OLEUNOR N9E EMULSION FOR INFUSION - patient leaflet, side effects, dosage

What is in this leaflet

• 1. What OLEUNOR N9E is and what it is used for

• 2. What you need to know before you are given OLEUNOR N9E

• 3. How OLEUNOR N9E is given

• 4. Possible side effects

• 5. How OLEUNOR N9E is stored

• 6. Contents of the pack and other information

1. what oleunor n9e is and what it is used for

Group of medicines: Solutions for parenteral nutrition, combinations. Classification of medicine: B05BA10.

OLEUNOR N9E is an emulsion for infusion in a bag with 3 compartments. One compartment contains a glucose solution with calcium, the second one contains a lipid emulsion and the third one contains an amino acid solution with other electrolytes.

OLEUNOR N9E is used to provide nutrition to adults and children older than two years of age by a tube into a vein when normal feeding by mouth is not suitable.

2. what you need to know before you are given oleunor n9e

OLEUNOR N9E must not be given:

• – In premature neonates, infants and children less than 2 years old.

• – If you are allergic to egg, soybean or peanut proteins or any of the other ingredients of this medicine (listed in section 6).

• – If your body has problems using certain amino acids.

• – If you have an especially high level of fats in your blood (hyperlipidaemia).

• – If you have too much sugar in your blood (hyperglycemia) which is uncontrolled

• – If you have an abnormally high blood (serum) levels of any of the salts (electrolytes: sodium, potassium, magnesium, calcium, and/or phosphorus) included in OLEUNOR N9E.

• – If you have a serious liver disorder.

• – If you have a serious kidney disease without acess to dialysis.

• – If you are in acute shock.

• – If you have fluid in your lungs (acute pulmonary oedema) or too much body fluid (hyperhydration).

• – If you are in an unstable condition, such as after serious trauma, uncontrolled diabetes, acute heart attack, stroke, blood clot (embolism), metabolic acidosis (a disturbance resulting in too much acid in the blood), serious infection (severe sepsis), coma and if you don’t have enough body fluid (hypotonic dehydration).

• – If you have heart failure that is not treated.

• – If you have a defect in your blood clotting system (haemophagocytotic syndrome).

In all cases, your doctor will decide on whether you can receive this medicine. The decision will depend on factors such as your age, weight, and medical condition, together with the results of any test performed.

Warnings and precautions

Talk to your doctor or nurse before OLEUNOR N9E is given to you.

If you are given total parenteral nutrition (TPN) solutions too fast, this may result in injury or death. If during the infusion you get fever, rash, swelling, difficulty in breathing, chills, sweating, nausea or vomiting, tell the healthcare professional immediately because these symptoms might be caused by an allergic reaction or that you have been given too much of the medicine.

This medicine contains egg phospholipids and soybean oil. Egg and soybean proteins may cause allergic reactions. Cross-allergic reactions between soybean and peanut proteins have been observed. Difficulty in breathing can also be a sign that small particles have been formed, blocking the pulmonary blood vessels (pulmonary vascular precipitates). If you have difficulty in breathing tell your doctor or nurse. They will decide what actions should be taken.

The antibiotic called ceftriaxone should not be mixed or given together with calcium-containing solutions (such as OLEUNOR N9E) that are given to you by a drip infusion into a vein.

These medicines must not be given at the same time even if different lines or sites of infusion are used. However, you may receive OLEUNOR N9E and ceftriaxone sequentially, one after another, if different infusion lines on different infusion sites are used or if the lines of infusion are replaced, or have been thoroughly rinsed between the infusions with a sodium choride solution, in order to avoid precipitation (formation of particles of ceftriaxonecal­cium).

Certain medicines and illnesses can increase the risk of developing infection or sepsis (bacteria in the blood). There is a particular risk of infection or sepsis when a tube (intravenous catheter) is placed in your vein. Your doctor will carefully watch you for any signs of infection. Patients who require parenteral nutrition (giving nutrition through a tube in your vein) may be more likely to develop infections from their medical conditions. Using aseptic (“germ-free”) techniques when placing and caring for the catheter and when making the nutritional formula (TPN) can reduce the risk of infection.

