TELEBRIX 12 SODIUM

אפורל ןולעב )תוחיטב עדימ ( הרמחה לע העדוה אפורל ןולעב )תוחיטב עדימ ( הרמחה לע העדוה

:ךיראת

28/07/2011

:תילגנאב רישכת םש

Telebrix 12 sodium

: םושיר רפסמ

26111

: םושירה לעב םש

Promedico Ltd

.

םי/שקובמה םי/יונישה לע םיטרפ ןולעב קרפ יחכונ טסקט שדח טסקט

4.3 Contraindications

Hypersensitivity to ioxitalamic acid or to any of the excipients;

History of major immediate or delayed skin reaction (see

section 4.8) to Telebrix 12 Sodium

(120 mg iodine/mL),

solution for injection;

Decompensated heart failure, when used by systemic injection;

Endoscopic retrograde pancreatography (ERP) for acute

pancreatitis;

Overt thyrotoxicosis;

Myelography

Hypersensitivity to ioxitalamic acid or to any of the excipients listed in

section 6.1

History of major immediate or delayed skin reaction (see section 4.8)

to Telebrix 12 Sodium Intra-vascular administration.

Intra-vascular administration

Manifest thyrotoxicosis

Intrathecal or subarachnoid (or epidural) administration of TELEBRIX

12 Sodium for myelography, cerebral ventriculography or

cisternography is contraindicated as severe and potentially life-

threatening neurotoxic reactions (e.g. myoclonus or epilepsy) can

occur

4.4 Special warnings

and precautions for

use

4.4.1.2.1. Intolerance to iodinated contrast media:

Prior to the examination:

Identify subjects at risk via

specific

questioning

concerning

history.

Corticosteroids

H1-antihistamines

were

suggested

4.4.1. Special Warnings

4.4.1.1 Hypersensitivity

Any All iodinated contrast medium can cause minor or major reactions that

may be life-threatening. They may be immediate (less than 60 minutes) or

delayed (up to 7 days). They are often unpredictable.

premedication in patients at the highest risk of intolerance reaction

(known to be intolerant to an iodinated contrast medium). However,

they do not prevent serious or fatal anaphylactic shock to occur.

During the examination, the following must be ensured:

Medical supervision

Maintenance of a venous

access.

After the examination:

Further to administration of a

contrast medium, the patient

must

remain

under

observation for at least 30

minutes, as most adverse

effects occur within this time.

The patient must be warned

that late onset reactions may

occur (up to 7 days later)

(see section 4.8).

4.4.1.2.2. Renal failure

Iodinated contrast media may temporarily alter renal function or

aggravate existing renal failure. The preventive measures to be

taken are as follows:

Identify

high

risk

patients:

dehydrated

subjects,

patients with renal failure,

diabetes,

severe

heart

failure,

monoclonal

gammapathy

(multiple

myeloma,

Waldenström’s

disease) or a history of renal

failure

following

administration of iodinated

The risk of major reaction requires the immediate availability of the means

necessary for emergency resuscitation.

Several mechanisms have been reported:

Direct

toxicity

affecting

vascular

endothelium and tissue proteins.

Pharmacological

action

altering

concentration of certain endogenous

factors

(histamine,

complement

fractions, inflammation mediators), more

frequent with hyperosmolar products.

immediate IgE-mediated allergy (anaphylaxis) to TELEBRIX 12 SODIUM

(120 mg I/mL), solution for intravesical administration.

Cell-mediated allergic reactions (delayed

skin reactions).

Patients having previously suffered a reaction during administration of an

iodinated contrast medium are at increased risk of experiencing a renewed

reaction during administration of the same, or another iodinated contrast

medium, and are therefore considered to be high risk subjects.

4.4.1.2 Iodinated contrast media and the thyroid (see also section 4.4.2.35.

Precautions for use - Dysthyroidism)

Before administering iodinated contrast media, it is recommended to make

sure that the patient is not to undergo thyroid scintigraphy or laboratory tests,

or to receive any radioactive iodine for therapy.

Iodinated contrast media, whatever the administration route, may interfere with

hormone assays and iodine binding within the thyroid gland and thyroid cancer

metastases until urine levels of iodine return to normal. Since thyroid tests are

altered, they should be performed prior to radiological examinations. If tests are

necessary in the weeks following the administration of an iodinated contrast

medium, thyroid hormones (thyroxine, triiodothyronine) should be assayed

contrast

media,

children

under

year

atheromatous

elderly

subjects.

Initiate appropriate hydration

by fluid and sodium solution

where required.

Avoid

combinations

nephrotoxic

medicines

such

combinations

necessary,

reinforce

renal

biological

monitoring). The

medicinal

products

question

notably

aminoglycosides,

organoplatins,

high-dose

methotrexate,

pentamidine,

foscarnet

certain

antivirals

(aciclovir,

ganciclovir,

valaciclovir,

adefovir,

cidofovir,

tenofovir),

vancomycin,

amphotericin

immunosuppressants

such

as ciclosporine or tacrolimus,

ifosfamide.

Allow for a 48-hour interval

between

X-ray

examinations

involving

injection

iodinated

contrast medium, or defer

further

examinations

until after initial renal function

has been restored.

Prevent

lactic

acidosis

directly.

