Version 07/2022
SUMMARY OF PRODUCT CHARACTERISTICS,
LABELLING AND PACKAGE LEAFLET
for
Gadovist 1.0 mmol/ml solution for injection
1
SUMMARY OF PRODUCT CHARACTERISTICS,
LABELLING AND PACKAGE LEAFLET
2
SUMMARY OF PRODUCT CHARACTERISTICS
3
1.
NAME OF THE MEDICINAL PRODUCT
Gadovist 1.0 mmol/ml solution for injection
2.
QUALITATIVE AND QUANTITATIVE COMPOSITION
1 ml of solution for injection contains 604.72 mg gadobutrol (equivalent to 1.0 mmol gadobutrol containing
157.25 mg gadolinium).
1 vial with 2 ml contains 1209.44 mg gadobutrol,
1 vial with 7.5 ml contains 4535.4 mg gadobutrol,
1 vial with 15 ml contains 9070.8 mg gadobutrol,
1 vial with 30 ml contains 18141.6 mg gadobutrol.
1 bottle with 65 ml contains 39306.8 mg gadobutrol.
Excipient with known effect: 1 ml contains 0.00056 mmol (equivalent to 0.013 mg) of sodium (see
section 4.4).
For the full list of excipients, see section 6.1.
3.
PHARMACEUTICAL FORM
Solution for injection
Clear, colourless to pale yellow liquid.
Physico-chemical properties:
Osmolality at 37 °C: 1603 mOsm/kg H2O
Viscosity at 37 °C: 4.96 mPa·s
4.
CLINICAL PARTICULARS
4.1
Therapeutic indications
This medicinal product is for diagnostic use only. Gadovist is indicated in adults and children of all ages
(including term neonates) for:
Contrast enhancement in cranial and spinal magnetic resonance imaging (MRI).
Contrast enhanced MRI of liver or kidneys in patients with high suspicion or evidence of having focal
lesions to classify these lesions as benign or malignant.
Contrast enhancement in magnetic resonance angiography (CE-MRA).
Gadovist can also be used for MR Imaging of pathologies of the whole body.
It facilitates visualisation of abnormal structures or lesions and helps in the differentiation between healthy
and pathological tissue.
Gadovist should be used only when diagnostic information is essential and not available with unenhanced
magnetic resonance imaging (MRI).
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4.2
Posology and method of administration
Gadovist should only be administered by healthcare professionals experienced in the field of clinical
MRI practice.
Method of administration
This medicinal product is for intravenous administration only.
The dose required is administered intravenously as a bolus injection. Contrast-enhanced MRI can commence
immediately afterwards (shortly after the injection depending on the pulse sequences used and the protocol
for the examination).
Optimal signal enhancement is observed during arterial first pass for CE-MRA and within a period of about
15 minutes after injection of Gadovist for CNS indications (time depending on type of lesion/tissue).
T1 -weighted scanning sequences are particularly suitable for contrast-enhanced examinations.
Intravascular administration of contrast media should, if possible, be done with the patient lying down. After
the administration, the patient should be kept under observation for at least half an hour, since experience shows
that the majority of undesirable effects occur within this time (see section 4.4).
Instructions for use:
This product is intended for single use only.
This medicinal product should be visually inspected before use.
Gadovist should not be used in case of severe discolouration, the occurrence of particulate matter or a defective
container. Contrast medium not used in one examination must be discarded.
Gadovist should not be drawn up into the syringe from the vial until immediately before use.
The rubber stopper should never be pierced more than once.
If this medicinal product is intended to be used with an automatic application system, its suitability for the
intended use has to be demonstrated by the manufacturer of the medicinal device.
Any additional instructions from the respective equipment manufacturer must also be strictly adhered to.
Posology
The lowest dose that provides sufficient enhancement for diagnostic purposes should be used. The dose
should be calculated based on the patient’s body weight, and should not exceed the recommended dose per
kilogram of body weight detailed in this section.
