XENETIX 350 mg Iodine/ml INJECTABLE SOLUTION

Introduction

Leaflet: information for the user

XENETIX 300 mg Iodo/ml injectable solution

XENETIX 350 mg Iodo/ml injectable solution

Iobitridol

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet, as you may need to read it again.

If you have any further questions, ask your doctor or pharmacist.

• If you experience any side effects, talk to your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

Contents of the pack and other information

1. What is XENETIX and what is it used for
2. What you need to know before you use XENETIX
3. How to use XENETIX
4. Possible side effects
5. Storage of XENETIX

Contents of the pack and additional information

1. What is XENETIX and what is it used for

XENETIX is a radiological contrast agent (iodinated, opacifying properties), hydrophilic, non-ionic, low-osmolar, for radiological examinations of the kidneys and urinary tract (urography), whole body and brain (tomography), heart (angiocardiography), venous blood vessels (venography) or arterial (arteriography) and breast (mammography with contrast).

This medicinal product is for diagnostic use only.

2. What you need to know before you use XENETIX

Do not use XENETIX:

• If you have previously suffered from a severe skin rash or skin peeling, blisters and/or sores in the mouth after administration of XENETIX.
• If you are allergic to the active substance (iobitridol) or to any of the other components of this medicinal product (listed in section 6).
• If you have had a significant skin allergic reaction, immediate or delayed, when you were administered XENETIX in previous examinations (see section 4. Possible Side Effects)
• If you have an overproduction of thyroid hormones (manifest thyrotoxicosis).

Warnings and precautions

Consult your doctor or pharmacist before starting to use XENETIX.

As with all iodine-based contrast agents, regardless of the route of administration and dose, all iodinated contrast agents can induce mild, severe, or even fatal reactions. These reactions can occur within the first hour or, less frequently, within 7 days after administration. These reactions are unpredictable and more frequent if you have already experienced a reaction after being administered an iodinated contrast agent (see section 4. Possible Side Effects). Therefore, you should inform the radiologist performing the examination if you have had an allergic reaction during a previous examination with an iodinated contrast agent.

Tell your doctor if you have any medical condition so that they can take all necessary precautions, especially:

• If you have had previous reactions to an iodinated contrast agent during an examination.
• If you have had a severe rash or skin peeling, blisters and/or sores in the mouth after administration of Xenetix or another iodinated contrast agent.
• If you have kidney failure (renal impairment) or diabetes or if you are undergoing dialysis, as iodinated contrast agents can cause a temporary alteration of renal function or worsen pre-existing kidney failure.
• If you have both kidney and liver failure (renal and hepatic impairment), as this increases the risk of contrast retention.
• If you are asthmatic and/or have had an asthma attack in the 8 days prior to the examination, as this increases the risk of bronchospasm (involuntary contraction of bronchial muscles).
• If you have a thyroid disorder or a history of thyroid disease, as this can exacerbate hyperthyroidism or develop hypothyroidism. Also, inform them if you are going to undergo a thyroid examination or treatment with radioactive iodine.
• If you have heart failure (cardiac impairment), coronary insufficiency, or any other severe cardiovascular disease, as the risk of certain adverse reactions is increased.
• If you have neurological disorders, cerebral edema, recent history of intracranial hemorrhage, acute cerebral infarction, transient ischemic attacks, epilepsy, or if you are addicted to alcohol or drugs, as the benefit/risk of undergoing the test should be evaluated.
• If you have pheochromocytoma (high hormonal secretion causing severe hypertension), as you should be monitored to prevent the development of a hypertensive crisis.
• If you have myasthenia gravis (autoimmune muscle disease), as symptoms may worsen.
• If you feel anxious, agitated, or afraid of the examination, do not hesitate to inform your doctor, as possible side effects can be intensified in these situations.
• If you have pancreatic disease (acute pancreatitis).
• If you have bone marrow disease (monoclonal gammopathy, multiple myeloma, or Waldenström's macroglobulinemia)

Be careful with XENETIX

There have been reports of severe skin reactions, including drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (Lyell's syndrome or TEN), and acute generalized exanthematous pustulosis (AGEP), which can be fatal, with the use of XENETIX.

During the image acquisition procedure or shortly after, you may experience a short-term brain disorder called encephalopathy. Seek medical attention immediately if you experience any of the symptoms related to this condition described in section 4.

Children

Thyroid disorders may be observed after administration of XENETIX. Special attention should be paid to newborns, including those whose mother received XENETIX during pregnancy, and premature and young children. Doctors should check the child's thyroid function.

