Numeta G19%E, emulsion for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

NUMETA G19%E emulsion for infusion

Read the entire leaflet carefully before starting to use this medicine, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your child's doctor, pharmacist or nurse.
• If your child experiences any adverse reactions, consult your child's doctor, pharmacist or nurse, even if they are adverse reactions not listed in this leaflet. See section 4.

Leaflet contents:

1. What Numeta G19%E is and what it is used for
2. What you need to know before Numeta G19%E is administered to your child
3. How Numeta G19%E will be administered
4. Possible adverse effects
5. How to store Numeta G19%E
6. Contents of the pack and other information

1. What Numeta G19%E is and what it is used for

Numeta G19%E is a specialized nutritional preparation intended for children over 2 years of age and adolescents up to 18 years. It is administered through a tube connected to your child's vein when they are unable to take all their food orally.

Numeta comes as a three-compartment bag containing three separate chambers with:

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, two (or three) of these solutions are mixed within the bag before administration to your child.

Numeta G19%E must only be used under medical supervision.

2. What you need to know before Numeta G19%E is administered to your child

Do not use Numeta G19%E in the following cases:

With 2 solutions mixed in the bag ("2-in-1"):

• If your child is allergic to any egg, soybean, or peanut proteins, or to any ingredient in the glucose or amino acid bag (listed in section 6).
• If your child's body has difficulty utilizing the components of proteins.
• If your child has high blood concentrations of any of the electrolytes included in Numeta G19%E.
• If your child has hyperglycemia (especially high levels of blood sugar).

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

• All the situations listed under "2-in-1" above, plus the following:
• If your child has particularly high levels of fats in the blood.

In all cases, your doctor will decide whether this medicine should be given to your child based on factors such as age, weight, clinical condition, and test results.

Warnings and precautions

Talk to your child's doctor or nurse before Numeta G19%E is administered.

Allergic reactions

Infusion must be stopped immediately if any signs or symptoms of an allergic reaction occur (such as fever, sweating, chills, headache, skin rash, or difficulty breathing). This medicine contains soybean oil, which may rarely cause hypersensitivity reactions. In rare cases, individuals who are allergic to peanut proteins may also be allergic to soybean proteins.

Numeta G19%E contains glucose derived from corn starch and should therefore be used with caution in patients with known allergy to corn or corn products.

Risk of particle formation with ceftriaxone (antibiotic):

A specific antibiotic called ceftriaxone must not be mixed or administered simultaneously with a solution containing calcium (including Numeta G19%E) via intravenous infusion.

Your doctor is aware of this and will not administer them together, even through separate lines or different infusion sites.

However, your 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 normal saline to prevent precipitate formation.

Formation of small particles in lung blood vessels:

Difficulty in breathing may also be a sign of small particles forming and blocking blood vessels in the lungs (pulmonary vascular precipitates). If your child experiences difficulty breathing, inform their doctor or nurse immediately. They will determine the necessary actions.

Infection and sepsis

Your doctor will closely monitor your child for signs of infection. Using an "aseptic technique" (germ-free technique) when placing and maintaining the catheter and when preparing the nutrition formula can reduce the risk of infection.

Children may occasionally develop infections and sepsis (bacteria in the blood) when they have a tube connected to a vein (intravenous catheter). Certain medications and medical conditions can increase the risk of developing sepsis or infection. Patients requiring parenteral nutrition (nutrition delivered through a tube connected to your child's vein) are at higher risk of infection due to their clinical condition.

Fat overload syndrome

Cases of fat overload syndrome have been reported with similar products. Reduced ability to eliminate the lipids contained in Numeta G19%E, or overdose, may lead to "fat overload syndrome" (see sections 3 and 4).

Changes in blood chemical levels

Your doctor will monitor and adjust fluid levels, blood chemical levels, and other blood values in your child. Re-feeding a severely malnourished individual may sometimes cause changes in blood chemistry. Excess fluid in tissues and swelling may also occur. It is recommended to start parenteral nutrition slowly and under supervision.

Monitoring and dose adjustment

Your doctor will monitor and adjust the dose of Numeta G19%E according to your child's individual needs if they have any of the following conditions:

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

Use with caution:

Numeta should be used with caution if your child has:

• Pulmonary edema (fluid in the lungs) or heart failure,
• Severe liver problems,
• Difficulty absorbing nutrients,
• High blood sugar levels,
• Kidney problems,
• Severe metabolic disorders (when the body cannot eliminate substances normally),
• Blood coagulation disorders.

