XENETIX

The dosage may vary depending on the type of examination, the age, weight, cardiac output and general condition of the patient and the technique used. Usually the same iodine concentration and volume are used as with other iodinated X-ray contrast in current use.

As with all contrast media, the lowest dose necessary to obtain adequate visualisation should be used. Adequate hydration should be assured before and after administration as for other contrast media.

As a guideline, the recommended dosages are as follows:

Indications Recommended dosage Adults Minimum dose: 1 ml/kg. g. obesity or impaired renal function. 5 ml/kg Brain CT Adults 1-2 ml/kg Whole-body CT Adults The doses of contrast medium and the rates of administration depend on the organs under investigation, the diagnostic problem and, in particular, the different scan and image- reconstruction times of the scanners in use.

Infusion is preferable for slow scanners and injection (bolus) for fast scanners. A dose of 3 ml/kg is usually considered as a maximum dose. 6 ml/kg Arch aortography 30-40 ml/inj. Selective cerebral arteriography 5-10 ml/inj. Aortography 40-50 ml/inj.

Femoral arteriography 30-50 ml/inj. 5 and 5 ml/s depending on the type of examination.

) 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.

Intravasal injection of the contrast medium may cause pulmonary oedema in patients with manifest or incipient heart failure, whereas administration in pulmonary hypertension and heart valve disorders may result in marked changes in haemodynamics.

The frequency and degree of severity appear related to the severity of the cardiac disorders. In case of severe and chronic hypertension, the risk of renal damage due to administration of the contrast medium and also due to the catheterisation itself may be increased.

Ischaemic ECG changes and severe rhythm disorders are most frequently observed in elderly and heart disease patients. Very rare cases of ventricular fibrillation which occurred immediately after administration of the contrast medium have been reported outside the context of hypersensitivity reactions.

A careful evaluation of the risk-benefit ratio is necessary in these patients. 7 Central nervous system disorders The benefit-to-risk ratio must be evaluated in 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.

• if the intra-arterial route is used in an alcoholic patient (acute or chronic alcoholism) and other drug-addicted subject. 8). Contrast-induced encephalopathy may manifest with symptoms and signs of neurological dysfunction such as headache, visual disturbance, cortical blindness, confusion, seizures, loss of coordination, hemiparesis, aphasia, unconsciousness, coma, and cerebral oedema.

Symptoms usually occur within minutes to hours after administration of iobitridol and generally resolve within days. g. encephalopathy. If contrast encephalopathy is suspected, appropriate medical management should be initiated and iobitridol should not be readministered.

8 Pheochromocytoma Patients with pheochromocytoma can develop a hypertensive crisis after intravascular administration of the contrast agent and must be monitored prior to the examination. 9 Myasthenia gravis Administration of a contrast agent can worsen the symptoms of myasthenia gravis.

10 Intensification of undesirable effects Undesirable effects linked to contrast agent administration may be intensified in patients showing pronounced agitation, anxiety or pain. Appropriate management such as sedation may be necessary.

11 Paediatric population Hypothyroidism or transient thyroid suppression may be observed after exposure to iodinated contrast media. 6). The incidence of hypothyroidism in patients younger than 3 years of age exposed to iodinated contrast media ranges between 1% and 15% depending on the age of the subjects and the dose of the iodinated contrast agent and is more commonly observed in neonates and premature infants.

Younger age, very low birth weight, prematurity, and the presence of other conditions, such as, admission to neonatal or paediatric intensive care units, and cardiac conditions are associated with an increased risk. Paediatric 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).

Special attention should be paid to paediatric patients below 3 years of age because an incident underactive thyroid during early life may be harmful for motor, hearing, and cognitive development and may require transient thyroxin (T4) replacement therapy.

Thyroid function should be evaluated in all paediatric 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.

1 Medicinal products administered via the intrauterine route Contraindication Hysterosalpingography is contraindicated during pregnancy. Special precautions for use Systematic screening for pregnancy should be carried out in women of child- bearing potential.

Exposure of the female genital tract to X-rays should be carefully evaluated when weighing up the benefit/risk ratio. In patients suffering from acute pelvic inflammation or infection, hysterosalpingography should only be performed after careful evaluation of the benefit/risk ratio.

2 Endoscopic retrograde cholangiopancreatography (ERCP) in patients with acute pancreatitis In case of ERP/ERCP there is a potential risk of pancreatitis and/or increase in amylase and lipase blood levels post-examination. e. is essentially “sodium-free”.

