Numeta

Package Leaflet: Information for the User

NUMETA G13E, emulsion for infusion

Read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your paediatrician, pharmacist, or nurse.
• If your child experiences any side effects, inform the paediatrician or nurse. This includes any side effects not listed in this leaflet. See section 4.

Contents of this leaflet:

1. What Numeta G13E is and what it is used for
2. What you need to know before your child is given Numeta G13E
3. How Numeta G13E is administered
4. Possible side effects
5. How to store Numeta G13E
6. Contents of the pack and other information

1. What Numeta G13E is and what it is used for

Numeta G13E is a specially formulated emulsion for nutrition in preterm infants.
It is administered through a tube inserted into your baby's vein when they are unable to take orally all the nutrients they need.
Numeta is supplied as a 3-compartment bag, with each separate compartment containing:
a 50% glucose solution
a 5.9% pediatric amino acid solution with electrolytes
a 12.5% lipid (fat) emulsion
Two or three of these solutions are mixed together in the bag before administration to your baby, depending on their needs.
Numeta G13E must be used exclusively under medical supervision.

2. What you should know before your child is given Numeta G13E

Your child must not be given Numeta G13E in the following cases:
With glucose and amino acid/electrolyte solutions mixed in the bag ("2 in 1"):

• If your child is allergic to eggs, soy, peanuts, or any other component of this medicine or component of the container (listed in section 6)
• If the use of protein components causes problems for your child’s body
• If your child has high blood concentrations of any of the electrolytes contained in Numeta G13E
• Numeta G13E (or other solutions containing calcium) must not be administered simultaneously with ceftriaxone (an antibiotic), even if separate infusion lines are used. There is a fatal risk of particle formation in the newborn’s bloodstream
• If your child suffers from hyperglycaemia (particularly high blood sugar levels)

With glucose, amino acid/electrolyte and lipid solutions mixed in the bag ("3 in 1"):
All situations listed under “2 in 1” plus the following:

• If your child has particularly high levels of fats in the blood.

In all cases, the doctor will decide whether your child should receive this medicine based on factors such as age, weight, and clinical condition. The doctor will also consider the results of laboratory tests performed.

Warnings and precautions
Talk to the paediatrician or nurse before your child is given Numeta G13E.
When used in neonates and children under 2 years of age, the solution (in bags and administration sets) must be protected from light exposure until administration is complete. Exposure of Numeta G13E to ambient light, especially after addition of trace elements and/or vitamins, may generate peroxides and other degradation products, which can be reduced by protecting from light.

Allergic reactions
Infusion must be stopped immediately if signs or symptoms of an allergic reaction occur (e.g. fever, sweating, chills, headache, skin rash, or breathing difficulties). This medicine contains soybean oil, which rarely may cause severe hypersensitivity reactions. It has been observed rarely that individuals allergic to peanut proteins may also be allergic to soybean proteins.
Numeta G13E contains glucose derived from corn starch. Therefore, Numeta G13E should be used with caution in patients with a known allergy to corn or corn-derived products.

Risk of particle formation with ceftriaxone (antibiotic):
A specific antibiotic called ceftriaxone must not be mixed or administered simultaneously with calcium-containing solutions (including Numeta G13E) given by intravenous infusion.
The doctor is aware of this and will not administer them together, even through different infusion lines or different infusion sites.

Formation of small particles in the blood vessels of the lungs:
Breathing difficulties may also be a sign that small particles have formed, blocking blood vessels in the lungs (pulmonary vascular precipitates). If your child experiences breathing difficulties, contact the paediatrician or nurse. They will decide which actions to take.

Infections and sepsis
The doctor will carefully monitor your child for any signs of infection.
The risk of infection can be reduced by using an aseptic technique (germ-free technique) during catheter placement and maintenance, as well as in the preparation of the nutritional formula.
Sometimes, children may develop infection and sepsis (presence of bacteria in the blood) when a tube is inserted into a vein (intravenous catheter). Some medicines and certain diseases may increase the risk of developing infection or sepsis. Patients requiring parenteral nutrition (administration of nutrients through a tube inserted into a vein) may be more susceptible to developing infections due to their underlying medical conditions.

Fat overload syndrome
Fat overload syndrome has been reported with similar medicines. A reduced or limited ability to clear the lipids present in Numeta G13E, or overdosing, may lead to a "fat overload syndrome". (See section 3 and section 4).

Changes in blood chemical parameters
The doctor will monitor and check your child’s fluids, blood chemical composition, and other blood parameters during treatment with Numeta G13E. Sometimes, refeeding severely malnourished patients may cause changes in blood chemical levels that require correction. Additionally, swelling and excessive fluid accumulation in tissues may occur. It is recommended to start parenteral nutrition slowly and with great care.

Monitoring and adjustments:
The doctor will keep your child under close surveillance and adjust the dose of Numeta G13E according to your child’s individual needs, especially if the following conditions are present:

• Severe post-traumatic conditions
• Severe diabetes mellitus
• Shock
• Heart attack
• Severe infection
• Certain types of coma

Use with caution:
Numeta G13E should be used with caution if your child has:

• Pulmonary oedema (fluid in the lungs) or heart failure
• Severe liver problems
• Problems in properly utilizing nutrients
• Hyperglycaemia
• Kidney problems
• Severe metabolic disorders (inability of the body to break down substances normally)
• Blood coagulation disorders

Your child’s fluid status, liver function values, and/or blood values will be closely monitored. Limited data are available on the use of this medicine in preterm neonates (premature infants) with a gestational age of less than 28 weeks.

Other medicines and Numeta G13E
Inform the doctor if your child is taking or using, has recently taken or used, or might take any other medicines.

• Numeta G13E must not be administered simultaneously with: ceftriaxone (an antibiotic), even through separate infusion lines, due to the risk of particle formation.
• Blood through the same infusion set due to the risk of pseudoagglutination (clumping of red blood cells).
• Ampicillin, fosphenytoin, or furosemide through the same infusion line due to the risk of particle formation.

Coumarin and warfarin (anticoagulants):
The doctor will carefully monitor your child if they are taking coumarin or warfarin. These medicines are anticoagulants that prevent blood clotting. Olive oil and soybean oil naturally contain vitamin K1. Vitamin K1 may interfere with medicines such as coumarin and warfarin.

Laboratory tests
The lipids contained in this emulsion may interfere with the results of certain laboratory tests. Laboratory tests should be performed after a 5–6 hour interval from lipid administration, provided no additional lipids are being administered.

Interactions of Numeta G13E with medicines that may alter potassium levels/metabolism
Numeta G13E contains potassium. High blood potassium levels may cause abnormal heart rhythms. Particular caution is required in patients taking diuretics (medicines that reduce fluid retention), ACE inhibitors (medicines for high blood pressure), angiotensin II receptor antagonists (medicines for high blood pressure), or immunosuppressants (medicines that may lower the body’s normal immune defences). These types of medicines may increase potassium levels.

3. How Numeta G13E is administered

Your child must always be given Numeta G13E exactly as indicated by the doctor.
Check with the doctor if you are unsure.

Age groups
Numeta G13E has been designed to meet the nutritional needs of preterm infants.
Numeta G13E may not be suitable for some preterm infants, as their clinical condition might require customized formulations to meet their specific nutritional requirements. The doctor will decide whether this medicine is appropriate for your child.

Administration
This medicine is an emulsion for infusion. It is administered through a plastic tube inserted into a vein in your child's arm or into a large vein in the chest.

The paediatrician might decide not to administer lipids to your child. The Numeta G13E bag is designed so that only the membrane separating the amino acid/electrolyte compartment from the glucose compartment can be broken. In this case, the membrane separating the amino acid compartment from the lipid compartment remains intact. Therefore, the contents of the bag can be infused without lipids.

When used in neonates and children under 2 years of age, the solution (in the bags and administration sets) must be protected from exposure to light until the end of administration (see section 2).

Dosage and duration of treatment
The doctor will decide the dose and how long it will be administered. The dosage depends on your child's nutritional needs. The dosage will be based on your child's body weight, clinical condition, and the ability of their body to break down and use the components of Numeta G13E. Additional nutrients or proteins may also be given orally/enterally.

If your child is given too much Numeta G13E

Symptoms
Excessive doses of this medicine, or administration that is too rapid, may cause the following:

• nausea (feeling sick)
• vomiting
• chills
• electrolyte imbalances (abnormal levels of electrolytes in the blood)
• signs of hypervolaemia (increased blood volume, excess fluid in the blood vessels)
• acidosis (increased acidity of the blood)

In such cases, stop the infusion immediately. The doctor will decide whether further measures are needed. An overdose of the fats contained in Numeta G13E may cause a "fat overload syndrome", which is usually reversible after stopping the infusion. In neonates and young children (infants), fat overload syndrome has been associated with respiratory disorders leading to reduced oxygen levels in the body (difficulty breathing) and conditions causing increased blood acidity (acidosis).

To prevent such events, the doctor will regularly monitor your child's condition and check their blood levels during treatment.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not all children will
experience them.
If you notice any changes in your child's health during or after treatment, inform the
doctor or nurse immediately.
The tests that the doctor will carry out while your child is receiving this medicine help
reduce the risk of side effects.
If signs of an allergic reaction occur, the infusion must be stopped and the doctor must
be contacted immediately. This may be serious and signs may include:

• sweating
• chills
• headache
• skin rash
• breathing difficulties

Other side effects that have been observed are:
Common (may affect up to 1 in 10 people):

• Low levels of phosphate in the blood (hypophosphatemia)
• High levels of sugar in the blood (hyperglycemia)
• High levels of calcium in the blood (hypercalcemia)
• High levels of triglycerides in the blood (hypertriglyceridemia)
• An electrolyte imbalance (hyponatremia)

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

• High levels of lipids in the blood (hyperlipidemia)
• A condition in which bile fails to flow from the liver to the duodenum (cholestasis). The duodenum is part of the intestine.

Not known: frequency cannot be estimated from the available data (These adverse
reactions have been reported only for Numeta G13E and G16E when administered
peripherally with insufficient dilution):

• Skin necrosis
• Soft tissue damage
• Extravasation

The following side effects have been reported with other parenteral nutrition medicines:
Reduced or limited ability to clear the lipids contained in Numeta may result in a
"fat overload syndrome". The following signs and symptoms of this syndrome are usually
reversible after stopping the lipid emulsion infusion:
o sudden and unexpected worsening of the patient's medical condition
o high levels of fat in the blood (hyperlipidemia)
o fever
o fat infiltration into the liver (hepatomegaly)
o worsening of liver function
o reduction in red blood cells, which may make the skin pale and cause weakness or shortness of breath (anemia)
o low white blood cell count, which may increase the risk of infection (leukopenia)
o low platelet count, which may increase the risk of bruising and/or bleeding (thrombocytopenia)
o coagulation disorders that impair the blood's ability to clot
o respiratory disorders leading to reduced oxygen in the body (dyspnoea)
o conditions leading to increased blood acidity (acidosis)
o coma, requiring hospitalization

• Formation of particles that may cause blockage of blood vessels in the lungs (pulmonary vascular precipitates) or breathing difficulties.

Reporting of side effects
If your child experiences any side effect, including those not listed in this leaflet, please
consult the doctor or nurse.
You may also report side effects directly (see details below).
By reporting side effects, you can help provide more information on the safety of this
medicine.
Side effects can also be reported directly via the national reporting system at the website https://www.aifa.gov.it/content/segnalazioni-
reazioni-avverse.

