)‫בטיחות‬
)‫מידע בטיחות‬
‫החמרה (( מידע‬
‫על החמרה‬
‫הודעה על‬
‫הודעה‬
30/8/2010
:‫תאריך‬
MULTIHANCE :‫שם תכשיר באנגלית‬
04 30033 00120
:‫ מלטיהנס‬:‫מספר רישום‬
‫ דקסון בע"מ‬:‫שם בעל הרישום‬
‫השינויים בעלון מסומנים על רקע צהוב‬
‫רופא‬
‫בעלון ללרופא‬
‫בעלון‬
‫ים‬/‫ים המבוקש‬/‫פרטים על השינוי‬
‫טקסט חדש‬
‫טקסט נוכחי‬
1 ml of solution for injection contains:
gadobenic acid 334 mg (0.5M) as the
dimeglumine salt. [gadobenate dimeglumine
529 mg = gadobenic acid 334 mg + meglumine
195 mg].
Osmolality at 37C: 1.97 osmol/kg
Viscosity at 37C: 5.3 mPa.s
Solution for injection.
Clear aqueous solution filled into colourless
glass vials.
Osmolality at 37C: 1.97 osmol/kg
Viscosity at 37C: 5.3 mPa.s
This medicinal product is for diagnostic use
only.
MultiHance is a paramagnetic contrast agent for
use in diagnostic magnetic resonance imaging
(MRI) of the liver and Central Nervous System
(CNS) indicated for:
1 ml of solution for injection contains:
gadobenic acid 334 mg (0.5M) as the
dimeglumine
salt.
[gadobenate
dimeglumine 529 mg = gadobenic acid 334
mg + meglumine 195 mg].
Osmolality at 37C: 1.97 osmol/kg
Viscosity at 37C: 5.3 mPa.s
Solution for injection.
Clear aqueous solution filled into
colourless glass vials.
Qualitative and
quantitative
composition
MultiHance is a paramagnetic contrast
agent for use in diagnostic magnetic
resonance imaging (MRI) of the liver and
Central Nervous System (CNS):
Therpeutic
indications
Multihance is indicated MRI of the liver for the
detection of focal liver lesions in patients with
known or suspected primary liver cancer (eg.
hepatocellular carcinoma) or metastatic disease.
Multihance is also indicated for the MRI of the
brain and spine where it improves the detection
of lesions and provides diagnostic information
additional to that obtained with unenhanced
MRI.
‫פרק בעלון‬
Pharmaceutical
form
Multihance is indicated for the detection of
focal liver lesions in patients with known
or suspected primary liver cancer (eg.
hepatocellular carcinoma) or metastatic
disease.
Multihance is also indicated for the MRI of
the brain and spine where it improves the
detection of lesions and provides
diagnostic information additional to that
obtained with unenhanced MRI.
MRI of the liver: the recommended dose
of MultiHance injection in adult patients
is 0.05 mmol/kg body weight. This
corresponds to 0.1 mL/kg of the 0.5 M
solution.
liver: the recommended dose of
MultiHance injection in adult patients is
0.05 mmol/kg body weight. This
corresponds to 0.1 mL/kg of the 0.5 M
solution.
MRI of the brain and spine CNS: the
recommended dose of MultiHance injection in
adult patients is 0.1 mmol/kg body weight. This
corresponds to 0.2 mL/kg of the 0.5 M solution.
CNS: the recommended dose of
MultiHance injection in adult patients is
0.1 mmol/kg body weight. This
corresponds to 0.2 mL/kg of the 0.5 M
Posology and
method of
administration
solution.
MultiHance should be drawn up into the syringe
immediately before use and should not be
diluted. Any unused product should be
discarded and not be used for other MRI
examinations.
To minimise the potential risks of soft tissue
extravasation of MultiHance, it is important to
ensure that the I.V. needle or cannula is
correctly inserted into a vein.
Liver and Brain and Spine: the product
should be administered intravenously either
as a bolus or slow injection (10 ml/min.).
Without dilution. Post-contrast imaging can be
performed immediately following bolus
injection (dynamic MRI).
In the CNS the imaging window has been
shown to be up to 60 minutes after the
administration. In the liver delayed imaging can
be performed between 40 and 120 minutes
following the injection, depending on the
individual imaging needs.