Using XENETIX with other medicines

Please inform your doctor or pharmacist if you have any other disease or:

• If you are taking Metformin (a drug for the treatment of diabetes), as lactic acidosis may occur.
• If you are taking beta-blockers, vasoactive drugs, ACE inhibitors, or angiotensin receptor antagonists, as these drugs reduce the cardiovascular compensation mechanism that is activated when a hemodynamic disorder occurs.
• If you are taking diuretics, as there is a risk of dehydration and your doctor should proceed with saline rehydration before administering the contrast agent.
• If you have recently been administered interleukin-2 intravenously, as this increases the risk of developing a reaction to contrast agents.
• If you are going to undergo tests with radiopharmaceuticals where iodine could interfere.
• If you are going to undergo a blood or urine test.
• If you are taking or have recently taken other medicines, even if they do not require a prescription, inform your doctor or pharmacist.

Using XENETIX with food, drinks, and alcohol

Ask your doctor or pharmacist if you need to abstain from eating or drinking before the examination.

Inform your doctor if you consume large amounts of alcohol (see section 2. Warnings and precautions).

Pregnancy and breastfeeding

Pregnancy

If you are pregnant or if you have missed your period, you should inform your doctor before the radiological examination.

Exposure to X-rays during pregnancy should be avoided, although it may be justified after careful evaluation by the doctor, considering the benefit of the examination versus the risk involved.

Consult your doctor or pharmacist before taking any medicine.

If this medicinal product is administered to a woman during pregnancy or to a newborn, the doctor should check the thyroid function of the newborn, as they may have temporarily lower thyroid activity (hypothyroidism).

Breastfeeding

It is recommended to suspend breastfeeding for at least 24 hours after administration of the iodinated contrast agent.

Consult your doctor or pharmacist before taking any medicine.

Driving and using machines

The effect of this medicinal product on the ability to drive and use machines is not known.

If you do not feel well after the examination, you should not drive or use machines.

XENETIX contains sodium

This medicinal product contains less than 1 mmol of sodium (23 mg) per 100 ml, so it is considered essentially "sodium-free".

3. How to use XENETIX

Follow exactly the administration instructions of this medicinal product as indicated by your doctor. In case of doubt, consult your doctor again.

The recommended doses should be adapted to the examination and the territories to be opacified, as well as to the patient's weight and renal function, especially in children.

Your doctor will determine the injected dose, which may vary depending on the type of examination, the technique used, your weight, cardiac output, and general health.

Xenetix is an injectable solution. The product should be administered intravenously or intra-arterially.

If you use more XENETIX than you should

Iobitridol is mainly eliminated by the kidneys, unchanged. Iobitridol is dialyzable.

In case of overdose or accidental ingestion, consult the Toxicological Information Service. Telephone: 91 562 04 20.

4. Possible side effects

Like all medicines, XENETIX can cause side effects, although not everybody gets them.

Most side effects occur during the injection or in the first hour after administration. Some effects may occur after several days of XENETIX injection.

XENETIX side effects are generally mild or moderate and temporary.

There is a small risk that allergic reactions (rare) may occur, which can sometimes be severe and exceptionally life-threatening.

Any of the following symptoms may be the first signs of shock. Inform your doctor or healthcare professional immediately if you have any of them:

• Swelling of the face, mouth, or throat that can cause difficulty swallowing or breathing

• Low blood pressure (hypotension)

• Difficulty breathing

• Wheezing

• Coughing

• Itching

• Nasal congestion (rhinitis)

• Sneezing

• Redness of the skin

• Itching (urticaria localized or widespread)

• Urticaria

• Severe and intense disorders with blisters all over the body (Stevens-Johnson syndrome or Lyell's syndrome), red, scaly, and widespread rash with bumps under the skin and blisters accompanied by fever at the beginning of treatment (acute generalized exanthematous pustulosis) or widespread rash, high body temperature, elevated liver enzymes, blood abnormalities (eosinophilia), lymph node enlargement, and alteration of other body organs (drug reaction with eosinophilia and systemic symptoms, also known as DRESS or drug hypersensitivity syndrome). See also section 2.

The following side effects have been described with XENETIX:

• Uncommon (may affect up to 1 in 100 people): nausea and feeling of heat

• Rare (may affect up to 1 in 1,000 people): swelling of several parts of the body, including the face, throat, low blood pressure (hypotension), high blood pressure, difficulty breathing, wheezing, coughing, sneezing, eye irritation, dizziness (feeling of dizziness or lightheadedness), discomfort, vomiting, heart rhythm disorders (tachycardia), urticaria (redness of the skin and intense itching), other skin reactions, pain at the injection site, chills, tremors, presyncope (dizziness), paresthesia (feeling of pins and needles or tingling in a limb).

• Very rare (may affect up to 1 in 10,000 people): thyroid disorders, coma*, convulsions*, confusion*, visual disturbances*, memory loss*, photophobia* (fear of light), transient blindness*, somnolence*, agitation*, feeling of agitation*, headache, hearing difficulties, cardiac arrest, increased creatinine in blood, heart rhythm disorders, angina or cardiac arrest (severe chest pain radiating to the left arm), failure of the heart and blood vessels, infarction, abdominal pain, renal impairment, difficulty breathing caused by oppression of the airway muscles or lungs, throat swelling, eczema, severe allergic reaction on the skin, including blisters. If XENETIX is accidentally injected outside the vein, pain may occur at the injection site with swelling, inflammation, and redness or necrosis (tissue degeneration), transient discomfort or pain caused by the transient spasm (contraction) of one or more coronary arteries of the heart, abnormal heartbeats (torsades de pointes).