5. How to store Numeta G13E

Keep this medicine out of the sight and reach of children when not in use.
When used in neonates and children under 2 years of age, the solution (in bags and administration sets) must be protected from light exposure until the end of administration (see section 2).
Do not use this medicine after the expiry date stated on the bag and outer packaging (MM/YYYY). The expiry date refers to the last day of the month.
Do not freeze.
Store in the outer packaging.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

Description of the appearance of Numeta G13 and contents of the pack
Numeta G13E is presented as a three-compartment bag. Each bag contains a sterile combination of a glucose solution, a pediatric amino acid solution with electrolytes, and a lipid emulsion, as described below.

Container size	50% glucose solution	5.9% amino acid solution with electrolytes	12.5% lipid emulsion
300 mL	80 mL	160 mL	60 mL

Appearance prior to reconstitution:
The solutions in the amino acid and glucose compartments are clear, colorless
or slightly yellow.
The lipid emulsion compartment contains a uniform liquid of milky white color.
Appearance after reconstitution:

• The "2-in-1" infusion solution (amino acids/electrolytes and glucose) is clear, colorless or slightly yellow. The "3-in-1" emulsion for infusion is uniform and milky white in color.

The three-compartment bag is a multilayer plastic bag.
To prevent contact with air, the Numeta G13E bag is packaged in an outer oxygen-barrier pouch, which also contains an oxygen absorber and an oxygen indicator.
Packaging:
300 ml bag: 10 units per cardboard box
1 bag of 300 ml
Not all pack sizes may be marketed.
Marketing Authorization Holder
Baxter S.p.A.
Via Del Serafico 89
00142 Rome
Italy
Responsible Lot Release Manufacturer:
Baxter SA
Boulevard René Branquart 80
7860 Lessines
(Belgium)
This medicinal product is authorized in the Member States of the European Economic Area with the following names:

Austria Germany	Numeta G 13 % E Emulsion for Infusion
Belgium Luxembourg	NUMETZAH G13%E, emulsion for infusion
France	NUMETAH G13%E PREMATURES, emulsion for infusion
Denmark Norway Sweden	Numeta G13E
Czech Republic	Numeta G 13 % E
Greece	NUMETA Preterm G 13 E
Netherlands	Numeta G13%E emulsion for infusion
Ireland Malta United Kingdom	Numeta G13%E Preterm, Emulsion for Infusion
Italy	Numeta G13E emulsion for infusion
Finland	Numeta G13E infusion solution, emulsion
Poland	Numeta G 13 % EPreterm
Portugal	Numeta G13%E
Spain	Numeta G13%E, emulsion for perfusion

This patient information leaflet was last approved on: May 2024
The following information is intended exclusively for medical professionals or
healthcare providers*
*Please note that in some cases this medicine may be administered at home
by parents or other caregivers. In such cases, parents or caregivers
must read this information.
Do not add anything to the bag before verifying its compatibility. Particles may form or the
lipid emulsion may break. This could lead to blockage of blood vessels.
Numeta G13E must be at room temperature before use.
Before using Numeta G13E, prepare the bag as shown below.
Check that the bag is not damaged. Use the bag only if it is undamaged.
The appearance of an intact bag is as follows:

• The non-permanent separation membranes are intact. This indicates that the contents of the three compartments have not mixed.
• The amino acid and glucose solutions are clear, colorless or slightly yellow, without visible particles.
• The lipid emulsion is a uniform white milky liquid.

Before opening the outer wrapper, check the color of the oxygen indicator.
Compare it with the reference color printed next to the OK symbol
in the printed area of the indicator label.
Do not use the bag if the color of the oxygen indicator does not match the
reference color printed next to the OK symbol.
Figures 1 and 2 illustrate how to remove the outer protective wrapper. Discard
the outer wrapper, the oxygen indicator, and the oxygen absorber.

Figure 1 Figure 2
Preparation of the mixed emulsion:
ensure that the medicine is at room temperature when breaking
the non-permanent separation membranes.
Place the bag on a flat, clean surface.
Activation of the 3-compartment bag (mixing the 3 solutions by
breaking the 2 non-permanent membranes)
Step 1: Begin by rolling the bag from the side of the D-ring

Step 2: Apply pressure until the separation membranes are opened.

Step 3: Change direction by rolling the bag toward the D-ring. Continue until
the membrane is completely open.
Repeat the same procedure to complete the opening of the second membrane.

Step 4: Invert the bag at least three times to completely mix the contents.
The appearance of the mixed solution should resemble a white milky emulsion.

Step 5: Remove the protective cap from the administration port and insert the
intravenous infusion set.

Activation of the 2-compartment bag (mixing the 2 solutions by
breaking the non-permanent membrane between the amino acid compartment and the
glucose compartment)
Step 1:
To mix only 2 solutions, roll the bag from the upper corner (end with the D-ring) of the membrane separating the solutions.
Apply pressure to open the membrane separating the glucose and
amino acid compartments.

Step 2: Position the bag so that the compartment containing the lipid emulsion
is closest to the operator.
Roll the bag, protecting the lipid emulsion compartment with the palms of your hands.

Step 3: With one hand, apply pressure while rolling the bag toward the injection ports.

Step 4:
Change direction by rolling the bag toward the upper side (end with the D-ring).
Press with the other hand, continuing until the membrane separating the
amino acid and glucose solutions is completely open.

Step 5: Invert the bag at least three times to completely mix the contents.
The appearance of the mixed solution should be clear, colorless or slightly yellow.

Step 6: Remove the protective cap from the administration port and insert the
intravenous infusion set.

The flow rate should be gradually increased during the first hour. The infusion rate
must be adjusted according to the following factors:
dose to be administered
daily volumes to be infused
duration of infusion
Method of administration
When used in neonates and children under 2 years of age, the solution (in bags
and administration sets) must be protected from light exposure until administration is complete.
Use of a 1.2 micron filter is recommended for the administration of Numeta
G13E.
Due to its high osmolarity, undiluted Numeta G13E can only be administered
through a central vein. However, adequate dilution of Numeta G13E with
water for injections reduces osmolarity and allows peripheral infusion.
The following formula indicates the effect of dilution on the osmolarity of the bags.

The following table shows examples of osmolarity for activated 2CB and activated 3CB mixtures after addition of water for injections:

	Amino acids and glucose (2-chamber bags activated)	Amino acids, glucose and lipids (3-chamber bags activated)
Initial volume in the bag (mL)	240	300
Initial osmolarity (approx. mOsm/L)	1400	1150
Volume of water added (mL)	240	300
Final volume after addition (mL)	480	600
Osmolarity after addition (approx. mOsm/L)	700	575

Addition of additives:
Exposure to light of intravenous parenteral nutrition solutions, especially after addition of trace elements and/or vitamins, may have adverse effects on clinical outcomes in neonates due to the formation of peroxides and other degradation products. When used in neonates and children under 2 years of age, Numeta G13E must be protected from ambient light until completion of administration.
Compatible additives may be added through the injection site into the reconstituted mixture (after opening the non-permanent membranes and after mixing the contents of the two or three compartments).
Vitamins may also be added to the glucose compartment before the mixture is reconstituted (before opening the non-permanent separation membranes and before mixing the solutions and the emulsion).
Additions of commercially available solutions of trace elements (identified as TE1 and TE4), vitamins (identified as lyophilisate V1 and emulsion V2), and electrolytes in defined quantities are shown in Tables 1–4.

1. 1. Compatibility with TE4, V1 and V2

Table 1: Compatibility of the 3-in-1 bag (3CB activated) with and without dilution with water

For 300 mL (3-in-1 mixture with lipids)
	Undiluted mixture			Diluted mixture
Additives	Level included	Maximum additional amount	Maximum total level	Level included	Maximum additional amount	Maximum total level
Sodium (mmol)	6.6	5.0	11.6	6.6	5.0	11.6
Potassium (mmol)	6.2	4.2	10.4	6.2	4.2	10.4
Magnesium (mmol)	0.47	0.83	1.3	0.47	0.83	1.3
Calcium (mmol)	3.8	3.5	7.3	3.8	3.5	7.3
Phosphate* (mmol)	3.8	2.5	6.3	3.8	2.5	6.3
Trace elements and vitamins		15 mL TE4 + 1.5 vials V1 + 25 mL V2	15 mL TE4 + 1.5 vials V1 + 25 mL V2		15 mL TE4 + 1.5 vials V1 + 25 mL V2	15 mL TE4 + 1.5 vials V1 + 25 mL V2
Water for injections					300 mL	300 mL

Table 2: Compatibility of the 2-in-1 bag (2CB activated) with and without dilution with water

For 240 mL (2 in 1 without lipids mixture)
	Undiluted mixture			Diluted mixture
Additives	Included level	Maximum additional amount	Maximum total level	Included level	Maximum additional amount	Maximum total level
Sodium (mmol)	6.4	17.6	24	6.4	0.0	6.4
Potassium (mmol)	6.2	17.8	24	6.2	0.0	6.2
Magnesium (mmol)	0.47	2.13	2.6	0.47	0.0	0.47
Calcium (mmol)	3.8	3.5	7.3	3.8	0.0	3.8
Phosphate* (mmol)	3.2	4.0	7.2	3.2	0.0	3.2
Trace elements and vitamins		2.5 mL TE4 + ¼ vial V1	2.5 mL TE4 + ¼ vial V1		2.5 mL TE4 + ¼ vial V1	2.5 mL TE4 + ¼ vial V1
Water for injections					240 mL	240 mL

1. 2. Compatibility with TE1, V1 and V2 Table 3: Compatibility of the 3-in-1 bag (activated 3CB) with and without dilution with water

For 300 mL (3-in-1 mixture with lipids)
	Undiluted mixture			Diluted mixture
Additives	Level included	Maximum additional amount	Maximum total level	Level included	Maximum additional amount	Maximum total level
Sodium (mmol)	6.6	5.0	11.6	6.6	0.0	6.6
Potassium (mmol)	6.2	4.2	10.4	6.2	0.0	6.2
Magnesium (mmol)	0.47	0.83	1.3	0.47	0.0	0.47
Calcium (mmol)	3.8	1.9	5.7	3.8	0.0	3.8
Phosphate* (mmol)	3.8	2.5	6.3	3.8	0.0	3.8
Trace elements and vitamins		2.5 mL TE1 + ¼ vial V1 + 2.5 mL V2	2.5 mL TE1 + ¼ vial V1 + 2.5 mL V2		2.5 mL TE1 + ¼ vial V1 + 2.5 mL V2	2.5 mL TE1 + ¼ vial V1 + 2.5 mL V2
Water for injections					300 mL	300 mL

Table 4: Compatibility of the 2-in-1 bag (activated 2CB) with and without dilution with water

Per 240 mL (2 in 1 non-lipid mixture)
	Undiluted mixture			Diluted mixture
Additives	Included level	Maximum additional amount	Maximum total level	Included level	Maximum additional amount	Maximum total level
Sodium (mmol)	6.4	17.6	24	6.4	0.0	6.4
Potassium (mmol)	6.2	17.8	24	6.2	0.0	6.2
Magnesium (mmol)	0.47	2.13	2.6	0.47	0.0	0.47
Calcium (mmol)	3.8	3.5	7.3	3.8	0.0	3.8
Phosphate* (mmol)	3.2	4.0	7.2	3.2	0.0	3.2
Trace elements and vitamins		2.5 mL TE1 + ¼ vial V1	2.5 mL TE1 + ¼ vial V1		2.5 mL TE1 + ¼ vial V1	2.5 mL TE1 + ¼ vial V1
Water for injections					240 mL	240 mL

