Special Warning : אזהרת שימוש

4.4. Special warnings and precautions for use
LIPIODOL ULTRA-FLUID should not be administered by systemic intravascular or intrathecal administration.
There is a risk of hypersensitivity, regardless of the dose administered.
Warnings
Warnings common to all therapeutic indications
Hypersensitivity
All iodinated contrast agents may cause minor or major hypersensitivity reactions that may be life- threatening. These hypersensitivity reactions may be allergic (so-called anaphylactic reactions if severe) or non-allergic. They can occur immediately (within 60 minutes) or may be delayed (up to 7 days). Anaphylactic reactions occur immediately and can be fatal. They are independent of the dose, may occur from the first administration of the product, and are often unpredictable.
The risk of major reactions implies having necessary emergency resuscitation equipment immediately available.
Patients who have already had a reaction with a previous administration of LIPIODOL ULTRA-FLUID or have a history of iodine hypersensitivity are at increased risk of another reaction in case of repeat administration of the product. They are therefore considered to be at-risk patients.
Injection of LIPIODOL ULTRA-FLUID may aggravate the symptoms of existing asthma. In patients whose asthma is not controlled with treatment, the decision to use LIPIODOL ULTRA-FLUID must be based on a careful consideration of the benefit- risk ratio.


Disturbed thyroid function
Due to their free iodine content, iodinated contrast agents may alter thyroid function and thus cause hyperthyroidism in predisposed patients. Patients at risk are those with latent hyperthyroidism and those with thyroid autonomy. Iodism occurs more frequently with LIPIODOL ULTRA FLUIDE than with water- soluble organic derivatives of iodine.
Thyroid function tests indicative of hypothyroidism or transient thyroid suppression have been reported following iodinated contrast media administration to adult and paediatric patients, including infants.
Some patients were treated for hypothyroidism. See also section on Paediatric population.
Paediatric population:
Thyroid Dysfunction in Pediatric Patients 0 to 3 Years of Age
Thyroid dysfunction characterized by hypothyroidism or transient thyroid suppression has been reported after both single exposure and multiple exposures to iodinated contrast media (ICM) in pediatric patients 0 to 3 years of age.
Younger age, very low birth weight, prematurity, underlying medical conditions affecting thyroid function, admission to neonatal or pediatric intensive care units, and congenital cardiac conditions are associated with an increased risk of hypothyroidism after ICM exposure. Pediatric patients with congenital cardiac conditions may be at the greatest risk given that they often require high doses of contrast during invasive cardiac procedures.


An underactive thyroid during early life may be harmful for cognitive and neurological development and may require thyroid hormone replacement therapy. After exposure to ICM, individualize thyroid function monitoring based on underlying risk factors, especially in term and preterm neonates.


See also section 4.4, “Specific warnings for lymphography”.
Embolic and thrombotic complications
The uncontrolled migration of Lipiodol Ultra Fluid into the arterio-venous system may induce the temporary obliteration of small vessels (oil embolism) in various organs. Signs of such embolism are infrequent and generally immediate, but they may also be delayed and appear after a few hours or days.
They are usually transient. However, cases of pulmonary embolism and cerebral embolism (possibly associated with a cerebral infarction) that are life-threatening or fatal have been reported with LIPIODOL ULTRA-FLUID in all its therapeutic indications. Patients should be informed of possible signs of embolism and should contact their doctor or hospital if any symptoms appear. The benefit/risk balance should be carefully evaluated prior to examination, particularly in patients with a known right-to-left cardiac shunt or a known intratumoral vascular shunt. The recommended dose should not be exceeded and the administration procedures should be followed.
Specific warnings for Lymphography
A Pulmonary embolism occurs in most patients undergoing lymphography with injection of LIPIODOL ULTRA-FLUID, as part of the product temporarily embolises pulmonary capillaries. For this reason, doses should be adjusted or the examination cancelled in subjects with impaired respiratory function, cardiorespiratory insufficiency, or pre-existing right heart overload, especially if the patient is elderly.
The doses must also be reduced after anti-cancer chemotherapy or radiotherapy, as the lymph nodes shrink considerably and therefore do not retain much contrast agent. It is recommended that the injection be carried out under radiological or radioscopic guidance.
Pulmonary embolisation can be reduced to a minimum via radiological confirmation that the injection is strictly intralymphatic (and not intravenous) and by interrupting the examination as soon as the contrast agent becomes visible in the thoracic duct or if lymphatic obstruction is observed.
Lymphography saturates the thyroid with iodine for several months and it is therefore necessary to perform a thyroid assessment prior to the radiological examination.