If you are severely malnourished such that you need to receive feedings by vein, your doctor should start the treatment slowly. Also, your doctor should monitor you closely before and when you receive this medicine in order to prevent sudden changes in your fluids, vitamins, electrolytes, blood glucose (sugar in the blood) and mineral levels. The balance of water and salt in your body and metabolic disorders will be corrected before starting the infusion. Children and patients with sensitivity to drugs that can lower levels of sodium (e.g. in acute illness, trauma, post-operative stress, central nervous system diseases) could get sudden decreased sodium concentration in the body, which may lead to sudden brain oedema and lifethreatening brain injury. Your doctor will monitor your condition while you receive this medicine and may change the dosage or give you additional nutrients, such as vitamins, electrolytes and trace elements, if this is necessary.

Your doctor may regularly need to check your blood for liver function tests and other values.

Your doctor should be aware if:

• – you suffer from a severe kidney problem. You also must inform your doctor if you are on dialysis (artificial kidney) or if you have another form of blood cleaning treatment.

• – you suffer from a severe liver problem

• – you have a blood clotting problem

• – your adrenal glands are not working properly (adrenal insufficiency). The adrenal glands are triangle shaped glands located on top of your kidneys.

• – you have hypothyroidism (thyroid problems)

• – you have pancreatitis (inflammation of the pancreas)

• – you suffer from heart failure

• – you have a lung disease

• – there is a build up of water in your body (hyperhydration)

• – there is not enough water in your body (dehydration)

• – you have high blood sugar (diabetes mellitus) that is not controlled

• – you have had a heart attack or shock due to a sudden heart failure

• – you suffer from a severe metabolic acidosis (when the blood is too acidic)

• – you suffer from a generalised serious infection (sepsis)

• – you are in coma

To check the effectiveness and ongoing safety of the administration, your doctor will perform clinical and laboratory tests while you are receiving this medicine. If you are given this medicine for several weeks, your blood will be monitored on a regular basis.

Reduced ability of the body to remove the fats contained in this medicine may result in a “fat overload syndrome” (see section 4 – Possible side effects). During the infusion, if you notice pain, burning or swelling at the infusion site or leakage of the infusion, tell your doctor or nurse. The administration will be stopped immediately and restarted in another vein. If your blood sugar gets too high, your doctor should adjust the administration rate of OLEUNOR N9E or give you medicines to control your blood sugar (insulin). OLEUNOR N9E can only be given via a tube (catheter) into a large vein of your chest (central vein).

Children and adolescents

OLEUNOR N9E is not meant for newborn babies or children younger than 2 years old. OLEUNOR N9E can be given to children from 2 to 16/18 years old. If your child is under 18 years old, special care will be taken to give him/her the correct dosage. Increased precautions will also be taken because of the greater sensitivity of children to the risk of infection. Vitamin and trace element supplementation is always required. Pediatric formulations must be used.

Other medicines and OLEUNOR N9E

Tell your doctor if you are taking or using, have recently taken or used or might take or use any other medicines.Medicines that can lower sodium in the blood, namely diuretics, non-steroid antiinflammatory drugs (NSAIDs), antipsychotics, selective serotonin reuptake inhibitors, opioids, antiepileptics, oxytocin, and chemotherapy. Simultaneous absorption of other medicinal products is not a contraindication, generally. If you take other medicinal products, with or without medical prescription, you should inform your doctor in advance to check compatibility.

OLEUNOR N9E must not be given together with blood through the same infusion tubing.

OLEUNOR N9E contains calcium. It should not be given at the same time or by the same tube with the antibiotic ceftriaxone because of the risk of particle formation. If the same device is used to administer these medicines successively, it must be thoroughly rinsed. Due to the risk of precipitation, OLEUNOR N9E should not be administered by the same infusion line as the ampicillin antibiotic or the antiepileptic fosphenytoin nor be mixed with these two products.