The composition of vitamin and trace element preparations is shown in tables 5 and 6.
Table 5: Composition of the commercial trace element preparation used:

Composition per vial	TE1 (10 ml)	TE4 (10 ml)
Zinc	38.2 µmol or 2.5 mg	15.3 µmol or 1 mg
Selenium	0.253 µmol or 0.02 mg	0.253 µmol or 0.02 mg
Copper	3.15 µmol or 0.2 mg	3.15 µmol or 0.2 mg
Iodine	0.0788 µmol or 0.01 mg	0.079 µmol or 0.01 mg
Fluoride	30 µmol or 0.57 mg
Manganese	0.182 µmol or 0.01 mg	0.091 µmol or 0.005 mg

Table 6: Composition of the commercial vitamin preparation used:

Composition per vial	V1	V2
Vitamin B1	2.5 mg
Vitamin B2	3.6 mg
Nicotinamide	40 mg
Vitamin B6	4.0 mg
Pantothenic Acid	15.0 mg
Biotin	60 µg
Folic Acid	400 µg
Vitamin B12	5.0 µg
Vitamin C	100 mg
Vitamin A		2300 IU
Vitamin D		400 IU
Vitamin E		7 IU
Vitamin K		200 µg

To perform additions:

• Work under aseptic conditions
• Prepare the injection site of the bag
• Pierce the injection site and inject the additives using an injection needle or reconstitution device
• Mix the contents of the bag and the additives

Preparation of the infusion:

• Work under aseptic conditions
• Suspend the bag
• Remove the plastic protector from the administration port
• Firmly insert the spike of the infusion set into the administration port

Administration of the infusion:

• For single use only
• Administer the medicinal product only after opening the non-permanent separation membranes between the two or three compartments and mixing the contents of the two or three compartments
• Ensure that the final infused emulsion from the three activated compartments shows no evidence of phase separation, or that the final infused solution from the two activated compartments shows no presence of particles
• After breaking the non-permanent membranes, the contents must be used immediately. Numeta G13E must not be stored for subsequent infusion
• Do not connect partially used bags
• Do not connect bags in series to avoid the risk of gas embolism due to possible residual gas in the main bag
• Use of a 1.2 micron filter is recommended when administering Numeta G13E
• When used in neonates and children under 2 years of age, protect from light exposure until completion of administration. Exposure of Numeta G13E to ambient light, especially after addition of trace elements and/or vitamins, may generate peroxides and other degradation products, which can be minimized by protecting from light exposure. Any unused product, waste materials, and all disposable devices must be properly discarded and not reused

Shelf life after reconstitution
Use the medicinal product immediately after opening the non-permanent membranes between the two or three compartments. Stability studies of mixtures have been conducted for 7 days at a temperature between 2°C and 8°C, followed by 48 hours at 30°C.

Shelf life after supplementation (electrolytes, trace elements, vitamins, water):
For specific mixtures, the physical stability of the Numeta formulation has been demonstrated at a temperature between 2°C and 8°C for 7 days, followed by 48 hours at 30°C. Information on these additions is specified in section 6.6 of the SmPC (Summary of Product Characteristics).

From a microbiological standpoint, the medicinal product should be used immediately. Otherwise, the duration and conditions of storage after mixing and prior to use are the responsibility of the user and must not exceed 24 hours at a temperature between 2°C and 8°C, unless reconstitution/dilution/supplementation was performed under controlled and validated aseptic conditions.

Do not use Numeta G13E if the bag is damaged. This is what a damaged bag looks like:

• the non-permanent separation membranes are broken
• one of the compartments contains a mixture of the solutions
• the amino acid and glucose solutions are not clear, colourless or slightly yellow and/or contain visible particles
• the lipid emulsion is not a uniform white milky liquid

Medicinal products must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

What Numeta G13E contains:
Active substances:

Composition
Active ingredient	2CB activated (240 ml)	3CB activated (300 ml)
Amino Acid Compartment
Alanine	0.75 g	0.75 g
Arginine	0.78 g	0.78 g
Aspartic acid	0.56 g	0.56 g
Cysteine	0.18 g	0.18 g
Glutamic acid	0.93 g	0.93 g
Glycine	0.37 g	0.37 g
Histidine	0.35 g	0.35 g
Isoleucine	0.62 g	0.62 g
Leucine	0.93 g	0.93 g
Lysine monohydrate (as lysine)	1.15 g (1.03 g)	1.15 g (1.03 g)
Methionine	0.22 g	0.22 g
Ornithine hydrochloride (as ornithine)	0.30 g (0.23 g)	0.30 g (0.23 g)
Phenylalanine	0.39 g	0.39 g
Proline	0.28 g	0.28 g
Serine	0.37 g	0.37 g
Taurine	0.06 g	0.06 g
Threonine	0.35 g	0.35 g
Tryptophan	0.19 g	0.19 g
Tyrosine	0.07 g	0.07 g
Valine	0.71 g	0.71 g
Potassium acetate	0.61 g	0.61 g
Calcium chloride dihydrate	0.55 g	0.55 g
Magnesium acetate tetrahydrate	0.10 g	0.10 g
Sodium glycerophosphate hydrate	0.98 g	0.98 g
Glucose Compartment
Glucose monohydrate (as anhydrous glucose)	44.00 g (40.00 g)	44.00 g (40.00 g)
Lipid Compartment
Purified olive oil (approximately 80%) + purified soybean oil (approximately 20%)		7.5 g

The reconstituted solution/emulsion provides the following:

Composition
	Activated 2CB		Activated 3CB
Per unit volume (ml) Nitrogen (g) Amino acids (g) Glucose (g) Lipids (g) Energy Total calories (kcal) Non-protein calories (kcal) Calories from glucose (kcal) Lipid calories (kcal)aNon-protein calories/nitrogen (kcal/g N) Lipid calories / non-protein calories (%) Lipid calories / total calories (%) Electrolytes Sodium (mmol) Potassium (mmol) Magnesium (mmol) Calcium (mmol) Phosphate (mmol)bAcetate (mmol) Malate (mmol) Chloride (mmol)	240 1.4 9.4 40.0 0 198 160 160 0 113 ND ND 6.4 6.2 0.47 3.8 3.2 7.2 3.2 9.3	100 0.59 3.9 16.7 0 82 67 67 0 113 ND ND 2.7 2.6 0.20 1.6 1.3 3.0 1.3 3.9	300 1.4 9.4 40.0 7.5 273 235 160 75 165 32 28 6.6 6.2 0.47 3.8 3.8 7.2 3.2 9.3	100 0.47 3.1 13.3 2.5 91 78 53 25 165 32 28 2.2 2.1 0.16 1.3 1.3 2.4 1.1 3.1
pH (approx.) Approximate osmolarity (mOsm/L)	5.5 1400	5.5 1400	5.5 1150	5.5 1150

The excipients are:

Package Leaflet: Information for the User

NUMETA G16E, emulsion for infusion

Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your paediatrician, pharmacist, or nurse.
• If your child experiences any side effects, inform your paediatrician or nurse. This includes any side effects not listed in this leaflet. See section 4. Contents of this leaflet:

1. What Numeta G16E is and what it is used for
2. What you need to know before your child is given Numeta G16E
3. How Numeta G16E is given
4. Possible side effects
5. How to store Numeta G16E
6. Contents of the pack and other information

1. What Numeta G16E is and what it is used for

Numeta G16E is a nutrition emulsion specifically formulated for full-term neonates and children up to 2 years of age. It is administered through a tube inserted into your child's vein when your child is unable to receive nutrition by mouth.
Numeta is supplied as a three-compartment bag, with each separate compartment containing:
a 50% glucose solution
a 5.9% pediatric amino acid solution with electrolytes
a 12.5% lipid (fat) emulsion
Depending on your child's needs, 2 or 3 of these solutions are mixed together within the bag before administration to your child.
Numeta must be used exclusively under medical supervision.

2. What you should know before your child is given Numeta G16E

Numeta G16E must not be given to your child in the following cases:
With 2 solutions mixed in the bag (2 in 1):

• If your child is allergic to egg proteins, soy, peanuts, or to any of the components of the glucose or amino acid compartments (listed in section 6).
• If your child’s body has problems forming protein "building blocks".
• If your child has high blood concentrations of any of the electrolytes included in Numeta G16E.
• If your child is a newborn (≤28 days of age), Numeta G16E (or other calcium-containing solutions) must not be administered simultaneously with ceftriaxone (an antibiotic), even if separate infusion lines are used. There is a risk of fatal particle formation in the newborn’s bloodstream.
• If your child suffers from hyperglycemia (particularly high blood sugar levels).

With 3 solutions mixed in the bag (3 in 1):

• All the situations listed under “2 in 1” plus the following:
• If your child has particularly high levels of fats in the blood. In all cases, your doctor will decide whether your child should receive this medicine based on factors such as age, weight, and clinical condition. Your doctor will also consider the results of laboratory tests.

Warnings and precautions
Talk to your pediatrician or nurse before your child is given Numeta G16E.
When used in newborns and children under 2 years of age, the solution (in bags and administration sets) must be protected from light exposure until the end of administration. Exposure of Numeta G16E to ambient light, especially after the addition of trace elements and/or vitamins, may generate peroxides and other degradation products, which can be minimized by protecting from light.

Allergic reactions:
Infusion must be stopped immediately if signs or symptoms of an allergic reaction occur (e.g., fever, sweating, chills, headache, skin rash, or breathing difficulties). This medicine contains soybean oil, which rarely may cause severe hypersensitivity reactions. It has been observed rarely that individuals allergic to peanut proteins may also be allergic to soybean proteins. Numeta G16E contains glucose derived from corn starch. Therefore, Numeta G16E should be used with caution in patients with known allergy to corn or corn-derived products.

Risk of particle formation with ceftriaxone (antibiotic):
An antibiotic called ceftriaxone must not be mixed or administered simultaneously with any calcium-containing solution (including Numeta G16E) given by intravenous infusion. The doctor is aware of this and will not administer them together, even through separate infusion lines or different infusion sites.

However, the doctor may administer calcium and ceftriaxone sequentially, one after the other, if different infusion sites are used, or if the infusion lines are replaced or thoroughly flushed with physiological saline solution between infusions to prevent precipitation.

Formation of small particles in lung blood vessels:
Breathing difficulties could also be a sign of small particles forming and blocking blood vessels in the lungs (pulmonary vascular precipitates). If your child experiences any breathing difficulties, inform the pediatrician or nurse immediately. They will determine the necessary actions.

Infections and sepsis:
Your doctor will carefully monitor your child for any signs of infection. The risk of infection can be reduced by using an "aseptic technique" (germ-free technique) during catheter placement and maintenance, as well as during the preparation of the nutritional formula.
Sometimes, children may develop an infection and sepsis (bacteria in the blood) when a tube is inserted into a vein (central venous catheter). Certain medicines and medical conditions may increase the risk of developing infection or sepsis. Patients requiring parenteral nutrition (nutrient delivery through a vein) may be more susceptible to infections due to their underlying medical conditions.

