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‫החמרה (( מידע‬
‫על החמרה‬
‫הודעה על‬
‫הודעה‬
))05.2013
05.2013 ‫(מעודכן‬
‫(מעודכן‬
8.07.2015 ‫תאריך‬
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Iomeron 300 (103-45-28521-11)
Iomeron 350 (103-46-28522-11)
Iomeron 400 (103-47-28523-11)
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Indication
Hypersensitivity to the active substance or any of the
excipients.
Hypersensitivity to the active principle and to
any of its ingredients.
Intravascular administration
There are no precise and absolute contraindications to the
use of non-ionic uroangiographic contrast media.
Investigations of the female genitalia are contraindicated in
suspected or confirmed pregnancy and in cases of acute
inflammation.
Intravascular administration
There are no precise and absolute
contraindications to the use of non-ionic
uroangiographic contrast media.
Investigations of the female genitalia are
contraindicated in suspected or confirmed
pregnancy and in cases of acute inflammation.
Intrathecal administration
Concomitant administration of Iomeprol with corticosteroids
is contraindicated (see Interactions).
Due to overdose considerations, immediate repeat
myelography in the event of technical failure is
contraindicated.
Contraindications
Intrathecal administration
Concomitant administration of Iomeprol with
corticosteroids is contraindicated (see
Interactions).
Precautions for use
Due to overdose considerations, immediate
repeat myelography in the event of technical
failure is contraindicated.
Precautions for use
a. In relation to the patient:
Hydration - Any severe disorders of water and electrolyte
balance should must be corrected prior to administration.
Especially in patients with multiple myeloma, diabetes
mellitus, polyuria, oliguria, hyperuricemia, as well as in
neonate, children and elderly patients adequate hydration
must be ensured before examination. Rehydration prior to
use of iomeprol is recommended in patients with sickle cell
disease.
a. In relation to the patient:
Hydration - Any severe disorders of water and
electrolyte balance should be corrected.
Especially in patients with multiple myeloma,
diabetes mellitus, polyuria, oliguria,
hyperuricemia, as well as in neonate, children
and elderly patients adequate hydration must be
ensured before examination.
Dietary advice - If not otherwise recommended
Precautions for
Use
Dietary advice - If not otherwise recommended by the
physician, a normal diet and adequate fluid intake is
maintained during the day preceding the examination.
However, patients should avoid eating or drinking during
the two hours preceding the X-ray examination.
Pre-medication - In pheochromocytoma patients, premedication with alpha and beta receptor blockers is
recommended, because of the risk of blood pressure
crises.
Hypersensitivity - A positive history of allergy, asthma or
untoward reaction during previous similar investigations
indicates a need for extra caution since, as with other
contrast media, this product may provoke anaphylaxis or
other manifestations of allergy with nausea, vomiting,
dyspnoea, erythema, urticaria and hypotension. The
benefits should clearly outweigh the risks in such patients
and appropriate resuscitative measures should be
immediately available.
The risk of bronchospasm-inducing reactions in asthmatic
patients is higher after contrast media administration,
especially in patients taking beta-blockers.
In patients with an allergic disposition, known
hypersensitivity to iodinated contrast media and a history of
asthma, pre-medication with antihistamines and/or
corticoids is recommended to prevent possible
anaphylactoid reactions.
Hypersensitivity testing - In patients with suspected or
known hypersensitivity to contrast media, sensitivity test
doses are not recommended, as severe or fatal reactions
to contrast media are not predictable from sensitivity test.
Anxiety - Pronounced states of excitement, anxiety and
malaise pain may cause or potentiate contrast related
reactions. In these cases, a sedative may be given.
Concomitant medication – Use of the product may
interfere with tests for thyroid function. Vasopressor agents
should not be administered prior to iomeprol. Treatment
with drugs that lower the seizure threshold such as certain
neuroleptics (MAO inhibitors, tricyclic antidepressants),
analeptics, analgesics, antiemetics and phenotiazine
derivatives should be discontinued 48 hours before the
examination. Treatment should not be resumed until 24
hours post-procedure.
Anticonvulsant therapy must not be discontinued and
should be administered in optimal dosage.
It has been reported that cardiac and/or hypertensive
patients under treatment with diuretics, ACE-inhibitors,
and/or beta blocking agents are at higher risk of adverse
reactions when administered iodinated contrast media.
Beta-blockers may impair the response to treatment of
bronchospasm induced by contrast medium.
Allergy-like reactions to contrast media are more frequent
and may manifest as delayed reactions in patients treated
with immuno-modulators, like Interleukin-2 (IL-2).
b. In relation to the imaging procedure:
Coagulation, catheter manipulation - A property of nonionic contrast media is the extremely low interference with
normal physiological functions. Non-ionic contrast media
have less anti-coagulant activity in-vitro than ionic media.
by the physician, a normal diet and adequate
fluid intake is maintained
during the day preceding the examination.
However, patients should avoid eating or
drinking during the two hours preceding
the X-ray examination.
Pre-medication - In pheochromocytoma
patients, pre-medication with alpha-receptor
blockers is recommended because of the risk of
blood pressure crises.
Hypersensitivity - In patients with an allergic
disposition, known hypersensitivity to iodinated
contrast media and a history of asthma, premedication with antihistamines and/or corticoids
is recommended to prevent possible
anaphylactoid reactions.
