Israel - English - Ministry of Health
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SUMMARY OF PRODUCT CHARACTERISTICS
1. NAME OF THE MEDICINAL PRODUCT
LIPIODOL ULTRA-FLUID (480 mg I/ml), solution for injection.
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Corresponding to an iodine content of .................................................................................................... 480 mg/mL
in the form of ethyl esters of iodized fatty acids of poppy seed oil per .............................................................. 1 mL
One 10 mL ampoule contains ...................................................................................................... 4800 mg of iodine
Viscosity at 15°C: 70 cP (centipoise)
Viscosity at 37°C: 25 cP
Relative density at 15°C: 1.280
This medicinal product does not contain any excipients.
3. PHARMACEUTICAL FORM
Solution for injection.
4. CLINICAL PARTICULARS
4.1. Therapeutic indications
In diagnostic radiology
4.2. Posology and method of administration
LIPIODOL ULTRA-FLUID must be administered by slow injection or by catheter, using an appropriate
glass syringe and a catheter (see Section 6.2 – Incompatibilities).
In diagnostic radiology:
Administer via a catheter inserted into a lymph duct. A dye can first be injected to locate the lymph
The usual dose is 5 to 7 mL via the strict lymphatic route to enhance contrast in an extremity
(depending on the height of the subject), i.e. 10 to 14 mL for bilateral lymphography of the feet.
Patients with low weight
The dose must be reduced proportionally in this population.
The product must be administered with special care in patients over 65 years of age with underlying
diseases of the cardiovascular, respiratory or nervous systems. Keeping in mind that part of the
product temporarily embolises the pulmonary capillaries, the dose must be adjusted in elderly patients
with cardiorespiratory failure or the examination must be cancelled.
This product must not be administered by intra-arterial, intravenous or intrathecal injection.
Hypersensitivity to LIPIODOL ULTRA-FLUID (ethyl esters of iodised fatty acids of poppyseed oil).
Traumatic lesions, haemorrhage or recent bleeding (risk of extravasation or embolism).
Bronchography (the product rapidly inundates the bronchioles and alveoli).
4.4. Special warnings and precautions for use
LIPIODOL ULTRA-FLUID must not be administered intravenously, intra-arterially (apart from selective
catheterisation) or intrathecally.
There is a risk of hypersensitivity whatever the dose administered.
Pulmonary embolism occurs in most patients undergoing lymphography with injection of LIPIODOL
ULTRA-FLUID, as part of the product temporarily embolises the pulmonary capillaries. It is uncommon
for this embolism to be manifested clinically; should this occur, the signs are immediate (though they
may appear several hours or even several days after administration) and are usually transient. For this
reason, doses must be adjusted or the examination cancelled in subjects with impaired respiratory
function, cardiorespiratory failure or right ventricular overload, particularly if the patient is elderly.
Doses must also be reduced after antineoplastic chemotherapy or radiotherapy because lymph nodes
shrink significantly and retain very little contrast agent. The injection should be carried out with
radiological or endoscopic guidance. Pulmonary invasion can be reduced to the minimum by intra-
arterial, confirming radiologically that the injection is strictly intralymphatic (and not intravenous or
intrathecal injection) and by discontinuing the examination as soon as the contrast agent becomes
visible in the thoracic duct or as soon as lymphatic obstruction is observed.
All iodinated contrast agents may cause minor or major hypersensitivity reactions that may be life-
threatening. These hypersensitivity reactions may be either allergic (described as anaphylactic
reactions when serious) or non-allergic. They may be immediate (within 60 minutes) or delayed (up to
7 days). Anaphylactic reactions occur immediately and can be fatal. They are independent of the
dose, can occur after even the first dose of the product, and are often unpredictable.
Emergency resuscitation equipment must be immediately available due to the risk of a major reaction.
Patients who have previously experienced a reaction during administration of LIPIODOL ULTRA-
FLUID or who have a history of hypersensitivity to iodine are at higher risk for another reaction if the
product is again administered.
They are thus considered to be patients at risk.
Injection of LIPIODOL ULTRA-FLUID may exacerbate symptoms of asthma. In patients whose asthma
is not controlled by treatment, the decision to use LIPIODOL ULTRA-FLUID must be based on a
careful consideration of the benefit-to-risk ratio.
Because of the free iodine content in iodinated contrast agents, they may modify thyroid function and
cause hyperthyroidism in predisposed patients. Patients at risk are those with latent hyperthyroidism
or thyroid autonomy. Iodism occurs more commonly with LIPIODOL ULTRA-FLUID than with water-
soluble organic iodine derivatives.
Lymphography saturates the thyroid with iodine for several months and consequently thyroid function
tests must be carried out before the radiological examination.
