Xenetix® 350, solution for injection (350 mgI/ml) ; Xenetix® 300, solution for injection (300 mgI/ml) ; Xenetix® 250, solution for injection (250 mgI/ml) – Composition per 100 ml : Xenetix® 350 : 76.78 g of iobitridol (corresponding to 35 g of iodine), Xenetix® 300 : 65.81 g of iobitridol (corresponding to 30 g of iodine), Xenetix® 250: 54.84 g of iobitridol (corresponding to 25 g of iodine) - Indications(**): this product is for diagnostic use only. Contrast agent for use in: Xenetix® 350 intravenous urography, whole body and cranial computed tomography, intravenous digital subtraction angiography, arteriography, angiocardiography, sialography, endoscopic retrograde cholangiopancreatography, contrast-enhanced spectral mammography – Xenetix® 300: intravenous urography, whole body and head computed tomography, intravenous digital subtraction angiography, arteriography, angiocardiography, endoscopic retrograde cholangiopancreatography, arthrography, hysterosalpingography, herniography, contrast-enhanced spectral mammography– Xenetix® 250: phlebography, whole body computed tomography, intra-arterial digital subtraction angiography, arteriography, endoscopic retrograde cholangiopancreatography – Posology and method of administration(*): the doses should be adapted to the examination and the territories intended  to be opacified, as well as to the weight and renal function of the subject, particularly  in children Contraindications (*): hypersensitivity to iobitridol or any of the excipients, history of major immediate or delayed skin reaction (see sections special warnings and special precautions for use) to Xenetix®, manifest thyrotoxicosis; hysterosalpingography during pregnancy (Xenetix® 300).

General comments for all iodinated contrast agents (*): There is a risk of allergic reactions regardless of the route of administration or the dose. All iodinated contrast media can cause minor or major reactions that can be life-threatening. They may occur immediately (within 60 minutes) or be delayed (within 7 days) and are often unpredictable. Because of the risk of major reactions, emergency resuscitation equipment should be available for immediate use. Patients who have already experienced a reaction during administration of an iodinated contrast agent are at higher risk of experiencing another reaction following administration of the same or possibly a different iodinated contrast agent, and are thus considered to be at-risk patients Before administering an iodinated contrast agent, it is important to ensure that the patient is not scheduled to undergo a scintigraphic examination or laboratory tests related to the thyroid or to receive radioactive iodine for therapeutic purposes. Administration of contrast agents via any route disrupts hormone concentrations and iodine uptake by the thyroid or by metastases of thyroid cancer, until urine iodine levels have returned to normal. Extravasation is a non-exceptional complication (0.04% to 0.9%) of intravenous injections of contrast media. More frequent with the high osmolar products, most of the injuries are minor, however severe injuries such as skin ulceration, tissue necrosis, and compartment syndrome may occur with any iodinated contrast medium. The risk and/or severity factors are patient-related (poor or fragile vascular conditions), and technique-related (use of a power injector, large volume). It is important to identify these factors, optimize the injection site and technique accordingly, and monitor the injection prior to, during and after the injection of Xenetix®.

