ISOPURAMIN

Patient Information Leaflet

Isopuramin – 10% infusion solution

10% 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 Isopuramin is and what it is used for
2. What you need to know before you are given Isopuramin
3. How Isopuramin will be administered to you
4. Possible side effects
5. How to store Isopuramin
6. Contents of the pack and other information

1. What ISOPURAMIN is and what it is used for

ISOPURAMIN contains amino acids (substances used by your body for protein production).
ISOPURAMIN is used to provide food (nutrition) directly into the bloodstream when sufficient amounts cannot be taken by mouth. This means it is administered through a vein, together with solutions rich in sugars and fats, in addition to salts, vitamins, and trace elements, in order to meet nutritional requirements.
ISOPURAMIN is indicated in adults and children:

• If you are in a state of malnutrition of various origins,
• If you are about to undergo or have recently undergone surgery,
• If you have extensive burns,
• If you suffer from a severe liver disease (decompensated liver cirrhosis),
• If you suffer from a kidney disease (nephrotic syndrome without renal insufficiency, acute and chronic uremia undergoing periodic peritoneal dialysis or extracorporeal dialysis), and are also undergoing dialysis, a blood filtration method,
• If you are in a condition requiring a significant nitrogen supply for protein rebuilding.
  Consult your doctor if you do not feel better or if you feel worse.

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

You must not be given ISOPURAMIN

• 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 you are not producing urine (acute and chronic uraemia under conservative medical treatment).
• If you are dehydrated.
• If you have severe liver disease (hepatic coma).
• If you have high levels of sodium in your blood.
• If you have a disorder related to amino acid metabolism.

Warnings and precautions
Talk to your doctor or nurse before ISOPURAMIN is administered to you.
When used in children under 2 years of age, the solution (in bottles and administration sets) must be protected from light exposure until administration is complete. Exposure of Isopuramin 10% 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.
If you experience any unusual signs or symptoms of an allergic reaction, such as fever, chills, skin rash, difficulty breathing, excessive sweating, nausea or headache, contact your doctor or nurse immediately: the infusion will be stopped immediately.
ISOPURAMIN may cause formation of precipitates in the blood. If you begin to experience difficulty breathing or shortness of breath, contact your doctor or nurse immediately: the infusion will be stopped immediately and additional treatment may be required.
Some medicines and medical conditions may increase the risk of developing infections or sepsis (bacteria in the blood). There is a particular risk of infection or sepsis when a tube (intravenous catheter) is placed into a vein. Your doctor will carefully examine you to assess for any signs of infection.
If you are severely malnourished and require intravenous feeding, parenteral nutrition should be started slowly and carefully.
ISOPURAMIN may cause a stinging sensation and redness at the site of intravenous administration when given in the arm.
Your doctor will monitor your condition during infusion, especially if you currently have liver, kidney, heart or circulatory problems.
Amino acid solutions may increase levels of ammonia or nitrogen-containing compounds in the blood. Your doctor will monitor your blood tests accordingly.
Your doctor must be informed of any serious medical conditions you have that affect fluids, sugars, fats, proteins, and salts (metabolic disorders). These conditions should be corrected before starting ISOPURAMIN.
Inform your doctor if you have or have had:

• Allergic reaction during infusion. The infusion will be stopped immediately.
• Liver disease or liver failure.
• Heart failure (special monitoring may be required in the above conditions).
• Haemodialysis. The maximum volume of infusion that you can tolerate should be taken into consideration.

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

• Fluid volume in the body;
• Levels of chemical substances in blood and urine;
• Acid-base balance (acidity in blood and urine);
• Liver and kidney function

Children and adolescents
Your doctor will perform frequent blood tests in your child to monitor blood nitrogen levels, in order to prevent hyperammonaemia (elevated nitrogen levels in blood), which may occur during prolonged treatment. Blood electrolyte levels should also be monitored to ensure they remain within acceptable ranges.
Elderly
Your doctor will ensure that elderly patients undergo frequent blood tests to monitor blood nitrogen levels, in order to prevent hyperammonaemia (elevated nitrogen levels in blood), which may occur during prolonged treatment.
Other medicines and ISOPURAMIN
Inform your doctor if you are taking, have recently taken, or might take/be administered any other medicines.
No specific interactions have been reported.
To minimize the risk of incompatibilities, it is recommended not to add other medicines to the solution.
Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or are breastfeeding, consult your doctor before this medicine is administered to you.
There are no definite data on toxicity or safety of use during pregnancy; use only if clearly needed and under strict medical supervision.
ISOPURAMIN contains sodium metabisulphite
Rarely, this may cause severe hypersensitivity reactions and bronchospasm.

3. How ISOPURAMIN will be administered to you

ISOPURAMIN will be administered to you by a healthcare professional. Your doctor will determine the dose based on your age, body weight, clinical condition (nutritional status and severity of illness), nitrogen requirements, and your tolerance. Your doctor will also decide how long the treatment will last.

Method of administration
When used in children under 2 years of age, the solution (in the vials and in the administration sets) must be protected from exposure to light until administration is completed (see section 2).
You will receive this medicine by injection into a vein.

If you are given more ISOPURAMIN than you should
Your doctor or nurse will monitor you during treatment.
If you are given too much ISOPURAMIN and/or it is administered too rapidly, you may develop the following symptoms:

• high levels of nitrogen in the blood (hyperazotaemia)
• high levels of ammonia in the blood (hyperammonaemia), especially if you have severe liver disorders
• high fluid levels (hypervolaemia)
• an electrolyte imbalance
• high levels of acid in the blood (acidosis)

If you have any doubts about the use of this medicine, consult your doctor or nurse.