• – The olive and soybean oils present in OLEUNOR N9E contain vitamin K. This does not normally affect blood thinning medicines (anticoagulants) like coumarin. However, if you take anticoagulant medicines you should tell your doctor.

• – The lipids contained in this emulsion may interfere with the results of certain laboratory tests if the blood sample is taken before the lipids have been eliminated from your bloodstream (these are generally eliminated after a period of 5 to 6 hours without receiving lipids).

• – OLEUNOR N9E contains potassium. Special care should be taken if you are taking diuretics (water pills) inhibitors of angiotensin (ACE), angiotensin II receptor antagonists (medicines to reduce high blood pressure) or immunosuppressants (used at the time of organ transplant). These types of medicines may increase potassium levels in your blood.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before you are given this medicine. There are no or limited amount of data from the use of OLEUNOR N9E in pregnant or breast-feeding women.

OLEUNOR N9E should be given during pregnancy and breast-feeding, if absolutely necessary. OLEUNOR N9E should only be given to pregnant women after careful consideration. When OLEUNOR N9E is given to pregnant women with oxytocin, may decrease sodium concentration in the body. Breast-feeding is not recommended for mothers on parenteral nutrition.

3. How OLEUNOR N9E is given

This medicine should only be given to adults and children older than 2 years of age. OLEUNOR N9E is an emulsion for infusion to be given via a tube (catheter) into a large vein of your chest. OLEUNOR N9E should be at room temperature before use. This medicine is for single use only. The infusion of 1 bag usually lasts between 12 and 24 hours.

Use in adults

Your doctor will specify a flow rate corresponding to your needs and clinical condition. The prescription may be continued for as long as it is needed, depending upon your clinical condition.

Use in children and adolescents

Dose – Children older than two years of age and adolescents

The doctor will decide the dose and for how long the medicine will be given. This will depend on age, weight, height, medical condition and the ability of the body to break down and use the ingredients in OLEUNOR N9E.

If you are given more OLEUNOR N9E than you should

If the dose given is too high or the infusion is too fast, the amino acid content may make your blood too acidic and signs of hypervolaemia (increase of circulating blood volume) may occur. The glucose levels in your blood and urine may increase, hyperosmolar syndrome (excessive blood viscosity) may develop and the lipid content may increase the level of triglycerides in your blood. Receiving a volume of OLEUNOR N9E that is too large may cause a feeling of sickness (nausea), vomiting, chills, headaches, hot flashes, excessive sweating (hyperhidrosis) and electrolyte disturbances. In such situations, the infusion must be stopped immediately. In some severe cases, your doctor may have to give you temporary kidney dialysis to help your kidneys eliminate the excess product.

To prevent these events occurring, your doctor will regularly monitor your condition and test your blood parameters. If you have any further questions on the use of this medicine, ask for more information your doctor or nurse.

4. possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. If you notice any changes in the way you feel during or after the treatment, tell your doctor or nurse right away. The tests your doctor will perform while you are taking the medicine should minimise the risk of side effects. If any abnormal signs or symptoms of an allergic reaction develop, such as sweating, fever, chills, headache, skin rashes, or breathing difficulties, the infusion should be stopped immediately.

The following side effects have been reported with the active substance of this medicine:

Common (may affect up to 1 in 10 people):

• – Fast heart rate (tachycardia)

• – Loss of appetite (anorexia)

• – Increased level of fat in the blood (hypertriglyce­ridemia)

• – Abdominal pain (stomachache)

• – Diarrhoea

• – Nausea

• – Increased blood pressure (hypertension)

Not known (frequency cannot be estimated from the available data):

• – Leakage of the infusion to the surrounding tissue (extravasation) which may result at infusion site level in pain, irritation, swelling/oedema, redness (erythema)/warmth, death of the tissue cells (skin necrosis) or blisters

• – abnormally low levels of sodium in the blood (hyponatraemia)

• – in combination with headache, nausea, vomiting, and lethargy (Hyponatraemic encephalopathy)

The following side effects have been reported with similar parenteral nutrition products:

Very rare (may affect up to 1 in 10,000 people): – Reduced ability to remove the lipids (fat overload syndrome) associated with sudden and abrupt worsening of your medical condition. The following signs of fat overload syndrome are usually reversible when the lipid emulsion infusion is stopped:

• Fever
• Reduction in red blood cells, which can make the skin pale and cause weakness or breathlessness (anaemia)
• Reduction in white blood cell count, which can

increase the risk of infection (leukopenia)

• Reduction in platelet count, which can increase the risk of bruising and/or bleeding (thrombocytopenia)
• Blood clotting (coagulation) disorders
• High levels of fats in the blood (hyperlipidaemia)
• Liver fatty infiltration (hepatomegaly)
• Worsening liver function
• Central nervous system manifestations (for example Coma).

Not known (frequency cannot be estimated from the available data

• – Allergic reactions

• – Abnormal blood test results for liver function

• – Problems with the elimination of bile (cholestasis)

• – Increase in the size of the liver (hepatomegaly)

• – Icterus (jaundice)

• – Decrease in the number of platelets (thrombocytopenia)

• – Increased nitrogen levels in the blood (azotemia) – Elevated liver enzymes

• – Formation of small particles that can block the pulmonary blood vessels (pulmonary vascular precipitates) and cause pulmonary embolism of vascular origin and difficulty in breathing (respiratory distress).

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via Yellow Card Scheme Website: or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine.

5. How OLEUNOR N9E is stored

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the container and the outer packaging after EXP. The expiry date refers to the last day of that month.

This medicine does not require any special storage conditions. Do not freeze. Store in the overpouch. Do not use this medicine if you notice visible signs of deterioration. Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

It is recommended that the product be used immediately after the peelabe seals between the 3 compartments have been opened. However, physical stability of the reconstituted emulsion has been demonstrated for 7 days (between 2°C and 8°C) followed by 48 hours at temperature not exceeding 25°C

6. contents of the pack and other information what oleunor n9e contains

• – The active substances for each bag of the reconstituted emulsion are:

• L-amino acid solution of 14.2% w/v (corresponding to 14.2 g/100 mL) (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)
• lipid emulsion of 20% w/v (corresponding to 20 g/100 mL) (refined olive oil and refined soybean oil)
• glucose solution of 27.5% w/v (corresponding to 27.5 g/100 mL) (as glucose monohydrate) with calcium.

– The other ingredients are:

What OLEUNOR N9E looks like and contents of the pack

OLEUNOR N9E is an emulsion for infusion packaged in a 3-compartment bag. One compartment contains a lipid emulsion, another compartment an amino acid solution with electrolytes and the third compartment a glucose solution with calcium. These compartments are separated by peelable seals. Before administration, the content of the compartments need to be mixed by rolling the bag onto itself, starting at the top of the bag until the peel seal is open.

Appearance prior to reconstitution:

• – The amino acid and glucose solutions are clear, colorless or slightly yellow, practically free from visible particles.

• – The lipid emulsion is homogeneous liquid with a milky appearance, showing no phase separation.

Appearance after reconstitution:

Milk-like homogeneous liquid, showing no phase separation. The 3-compartment bag is a multilayer polypropylene soft bag with peelable seals, appropriate for parenteral nutrition solutions, allowing the mixing of the three solutions prior to administration upon breakage of the seals. To prevent contact with oxygen, the bag is packaged in

a suitable overpouch under vacuum with an oxygen absorber sachet citing between the overpouch and the bag, so as to further assure the complete absence of oxygen.

Pack sizes:

1000 mL bag: 1 carton with 6 bags

1500 mL bag: 1 carton with 4 bags

2000 mL bag: 1 carton with 4 bags

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder:

Noridem Enterprises Ltd.,

Evagorou & Makariou, Mitsi Building 3, Office 115, 1065 Nicosia, Cyprus.

Manufacturer:

DEMO S.A. PHARMACEUTICAL INDUSTRY, 21st km National Road Athens-Lamia, 14568 Krioneri, Attiki, Greece,

T: +30 210 8161802, F: +30 2108161587.