1. 4 Precautions for use — renal insufficiency). 4 Special warnings and precaution for use) Iodinated contrast media may affect the uptake of radioactive iodine by the thyroid for several weeks. This may lead to impaired uptake in thyroid scintigraphy, and/or to a decrease in the efficacy of […]

Risk of allergy exists, regardless of the route of administration and the dose. e. systemic effects may be observed. b) Oral or rectal administration normally results in very limited systemic diffusion. If the intestinal mucosa is normal, not more than 5% of the administered dose is found in urine and the rest is eliminated in faeces.

Conversely, absorption is increased if the mucosa is damaged. In the event of perforation, the absorption is rapid and total with diffusion into the peritoneal cavity and the product is eliminated in urine. The occurrence of dose- dependent systemic effects is therefore dependent on the status of the intestinal mucosa.

c) However, the allergic immune mechanism is not dose-dependent and immuno- allergic reactions may occur at any time, regardless of the administration route. Thus, in terms of the frequency and intensity of undesirable effects, there is a difference between: • products administered via the vascular route and certain local routes, and • products administered via the GI tract which are only slightly absorbed under normal conditions.

1. 1 Special warnings In the absence of any specific studies, myelography is not an indication for Xenetix. All iodinated contrast media can cause minor or major reactions that can be life- threatening. These can occur immediately (within 60 minutes) or be delayed (within 7 days) and are often unpredictable.

Due to risk of major reactions, emergency resuscitation equipment should be available for immediate use. As in the case of all iodinated contrast agents, non-ionic water-soluble tri- iodinated contrast media can result in minor, severe, or fatal intolerance reactions, anaphylaxis or other manifestations of hypersensitivity which are often early and sometimes delayed.

They are unpredictable but are more frequent in patients with a history of allergy (hives, asthma, hay fever, eczema, various food or drug allergies) or who have shown particular sensitivity during a previous examination with an iodinated contrast agent.

They cannot be screened using iodine reaction tests or any other currently available test. Patients who have already experienced a reaction after previous administration of an iodinated contrast agent present an increased risk of experiencing a further reaction following administration of the same or possibly another iodinated contrast agent, and are thus considered to be at-risk patients.

Non-ionic contrast media show extremely low interference with normal physiological functions. As a consequence, non-ionic contrast media have less anti-coagulant activity in vitro than ionic contrast media. Therefore, the period of contact between blood and contrast media in syringes and catheters should be kept as short as possible and close attention should be paid to the angiographic technique and catheter flushing with physiological saline (if necessary with heparin added) so as to minimise the risk of procedure-related thrombosis and embolism.

5 Dysthyroidism) Before the administration of iodinated contrast agents, it is important to ensure that the patient is not due to undergo a scintigraphic or biological examination of the thyroid or to receive radioactive iodine for therapeutic purposes.

Regardless of the route of administration, the administration of iodinated contrast agents disrupts hormone concentrations and the uptake of iodine by the thyroid or thyroid cancer metastases, until urine iodine levels have returned to normal.

9%) of intravenous injections of contrast media. This occurs more frequently 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.

2. Precautions for use Any severe disorder of water or electrolyte balance should be corrected, especially in patients with multiple myeloma, polyuria, oliguria, hyperuricemia, as well as in small children and elderly patients. Adequate hydration must be ensured before the examination.

1 Intolerance to iodinated contrast agents: Prior to the examination: • Identify at-risk patients by thorough screening of clinical history. Corticosteroids and antihistamines H1 have been proposed for pre-medication in patients presenting with the highest risk of reaction to contrast media (known intolerance to an iodinated contrast agent).

These drugs may not, however, protect from the occurrence of severe or fatal anaphylactic shock. During the procedure the following measures must be taken: o Medical surveillance; o In situ venous access. After the procedure: • After administration of the contrast agent, the patient must be monitored for at least 30 minutes since the majority of serious undesirable effects occur within this period of time.

8). • Severe cutaneous adverse reactions Severe cutaneous adverse reactions (SCARs) such as drug reaction/rash with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (Lyell’s syndrome or TEN) and acute generalised exanthematous pustulosis (AGEP), […]

8) to Iobitridol injection; • Manifest thyrotoxicosis; • Hysterosalpingography during pregnancy.