Your child's fluid levels, liver function tests, and/or blood values will be carefully monitored.

Use of Numeta G19%E with other medicines

Inform your doctor if your child is taking, has recently taken, or might need to take any other medicines.

Numeta G19%E must not be administered at the same time as:

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

Coumarin and warfarin (anticoagulants)

Your doctor will closely monitor your child if they are taking coumarin or warfarin. Olive and soybean oils contain vitamin K1. Vitamin K1 may interfere with the action of medications such as coumarin and warfarin. These drugs are anticoagulants used to prevent blood clotting.

Laboratory tests

The lipids in this emulsion may interfere with the results of certain laboratory tests. Laboratory tests should be performed after a 5 to 6-hour interval if no further lipids are administered.

Interaction of Numeta G19%E with medicines that may affect potassium levels/metabolism:

Numeta G19%E contains potassium. High blood potassium levels can cause abnormal heart rhythms. Special attention should be paid to patients taking diuretics (medications that reduce fluid retention), ACE inhibitors, angiotensin II receptor antagonists (all used to treat high blood pressure), or immunosuppressants (medications that may reduce the body's natural defenses). These types of medications can increase potassium levels.

Pregnancy, breastfeeding, and fertility

There are insufficient data on the use of Numeta in pregnant or breastfeeding women. Your doctor must carefully evaluate the benefits and potential risks for each individual patient before prescribing Numeta.

3. How Numeta G19%E will be administered to your child

Your child will always be given Numeta G19%E exactly as prescribed by their doctor. If you have any doubts, consult your doctor.

Age Range

Numeta G19%E has been designed to meet the nutritional needs of children over two years of age and adolescents up to 18 years.

The physician will determine whether this medicine is suitable for your child.

Administration

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

Your child's doctor may decide not to administer lipids to your child. The design of the Numeta G19%E bag allows only the non-permanent seal between the amino acid/electrolyte and glucose compartments to be broken, if necessary. In this case, the seal between the amino acid and lipid compartments remains intact. The contents of the bag can thus be infused without lipids.

Dosage and duration of treatment

Your child's doctor will decide the dose your child needs and how long it will be administered. The dose depends on your child's nutritional requirements and will be based on weight, medical condition, and your child's body's ability to digest and absorb the ingredients in Numeta G19%E. Additional protein or nutrition may also be given orally or via intestinal administration.

If your child is given more NumetaG19%Edel than they should receive

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

Symptoms

Receiving too much medication or receiving it too quickly may cause:

• nausea (feeling unwell)
• vomiting
• chills
• electrolyte disturbances (abnormal levels of electrolytes in the blood)
• signs of hypervolemia (increased blood circulation volume)
• acidosis (increased blood acidity)

In such cases, the infusion must be stopped immediately. Your child's doctor will decide whether further actions are necessary.

An overdose of the fats contained in Numeta G19%E may cause a "fat overload syndrome," which is usually reversible once the infusion is discontinued. In newborns (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 causing increased blood acidity (acidosis).

To prevent these reactions from occurring, your doctor will regularly monitor your child's condition and perform blood tests during treatment.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not all children will experience them.

If you notice any changes in how your child feels during or after treatment, inform the doctor or nurse immediately.

The tests that the doctor will perform on your child during treatment are intended to minimize the risk of adverse effects.

If symptoms of an allergic reaction occur, the infusion must be stopped and the doctor contacted immediately. This may be serious, and symptoms may include:

• Sweating
• Chills
• Headache
• Skin rash
• Difficulty breathing

Other adverse effects that have been observed are:

Frequent: may affect up to 1 in 10 people

• Low blood phosphate levels (hypophosphatemia)
• High blood sugar levels (hyperglycemia)
• High blood calcium levels (hypercalcemia)
• High blood triglyceride levels (hypertriglyceridemia)
• Electrolyte imbalances (hyponatremia)

Uncommon: may affect up to 1 in 100 people

• High blood lipid levels (hyperlipidemia)
• A disorder in which bile cannot flow from the liver to the duodenum (cholestasis). The duodenum is part of the intestine.