Anxiety - Pronounced states of excitement,
anxiety and malaise may cause or potentiate
contrast related reactions. In these cases, a
sedative may be given.
Concomitant medication - Treatment with
drugs that lower the seizure threshold such as
neuroleptics, analgesics, antiemetics,
and phenotiazine derivatives should be
discontinued 48 hours before the examination.
Treatment should not be resumed until 24 hours
post-procedure.
Anticonvulsant therapy must not be
discontinued and should be administered in
optimal dosage.
b. In relation to the imaging procedure:
Coagulation, catheter manipulation - A
property of non-ionic contrast media is the
extremely low interference with normal
physiological functions. Non-ionic contrast
media have less anti-coagulant activity in-vitro
than ionic media. Medical and
paramedical personnel performing vascular
catheterization procedures should be aware of
this and pay meticulous attention to the
angiographic technique so as to minimize the
risk of procedure-related thrombosis and
embolism, including catheter flushing with
physiological saline solution (if necessary with
heparin added).
Observation of the patient
Intravascular administration of contrast media
should be performed, whenever possible, with
the patient lying down. The
patient should be kept under observation for at
least 30 minutes after the administration.
Hypersensitivity testing - Reactions to
contrast media are not predictable from
sensitivity test.
Extravasation - Extreme caution during
injection of contrast media is necessary to avoid
extravasation. This is especially
important in patients with severe arterial or
venous disease
Medical and paramedical personnel performing vascular
catheterization procedures should be aware of this and pay
meticulous attention to the angiographic technique. so as to
minimize the risk of procedure-related thrombosis and
embolism, including catheter flushing with physiological
saline solution (if necessary with heparin added). Non ionic
media should not be allowed to remain in contact with
blood in a syringe, and intravascular catheters should be
flushed frequently to minimise the risk of clotting which,
rarely, has led to serious thromboembolic complications.
Observation of the patient
Intravascular administration of contrast media should be
performed, whenever possible, with the patient lying down.
The patient should be kept under observation for at least
30 minutes after the administration.
Hypersensitivity testing - Reactions to contrast media are
not predictable from sensitivity test.
Extravasation - Extreme caution during injection of
contrast media is necessary to avoid extravasation. This is
especially important in patients with severe arterial or
venous disease.
c. In relation to the contrast medium:
Single use - Bottles containing contrast media solution are
not intended for the withdrawal of multiple doses. The
rubber stopper should never be pierced more than once.
The use of proper withdrawal cannulae for piercing the
stopper and drawing up the contrast medium is
recommended. The contrast medium should not be drawn
into the syringe until immediately before use and should not
be diluted. Solutions not used in one examination session
or waste material, such as the connecting tubes, should be
disposed.
Any residue of contrast medium in the syringe must be
discarded.
Bottles of 500 ml should be used in conjunction with an
injector system. After each patient examination, the
connecting tubes (to the patient) and relevant disposable
parts should be disposed because could be contaminated
with blood.
At the end of the sessions, the left over solution in the
bottle and in the connecting tubes as well as any
disposable parts of the injector system should be
discarded. Any additional instructions from the respective
equipment manufacturer must also be adhered to.
Incompatibilities with other drugs - Contrast media
should never be admixed with any other drug to avoid
incompatibility.
Thyroid function tests - Administration of iodinated
contrast media reduces thyroid-targeted radioisotopeuptake by the thyroid tissue for a period of at least two
weeks.
The results of “Protein Binding Iodine” and “radioactive
iodine uptake” studies may not reflect thyroid function
accurately for up to two weeks following administration of
iodinated contrast media. When such tests should be
performed, it is advisable to use T3 resin uptake and total
or free thyroxine (T4) assays.
Oral cholecystographic agents - Recent literature has
revealed no evidence of interactions of renally-excreted
c. In relation to the contrast medium:
Single use - Bottles containing contrast media
solution are not intended for the withdrawal of
multiple doses. The rubber
stopper should never be pierced more than
once. The use of proper withdrawal cannulae for
piercing the stopper and drawing up the contrast
medium is recommended. The contrast medium
should not be drawn into the syringe until
immediately before use and should not be
diluted. Solutions not used in one examination
session or waste material, such as the
connecting tubes, should be disposed.
Any residue of contrast medium in the syringe
must be discarded.
Bottles of 500 ml should be used in conjunction
with an injector system. After each patient
examination, the connecting
tubes (to the patient) and relevant disposable
parts should be disposed because could be
contaminated with blood.
At the end of the sessions, the left over solution
in the bottle and in the connecting tubes as well
as any disposable parts of the injector system
should be discarded. Any additional instructions
from the respective equipment manufacturer
must also be adhered to.
Incompatibilities with other drugs - Contrast
media should never be admixed with any other
drug to avoid incompability.
Thyroid function tests - Administration of
iodinated contrast media reduces thyroidtargeted radioisotope-uptake by the thyroid
tissue for a period of at least two weeks.
The results of “Protein Binding Iodine” and
“radioactive iodine uptake” studies may not
reflect thyroid function accurately for up to two
weeks following administration of iodinated
contrast media. When such tests should be
performed, it is advisable to use T3 resin uptake
and total or free thyroxine (T4) assays.