Adults
CNS indications
The recommended dose for adults is 0.1 mmol per kilogram body weight (mmol/kg BW). This is equivalent
to 0.1 ml/kg BW of the 1.0 M solution.
If a strong clinical suspicion of a lesion persists despite an unremarkable MRI or when more accurate
information might influence therapy of the patient, a further injection of up to 0.2 ml/kg BW within
30 minutes of the first injection may be performed.
A dose of 0.075 mmol gadobutrol per kg body weight (equivalent to 0.075 ml Gadovist per kg body weight)
may be administered at minimum for imaging of the CNS (see section 5.1).
Whole Body MRI (except MRA)
In general, the administration of 0.1 ml Gadovist per kg body weight is sufficient to answer the clinical
question.
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CE-MRA
Imaging of 1 field of view (FOV): 7.5 ml for body weight below 75 kg; 10 ml for body weight of 75 kg and
higher (corresponding to 0.1-0.15 mmol/kg BW).
Imaging of >1 field of view (FOV): 15 ml for body weight below 75 kg; 20 ml for body weight of 75 kg and
higher (corresponding to 0.2-0.3 mmol/kg BW).
Special Populations
Renal impairment
Gadovist should only be used in patients with severe renal impairment (GFR < 30 ml/min/1.73 m2) and in
patients in the perioperative liver transplantation period after careful risk/benefit assessment and if the
diagnostic information is essential and not available with non-contrast enhanced MRI (see section 4.4). If it
is necessary to use Gadovist, the dose should not exceed 0.1 mmol/kg body weight. More than one dose
should not be used during a scan. Because of the lack of information on repeated administration, Gadovist
injections should not be repeated unless the interval between injections is at least 7 days.
Paediatric population
For children of all ages (including term neonates) the recommended dose is 0.1 mmol gadobutrol per kg
body weight (equivalent to 0.1 ml Gadovist per kg body weight) for all indications (see section 4.1).
Neonates up to 4 weeks of age and infants up to 1 year of age
Due to immature renal function in neonates up to 4 weeks of age and infants up to 1 year of age, Gadovist
should only be used in these patients after careful consideration at a dose not exceeding 0.1 mmol/kg body
weight. More than one dose should not be used during a scan. Because of the lack of information on
repeated administration, Gadovist 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).
4.3
Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
4.4
Special warnings and precautions for use
While injecting Gadovist into veins with a small lumen there is the possibility of adverse effects such as
reddening and swelling.
The usual safety requirements for magnetic resonance imaging, especially the exclusion of ferromagnetic
materials, also apply when using Gadovist.
Hypersensitivity reactions
As with other intravenous contrast agents, Gadovist can be associated with anaphylactoid/hypersensitivity or
other idiosyncratic reactions, characterized by cardiovascular, respiratory or cutaneous manifestations, and
ranging to severe reactions including shock. In general, patients with cardiovascular disease are more
susceptible to serious or even fatal outcomes of severe hypersensitivity reactions.
The risk of hypersensitivity reactions may be higher in case of:
previous reaction to contrast media
history of bronchial asthma
history of allergic disorders
In patients with an allergic disposition the decision to use Gadovist must be made after particularly careful
evaluation of the risk-benefit ratio.
6
Most of these reactions occur within half an hour of administration. Therefore, post-procedure
observation of the patient is recommended.
Medication for the treatment of hypersensitivity reactions as well as preparedness for institution of
emergency measures are necessary (see section 4.2).
Delayed reactions (after hours up to several days) have been rarely observed (see section 4.8).
Impaired renal function
Prior to administration of Gadovist, 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 gadoliniumcontaining contrast agents in patients with acute or chronic severe renal impairment
(GFR < 30 ml/min/1.73 m2). 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 Gadovist, it should therefore only be used in patients with
severe renal impairment and in patients in the perioperative liver transplantation period after careful
risk/benefit assessment and if the diagnostic information is essential and not available with non-contrast
enhanced magnetic resonance imaging (MRI).