4.4.2. Precautions for use

4.4.2.1. Intolerance to iodinated contrast media:

Before the examination:

identify high-risk patients by conducting an interview focusing on medical

history.

Corticosteroids and histamine H1-antagonists have been proposed for

premedicating patients at the highest risk of hypersensitivity.However, this

alone cannot entirely preclude a serious reaction, including serious or fatal

anaphylactic shock. During the examination, it is important to:

monitor the patient closely.

maintain venous access.

have drugs and equipment for resuscitation readily available

After the examination:

after the contrast medium has been administered, the patient must be

monitored closely for at least 30 minutes as most serious undesirable

effects occur within that period.

the patient must be warned of the possibility that allergic reactions may

occur after some delay (up to 7 days) (see section 4.8 Undesirable effects

The following precautions for use must be considered if the integrity of the

bladder wall cannot be confirmed before product administration:

4.4.2.2. Asthma

It is preferable to control asthma well before injecting an iodinated contrast

medium.

Special care is necessary where the patient has suffered an asthma attack in

the eight days prior to the examination, as this exacerbates the risk of

diabetic patients treated with

metformin,

according

blood

creatinine

levels.

Normal

renal

function:

administration of metformin

should be interrupted for at

least

hours

iodinated contrast medium is

administered, or until normal

renal

function is restored.

Abnormal

renal

function:

metformin is contraindicated.

In an emergency: if the

examination

required,

precautions must be taken:

interruption

metformin

treatment,

hydration,

monitoring of renal function

and detection of symptoms

of lactic acidosis.

Haemodialysis patients may receive iodinated contrast media as

these products are dialysable. The haemodialysis department must

first be consulted.

4.4.1.2.3. Liver failure

Special attention must be paid when a patient suffers both from

liver failure and renal failure, as this situation increases the risk of

contrast medium retention.

4.4.1.2.4. Asthma

Asthma must be stabilized prior to injection of an iodinated contrast

medium.

Special attention must be paid in cases of asthma attacks occurring

8 days prior to the examination, due to the increased risk of

bronchospasm.

4.4.2.3. Dysthyroidism

An injection of iodinated contrast media may cause episodes of

hyperthyroidism or may induce hypothyroidism, particularly in patients

presenting with goitre, or with a history of dysthyroidism. Hypothyroidism may

also occur in neonates who have received, or whose mothers received, an

iodinated contrast medium

Their thyroid function should be therefore evaluated and monitored

4.4.2.4. Central nervous system disorders

The benefit/risk ratio must be assessed case-by-case:

due to the risk of aggravating neurological symptoms in patients suffering a

transient ischaemic attack, acute cerebral infarction, recent intra-cranial

haemorrhage, cerebral oedema, idiopathic or secondary (tumour, scar)

epilepsy.

4.4.2.5. Pheochromocytoma

Patients with pheochromocytoma may suffer an attack of hypertension after

intra-vascular administration of contrast media and suitable management

should be implemented before the examination.

4.4.2.6. Myasthenia

Administration of contrast media may exacerbate the symptoms.

4.4.2.7. Exacerbation of side effects

The undesirable effects of iodinated contrast media may be exacerbated by

excitement, anxiety or pain. Suitable management, including sedation, may be

required.

bronchospasm.

4.4.2.1.5. Dysthyroidism

Following injection of an iodinated contrast medium, in particular in

patients with goitre or with a history of dysthyroidism, the risk of

hyperthyroidism or induction of hypothyroidism also exists.

Hypothyroidism may also occur in newborns that have received, or

whose mother has received an iodinated contrast medium.

4.4.1.2.6. Severe cardiovascular disease

In the event of existing or early stage heart failure, coronary artery

disease, pulmonary arterial hypertension or valvular heart disease,

the risk of pulmonary oedema, myocardial ischemia and arrhythmia

severe

hemodynamic

disorders

increased

following

administration of an iodinated contrast medium.

4.4.1.2.7. Central nervous system disorders

The benefit/risk ratio must be estimated on a case per case basis:

due to the risk of worsening of

neurological

symptoms

patients

presenting

with

transient

ischemic

attack,

acute

cerebral

infarction,

recent

intracranial

haemorrhage, and cerebral

oedema,

idiopathic

secondary epilepsy (tumour,

scar).

during

intra-arterial

route in alcoholics (acute or

chronic

alcoholism)

users of other drugs.

4.4.1.2.8. Phaechromocytoma

Patients

suffering

from

phaechromocytoma

experience

hypertension surge following intravascular administration of a

contrast medium and may require appropriate treatment prior to the

procedure.

4.4.1.2.9. Myasthenia

Administration of a contrast medium may worsen myasthenia

symptoms.

4.4.1.2.10. Enhanced side effects

Side effects related to administration of iodinated contrast media

may be enhanced by pronounced states of excitation, anxiety and

pain. Appropriate treatment, and possibly sedation, may be

necessary.

4.5.

Interaction

with other medicinal

products and other

forms of interaction

4.5.1. Medicinal products

Metformin in diabetics (see section 4.4.1.2.2. Precautions for

use – Renal Failure).

Radiopharmaceuticals (see section 4.4.1. Special Warnings)

Iodinated contrast media disturb radioactive iodine uptake by

thyroid tissue during several weeks, and this may lead to poor

fixation in the thyroid scintigraphy and reduced effectiveness of

iodine 131 treatment.