Oral cholecystographic agents - Recent
literature has revealed no evidence of
interactions of renally-excreted contrast media
with oral cholecystographic contrast media.
Laboratory tests - High concentrations of
contrast media in serum and urine can interfere
with laboratory test results of
bilirubin, proteins or inorganic substances (e.g.
iron, copper, calcium, phosphate).
contrast media with oral cholecystographic contrast media.
Laboratory tests - High concentrations of contrast media
in serum and urine can interfere with laboratory test results
of bilirubin, proteins or inorganic substances (e.g. iron,
copper, calcium, phosphate).
Special warnings
Consideration of possible serious side effects, the use of
iodinated contrast media should be limited to cases for
which there is a precise need for a contrast examination.
The need should be evaluated on the basis of the clinical
status of the patient, in particular in relation to history of
pathologies of the cardiovascular, renal and/or
hepatobiliary systems. The use of contrast media should be
avoided in case of Waldenstroem's paraproteinemia, and
multiple myeloma and of advanced hepato and/or renal
diseases.
Cardioangiographic diagnostic procedures that involve the
use of any radiopaque contrast media should be carried out
in hospitals where appropriate emergency facilities and
personnel trained in life support is readily available.
After any other contrast-enhanced X-ray procedures,
competent personnel and adequate emergency facilities
should be available (AMBU, oxygen, antihistaminics,
vasoconstrictors, cortisonics, etc.) in the radiology
departments of public or private clinics.
Special care should be taken when venography is
performed in patients with suspected thrombosis, phlebitis,
severe ischaemic disease, local infection or a totally
obstructed artero-venous system.
Use in:
New-borns, children -Young infants aged less than one
year, new-borns in particular, are highly susceptible to
electrolyte imbalances and haemodynamic alterations.
Care should be taken regarding the dosage to be used, the
details of the procedure and the patient's status.
Pregnancy - Animal studies do not indicate any
teratogenic or foetotoxic effects. As with other non-ionic
contrast media, there are no adequate and well-controlled
studies in pregnant women to confirm no harmful affect
also in human beings. Therefore avoid in pregnancy unless
there is no safer alternative.
Wherever possible, radiation exposure, either with or
without contrast media use, should be avoided during
pregnancy and its benefit accurately weighted against the
possible risks.
Nursing women - Iodinated contrast media are poorly
excreted in human breast milk and from experience it
appears there should be no damage to the breast-fed baby.
Stopping breastfeeding is unnecessary.
However, as a cautionary measure, breast-feeding should
be discontinued prior to the administration of iomeprol and
should not be recommenced until at least 24 hours after the
administration of the contrast medium.
Women Of Child-Bearing Potential - Appropriate
investigations and measures should be taken when
exposing women of child-bearing potential to any X-ray
examination, whether with or without contrast medium.
Special warnings
a) General for all administration routes
Consideration of possible serious side effects,
the use of iodinated contrast media should be
limited to cases for which there is a precise
need for a contrast examination. The need
should be evaluated on the basis of the clinical
status of the
patient, in particular in relation to history of
pathologies of the cardiovascular, renal and/or
hepatobiliary systems. The use
of contrast media should be avoided in case of
Waldenstroem's paraproteinemia, and multiple
myeloma and of advanced
hepato and/or renal diseases.
Cardioangiographic diagnostic procedures that
involve the use of any radiopaque contrast
media should be carried out in hospitals where
appropriate emergency facilities and personnel
trained in life support is readily available.
After any other contrast-enhanced X-ray
procedures, competent personnel and adequate
emergency facilities should be available (AMBU,
oxygen, antihistaminics, vasoconstrictors,
cortisonics, etc.) in the radiology departments of
public or private clinics.
Special care should be taken in patients with
suspected thrombosis, phlebitis, severe
ischemia, local infection or arterovenous
obstruction.
Use in:
New-borns, children -Young infants aged less
than one year, new-borns in particular, are
highly susceptible to electrolyte
imbalances and haemodynamic alterations.
Care should be taken regarding the dosage to
be used, the details of the procedure and the
patient's status.
Pregnancy - Animal studies do not indicate any
teratogenic or foetotoxic effects. As with other
non-ionic contrast media, there are no adequate
and well-controlled studies in pregnant women
to confirm no harmful affect also in human
beings.
Wherever possible, radiation exposure, either
with or without contrast media use, should be
avoided during pregnancy and its benefit
accurately weighted against the possible risks.
Nursing women - Iodinated contrast media are
poorly excreted in human breast milk and from
experience it appears there should be no
damage to the breast-fed baby.
Special
warnings
Elderly - The elderly are at special risk of reactions to
contrast media especially when high dosage of contrast
medium is used. Myocardial ischemia, major arrhythmias
and extrasystoles are more likely to occur in these patients.
The higher probability of neurological diseases and severe
vascular disease represents an aggravating factor.
Probability of acute renal insufficiency is higher in these
subjects.
In elderly patients the lowest effective dose should be
used.
Use in patients with particular pathological conditions:
Hypersensitivity to iodinated contrast media Hypersensitivity or a previous history of a reaction to
iodinated contrast media increase the risk of recurrence of
a severe reaction even with non-ionic media.
Allergic predisposition - It is generally agreed that
adverse reactions to iodinated contrast media are more
common in patients having a history of allergy such as hay
fever, hives and food allergy.