Haemodialysis shortly after Gadovist administration may be useful at removing Gadovist from the body.
There is no evidence to support the initiation of haemodialysis for prevention or treatment of NSF in patients
not already undergoing haemodialysis.
Neonates and infants
Due to immature renal function in neonates up to 4 weeks of age and infants up to 1 year of age, Gadovist
should only be used in these patients after careful consideration.
Elderly
As the renal clearance of gadobutrol may be impaired in the elderly, it is particularly important to screen
patients aged 65 years and older for renal dysfunction.
Seizure disorders
Like with other gadolinium containing contrast agents special precaution is necessary in patients with a low
threshold for seizures.
Excipients
This medicinal product contains less than 1 mmol sodium (23 mg) per dose (based on the average amount
given to a 70 kg person), i.e. essentially ‘sodium-free’.
4.5
Interaction with other medicinal products and other forms of interaction
No interaction studies have been performed.
4.6
Fertility, pregnancy and lactation
Pregnancy
There are no data from the use of gadobutrol in pregnant women. Animal studies have shown reproductive
toxicity at repeated high doses (see section 5.3).
Gadovist should not be used during pregnancy unless the clinical condition of the woman requires use of
gadobutrol.
Breast-feeding
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 in milk and poor
7
absorption from the gut. Continuing or discontinuing of breast feeding for a period of 24 hours after
administration of Gadovist, should be at the discretion of the doctor and lactating mother.
Fertility
Animal studies do not indicate impairment of fertility.
4.7
Effects on ability to drive and use machines
Not relevant.
4.8
Undesirable effects
The overall safety profile of Gadovist is based on data from more than 6,300 patients in clinical trials and
from post-marketing surveillance.
The most frequently observed adverse drug reactions ( 0.5 %) in patients receiving Gadovist are headache,
nausea and dizziness.
The most serious adverse drug reactions in patients receiving Gadovist are cardiac arrest and severe
anaphylactoid reactions (including respiratory arrest and anaphylactic shock).
Delayed anaphylactoid reactions (hours later up to several days) have been rarely observed (see section 4.4).
Most of the undesirable effects were of mild to moderate intensity.
The adverse drug reactions observed with Gadovist are represented in the table below. They are classified
according to System Organ Class (MedDRA). The most appropriate MedDRA term is used to describe a
certain reaction and its synonyms and related conditions.
Adverse drug reactions from clinical trials are classified according to their frequencies.
Frequency groupings are defined according to the following convention: common: 1/100 to < 1/10;
uncommon: 1/1,000 to < 1/100; rare: 1/10,000 to < 1/1,000. The adverse drug reactions identified only
during post-marketing surveillance, and for which a frequency could not be estimated, are listed under ‘not
known’.
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Table 1: Adverse drug reactions reported in clinical trials or during post-marketing surveillance in
patients treated with Gadovist
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Frequency
System Organ
Class
Common
Immune system
disorders
Nervous system
disorders
Headache
Uncommon
Hypersensitivity
/anaphylactoid
reaction*# (e.g.