Where renal scintigraphy performed by injection of renal tubular

secreted radiopharmaceuticals is planned, it is recommended

to carry out this procedure prior to injection of the iodinated

contrast medium.

Beta-blockers, vasoactive substances, angiotensin-converting

enzyme inhibitors, angiotensin receptor antagonists.

These medicinal

products lead to a reduction in the

effectiveness of cardiovascular compensation mechanisms in

blood pressure disorders: The doctor must be informed if the

patient is taking such treatment prior to injection of the

Radiopharmaceuticals (see also section 4.4.1. Special Warnings)

Iodinated contrast media disturb the uptake of radioactive iodine by thyroid

tissue for several weeks, and this may result in poor binding during thyroid

scintigraphy and may reduce the efficacy of 131-iodine treatment.

patient

undergo

renal

scintigraphy

injecting

radiopharmaceutical product secreted by the renal tubule, it is preferable to

conduct such an examination prior to the injection of a contrast medium.

Beta-blockers, vasoactive substances, angiotensin-converting enzyme

inhibitors, angiotensin receptor antagonists.

These drugs reduce the efficacy of cardiovascular mechanisms that

compensate for blood pressure disorders.

Hypersensitivity reactions can be aggravated in patients on beta-blockers,

and particularly in the presence of bronchial asthma. These patients may

be refractory to standard treatment of hypersensitivity reactions with beta-

agonists.

The physician must be informed prior to injecting a contrast medium and

must have resuscitation equipment at hand.

iodinated

contrast

medium

have

necessary

resuscitation means at hand.

Diuretics

Due to the risk of dehydration induced by diuretics, fluid and

electrolyte rehydration is initially necessary for minimizing the

risk of acute kidney failure.

Interleukin-2

Enhanced reaction to contrast media during treatment with

interleukin-2 (intravenous route) may occur: rash or more rarely

hypotension, oliguria or even kidney failure.

Interleukin 2

Treatment with interleukin 2 (iv route) may exacerbate any reaction to

contrast media: i.e. rash, flushing, erythema, fever or flu-like symptoms

or,more rarely, hypotension, oliguria or even renal failure.

4.5.2. Other forms of interaction

High concentrations of iodinated contrast media in plasma and urine may

interfere with in vitro assays of bilirubin, proteins and inorganic substances

(iron, copper, calcium and phosphate). It is therefore recommended to avoid

such assays in the 24 hours following the examination:

Thyroid function, thyroid tests (see section 4.4.1.2 Special warnings - Iodinated

contrast media and the thyroid, and section 4.4.2.5. Precautions for use -

Dysthyroidism).

4.6.

Ferti

lity,

pregnancy

and

lactation

4.7.

Fertility, pregnancy and lactation

Embryotoxicity

Studies conducted in animals have not shown any teratogenic

effects.

In the absence of teratogenic effects in animals, no malformation in

humans

expected.

date,

substances

causing

malformations in humans have been found to be teratogenic in

animals in well conducted studies in two species.

Foetotoxicity

Occasional iodine overload following administration of the medium

in the mother may lead to foetal dysthyroidism if the examination is

carried out after 14 weeks' amenorrhea. However, reversibility of

this effect and the expected maternal benefit indicate that

occasional administration of an iodinated contrast medium should

not be delayed where the indication for radiological examination in

pregnant women is carefully assessed.

Fertility

Toxicological studies conducted on reproduction function did not

show any effects on reproduction, fertility or foetal or post-natal

development.

Breastfeeding

Small quantities of iodinated contrast media are excreted in breast

milk. Occasional administration in mothers therefore bears a low

risk of causing adverse effects in infants. It is advisable to suspend

breastfeeding for 24 hours following administration of an iodinated

contrast medium.

4.8.

Pregnancy

Since radiation exposure during pregnancy should be generally avoided,

regardless of whether a contrast agent is used or not, the benefit of X-ray

examination has to be considered carefully.

Embryotoxicity

Animal studies have not revealed any teratogenic effect.

In view of this, no malformative effect is expected in man. To date, substances

causing malformation in man have been found to be teratogenic in animals

during well-conducted studies on two species.

Foetotoxicity

The short-term iodine overload after the administration of a contrast medium to

a pregnant mother may cause foetal dysthyroidism, should the examination be

carried out after the 14th week of amenorrhoea. The thyroid function of

neonates exposed in utero should be evaluated and monitored. However, the

reversibility of the effect, and the expected benefit for the mother, justify the

single administration of an iodinated contrast medium where a radiological

examination of a pregnant woman is necessary.

Fertility

Reproductive toxicology studies did not reveal an effect on reproduction,

fertility or fœtal and post-natal development.

Lactation

Only small quantities of iodinated contrast media are secreted into breast milk.

There is therefore little risk of a single administration to mothers causing

undesirable effects in the infants. It is preferable to discontinue breast-feeding

for 24 hours after the administration of an iodinated contrast medium.

4.7.

Effects

on

the ability to

drive

and

use

machines

Not applicable.

No studies on the effects on the ability to drive and use machines have been

performed.

Due to the pharmacological properties of TELEBRIX 12 SODIUM itself, an

effect on the ability to drive and use machines is unlikely.

