Isoren

Package leaflet: Information for the patient

ISOREN 5.4%, infusion solution

Amino acid solution
Please read this leaflet carefully before you are given 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 doctor or nurse.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or nurse. See section 4.

Contents of this leaflet:

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

1. What ISOREN is and what it is used for

ISOREN contains amino acids (substances used by your body for protein production).
ISOREN is a solution for parenteral nutrition, meaning it is administered intravenously
together with glucose- and fat-rich solutions, supplemented with salts, vitamins and trace elements, to
meet nutritional requirements.
ISOREN is indicated for nutritional treatment of patients with impaired kidney function or who are undergoing continuous ambulatory peritoneal dialysis (CAPD), a blood filtration system.
Consult your doctor if you do not feel better or if you feel worse.

2. What you need to know before ISOREN is administered to you

You must not be given ISOREN

• if you are allergic to one or more of the amino acids or to any of the other ingredients of this medicine (listed in section 6).
• if your body has problems utilizing amino acids.

Warnings and precautions
Talk to your doctor or nurse before ISOREN is administered to you:
When used in children under 2 years of age, the solution (in bottles and administration sets) must be protected from exposure to light until administration is complete. Exposure of ISOREN to ambient light, especially after the addition of trace elements and/or vitamins, generates peroxides and other degradation products, which can be minimized by protecting from light exposure.

• If you have liver disease (hepatic insufficiency). Your doctor will perform frequent blood tests/monitoring during treatment.
• If unusual signs or symptoms of an allergic reaction occur, such as fever, chills, skin rash, breathing difficulties, excessive sweating, nausea, or headache, inform your doctor or nurse immediately: the infusion will be stopped immediately.
• Some medications and diseases may increase the risk of developing infections or sepsis (bacteria in the blood). There is a particular risk of infection or sepsis when an intravenous catheter is inserted into a vein. Your doctor will carefully examine you to assess for any signs of infection.
• If you begin to experience difficulty breathing or shortness of breath, inform your doctor or nurse, as ISOREN may cause the formation of precipitates in the blood. The infusion will be stopped immediately and additional treatment may be required.
• In some cases, re-feeding a severely malnourished individual may cause changes in blood chemistry. Excess fluid in tissues and swelling may also develop. Parenteral nutrition should be started slowly and carefully.

During the infusion, blood and urine samples will be taken to monitor:

• Complete blood count,
• Blood acidity (pH) and levels of oxygen and carbon dioxide in the blood,
• Serum concentration (serum osmolarity),
• Electrolyte levels (electrolyte balance),
• Serum protein electrophoresis (measurement of specific proteins in the blood),
• Blood sugar levels (glycaemia),
• Ammonia levels,
• Kidney function.

Your doctor will carefully monitor you if you have:

• Liver disease or hepatic insufficiency,
• Renal insufficiency.

ISOREN must be used with caution if you have:

• Liver disease or hepatic insufficiency,
• Renal insufficiency,
• Fluid in the lungs (pulmonary edema) or heart disease (heart failure).

If symptoms occur at the injection site, administration will be suspended immediately. Appropriate therapy will be initiated and the injection site will be changed.

Newborns and children
Your doctor will perform frequent blood tests on your child to monitor blood nitrogen levels, in order to prevent hyperammonaemia (elevated nitrogen levels in the blood), which may occur if the patient has low body weight or if high doses are administered.

Other medicines and ISOREN
Inform your doctor if you are taking, have recently taken, or might take any other medicines.
No specific interactions have been reported.
To minimize the risk of potential incompatibilities, it is recommended not to add other medications to the solution.

Pregnancy, breastfeeding and fertility
If you are pregnant, think you might be pregnant, planning a pregnancy, or breastfeeding, consult your doctor before this medicine is administered to you.
ISOREN will be administered during pregnancy or breastfeeding only at the doctor’s discretion and in cases of absolute necessity.

Driving and using machines
Not applicable

ISOREN contains sodium metabisulfite.
Rarely, this may cause severe hypersensitivity reactions and bronchospasm.

3. How ISOREN will be administered

Dosage
Your doctor will decide how much you need and when it should be administered. This will depend on your age, body weight, clinical condition, reason for treatment, and your body's ability to metabolize and utilize the components of ISOREN. The dose you are given may also be influenced by other treatments you are receiving.