Special warnings for transarterial chemoembolisation
Transarterial chemoembolisation is not recommended in patients with decompensated cirrhosis of the liver (Child-Pugh ≥ 8), severe hepatic dysfunction, macroscopic portal vein invasion, portal thrombosis (partial or total), and/or extrahepatic tumour dissemination.
An intra-arterial hepatic procedure may cause irreversible liver failure in patients with severe hepatic dysfunction and/or treated over several sessions close together. Tumour invasion of greater than 50% of the liver, bilirubin levels over 2 mg/dl, lactate dehydrogenase levels over 425 mg/dl, aspartate aminotransferase levels over 100 IU/l and decompensated cirrhosis have been described as being associated with an increase in the post-procedure mortality rate.
Oesophageal varices should be monitored carefully as they may rupture immediately after treatment. If a risk of rupture is identified, an endoscopic sclerotherapy/ligation should be performed prior to the transarterial chemoembolisation procedure.
Iodinated contrast-induced renal failure risk should be prevented by systematic hydration before and after the procedure.
The risk of superinfection in the treated area can be prevented by the administration of antibiotics.


Precautions for use
Hypersensitivity
Before the examination: identify patients at risk in a detailed interview on their history.
Corticosteroids and H1 antihistamines have been proposed as pre-medication for patients with the highest risk of intolerance reactions (those with known intolerance to a contrast agent). However, they do not prevent the occurrence of severe or fatal anaphylactic shock.
During the examination, the following should be maintained:
•   medical monitoring
•   an indwelling intravenous catheter.
After the examination:
After contrast agent administration, the patient must be observed for at least 30 minutes, as the majority of serious adverse reactions occur within this time frame.
The patient must be informed of the possibility of delayed reactions (up to 7 days after administration) (see Section 4.8 - Undesirable effects).
Thyroid
It is essential to look for any thyroid risk factors to prevent any metabolic disorders. If administration of an iodinated contrast agent is planned for such at risk patients, an assessment of thyroid function should be performed before the examination.
Transarterial chemoembolisation/Embolisation
Iodinated contrast agents may cause temporary deterioration of renal function or aggravate pre- existing renal impairment. Preventive measures include:
•   Identifying at-risk patients, i.e. patients with dehydration or renal insufficiency, diabetes, severe heart failure, monoclonal gammopathy (multiple myeloma, Waldenstrom's macroglobulinemia), subjects with a history of renal failure after administration of iodinated contrast agents, infants under one year of age and elderly subjects with atheroma.
•   Hydrating before and after the procedure.
•   Avoiding combining nephrotoxic medicinal products. If this is necessary, increase renal function monitoring. The medicinal products concerned include aminoglycosides, organoplatinums, high doses of methotrexate, pentamidine, foscarnet and certain antiviral agents [aciclovir, ganciclovir, valaciclovir, adefovir, cidofovir, tenofovir], vancomycin, amphotericin B, immunosuppressors such as cyclosporine or tacrolimus, ifosfamide.
•   Allowing at least 48 hours between radiological examinations or interventions with iodinated contrast agent injections, or delaying further examinations or interventions until renal function returns to baseline.
•   Preventing lactic acidosis in diabetics treated with metformin by monitoring serum creatinine levels. Normal renal function: treatment with metformin must be stopped at least 48 hours before injection of the contrast agent or until normal renal function has been restored. Abnormal renal function: metformin is contraindicated. In an emergency, if the examination is required, precautions must be taken, i.e. discontinuation of metformin, hydration, renal function monitoring and looking for signs of lactic acidosis.
•   Cardiovascular and/or pulmonary risk factors should be evaluated prior to initiating a transarterial chemoembolisation procedure.
Other
Injection into certain fistulas requires the utmost caution to avoid any vascular penetration, considering the risk of fat embolisms.
Care should be taken not to inject the product into a haemorrhagic or traumatized area.
Indications for the use of LIPIODOL ULTRA-FLUID should be carefully assessed in patients with primary lymph oedema, as the oedema can be exacerbated.

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