MultiHance should be drawn up into the syringe
immediately before use and should not be
diluted. Any unused product should be
discarded and not be used for other MRI
examinations.
To minimise the potential risks of soft tissue
extravasation of MultiHance, it is important to
ensure that the I.V. needle or cannula is
correctly inserted into a vein.
The injection should be followed by a saline
flush.
Post-contrast imaging acquisition:
Liver
Brain and
Spine
Dynamic
imaging;
Immediatley
following
bolus
injection.
Delayed
imaging:
Between 40
and 120
minutes
following the
injection,
depending on
the
individual
imaging
needs.
Up to 60 minutes after the
administration.
The product should be administered
intravenously either as a bolus or slow
injection (10 ml/min.). Without dilution.
Post-contrast imaging can be performed
immediately following bolus injection
(dynamic MRI).
In the CNS the imaging window has been
shown to be up to 60 minutes after the
administration. In the liver delayed
imaging can be performed between 40 and
120 minutes following the injection,
depending on the individual imaging
needs.
MultiHance should be drawn up into the
syringe immediately before use and should
not be diluted. Any unused product should
be discarded and not be used for other MRI
examinations.
To minimise the potential risks of soft
tissue extravasation of MultiHance, it is
important to ensure that the I.V. needle or
cannula is correctly inserted into a vein.
The injection should be followed by a
saline flush.
Special Populations
Impaired renal function
Use of MultiHance should be avoided in
patients with severe renal impairment (GFR <
30 ml/min/1.73m2) and in patients in the
perioperative liver transplantation period unless
the diagnostic information is essential and not
available with non-contrast enhanced MRI (see
section 4.4). If use of MultiHance cannot be
avoided, the dose should not exceed 0.1
mmol/kg body weight when used for MR of the
brain and spine or MR-angiography and should
not exceed 0.05 mmol/kg body weight when
used for MR of the liver. More than one dose
should not be used during a scan. Because of the
lack of information on repeated administration,
MultiHance injections should not be repeated
unless the interval between injections is at least
7 days.
Elderly (aged 65 years and above)
No dosage adjustment is considered necessary.
Caution should be exercised in elderly patients
(see section 4.4).
…
Caution is advised in patients with renal
impairment (creatinine clearance <30 ml/min).
…
Impaired renal function
Prior to administration of MultiHance, it is
recommended that all patients are screened
for renal
dysfunction by obtaining laboratory tests.
There have been reports of nephrogenic
systemic fibrosis (NSF) associated with use of
some gadolinium containing contrast agents in
patients with acute or chronic severe renal
impairment (GFR<30ml/min/1.73m2).
Patients undergoing liver transplantation are at
particular risk since the incidence of acute renal
failure is high in this group. As there is a
possibility that NSF may occur with
MultiHance, it should therefore be avoided in
patients with severe renal impairment and in
patients in the perioperative liver transplantation
period unless the diagnostic information is
essential and not available with non-contrast
enhanced MRI.
Haemodialysis shortly after MultiHance
administration may be useful at removing
MultiHance from the body. There is no
…
Caution is advised in patients with renal
impairment (creatinine clearance <30
ml/min).
…
Special warnings
and special
precaution for use
evidence to support the initiation of
haemodialysis for prevention or treatment of
NSF in patients not already undergoing
haemodialysis.
Elderly
As the renal clearance of gadobenate
dimeglumine may be impaired in the elderly, it
is particularly important to screen patients aged
65 years and older for renal dysfunction.
Pregnancy
There are no adequate data from for the use of
gadobenate dimeglumine in pregnant women.
Animal studies Studies in animals have shown
reproductive toxicity at repeated high doses (see
section 5.3). The potential risk for humans is
unknown.
MultiHance should not be used during
pregnancy unless the clinical condition of the
woman requires use of
gadobenate dimeglumine clearly necessary.
Lactation
Gadolinium containing contrast agents are
excreted into breast milk in very small amounts
(see section 5.3). At clinical doses, no effects on
the infant are anticipated due to the small
amount excreted into milk and poor absorption
from the gut. Continuing or discontinuing breast
feeding for a period of 24 hours after
administration of MultiHance should be at the
discretion of the doctor and lactating mother.