Use in neonates, children and adolescents
The dose will be determined by the doctor based on body weight and health status, as cases of hyperammonaemia (elevated levels of nitrogen in the blood) may occur if the patient has low body weight or if high doses are administered.

Method of administration
When used in children under 2 years of age, the solution (in vials and administration sets) must be protected from light exposure until administration is complete (see section 2).
This medicinal product will be administered intravenously by a healthcare professional.

If you are given more ISOREN than you should
Your doctor or nurse will monitor you during treatment.
If you are given high doses of Isoren, your doctor will carry out frequent laboratory tests.
Overdose or infusion rate higher than recommended may cause:

• hypervolaemia (increased volume of circulating blood),
• electrolyte disturbances (abnormal levels of electrolytes in the blood),
• acidosis (increased blood acidity),
• hyperazotaemia (high levels of nitrogen-containing compounds in the blood),
• hyperammonaemia (elevated levels of ammonia in the blood).

There is no specific antidote for overdose. In such cases, the infusion must be stopped immediately. Your doctor will decide whether further actions are necessary.
If you have any doubts about the use of this medicinal product, consult your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Before administration, your doctor will carry out blood tests.
If you experience any of the following symptoms, your doctor will IMMEDIATELY STOP the
administration of ISOREN and will initiate appropriate and specific treatment:

• severe allergic reaction causing difficulty in breathing or dizziness (anaphylactic reaction, anaphylactoid reaction), swelling of the skin of the face, lips, and throat,
• increased levels of ammonia in the blood,
• fever,
• chills, feeling unwell (nausea),
• malaise (vomiting),
• skin rash with itching and spots (urticaria),
• widening of blood vessels (vasodilation),
• abdominal pain,
• uncontrolled body movements (seizures).

If you experience any of the following symptoms, your doctor will change the injection site and will initiate appropriate and specific treatment:

• formation of blood clots in a vein (venous thrombosis) at the infusion site, causing pain, swelling or redness in the area of the clot,
• irritation and inflammation of a vein into which the solution is infused (phlebitis). This may cause redness, pain or burning, and swelling along the course of the vein where the solution is infused.

If you suffer from severe liver disease, you may experience excess amino acids (substances used by your body for protein production) in the blood (aminoacidemia) and increased levels of ammonia in the blood (hyperammonaemia).
The following side effects have been reported with medicines similar to ISOREN and may occur when using ISOREN:

• increased acidity of the blood (metabolic acidosis),
• headache,
• rapid heartbeat (tachycardia), bluish discoloration of lips, tongue and skin due to lack of oxygen in the blood (cyanosis),
• unstable circulatory condition with risk of death (shock), low blood pressure (hypotension), high blood pressure (hypertension),
• respiratory disorder, lack of oxygen in organs (hypoxia), stridor, shortness of breath (dyspnoea), sensation of suffocation, breathing faster or deeper than normal (hyperventilation),
• tingling or numbness sensation around the lips and mouth, mouth and throat pain,
• elevated levels of ammonia in the blood (hyperammonaemia), liver failure, liver disorders leading to replacement of normal liver tissue with scar tissue resulting in loss of liver function (hepatic cirrhosis, hepatic fibrosis), obstruction of normal bile flow (cholestasis), liver disorders including fatty liver disease (hepatic steatosis), inflammation of the gallbladder (cholecystitis), gallstones or bile duct stones (cholelithiasis),
• skin rashes, itching, skin redness,
• joint pain, muscle pain,
• elevated levels of nitrogen-containing compounds in the blood (azotaemia),
• reactions related to the administration technique:
• hot flushes, pallor, fluid accumulation under the skin,
• local pain or reactions (redness, warmth, swelling, skin cell death, blistering, scarring, discoloration) at the infusion site,
• hardness (induration) around the area where the product is injected,
• increased bilirubin levels in the blood, increased liver enzymes.

Additional side effects in children
If ISOREN is administered to your child/newborn who has low body weight, it may cause increased levels of ammonia in the blood (hyperammonaemia), especially if high doses are used.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or nurse. You can also report side effects directly via the website:
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store ISOREN

When used in children under 2 years of age, the solution (in the vials and administration sets) must be protected from exposure to light until administration is complete (see section 2).
Keep this medicine out of the sight and reach of children.
This medicine does not require any special storage conditions.
Do not use this medicine after the expiry date stated on the vial after "Exp".
The expiry date refers to the last day of that month.
The expiry date on the packaging refers to the product in its original, undamaged packaging that has been stored correctly.
This medicine does not require any special storage conditions.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What ISOREN contains

