Numeta G13% E emulsion for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

NUMETA G13%E emulsion for infusion

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

• Keep this leaflet, as you may need to read it again.
• If you have any questions, 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 G13%E is and what it is used for
2. What you need to know before Numeta G13%E is administered to your child
3. How Numeta G13%E will be administered
4. Possible side effects
5. How to store Numeta G13%E
6. Contents of the pack and other information

1. What Numeta G13%E is and what it is used for

Numeta G13%E is an emulsion for specialized nutrition designed for premature newborns. It is administered through a tube connected to your child's vein when they are unable to take all their food orally.

Numeta is supplied as a tricompartmental bag containing three separate chambers which hold:

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 G13%E must only be used under medical supervision.

2. What you need to know before Numeta G13%E is administered to your child

Numeta G13%E must not be given to your child in the following cases:

With glucose and amino acid/electrolyte solutions mixed in the bag ("2 in 1"):

• If your child is allergic to egg, soy, peanuts, or any of the ingredients of this medicine or components of the container (listed in section 6).
• If your child's body has problems utilizing the constituents of proteins.
• If your child has high blood concentrations of any of the electrolytes included in Numeta G13%E.
• Numeta G13%E (or other solutions containing calcium) must not be administered at the same time as ceftriaxone (an antibiotic), even if different infusion lines are used. There is a risk of forming particles in the newborn's bloodstream, which may be fatal.
• If your child has hyperglycemia (especially high levels of sugar in the blood).

With glucose, amino acid/electrolyte, and lipid solutions mixed in the bag ("3 in 1"):

All the situations listed for the "2 in 1" formulation, plus the following:

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

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

Warnings and precautions

Consult your child’s doctor or nurse before Numeta G13%E is administered.

When used in newborns and children under 2 years of age, the emulsion (in bags and administration sets) must be protected from exposure to light until administration is complete. Exposure of Numeta G13%E to ambient light, especially after mixing with trace elements or vitamins, may generate peroxides and other degradation products. These can be minimized by protecting the product from light exposure.

Allergic reactions:

Infusion must be stopped immediately if any sign or symptom of an allergic reaction occurs (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 seed proteins.

Numeta G13%E contains glucose derived from corn starch and should therefore be used with caution in patients with a known allergy to corn or corn products.

Risk of particle formation with ceftriaxone (antibiotic):

Do not mix or administer a specific antibiotic called ceftriaxone at the same time as a solution containing calcium (including Numeta G13%E) via intravenous infusion.

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

Formation of small particles in the lung blood vessels:

Difficulty breathing may also be a sign of formation of small particles that block blood vessels in the lungs (pulmonary vascular precipitates). If your child experiences difficulty breathing, inform your child’s doctor or nurse. They will decide what measures should be taken.

Infection and sepsis:

Your child’s doctor will closely monitor for any signs of infection. Using an “aseptic technique” (germ-free technique) when placing and maintaining the catheter, as well as when preparing the nutritional formula, can reduce the risk of infection.

Sometimes, children may develop infections and sepsis (bacteria in the blood) when a tube is connected to a vein (intravenous catheter). Certain medications and medical conditions may increase the risk of developing infection or sepsis. Patients requiring parenteral nutrition (nutrition administered 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. A reduced or limited capacity of the body to eliminate the fats contained in Numeta G13%E, or overdosage, may result in a “fat overload syndrome” (see sections 3 and 4).

Changes in blood chemical levels:

Your child’s doctor will check and monitor your child’s fluid balance, blood chemicals, and other blood values during treatment with Numeta G13%E. In some cases, refeeding a severely malnourished individual may lead to changes in blood chemical levels that may need correction. Excess fluid in tissues and swelling may also occur. It is recommended to start parenteral nutrition slowly and under supervision.

Monitoring and adjustment

The doctor will closely monitor and adjust the dose of Numeta G13%E according to your child’s individual needs, especially if they have any of the following conditions:

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

Use with caution:

Numeta G13%E should be used with caution if your child has:

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

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

There is limited data on the use of this medicine in premature infants less than 28 weeks of gestational age.

Use of Numeta G13%E with other medicines

Inform your doctor if your child is taking or using, has recently taken or used, or might need to take or use any other medicine.