Asthmatic patients – These patients are at higher risk of
bronchospasm and related events after contrast media
administration.
Hyperthyroidism, nodular goitre - The product should be
used with caution in patients with hyperthyroidism or goitre.
The small amount of free inorganic iodide that may be
present in contrast media, might have some effects on
thyroid function: these effects appear more evident in
patients with latent or overt hyperthyroidism or goitre.
Thyroid storms have been reported following administration
of iodinated contrast media. Use may interfere with thyroid
function tests.
Effect on ability to drive and use machinery – No data is
available. However, given the rare possibility of delayed
adverse reactions to contrast media, driving or using
machinery should be avoided for 24 hours following the
administration.
Renal failure - Pre-existing renal impairment may
predispose to acute renal dysfunction following contrast
media administration.
Preventive measures include: identification of high-risk
patients; ensuring adequate hydration before contrast
medium administration, preferably by maintaining i.v.
infusion before and during the procedure and until the
contrast medium has been cleared by the kidneys; avoiding
whenever possible, the administration of nephrotoxic drugs
or major surgery or procedure such as renal angioplasty,
until the contrast medium has been cleared; postponing a
new contrast agent examination until renal function returns
to pre-examination levels.
Patients on dialysis may receive contrast media which are
easily dialysable such is the case with iomeprol.
Diabetes mellitus - Care should be taken in renal
impairment and diabetes. In these patients it is important
to maintain hydration in order to minimise deterioration in
renal function.
Diabetic nephropathy The presence of renal damage in
diabetic patients may predispose to renal impairment
However, as a cautionary measure, breastfeeding should be discontinued prior to the
administration of iomeprol and should not be
recommenced until at least 24 hours after the
administration of the contrast medium.
Women Of Child-Bearing Potential Appropriate investigations and measures should
be taken when exposing women of
child-bearing potential to any X-ray examination,
whether with or without contrast medium.
Elderly - The elderly are at special risk of
reactions to contrast media especially when
high dosage of contrast medium is
used. Myocardial ischemia, major arrhythmias
and extrasystoles are more likely to occur in
these patients. The higher
probability of neurological diseases and severe
vascular disease represents an aggravating
factor.
Probability of acute renal insufficiency is higher
in these subjects.
Use in patients with particular pathological
conditions:
Hypersensitivity to iodinated contrast media
- Hypersensitivity or a previous history of a
reaction to iodinated contrast media increase
the risk of recurrence of a severe reaction even
with non-ionic media.
Allergic predisposition - It is generally agreed
that adverse reactions to iodinated contrast
media are more common in patients having a
history of allergy such as hay fever, hives and
food allergy.
Asthmatic patients – These patients are at
higher risk of bronchospasm and related events
after contrast media administration.
Hyperthyroidism, nodular goitre -The small
amount of free inorganic iodide that may be
present in contrast media, might
have some effects on thyroid function: these
effects appear more evident in patients with
latent or overt hyperthyroidism or goitre. Thyroid
storms have been reported following
administration of iodinated contrast media.
Effect on ability to drive and use machinery
– No data is available. However, given the rare
possibility of delayed adverse reactions to
contrast media, driving or using machinery
should be avoided for 24 hours following the
administration.
Intraarterial and intravenous administration
Use in patients with special pathological
conditions
Renal failure - Pre-existing renal impairment
may predispose to acute renal dysfunction
following contrast media administration.
Preventive measures include: identification of
high-risk patients; ensuring adequate hydration
following intravascular contrast medium administration.
This may precipitate lactic acidosis in patients who are
taking biguanides metformin.
As a precaution, biguanides should be stopped 48 hours
prior to the administration of the contrast medium.
Antidiabetic treatment with biguanides should be reinstated only after renal function has been regained.
In diabetic patients with diabetic nephropathy, under
treatment with metformin and with moderate renal
impairment, metformin should be stopped at the time of, or
prior to the procedure and withheld for 48 hours
subsequent to the procedure and reinstituted only after
renal function has been re-evaluated and found to be
normal. In emergency patients in whom renal function is
either impaired or unknown, the physician shall weigh out
risk and benefit of an examination with a contrast medium
and take precautions. Metformin should be stopped from
time of contrast medium administration. After the procedure
the patient should be monitored for signs of lactic acidosis.
Metformin should be restarted 48 hours after contrast
medium if serum creatinine/eGFR is unchanged from the
pre-imaging level.
Patients with normal renal function can continue to take
metformin normally.
Multiple myeloma, Waldestroem’s paraproteinaemia The use of the product is generally contraindicated. It is
noteworthy that Myelomatosis or paraproteinaemias are
conditions predisposing to renal impairment following
contrast medium administration. The benefits of the use of
a contrast-enhanced procedure should be carefully
weighted against the possible risk. Adequate hydration and
monitoring of renal function are recommended after CM
administration.
Pheochromocytoma - These patients may develop severe
hypertensive crises (at times uncontrollable) during
radiological procedures with contrast media (see also
premedication).
Sickle cell disease - Contrast media may promote sickling
in individuals who are homozigous for sickle cell disease.
Adequate hydration is recommended.
Myasthenia gravis - The administration of iodinated
contrast media may aggravate myasthenia signs and
symptoms.