anaphylactoid shock§*,
circulatory collapse§*,
respiratory arrest§*,
pulmonary oedema§*,
bronchospasm§,
cyanosis§,
oropharyngeal
swelling§*, laryngeal
oedema§,
hypotension*, blood
pressure increased§,
chest pain§, urticaria,
face oedema,
angioedema§,
conjunctivitis§, eyelid
oedema, flushing,
hyperhidrosis§, cough§,
sneezing§, burning
sensation§, pallor§)
Dizziness, Dysgeusia,
Paresthesia
General
disorders and
administration
site conditions
Cardiac
arrest*
Dyspnoea*
Respiratory,
thoracic and
mediastinal
disorders
Skin and
subcutaneous
tissue disorders
Not known
Loss of
consciousness*,
Convulsion,
Parosmia
Tachycardia,
Palpitations
Cardiac
disorders
Gastrointestinal
disorders
Rare
Nausea
Vomiting
Erythema,
Pruritus (including
generalized pruritus),
Rash (including
generalized, macular,
papular, pruritic rash)
Injection site reaction0,
Feeling hot
Dry mouth
Nephrogenic
Systemic
Fibrosis (NSF)
Malaise, Feeling
cold
* There have been reports of life-threatening and/or fatal outcomes from this ADR
#
None of the individual symptoms ADRs listed under hypersensitivity/anaphylactoid reactions identified in
clinical trials reached a frequency greater than rare (except for urticarial)
9
§
Hypersensitivity/anaphylactoid reactions identified only during post-marketing surveillance (frequency not
known)
0
Injection site reactions (various kinds) comprise the following terms: Injection site extravasation, injection
site burning, injection site coldness, injection site warmth, injection site erythema or rash, injection site
pain, injection site hematoma
Patients with an allergic disposition suffer more frequently than others from hypersensitivity reactions.
Isolated cases of nephrogenic systemic fibrosis (NSF) have been reported with Gadovist (see section 4.4).
Fluctuations of renal function parameters including increases of serum creatinine have been observed after
administration of Gadovist.
Paediatric population
Based on two single dose phase I/III studies in 138 subjects aged 2-17 years and 44 subjects aged 0-<2 years
(see section 5.1) the frequency, type and severity of adverse reactions in children of all ages (including term
neonates) are consistent with the adverse drug reaction profile known in adults. This has been confirmed in a
phase IV study including more than 1,100 paediatric patients and postmarketing surveillance.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows
continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked
to report any suspected adverse reactions via the national reporting system listed in Appendix V.
4.9
Overdose
The maximum daily single dose tested in humans is 1.5 mmol gadobutrol/kg body weight.
No signs of intoxication from an overdose have so far been reported during clinical use.
In case of inadvertent overdosage, cardiovascular monitoring (including ECG) and control of renal function
is recommended as a measure of precaution.
In case of overdose in patients with renal insufficiency, Gadovist can be removed by haemodialysis. After
3 haemodialysis sessions approx. 98 % of the agent are removed from the body. However, there is no
evidence that haemodialysis is suitable for prevention of nephrogenic systemic fibrosis (NSF).
5.
PHARMACOLOGICAL PROPERTIES
5.1
Pharmacodynamic properties
Pharmacotherapeutic group: Paramagnetic contrast media, ATC code: V08C A09
Mechanism of action
The contrast-enhancing effect is mediated by gadobutrol, the nonionic complex consisting of gadolinium(III)
and the macrocyclic ligand dihydroxy-hydroxymethylpropyl-tetraazacyclododecane-triacetic acid (butrol).
Pharmacodynamic effects
The relaxivity of gadobutrol, measured in vitro in human blood/plasma at physiological conditions and at
clinical relevant field strengths (1.5 and 3.0 T), is in the range of 3.47 – 4.97 L/mmol/sec.
In clinical doses, the pronounced relaxivity of gadobutrol leads to a shortening of the relaxation times of
protons in tissue water.
10
The stability of the gadobutrol complex has been studied in vitro at physiological conditions (in native human
serum, at pH 7.4 and 37°C) over the time period of 15 days. The amounts of released gadolinium ions from
gadobutrol were below the limit of quantification of 0.1mol% of total gadolinium demonstrating the high
complex stability of gadobutrol under the tested conditions.
Clinical efficacy
In a pivotal phase III liver study average sensitivity in combined pre and postcontrast MRI for Gadovisttreated patients was 79 % and specificity was 81 % for lesion detection and classification of suspected
malignant liver lesions (patientbased analysis).