4.8.

Undesirable

effects

An adverse reaction is said to be:

very common if its frequency is ≥ 10 %

common if its frequency is ≥ 1% and < 10%

uncommon if its frequency is ≥ 0.1% and < 1%

rare if its frequency is ≥ 0.01% and < 0.1 %

very rare if its frequency is <

0.01%

4.8.1. Anaphylactoid and hypersensitivity reactions

Hypersensitivity reactions, including anaphylactic or anaphylactoid

reactions, possibly leading to death, include one or more of the

following effects:

4.8.1.1. Skin and subcutaneous tissue (very rare):

Immediate: pruritus, erythema,

localised or extensive urticaria,

facial oedema, angioedema.

Late

onset:

maculopapular

exanthema, and in exceptional

cases:

Stevens-Johnson

syndrome or Lyell’s syndrome.

Not reported with TELEBRIX 12

SODIUM (120 mg I/mL), solution

for injection: eczema, erythema

multiforme.

Since post-marketing, the most commonly reported adverse reactions

following the administration of TELEBRIX (any form) are hypersensitivity

(including anaphylactic reaction, anaphylactoid reaction and anaphylactic

shock), urticaria, rash (including erythema and maculo-papular rash) and

injection site reactions (such as oedema, pain and inflammation).

The hypersensitivity

reactions

usually

immediate

(during

administration or over the hour following the start of the administration) or

sometimes delayed (one hour to several days after the administration), and

then appear in the form of adverse skin reactions.

Immediate reactions comprise one or several, successive or concomitant

effects, usually including skin reactions, respiratory and/or cardiovascular

disorders, which may be the first signs of shock, which can rarely be fatal.

The adverse reactions are listed in the table below by SOC (System Organ

Class) and with frequency as follows: very common (1/10), common

(1/100 to <1/10), uncommon (1/1000 to <1/100), rare (1/10000 to

<1/1000), very rare (<1/10000), not known (cannot be estimated from the

available data).

Tabulated list of adverse reactions reported with TELEBRIX 12 Sodium or

another form of TELEBRIX following intravesical administration:

4.8.1.2. Respiratory (very rare):

Cough, feeling of tightening of the

throat, dyspnoea, bronchospasm,

laryngeal oedema, laryngospasm,

respiratory arrest.

Not reported with TELEBRIX 12

SODIUM (120 mg I/mL), solution

for injection: sneezing fits.

4.8.1.3. Cardiovascular (very rare):

Hypotension,

vertigo,

faintness,

tachycardia,

cardiac

arrest.

Not reported with TELEBRIX 12

SODIUM (120 mg I/mL), solution

for injection: bradycardia.

4.8.1.4. Other events (very rare):

Nausea, vomiting, abdominal pain.

4.8.2. Other undesirable effects

4.8.2.1. Cardiovascular (very rare)

Vagal

syncope,

arrhythmia,

angina,

myocardial

infarction, more common in

the case of intracoronary

injection.

Cardiovascular

collapse

varying seriousness that may

occur

abruptly

with

warning signs, or complicate

the cardiovascular symptoms

described above.

System Organ Class

Frequency: Adverse reaction

Immune system

disorders

Frequency not known: Anaphylactic shock, anaphylactic

reaction, anaphylactoid reaction, hypersensitivity

Endocrine disorders

Frequency not known: Thyrotoxic crisis*, hyperthyroidism*,

thyroid disorder**

Nervous system

disorders

Frequency not known: Syncope, convulsion, tremor, dizziness,

headache

Cardiac disorders

Frequency not known: Tachycardia

Vascular disorders

Frequency not known: Hypotension

Respiratory, thoracic

and mediastinal

disorders

Frequency not known: Laryngeal oedema, pulmonary oedema,

dyspnoea, cough

Gastrointestinal

disorders

Frequency not known: Diarrhoea, nausea, vomiting, abdominal

pain

Skin and

subcutaneous tissue

disorders

Frequency not known:

Immediate: Angioedema, urticaria, pruritus, erythema,

hyperhidrosis

Delayed: Rash, rash maculo-papular

Renal and urinary

disorders

Frequency not known: Renal failure acute, anuria

General disorders

and administration

site conditions

Frequency not known: Oedema, face oedema, pain, malaise,

feeling hot, pyrexia, chills

Investigations

Frequency not known: Blood creatinine increased

*Thyrotoxicosis may occur in patients with asymptomatic or uncontrolled

hyperthyroidism as well as in patients with autonomous thyroid nodules

(take special care with elderly patients). The occurrence of symptoms may

be delayed (for several months) after the administration.

4.8.2.2. Neurosensory (very rare)

Systemic

administration:

sensation

warmth.

Headache

Examinations during which

iodinated

contrast

medium is found at high

levels in the cerebral arterial

blood: agitation, confusional

state, tremor, paresthesiae,

paresis/paralysis,

convulsion, coma.

Not reported with TELEBRIX 12

SODIUM (120 mg I/mL), solution

injection:

hallucinations,

amnesia, speech disorders, visual

disturbances

(photophobia,

transient

blindness),

hearing

disorders, minor EEG alterations,

drowsiness.

4.8.2.3. Gastro-intestinal (very rare)

Nausea, vomiting.