This medicinal product is authorised in the Member States of the EEA under the following names:

United Kingdom: OLEUNOR N9E, Emulsion for infusion

Austria: OLEUNOR 5,7% mit Elektrolyten,

Emulsion zur Infusion

Belgium: Demoleum N9E,

emulsion pour perfusion Demoleum N9E, Emulsion zur Infusion Demoleum N9E, emulsie voor infusie

France: OLEUNOR N9E,

emulsion pour perfusion

Germany: OLEUNOR N9E,

Emulsion zur Infusion

Greece: OLEUNOR N9E,

raAdKiwpa Yia £YXUoq

Luxemburg: OLEUNOR N9E,

emulsion pour perfusion

Sweden: OLEUNOR N9E,

emulsion for infusion

Italy: Demoleum N9E,

emulsione per infusione

This leaflet was last revised in 11/2018.

The following information is intended for healthcare professionals only.

Pharmacotherapeutic group: Solutions for parenteral nutrition/com­binations. ATC code: B05 BA10.

A. QUALITATIVE AND QUANTITATIVE COMPOSITION

OLEUNOR N9E is presented in the form of a 3-compartment bag.

Each bag contains a glucose solution with calcium, a lipid emulsion and an amino acid solution with other electrolytes.

Composition of the reconstituted emulsion after mixing the contents of the 3 compartments:

• a: Mixture of refined olive oil (approximately 80%) and refined soybean oil (approximately 20%) corresponding to a ratio essential fatty acids / total fatty acids of 20%.

The excipients are:

Nutritional intakes of reconstituted emulsion for each of the bag sizes:

a: Includes calories from purified egg phospholipids

• b: Includes phosphate provided by the lipid emulsion

B. POSOLOGY AND METHOD OF ADMINISTRATION

Posology

OLEUNOR N9E is not recommended for use in children less than 2 years of age due to inadequate composition and volume (see sections 4.4, 5.1 and 5.2 of the SmPC).

The patient’s ability to eliminate fat and metabolise nitrogen and glucose, and the nutritional requirements should govern the dosage and infusion rate.

The dose should be individualised with regard to the patient’s clinical condition and body weight (bw). The maximum daily dose varies with the clinical condition of the patient and may even change from day to day. The recommended maximum daily dose mentioned below should not be exceeded. Due to the fixed composition of the multi-compartmental bag it may not be possible to meet all the patient’s nutri­tional needs at the same time. There are clinical situations where patients need a different amount of nutrients from this of the bag’s composition. In this case, any volume adjustment (dose) must take into account the effect that this change will have on the dosage of all other nutritional components of OLEUNOR N9E. For example, pediatric patients may need more than 0.2 mmol / kg / day of phosphate. In this case, the health care professionels may consider adjusting the volume (dose) of OLEUNOR N9E to meet these increased needs.

In adults

The dosage depends on the patient’s energy expenditure, clinical status, body weight and the ability to metabolise the constituents of OLEUNOR N9E, as well as additional energy or proteins provided orally / enterally: therefore, the bag size should be chosen accordingly.

The average daily requirements are:

• The requirements are 0.10 – 0.15 g nitrogen / kg bw / day (0.6 – 0.9 g amino acids / kg bw / day) in the normal nutritional state or in conditions with mild catabolic stress. In patients with moderate to high metabolic stress with or without malnutrition, the requirements are in the range of 0.15 – 0.25 g nitrogen / kg bw / day (0.9 – 1.6 g amino acids / kg bw / day). In some very special conditions (e.g. burns or marked anabolism) the nitrogen need may be even higher
• 20 to 40 kcal / kg
• 20 to 40 mL fluid / kg or 1 to 1.5 mL per expended kcal

In obese patients the dose should be based on the estimated ideal weight.