Unknown frequency: frequency cannot be estimated from available data (*these adverse effects have been reported with Numeta G13%E and G16%E when administered peripherally with insufficient dilution)

• Skin necrosis
• Soft tissue damage
• Extravasation

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

• Reduced or limited ability to eliminate the lipids contained in Numeta may lead to a "fat overload syndrome." The following signs and symptoms of this syndrome are usually reversible when the lipid emulsion infusion is stopped:
  • • Sudden and abrupt worsening of the patient's clinical condition.
    • High levels of fat in the blood (hyperlipidemia).
    • Fever.
    • Fatty infiltration of the liver (hepatomegaly).
    • Worsening of liver function.
    • Decrease in red blood cells, which may cause paleness, weakness, or difficulty breathing (anemia).
    • Low white blood cell count, which may increase the risk of infection (leukopenia).
    • Low platelet count, which may increase the risk of bruising and/or bleeding (thrombocytopenia).
    • Coagulation disorders, affecting the blood's ability to clot.
    • Respiratory disorder causing reduced oxygen levels in the body (dyspnea).
    • Conditions causing increased blood acidity (acidosis).
    • Comatose state requiring hospitalization.
  • Formation of small particles that may cause blockage of blood vessels in the lungs (pulmonary vascular precipitates) or difficulty breathing.

Reporting of adverse effects:

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

5. Storage of Numeta G19%E

Keep this medicine out of 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 indicated.

Do not freeze.

Store in the overpouch.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Appearance of the product and contents of the pack

Numeta G19%E 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:

Appearance before reconstitution:

• The solutions in the amino acid and glucose compartments are clear, colorless or slightly yellowish.
• The lipid emulsion compartment has a milky, whitish appearance.

Appearance after reconstitution:

• The "2-in-1" solution is clear, colorless or slightly yellowish.
• The "3-in-1" perfusion emulsion has a uniform milky, whitish appearance.

The three-compartment bag is a multilayer plastic bag.

To avoid contact with air, Numeta is packaged inside an oxygen-barrier overpouch containing an oxygen-absorbing sachet and an oxygen indicator.

Pack sizes

1000 ml bag: 6 units per carton

1 bag of 1000 ml

Only certain pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Baxter, S.L.

Pouet de Camilo 2, 46394 Ribarroja del Turia (Valencia), Spain

Manufacturer

Baxter S.A.

Boulevard Rene Branquart, 80

7860 Lessines, Belgium

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

Date of the most recent review of this leaflet: May 2024

Up-to-date detailed information on this medicine is available on the website of the Spanish Agency for Medicinal Products and Medical Devices (AEMPS) http://www.aemps.gob.es/

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This information is intended for healthcare professionals only:*

(*) Please note that in certain cases these medicines may be administered at home by parents or other caregivers. In such cases, parents/caregivers should read the following information.

No medication should be added to the bag without first checking compatibility. Particles may form or the lipid emulsion may break down, which could block blood vessels.

Numeta G19%E must be at room temperature before use.

Before administering Numeta G19%E, prepare the bag as shown below.

Ensure the bag is undamaged and use only if no damage is present. An undamaged bag looks like this:

• The non-permanent seals are intact. This is evident because there is no mixing of the three chambers.
• The amino acid and glucose solution is clear, colorless or slightly yellowish, and free from visible particles.
• The lipid emulsion is a milky white liquid in appearance.

Before opening the overpouch, examine the color of the oxygen absorber.

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

Figures 1 and 2 illustrate how to remove the overpouch. Discard it together with the oxygen indicator and the oxygen absorber.

Figure 1 Figure 2

Preparation of the mixture

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

Activation of the 3-chamber bag (breaking the two non-permanent seals)

Step 1: Roll the bag from the D-hanger side

Step 2: Press until the non-permanent seals open.

Step 3: Reverse direction and roll the bag toward the D-hanger until the seal is completely open. Follow the same steps to open the second non-permanent seal.

Step 4: Rotate the bag at least three times to thoroughly mix the contents. The mixed solution should appear as a milky white emulsion.

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

Activation of the 2-chamber bag (breaking the non-permanent seal between the amino acid and glucose chambers)

Step 1: To break only the amino acid/glucose non-permanent seal, begin rolling the bag from the D-hanger corner of the seal separating the amino acid and glucose chambers, and press to open the seal between the two compartments.

Step 2: Position the bag so that the lipid emulsion compartment faces the operator, and roll the bag while protecting the lipid emulsion compartment in the palms of your hands.

Step 3: With one hand, apply pressure by rolling the bag toward the tubes.

Step 4: Then reverse direction and roll the bag toward the D-hanger, pressing with the other hand until the seal separating the amino acid and glucose solutions is fully open.