Although it is not known to what extent
gadobenate dimeglumine is excreted in human
milk, it is known from animal experiments that
minimal amounts, less than 0.5% of the
administered dose were transferred via milk
from mother to neonates. Although the clinical
relevance of this observation is unknown,
breast-feeding should be discontinued prior to
the administration of MultiHance and should
not be recommenced until at least 24 hours after
the administration of MultiHance.
The following adverse events were seen during
the clinical development of MultiHance among
2637 adult subjects. There were no adverse
reactions with a frequency greater than 2%.
System organ
classes
Nervous system
disorders
…
System organ
Rare (1/10,000,
1/1,000)
Hyperaesthesia,
tremor, intracranial
hypertension,
hemiplegia
Common (≥1/100,
There are no adequate data for the use of
gadobenate dimeglumine in pregnant
women. Studies in animals have shown
reproductive toxicity (see section 5.3). The
potential risk for humans is unknown.
MultiHance should not be used during
pregnancy unless clearly necessary.
Pregnancy and
lactation
Although it is not known to what extent
gadobenate dimeglumine is excreted in
human milk, it is known from animal
experiments that minimal amounts, less
than 0.5% of the administered dose were
transferred via milk from mother to
neonates. Although the clinical relevance
of this observation is unknown, breastfeeding should be discontinued prior to the
administration of MultiHance and should
not be recommenced until at least 24 hours
after the administration of MultiHance.
The following adverse events were seen
during the clinical development of
MultiHance among 2637 adult subjects.
There were no adverse reactions with a
frequency greater than 2%.
System organ
Rare (1/10,000,
classes
1/1,000)
Nervous system
Hyperaesthesia,
disorders
tremor
…
System organ
Common (≥1/100,
classes
1/10)
Undesirable
effects
classes
Vascular disorders
…
System organ
classes
Respiratory,
thoracic and
mediastinal
disorders
…
System organ
classes
Gastrointestinal
disorders
…
System organ
classes
General disordes
and administration
site conditions
1/10)
Vasodilation
Rare (1/10,000,
1/1,000)
Dispnoea N.O.S.,
laryngospasm,
wheezing,
pulmonary
congestion,
pulmonary oedema
Rare (1/10,000,
1/1,000)
Constipation,
faecal
incontinence,
necrotising
pancreatitis
Common (≥1/100,
1/10)
Injection Site
Reaction, feeling
hot
Vascular disorders
…
System organ
classes
Respiratory,
thoracic and
mediastinal
disorders
…
System organ
classes
Gastrointestinal
disorders
…
System organ
classes
General disordes
and administration
site conditions
Vasodilation
Rare (1/10,000,
1/1,000)
Dispnoea N.O.S.,
laryngospasm,
wheezing,
pulmonary
congestion
Rare (1/10,000,
1/1,000)
Constipation,
faecal incontinence
Common (≥1/100,
1/10)
Injection Site
Reaction
Also reported were single individual
serious incidents include necrotising
pancreatitis, pulmonary oedema,
intracranial hypertension and/or
hemiplegia.
Laboratory abnormalities such as
Also reported were single individual serious
hypochromic anaemia, leukocytosis,
incidents include necrotising pancreatitis,
leukopenia, basophilia, hypoproteinaemia,
pulmonary oedema, intracranial hypertension
hypocalcaemia, hyperkalaemia,
and/or hemiplegia.
hyperglycaemia or hypoglycaemia,
Laboratory abnormalities such as cited above
albuminuria, glycosuria, haematuria,
include hypochromic anaemia, leukocytosis,
hyperlipidaemia, hyperbilirubinaemia,
leukopenia, basophilia, hypoproteinaemia,
hypocalcaemia, hyperkalaemia, hyperglycaemia serum iron increased, and increases in
serum transaminases, alkaline phosphatase,
or hypoglycaemia, albuminuria, glycosuria,
lactic dehydrogenase, and in serum
haematuria, hyperlipidaemia,
creatinine and were reported in equal or
hyperbilirubinaemia, serum iron increased, and
less than 0.4% of patients following the
increases in serum transaminases, alkaline
phosphatase, lactic dehydrogenase, and in serum administration of MultiHance. However
these findings were mostly seen in patients
creatinine and were reported in equal or less
with evidence of pre-existing impairment
than 0.4% of patients following the
of hepatic function or pre-existing
administration of MultiHance. However these
metabolic disease.
findings were mostly seen in patients with
…
evidence of pre-existing impairment of hepatic
function or pre-existing metabolic disease.