Special warnings and precautions for use (*): In the absence of specific studies, myelography is not an indication for Xenetix®. 1) Intolerance to iodinated contrast agents: Prior the examination, at-risk patients should be identified by a precise screening of histories. During the procedure, the medical surveillance and permanent venous access must be maintained. After the examination the patient must be monitored for at least 30 minutes, since most serious adverse reactions occur within this time period and the patient must be informed of the possibility of delayed reactions (for up to seven days), 2) Severe cutaneous adverse reactions: At the time of initiation patients should be advised of the signs and symptoms and monitored closely for severe skin reactions. Xenetix® should be discontinued immediately upon suspicion of a severe hypersensitivity reaction. If the patient has developed a severe cutaneous adverse reaction with the use of Xenetix®, Xenetix® must not be re-administered in this patient at any time, 3) Renal insufficiency and/or hepatic insufficiency: Care should be taken in renal or hepatic impairment, diabetes or in patients with sickle-cell disease. Iodinated contrast agents can induce a transient alteration in renal function or worsen pre-existing renal insufficiency.. Preventive measures include: identify at-risk patients; avoid combinations with nephrotoxic medicines (if this cannot be avoided, laboratory monitoring or renal function must be intensified); allow at least 48 hours between two radiological examinations with injection of contrast agents, or postpone any new examination until renal function returns to baseline; prevent lactic acidosis in diabetics treated with metformin. Adequate hydration should be ensured in all patients before and after contrast media administration and particularly in patients with renal impairment or diabetes. 4) Asthma: Stabilisation of asthma is recommended before the injection of an iodinated contrast agent. Due to an increased risk of bronchospasm, special caution should be taken in patients who suffered an asthmatic attack within eight days prior to the examination.5) Dysthyroidism: After iodinated contrast agent injection, particularly in patients with a goitre or a history of dysthyroidism, there is a risk either of a flare-up of hyperthyroidism or development of hypothyroidism. There is also a risk of hypothyroidism in neonates who have received, or whose mother has received, an iodinated contrast agent. Therefore, thyroid function in such neonates should be evaluated and closely monitored to ensure thyroid function is normal.6) Cardiovascular diseases: In patients with cardiovascular disease (such as early or patent heart failure, coronaropathy, pulmonary hypertension, valvulopathy, cardiac arrhythmias), the risk of cardiovascular reactions is increased after administration of an iodinated contrast agent. Careful weighing up of the risk-benefit ratio is necessary in these patients. 7) Central nervous system disorders: The benefit-to-risk ratio must be evaluated for each case: due to the risk of aggravation of neurological symptoms in patients with a transient ischaemic attack, acute cerebral infarct, recent intracranial haemorrhage, cerebral oedema, or idiopathic or secondary (tumour, scar) epilepsy and if the intra-arterial route is used in an alcoholic patient (acute or chronic alcoholism) and other drug-addicted subject. Encephalopathy has been reported with the use of iobitridol. Symptoms usually occur within minutes to hours after administration of iobitridol and generally resolve within days. If contrast encephalopathy is suspected, appropriate medical management should be initiated and iobitridol should not be readministered 8) Pheochromocytoma: Patients with pheochromocytoma may develop a hypertensive crisis after intravascular administration of a contrast agent and must be monitored prior to the examination. 9) Myasthenia: Administration of a contrast agent may worsen the symptoms of myasthenia gravis.10) Intensification of side effects: Adverse reactions related to iodinated contrast agent administration may be intensified in patients showing pronounced agitation, anxiety and pain. Appropriate management such as sedation may be necessary.

Paediatric population: Hypothyroidism or transient thyroid suppression may be observed after exposure to iodinated contrast media. Younger age, very low birth weight, prematurity, and the presence of other conditions, such as, admission to neonatal or pediatric intensive care units, and cardiac conditions are associated with an increased risk. Pediatric patients with cardiac conditions may be at the greatest risk given that they often require high doses of contrast during invasive cardiac procedures, such as catheterization, and computed tomography (CT).. Thyroid function should be evaluated in all pediatric patients after exposure to iodinated contrast media, especially in premature infants and neonates. If hypothyroidism is detected, thyroid function should be monitored as appropriate even when replacement treatment is given.
 

Warnings and precautions for use specific to certain administration routes with appreciable systemic diffusion (*): - Products administered via the intra-uterine route (Xenetix® 300): In the interview and with appropriate tests, systematically check for possible pregnancy in women of childbearing age. Exposure of the female genital routes to x-rays must be subject to careful evaluation of the benefit-to-risk ratio. In the event of inflammation or acute pelvic infection, hysterosalpingography can only be performed after a careful assessment of the benefit-to-risk ratio. - Risk of acute pancreatitis in the context of endoscopic retrograde pancreatography -Interaction with other medicinal products and other forms of interaction (*): beta-blocker substances, diuretics, metformin, radiopharmaceuticals, interleukin 2.
 