For OLEUNOR N9E, the maximal daily dose is defined by amino acids intake, 35 mL / kg corresponding to 2.0 g / kg amino acids, 3.9 g / kg glucose, 1.4 g / kg lipids, 1.2 mmol / kg sodium and 1.1 mmol / kg potassium. For a 70 kg patient, this would be equivalent to 2450 mL OLEUNOR N9E per day, resulting in an intake of 140 g amino acids, 270 g glucose, and 98 g lipids (i.e., 2058 non-protein kcal and 2622 total kcal).

Normally, the flow rate must be increased gradually during the first hour and then be adjusted to take into account the dose being administered, the daily volume intake and the duration of the infusion. The maximum infusion rate for glucose is 0.25 g / kg bw / h, for amino acid 0.1 g / kg bw / h, and for fat 0.15 g / kg bw / h.

For OLEUNOR N9E, the maximal infusion rate is 1.8 mL / kg / hour, corresponding to 0.10 g / kg / hour amino acids, 0.19 g / kg / hour glucose and 0.07 g / kg / hour lipids. The recommended infusion period is 14 – 24 hours.

In children older than 2 years of age

OLEUNOR N9E is not recommended for use in children. There have been no studies performed in the paediatric population.

The dosage depends on the patient’s energy expenditure, clinical status, body weight and the ability to metabolise constituents of OLEUNOR N9E, as well as additional energy or proteins given orally / enterally: therefore, the bag size should be chosen accordingly.

In addition, daily fluid, nitrogen and energy requirements continuously decrease with age. Two groups, ages 2 to 11 years and 12 to 18 years, are considered.

For OLEUNOR N9E in the 2 to 11 year age group, the limiting factors are phosphate concentration for daily dose (0.2 mmol / kg / day)a and lipid concentration for hourly rate. In the 12 to 18 year age group, the limiting factors are phosphate concentration for daily dose (0.2 mmol / kg / day)a and amino acid concentration for hourly rate. The resulting intakes are displayed below:

a: Recommended values from ESPEN-ESPGHAN Guidelines

Normally, the flow rate must be increased gradually during the first hour and then be adjusted to take into account the dose being administered, the daily volume intake, and the duration of the infusion.

In general, it is recommended to start the infusion in young children with low daily dose and gradually increase it up to the maximal dosage (see above).

Method and duration of administration

i For single use only. Intravenous use, infusion into a central vein.

It is recommended that, after opening the bag, the contents are used immediately and not stored for subsequent infusion.

After reconstitution, the mixture is milk-like homogeneous liquid, showing no phase separation.

For instructions for preparation and handling of the emulsion for infusion, see section 6.6 of the SmPC. Due to its high osmolarity OLEUNOR N9E can only be administered through a central vein.

The recommended duration of infusion for a parenteral nutrition bag is between 12 and 24 hours. Treatment with parenteral nutrition may be continued for as long as required by the patient’s clinical conditions.

C. INCOMPATIBILITIES

Do not add other medicinal products or substances to any components of the bag or to the reconstituted emulsion without first confirming their compatibility and the stability of the resulting preparation (in particular, the stability of the lipid emulsion).

Incompatibilities may be produced, for example, by excessive acidity (low pH) or inappropriate content of divalent cations (Ca2+ and Mg2+), which may destabilize the lipid emulsion.

As with any parenteral nutrition admixture, calcium and phosphate ratios must be considered. Excess addition of calcium and phosphate, especially in the form of mineral salts, may result in the formation of calcium phosphate precipitates.

OLEUNOR N9E contains calcium ions which pose an additional risk of coagulation in case of precipitation in blood or blood components containing a citrate preservative / anticoagulant. Ceftriaxone must not be mixed or administered simultaneously with intravenous calcium-containing solutions, including OLEUNOR N9E, through the same infusion line (e.g., via Y-connector) because of the risk of precipitation of ceftriaxone-calcium salt (see sections 4.4 and 4.5 of the SmPC).

Due to the risk of precipitation, OLEUNOR N9E should not be administered by the same infusion line as ampicillin or fosphenytoin or mixed with these two products.

Ceftriaxone and calcium-containing solutions can be administered sequentially, one after another, if different infusion lines or sites are used or if the lines of infusion are replaced or have been thoroughly rinsed between the infusions with a compatible fluid.

