol	52.5 mmol
Potassium	16.0 mmol	24.0 mmol	32.0 mmol	40.0 mmol
Magnesium	2.2 mmol	3.3 mmol	4.4 mmol	5.5 mmol
Calcium	2.0 mmol	3.0 mmol	4.0 mmol	5.0 mmol
Phosphate (b)	8.5 mmol	12.7 mmol	17.0 mmol	21.2 mmol
Acetate	27 mmol	41 mmol	55 mmol	69 mmol
Chloride	24 mmol	37 mmol	49 mmol	61 mmol
pH	6.4	6.4	6.4	6.4
Osmolarity	760 mOsm/l	760 mOsm/l	760 mOsm/l	760 mOsm/l

a Includes calories from purified egg phospholipids

b Includes phosphate provided by the lipid emulsion

B. Posology and method of administration

Posology

The use of PERIOLIMEL is not recommended in children under 2 years of age, as neither the composition nor the volume are appropriate (see sections 4.4, 5.1 and 5.2 of the Summary of Product Characteristics).

The maximum daily dose mentioned below must not be exceeded. Due to the fixed composition of the multi-chamber bag, it may not be possible to simultaneously meet all the patient's nutrient requirements. There may be clinical situations in which the patient requires nutrient amounts differing from the bag's composition. In such cases, any adjustment in volume (dose) must take into account the resulting effect on the dosing of the other nutrients in PERIOLIMEL.

In adults

The dose depends on the patient's energy expenditure, clinical condition, body weight, and ability to metabolize the components of PERIOLIMEL, as well as on additional energy or protein intake administered orally or enterally. Therefore, the appropriate bag size should be selected.

Average daily requirements are:

• 0.16 to 0.35 g of nitrogen/kg body weight (1 to 2 g of amino acids/kg), depending on the patient's nutritional status and level of catabolic stress.
• 20 to 40 kcal/kg.
• 20 to 40 ml of fluid/kg, or 1 to 1.5 ml per kcal expended.

For PeriOlimel, the maximum daily dose is defined by fluid intake at 40 ml/kg, corresponding to 1 g/kg of amino acids, 3 g/kg of glucose, 1.2 g/kg of lipids, 0.8 mmol/kg of sodium, and 0.6 mmol/kg of potassium. For a 70 kg patient, this would correspond to 2800 ml of PeriOlimel per day, providing 71 g of amino acids, 210 g of glucose, and 84 g of lipids, i.e., 1680 non-protein kcal and 1960 total kcal.

Normally, the infusion rate should be gradually increased during the first hour, then adjusted according to the administered dose, daily volume intake, and duration of infusion.

For PeriOlimel, the maximum infusion rate is 3.2 ml/kg/hour, corresponding to 0.08 g/kg/hour of amino acids, 0.24 g/kg/hour of glucose, and 0.10 g/kg/hour of lipids.

In children over 2 years of age and adolescents

No studies have been conducted in the pediatric population.

The dose depends on the patient's energy expenditure, clinical condition, body weight, and ability to metabolize the components of PERIOLIMEL, as well as on additional energy and protein intake administered orally or enterally. Therefore, the appropriate bag size should be selected.

In addition, daily requirements for fluid, nitrogen, and energy decrease progressively with age. Two age groups are considered: one between 2 and 11 years, and another from 12 to 18 years.

For PERIOLIMEL N4E, in both age groups, magnesium concentration is the limiting factor for the daily dose. In the 2- to 11-year age group, lipid concentration is the limiting factor for the hourly rate. In the 12- to 18-year age group, glucose concentration is the limiting factor for the hourly rate. The resulting intakes are as follows:

Constituent	From 2 to 11 years	From 12 to 18 years
Recommendeda	PERIOLIMEL N4E Vol. Max	Recommendeda	PERIOLIMEL N4E Vol. Max
Maximum daily dose
Liquid (ml/kg/day)	60 – 120	45	50 – 80	45
Amino acids (g/kg/day)	1 – 2 (up to 2.5)	1.1	1 – 2	1.1
Glucose (g/kg/day)	1.4 – 8.6	3.4	0.7 – 5.8	3.4
Lipids (g/kg/day)	0.5 – 3	1.4	0.5 – 2 (up to 3)	1.4
Total energy (kcal/kg/day)	30 – 75	31.5	20 – 55	31.5
Maximum infusion rate per hour
PERIOLIMEL N4E (ml/kg/h)		4.3		3.2
Amino acids (g/kg/h)	0.20	0.11	0.12	0.08
Glucose (g/kg/h)	0.36	0.33	0.24	0.24
Lipids (g/kg/h)	0.13	0.13	0.13	0.10

a: Recommended values according to the 2018 ESPGHAN/ESPEN/ESPR Guidelines

The infusion rate should normally be gradually increased during the first hour, and then adjusted according to the dose being administered, the daily volume intake, and the duration of the infusion.

In general, for young children, it is recommended to start infusion with a reduced daily dose and gradually increase it to the maximum dose (see previous point).

Administration Form and Duration

For single use only.

Once the bag has been opened, it is recommended to use its contents immediately and not to save it for subsequent infusions.

After reconstitution, the mixture appears as a homogeneous emulsion resembling milk.

For instructions on the preparation and handling of the emulsion for infusion, see section 6.6 of the Summary of Product Characteristics.

Due to its low osmolarity, PeriOlimel may be administered through either a peripheral or a central vein.

The recommended duration for the infusion of one parenteral nutrition bag is between 12 and 24 hours.

Parenteral nutrition treatment may continue for as long as the patient's clinical condition requires.

C. Incompatibilities

No other medicinal product or drug should be added to any of the components in the bag or to the reconstituted emulsion without first confirming the compatibility and stability of the resulting preparation (particularly the stability of the lipid emulsion).

Incompatibilities may occur, for example, due to excessive acidity (low pH) or inappropriate levels of divalent cations (Ca²⁺ and Mg²⁺), which may destabilize the lipid emulsion.

As with any parenteral nutrition mixture, the proportions of calcium and phosphate should be carefully considered. Excessive addition of calcium and phosphate, especially in the form of mineral salts, may lead to precipitation of calcium phosphate.

PERIOLIMEL contains calcium ions, which poses an additional risk of blood coagulation when anticoagulated or citrate-preserved blood is administered.

Ceftriaxone must not be mixed or administered simultaneously with intravenous solutions containing calcium, including PERIOLIMEL, via the same infusion line (e.g., Y-connector), due to the risk of ceftriaxone-calcium salt precipitation (see sections 4.4 and 4.5 of the Summary of Product Characteristics). Ceftriaxone and calcium-containing solutions may be administered sequentially if different infusion sites are used, or if the infusion lines are replaced or thoroughly flushed between administrations.

Due to the risk of precipitation, PERIOLIMEL must not be administered through the same infusion line or mixed with ampicillin or fosphenytoin.

Check compatibility with solutions administered simultaneously through the same administration set, catheter, or cannula.

PERIOLIMEL must not be administered before, simultaneously, or after blood through the same administration set due to the risk of pseudoagglutination.

D. Special Precautions for Disposal and Other Handling

Table 1 provides an overview of the preparation steps for administering PERIOLIMEL.

To Open

Remove the protective overpouch.

Discard the sachet containing the oxygen absorber.

Check the integrity of the bag and the non-permanent seals. Use only if the bag is undamaged, the non-permanent seals are intact (i.e., the contents of the three compartments have not yet mixed), the amino acid solution and glucose solution are clear, colorless or slightly yellowish, and practically free from visible particles, and the lipid emulsion is a homogeneous milky-appearing liquid.

Mixing the Solutions and Emulsion

Ensure the product is at room temperature when breaking the non-permanent seals.

Manually roll the bag onto itself, starting from the top of the bag (hanger end). The non-permanent seals will disappear from the side near the ports. Continue rolling until the seals open approximately halfway along their length.