Numeta G13%E must not be administered at the same time as:

• ceftriaxone (an antibiotic), not 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 stacking together).
• ampicillin, fosphenytoin, and furosemide through the same infusion line, as there is a risk of particle formation.

Coumarin and warfarin (anticoagulants)

Your doctor will closely monitor your child if they are taking coumarin or warfarin. These medicines are anticoagulants used to prevent blood clotting. Olive and soybean oils naturally contain vitamin K1. Vitamin K1 may interfere with the action of drugs 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 5 to 6 hours after lipid administration or when no further lipids are being administered.

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

Numeta G13%E contains potassium. High levels of potassium in the blood may cause abnormal heart rhythm. Particular caution is required in patients receiving diuretics (medicines that reduce fluid retention), ACE inhibitors (medicines used to treat high blood pressure), angiotensin II receptor antagonists (medicines used to treat high blood pressure), or immunosuppressants (medicines that may reduce the body's natural defenses). These types of medicines may increase potassium levels.

3. How Numeta G13%E will be given to your child

Your child must always be given Numeta G13%E exactly as prescribed by the doctor. Please consult your doctor if you have any questions.

Age group

Numeta G13%E has been designed to meet the nutritional needs of premature newborns.

Numeta G13%E may not be suitable for some premature infants, as their clinical condition may 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 connected to a vein in your child's arm or a large vein in the chest.

The doctor may decide not to administer lipids to your child. The design of the Numeta G13%E bag allows only the non-permanent seal between the amino acids/electrolytes and glucose compartments to be broken, if necessary. In this case, the seal between the amino acids and lipid compartments remains intact. The contents of the bag may then be infused without lipids.

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

Dosage and duration of treatment

The doctor will determine the dose required by the child and how long the treatment will last. The dose depends on your child's nutritional needs and will be based on body weight, medical condition, and the body's ability to metabolize and absorb the components of Numeta G13%E. Additional proteins or nutrition may also be administered orally or enterally.

If your child is given more Numeta G13%E than they should

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

Symptoms

Receiving too much medicine or receiving it too rapidly may cause:

• Nausea (feeling unwell).
• Vomiting.
• Chills.
• Electrolyte disturbances (abnormal levels of electrolytes in the blood).
• Signs of hypervolemia (increased blood circulation volume, too much fluid in the blood vessels).
• Acidosis (increased blood acidity).

In such cases, the infusion must be stopped immediately. The doctor will decide whether further actions are necessary.

An overdose of the fats contained in Numeta G13%E may cause a "fat overload syndrome," which is usually reversible once the infusion is stopped. 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, the 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 change in how your child feels during or after treatment, inform the doctor or nurse immediately.

The tests the doctor will perform on your child while receiving this medicine should 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:

Common: 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 disturbances (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 the 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 capacity 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 medical condition.
    • High fat levels in the blood (hyperlipidemia).
    • Fever.
    • Fatty infiltration of the liver (hepatomegaly).
    • Worsening of liver function.
    • Decrease in red blood cells, which may cause paleness of the skin and lead to 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 adverse effects, consult your doctor or nurse, even if they are possible adverse effects 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 G13%E

Keep this medicine out of the sight and reach of children when not in use.

When used in newborns and children under 2 years of age, the emulsion (in the 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 outer packaging (MM/YYYY). The expiry date refers to the last day of the month indicated.

Do not freeze.

Store within the overpouch.

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

6. Contents of the pack and other information

Appearance of Numeta G13%E and contents of the pack

Numeta G13%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 contains a uniform liquid with a milky white appearance.

Appearance after reconstitution:

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

The three-compartment bag is a multilayer plastic bag.

To avoid contact with air, Numeta G13%E is packaged inside an overpouch with an oxygen barrier, which also contains an oxygen absorber and an oxygen indicator.

Pack sizes

300 ml bag: 10 units per box

1 bag of 300 ml

Only some pack sizes may be marketed.

Marketing Authorization Holder and Manufacturing Responsible

Marketing Authorization Holder

Baxter, S.L.

