Package Insert: Information for the User

SYNTHAMIN 14 REFORMULADO Infusion Solution

Read this package insert carefully before starting to use this medication, as it contains important information for you.

• Keep this package insert, as you may need to read it again.
• If you have any questions, consult your doctor or nurse.
• If you experience any adverse effects, consult your doctor or nurse, even if they are not listed in this package insert. See section 4.

1. What Synthamin is and how it is used

2. What you need to know before Synthamin is administered

3. How Synthamin will be administered

4. Possible adverse effects

5. Storage of Synthamin

6. Contents of the package and additional information

Synthamin is a sterile solution that contains a large number of compounds called amino acids. These are the building blocks for proteins that are vital for your body. It also contains some chemical substances called electrolytes, which are very important for your body to function correctly.

Along with other compounds such as minerals and vitamins, it is used to give you direct nutrition (food) through your blood when you cannot take food by mouth. It is essential that you are administered this medication to help you improve.

It is usually administered along with other nutrition solutions.

You should not be administered Synthamin if you have any of the following clinical situations

• If you are allergic to the active ingredients or to any of the other components of this medication (listed in section 6).

medication (including in the section 6).

• If you have any disease in the amino acid metabolism.
• If you have high levels of sodium, potassium, magnesium, and/or phosphate in your blood.

Warnings and precautions

Consult your doctor or nurse before starting to use Synthamin

• Synthamin will only be used if the solution is transparent and the container is not damaged.
• If symptoms of respiratory disorders appear.
• If you have a fever or feel unwell.
• You will have regular blood and urine tests to ensure you are receiving the correct amount of the solution. If necessary, you will be given other treatments.
• You will be closely monitored if you have liver, heart, or kidney problems. Please inform your doctor of this.
• You will be closely monitored if you have diabetes.
• If you are a very small child, more controls will be made.
• If necessary, you may also be given a vitamin called folic acid, fatty acids (the building blocks of fats), and sugar solutions (such as glucose) to ensure your body has all the necessary elements for good health.
• Synthamin should not be administered simultaneously with, before or after blood transfusion through the same infusion equipment.
• The concurrent administration of Synthamin solutions with concentrated glucose solutions may lead to hyperglycemia, glycosuria, and hyperosmolar syndrome. Therefore, in patients receiving this treatment, routine blood and urine glucose control should be performed. In certain patients, exogenous insulin may be necessary.

control of glucose in blood and urine. In certain patients, exogenous insulin may be necessary.

• If any abnormal sign or symptom of hypersensitivity or allergic reaction is observed, the infusion should be stopped immediately.

When used in newborns and children under 2 years, the solution (in bags and infusion equipment) should be protected from exposure to light until the end of administration. Exposure of Synthamin to ambient light, especially after mixing it with oligoelements or vitamins, generates peroxides and other degradation products that can be reduced if the product is protected from exposure to light.

Use of Synthamin with other medications

Inform your doctor or nurse if you are taking or have taken recently or may need to take any other medication.

No interactions with Synthamin have been studied.

Due to the content of potassium in Synthamin, special care is necessary in patients treated with potassium-sparing diuretics (e.g. amiloride, spironolactone, triamterene), with angiotensin-converting enzyme inhibitors, with angiotensin II receptor antagonists, or with immunosuppressants tacrolimus or cyclosporin due to the risk of hyperkalemia.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, or think you may be pregnant or plan to become pregnant, consult your doctor or pharmacist before using this medication.

The safety of amino acid solutions in pregnant women or during breastfeeding has not been demonstrated. Your doctor will carefully evaluate the benefits and potential risks before prescribing Synthamin.

Driving and operating machinery

Synthamin does not affect your ability to drive or operate machinery

Use in Adults

Your doctor will determine a perfusion rate based on your needs and clinical condition, which will depend on your weight, your body's needs, the amount of sugar solution (such as glucose) you can receive, and the reason for your treatment.

The solution will be administered through a slow drip injection (called perfusion) through a plastic tube carefully placed in a large vein in your chest (the vena cava). The drip rate will not exceed 70 ml per hour, and you will not receive more than 40 ml per kilogram of body weight per day.