Severe liver and renal dysfunction - Generally, contrast
media use is contraindicated Indeed., Combination of
severe hepatic and renal impairment can delay contrast
medium excretion, hence predisposing to increased risk of
untoward reactions. therefore such patients should not be
examined unless absolutely necessary.
Severe cardiovascular disease - There is an increased
risk of severe reactions in individuals with severe
cardiovascular disease and particularly in those with heart
failure and coronary artery disease. Intravascular contrast
medium injection may precipitate pulmonary oedema in
patients with manifest or incipient heart failure, whereas
administration in pulmonary hypertension and valvular
heart diseases, may lead to pronounced haemodynamic
changes.
Ischaemic ECG changes and major arrhythmias are
before contrast medium
administration, preferably by maintaining i.v.
infusion before and during the procedure and
until the contrast medium has been cleared by
the kidneys; avoiding whenever possible, the
administration of nephrotoxic drugs or major
surgery or
procedure such as renal angioplasty, until the
contrast medium has been cleared; postponing
a new contrast agent examination until renal
function returns to pre-examination levels.
Patients on dialysis may receive contrast media
which are easily dialysable such is the case with
iomeprol.
Diabetes mellitus - Diabetic nephropathy may
predispose to renal impairment following
intravascular contrast medium
administration. This may precipitate lactic
acidosis in patients who are taking biguanides.
As a precaution, biguanides should be stopped
48 hours prior to the administration of the
contrast medium. Antidiabetic treatment with
biguanides should be re-instated only after renal
function has been regained.
Multiple myeloma, Waldestroem’s
paraproteinaemia - The use of the product is
generally contraindicated. It is noteworthy
that myelomatosis or paraproteinaemias are
conditions predisposing to renal impairment
following contrast medium administration.
Adequate hydration is recommended.
Pheochromocytoma - These patients may
develop severe hypertensive crises (at times
uncontrollable) during radiological procedures
with contrast media.
Sickle cell disease - Contrast media may
promote sickling in individuals who are
homozigous for sickle cell disease. Adequate
hydration is recommended.
Myasthenia gravis - The administration of
iodinated contrast media may aggravate
myasthenia signs and symptoms.
Severe liver and renal dysfunction Generally, contrast media use is contraindicated
Indeed, combination of severe hepatic and renal
impairment can delay contrast medium
excretion, hence predisposing to increased risk
of untoward reactions.
Severe cardiovascular disease - There is an
increased risk of severe reactions in individuals
with severe cardiovascular disease and
particularly in those with heart failure and
coronary artery disease. Intravascular contrast
medium injection may precipitate pulmonary
oedema in patients with manifest or incipient
heart failure, whereas administration in
pulmonary hypertension and valvular heart
commonest in elderly patients and in those with preexisting cardiac disease: their frequency and severity
appear to be related to the severity of cardiac impairment.
Severe and chronic hypertension may increase the risk of
renal damage following contrast medium administration
and the risks associated with the catheterization procedure.
Cardiovascular diseases - Care should be taken in
severe cardiac disease particularly heart failure and
coronary artery disease. Reactions may include pulmonary
oedema, haemodynamic changes, ischaemic ECG
changes and arrhythmias. In severe, chronic hypertension
the risk of renal damage following administration of a
contrast medium is increased. In these cases the risks
associated with the catheterization procedure are
increased.
CNS disorders - Particular care should be paid in patients
with acute cerebral infarction, acute intracranial
haemorrhage, and conditions involving blood-brain-barrier
(BBB) damage, brain oedema and acute demyelination.
The presence of intracranial tumors or metastases and a
history of epilepsy may increase the probability of the
occurrence of convulsions.
Neurological symptoms due to degenerative, inflammatory
or neoplastic cerebrovascular pathologies may be
exacerbated by contrast medium administration.
Vasospasm and consequent Cerebral ischaemic
phenomena may be caused by intravascular injections of
contrast medium. Patients with symptomatic
cerebrovascular diseases, e.g. recent stroke or frequent
TIA (transient ischaemic attack) have an increased risk of
transient neurological complications.
Alcoholism - Acute and chronic alcoholism have been
proven both experimentally and clinically to increase BBB
permeability. This facilitates the passage of iodinated
agents the contrast medium into the cerebral tissue,
possibly leading to CNS disorders. Alcoholism may reduce
seizure threshold.
Drug addiction - Also the abuse of drugs may reduce
seizure threshold.
Effect on ability to drive and use machinery - There is
no known effect on the ability to drive and operate
machines.
diseases, may lead to pronounced
haemodynamic changes.
Ischaemic ECG changes and major arrhythmias
are commonest in elderly patients and in those
with pre-existing cardiac disease: their
frequency and severity appear to be related to
the severity of cardiac impairment.
Severe and chronic hypertension may increase
the risk of renal damage following contrast
medium administration and the risks associated
with the catheterization procedure.
CNS disorders - Particular care should be paid
in patients with acute cerebral infarction, acute
intracranial haemorrhage,
and conditions involving blood-brain-barrier
(BBB) damage, brain oedema and acute
demyelination. The presence of intracranial
tumors or metastases and a history of epilepsy
may increase the probability of the occurrence
of convulsions.
Neurological symptoms due to degenerative,
inflammatory or neoplastic cerebrovascular
pathologies may be exacerbated by contrast
medium administration.