Abdominal pain and diarrhoea,

especially

related

administration via upper or

lower gastro-intestinal route.

Not reported with TELEBRIX 12

SODIUM (120 mg I/mL), solution

for injection: parotid hypertrophy

subsequent to the examination,

hypersalivation,

transient

taste

disorders,

increased

serum

amylase levels, due to the injection

**

Thyroid disorder may be the exacerbation of a goitre.

Temporary

hypothyroidism may also occur in newborns (premature infants) that have

received, or whose mother has received an iodinated contrast medium.

The following adverse reactions were reported with any form of

TELEBRIX following non-intravesical administration and/or with other

iodinated contrast media:

System Organ Class

Adverse reaction

Psychiatric disorders

Confusional state, hallucination, agitation, anxiety

Nervous system

disorders

Coma, brain oedema, loss of consciousness, paresis/paralysis,

paraesthesia, amnesia, speech disorder, somnolence, dysgeusia

Eye disorders

Visual impairment, photophobia, blindness transient, eyelid

oedema

Ear and labyrinth

disorders

Vertigo, hearing impaired

Cardiac disorders

Cardiac arrest, myocardial infarction, angina pectoris,

arrhythmia, bradycardia, cyanosis

Vascular disorders

Shock, hypertension, thrombophlebitis

1

, flushing, pallor

Respiratory, thoracic and

mediastinal disorders

Respiratory arrest, respiratory failure, pneumonia aspiration

laryngospasm, bronchospasm, throat tightness, sneezing

Gastrointestinal disorders

Pancreatitis

, ileus

, enterocolitis

parotid gland enlargement,

salivary hypersecretion

Skin and subcutaneous

tissue disorders

Stevens-Johnson syndrome, toxic epidermal necrolysis,

erythema multiforme, eczema, dermatitis bullous

Musculoskeletal and

connective tissue

disorders

Arthralgia

, muscle spasms

Reproductive system and

breast disorders

Pelvic pain

General disorders and

administration site

Injection site extravasation, injection site pain, injection site

inflammation, injection site oedema, injection site necrosis

pressure,

and,

rarely,

acute

pancreatitis following ERCP.

4.8.2.4. Respiratory (very rare)

Pulmonary oedema.

4.8.2.5. Renal (see section 4.4)

Transient increase in blood creatinine levels may be observed but

anuric acute renal failure is very rare.

4.8.2.6. Thyroid (see sections 4.4 and 4.5)

4.8.2.7. Local effects (very rare)

Transient,

benign

local

oedema and pain may occur

at the injection site in the

absence of extravasation of

product

injected.

intra-arterial

administration,

the painful sensation at the

injection site depends on the

osmolality

product

injected. In the event of

extravasation

)<

0.01%),

local inflammatory reaction

or even tissue necrosis may

be observed.

Thrombophlebitis

Not reported with TELEBRIX 12

SODIUM (120 mg I/mL), solution

for injection: joint pain in the event

of arthrography.

conditions

Investigations

Electroencephalogram abnormal, blood amylase increased

following intravascular administration

in patients with swallowing impairment, oral route

following endoscopic retrograde cholangiopancreatography (ERCP)

following enteral administration

in the event of arthrography

in the event of extravasation

Adverse reactions in children

The expected nature of the undesirable effects connected with TELEBRIX

12 SODIUM is the same at that of the effects reported in adults. Their

frequency cannot be estimated from the available data.

4.9.Overdos

e

With very high doses, fluid and electrolyte losses must be

compensated by appropriate rehydration. Renal function must be

monitored during at least three days. Haemodialysis may be carried

out if necessary.

Toxicity from overdose of TELEBRIX 12 SODIUM is unlikely due to the

intravesical administration.

Overdose increases the risk of nephropathy and can result in diarrhoea,

dehydration,

electrolyte

imbalance,

haemodynamic

cardiovascular

disorders.

With very high doses, fluid and electrolyte losses must be compensated by

appropriate rehydration. Renal function must be monitored during at least three

days. Haemodialysis may be carried out if necessary.

SUMMARY OF PRODUCT CHARACTERISTICS

1.

NAME OF THE MEDICINAL PRODUCT

TELEBRIX 12 SODIUM , solution for injection for intravesical administration

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

For 100 mL of solution:

Sodium ioxitalamate ................................................................................................ 21.00 g

Equivalent to iodine ...................................................................................................... 12 g

Iodine content per mL: 120 mg

Iodine mass per 250 mL bottle: 30g

For a full list of excipients, see section 6.1.

3.

PHARMACEUTICAL FORM

Solution for intravesical administration

Viscosity at 20°C: 1.7 mPa.s

Viscosity at 37 °C: 1.1 mPa.s

Osmolality: 640 mOsm / kg

4.

CLINICAL PARTICULARS

4.1.

Therapeutic indications

For diagnostic use only.

Contrast medium for:

Retrograde cystography;

4.2

Posology

Indications

Average dose

Total volume

mL/kg

(min.-max.) mL

Retrograde cystography

Dose to be adapted to the volume

of the organ to be injected

20 - 100

U

Method of administration

The product must be administered by intravesical administration only

4.3

Contraindications

Hypersensitivity to ioxitalamic acid or to any of the excipients listed in section 6.1

History of major immediate or delayed skin reaction (see section 4.8) to Telebrix 12

Sodium Intra-vascular administration.