You will not receive blood transfusions through this tube.

Use in Children

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

In children, the parenteral nutrition dose must be adjusted individually based on the patient's requirements for amino acids, electrolytes, and energy.

If You Are Given More Synthamin Than You Should

Since your doctor will be administering Synthamin to you, it is unlikely that you will receive too much. However, if you think you have received more than you should, tell your doctor or nurse.

In case of overdose or accidental ingestion, consult the Toxicology Information Service. Phone 915.620.420

Like all medications, this medication may produce adverse effects, although not all people may experience them.

Cases of a stinging pain and redness at the site where the medication is placed in your vein have been reported.

Severe hypersensitivity reactions, including a severe allergic reaction called anaphylaxis and other skin reactions (urticaria, hives, pruritus, erythema), gastrointestinal reactions, and circulatory or respiratory manifestations have also been notified.

The following may appear:

• fever,
• chills,
• high or low blood pressure (hypertension or hypotension),
• joint pain (arthralgia),
• muscle pain (myalgia),
• headache (cephalea).
• increased levels of nitrogen in the blood (azotemia) or ammonia (hyperammonemia),
• liver abnormalities.
• venous irritation (thrombosis, pain, erythema, heat, inflammation, hardening).

Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor or nurse, even if it is a possible adverse effect not listed in this prospectus. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Usewww.notificaRAM.es. By reporting adverse effects, you can contribute to providing more information about the safety of this medication.

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

When used in newborns and children under 2 years, the solution (in the bags and administration equipment) must be protected from exposure to light until the administration is completed (see section 2).

Do not store above 25°C.

Protect from light until immediately before use.

Do not refrigerate.

Do not use this medication after the expiration date that appears on the bag and the box

after CAD. The expiration date is the last day of the month indicated.

Dispose of partially unused containers. Any remaining solution must be discarded by a healthcare professional.

Composition of Synthamin

The active principles per 1000 ml are: Glycine 8.76 g, L-Alanine 17.60 g, L-Arginine 9.78 g, L-Phenylalanine 4.76 g, L-Histidine 4.08 g, L-Isoleucine 5.10 g, L-Leucine 6.20 g, L-Lysine hydrochloride 6.16 g, L-Methionine 3.40 g, L-Proline 5.78 g, L-Serine 4.25 g,

L-Tyrosine 34 mg, L-Threonine 3.57 g, L-Tryptophan 1.53 g, L-Valine 4.93 g, Sodium acetate trihydrate 5.94 g, Potassium phosphate dibasic 5.22 g, Sodium chloride 1.54 g, Magnesium chloride hexahydrate 1.02 g.

The other components are Water for injection preparations and acetic acid

Approximate electrolyte concentrations (mmol/l) of the solution

Sodium: 70

Potassium: 60

Magnesium: 5

Acetate(1): 140

Chloride: 70

Phosphate (as HPO4-2): 30

Amino acid concentration: 85 g/l

Nitrogen equivalence: 14 g/l

Protein equivalence: 88 g/l

Essential AA/Total AA ratio: 0.45

Approximate pH: 6

Calculated osmolality (mOsm/l): 1160

(1) Acetate is added as sodium acetate and/or acetic acid for pH adjustment.

Appearance of the product and packaging contents

Synthamin is a transparent, particle-free solution. It is presented in Viaflex plastic bags. Each bag is packaged in a sealed plastic protective overbag.

The bag sizes can be 500 and 1000 ml

The bags are delivered in boxes, each containing the following quantities:

• 10 bags of 500 ml
• 10 bags of 1.000 ml

Only some packaging sizes may be commercially available.

Marketing Authorization Holder

Baxter S.L.

Camilo Pouet 2, 46394 Ribarroja del Turia (Valencia)

Spain

Responsible for manufacturing

Baxter S.A

Boulevard René Branquart, 80

7860 Lessines

Belgium

Last review date of this leaflet: March 2020

Detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/

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This information is intended solely for healthcare professionals

Dosage and administration

Dosage

The total daily dose of these solutions depends on the patient's metabolic needs and clinical response.