Mix the bag by inverting it at least three times.

The appearance after reconstitution is a homogeneous emulsion resembling milk.

Additions

The bag has sufficient capacity to allow the addition of vitamins, electrolytes, and trace elements.

Any addition (including vitamins) must be made to the reconstituted mixture (after breaking the non-permanent seals and mixing the contents of the three compartments).

Vitamins may also be added to the glucose compartment prior to reconstitution (before breaking the non-permanent seals and mixing the contents of the three compartments).

When additions are made to formulations containing electrolytes, the amount of electrolytes already present in the bag must be taken into account.

All additions must be performed by trained personnel under aseptic conditions.

PERIOLIMEL may be supplemented with electrolytes according to the following table:

Per 1000 ml
	Level included	Maximum additional added	Total maximum level
Sodium	21 mmol	129 mmol	150 mmol
Potassium	16 mmol	134 mmol	150 mmol
Magnesium	2.2 mmol	3.4 mmol	5.6 mmol
Calcium	2.0 mmol	3.0 (1.5(a)) mmol	5.0 (3.5(a)) mmol
Inorganic phosphate	0 mmol	8.0 mmol	8.0 mmol
Organic phosphate	8.5 mmol (b)	15.0 mmol	23.5 mmol (b)

a Value corresponding to the addition of inorganic phosphate

b Including the phosphate provided by the lipid emulsion

Trace elements and vitamins:

Stability has been demonstrated with commercially available preparations of vitamins and trace elements (containing up to 1 mg of iron).

Compatibility with other additives can be obtained upon request.

When making additions, the final osmolarity of the mixture must be measured before administration through a peripheral vein.

For making an addition:

• It must be carried out under aseptic conditions.
• Prepare the injection site of the bag.
• Pierce the injection site and inject the additives using an injection needle or a reconstitution device.
• Mix the contents of the bag and the additives.

Preparation of the infusion

Must be performed under aseptic conditions.

Hang the bag.

Remove the plastic protector from the administration outlet.

Firmly insert the tip of the infusion set into the administration outlet.

Table 1: Preparation steps for administration of PERIOLIMEL

1.		2.		3.
Break from the top to open the overpouch.	Remove the front part of the overpouch to access the PERIOLIMEL bag. Discard the overpouch and the oxygen sachet.	Place the bag on a clean, flat surface with the handle facing toward you.
4.		5.		6.
Lift the hanger area to remove the solution from the top of the bag. Roll the top of the bag firmly until the seals are completely open (approximately halfway).	Mix the contents by inverting the bag at least three times.	Hang the bag. Rotate the protector to remove it from the administration port. Firmly connect the spike connector.

Administration

For single use only.

Administer the product only after the non-permanent seals between the three compartments have been broken and the contents of the three compartments have been mixed.

Ensure that the final emulsion for infusion shows no phase separation.

After opening the bag, the contents must be used immediately. An opened bag must never be stored for subsequent infusion. Do not reconnect a partially used bag.

Do not connect bags in series, to avoid the risk of gas embolism due to air present in the first bag.

All unused medicinal product, materials that have come into contact with it, and all necessary devices must be discarded.

Extravasation

The catheter site should be regularly inspected for signs of extravasation.

If extravasation occurs, administration must be stopped immediately, while maintaining the cannula or catheter in place for immediate patient treatment. If possible, aspiration should be performed through the inserted cannula/catheter to reduce the amount of fluid present in the tissues before removing the cannula/catheter. When an extremity is affected, the involved limb should be elevated.

Specific measures should be taken depending on the stage or extent of any injury caused by the extravasated product (including any products mixed with PERIOLIMEL).

Treatment options may include pharmacological, non-pharmacological, and/or surgical interventions. In the case of significant extravasation, a plastic surgeon should be consulted within the first 72 hours.

The extravasation site should be inspected at least every 4 hours during the first 24 hours, and thereafter once daily.

Infusion must not be resumed in the same peripheral or central vein.