Fat overload syndrome:
Fat overload syndrome has been reported with similar products. A reduced or limited ability to clear lipids present in Numeta G16E, or an overdose, may lead to a "fat overload syndrome." (See section 3 and section 4.)

Changes in blood chemical parameters:
Your doctor will monitor and assess your child’s fluid balance, blood chemistry, and other blood parameters, as refeeding severely malnourished patients may sometimes cause changes in blood chemical levels. Additionally, swelling and excessive fluid accumulation in tissues may occur. Parenteral nutrition should be initiated slowly and with great care.

High magnesium levels in blood:
The amount of magnesium in Numeta G16E may cause elevated magnesium levels in the blood. Signs of this condition may include weakness, slow reflexes, nausea, vomiting, low calcium levels in blood, breathing difficulties, low blood pressure, and irregular heartbeat. Because these signs may be difficult to detect, the doctor may monitor your child’s blood values, especially if your child has risk factors for high magnesium levels, including reduced kidney function. If blood magnesium levels are high, the infusion will be stopped or reduced.

Monitoring and adjustments:
Your doctor will closely monitor your child and adjust the dosage of Numeta G16E according to your child’s individual needs if they have any of the following conditions:

• Severe post-traumatic conditions
• Severe diabetes mellitus
• Shock
• Heart attack
• Severe infection
• Certain types of coma

Use with caution:
Numeta must be used with caution if your child has:

• Pulmonary edema (fluid in the lungs) or heart failure
• Severe liver problems
• Problems with nutrient utilization
• High blood sugar levels
• Kidney problems
• Severe metabolic imbalances (when the body cannot break down substances normally)
• Coagulation disorders

Your child’s fluid status, liver function tests, and/or blood values will be closely monitored.

Other medicines and Numeta G16E
Inform your doctor if your child is taking or using, has recently taken, or might take any other medicines.

Numeta must not be given at the same time as:

• Ceftriaxone (an antibiotic), even through separate infusion lines, due to the risk of precipitate (particle) formation.
• Blood through the same infusion set, due to the risk of pseudoagglutination (clumping of red blood cells).
• Ampicillin, fosphenytoin, or furosemide through the same infusion line, due to the risk of particle formation.

Coumarin and warfarin (anticoagulants):
Your doctor will monitor your child carefully if they are taking coumarin or warfarin. Olive oil and soybean oil contain natural vitamin K1. Vitamin K1 may interfere with medicines such as coumarin and warfarin. These drugs are anticoagulants that prevent blood clotting.

Laboratory tests:
The lipids contained in this emulsion may interfere with the results of certain laboratory tests. Laboratory tests should be performed after a 5–6 hour interval from lipid administration, provided no additional lipids are being administered.

Interactions of Numeta G16E with drugs that may alter potassium levels/metabolism:
Numeta contains potassium. High potassium levels in the blood may cause abnormal heart rhythms. Exercise particular caution in patients taking diuretics (medicines that reduce fluid retention), ACE inhibitors (medicines for high blood pressure), angiotensin II receptor antagonists (medicines for high blood pressure), or immunosuppressants (medicines that may lower the body’s normal immune defenses). These types of medicines may increase potassium levels.

3. How Numeta G16E is administered

Your child must always be given Numeta G16E exactly as indicated by the doctor. Check with your doctor if you are unsure.
Age groups
Numeta G16E has been designed to meet the nutritional needs of full-term neonates and children up to 2 years of age.
Your doctor will decide whether this medicine is suitable for your child.
Administration
This medicine is an infusion emulsion. It is administered through a plastic tube into a vein in the arm or into a large vein in the chest of your child.
Your paediatrician may decide not to administer lipids to your child. The Numeta G16E bag is designed so that, if necessary, only the membrane separating the amino acid/electrolyte compartment from the glucose compartment can be broken. The membrane separating the amino acid compartment from the lipid compartment remains intact in this case. Thus, the contents of the bag can be infused without lipids.
When used in neonates and children under 2 years of age, the solution (in the bags and administration sets) must be protected from exposure to light until completion of administration (see section 2).
Dosage and duration of treatment
Your paediatrician will decide the dosage and duration of treatment. The dosage depends on your child's nutritional needs. The dosage will be based on your child's body weight, clinical condition, and your child's ability to metabolise and utilise the components of Numeta G16E. Additional nutrients or proteins may also be given orally/enterally.
If your child is given too much Numeta G16E
Symptoms
Overdose of this medicine or administration that is too rapid may result in:

• nausea (feeling sick)
• vomiting
• chills
• electrolyte imbalances (abnormal levels of electrolytes in the blood)
• signs of hypervolaemia (increased blood volume in circulation)
• acidosis (increased blood acidity)

In such situations, stop the infusion immediately. Your child's doctor will decide whether further measures are necessary.
An overdose of the fats contained in Numeta G16E may cause a "fat overload syndrome", which is usually reversible after stopping the infusion. In neonates and young children (infants), fat overload syndrome has been associated with respiratory disorders leading to reduced oxygen levels in the body (respiratory distress) and conditions leading to increased blood acidity (acidosis).
To prevent such events from occurring, the doctor will regularly monitor your child's condition and check blood levels during treatment.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not all children will
experience them.
If you notice any changes in your child's health status during or after treatment, inform
your doctor or nurse immediately.
The tests your doctor performs while your child is receiving this medicine help reduce
the risks of side effects.
If signs of an allergic reaction occur, the infusion must be stopped and you must contact
the doctor immediately. This may be serious, and signs may include:

• sweating
• chills
• headache
• skin rash
• breathing difficulties

Other side effects that have been observed are:

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

• Low level of phosphates in the blood (hypophosphatemia)
• High blood sugar level (hyperglycemia)
• High level of calcium in the blood (hypercalcemia)
• High level of triglycerides in the blood (hypertriglyceridemia)
• Electrolyte imbalance (hyponatremia)

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

• High level of lipids in the blood (hyperlipidemia)
• A condition in which bile fails to flow from the liver to the duodenum (cholestasis). The duodenum is part of the intestine.

Not known: frequency cannot be estimated from the available data (These adverse
reactions have been reported only for Numeta G13E and G16E when administered
peripherally with insufficient dilution):

• Skin necrosis
• Soft tissue damage
• Extravasation

The following side effects have been reported with other parenteral nutrition products:
Reduced or limited ability to clear the lipids contained in Numeta may result in a "fat
overload syndrome". The following signs and symptoms of this syndrome are usually
reversible after discontinuation of the lipid emulsion infusion:

• sudden and unexpected worsening of the patient's medical condition
• high levels of fat in the blood (hyperlipidemia)
• fever
• fat infiltration into the liver (hepatomegaly)
• deterioration of liver function
• reduction in red blood cells, which may make the skin pale and cause weakness or shortness of breath (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
• respiratory disorders leading to reduced oxygen levels in the body (dyspnea)
• conditions leading to increased blood acidity (acidosis)
• coma, requiring hospitalization
• formation of small particles that may cause blockage of blood vessels in the lungs (pulmonary vascular precipitates), or breathing difficulties.

Reporting of side effects
If your child experiences any of the side effects, inform your doctor or nurse. This
includes any possible side effect not listed in this leaflet.
You may also report side effects directly (see details below).
By reporting side effects, you can help provide more information on the safety of this
medicine. Adverse effects may also be reported directly via the national reporting system at
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse .

5. How to store Numeta G16E

Keep this medicine out of the sight and reach of children when not in use.
When used in neonates and children under 2 years of age, the solution (in bags and administration sets) must be protected from exposure to light until administration is complete (see section 2).
Do not use this medicine after the expiry date stated on the bag and the outer packaging (MM/YYYY). The expiry date refers to the last day of the month.
Do not freeze.
Store in the outer packaging.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

Description of the appearance of Numeta G16E and package contents
Numeta is supplied as a three-compartment bag. Each bag contains a sterile combination of a glucose solution, a pediatric amino acid solution with electrolytes, and a lipid emulsion, as described below.

Container size	50% glucose solution	5.9% amino acid solution with electrolytes	12.5% lipid emulsion
500 mL	155 mL	221 mL	124 mL

Appearance before reconstitution:

• The solutions in the amino acid and glucose compartments are clear, colorless or slightly yellow
• The lipid emulsion compartment contains a uniform, milky-white liquid

Appearance after reconstitution:

• The "2-in-1" infusion solution is clear, colorless or slightly yellow
• The "3-in-1" infusion emulsion is uniform, milky-white

The three-compartment bag is a multilayer plastic bag.
To prevent contact with air, the Numeta bag is packaged in an outer oxygen-barrier pouch, which also contains an oxygen absorber and an oxygen indicator.
Packaging:
500 ml bag: 6 units per cardboard box
1 bag of 500 ml
It is possible that not all pack sizes are marketed.
Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
Baxter S.p.A.
Via Del Serafico 89
00142 Rome
Italy
Manufacturer:
Baxter S.A.
Boulevard Rene Branquart, 80
7860 Lessines
Belgium
This medicinal product is authorized in the Member States of the European Economic Area under the following names:

Austria Germany	Numeta G 16 % E Emulsion for Infusion
Belgium Luxembourg	NUMETZAH G16%E emulsion for infusion
France	NUMETAH G16%E emulsion for infusion
Denmark Norway Sweden	Numeta G16E
Czech Republic Greece	Numeta G 16 % E
Netherlands	Numeta G16%E emulsion for infusion
Ireland United Kingdom	Numeta G16%E, Emulsion for Infusion
Italy	Numeta G16%E emulsion for infusion
Finland	Numeta G16E infusion emulsion
Poland	Numeta G 16 % E
Portugal	Numeta G16%E
Spain	Numeta G16%E, emulsion for perfusion

This summary of product characteristics was last approved in: May 2024
The following information is intended exclusively for medical professionals or
healthcare providers*
*Please note that in some cases this product may be administered at home by
parents or other caregivers. In such cases, parents or caregivers must read this information.
Do not add anything to the bag before verifying its compatibility. Particles may form or the
lipid emulsion may break, potentially leading to blockage of blood vessels.
Numeta G16E must be at room temperature before use.
Before using Numeta G16E, prepare the bag as shown below.
Check that the bag is undamaged. Use the bag only if it is not damaged.
The appearance of an intact bag is as follows:

• The non-permanent separation membranes are intact. This indicates that the contents of the three compartments have not mixed.
• The amino acid and glucose solutions are clear, colorless or slightly yellow, without visible particles.
• The lipid emulsion is a uniform white, milky liquid.

Before opening the outer protective envelope, check the color of the oxygen indicator.

• Compare it with the reference color printed next to the OK symbol in the printed area of the indicator label.
• Do not use the bag if the color of the oxygen indicator does not match the reference color printed next to the OK symbol.

Figures 1 and 2 illustrate how to remove the outer protective envelope. Discard
the outer envelope, the oxygen indicator, and the oxygen absorber.

Figure 1 Figure 2
Preparation of the mixed emulsion:

• Ensure the product is at room temperature when breaking the non-permanent separation membranes.
• Place the bag on a clean, flat surface.

Activation of the 3-compartment bag (mixing the 3 solutions by breaking the 2 non-permanent membranes)
Step 1: Begin by rolling the bag from the side of the D-ring.

Step 2: Apply pressure until the separation membranes are opened.

Step 3: Change direction and roll the bag toward the D-ring.
Continue until the membrane is completely open.
Repeat the same procedure to complete the opening of the second membrane.