In a pivotal phase III kidney study average sensitivity was 91 % (patient-based analysis) and 85 % (lesionbased analysis) for classification of malignant and benign renal lesions. Average specificity in a patientbased analysis was 52 % and in a lesion-based analysis 82 %.
The increase of sensitivity from precontrast to combined pre and postcontrast MRI for Gadovist-treated
patients was 33 % in the liver study (patient-based analysis) and 18 % in the kidney study (patient-based
analysis as well as lesion-based analysis). The increase in specificity from precontrast to combined pre and
postcontrast MRI was 9 % in the liver study (patient based analysis) while there was no increase in
specificity in the kidney study (patient-based analysis as well as lesion-based analysis).
All results are average results obtained in blinded reader studies.
In a study designed as an intra-individual, crossover comparison, Gadovist was compared to gadoterate
meglumine (both at 0.1 mmol/kg) in the visualization of cerebral neoplastic enhancing lesions in
132 patients.
The primary efficacy endpoint was the overall preference for either Gadovist or gadoterate meglumine by the
median blinded reader. Superiority of Gadovist was demonstrated by a p-value of 0.0004. In detail, a
preference of Gadovist was given for 42 patients (32 %) compared to an overall preference for gadoterate
meglumine for 16 patients (12 %). For 74 patients (56 %) no preference for one or the other contrast agent
was given.
For the secondary variables lesion-to-brain ratio was found to be statistically significantly higher for
Gadovist (p < 0.0003). Percent of enhancement was higher with Gadovist compared to gadoterate
meglumine, with a statistical significant difference for the blinded reader (p < 0.0003).
Contrast-to-noise ratio, showed a higher mean value following Gadovist (129) compared to gadoterate
meglumine (98). The difference was not statistically significant.
In a study designed as an intra-individual, crossover comparison, gadobutrol at a reduced dose of 0.075
mmol/kg was compared to gadoterate meglumine at its standard dose of 0.1 mmol/kg for contrast enhanced
MRI of the CNS in 141 patients with enhancing CNS lesions on gadoterate meglumine enhanced MRI. The
primary variables included lesion contrast enhancement, lesion morphology, and lesion border delineation.
Images were analysed by three independent blinded readers. Noninferiority to gadoterate meglumine for the
degree of improvement over unenhanced imaging was demonstrated for all three primary variables (at least
80% of effect retained) based on the average reader. The mean number of lesions detected by gadobutrol
(2.14) and gadoterate (2.06) were similar.
Paediatric population
Two single dose phase I/III studies in 138 paediatric subjects scheduled for CE-MRI of CNS, liver and
kidneys or CE-MRA and in 44 subjects aged 0-<2 years (including term neonates) scheduled to undergo
routine CE-MRI of any body region have been performed. Diagnostic efficacy and an increase in diagnostic
confidence was demonstrated for all parameters evaluated in the studies and there was no difference among
the paediatric age groups and when compared to adults. Gadovist was well tolerated in these studies with the
same safety profile of gadobutrol as in adults.
Clinical Safety:
The type and frequency of adverse reactions following the administration of Gadovist in various indications
was evaluated in a large international prospective non-interventional trial (GARDIAN). The safety population
encompassed 23,708 patients of all age groups including children (n = 1,142; 4.8%) and elderly (n = 4,330;
18.3% between the ages of 65 and < 80 and n = 526; 2.2% of ≥ 80 years of age). Median age was 51.9 years.
11
Two hundred and two patients (0.9 %) reported overall 251 adverse events (AEs), and 170 (0.7%) reported 215
events categorized as adverse drug reactions (ADRs), majority (97.7%) of which were mild or moderate in
intensity.
Most commonly documented ADRs were nausea (0.3 %), vomiting (0.1 %) and dizziness (0.1 %). ADR rates
were 0.9 % in females and 0.6 % in males. There were no differences in ADR rates according to the dose of
gadobutrol. Four of the 170 patients with ADRs (0.02 %) experienced a serious adverse event, with one event
(Anaphylactic shock) leading to fatal outcome.