Step 5: Rotate the bag at least three times to thoroughly mix the contents. The mixed solution should appear clear, colorless or slightly yellowish.

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

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

The dose to be administered

The volume of daily intake

The duration of the infusion.

Method of administration

The emulsion (in the bag and in the administration set) must be protected from exposure to light from the point of administration of the mixture and throughout the infusion.

A 1.2-micron filter is recommended for the administration of Numeta G19%E.

Due to its high osmolarity, Numeta G19%E may only be administered undiluted via a central vein; however, appropriate dilution of Numeta G19%E 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 additions to the activated 3-chamber bag (B3C) after the addition of water for injectable preparations:

Addition of medication

Mixtures containing trace elements and vitamins must be protected from light from the point of administration of the mixture and during administration. Exposure to ambient light generates peroxides and other degradation products, which can be reduced by photoprotection.

Compatible medications may be added to the reconstituted mixture (after opening the non-permanent seals and mixing the contents of the two or three chambers) through the injection site.

Vitamins may also be added to the glucose chamber before reconstituting the mixture (before opening the non-permanent seals and mixing the solutions and emulsion).

Tables 1–6 show possible 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.

1 Compatibility with TE4, V1, and V2

Table 1: Compatibility of 3-in-1 (activated B3C) with or without dilution in water

• Organic phosphate

Table 2: 2-in-1 compatibility (activated B2C)

• Organic phosphate

2 Compatibility with TE1, V1 and V2

Table 3: 3-in-1 compatibility (activated B3C)

• Organic phosphate

Table 4: 2-in-1 compatibility (activated B2C)

• Organic phosphate

3 Compatibility with TE2, V1 and V2

Table 5: 2-in-1 compatibility (B2C activated)

• Organic phosphate

Table 6: Compatibility of 3-in-1 (activated B3C)

• Organic phosphate

The composition of vitamin and trace element preparations is illustrated below in Tables 7 and 8:

Table 7: Composition of the commercial trace element preparation used:

Table 8: Composition of the commercial vitamin preparations used:

If desired, you may also consult us regarding compatibility with other additives.

To perform an addition:

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

Preparation of the infusion:

• It must be carried out under aseptic conditions.
• Hang the bag.
• Remove the plastic protector from the administration outlet.
• Firmly insert the tip of the infusion set into the administration outlet.

Administration of the infusion:

• For single use only.
• Administer the product only after breaking the non-permanent seals between the two or three chambers and mixing the contents of the two or three chambers.
• Ensure that the final activated three-chamber bag emulsion for infusion shows no signs of phase separation, and that the final two-chamber bag solution for infusion shows no signs of particles.
• Immediate use after breaking the non-permanent seals is recommended. It should not be stored for subsequent infusion.
• Do not connect a partially used bag.
• Do not connect bags in series to avoid the risk of gas embolism due to residual air in the primary bag.
• The use of a 1.2-micron filter is recommended for the administration of Numeta G19%E.
• Unused product, materials that have been in contact with it, and all necessary disposable devices must be properly discarded.

Shelf life after mixing the solutions

Use the product immediately after opening the non-permanent seals between the two or three chambers. Studies have demonstrated the stability of the mixtures for 7 days at a temperature between 2 °C and 8 °C, followed by 48 hours at a temperature not exceeding 30 °C.

Shelf life after supplementation (electrolytes, trace elements, vitamins, water):

For certain additions, physical stability of the Numeta formulation has 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 conditions and duration of storage prior to use are the responsibility of the user and normally should not exceed 24 hours at 2 °C to 8 °C, unless reconstitution/dilution/addition has been carried out under controlled and validated aseptic conditions.

Do not use Numeta if the bag is damaged. A damaged bag may appear as follows:

• The non-permanent seals are broken.
• One of the chambers contains a mixture of any of the solutions.
• The amino acid and glucose solution is not clear, colorless, or slightly yellowish and/or contains visible particles.
• The lipid emulsion does not have a milky, whitish appearance.

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

Composition of Numeta G19%E

The active substances are:

B2C = 2-chamber bag, B3C = 3-chamber bag

The reconstituted solution/emulsion contains the following:

(a) Includes calories from egg phospholipids for infusion.

(b) Includes phosphate provided by egg phospholipids for infusion from lipids.

The other components are:

a for pH adjustment

Baxter and Numeta are trademarks of Baxter International Inc.