Step 4: Invert the bag at least three times to thoroughly mix the contents.
The appearance of the mixed solution should resemble a white, milky emulsion.

Step 5: Remove the protective cap from the administration port and insert the infusion set.

Activation of 2 compartments (mixing the 2 solutions by breaking the non-permanent membrane between the amino acid compartment and the glucose compartment)
Step 1: To mix only 2 solutions, roll the bag from the upper corner (end with the D-ring) of the membrane separating the solutions.
Apply pressure to open the membrane separating the glucose and amino acid compartments.

Step 2: Position the bag so that the compartment containing the lipid emulsion is closest to the operator.
Roll the bag while protecting the lipid emulsion compartment with the palms of your hands.

Step 3: With one hand, apply pressure and roll the bag toward the injection ports.

Step 4: Change direction and roll the bag toward the upper side (end with the D-ring).
Pressing with the other hand, continue until the membrane separating the amino acid and glucose solutions is completely open.

Step 5: Invert the bag at least three times to thoroughly mix the contents.
The appearance of the mixed solution should be clear, colorless or slightly yellow.

Step 6: Remove the protective cap from the administration port and insert the infusion set.

The flow rate should be gradually increased during the first hour. The infusion rate must be adjusted according to the following factors:

• dose to be administered
• daily volume requirements
• duration of infusion.

Method of administration
When used in neonates and children under 2 years of age, the solution (in bags and administration sets) must be protected from light exposure until administration is complete.
Use of a 1.2-micron filter is recommended for the administration of Numeta G16E.
Due to its high osmolarity, undiluted Numeta G16E can only be administered through a central vein. However, adequate dilution of Numeta G16E with water for injections reduces osmolarity and allows peripheral infusion.
The following formula indicates the effect of dilution on the osmolarity of the bags.

The table below shows examples of osmolarity for activated 2CB and 3CB mixtures after addition of water for injections:

	Amino Acids and Glucose (2 activated CBs)	Amino Acids, Glucose and Lipids (3 activated CBs)
Initial volume in the bag (mL)	376	500
Initial osmolarity (approx. mOsm/L)	1585	1230
Volume of water added (mL)	376	500
Final volume after addition (mL)	752	1000
Osmolarity after addition (approx. mOsm/L)	792.5	615

Addition of additives:
Exposure to light of parenteral nutrition solutions for intravenous use, especially after the addition of trace elements and/or vitamins, may have adverse effects on clinical outcomes in neonates due to the formation of peroxides and other degradation products. When used in neonates and children under 2 years of age, Numeta G16E must be protected from ambient light until the end of administration.
Compatible additives may be added through the injection site into the reconstituted mixture (after opening the non-permanent membranes and after mixing the contents of the two or three compartments).
Vitamins may also be added into the glucose compartment before the mixture is reconstituted (before opening the non-permanent separation membranes and before mixing the solutions and emulsion).
Additions of commercially available trace element solutions (identified as TE1, TE2, and TE4), vitamins (identified as lyophilisate V1 and emulsion V2), and electrolytes in defined quantities are shown in Tables 1–6.

1. 1. Compatibility with TE4, V1, and V2

Table 1: Compatibility of the 3-in-1 bag (3CB activated) with and without dilution with water

For 500 mL (3-in-1 mixture with lipids)
	Undiluted mixture			Diluted mixture
Additives	Included level	Maximum additional amount	Maximum total level	Included level	Maximum additional amount	Maximum total level
Sodium (mmol)	12.0	25.6	37.6	12.0	25.6	37.6
Potassium (mmol)	11.4	26.2	37.6	11.4	26.2	37.6
Magnesium (mmol)	1.6	3.6	5.2	1.6	3.6	5.2
Calcium (mmol)	3.1	16.4	19.5	3.1	8.2	11.3
Phosphate* (mmol)	4.4	6.9	11.3	4.4	6.9	11.3
Trace elements and vitamins		10 mL TE4 + 1 vial V1 + 30 mL V2	10 mL TE4 + 1 vial V1 + 30 mL V2		5 mL TE4 + ½ vial V1 + 5 mL V2	5 mL TE4 + ½ vial V1 + 5 mL V2
Water for injections					350 mL	350 mL

Table 2: Compatibility of the 2-in-1 bag (2CB activated) with and without dilution

For 376 mL (2-in-1 mixture without lipids)
	Undiluted mixture			Diluted mixture
Added components	Included level	Maximum additional addition	Maximum total level	Included level	Maximum additional addition	Maximum total level
Sodium (mmol)	11.6	26.0	37.6	11.6	0.0	11.6
Potassium (mmol)	11.4	26.2	37.6	11.4	0.0	11.4
Magnesium (mmol)	1.6	3.6	5.2	1.6	0.0	1.6
Calcium (mmol)	3.1	8.2	11.3	3.1	0.0	3.1
Phosphate* (mmol)	3.2	8.1	11.3	3.2	0.0	3.2
Trace elements and vitamins		5 mL TE4 + ½ vial V1	5 mL TE4 + ½ vial V1		5 mL TE4 + ½ vial V1	5 mL TE4 + ½ vial V1
Water for injections					450 mL	450 mL

1. 2. Compatibility with TE1, V1 and V2

Table 3: Compatibility of the 3-in-1 bag (activated 3CB) with and without dilution with water

For 500 mL (3-in-1 mixture with lipids)
	Undiluted mixture			Diluted mixture
Additives	Level included	Maximum additional amount	Maximum total level	Level included	Maximum additional amount	Maximum total level
Sodium (mmol)	12.0	4.0	16.0	12.0	0.0	12.0
Potassium (mmol)	11.4	6.2	17.6	11.4	0.0	11.4
Magnesium (mmol)	1.6	0	1.6	1.6	0.0	1.6
Calcium (mmol)	3.1	2.1	5.2	3.1	0.0	3.1
Phosphate* (mmol)	4.4	2.0	6.4	4.4	0.0	4.4
Trace elements and vitamins		5 mL TE1 + ½ vial V1 + 5 mL V2	5 mL TE1 + ½ vial V1 + 5 mL V2		5 mL TE1 + ½ vial V1 + 5 mL V2	5 mL TE1 + ½ vial V1 + 5 mL V2
Water for injections					350 mL	350 mL

Table 4: Compatibility of the 2-in-1 bag (2CB activated) with and without dilution with water

For 376 mL (2 in 1 mixture without lipids)
	Undiluted mixture			Diluted mixture
Additives	Base level included	Maximum additional amount	Maximum total level	Base level included	Maximum additional amount	Maximum total level
Sodium (mmol)	11.6	26.0	37.6	11.6	0.0	11.6
Potassium (mmol)	11.4	26.2	37.6	11.4	0.0	11.4
Magnesium (mmol)	1.6	3.6	5.2	1.6	0.0	1.6
Calcium (mmol)	3.1	8.2	11.3	3.1	0.0	3.1
Phosphate* (mmol)	3.2	8.1	11.3	3.2	0.0	3.2
Trace elements and vitamins		5 mL TE1 + ½ vial V1	5 mL TE1 + ½ vial V1		5 mL TE1 + ½ vial V1	5 mL TE1 + ½ vial V1
Water for injections					450 mL	450 mL

3 Compatibility with TE2, V1 and V2
Table 5: Compatibility of the 3-in-1 bag (activated 3CB) with and without dilution with water

Per 500 mL (3-in-1 mixture with lipids)
	Undiluted mixture			Diluted mixture
Additives	Included level	Maximum additional amount	Maximum total level	Included level	Maximum additional amount	Maximum total level
Sodium (mmol)	12.0	4.0	16.0	12.0	0.0	12.0
Potassium (mmol)	11.4	6.2	17.6	11.4	0.0	11.4
Magnesium (mmol)	1.6	0	1.6	1.6	0.0	1.6
Calcium (mmol)	3.1	2.1	5.2	3.1	0.0	3.1
Phosphate* (mmol)	4.4	2.0	6.4	4.4	0.0	4.4
Trace elements and vitamins		5 mL TE2 + ½ vial V1 + 5 mL V2	5 mL TE2 + ½ vial V1 + 5 mL V2		5 mL TE2 + ½ vial V1 + 5 mL V2	5 mL TE2 + ½ vial V1 + 5 mL V2
Water for injections					350 mL	350 mL

Table 6: Compatibility of the 2-in-1 bag (2CB activated) with and without dilution with water

For 376 mL (2 in 1 without lipids)
	Undiluted mixture			Diluted mixture
Added	Included level	Maximum additional amount	Maximum total level	Included level	Maximum additional amount	Maximum total level
Sodium (mmol)	11.6	26.0	37.6	11.6	0.0	11.6
Potassium (mmol)	11.4	26.2	37.6	11.4	0.0	11.4
Magnesium (mmol)	1.6	3.6	5.2	1.6	0.0	1.6
Calcium (mmol)	3.1	8.2	11.3	3.1	0.0	3.1
Phosphate* (mmol)	3.2	8.1	11.3	3.2	0.0	3.2
Trace elements and vitamins		5 mL TE2 + ½ vial V1	5 mL TE2 + ½ vial V1		5 mL TE2 + ½ vial V1	5 mL TE2 + ½ vial V1
Water for injections					450 mL	450 mL

The composition of vitamin and trace element preparations is shown in tables 7 and 8.
Table 7: Composition of the commercial trace element preparation used:

Composition per 10 mL	TE1	TE2	TE4
Iron		8.9 µmol or 0.5 mg
Zinc	38.2 µmol or 2.5 mg	15.3 µmol or 1 mg	15.3 µmol or 1 mg
Selenium	0.253 µmol or 0.02 mg	0.6 µmol or 0.05 mg	0.253 µmol or 0.02 mg
Copper	3.15 µmol or 0.2 mg	4.7 µmol or 0.3 mg	3.15 µmol or 0.2 mg
Iodine	0.0788 µmol or 0.01 mg	0.4 µmol or 0.05 mg	0.079 µmol or 0.01 mg
Fluoride	30 µmol or 0.57 mg	26.3 µmol or 0.5 mg
Molybdenum		0.5 µmol or 0.05 mg
Manganese	0.182 µmol or 0.01 mg	1.8 µmol or 0.1 mg	0.091 µmol or 0.005 mg
Cobalt		2.5 µmol or 0.15 mg
Chromium		0.4 µmol or 0.02 mg

Table 8: Composition of the commercial vitamin preparation used:

Composition per vial	V1	V2
Vitamin B1	2.5 mg
Vitamin B2	3.6 mg
Nicotinamide	40 mg
Vitamin B6	4.0 mg
Pantothenic Acid	15.0 mg
Biotin	60 µg
Folic Acid	400 µg
Vitamin B12	5.0 µg
Vitamin C	100 mg
Vitamin A		2300 IU
Vitamin D		400 IU
Vitamin E		7 IU
Vitamin K		200 µg

To perform an addition:

• Work under aseptic conditions
• Prepare the injection site of the bag
• Pierce the injection site and inject additives using an injection needle or reconstitution device
• Mix the contents of the bag and the added substances

Preparation of the infusion:

• Work under aseptic conditions
• Suspend the bag
• Remove the plastic protector from the administration port
• Firmly insert the spike of the infusion set into the administration port

Administration of the infusion:

• For single use only
• Administer the product only after opening the non-permanent separation membranes between the two or three compartments and mixing the contents of the two or three compartments
• Ensure that the final 3-compartment activated infusion emulsion shows no evidence of phase separation, or that the final 2-compartment activated infusion solution shows no particulate matter
• After breaking the non-permanent membranes, the contents must be used immediately. Numeta G16E must not be stored for subsequent infusion. Do not connect partially used bags
• Do not connect bags in series to avoid the risk of gas embolism due to possible residual gas in the primary bag
• A 1.2 micron filter is recommended for administration of Numeta G16E
• When used in neonates and children under 2 years of age, protect from light exposure until completion of administration. Exposure of Numeta G16E to ambient light, especially after addition of trace elements and/or vitamins, generates peroxides and other degradation products, which can be minimized by protecting from light exposure
• Any unused product, waste materials, and disposable devices must be properly discarded and not reused

Shelf life after mixing of solutions
Use the product immediately after opening the non-permanent membranes between the two or three compartments. Stability studies of the mixtures have been conducted for 7 days at a temperature between 2°C and 8°C, followed by 48 hours at 30°C.