Vasospasm and consequent ischaemic
phenomena may be caused by intravascular
injections of contrast medium. Patients with
symptomatic cerebrovascular diseases, recent
stroke or frequent TIA (transient ischaemic
attack) have an increased risk of transient
neurological complications.
Alcoholism - Acute and chronic alcoholism
have been proven both experimentally and
clinically to increase BBB permeability.
This facilitates the passage of iodinated agents
into the cerebral tissue, possibly leading to CNS
disorders. Alcoholism may reduce seizure
threshold.
Drug addiction - Also the abuse of drugs may
reduce seizure threshold.
Undesirable Effects
General
The use of iodinated contrast media may cause untoward
side effects. They are usually mild to moderate and
transient in nature. However, more serious reactions up to
anaphylactoid shock, with possible fatal outcome, may
occur.
In most cases reactions occur within minutes of dosing up.
However, reactions may manifest also later on up to 24
hours from the injection, depending on the administration
route.
Anaphylaxis (anaphylactoid/hypersensitivity reactions) may
manifest with various symptoms, and rarely does any one
patient develop all the symptoms. Typically, in 1 to 15 min
(but rarely after as long as 2 h), the patient complains of
feeling abnormal, agitation, flushing, feeling hot, sweating
increased, dizziness, lacrimation increased, rhinitis,
palpitations, paraesthesia, pruritus, head throbbing,
pharyngolaryngeal pain and throat tightness, dysphagia,
cough, sneezing, urticaria, erythema, mild localised
oedema, angioneurotic oedema and dyspnoea owing to
tongue glottic and /laryngeal/ pharyngeal oedema and/or
laryngospasm manifesting with wheezing and
bronchospasm.
Nausea, vomiting, abdominal pain, and diarrhoea are less
common also reported.
These reactions, which can occur independently of the
dose administered or the route of administration, may
represent the first signs of circulatory collapse.
Administration of the contrast medium must be
discontinued immediately and, if needed, appropriate
specific treatment urgently initiated via venous access.
Severe anaphylactic reactions involving the cardiovascular
system, such as vasodilatation, with pronounced
hypotension, reflex tachycardia, dyspnoea, agitation,
cyanosis and loss of consciousness progressing to
respiratory and/or cardiac arrest may result in death. These
events can occur rapidly and require full and aggressive
cardio-pulmonary resuscitation.
Primary circulatory collapse can occur as the only and/or
initial presentation without respiratory symptoms or without
other signs or symptoms outlined above.
The adverse reactions reported in clinical trials among
4,903 adult patients and from post-marketing surveillance
are represented in the tables below by frequency and
classified by MedDRA system organ class.
Within each frequency grouping, adverse reactions are
presented in order of decreasing seriousness.
Blood and
lymphatic system
disorders
Immune system
disorders
Frequency
unknown*
Thrombocytopenia
Frequency
unknown*
Anaphylactoid
reaction
Psychiatric
disorders
Frequency
unknown*
Anxiety,
Confusional state
Undesirable Effects
General
The use of iodinated contrast media may cause
untoward side effects. They are usually mild to
moderate. However, more serious reactions up
to anaphylactoid shock, with possible fatal
outcome, may occur.
In most cases reactions occur within minutes of
dosing up. However, reactions may manifest
also later on up to 24 hours from the injection,
depending on the administration route.
Anaphylaxis (anaphylactoid/hypersensitivity
reactions) may manifest with various symptoms,
and rarely does any one patient develop all the
symptoms. Typically, in 1 to 15 min (but rarely
after as long as 2 h), the patient complains of
feeling abnormal, agitation, flushing, feeling hot,
sweating increased, dizziness, lacrimation
increased, rhinitis, palpitations,
paraesthesia, pruritus, head throbbing,
pharyngolaryngeal pain and throat tightness,
dysphagia, cough, sneezing, urticaria,
erythema, and mild localised oedema or
angioneurotic oedema and dyspnoea owing to
tongue and laryngeal oedema and/or
laryngospasm manifesting with wheezing and
bronchospasm.
Nausea, vomiting, abdominal pain, and
diarrhoea are less common.
These reactions, which can occur independently
of the dose administered or the route of
administration, may represent the first signs of
circulatory collapse.
Administration of the contrast medium must be
discontinued immediately and, if needed,
appropriate specific treatment urgently initiated
via venous access.
Severe anaphylactic reactions involving the
cardiovascular system, such as vasodilatation,
with pronounced hypotension, reflex
tachycardia, dyspnoea, agitation, cyanosis and
loss of consciousness progressing to respiratory
and/or cardiac arrest may result in death. These
events can occur rapidly and require full and
aggressive cardio-pulmonary resuscitation.
Primary circulatory collapse can occur as the
only and/or initial presentation without
respiratory symptoms or without other signs or
symptoms outlined above.
From clinical trials
Adverse experiences reported among patients
treated with Iomeprol during clinical trials are
shown below.