Fertility, pregnancy and lactation (*): Pregnancy: In the absence of any teratogenic effects in animal species, no malformative effect is expected in humans. The transient iodine overload following administration to the mother may induce foetal dysthyroidism if the examination takes place after more than 14 weeks of amenorrhoea. However, in view of the reversibility of the effect and expected benefit to the mother, the isolated administration of an iodinated contrast agent is justifiable if the indication for the radiological examination in a pregnant woman has been carefully evaluated. Thyroid function of neonates should be closely monitored during the first week of life if the iodinated contrast agent was administered to the mother during pregnancy. The product was not found to be mutagenic under the test conditions used. Breast-feeding: Iodinated contrast agents are only excreted in breast milk in very small amounts. Consequently, isolated administration to the mother involves a minor risk of adverse reactions in the infant. It is advisable to stop breastfeeding for 24 hours after administration of the iodinated contrast agent. Fertility: No data on reproductive function is available.

Undesirable effects(*): Uncommon (1/1000 to <1/100): nausea, feeling hot - Rare (1/10 000 to <1/1 000): hypersensitivity , presyncope, tremor, paresthesia, vertigo, tachycardia, bradycardia, hypotension, hypertension, dyspnoea, cough, throat tightness, sneezing, , vomiting, , angioedema, urticaria, erythema, pruritus, face oedema, malaise, chills, injection site pain - Very rare (<1/10 000): anaphylactic shock, anaphylactic reaction, anaphylactoid reaction, thyroid disorder, coma, seizure, visual pathway disorders, amnesia, somnolence, headache, confusional state, agitation, photophobia, blindness transient, hypoacusis, cardiac arrest, myocardial, infarction (more frequent after intracoronary injection), arrhythmia, ventricular fibrillation, angina pectoris, torsades de pointes, arteriospasm coronary , circulatory collapse, respiratory arrest, pulmonary oedema, bronchospasm, laryngospasm, laryngeal oedema, abdominal pain, acute generalized exanthematous pustulosis, Stevens-Johnson syndrome, toxic epidermal necrolysis, eczema, rash maculo-papular, acute kidney injury, anuria, injection site necrosis following extravasation, injection site inflammation following extravasation, injection site oedema, blood creatinine increased -– Not known: transient neonatal hypothyroidism, hypothyroidism (pediatric population), , dizziness, contrast encephalopathy, cyanosis, drug reaction with eosinophilia and systemic symptoms (DRESS) - Compartment syndrome may be observed following extravasation 
 

Overdose (*): If a very high dose of contrast agent is administered, the water and electrolyte loss must be compensated by suitable rehydration. Renal function must be monitored for at least three days. Haemodialysis may be performed if necessary. – Pharmacodynamic properties (*): Pharmacotherapeutic group: Water-soluble, nephrotropic radiology contrast medium with low osmolarity; ATC code: V08AB11. Presentation (**): Xenetix® 250: 50 ml, 100 ml, 200 ml or 500 ml glass vials, Xenetix® 300/350: 20 ml, 50 ml, 60 ml, 75 ml, 100 ml, 150 ml, 200 ml or 500 ml glass vials and 100 ml, 150 ml, 200 ml or 500 ml polypropylene bags. Marketing authorisation holder (*): Guerbet - BP 57400 - 95943 Roissy CdG cedex – FRANCE. 

Information: tel: 33 (0) 1 45 91 50 00. Revision:  February 2025.

(*) For complete information please refer to the local Summary of Product Characteristics
(**) Indications, volumes, and presentations may differ from country to country.

Reporting of suspected adverse reactions is important as it helps to continuously assess the benefit-risk balance. Therefore, Guerbet encourages you to report any adverse reactions to your health authorities or to our local Guerbet representative.

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