Shelf life after supplementation (electrolytes, trace elements, vitamins, water):
For specific mixtures, in-use stability data for the Numeta formulation have been demonstrated for 7 days at a temperature between 2°C and 8°C, followed by 48 hours at 30°C.
From a microbiological standpoint, the product should be used immediately. If not used immediately, the storage times and conditions prior to use are the responsibility of the user and must not exceed 24 hours at temperatures between 2°C and 8°C, unless reconstitution/dilution/supplementation has been performed under controlled and validated aseptic conditions.

Do not use Numeta G16E if the bag is damaged. This is what a damaged bag looks like:

• the non-permanent separation membranes are broken
• one of the compartments contains a mixture of solutions
• the amino acid and glucose solutions are not clear, colorless or slightly yellow, and/or contain visible particles
• the lipid emulsion is not a uniform white milky liquid

Medicinal products must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

What Numeta G16E contains
The active substances are:

Composition
Active ingredient	2CB activated (376 mL)	3CB activated (500 mL)
Amino Acid Compartment
Alanine	1.03 g	1.03 g
Arginine	1.08 g	1.08 g
Aspartic acid	0.77 g	0.77 g
Cysteine	0.24 g	0.24 g
Glutamic acid	1.29 g	1.29 g
Glycine	0.51 g	0.51 g
Histidine	0.49 g	0.49 g
Isoleucine	0.86 g	0.86 g
Leucine	1.29 g	1.29 g
Lysine monohydrate (as lysine)	1.59 g (1.42 g)	1.59 g (1.42 g)
Methionine	0.31 g	0.31 g
Ornithine hydrochloride (as ornithine)	0.41 g (0.32 g)	0.41 g (0.32 g)
Phenylalanine	0.54 g	0.54 g
Proline	0.39 g	0.39 g
Serine	0.51 g	0.51 g
Taurine	0.08 g	0.08 g
Threonine	0.48 g	0.48 g
Tryptophan	0.26 g	0.26 g
Tyrosine	0.10 g	0.10 g
Valine	0.98 g	0.98 g
Sodium chloride	0.30 g	0.30 g
Potassium acetate	1.12 g	1.12 g
Calcium chloride dihydrate	0.46 g	0.46 g
Magnesium acetate tetrahydrate	0.33 g	0.33 g
Sodium glycerophosphate hydrate	0.98 g	0.98 g
Glucose Compartment
Composition
Active ingredient	2CB activated (376 mL)	3CB activated (500 mL)
Glucose monohydrate (as anhydrous glucose)	85.25 g (77.50 g)	85.25 g (77.50 g)
Lipid Compartment
Refined olive oil (approx. 80%) + refined soybean oil (approx. 20%)		15.5 g

The reconstituted solution/emulsion provides the following:

Composition
	Activated 2CB		Activated 3CB
Per unit of volume (mL) Nitrogen (g) Amino acids (g) Glucose (g) Lipids (g) Energy Total calories (kcal) Non-protein calories (kcal) Calories from glucose (kcal) Lipid calories (kcal) Non-protein calories/nitrogen (kcal/g N) Lipid calories (percentage of non-protein calories) Lipid calories (percentage of total calories) Electrolytes Sodium (mmol) Potassium (mmol) Magnesium (mmol) Calcium (mmol) Phosphateb (mmol) Acetate (mmol) Malate (mmol) Chloride (mmol)	376 2.0 13.0 77.5 0 362 310 310 0 158 NA NA 11.6 11.4 1.6 3.1 3.2 14.5 4.3 13.8	100 0.52 3.5 20.6 0 96 82 82 0 158 N/A N/A 3.1 3.0 0.41 0.82 0.85 3.9 1.1 3.7	500 2.0 13.0 77.5 15.5 517 465 310 155 237 33 30 12.0 11.4 1.6 3.1 4.4 14.5 4.3 13.8	100 0.39 2.6 15.5 3.1 103 93 62 31 237 33 30 2.4 2.3 0.31 0.62 0.87 2.9 0.86 2.8
pH (approx.)	5.5	5.5	5.5	5.5
Composition
	Activated 2CB		Activated 3CB
Per unit of volume (mL) Approximate osmolarity (mOsm/L)	376 1585	100 1585	500 1230	100 1230

The other components are:
L-malic acid
Hydrochloric acid
Egg phospholipids for
injectable preparations
Glycerol
Sodium oleate
Sodium hydroxide
Water for injectable preparations
for pH adjustment

Package Leaflet: Information for the user

NUMETA G19E, emulsion for infusion

Please read this leaflet carefully before using this medicine because
it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your paediatrician, pharmacist, or nurse.
• If your child experiences any side effects, inform your paediatrician or nurse. This includes any side effects not listed in this leaflet. See section 4.

Contents of this leaflet:

1. What Numeta G19E is and what it is used for
2. What you need to know before your child is given Numeta G19E
3. How Numeta G19E is given
4. Possible side effects
5. How to store Numeta G19E
6. Contents of the pack and other information

1. What Numeta G19E is and what it is used for

Numeta G19E is a nutritional emulsion specifically formulated for children over 2 years of age and adolescents up to 18 years of age. It is administered through a tube inserted into your child's vein when they are unable to take in orally all the necessary nutrition.
Numeta comes as a three-compartment bag, with each separate compartment containing:
a 50% glucose solution
a 5.9% pediatric amino acid solution with electrolytes
a 12.5% lipid (fat) emulsion
Depending on your child's needs, 2 or 3 of these solutions are mixed together within the bag before being administered to your child.
Numeta G19E must be used exclusively under medical supervision.

2. What you should know before your child is given Numeta G19E

Numeta G19E must not be given to your child in the following cases:
With 2 solutions mixed in the bag (2 in 1):

• If your child is allergic to egg proteins, soy, peanuts, or any of the excipients in the glucose or amino acid compartments (listed in section 6).
• If your child’s body has problems forming protein "building blocks".
• If your child has high blood levels of any of the electrolytes contained in Numeta G19E.
• If your child suffers from hyperglycemia (particularly high blood sugar levels).

With 3 solutions mixed in the bag (3 in 1):

• All situations listed under “2 in 1” plus the following:
• If your child has particularly high levels of fats in the blood.

In all cases, your doctor will decide whether your child should receive this medicine based on factors such as age, weight, and clinical condition. Your doctor will also take into account the results of performed tests.
Warnings and precautions
Talk to your pediatrician or nurse before your child is given Numeta G19E.
Allergic reactions:
Infusion must be stopped immediately if signs or symptoms of an allergic reaction occur (e.g., fever, sweating, chills, headache, skin rash, or breathing difficulties). This medicine contains soybean oil, which rarely may cause severe hypersensitivity reactions. It has been observed rarely that individuals allergic to peanut proteins may also be allergic to soybean proteins.
Numeta G19E contains glucose derived from corn starch. Therefore, Numeta G19E must be used with caution in patients with a known allergy to corn or corn-derived products.
Risk of particle formation with ceftriaxone (antibiotic):
An antibiotic called ceftriaxone must not be mixed or administered simultaneously with any calcium-containing solution (including Numeta G19E) when given by intravenous infusion.
The doctor is aware of this and will not administer them together, even through separate infusion lines or different infusion sites.
However, the doctor may administer calcium and ceftriaxone sequentially if different infusion sites or lines are used, or if the infusion lines are replaced or thoroughly flushed with physiological saline solution between infusions to prevent precipitation.
Formation of small particles in lung blood vessels:
Breathing difficulties may also be a sign of small particles forming and blocking blood vessels in the lungs (pulmonary vascular precipitates). If your child experiences any breathing difficulties, inform the pediatrician or nurse immediately. They will decide which actions to take.
Infections and sepsis:
Your doctor will carefully monitor your child for any signs of infection.
The risk of infection can be reduced by using an "aseptic technique" (germ-free technique) during catheter placement and maintenance, as well as in the preparation of the nutritional formula.
Sometimes, children may develop an infection and sepsis (presence of bacteria in the blood) when an intravenous catheter is inserted. Some medicines and certain diseases may increase the risk of developing an infection or sepsis. Patients requiring parenteral nutrition (administration of nutrients through a tube inserted into a vein) may be more susceptible to infections due to their underlying medical conditions.
Fat overload syndrome:
Fat overload syndrome has been reported with similar products. A reduced or limited ability to clear lipids present in Numeta G19E, or overdosing, may lead to a "fat overload syndrome". (See section 3 and section 4).
Changes in blood chemical parameters:
Your doctor will monitor and assess your child’s fluids, blood chemical composition, and other blood parameters, as refeeding severely malnourished patients may sometimes cause changes in blood chemical levels.
Additionally, swelling and excessive fluid accumulation in tissues may occur.
It is recommended to start parenteral nutrition slowly and with great care.
Monitoring and adjustments:
Your doctor will keep your child under close surveillance and adjust the dosage of Numeta G19E according to the child’s individual needs if the following conditions are present:

• Severe post-traumatic conditions
• Severe diabetes mellitus
• Shock
• Myocardial infarction
• Severe infection
• Certain types of coma

Use with caution:
Numeta must be used with caution if your child has:

• Pulmonary edema (fluid in the lungs) or heart failure
• Severe liver problems
• Problems with nutrient utilization
• High blood sugar levels
• Kidney problems
• Severe metabolic imbalances (when the body cannot break down substances normally)
• Coagulation disorders
  Your child’s fluid status, liver function tests, and/or blood values will be closely monitored.

Other medicines and Numeta G19E
Inform your doctor if your child is taking or using, has recently taken or used, or might take or use any other medicines.
Numeta must not be administered simultaneously with:

• Ceftriaxone (an antibiotic), even through separate infusion lines, due to the risk of particle formation.
• Blood through the same infusion set due to the risk of pseudoagglutination (clumping of red blood cells).
• Ampicillin, fosphenytoin, or furosemide through the same infusion line due to the risk of particle formation.