184.108.40.206. Embolisation with surgical glues
An early polymerisation reaction may exceptionally occur between LIPIODOL ULTRA-FLUID and
certain surgical glues, or even certain batches of glue. Before using new batches of LIPIODOL
ULTRA-FLUID or surgical glue, the compatibility of LIPIODOL ULTRA-FLUID and the glue must be
tested in vitro.
4.4.2 Precautions for use
Before the examination:
identify patients at risk in a detailed interview on their history.
Corticosteroids and H1 antihistamines have been proposed as premedication in patients at greatest
risk for hypersensitivity reactions (patients with known hypersensitivity to a contrast agent). However,
they do not prevent the occurrence of serious or fatal anaphylactic shock.
Throughout the examination, maintain:
an indwelling intravenous catheter.
After the examination:
After contrast agent administration, the patient must be monitored for at least 30 minutes, as most
serious adverse reactions occur within this time period.
The patient must be warned of the possibility of delayed reactions (for up to seven days) (see Section
4.8 - Undesirable effects).
Possible thyroid risk factors must be investigated to prevent metabolic disorders. If iodinated contrast
agents are to be administered to patients at risk, thyroid function tests must be carried out before the
Iodinated contrast agents can induce a transient deterioration of renal function or exacerbate pre-
existing renal failure. The preventive measures are as follows:
Identify patients at risk, i.e. patients who are dehydrated or who have renal failure, diabetes,
severe heart failure, monoclonal gammopathy (multiple myeloma, Waldenstrom's
macroglobulinemia), a history of renal failure after administration of iodinated contrast agents,
children under one year of age and elderly atheromatous subjects.
Hydrate the patient before and after the examination.
Avoid combinations with nephrotoxic medicines. If such a combination is necessary, laboratory
monitoring of renal function must be intensified. The medicines concerned are in particular the
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)
Allow at least 48 hours between radiological examinations or interventions with iodinated contrast
agent injections, or delay further examinations or interventions until renal function returns to
Check for lactic acidosis in diabetics treated with metformin, by monitoring serum creatinine.
Normal renal function: discontinue metformin before and for at least 48 hours after contrast agent
administration or until renal function returns to baseline. Abnormal renal function: metformin is
contraindicated. In emergencies, if the examination is required, precautions must be taken, i.e.
discontinue metformin, hydrate the patient, monitor renal function and test for signs of lactic
Injection into certain fistulas requires the utmost caution to avoid any vascular penetration, taking into
account the risk of fat embolisms.
Care should be taken not to inject the product into areas of bleeding or trauma.
4.5. Interaction with other medicinal products and other forms of interaction
Interactions with other medicines
In diabetic patients, intra-arterial administration LIPIODOL ULTRA-FLUID may cause lactic acidosis
induced by diminished renal function. In patients undergoing embolisation, metformin must be
discontinued 48 hours before the examination and resumed no earlier than two days after the
Combinations requiring caution
Beta-blockers, vasoactive substances, angiotensin-converting enzyme inhibitors,
angiotensin receptor antagonists.
These medicinal products reduce the efficacy of cardiovascular compensation mechanisms for blood
pressure disorders. The physician must be aware of this before administering LIPIODOL ULTRA-
FLUID and emergency measures must be available.
As diuretics may cause dehydration, the risk of acute renal failure is increased, particularly when high
doses of contrast agents are administered.
Precautions for use: rehydration before intra-arterial administration of LIPIODOL ULTRA-FLUID for
Reactions to contrast agents may be increased if the patient has recently been treated with interleukin
2 (i.v.), i.e. skin eruptions or more rarely hypotension, oliguria, or renal failure.
Interference with laboratory tests
As LIPIODOL ULTRA-FLUID remains in the body for several months, thyroid laboratory tests may be
falsified for as long as two years after lymphography.
4.6. Pregnancy and lactation
The safety of LIPIODOL ULTRA-FLUID has not been demonstrated in pregnant women. The use of
LIPIODOL ULTRA-FLUID during pregnancy increases the transplacental transfer of iodine, which
probably interferes with thyroid function in the fœtus. Although transient, this abnormality may involve
a risk of cerebral lesions and permanent hypothyroidism, calling for monitoring of thyroid function and
close medical follow-up of the neonate.
Consequently, LIPIODOL ULTRA-FLUID should not be used in pregnant women unless it is absolutely
necessary, and only with strict medical monitoring.
Pharmacokinetic studies have shown significant secretion of iodine in breast milk after intramuscular
administration of LIPIODOL ULTRA-FLUID. It has been demonstrated that the iodine enters the
vascular system of the breastfed infant via the gastrointestinal tract and this could interfere with thyroid
function. Consequently, breastfeeding should be discontinued if LIPIODOL ULTRA-FLUID must be
used, or else thyroid function should monitored more frequently in the neonate.