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

Manufacturer Responsible

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:

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

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

---

This information is intended for healthcare professionals only:*

• Please note that in certain cases this product may be administered at home by parents or other caregivers. In such cases, parents/caregivers should read the following information.

Do not add any medication to the bag without first checking compatibility. Particles may form or the lipid emulsion may break down, which could block blood vessels.

Numeta G13%E must be at room temperature before use.

Before administering Numeta G13%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 between any of the three chambers.
• The amino acid solution and glucose solution are clear, colorless or slightly yellowish, and free from visible particles.
• The lipid emulsion is a uniform milky white liquid.

Before opening the outer bag, examine the color of the oxygen indicator.

• 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 indicator does not match the reference color printed next to the OK symbol.

Figures 1 and 2 illustrate how to remove the outer bag. Discard it together with the oxygen indicator and 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: Change 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 appearance of the mixed solution should be 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 with the palms of your hands.

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

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 appearance of the mixed solution should be 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

Daily volume intake

Duration of infusion.

Method of administration

When used in newborns and children under 2 years of age, the emulsion (in the bag and in the administration set) must be protected from exposure to light until administration is complete.

Use of a 1.2-micron filter is recommended for administration of Numeta G13%E.

Due to its high osmolarity, Numeta G13%E may only be administered undiluted via a central vein; however, appropriate dilution of Numeta G13%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 the additions to the 2- and 3-chamber bags after the addition of water for injectable preparations:

Addition of medication

Exposure to light of intravenous parenteral nutrition solutions, especially after mixing with trace elements 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 G13%E must be protected from ambient light until administration is complete.

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

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

Tables 1–4 show possible additions of commercially available trace element solutions (identified as TE1 and TE4), vitamins (identified as lyophilized V1 and emulsion V2), and electrolytes in defined amounts.

1 Compatibility with TE4, V1, and V2

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

• Organic phosphate

Table 2: Compatibility of 2-in-1 (activated B2C) with or without dilution in water

• Organic phosphate

2 Compatibility with TE1, V1 and V2

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

• Organic phosphate

Table 4: Compatibility of 2-in-1 (activated B2C) with or without dilution in water

• Organic phosphate

The composition of vitamin and trace element preparations is illustrated below in Tables 5 and 6:

Table 5: Composition of the commercial trace element preparation used:

Table 6: Composition of the commercial vitamin preparations used:

To perform an addition:

• 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:

• 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 visible particles.
• Immediate use after breaking the non-permanent seals is recommended. It must not be stored for subsequent infusion.
• Do not connect a partially used bag.
• The use of a 1.2-micron filter is recommended for the administration of Numeta G13%E.
• Do not connect bags in series to avoid the risk of gas embolism due to residual air in the primary bag.
• When used in neonates and children under 2 years of age, the product must be protected from light exposure until administration is complete. Exposure of Numeta G13%E to ambient light, especially after mixing with trace elements or vitamins, may generate peroxides and other degradation products, which can be minimized by protecting the product from light.
• Unused product, materials that have been in contact with it, and all necessary disposable devices must be properly discarded.

Validity period after mixing the solutions

Use the product immediately after breaking 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.

Validity period after supplementation (electrolytes, trace elements, vitamins, water)

For specific mixtures of Numeta formulation, physical stability has been demonstrated for 7 days at temperatures of 2 °C to 8 °C, followed by 48 hours at 30 °C. Information on these additions is specified in section 6.6 of the Summary of Product Characteristics.

From a microbiological standpoint, the product should be used immediately. If not used immediately, the conditions and duration of storage before use are the responsibility of the user and normally should not exceed 24 hours at 2 °C to 8 °C, unless the reconstitution/dilution/addition has been carried out under controlled and validated aseptic conditions.

Do not use Numeta G13%E if the bag is damaged. A damaged bag may show the following characteristics:

• 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 appear milky and white.

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

Composition of Numeta G13%E

The active substances are:

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

The reconstituted solution/emulsion provides the following:

(a) Includes calories from egg phospholipids for perfusion.

(b) Includes the phosphate provided by egg phospholipids for perfusion.

The other components are:

(a) for pH adjustment

Baxter and Numeta are registered trademarks of Baxter International Inc.