In marketed use, adverse reactions were
…
reported in fewer than 0.1 % of patients.
Most commonly reported were: nausea,
In marketed use, adverse reactions were
vomiting, signs and symptoms of
reported in fewer than 0.1 % of patients.
hypersensitivity reactions including
Most commonly reported were: nausea,
anaphylactic shock, anaphylactoid
vomiting, signs and symptoms of
reactions, angioedema, laryngeal spasm
hypersensitivity reactions including
and rash.
anaphylactic shock, anaphylactoid reactions,
Injection site reactions due to extravasation
angioedema, laryngeal spasm and rash.
of the contrast medium leading to local
Injection site reactions due to extravasation of
the contrast medium leading to local pain or
burning sensations, swelling and blistering have
been reported.
Isolated cases of nephrogenic systemic fibrosis
(NSF) have been reported with MultiHance in
patients co-administered other gadoliniumcontaining contrast agents (see Section 4.4).
…
pain or burning sensations, swelling and
blistering have been reported.
MultiHance can has been shown to be removed
by haemodialysis. However there is no evidence
that haemodialysis is suitable for prevention of
nephrogenic systemic fibrosis (NSF) dialysable.
Pharmacotherapeutic group: paramagnetic
contrast media, ATC code V08CA08
…
MultiHance has been shown to be
dialysable.
In CNS imaging MRI of the brain and spine,
Multihance enhances normal tissues lacking a
blood-brain barrier, extra axial tumors and
regions in which the blood-brain-barrier has
broken down. In the pivotal phase III clinical
trials in this indication, off-site readers reported
an improvement in level of diagnostic
information in 32-69% of images with
Multihance, and 35-69% of images with the
active comparator.
3 years
From a microbiological point of view, the
product should be used immediately after
drawing into the syringe.
5 mL, 10 mL, 15 mL and 20 mL of a clear
aqueous solution filled into colourless type I
glass vials with elastomeric closures, aluminium
sealing crimps and polypropylene caps.
Not all pack sizes may be marketed.
MultiHance should be drawn up into the syringe
immediately before use and should not be
diluted.
Before use, examine the product to assure that
the container and closure have not been
damaged, the solution is not discoloured and no
particulate matter is present.
In CNS imaging, Multihance enhances
normal tissues lacking a blood-brain
barrier, extra axial tumors and regions in
which the blood-brain-barrier has broken
down. In the pivotal phase III clinical trials
in this indication, off-site readers reported
an improvement in level of diagnostic
information in 32-69% of images with
Multihance, and 35-69% of images with
the active comparator.
3 years
When MultiHance is used in conjunction with
an injector system, the connecting tubes to the
patient and the relevant disposable parts should
be disposed after each patient examination. Any
additional instructions from the respective
equipment manufacturer must also be adhered
to.
The peel-off tracking label on the vials should
be stuck onto the patient records to enable
accurate recording of the gadolinium contrast
agent used. The dose used should also be
…
Pharmacotherapeutic group:ATC code
V08CA08
…
5 mL, 10 mL, 15 mL and 20 mL of a clear
aqueous solution filled into colourless type
I glass vials with elastomeric closures,
aluminium sealing crimps and
polypropylene caps.
MultiHance should be drawn up into the
syringe immediately before use and should
not be diluted.
Before use, examine the product to assure
that the container and closure have not
been damaged, the solution is not
discoloured and no particulate matter is
present.
Any unused product should be discarded.
Not all pack sizes may be marketed.
Overdose
Pharmacodynamic
properties
Shelf life
Nature and
contents of
container
Interaction for
use/handling
Special
precautions for
disposal and other
handling
recorded.
For single use only. Any unused product should
be discarded.
Not all pack sizes may be marketed.