• Active substances per 1000 ml of solution:

L-Phenylalanine 3.00 g
L-Isoleucine 7.00 g
L-Histidine 5.00 g
L-Leucine 7.00 g
L-Lysine hydrochloride 8.00 g equivalent to L-Lysine 6.40 g
L-Methionine 6.80 g
L-Threonine 8.00 g
L-Tryptophan 2.00 g
L-Valine 9.00 g
Total Amino Acids 54.20 g/l
Total Nitrogen 7.26 g/l
Theoretical total osmolarity 482 mOsm/l
Sodium (Na+) 5 mEq/l
Chloride (Cl\−) 76 mEq/l
pH 4.2 – 4.7

• Other components: hydrochloric acid 37%, sodium metabisulfite (see section 2. Isoren contains sodium metabisulfite), water for injections q.s. to 1000 ml of solution.

Description of the appearance of ISOREN and contents of the pack
ISOREN is a solution for infusion supplied in 250 ml and 500 ml vials. The following pack sizes are available:

• 30 vials of 250 ml
• 20 vials of 500 ml

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
BAXTER S.p.A.
Via del Serafico 89
00142 Rome
Manufacturer
Bieffe Medital S.p.A.
Via Nuova Provinciale
23034 Grosotto (So)

The following information is intended exclusively for physicians or healthcare professionals:
PRECAUTIONS FOR USE
Administration of amino acids or protein hydrolysates to patients with hepatic insufficiency may cause imbalances in serum amino acids, pre-renal azotemia, and hyperammonemia. Therefore, careful patient monitoring is generally recommended through frequent hematobiochemical evaluations, particularly regarding: complete blood count, blood gas analysis, serum osmolarity, electrolyte and serum protein profile, renal function tests, blood glucose, and ammonia levels.
If symptoms of hyperammonemia occur, administration should be suspended and the patient's clinical status reassessed.

DOSAGE, METHOD AND DURATION OF ADMINISTRATION
The recommended dosage is approximately 250–500 ml per day; however, administration of the product depends on the individual patient's renal clearance. For this reason, careful monitoring of the patient with frequent hematobiochemical evaluations is generally advisable, particularly regarding: complete blood count, blood gas analysis, serum osmolarity, electrolyte and serum protein profile, renal function tests, blood glucose, and ammonia levels.

OVERDOSE
Hyperammonemia may occur if the amount of infused amino acids exceeds the non-protein caloric intake or if the infusion rate is too rapid.
If the increase in BUN exceeds 20 mg within 48 hours, infusion of amino acids should be suspended or the infusion rate reduced.
Periodic monitoring of blood ammonia levels is recommended throughout the entire treatment period.
In cases of inappropriate administration (overdose and/or rapid infusion rate), hypervolemia, electrolyte disturbances, and acidosis may occur. Hyperazotemia may develop if the amount of infused amino acids is excessive relative to the caloric intake. Hyperammonemia may occur, particularly in patients with severe liver disease. In such cases, infusion must be immediately discontinued and appropriate corrective measures implemented.
There is no specific antidote for overdose.

Handling and preparation
Use only if the container is undamaged and the solution is clear and colourless, ensuring that the vial shows no defects in closure or cracks, as these could compromise the sterility of the product.
When used in children under 2 years of age, the solution (in vials and administration sets) must be protected from light exposure until administration is complete.

Special warnings and precautions for use
Exposure to light of parenteral nutrition solutions, especially after addition of trace elements and/or vitamins, may lead to the formation of peroxides and other degradation products. When used in children under 2 years of age, Isoren must be protected from ambient light until administration is complete.

• Warm the solution to room temperature before use.
• Observe aseptic techniques.
• Each vial is for single use only, even if the solution is only partially used.
• Do not reconnect any partially used container.
• Inspect the final solution for any change in colour or presence of particles.
• Do not connect containers in series, to avoid gas embolism due to possible residual air in the primary container.
• ISOREN must not be infused through the same tubing as blood or blood components, unless documentation confirming safety is available.

Incompatibilities

• Additives may be incompatible.
• Do not add other medicinal products or substances without first confirming their compatibility and the stability of the resulting preparation.
• Excessive addition of calcium and phosphate increases the risk of calcium phosphate precipitate formation.

Special precautions for disposal and handling:
When used in children under 2 years of age, protect from light exposure until administration is complete. Exposure of Isoren 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.