Adverse events
Eye disorders
Cardiac disorders
Frequency
unknown*
Uncommon
(≥1/1000 to
<1/100)
Rare
(≥1/10,000 to
<1/1000)
Frequency
unknown*
Vascular disorders
Nervous system
disorders
Uncommon
(≥1/1000 to
<1/100)
Rare
(≥1/10,000 to
<1/1000)
Frequency
unknown*
Blindness
transient,
Visual
disturbance,
Conjunctivitis,
Lacrimation
increased,
Photopsia
Bradycardia,
tachycardia,
hypertension,
hypotension
Bradycardia,
tachycardia
Vasodilatation,
cyanosis,
circulatory collapse
Cardiac arrest,
Myocardial
infarction,
Cardiac failure,
Angina pectoris,
Arrhythmia,
Ventricular or
atrial fibrillation,
Atrioventricular
block,
Extrasystoles,
Palpitations,
Cyanosis
Hypertension
Hypotension
Common
(≥1/100 to <1/10)
Circulatory
collapse or
shock,
Hot flush,
Flushing,
Pallor
Asthenia, syncope,
headache
Uncommon
(≥1/1000 to
<1/100)
Headache,
dizziness,
paralysis, agitation
Rare
(≥1/10,000 to
<1/1000)
Presyncope
Tremor, muscle
spams, confusion,
loss of
consciousness,
visual field defect,
aphasia,
convulsions, coma
Frequency
unknown*
Coma,
Transient
ischaemic attack,
Paralysis,
Syncope,
Convulsions,
Loss of
Cardiovascular
(mainly after
cardiovascular
procedures/
Uncommon
Bradycardia ,
tachycardia,
hypertension,
hypotension
Rare
Vasodilatation,
cyanosis,
circulatory
collapse
interventions)
Nervous
System
Common
Uncommon
Rare
Gastrointestinal system
Asthenia, syncope,
headache
Dizziness, paralysis,
agitation
Tremor, muscle
spasms, confusion,
loss of consciousness,
visual field defect,
aphasia, convulsions,
coma
Common
Nausea
Uncommon
Vomiting
Common
Dyspnoea, nasal
congestion, laryngeal
oedema
Skin and
Subcutaneous
Tissue
Uncommon
Wheals, pruritus, rash
General
Common
Injection site warmth
and pain, pallor
Respiratory
system
Uncommon
Renal and
Urinary
Disorders
Back pain, chest pain,
rigors, injection site
haemorrhage, pyrexia,
sweating increased
Rare
Anaphylactoid
reaction
(characterized by
cardiovascular,
respiratory and
cutaneous symptoms)
Rare
Renal insufficiency,
oliguria, proteinuria,
blood creatinine
increased
Some of these events may occur as a
consequence of the procedure.
Post Marketing Surveillance
The following undesirable effects have been
Gastrointestinal
disorders
Common
(≥1/100 to <1/10)
Uncommon
(≥1/1000 to
<1/100)
Frequency
unknown*
Respiratory,
thoracic and
mediastinal
disorders
Common
(≥1/100 to <1/10)
Uncommon
(≥1/1000 to
<1/100)
Frequency
unknown*
Skin and
subcutaneous
tissue disorders
Uncommon
(≥1/1000 to
<1/100)
Rare
(≥1/10,000 to
<1/1000)
Frequency
unknown*
General
disorders and
administration
site conditions
Common
(≥1/100 to <1/10)
Uncommon
(≥1/1000 to
<1/100)
consciousness,
Dysarthria,
Paraesthesia,
Amnesia,
Somnolence,
Taste abnormality
Nausea
reported during post- marketing in <3/10,000
patients.
Intravascular and intra-thecal
administration:
-
Nausea,
vomiting
Diarrhoea,
Abdominal pain,
Salivary
hypersecretion,
Dysphagia,
Salivary gland
enlargement
-
Dyspnea, nasal
congestion,
laryngeal oedema
Dyspnoea
Respiratory
arrest,
Acute respiratory
distress
syndrome
(ARDS),
Pulmonary
oedema,
Laryngeal
oedema,
Pharyngeal
oedema,
Bronchospasm,
Asthma,
Cough,
Hyperventilation,
Pharynx
discomfort,
Laryngeal
discomfort,
Rhinitis,
Dysphonia
Wheals,
Erythema,
Urticaria,
Pruritus rash
Rash
Angioedema
Cold sweat
Sweating increased
Injection site
warmth and pain,
pallor Feeling hot
Back pain,
Chest pain,
Injection site
-
-
-
-
-
General: shock, malaise, fatigue, hot
flushes, flushing, cold sweat, coldness local,
taste abnormality, thirst, injection site
reaction.
Nervous system: hyperkinetic syndrome,
encephalopathy, paralysis, oculomotor
nerve paralysis, paraesthesia, dysarthria,
dizziness, dysphonia, faecal incontinence,
brain oedema,
Cardiovascular: cardiac arrest, myocardial
infarction, angina pectoris, extrasystoles,
arrhythmia, ventricular or atrial fibrillation,
tachycardia, palpitations, atrioventricular
block, electrocardiogram abnormal, ST
segment elevation.
Respiratory: respiratory arrest, pulmonary
oedema, acute respiratory distress
syndrome (ARDS), bronchospasm, asthma,
pharyngeal oedema, laryngeal stridor,
rhinitis, cough, hyperventilation, hypoxia,
pharynx and/or laryngeal discomfort.
Skin and subcutaneous tissue disorders:
angioneurotic oedema, eczema, urticaria,
wheals
cold sweat
Vascular (extracardiac): cerebrovascular
disorder, transient ischaemic attack.