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

Do not administer before, simultaneously with, or after a blood transfusion through the same equipment because of the risk of pseudoaggluti­nation.

D. SPECIAL PRECAUTIONS FOR DISPOSAL AND OTHER HANDLING

An overview of the preparation steps for the administration of OLEUNOR N9E are provided in Figure 1, as follows.

To open

• – Remove the protective overpouch.

• – Discard the oxygen absorber sachet.

• – Confirm the integrity of the bag and of the peelable seals. Use only if the bag is not damaged; if the peelable seals are intact (i.e., no mixture of the contents of the 3 compartments); if the amino acid solution and the glucose solution are clear, colourless, or slightly yellow, and practically free of visible particles; and if the lipid emulsion is a homogeneous liquid with a milky appearance, showing no phase separation.

Mixing the solutions and the emulsion

• – Ensure that the product is at room temperature when breaking the peelable seals.

• – Manually roll the bag onto itself, starting at the top of the bag (hanger end). The peelable seals will disappear from the side near the inlets. Continue to roll the bag until the seals are open along approximately half of their length.

• – Mix by inverting the bag at least 3 times.

• – After reconstitution, the mixture is a homogeneous emulsion with a milky appearance.

i

Additions

The capacity of the bag is sufficient to enable additions such as vitamins, electrolytes and trace elements. Any additions (including vitamins) may be made into the reconstituted mixture (after the peelable seals have been opened and after the contents of the 3 compartments have been mixed). Vitamins may also be added into the glucose compartment before the mixture is reconstituted (before opening the peelable seals and before mixing the 3 compartments). When making additions to formulations containing

X electrolytes, the amount of electrolytes already present in the bag should be taken into account. Additions must be performed by qualified personnel under aseptic conditions.

OLEUNOR N7E may be supplemented with electrolytes according to the tables below:

• a: Value corresponding to the addition of inorganic phosphate.

• b: Including phosphate provided by the lipid emulsion.

Trace elements and vitamins:

To perform an addition:

• – Aseptic conditions must be respected.

• – Prepare the injection site of the bag.

• – Puncture the injection site and inject the additives using an injection needle or a reconstitution device.

• – Mix content of the bag and the additives.

Preparation of the infusion

• – Aseptic conditions must be respected.

• – Suspend the bag.

• – Remove the plastic protector from the administration outlet.

• – Firmly insert the spike of the infusion set into the administration outlet.

• Figure 1: Preparation steps prior to administration of OLEUNOR N9E:

1.

2.

3.

4.

5.

6.

Lift the hanger area to remove solution from the upper bag. Roll the upper part of the bag firmly until peel seals are fully open (approximately half of the length).

X Administration

For single use only.

• i Only administer the product after the peelable seals between the 3 compartments have been broken and the contents of the 3 compartments have been mixed.
• Ensure that the final emulsion for infusion does not show any evidence of phase separation.
• After opening the bag, the contents must be used immediately. The opened bag must never be stored for a subsequent infusion. Do not reconnect any partially used-bag.
• Do not connect bags in series in order to avoid the possibility of air embolism due to gas contained in the primary bag.
• Any unused product or waste material and all necessary devices must be discarded.

Extravasation

Catheter site should be monitored regularly to identify signs of extravasation.

If extravasation occurs, the administration should be stopped immediately, keeping the inserted catheter or cannula in place for immediate management of the patient. If possible, aspiration should be performed through the inserted catheter / cannula in order to reduce the amount of fluid present in the tissues before removing the catheter / cannula.

When involving an extremity, the concerned limb should be elevated.

Depending on the extravasated product (including the product(s) being mixed with OLEUNOR N9E, if applicable) and stage / extend of any injury, appropriate specific measures should be taken. Options for management may include non-pharmacologic, pharmacologic and/or surgical intervention. In case of large extravasation, plastic surgeon advice should be sought within the first 72 hours. The extravasation site should be monitored at least every 4 hours during the first 24 hours, then at least once per day. The infusion should not be restarted in the same central vein.

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