In radiology, diagnosis
· Lymphography.

· Diagnosis of liver damage.

Diagnosis by arterial route, hepatic selective liver extension, liver malignancies or not.

In interventional radiology

Visualization, localization and vectorization during transarterial chemo-embolization of carcinoma, hepatocellular at the intermediate stage, in the adult

· Embolization with surgical adhesives.

Diagnosis of hepatic lesions Diagnosis by arterial route Hepatic selective liver extension Hepatic or non-hepatic malignant lesions Interventional radiology Visualization, localization and vectorization During transarterial chemoembolization of carcinoma, intermediate-stage hepatocellular disease in adults, embolization with surgical adhesives, in combination with surgical adhesives during embolization, vascular The use of Lipiodol in the prevention of iodine deficiency should be reserved exclusively for the countries where it exists, the impossibility of putting in place the other methods of supplementation, in particular iodization, salt and / Or drinking water

In association with surgical adhesives during embolization, vascular

Endocrinology

The use of Lipiodol for the prevention of iodine deficiency should be reserved exclusively for the countries where it exists, the impossibility of putting in place the other methods of supplementation, in particular iodization, salt and / or Drinking water

LIPIODOL ULTRA FLUID should be administered by slow injection or catheterization, using a suitable glass syringe and a catheter (see section Incompatibilities). >
In radiology, diagnosis
· Lymphography

Administration is by lymphatic catheterization. It may be preceded by the injection of a dye to localize the lymphatic vessels.

The usual dose is 5 to 7 mL by strict intralymphatic route, for opacification of a limb (modulated according to the size of the subject), ie 10 to 14 mL for bilateral lymphography. The dose should be decreased proportionally in the child. In infants aged 1 to 2 years, a dose of 1 mL per end is sufficient.
· Diagnosis of liver lesions

Strict intra-arterial use.

The usual dose varies according to the size of the lesions and may range from 2 to 10 mL per patient. LIPIODOL ULTRA FLUIDE is sometimes mixed with small amounts of water-soluble iodinated contrast media. The scanner must be performed 7 to 15 days after the injection, selective to allow the elimination of LIPIODOL, ULTRA FLUIDE from the non-tumorous liver

Pediatric population

The dose should be decreased proportionally in children

Patients with underweight

The dose should be decreased proportionately in this population

Elderly subjects

The product should be administered with caution in patients over the age of 65 with underlying conditions of the cardiovascular system, respiratory system or neurological system. Knowing that part of the product temporarily embolizes the pulmonary capillaries, the presence of cardiorespiratory insufficiency in the elderly patient requires an adaptation of the dose or even cancellation of the examination. Br>

In radiology, interventional
Trans-arterial Chimioembolization of Hepatocellular Carcinoma

Administration is by selective intra-arterial catheterization of the hepatic artery. The procedure must be performed in an interventional radiology room with appropriate equipment. The dose of LIPIODOL ULTRA FLUID depends on the extent of the lesion but should generally not exceed a total adult dose of 15 mL

LIPIODOL ULTRA FLUIDE can be mixed with anti-cancer medicines such as cisplatin, doxorubicin, epirubicin and mitomycin.


Instructions for the preparation of the mixture of LIPIODOL ULTRA FLUID with a drug anti-cancer

· Prepare two syringes large enough to hold the total volume of the mixture. The first syringe containing the anticancer drug solution, the second syringe containing LIPIODOL ULTRA FLUIDE.

· Connect the two syringes to a 3-way faucet.

· Make 15 to 20 back and forth between the two syringes, to obtain a homogeneous mixture. It is recommended to start by pushing the syringe containing the anti-cancer drug.

· The mixture should be prepared extemporaneously and should be used immediately after preparation (within 3 hours). If necessary, the mixture may be further homogenized as described above in the interventional radiology procedure.

· When the appropriate mixture is obtained, use a 1 to 3 mL syringe to inject into the microcatheter

The procedure can be repeated, every 4 to 8 weeks depending on the tumor response and the condition of the patient.

Population, pediatric

The efficacy and safety of LIPIODOL ULTRA FLUID in trans-arterial chemo-embolization of hepatocellular carcinomas has not been established in children.
Elderly people

The product should be administered with caution to patients who are over 65 years of age and have pathologies underlying cardiovascular, respiratory or nervous systems.
· Embolization with surgical adhesives

Selective arterial catheterization, exclusive.

The dose of LIPIODOL ULTRA FLUID by embolization session is determined according to the size of the lesions. The mixture of LIPIODOL ULTRA FLUIDE and liquid embolic agent may vary from 20 to 80% but most often consists of a mixture of 50/50. Code>
The volume injected shall not exceed 15 mL.