In the pediatric population AEs were reported in 8 of the 1,142 (0.7%) children. In six children these AEs were
classified as ADRs (0.5%).
Renal impairment:
In a prospective pharmacoepidemiologic study (GRIP) to assess the magnitude of potential risk for
development of NSF in renally impaired patients, 908 patients with varying degrees of renal impairment
received Gadovist at the standard approved dose for CE-MRI.
All patients, including 234 with severe renal impairment (eGFR <30 mL/min/1.73 m2) who had not received
other GBCAs were followed over the course of two years for signs and symptoms of NSF. No patient
enrolled in the study developed NSF.
5.2
Pharmacokinetic properties
Distribution
After intravenous administration, gadobutrol is rapidly distributed in the extra cellular space. Plasma protein
binding is negligible. The pharmacokinetics of gadobutrol in humans are dose proportional. After doses up to
0.4 mmol gadobutrol/kg body weight, the plasma level declines in a biphasic manner. At a dose of 0.1 mmol
gadobutrol/kg BW, an average of 0.59 mmol gadobutrol/l plasma was measured 2 minutes after the injection
and 0.3 mmol gadobutrol/l plasma 60 minutes post injection.
Biotransformation
No metabolites are detected in plasma or urine.
Elimination
Within two hours more than 50 % and within 12 hours more than 90 % of the given dose is eliminated via
urine with a mean terminal half-life of 1.8 hours (1.3 – 2.1 hours), corresponding to the renal elimination
rate. At a dose of 0.1 mmol gadobutrol/kg BW, an average of 100.3 ± 2.6 % of the dose was excreted within
72 h after administration. In healthy persons renal clearance of gadobutrol is 1.1 to 1.7 ml min-1 kg-1 and thus
comparable to the renal clearance of inulin, pointing to the fact that gadobutrol is eliminated primarily by
glomerular filtration. Less than 0.1 % of the dose is eliminated via faeces.
Characteristics in special patient populations
Paediatric population
Pharmacokinetics of gadobutrol in paediatric population aged <18 years and in adults are similar (see
section 4.2).
Two single dose phase I/III studies in paediatric patients <18 years have been performed. The
pharmacokinetics were evaluated in 130 paediatric patients aged 2-<18 years and in 43 paediatric patients
<2 years of age (including term neonates).
It was shown that the pharmacokinetic (PK) profile of gadobutrol in children of all ages is similar to that in
adults resulting in similar values for area under the curve (AUC), body weight normalized plasma clearance
(CLtot) and volume of distribution (Vss), as well as elimination half-life and excretion rate.
Approximately 99% (median value) of the dose was recovered in urine within 6 hours (this information was
derived from the 2 to <18 year old age group).
12
Elderly (aged 65 years and above)
Due to physiological changes in renal function with age, in elderly healthy volunteers (aged 65 years and
above) systemic exposure was increased by approximately 33 % (men) and 54 % (women) and terminal halflife by approximately 33 % (men) and 58 % (women). The plasma clearance is reduced by approximately
25 % (men) and 35 % (women), respectively. The recovery of the administered dose in urine was complete
after 24 h in all volunteers and there was no difference between elderly and non-elderly healthy volunteers.
Renal impairment
In patients with impaired renal function, the serum half-life of gadobutrol is prolonged due to the reduced
glomerular filtration. The mean terminal half-life was prolonged to 5.8 hours in moderately impaired patients
(80>CLCR>30 ml/min) and further prolonged to 17.6 hours in severely impaired patients not on dialysis
(CLCR30 ml/min). The mean serum clearance was reduced to 0.49 ml/min/kg in mild to moderately
impaired patients (80>CLCR>30 ml/min) and to 0.16 ml/min/kg in severely impaired patients not on dialysis
(CLCR30 ml/min). Complete recovery in the urine was seen in patients with mild or moderate renal
impairment within 72 hours. In patients with severely impaired renal function about 80 % of the
administered dose was recovered in the urine within 5 days (see also sections 4.2 and 4.4).