Intra-vascular administration

Manifest thyrotoxicosis

Intrathecal or subarachnoid (or epidural) administration of TELEBRIX 12 Sodium for

myelography, cerebral ventriculography or cisternography is contraindicated as

severe and potentially life-threatening neurotoxic reactions (e.g. myoclonus or

epilepsy) can occur

4.4.

Special warnings and precautions for use

There is a risk of allergy, whatever the administration route or dosage.

The risk of intolerance cannot be ruled out when medicinal products are administered

locally to opacify body cavities:

a) administration via certain routes (e.g. articular, biliary, intrathecal, intra-uterine) results in

considerable systemic diffusion so systemic effects may occur.

b) oral or rectal administration usually results in a very limited systemic diffusion. If the

gastrointestinal mucosa is healthy, no more than 5% of the administered dose passes

into the urine, the rest being excreted in the faeces. However, when the gastrointestinal

mucosa is damaged, absorption is increased. Where the gut is perforated, the entire

dose may pass rapidly into the peritoneal cavity, to be eliminated in the urine. The onset

dose-related,

systemic

effect

therefore

related

integrity

gastrointestinal mucosa.

c) the immuno-allergic mechanism, however, is not dose-related and may be involved,

whatever the route of administration.

Hence, the frequency and intensity of undesirable effects differ for:

medicinal products administered via the intra-vascular and certain topical routes,

medicinal products administered via the gastrointestinal route and only slightly absorbed

under normal conditions.

4.4.1. Special Warnings

4.4.1.1 Hypersensitivity

All iodinated contrast medium can cause minor or major reactions that may be life-

threatening. They may be immediate (less than 60 minutes) or delayed (up to 7 days). They

are often unpredictable.

The risk of major reaction requires the immediate availability of the means necessary for

emergency resuscitation.

Several mechanisms have been reported:

Direct toxicity affecting the vascular endothelium and tissue proteins.

Pharmacological

action

altering

concentration

certain

endogenous

factors

(histamine,

complement

fractions,

inflammation

mediators),

more

frequent

with

hyperosmolar products.

Immediate IgE-mediated allergy (anaphylaxis) to TELEBRIX 12 SODIUM (120 mg I/mL),

solution for intravesical administration.

Cell-mediated allergic reactions (delayed skin reactions).

Patients having previously suffered a reaction during administration of an iodinated contrast

medium are at increased risk of experiencing a renewed reaction during administration of

the same, or another iodinated contrast medium, and are therefore considered to be high

risk subjects.

4.4.1.2 Iodinated contrast media and the thyroid (see also section 4.4.2.35. Precautions for

use - Dysthyroidism)

Before administering iodinated contrast media, it is recommended to make sure that the

patient

undergo

thyroid

scintigraphy

laboratory

tests,

receive

radioactive iodine for therapy.

Iodinated contrast media, whatever the administration route, may interfere with hormone

assays and iodine binding within the thyroid gland and thyroid cancer metastases until urine

levels of iodine return to normal. Since thyroid tests are altered, they should be performed

prior

radiological

examinations. If

tests

necessary

weeks following

administration

iodinated

contrast

medium,

thyroid

hormones

(thyroxine,

triiodothyronine) should be assayed directly.

4.4.2. Precautions for use

4.4.2.1. Intolerance to iodinated contrast media:

Before the examination:

identify high-risk patients by conducting an interview focusing on medical history.

Corticosteroids

histamine

H1-antagonists

have

been

proposed

premedicating

patients at the highest risk of hypersensitivity.However, this alone cannot entirely preclude a

serious reaction, including serious or fatal anaphylactic shock. During the examination, it is

important to:

monitor the patient closely.

maintain venous access.

have drugs and equipment for resuscitation readily available

After the examination:

after the contrast medium has been administered, the patient must be monitored closely

for at least 30 minutes as most serious undesirable effects occur within that period.

the patient must be warned of the possibility that allergic reactions may occur after some

delay (up to 7 days) (see section 4.8 Undesirable effects ).

The following precautions for use must be considered if the integrity of the bladder wall

cannot be confirmed before product administration:

4.4.2.2. Asthma

It is preferable to control asthma well before administering an iodinated contrast medium.

Special care is necessary where the patient has suffered an asthma attack in the eight days

prior to the examination, as this exacerbates the risk of bronchospasm.

4.4.2.3. Dysthyroidism

An administration of iodinated contrast media may cause episodes of hyperthyroidism or

may induce hypothyroidism, particularly in patients presenting with goitre, or with a history

of dysthyroidism. Hypothyroidism may also occur in neonates who have received, or whose

mothers received, an iodinated contrast medium.

Their thyroid function should be therefore

evaluated and monitored.

4.4.2.4. Central nervous system disorders

The benefit/risk ratio must be assessed case-by-case:

due to the risk of aggravating neurological symptoms in patients suffering a transient

ischaemic attack, acute cerebral infarction, recent intra-cranial haemorrhage, cerebral

oedema, idiopathic or secondary (tumour, scar) epilepsy.

4.4.2.5. Pheochromocytoma

Patients with pheochromocytoma may suffer an attack of hypertension after intra-vascular

administration of contrast media and suitable management should be implemented before

the examination.