In endocrinology

Strict intramuscular use.

· Adult and child over 4 years: 1 mL every 3 years.

· Children under 4 years of age: 0.5 mL every 2 years without exceeding 3 mL.

In case of thyroid nodule, the dosage is 0.2 mL.
NON WATER-SOLUBLE CONTRAST PRODUCTS, Code, ATC: V08AD01

(V: Miscellaneous)

ULTRA FLUIDE allows, as an oily contrast agent, to visualize and control the procedure due to its opacifying properties as a vehicle, To transport and elute anti-cancer drugs in the nodules of hepatocellular carcinoma and, as a transient embolic agent, to contribute to vascular embolization induced during the procedure. In the case of a selective liver intra-arterial injection procedure, conventional chemoembolization combines the effect of an anti-cancer drug, targeted loco-regionally with necrosis, ischemic induced by double embolization, Portal. The opacifying properties and the tropism for the liver tumors of LIPIODOL ULTRA FLUIDE make it possible to carry out post-procedure imaging for several months for an effective follow-up of the patient. Br>
The effects of LIPIODOL ULTRA FLUIDE on the ability to drive and use machines have not been evaluated

· Hypersensitivity to LIPIODOL ULTRA FLUIDE (ethyl esters of iodized fatty acids in oil, flaxseed)

· Pregnant woman

· Hyperthyroidism is known.

Traumatic lesions, haemorrhage or bleeding, recent (risk of extravasation or embolism)

· Bronchography (the product would quickly inundate the bronchioles and the alveoli).

Contra-indications, specific to the use in radiology, interventional

· Trans-arterial embolization

Administration in hepatic areas where the bile ducts are dilated without drainage has been carried out in advance

· Embolization with surgical adhesives.

There are no particular contraindications except those of embolization, in particular the presence of thrombosis, portal.


· Large and multinodular goiter in persons over 45 years of age because of the high risk of hyperthyroidism

· During breastfeeding.

LIPIODOL ULTRA FLUID should not be administered intravenously, intra-arterially (excluding selective catheterization) or intrathecally.


4.4.1 Warnings

4.4.1.1. Lymphography

Pulmonary embolism occurs in the majority of patients undergoing a lymphography with injection of LIPIODOL ULTRA FLUIDE, part of the product temporarily embolizing the capillaries, pulmonary. It is infrequent that this embolism manifests itself clinically, if it is the case, the signs are immediate (they can however also appear, several hours or even several days after the administration) and are usually transient. For this reason, the doses should be adjusted or the examination canceled in subjects with impaired respiratory function, cardiorespiratory insufficiency or right cardiac overload, pre-existing, especially if the patient is Doses should also be reduced after cancer chemotherapy or radiotherapy because the lymph nodes decrease significantly and therefore retain only a small amount of contrast agent It is recommended to carry out the injection under radiological control Or scopic. It is possible to minimize pulmonary invasion by obtaining a radiological confirmation that the injection is intra-lymphatic (and not intravenous) and by interrupting the examination as soon as the contrast product becomes; Visible in the thoracic duct or that the presence of a lymphatic obstruction is observed.
4.4.1.2 Hypersensitivity

All iodized contrast media may cause minor or major hypersensitivity reactions that may be life threatening. These hypersensitivity reactions are allergic in nature (so-called anaphylactic reactions) or non-allergic. They may be immediate (less than 60 min) or delayed (up to 7 days) .The anaphylactic reactions are immediate and may result in death. They are dose-independent and may occur as of the first administration of the product and are often unpredictable.
The risk of a major reaction implies immediate availability of the means necessary for emergency resuscitation.

Patients who have already experienced a reaction in previous administration of LIPIODOL ULTRA FLUID or with a history of hypersensitivity to iodine are at increased risk of further reaction in the event of re-administration of the drug. product. They are therefore considered as patients at risk.