4. Possible side effects

The following side effects have been reported with ISOPURAMIN with a frequency not known (frequency cannot be estimated from the available data).
Laboratory tests:
An increase in liver enzymes known as transaminases.

The following adverse reactions are considered to be associated with the use of ISOPURAMIN. These have been reported for similar products, with a frequency not known (cannot be estimated from the available data):

• Severe allergic reactions, called anaphylactic and anaphylactoid reactions, which may cause: rapid heartbeat, shock, low blood pressure, breathing difficulties, noisy breathing, sensation of throat tightness, fast or deep breathing, vomiting, nausea, generalised swelling, pallor, circulatory instability, life-threatening condition
• Other symptoms of allergic reaction: urticaria, hypertension, skin reaction, skin redness (erythema), facial swelling, swelling of the eyelids
• Excess ammonia in the blood
• Disturbance of the acid-base balance in the blood
• Headache
• Increased heart rate
• Bluish discoloration of the skin
• Respiratory disorders
• Reduced oxygen supply to tissues
• Sensation of throat tightness
• Increased respiratory rate
• Nausea and vomiting
• Tingling or numbness of the mouth
• Pain at the back of the mouth
• Liver failure
• Chronic liver disease, known as cirrhosis
• Liver thickening
• Fatty liver
• Condition in which bile cannot flow from the liver to the duodenum
• Inflammation of the gallbladder
• Presence of one or more stones (gallstones) in the gallbladder
• Skin reactions
• Joint and muscle pain
• Elevated levels of urea and nitrogenous waste products in the blood
• Local pain or reaction at the infusion site (irritation, swelling, warmth, formation of a hard nodule, necrotic tissue formation)
• Irritation, inflammation, and blood clot formation in the vein into which the solution is infused
• Increased bilirubin in the blood
• Increased liver enzymes
• Increased body temperature

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, consult your doctor. You may also report side effects directly via the national reporting system at the following 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 ISOPURAMIN

When used in children under 2 years of age, the solution (in vials and administration sets) must be protected from light exposure until the end of administration (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 bag after Exp. The expiry date refers to the last day of that month.
Do not dispose of medicines 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 ISOPURAMIN contains

• The active substances in 1000 ml of 10% amino acid solution are: L-Alanine g 7.00, L-Arginine g 11.70, L-Phenylalanine g 7.90, Glycine g 6.40, L-Isoleucine g 8.00, L-Histidine g 5.10, L-Leucine g 10.60, L-Lysine Acetate g 16.23 equivalent to L-Lysine g 11.50, L-Methionine g 7.20, L-Tyrosine g 0.30, L-Threonine g 9.50, L-Tryptophan g 3.20, L-Valine g 11.60.
• The other components are L-Cysteine, glacial Acetic Acid, Sodium metabisulfite (see section 2). ISOPURAMIN contains sodium metabisulfite, Water for injections.

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

• 30 bottles of 250 ml of 10% amino acid solution
• 20 bottles of 500 ml of 10% amino acid solution. Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer
Baxter S.p.A.
Via del Serafico 89
00142 Rome
Manufacturer
BIEFFE MEDITAL S.p.A. – Pharmaceutical plant in Grosotto (SO)

The following information is intended exclusively for physicians or healthcare professionals:
The solution should be administered only if perfectly clear, and the bottle must be checked for closure defects or cracks, as these could compromise the sterility of the product.
Each bottle is for single use only, even if only part of the solution is used. Any unused portion must not be reused.
Infusion should be discontinued at the onset of chills or any signs of intolerance.
The product must be used with caution in patients with renal impairment or hyperazotemia.
To minimize the risk of possible incompatibilities, it is advisable not to add other drugs to the solution.
Do not reconnect partially used infusions. Do not connect containers in series to avoid gas embolism due to possible residual air in the primary container.

DOSAGE, METHOD AND DURATION OF ADMINISTRATION
Dosage depends on the patient's clinical condition, according to medical prescription. It is advisable to start infusion at less than 40 drops per minute.
For proper nutritional therapy with Isopuramin 10%, it is recommended to administer 35–45 kcal/kg/day in the form of glucose or lipids. In such cases, administration of insulin, potassium, sodium, chloride, phosphorus, magnesium, and other elements should be considered based on clinical requirements. Dosage depends on the patient's clinical condition, according to medical prescription.
The initiation of parenteral nutrition, as well as dosage (dose and frequency of administration), depends on the following patient characteristics:

• age, weight, clinical condition,
• nitrogen requirements,
• metabolic capacity,
• supplementary nutrition that may be provided via parenteral and/or enteral routes.

As determined individually, vitamins, trace elements, and other components (including glucose and lipids) may be added to the parenteral nutrition regimen to meet nutritional needs and prevent deficiencies and complications. When prolonged parenteral nutrition is required, concomitant administration of a fat emulsion should be considered to prevent essential fatty acid deficiency.

Method of administration
Isopuramin 10% is intended for intravenous use.
The osmolarity of a specific infusion solution must be considered when evaluating peripheral administration.
Highly hypertonic parenteral solutions (>900 mOsm/l) must be administered through a central venous catheter with the tip positioned in a large central vein.
Flow rate should be adjusted according to the administered dose, daily volume intake, and duration of infusion.
Parenteral medicinal products should be visually inspected for the presence of particles and discoloration prior to administration.
When used in children under 2 years of age, the solution (in bottles and administration sets) must be protected from light exposure until the end of administration.

Special warnings and precautions for use
Exposure to light of parenteral intravenous 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, Isopuramin 10% must be protected from ambient light until the end of administration.

Special precautions for disposal and handling:
When used in children under 2 years of age, protect from light exposure until the end of administration. Exposure of Isopuramin 10% to ambient light, particularly after addition of trace elements and/or vitamins, generates peroxides and other degradation products, which can be minimized by protecting from light.