In patients requiring dialysis, gadobutrol was almost completely removed from serum after the third dialysis.
5.3
Preclinical safety data
Preclinical data reveal no special hazard for humans based on conventional studies of safety pharmacology,
repeated dose toxicity and genotoxicity.
Repeated intravenous treatment in reproductive toxicology studies caused a retardation of embryonal
development in rats and rabbits and an increase in embryolethality in rats, rabbits and monkeys at dose levels
being 8 to 16 times (based on body surface area) or 25 to 50 times (based on body weight) above the
diagnostic dose in humans. It is not known whether these effects can also be induced by a single
administration. Single and repeat-dose toxicity studies in neonatal and juvenile rats did not reveal findings
suggestive of a specific risk for use in children of all ages including term neonates and infants.
Radioactively labelled gadobutrol administered intravenously to lactating rats was transferred to the neonates
via milk at less than 0.1 % of the administered dose.
In rats, absorption after oral administration was found to be very small and amounted to about 5 % based on
the fraction of the dose excreted in urine.
In preclinical cardiovascular safety pharmacology studies, depending on the dose administered, transient
increases in blood pressure and myocardial contractility were observed. These effects have not been
observed in humans.
Environmental studies have shown that persistence and mobility of GBCAs indicate a potential for
distribution in the water column and possibly into groundwater.
6.
PHARMACEUTICAL PARTICULARS
6.1
List of excipients
Calcobutrol sodium
Trometamol
Hydrochloric acid 1N (pH-adjustment)
Water for injections
13
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
Shelf life after first opening of the container:
Any solution for injection not used in one examination must be discarded. Chemical, physical and
microbiological in-use stability has been demonstrated for 24 hours at 20-25°C. From a microbiological point
of view, the product should be used immediately. If not used immediately, in-use storage times and conditions
prior to use are the responsibility of the user.
6.4
Special precautions for storage
This medicinal product does not require any special storage conditions.
For storage conditions after first opening of the medicinal product, see section 6.3.
6.5
Nature and contents of container
1 vial (type I glass) with a stopper (chlorobutyl elastomer) and a pure aluminium with internal and external
lacquer flanged cap containing 2 ml, 7.5 ml, 15 ml or 30 ml solution for injection.
1 bottle (type II glass) with a stopper (chlorobutyl elastomer) and a pure aluminium with internal and
external lacquer flanged cap containing 65 ml solution for injection.
Pack sizes of:
1 and 3 vials with 2 ml solution for injection
1 and 10 vials with 7.5, 15 or 30 ml solution for injection
1 and 10 bottles with 65 ml solution for injection
Hospital pack:
3 vials with 2 ml solution for injection
10 vials with 7.5, 15 or 30 ml solution for injection
10 bottles with 65 ml solution for injection
Not all pack sizes may be marketed.
6.6
Special precautions for disposal and other handling
Contrast medium not used in one examination must be discarded.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
The peel-off tracking label on the vials/bottles should be stuck onto the patient record to enable accurate
recording of the gadolinium contrast agent used. The dose used should also be recorded. If electronic patient
records are used, the name of the product, the batch number and the dose should be entered into the patient
record.
7.
MARKETING AUTHORISATION HOLDER
[To be completed nationally]
14
8.
MARKETING AUTHORISATION NUMBER(S)
[To be completed nationally]
9.
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
Date of first authorisation: [To be completed nationally]
Date of last renewal: 24 January 2010
10.
DATE OF REVISION OF THE TEXT
{MM/YYYY}
[To be completed nationally]
15
LABELLING
16
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
Carton / Outer package of 2 ml, 7.5 ml, 15 ml, 30 ml vial and 65 ml bottle
1.