*If there is a high concentration of the iodinated contrast agent in the blood

Frequency not known (cannot be estimated from the available data): transient neonatal hypothyroidism, hypothyroidism*, dizziness in cases of hypersensitivity, blue discoloration of the skin due to low oxygen levels in the blood (cyanosis), short-term brain disorders (encephalopathy) that can cause headache, confusion, visual disturbances, loss of vision, convulsions, loss of coordination, weakness on one side of the body, speech disturbances, and loss of consciousness.

Additional side effects in children

• Cases of short-term low thyroid activity (transient hypothyroidism) have been described in young children after exposure to similar iodinated contrast agents.

Reporting of side effects

If you experience any side effects, talk to your doctor or nurse, even if they are not listed in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use:

www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicinal product.

5. Storage of XENETIX

Keep this medicinal product out of the sight and reach of children.

Do not use this medicinal product after the expiry date stated on the vial or bag after EXP. The expiry date is the last day of the month indicated.

Store protected from light.

For the vial presentation, do not store above 30°C. However, stability tests have shown that the product can be stored at temperatures below 35°C.

Do not use XENETIX after the expiry date indicated on the packaging.

Do not use this medicinal product if you notice visible signs of deterioration.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of the packaging and any unused medicinal products. This will help protect the environment.

6. Container Contents and Additional Information

XENETIX Composition

• The active ingredient is: iobitridol

XENETIX 300 mg Iodo/ml injectable solution

1 ml of injectable solution contains 658.1 mg of iobitridol/ml, which is equivalent to 300 mg of iodine.

100 ml of injectable solution contains 65.81 g of iobitridol, which is equivalent to 30 g of iodine

XENETIX 350 mg Iodo/ml injectable solution

1 ml of injectable solution contains 767.8 mg of iobitridol/ml, which is equivalent to 350 mg of iodine.

100 ml of injectable solution contains 76.78 g of iobitridol, which is equivalent to 35 g of iodine

• Other components are: calcium and sodium edetate, trometamol, trometamol hydrochloride, sodium hydroxide or hydrochloric acid (for pH adjustment), nitrogen and water for injectables.

Product Appearance and Container Contents

XENETIX is an iodinated radiological contrast medium (opacifying properties), hydrophilic, non-ionic, low osmolality, for radiological examinations.

XENETIX injectable solution is a clear, colorless or light yellow solution that contains iodine.

Container Sizes:

XENETIX 300 mg Iodo/ml injectable solution is available in vials of 50, 100 (single-dose) and 500 ml (multi-dose) or polypropylene bags of 100, 150, 200 (single-dose) and 500 ml (multi-dose).

XENETIX 350 mg Iodo/ml injectable solution is available in vials of 50, 100, 150, 200 (single-dose) and 500 ml (multi-dose) or polypropylene bags of 100, 150, 200 (single-dose) and 500 ml (multi-dose).

Only some container sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Guerbet

BP 57400

95943 ROISSY CDG Cedex - France

Local Representative of the Marketing Authorization Holder:

Guerbet Pharmaceutical Laboratories, S.A.

Pº de la Castellana, 91, 3rd floor

28046 Madrid

+ (34) 91 504 50 00

Date of the Last Revision of this Prospectus: May 2025

Other Sources of Information

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

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This information is intended only for healthcare professionals:

Instructions for filling the syringes of the injector: A specific transfer or filling equipment for this use should be used, as well as suitable disposable materials, and discarded when necessary, strictly following the manufacturer's instructions.

Specific precautions for the use of 500 ml containers: It is recommended that the contrast medium be extracted after puncturing the stopper with a suitable device. The instructions for use provided by the manufacturer of all disposable materials should be followed. At the end of the day, any unused or leftover product should be eliminated in accordance with local legislation.

Instructions for administration if single-dose vials are used:

• The product should be introduced into the syringe immediately before use.
• After disinfecting the stopper, the solution should be extracted through the stopper using a single-use syringe

and single-use sterile needles.

• Any unused amount of the contrast medium remaining in the single-dose vial should be

discarded after each examination.

Instructions for administration if multi-dose vials are used:

• Multi-dose vials should only be used connected to autoinjectors/pumps.
• Autoinjectors/pumps should not be used in small children.
• A single puncture should be performed.
• The patient connection line can only be maintained for a working day (8 hours) if the instructions for use allow it, and the patient connection line should be changed after each patient, following the manufacturer's instructions.
• The leftover contrast medium solution remaining in the vial, as well as the connection tubes and all the disposable elements of the injection system, should be discarded at the end of the working day.

It is essential to strictly follow the additional instructions provided by the manufacturer

• of the autoinjector/pump as well as the disposable elements.