4.7. Effects on ability to drive and use machines
No studies on the effects of LIPIODOL ULTRA-FLUID on the ability to drive and use machines have
4.8. Undesirable effects
Most of the adverse reactions are dose-related and consequently the dose should be as low as
Use of LIPIODOL ULTRA-FLUID causes a foreign body reaction, with the formation of macrophages
and foreign-body giant cells and the occurrence of sinus catarrh, plasmacytosis and subsequently
changes in lymph node connective tissue. Healthy lymph nodes tolerate the resulting decrease in
transport capacity. In patients with lymph node lesions or hypoplasia, these changes may exacerbate
Hypersensitivity reactions are possible.
A sharp increase in temperature followed by a fever of 38 to 39°C may occur within 24 hours following
Fat micro-embolisms may occur, with or without symptoms. In very rare cases, they may resemble
embolisms originating in the body, in terms of their appearance and size. They usually appear as
punctiform opacities on radiographic images of the lungs. Transient increases in temperature are
possible. Fat micro-embolisms usually occur following an overdose of contrast agent or excessively
rapid infusion. Anatomic anomalies such as lymphovenous fistulas or a decrease in the capacity of
lymph nodes to retain the contrast agent (in elderly patients or after radiotherapy or cytostatic therapy)
favour their occurrence.
Patients with a right-to-left cardiac shunt and those with a massive pulmonary embolism are
particularly at risk for fat micro-embolisms in the brain.
Adverse reactions are given in the following table according to system organ class and frequency,
using the following classification: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon
(≥ 1/1000 to < 1/100), rare (≥ 1/10 000 to < 1/1000), very rare (< 1/10 000), undetermined frequency
(cannot be estimated on the basis of available data).
System organ class
Frequency: adverse reactions
Immune system disorders
Undetermined frequency: hypersensitivity, anaphylactic reaction.
Undetermined frequency: hyperthyroidism.
Nervous system disorders
Undetermined frequency: cerebral embolism.
Respiratory, thoracic and
Undetermined frequency: pulmonary embolism.
Undetermined frequency: vomiting, diarrhoea, nausea.
General disorders and
administration site conditions
Undetermined frequency: fever, pain.
Injury, poisoning and
Rare: spinal cord injury.
Undetermined frequency: fat embolism.
Adverse reactions in children
The types of adverse reactions to LIPIODOL ULTRA-FLUID are the same as those reported in adults.
Their frequency cannot be estimated on the basis of available data.
Overdose can cause respiratory, cardiac or cerebral complications, which can be fatal. The frequency
of micro-embolisms may be increased after an overdose.
The total dose of LIPIODOL ULTRA-FLUID must not exceed 20 mL.
The treatment of an overdose involves immediate symptomatic treatment and maintenance of vital
functions. Establishments performing examinations with contrast agents must have emergency
medicines and equipment available.
5. PHARMACOLOGICAL PROPERTIES
5.1. Pharmacodynamic properties
NON-WATER-SOLUBLE CONTRAST AGENTS, Code ATC: V08AD01
5.2. Pharmacokinetic properties
After intralymphatic injection
Lipiodol is released into the blood, taken up by the liver and lungs where the oily droplets are
degraded in the pulmonary alveoli, spleen and adipose tissue.
After being taken up by the tissues and storage organs, reabsorption of Lipiodol occurs over a period
lasting from a few days to several months or years. This is continuous and regular and the presence of
iodides in the urine can be detected as long as contrast material is visible on the images.
A portion of the oil accumulates in the muscle and adjacent tissues. Another portion is deiodinated via
the metabolic route, the iodine being used to compensate for the iodine losses of the thyroid.
Urinary iodine excretion is massive and occurs rapidly (within the first few hours after the injection) but
continues over the following months.
Urinary iodine excretion falls to 50 µg/day in adults within 3 to 5 years.
After selective intra-arterial injection
The iodine is eliminated mainly in the urine. The iodinated contrast agent is significantly more
concentrated in the tumour than in the surrounding tissue, especially in the case of hepatocellular
5.3. Preclinical safety data
Preclinical data from conventional studies on pharmacological safety, single- and repeated-dose
toxicology, genotoxicity and reproductive and developmental functions showed no particular risks for
6. PHARMACEUTICAL PARTICULARS
6.1. List of excipients
This medicinal product contains no excipients.
Plastic is not suitable for the storage of LIPIODOL ULTRA-FLUID. In the absence of any specific
compatibility studies, plastic containers and syringes should not be used.
6.3. Shelf life
6.4. Special precautions for storage
Store below 25ºC, protected from light.
6.5. Nature and contents of container
10 mL glass (type 1) ampoules.
6.6. Special precautions for disposal and other handling
Any unused product or waste material should be discarded in accordance with current regulations.
7. MARKETING AUTHORISATION NUMBERS
F-95943 Roissy CdG cedex
9. MARKETING AUTHORISATION HOLDER
6 Hashiloach St.