4.4.2.6. Myasthenia

Administration of a contrast medium may worsen myasthenia symptoms.

4.4.2.7 Exacerbation of side effects

The undesirable effects of iodinated contrast media may be exacerbated by excitement,

anxiety or pain. Suitable management, including sedation, may be required.

4.5.

Interaction with other medicinal products and other forms of interaction

4.5.1. Medicinal products

Radiopharmaceuticals (see also section 4.4.1. Special Warnings)

Iodinated contrast media disturb the uptake of radioactive iodine by thyroid tissue for

several weeks, and this may result in poor binding during thyroid scintigraphy and may

reduce the efficacy of 131-iodine treatment.

If the patient is to undergo renal scintigraphy by injecting a radiopharmaceutical product

secreted by the renal tubule, it is preferable to conduct such an examination prior to the

injection of a contrast medium.

Beta-blockers,

vasoactive

substances,

angiotensin-converting

enzyme

inhibitors,

angiotensin receptor antagonists.

These drugs reduce the efficacy of cardiovascular mechanisms that compensate for

blood pressure disorders.

Hypersensitivity

reactions

aggravated

patients

beta-blockers,

particularly in the presence of bronchial asthma. These patients may be refractory to

standard treatment of hypersensitivity reactions with beta-agonists.

The physician must be informed prior to injecting a contrast medium and must have

resuscitation equipment at hand.

Interleukin 2

Treatment with interleukin 2 (iv route) may exacerbate any reaction to contrast media:

i.e. rash, flushing, erythema, fever or flu-like symptoms or,more rarely, hypotension,

oliguria or even renal failure.

4.5.2. Other forms of interaction

High concentrations of iodinated contrast media in plasma and urine may interfere with in

vitro assays of bilirubin, proteins and inorganic substances (iron, copper, calcium and

phosphate). It is therefore recommended to avoid such assays in the 24 hours following the

examination:

Thyroid function, thyroid tests (see section 4.4.1.2 Special warnings - Iodinated contrast

media and the thyroid, and section 4.4.2.5. Precautions for use - Dysthyroidism).

4.6.

Fertility, pregnancy and lactation

Pregnancy

Since radiation exposure during pregnancy should be generally avoided, regardless of

whether a contrast agent is used or not, the benefit of X-ray examination has to be

considered carefully.

Embryotoxicity

Animal studies have not revealed any teratogenic effect.

In view of this, no malformative effect is expected in man. To date, substances causing

malformation in man have been found to be teratogenic in animals during well-conducted

studies on two species.

Foetotoxicity

The short-term iodine overload after the administration of a contrast medium to a pregnant

mother may cause foetal dysthyroidism, should the examination be carried out after the

14th week of amenorrhoea. The thyroid function of neonates exposed in utero should be

evaluated and monitored. However, the reversibility of the effect, and the expected benefit

for the mother, justify the single administration of an iodinated contrast medium where a

radiological examination of a pregnant woman is necessary.

Fertility

Reproductive toxicology studies did not reveal an effect on reproduction, fertility or fœtal

and post-natal development.

Lactation

Only small quantities of iodinated contrast media are secreted into breast milk. There is

therefore little risk of a single administration to mothers causing undesirable effects in the

infants. It is preferable to discontinue breast-feeding for 24 hours after the administration of

an iodinated contrast medium.

4.7.

Effects on the ability to drive and use machines

No studies on the effects on the ability to drive and use machines have been performed.

Due to the pharmacological properties of TELEBRIX 12 SODIUM itself, an effect on the

ability to drive and use machines is unlikely.

4.7.

Undesirable effects

Since post-marketing, the most commonly reported adverse reactions following the

administration of TELEBRIX (any form) are hypersensitivity (including anaphylactic

reaction, anaphylactoid reaction and anaphylactic shock), urticaria, rash (including

erythema and maculo-papular rash) and injection site reactions (such as oedema, pain

and inflammation).

The hypersensitivity reactions are usually immediate (during the administration or over

the hour following the start of the administration) or sometimes delayed (one hour to

several days after the administration), and then appear in the form of adverse skin

reactions.

Immediate

reactions

comprise

several,

successive

concomitant

effects,

usually including skin reactions, respiratory and/or cardiovascular disorders, which may

be the first signs of shock, which can rarely be fatal.

The adverse reactions are listed in the table below by SOC (System Organ Class) and

with

frequency

follows:

very

common

1/10), common (1/100 to <1/10),

uncommon (

1/1000 to <1/100), r

are (

1/10000 to <1/1000), very rare (<1/10000), not

known (cannot be estimated from the available data).