Coumarin and warfarin (anticoagulants):
Your doctor will carefully monitor your child if they are taking coumarin or warfarin. Olive oil and soybean oil naturally contain vitamin K1. Vitamin K1 may interfere with medicines such as coumarin and warfarin.
These drugs are anticoagulants that prevent blood clotting.
Laboratory tests:
The lipids contained in this emulsion may interfere with the results of certain laboratory tests. Laboratory tests should be performed after a 5–6 hour interval following lipid administration, provided no additional lipids are being administered.
Interactions of Numeta G19E with drugs that may alter potassium levels/metabolism:
Numeta G19E contains potassium. High blood potassium levels may cause abnormal heart rhythms. Exercise particular caution in patients receiving diuretics (medicines that reduce fluid retention), ACE inhibitors (medicines for high blood pressure), angiotensin II receptor antagonists (medicines for high blood pressure), or immunosuppressants (medicines that may lower the body’s normal immune defenses). These types of medicines may increase potassium levels.
Pregnancy, breastfeeding, and fertility
There are insufficient data on the use of Numeta in pregnant or breastfeeding women. Before prescribing Numeta, your doctor must carefully evaluate the potential risks and benefits for each individual patient.

3. How Numeta G19E is given

Your child must always be given Numeta G19E exactly as your doctor has told you.
Check with your doctor if you are not sure.
Age groups
Numeta G19E has been designed to meet the nutritional needs of children over 2 years of age and adolescents up to 18 years of age.
Your doctor will decide whether this medicine is suitable for your child.
Administration
This medicine is an infusion emulsion. It is administered through a plastic tube into a vein in your child's arm or into a large vein in the chest.
Your paediatrician may decide not to administer lipids to your child. The Numeta G19E bag is designed so that, if necessary, only the partition membrane between the amino acid/electrolyte compartment and the glucose compartment can be broken. The partition membrane between the amino acid and lipid compartment remains intact in this case. The bag contents can thus be infused without lipids.
Dosage and duration of treatment
Your paediatrician will decide the dosage and duration of treatment. The dosage depends on your child's nutritional needs. The dosage will be based on your child's body weight, clinical condition, and the ability of your child's body to metabolise and utilise the components of Numeta G19E. Additional nutrients or proteins may also be given orally/enterally.
If your child is given too much Numeta G19E
Symptoms
Overdose of this medicine or administration that is too rapid may cause the following:

• nausea (feeling sick)
• vomiting
• chills
• electrolyte imbalances (abnormal levels of electrolytes in the blood)
• signs of hypervolaemia (increased circulating blood volume)
• acidosis (increased blood acidity)

In such situations, stop the infusion immediately. Your child's doctor will decide whether further measures are necessary.
An overdose of the fats contained in Numeta G19E may cause a "fat overload syndrome", which is usually reversible after stopping the infusion. In neonates and young children (infants), fat overload syndrome has been associated with respiratory disturbances leading to reduced oxygen levels in the body (respiratory distress) and conditions causing increased blood acidity (acidosis).
To prevent such events, your doctor will regularly monitor your child's condition and check blood levels during treatment.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not all children will
experience them.
If you notice any changes in your child's health during or after treatment, inform your
doctor or nurse immediately.
The tests your doctor performs while your child is receiving this medicine help reduce
the risk of side effects.
If signs of an allergic reaction occur, the infusion must be stopped and medical advice
must be sought immediately. This may be serious, and signs may include:

• sweating
• chills
• headache
• skin rash
• difficulty breathing

Other side effects that have been observed are:
Common (may affect up to 1 in 10 people):

• Low level of phosphates in the blood (hypophosphatemia)
• High blood sugar levels (hyperglycemia)
• High level of calcium in the blood (hypercalcemia)
• High level of triglycerides in the blood (hypertriglyceridemia)
• Electrolyte imbalance (hyponatremia)

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

• High level of lipids in the blood (hyperlipidemia)
• A condition in which bile fails to flow from the liver to the duodenum (cholestasis). The duodenum is part of the intestine.

Not known: frequency cannot be estimated from the available data (These
adverse reactions have been reported only for Numeta G13E and G16E when
administered peripherally with insufficient dilution):

• Skin necrosis
• Soft tissue damage
• Extravasation

The following side effects have been reported with other parenteral nutrition products:
Reduced or limited ability to clear the lipids contained in Numeta may result in a
"fat overload syndrome". The following signs and symptoms of this syndrome are
usually reversible after discontinuation of the lipid emulsion infusion:

• Sudden and unexpected worsening of the patient's medical condition
• High levels of fat in the blood (hyperlipidemia)
• Fever
• Fat infiltration into the liver (hepatomegaly)
• Worsening of liver function
• Reduction in red blood cells, which may cause pale skin and lead to feelings of
  weakness or breathlessness (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
• Respiratory disorders leading to reduced oxygen levels in the body
  (difficulty breathing)
• Conditions leading to increased acidity of the blood (acidosis)
• Coma, requiring hospitalization
  Formation of small particles that may cause blockage of blood vessels in the lungs
  (pulmonary vascular precipitates), or breathing difficulties.

Reporting of side effects
If your child experiences any of the side effects, inform your doctor or nurse. This
includes any possible side effects not listed in this leaflet. You may also report side
effects directly (see details below). By reporting side effects, you can help provide more
information on the safety of this medicine.
Side effects can also be reported directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-
reazioni-avverse.

5. How to store Numeta G19E

Keep this medicine out of the sight and reach of children when not in use.
Do not use this medicine after the expiry date stated on the bag and outer packaging (MM/YYYY). The expiry date refers to the last day of the month.
Do not freeze.
Store in the original outer packaging.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Pack contents and other information

Description of the appearance of Numeta G19E and pack contents
Numeta G19E is presented as a three-compartment bag. Each bag contains a sterile combination of a glucose solution, a pediatric amino acid solution with electrolytes, and a lipid emulsion, as described below.

Container size	50% glucose solution	5.9% amino acid solution with electrolytes	12.5% lipid emulsion
1000 mL	383 mL	392 mL	225 mL

Appearance prior to reconstitution:

• The solutions in the amino acid and glucose compartments are clear, colorless or slightly yellow
• The lipid emulsion compartment contains a uniform, milky white liquid

Appearance after reconstitution:

• The "2 in 1" infusion solution is clear, colorless or slightly yellow
• The "3 in 1" infusion emulsion is uniform, milky white

The three-compartment bag is a multilayer plastic bag. To prevent contact with air, the Numeta bag is packaged in an outer oxygen-barrier container containing an oxygen absorber and an oxygen indicator.

Packaging:
1000 mL bag: 6 units per cardboard box
1 bag of 1000 mL
It is possible that not all pack sizes are marketed.

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder:
Baxter S.p.A.
Via del Serafico 89
00142 Rome, Italy

Manufacturer:
Baxter S.A.
Boulevard Rene Branquart, 80
7860 Lessines, Belgium

This medicinal product is authorized in the European Economic Area countries under the following names:

Austria Germany	Numeta G 19 % E Emulsion for Infusion
Belgium Luxembourg	NUMETZAH G19%E, emulsion for infusion
France	NUMETAH G 19 %E emulsion for infusion
Denmark Norway Sweden	Numeta G19E
Czech Republic Greece	Numeta G 19 % E
Netherlands	Numeta G19%E emulsion for infusion
Ireland United Kingdom	Numeta G19%E, Emulsion for Infusion
Italy	Numeta G19%E emulsion for infusion
Finland	Numeta G19E infusion concentrate, emulsion
Poland	Numeta G 19 % E
Portugal	Numeta G19%E
Spain	Numeta G19%E, emulsion for perfusion

This patient information leaflet was last approved on: May 2024
The following information is intended exclusively for medical professionals or
healthcare providers*
*Please note that in some cases this product may be administered at home by
parents or other caregivers. In such cases, parents or caregivers must read this information.
Do not add anything to the bag before checking its compatibility. Particles may form or the lipid emulsion may break, which could lead to blockage of blood vessels.
Numeta G19E must be at room temperature before use.
Before using Numeta G19E, prepare the bag as shown below.
Check that the bag is not damaged. Use the bag only if it is undamaged.
The appearance of an intact bag is as follows:

• The non-permanent separation membranes are intact. This indicates that the contents of the three compartments have not mixed.
• The amino acid and glucose solutions are clear, colorless or slightly yellow, without visible particles.
• The lipid emulsion is a uniform white, milky liquid.

Before opening the outer protective wrapper, check the color of the oxygen indicator.

• Compare it with the reference color printed next to the OK symbol in the printed area of the indicator label.
• Do not use the bag if the color of the oxygen indicator does not match the reference color printed next to the OK symbol. Figures 1 and 2 illustrate how to remove the outer protective wrapper. Discard the outer wrapper, the oxygen indicator, and the oxygen absorber.

Figure 1 Figure 2
Preparation of the mixed emulsion:

• Ensure that the medicinal product is at room temperature when breaking the non-permanent separation membranes.

Place the bag on a flat, clean surface.
Activation of the 3-compartment bag (mixing the 3 solutions by breaking the 2 non-permanent membranes)
Step 1: Begin by rolling the bag from the side of the D-ring.

Step 2: Apply pressure until the separation membranes are open.

Step 3:
Change direction by rolling the bag toward the D-ring. Continue until the membrane is completely open.
Repeat the same procedure to complete the opening of the second membrane.

Step 4: Invert the bag at least three times to thoroughly mix the contents.
The appearance of the mixed solution should resemble a milky white emulsion.

Step 5: Remove the protective cap from the administration port and insert the infusion set.

Activation of 2 compartments (mixing the 2 solutions by breaking the non-permanent membrane between the amino acid compartment and the glucose compartment)
Step 1: To mix only 2 solutions, roll the bag from the upper corner (end with the D-ring) of the membrane separating the solutions. Apply pressure to open the membrane separating the glucose and amino acid compartments.

Step 2: Position the bag so that the compartment containing the lipid emulsion is closest to the operator. Roll the bag while protecting the lipid emulsion compartment with the palms of your hands.

Step 3: With one hand, apply pressure and roll the bag toward the injection ports.

Step 4: Change direction by rolling the bag toward the top (end with the D-ring).
Apply pressure with the other hand, continuing until the membrane separating the amino acid and glucose solutions is completely open.

Step 5: Invert the bag at least three times to thoroughly mix the contents.
The appearance of the mixed solution should be clear, colorless or slightly yellow.

Step 6: Remove the protective cap from the administration port and insert the infusion set.

The infusion flow rate should be gradually increased during the first hour. The infusion rate must be adjusted according to the following factors:

• dose to be administered
• daily volumes to be infused
• duration of infusion

Method of administration
The solution (in bags and administration sets) must be protected from exposure to light from the moment of mixing until administration.
Use of a 1.2 micron filter is recommended for administration of Numeta G19E.
Due to its high osmolarity, undiluted Numeta G19E can only be administered through a central vein. However, adequate dilution of Numeta G19E with water for injections reduces osmolarity and allows peripheral infusion.
The following formula shows the effect of dilution on the osmolarity of the bags.

The table below shows examples of osmolarity for activated 3CB mixtures after addition of water for injections:

	Amino acids, glucose and lipids (3CB activated)
Initial volume in bag (mL)	1000
Initial osmolarity (approx. mOsm/L)	1460
Volume of added water (mL)	1000
Final volume after addition (mL)	2000
Osmolarity after addition (approx. mOsm/L)	730

Addition of additives:
Mixtures containing trace elements and vitamins must be protected from light
from the time of mixing until administration. Exposure to ambient light
generates peroxides and other degradation products, which can be reduced by
photoprotection.
Compatible additives may be added through the injection site into the reconstituted
mixture (after opening the non-permanent membranes and after mixing the contents of the two or three compartments).
Vitamins may also be added into the glucose compartment before the mixture is reconstituted (before opening the non-permanent separating membranes and before mixing the solutions and emulsion).
Possible additions of trace element solutions (identified as TE1, TE2, and TE4),
vitamins (identified as lyophilisate V1 and emulsion V2), and electrolytes available commercially in defined quantities are shown in tables 1–6.