Probably, the best procedure for setting individual nitrogen needs is to determine the fluid balance. Daily doses of amino acids of approximately 1.0-1.5 g/kg in adults and 2-3 g/kg in children, with an adequate amount of calories (approximately 180 Kcal/g of nitrogen or +/-30 Kcal/g of amino acids) are generally sufficient to meet protein needs and promote a positive nitrogen balance.

Use of higher doses, mainly in children, should be monitored by more frequent laboratory tests. The infusion rate should not exceed 0.1 g/kg per hour. The maximum infusion rate depends on the concentration of amino acids used. In the case of Synthamin 14 (8.5% Amino Acids) it will be 100 ml/h.

It is necessary to ensure the maintenance of serum potassium levels. An amount of potassium equivalent to 60-180 mEq/day may be indicated. It may be useful to add electrolytes and potassium, depending on the amount of carbohydrates administered and metabolized by the patient. It is essential to frequently monitor serum electrolyte levels, particularly phosphate, magnesium, and chloride.

Individuals may add vitamins, oligoelements, and other components (including glucose and lipids) to the parenteral nutrition regimen to meet nutritional needs and prevent deficiencies and the development of complications.

The co-administrationof anintravenous fat emulsion should be evaluated whenlong-term parenteral nutrition is required toprevent essential fatty acid deficiency (EFAD).

In the case of peripheral administration, the osmolality of the solution should be taken into account.

The solution should be visually inspected for particles and color before administration.

The infusion rate of the solution should be gradually increased during the first hour, and adjusted according to the dose to be administered, the daily volume indicated, and the duration of the infusion.

The use of a final filter during the administration of parenteral nutrition solutions is recommended.

Administration

When used in newborns and children under 2 years, the solution (in bags and administration equipment) should be protected from exposure to light until the end of administration.

Hyperosmolar amino acid and glucose mixtures are preferably administered through a central catheter. If central access is not indicated, they can be administered peripherally to patients who require parenteral nutrition, amino acid solutions with glucose solutions of appropriate concentration, simultaneously with lipid emulsions.

Do not administer unless the solution is clear and colorless or slightly yellow and the packaging is in good condition.

Special warnings and precautions for use:

Exposure to light of parenteral nutrition solutions for intravenous use, especially after mixing with oligoelements or vitamins, may have adverse effects on the clinical outcome of newborns due to the generation of peroxides and other degradation products.

When used in newborns and children under 2 years, Synthamin should be protected from ambient light until the end of administration.

Handling and preparation

Instructions for use of the Viaflex bag

Use an aseptic technique.

1. Remove the Viaflex bag from its protective overbag at the time of use. Discard the absorbent oxygen bag.

1. Ensure the absence of leaks by pressing the Viaflex bag. Check the transparency of the solution, as well as the absence of foreign particles.

1. Hang the Viaflex bag. Prepare the administration equipment and close the flow regulator.

1. Remove the protective cap from the outlet tube of the Viaflex bag and the protective cap from the puncture of the administration equipment. Insert the puncture of the administration equipment into the outlet tube of the Viaflex bag.

1. Follow the administration equipment usage instructions to purge it and administer the solution.

In the case of additions to the bag:

Use an aseptic technique.

Verify the stability and compatibility of the additives.

Prepare the injection point of the bag.

Puncture the injection point and inject the additives using a syringe or a reconstitution device.

Mix the contents of the bag and additives.

Inspect the final mixture for color and foreign particles.

Check the absence of leaks in the bag.

Ensure that the storage conditions for the additive are met.

Administration of the infusion:

Do not administer blood before, at the same time, or after, through the same equipment due to the risk of

pseudoagglutination.

Do not connect bags in series to avoid gas embolism due to residual air in the primary packaging.

Discard after single use.

Discard any remaining portion.

Do not reconnect partially used bags.

Special precautions for disposal and other manipulations:

When used in newborns and children under 2 years, it should be protected from exposure

to light until the end of administration. Exposure of Synthamin to ambient light, especially after mixing with oligoelements or vitamins, generates peroxides and other degradation products that can be reduced if the product is protected from exposure to light.

Baxter, Viaflex, and Synthamin are registered trademarks of Baxter International Inc.