Tabulated list of adverse reactions reported with TELEBRIX 12 Sodium or another

form of TELEBRIX following intravesical administration:

System Organ Class

Frequency: Adverse reaction

Immune system

disorders

Frequency not known: Anaphylactic shock, anaphylactic

reaction, anaphylactoid reaction, hypersensitivity

Endocrine disorders

Frequency not known: Thyrotoxic crisis*, hyperthyroidism*,

thyroid disorder**

Nervous system

disorders

Frequency not known: Syncope, convulsion, tremor,

dizziness, headache

Cardiac disorders

Frequency not known: Tachycardia

Vascular disorders

Frequency not known: Hypotension

Respiratory,

thoracic and

mediastinal

disorders

Frequency not known: Laryngeal oedema, pulmonary

oedema, dyspnoea, cough

Gastrointestinal

disorders

Frequency not known: Diarrhoea, nausea, vomiting,

abdominal pain

Skin and

subcutaneous

tissue disorders

Frequency not known:

Immediate: Angioedema, urticaria, pruritus, erythema,

hyperhidrosis

Delayed: Rash, rash maculo-papular

Renal and urinary

disorders

Frequency not known: Renal failure acute, anuria

General disorders

and administration

site conditions

Frequency not known: Oedema, face oedema, pain,

malaise, feeling hot, pyrexia, chills

Investigations

Frequency not known: Blood creatinine increased

*Thyrotoxicosis may occur in patients with asymptomatic or uncontrolled hyperthyroidism

as well as in patients with autonomous thyroid nodules (take special care with elderly

patients). The occurrence of symptoms may be delayed (for several months) after the

administration.

** Thyroid disorder may be the exacerbation of a goitre. Temporary hypothyroidism may

also occur in newborns (premature infants) that have received, or whose mother has

received an iodinated contrast medium.

The following adverse reactions were reported with any form of TELEBRIX following

non-intravesical administration and/or with other iodinated contrast media:

System Organ Class

Adverse reaction

Psychiatric disorders

Confusional state, hallucination, agitation, anxiety

Nervous system

disorders

Coma, brain oedema, loss of consciousness,

paresis/paralysis, paraesthesia, amnesia, speech disorder,

somnolence, dysgeusia

Eye disorders

Visual impairment, photophobia, blindness transient, eyelid

oedema

Ear and labyrinth

disorders

Vertigo, hearing impaired

Cardiac disorders

Cardiac arrest, myocardial infarction, angina pectoris,

arrhythmia, bradycardia, cyanosis

Vascular disorders

Shock, hypertension, thrombophlebitis

1

, flushing, pallor

Respiratory, thoracic

and mediastinal

disorders

Respiratory arrest, respiratory failure, pneumonia

aspiration

, laryngospasm, bronchospasm, throat

tightness, sneezing

Gastrointestinal

disorders

Pancreatitis

, ileus

, enterocolitis

parotid gland

enlargement, salivary hypersecretion

Skin and subcutaneous

tissue disorders

Stevens-Johnson syndrome, toxic epidermal necrolysis,

erythema multiforme, eczema, dermatitis bullous

Musculoskeletal and

connective tissue

disorders

Arthralgia

, muscle spasms

Reproductive system

and breast disorders

Pelvic pain

General disorders and

administration site

conditions

Injection site extravasation, injection site pain, injection site

inflammation, injection site oedema, injection site necrosis

Investigations

Electroencephalogram abnormal, blood amylase increased

following intravascular administration

in patients with swallowing impairment, oral route

following endoscopic retrograde cholangiopancreatography (ERCP)

following enteral administration

in the event of arthrography

in the event of extravasation

Adverse reactions in children

The expected nature of the undesirable effects connected with TELEBRIX 12 SODIUM is

the same at that of the effects reported in adults. Their frequency cannot be estimated

from the available data.

4.9.

Overdose

Toxicity from overdose of TELEBRIX 12 SODIUM is unlikely due to the intravesical

administration.

Overdose increases the risk of nephropathy and can result in diarrhoea, dehydration,

electrolyte imbalance, haemodynamic and cardiovascular disorders.

With very high doses, fluid and electrolyte losses must be compensated by appropriate

rehydration. Renal function must be monitored during at least three days. Haemodialysis

may be carried out if necessary.

5.

PHARMACOLOGICAL PROPERTIES

5.1.

Pharmacodynamic properties

Pharmacotherapeutic group: IODINATED CONTRAST MEDIUM (V: miscellaneous)

ATC Code: V08AA05

TELEBRIX

SODIUM (120

I/mL),

solution

intravesical

administration,

hydrosoluble, ionic contrast medium (640 mOsm/kg).

5.2.

Pharmacokinetic properties

After intravesical administration, ioxitalamic acid is excreted rapidly, in unchanged form, in

the urine.

5.3.

Preclinical safety data

Effects have only been observed in animals at a level of exposure significantly higher than

the maximum dose in humans, and are therefore of little clinical significance.

6.

PHARMACEUTICAL DATA

6.1

List of excipients

Sodium hydroxide, sodium calcium edetate, sodium dihydrogen phosphate dihydrate, water

for injection.

6.2.

Incompatibilities

In the absence of compatibility studies, this medicinal product must not be mixed with other

medicinal products.

6.3.

Shelf life

3 years.

6.4.

Special precautions for storage

Store below 25ºC. Keep protected from light.

6.5.

Nature and contents of container

250 mL colourless glass bottle (type II) with an elastomer stopper (chlorobutyl).

6.6.

Special precautions for disposal and other handling

Any unused product or waste material should be disposed of in accordance with local

requirements.

7.

MANUFACTURER

GUERBET

BP 57400

95943 ROISSY CDG CEDEX

FRANCE

8. REGISTRATION HOLDER:

Promedico Ltd.

Hashiloach Str., P.O.B. 3340, Petach Tiqva.

The format of this leaflet has been defined by the MOH and its content has been checked

and approved -October 2012