1. 3. Compatibility with TE4, V1, and V2

Table 1: Compatibility of the 3-in-1 bag (activated 3CB) with and without dilution with water

Per 1000 mL (3 in 1 mixture with lipids)
	Undiluted mixture			Diluted mixture
Additives	Level included	Maximum additional amount	Maximum total level	Level included	Maximum additional amount	Maximum total level
Sodium (mmol)	45.8	105	151	45.8	105	151
Potassium (mmol)	32.0	118	150	32.0	118	150
Magnesium (mmol)	2.6	7.8	10.4	2.6	7.8	10.4
Calcium (mmol)	3.8	20.5	24.3	3.8	20.5	24.3
Phosphate* (mmol)	9.4	14.6	24.0	9.4	14.6	24.0
Trace elements and vitamins		34 mL TE4 + 3.4 vials V1 + 38 mL V2	34 mL TE4 + 3.4 vials V1 + 38 mL V2		34 mL TE4 + 3.4 vials V1 + 38 mL V2	34 mL TE4 + 3.4 vials V1 + 38 mL V2
Water for injections					1450 mL	1450 mL

Table 2: Compatibility of the 2-in-1 bag (2CB activated)

For 775 mL (2-in-1 non-lipid mixture)
Additives	Included level	Maximum additional amount	Maximum total level
Sodium (mmol)	45.1	32.0	77.1
Potassium (mmol)	32.0	45.6	77.6
Magnesium (mmol)	2.6	5.2	7.8
Calcium (mmol)	3.8	19.4	23.2
Phosphate* (mmol)	7.2	16.0	23.2
Trace elements and vitamins		10 mL TE4 + 1 vial V1	10 mL TE4 + 1 vial V1

1. 4. Compatibility with TE1, V1 and V2 Table 3: Compatibility of the 3-in-1 bag (activated 3CB)

Per 1000 mL (3 in 1 mixture with lipids)
Additives	Included level	Maximum additional amount	Maximum total level
Sodium (mmol)	45.8	0	45.8
Potassium (mmol)	32.0	0	32.0
Magnesium (mmol)	2.6	0	2.6
Calcium (mmol)	3.8	6.4	10.2
Phosphate* (mmol)	9.4	0	9.4
Trace elements and vitamins		15 mL TE1 + 1 vial V1 + 10 mL V2	15 mL TE1 + 1 vial V1 + 10 mL V2

Table 4: Compatibility of the 2-in-1 bag (activated 2CB)

For 775 mL (2 in 1 mixture without lipids)
Additives	Included level	Maximum additional addition	Maximum total level
Sodium (mmol)	45.1	32.0	77.1
Potassium (mmol)	32.0	45.6	77.6
Magnesium (mmol)	2.6	5.2	7.8
Calcium (mmol)	3.8	19.4	23.2
Phosphate* (mmol)	7.2	16.0	23.2
Trace elements and vitamins		10 mL TE1 + 1 vial V1	10 mL TE1 + 1 vial V1

1. 5. Compatibility with TE2, V1 and V2

Table 5: Compatibility of the 2-in-1 bag (activated 2CB)

For 775 mL (2 in 1 without lipid mixture)
Additions	Included level	Maximum additional amount	Maximum total level
Sodium (mmol)	45.1	32.0	77.1
Potassium (mmol)	32.0	45.6	77.6
Magnesium (mmol)	2.6	5.2	7.8
Calcium (mmol)	3.8	19.4	23.2
Phosphate* (mmol)	7.2	16.0	23.2
Trace elements and vitamins		15 mL TE2 + 1 vial V1	15 mL TE2 + 1 vial V1

Table 6: Compatibility of the 3-in-1 bag (activated 3CB)

Per 1000 mL (3-in-1 mixture with lipids)
Additives	Level included	Maximum additional amount	Maximum total level
Sodium (mmol)	45.8	0	45.8
Potassium (mmol)	32.0	0	32.0
Magnesium (mmol)	2.6	0	2.6
Calcium (mmol)	3.8	6.4	10.2
Phosphate* (mmol)	9.4	0	9.4
Trace elements and vitamins		15 mL TE2 + 1 vial V1 + 10 mL V2	15 mL TE2 + 1 vial V1 + 10 mL V2

The composition of vitamin and trace element preparations is shown in Tables 7 and
Table 7: Composition of the commercial trace element preparation used

Composition per 10 mL	TE1	TE2	TE4
Iron		8.9 µmol or 0.5 mg
Zinc	38.2 µmol or 2.5 mg	15.3 µmol or 1 mg	15.3 µmol or 1 mg
Selenium	0.253 µmol or 0.02 mg	0.6 µmol or 0.05 mg	0.253 µmol or 0.02 mg
Copper	3.15 µmol or 0.2 mg	4.7 µmol or 0.3 mg	3.15 µmol or 0.2 mg
Iodine	0.0788 µmol or 0.01 mg	0.4 µmol or 0.05 mg	0.079 µmol or 0.01 mg
Fluoride	30 µmol or 0.57 mg	26.3 µmol or 0.5 mg
Molybdenum		0.5 µmol or 0.05 mg
Manganese	0.182 µmol or 0.01 mg	1.8 µmol or 0.1 mg	0.091 µmol or 0.005 mg
Chromium		0.4 µmol or 0.02 mg
Cobalt		2.5 µmol or 0.15 mg

Table 8: Composition of the commercial vitamin preparation used:

Composition per vial	V1	V2
Vitamin B1	2.5 mg
Vitamin B2	3.6 mg
Nicotinamide	40 mg
Vitamin B6	4.0 mg
Pantothenic acid	15.0 mg
Biotin	60 µg
Folic acid	400 µg
Vitamin B12	5.0 µg
Vitamin C	100 mg
Vitamin A		2300 IU
Vitamin D		400 IU
Vitamin E		7 IU
Vitamin K		200 µg

To perform an addition:

• Work under aseptic conditions
• Prepare the injection site of the bag
• Pierce the injection site and inject additives using an injection needle or reconstitution device
• Mix the contents of the bag and the added substances

Preparation of the infusion:

• Work under aseptic conditions
• Suspend the bag
• Remove the plastic protector from the administration port
• Firmly insert the spike of the infusion set into the administration port

Administration of the infusion:

• For single use only
• Administer the product only after opening the non-permanent separating membranes between the two or three compartments and mixing the contents of the two or three compartments
• Ensure that the final 3-compartment infusion emulsion shows no evidence of phase separation, or that the final 2-compartment infusion solution shows no visible particles
• After breaking the non-permanent membranes, the contents must be used immediately. Numeta G19E must not be stored for subsequent infusion. Do not connect partially used bags
• Do not connect bags in series to avoid the risk of gas embolism due to possible residual gas in the primary bag
• Use of a 1.2 micron filter is recommended for administration of Numeta G19E
• Any unused product, waste materials, and disposable devices must be properly discarded and not reused

Shelf life after mixing of solutions: Use the product immediately after opening the non-permanent membranes between the two or three compartments. Stability studies of the mixtures have been conducted for 7 days at a temperature between 2°C and 8°C, followed by 48 hours at 30°C.

Shelf life after supplementation (electrolytes, trace elements, vitamins, water):
For specific mixtures, in-use stability data for the Numeta formulation have been demonstrated for 7 days at a temperature between 2°C and 8°C, followed by 48 hours at 30°C.
From a microbiological standpoint, the product should be used immediately. If not used immediately, the storage times and conditions prior to use are the responsibility of the user and must not exceed 24 hours at temperatures between 2°C and 8°C, unless reconstitution/dilution/supplementation has been performed under controlled and validated aseptic conditions.
Do not use Numeta if the bag is damaged. This is what a damaged bag looks like:

• The non-permanent separating membranes are broken
• One of the compartments already contains a mixture of solutions
• The amino acid and glucose solutions are not clear, colorless or slightly yellow, and/or contain visible particles
• The lipid emulsion is not a uniform white milky liquid

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.
What Numeta G19E contains
The active substances are:

Active Ingredient	2CB activated (775 mL)	3CB activated (1000 mL)
Amino Acid Compartment
Alanine	1.83 g	1.83 g
Arginine	1.92 g	1.92 g
Aspartic acid	1.37 g	1.37 g
Cysteine	0.43 g	0.43 g
Active Ingredient	2CB activated (775 mL)	3CB activated (1000 mL)
Glutamic acid	2.29 g	2.29 g
Glycine	0.91 g	0.91 g
Histidine	0.87 g	0.87 g
Isoleucine	1.53 g	1.53 g
Leucine	2.29 g	2.29 g
Lysine monohydrate (as lysine)	2.82 g (2.51 g)	2.82 g (2.51 g)
Methionine	0.55 g	0.55 g
Ornithine hydrochloride (as ornithine)	0.73 g (0.57 g)	0.73 g (0.57 g)
Phenylalanine	0.96 g	0.96 g
Proline	0.69 g	0.69 g
Serine	0.91 g	0.91 g
Taurine	0.14 g	0.14 g
Threonine	0.85 g	0.85 g
Tryptophan	0.46 g	0.46 g
Tyrosine	0.18 g	0.18 g
Valine	1.74 g	1.74 g
Sodium chloride	1.79 g	1.79 g
Potassium acetate	3.14 g	3.14 g
Calcium chloride dihydrate	0.56 g	0.56 g
Magnesium acetate tetrahydrate	0.55 g	0.55 g
Sodium glycerophosphate hydrate	2.21 g	2.21 g
Glucose Compartment
Glucose monohydrate (as anhydrous glucose)	210.65 g (191.50 g)	210.65 g (191.50 g)
Lipid Compartment
Refined olive oil (approx. 80%) + refined soybean oil (approx. 20%)		28.1 g

The reconstituted solution/emulsion provides the following:

Composition
	Activated 2CB		Activated 3CB
Per unit of volume (ml) Nitrogen (g)	775 3.5	100 0.45	1000 3.5	100 0.35
Composition
	Activated 2CB		Activated 3CB
Per unit of volume (ml) Amino acids (g) Glucose (g) Lipids (g) Energy Total calories (kcal) Non-protein calories (kcal) Calories from glucose (kcal) Lipid calories (kcal) Non-protein calories/nitrogen (kcal/g N) Lipid calories/non-protein calories (%) Lipid calories/total calories (%) Electrolytes Sodium (mmol) Potassium (mmol) Magnesium (mmol) Calcium (mmol) Phosphate (mmol)b Acetate (mmol) Malate (mmol) Chloride (mmol)	775 23.0 192 0 858 766 766 0 220 NA NA 45.1 32.0 2.6 3.8 7.2 37.1 8.8 42.6	100 3.0 24.7 0 111 99 99 0 220 N/A N/A 5.8 4.1 0.33 0.50 0.93 4.8 1.1 5.5	1000 23.0 192 28.1 1139 1047 766 281 301 27 25 45.8 32.0 2.6 3.8 9.4 37.1 8.8 42.6	100 2.3 19.2 2.8 114 105 77 28 301 27 25 4.6 3.2 0.26 0.38 0.93 3.71 0.88 4.3
pH (approx.) Approximate osmolarity (mOsm/L)	5.5 1835	5.5 1835	5.5 1460	5.5 1460

The other components are:
for pH adjustment