Injection of LIPIODOL ULTRA FLUID can aggravate the symptoms of existing asthma. In patients whose asthma is not balanced by treatment, the decision to use LIPIODOL ULTRA FLUIDE should do well to weigh the benefit / risk ratio in advance.
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4.4.1.3. Thyroid

Due to their free iodine content, iodinated contrast media may alter thyroid function and thus cause hyperthyroidism in predisposed patients.Patients at risk are those with latent hyperthyroidism and Those with autonomy, thyroid function. Iodism occurs more frequently with LIPIODOL ULTRA FLUID than with water-soluble organic derivatives of iodine

Lymphography saturates the thyroid with iodine for several months, and it is therefore necessary to perform a thyroid test prior to radiological examination.
4.4.1.4. Chimio-embolization, trans-arterial

Trans-arterial chemoembolization is not recommended in patients with decompensated cirrhosis, liver (Child-Pugh ≥ 8), hepatic dysfunction, severe, macroscopic invasion and / or extrahepatic dissemination Of the tumor

An intra-arterial hepatic procedure can lead to irreversible hepatic failure in patients with severe hepatic dysfunction and / or treatment with several close-ups. A tumor invasion greater than 50% of the liver, a bilirubin level greater than 2 mg / dl, a lactate dehydrogenase level greater than 425 mg / dl, a higher aspartate aminotransferase level, 100 IU / L And decompensated cirrhosis have been described as being associated with an increase in mortality, post-procedure.

Esophageal varices should be monitored carefully as they may rupture immediately after treatment. If a risk of rupture is identified, endoscopic sclerotherapy / ligation should be performed prior to the trans-arterial chemo-embolization procedure.
The risk of renal insufficiency induced by iodinated contrast agents should be prevented by preventive hydration, systematic before and after the procedure

The risk of superinfection in the treated area can be prevented by administration of antibiotics

4.4.1.5. Embolization with glue, surgical

An early polymerization reaction is likely to occur, exceptionally between LIPIODOL ULTRA FLUIDE and certain surgical adhesives, or even certain lots of glue. Before any use of new batches of LIPIODOL ULTRA FLUIDE or surgical adhesive, it is necessary to ensure in vitro compatibility between LIPIODOL ULTRA FLUIDE and the adhesive

4.4.2 Precautions for use

4.4.2.1. Hypersensitivity

Before the examination

Identify patients at risk by accurate questioning about their history

Corticosteroids and H1 antihistamines have been proposed as premedication in patients with the greatest risk of reactions, intolerance (known intolerance to a product, contrast). They do not, however, prevent the occurrence of severe or fatal anaphylactic shock.
During the period of the examination, it is appropriate to ensure

· Medical surveillance.

· Maintaining a venous approach.

After the exam

After administration of a contrast product, the patient should remain under observation for at least 30 minutes, as the majority of serious adverse effects occur within this time.
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The patient should be warned of the possibility of delayed reactions (up to 7 days after administration) (see section Undesirable effects)

4.4.2.2. Thyroid

It is imperative to look for possible thyroid risk factors to prevent any metabolic disorder. If an iodinated contrast agent is to be administered in such patients at risk, an assessment of thyroid function should be made prior to the examination. >

4.4.2.3. Chimio-embolization, trans-arterial / Embolization

Iodinated contrast media may cause transient impairment of renal function or aggravate renal impairment. Preventive measures are the following

· Identify patients at risk: patients with dehydration or renal insufficiency, diabetics, severe cardiac insufficiency, monoclonal gammopathy (multiple myeloma, Waldenström macroglobulinemia), subjects with a history of renal insufficiency after administration of products Of contrast iodine, children less than one year old, atheromatous aged subjects

· Moisturize before and after performing the gesture

· Avoid associating nephrotoxic drugs. If such an association is necessary, renal biological monitoring should be strengthened. The drugs concerned include aminoglycosides, organoplatin, high-dose methotrexate, pentamidine, foscarnet and certain antivirals [aciclovir, ganciclovir, valaciclovir, adefovir, cidofovir, tenofovir], vancomycin, amphotericin B, Immunosuppressants, such as ciclosporin or tacrolimus, ifosfamide.

· Observe an interval of at least 48 hours between radiological investigations or interventions with injection of iodinated contrast media or postpone any further examination or intervention until the restoration of the initial renal function.

· Prevent lactic acidosis in diabetics, treated with metformin on the basis of serum creatinine. Normal renal function: treatment with metformin should be discontinued prior to injection of the contrast medium for a period of at least 48 hours or until the return of normal renal function. Abnormal renal function: Metformin is contraindicated. In urgent cases, if necessary, precautions should be taken, such as discontinuation of metformin, hydration, follow-up of renal function and search for signs of acidosis, lactic. >

Cardiovascular and / or pulmonary risk factors should be evaluated before initiating a chemo-embolization, trans-arterial procedure

4.4.2.4. Miscellaneous

The injection in certain fistulas requires the utmost caution in order to avoid any vascular penetration taking into account the risk of fat embolism

Care should be taken not to inject the product into a haemorrhagic or traumatized area.
Drug Interactions

+; Metformine

In patients with diabetes, the intra-arterial administration of LIPIODOL ULTRA FLUIDE is liable to cause lactic acidosis, triggered by renal insufficiency, and functional. In patients undergoing embolization or trans-arterial chemoembolization, treatment with metformin should be suspended 48 hours before the procedure and should be resumed only 2 days after.
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Associations to be taken into account

Beta blockers, vasomotor substances, angiotensin converting enzyme inhibitors, angiotensin receptor antagonists

These drugs cause a reduction in the effectiveness of the cardiovascular compensation mechanisms of tension disorders: the physician must be informed beforehand, the administration of LIPIODOL ULTRA FLUID and have the means of resuscitation.