Gastrointestinal disorders: pancreatitis
acute, ileus, diarrhea, abdominal pain,
salivary hypersecretion, dysphagia.
Urogenital: urinary incontinence, blood
urea increased.
Senses: parosmia
Eye disorders: blindness transient, visual
disturbance, conjunctivitis, lacrimation
increased, photopsia, photophobia.
Musculoskeletal: arthralgia, muscle
stiffness.
Psychiatric disorders: amnesia, anorexia,
anxiety, somnolence.
Liver and biliary system: liver function tests
abnormal.
Platelets, bleeding and coagulation:
thrombocytopenia.
Administration to body cavities
Blood amylase increase is common following
ERCP (Endoscopic retrograde
cholangiopancreatography). Rare cases of
pancreatitis have been described.
The reactions reported in cases of arthrography
and fistulography usually represent irritative
manifestations superimposed on pre-existing
warmth and pain
rigors, injection site
haemorrhage,,
pyrexia, sweating
increased
Rare
(≥1/10,000 to
<1/1000)
Frequency
unknown*
Musculoskeletal
and connective
tissue disorder
Renal and urinary
disorders
Rare
(≥1/10,000 to
<1/1000)
Frequency
unknown
Rare
(≥1/10,000 to
<1/1000)
Frequency
unknown
Investigations
Rare
(≥1/10,000 to
<1/1000)
Frequency
unknown
Asthenia,
Rigors,
Pyrexia
Anaphylactoid
reaction
(characterized
by
cardiovascular,
respiratory and
cutaneous
symptoms)
Injection site
reaction**,
Coldness local,
Fatigue,
Malaise,
Thirst
Back pain
Arthralgia
Renal
insufficiency,
oliguria,
proteinuria, blood
creatinine
increased
Renal failure
Blood creatinine
increased
Electrocardiogram
ST segment
elevation,
Electrocardiogram
abnormal
* Since the reactions were not observed during clinical trials with
4515 patients, best estimate is that their relative occurrence is rare
( ≥1/10,000 to <1/1000).
The most appropriate MedDRA term is used to describe a certain
reaction and its symptoms and related conditions.
** Injection site reactions comprise injection site pain and swelling.
In the majority of cases they are due to extravasation of contrast
medium. These reactions are usually transient and result in
recovery without sequelae. Cases of extravasation with
inflammation, skin necrosis and even development of compartment
syndrome have been reported.
Coronary artery thrombosis and coronary artery embolism
have been reported as a complication of coronary
catheterization procedures.
Vasospasm and consequent ischaemia have been observed
during intra-arterial injections of contrast medium, in
conditions of tissue inflammation.
Generalised hypersensitivity reactions are rare,
generally mild and in the form of skin reactions.
However, the possibility of severe anaphylactoid
reactions cannot be excluded. (See beginning of
chapter “Undesirable effects” ).
As with other iodinated contrast media, pelvic
pain and malaise may occur after
hysterosalpingography.
Compliance with the instruction contained in the
package insert reduces the risk of untoward
effects. It is important to inform the physician or
the pharmacist of any untoward effect, even if
not mentioned in this package insert.
particular after coronary and cerebral angiography often
procedurally related and possibly triggered by the tip of the
catheter or excess catheter pressure.
As with other iodinated contrast media, very rare cases of
mucocutaneous syndromes, including Stevens-Johnson
syndrome, toxic epidermal necrolysis (Lyell syndrome) and
erythema multiforme, have been reported following the
administration of Iomeprol injection.
Paediatric patients
There is limited experience with paediatric patients. The
clinical trial paediatric safety database comprises 167
patients.
The Iomeprol safety profile is similar in children and adults.
Some of these events may occur as a consequence of the
procedure.
Post marketing surveillance
and intra-thecal administration:
- Nervous system: hyperkinetic syndrome, encephalopathy,
oculomotor nerve paralysis, dizziness, faecal incontinence,
brain oedema,
- Cardiovascular: tachycardia,
- Respiratory: laryngeal stridor, hypoxia,
- Skin and subcutaneous tissue disorders: angioneurotic
oedema, eczema, urticaria, wheals, - Vascular
(extracardiac): cerebrovascular disorder,
- Gastrointestinal disorders: pancreatitis acute, ileus,
- Urogenital: urinary incontinence, blood urea increased.
- Senses: parosmia
- Eye disorders: photophobia.
- Musculoskeletal: muscle stiffness.
- Psychiatric disorders: anorexia,
- Liver and biliary system: liver function tests abnormal.
- Platelets, bleeding and coagulation:
Administration to body cavities
Blood amylase increase is common following ERCP
(Endoscopic retrograde cholangiopancreatography). Rare
cases of pancreatitis have been described.
The reactions reported in cases of arthrography and
fistulography usually represent irritative manifestations
superimposed on pre-existing conditions of tissue
inflammation.
Generalised hypersensitivity reactions are rare, generally
mild and in the form of skin reactions. However, the
possibility of severe anaphylactoid reactions cannot be
excluded. (See beginning of chapter “Undesirable effects” ).
As with other iodinated contrast media, pelvic pain and
malaise may occur after hysterosalpingography.
Compliance with the instruction contained in the package
insert reduces the risk of untoward effects. It is important to
inform the physician or the pharmacist of any untoward
effect, even if not mentioned in this package insert.