+; Diuretics

Since diuretics are liable to induce dehydration, the risk of acute renal failure is increased, especially when the contrast media are administered at high doses.

Precautions for use, rehydration before intra-arterial administration, LIPIODOL ULTRA FLUIDE for embolization

+; + Interleukin II

There is a risk of increased response to contrast agents in case of recent treatment with interleukin II (IV), rash or, more rarely, hypotension, oliguria or even renal insufficiency

Interference with examinations, diagnosis

As LIPIODOL ULTRA FLUID remains in the body for several months, the thyroid-related diagnostic results may be found distorted up to two years after lymphography. >
LIPIODOL ULTRA; FLUIDE is poorly preserved in plastics. In the absence of precise compatibility studies, plastic containers and syringes are to be avoided.

An overdose may be the cause of respiratory, cardiac or cerebral complications which may result in death. The frequency of micro-embolisms may be increased in an overdose context.
The total dose of LIPIODOL ULTRA FLUID administered should not exceed 20 mL.

The management of an overdose is intended to provide symptomatic treatment and to ensure the maintenance of vital functions in the shortest possible time. Testing facilities with contrast media must have the medicines and equipment necessary for emergency care.

Pregnancy

LIPIODOL ULTRA FLUIDE should not be used in pregnant women because of the transplacental passage of iodine over a long period which probably interferes with the thyroid function of the fetus with a potential risk of lesions, cerebral, Permanent hypothyroidism.
Breastfeeding

Pharmacokinetic studies reveal a significant excretion of iodine in breast milk, after intramuscular administration of LIPIODOL ULTRA, FLUID. It has been shown that iodine passes through the vascular system of the infant, is breastfed via the gastrointestinal tract, and can interfere with its thyroid function. Therefore, breast-feeding should be discontinued if LIPIODOL ULTRA FLUIDE is to be used.

Most adverse reactions are dose-related and the dosage should be as low as possible

The use of LIPIODOL ULTRA FLUID induces a foreign body reaction with the formation of macrophages and giant cells with foreign body and the occurrence of sinus catarrh, plasmocytosis and as a result of tissue rearrangements Connective tissue of the lymph nodes. Healthy lymph nodes tolerate the resulting decrease in transport capacity. In the case of lesions or lymph node hypoplasia, these rearrangements may exacerbate existing lymphatic stasis.

Hypersensitivity reactions are possible. These reactions include one or more effects of concomitant or sequential appearance, most often including cutaneous, respiratory and / or cardiovascular manifestations, each of which may indicate a state of shock, beginner and, in very Rare cases, go up to death

In radiology, diagnosis
· Lymphography

A severe increase in temperature followed by fever between 38 and 39 ° C may be noted within 24 hours of the examination

Fatty micro-emboli can occur with or without symptoms. In very rare cases, they may resemble emboli of organic origin, by their appearance and size. They present themselves most frequently in the form of punctiform opacities on the radiographic images of the lungs. Temporary increases in temperature are possible. Fatty micro-emboli appear most often after overdosage of the contrast medium or an infusion too fast. Anatomical abnormalities such as lymph node fistulas or a decrease in the ability of the lymph nodes to fix the contrast medium (in the elderly or after radiotherapy or cytostatic treatment) promote their occurrence.

Patients with cardiac shunt, right-left and those with massive pulmonary embolism are particularly exposed to the occurrence of fatty micro-embolisms at the cerebral level.
· Diagnosis of liver lesions

Nausea, vomiting and diarrhea are frequently observed.

· Trans-arterial embolization

Most undesirable effects are not caused by LIPIODOL ULTRA, FLUID, but are due to anticancer drugs, or to embolization itself.


· Embolization with surgical adhesives

It has not been described specifically for adverse reactions directly related to LIPIODOL ULTRA FLUIDE

Endocrinology

· Hyperthyroidism (see Warnings and Precautions for Use)

The undesirable effects are presented in the table below, by organ organ class and frequency according to the following categories, very common (≥ 1/10), frequent (≥ 1/100,