NAME OF THE MEDICINAL PRODUCT
Gadovist 1.0 mmol/ml solution for injection
Gadobutrol
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
1 ml contains 604.72 mg gadobutrol (equivalent to 1.0 mmol gadobutrol containing 157.25 mg gadolinium).
1 vial with 2 ml contains 1209.44 mg gadobutrol
1 vial with 7.5 ml contains 4535.4 mg gadobutrol
1 vial with 15 ml contains 9070.8 mg gadobutrol
1 vial with 30 ml contains 18141.6 mg gadobutrol
1 bottle with 65 ml contains 39306.8 mg gadobutrol
3.
LIST OF EXCIPIENTS
Excipients: Calcobutrol sodium, Trometamol, Hydrochloric acid 1N, Water for injections
See leaflet for further information.
4.
PHARMACEUTICAL FORM AND CONTENTS
Solution for injection
1 vial with 2 ml
1 vial with 7.5 ml
1 vial with 15 ml
1 vial with 30 ml
1 bottle with 65 ml
3 vials with 2 ml
10 vials with 7.5 ml
10 vials with 15 ml
10 vials with 30 ml
10 bottles with 65 ml
[for hospital packs (3/10 vials/bottles with 2 ml, 7.5 ml, 15 ml, 30 ml, 65 ml):] hospital pack
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Intravenous use
For single use only.
Read the package leaflet before use.
17
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF
THE SIGHT AND REACH OF CHILDREN
Keep out of the sight and reach of children.
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
8.
EXPIRY DATE
EXP {MM/YYYY}
Chemical, physical and microbiological in-use stability has been demonstrated for 24 hours at 20-25°C.
From a microbiological point of view, the product should be used immediately after opening.
9.
SPECIAL STORAGE CONDITIONS
10.
SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR
WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
Discard any unused medium after each investigation.
11.
NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER
[To be completed nationally]
12.
MARKETING AUTHORISATION NUMBER(S)
[To be completed nationally]
13.
BATCH NUMBER
Lot
14.
GENERAL CLASSIFICATION FOR SUPPLY
[To be completed nationally]
15.
INSTRUCTIONS ON USE
The peel-off label on the vial/vials/bottle/bottles should be stuck onto the patient record and the dose recorded,
or product name, batch number and dose entered in the electronic patient record.
18
16.
INFORMATION IN BRAILLE
<Justification for not including Braille accepted.>
17.
UNIQUE IDENTIFIER – 2D BARCODE
<Not applicable.>
18.
UNIQUE IDENTIFIER – HUMAN READABLE DATA
<Not applicable.>
19
PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING
Label of 30 ml vial and 65 ml bottle
1.
NAME OF THE MEDICINAL PRODUCT
Gadovist 1.0 mmol/ml solution for injection
Gadobutrol
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
1 ml contains 604.72 mg gadobutrol (equivalent to 1.0 mmol gadobutrol containing 157.25 mg gadolinium).
1 vial with 30 ml contains 18141.6 mg gadobutrol
1 bottle with 65 ml contains 39306.8 mg gadobutrol
3.
LIST OF EXCIPIENTS
Excipients: Calcobutrol sodium, Trometamol, Hydrochloric acid 1N, Water for injections
See leaflet for further information.
4.
PHARMACEUTICAL FORM AND CONTENTS
Solution for injection
1 vial with 30 ml
1 bottle with 65 ml
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Intravenous use
For single use only.
Read the package leaflet before use.
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF
THE SIGHT AND REACH OF CHILDREN
Keep out of the sight and reach of children.
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
20
8.
EXPIRY DATE
EXP {MM/YYYY}
Chemical, physical and microbiological in-use stability has been demonstrated for 24 hours at 20-25°C.
From a microbiological point of view, the product should be used immediately after opening.
9.
SPECIAL STORAGE CONDITIONS
10.
SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR
WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
Discard any unused medium after each investigation.
11.
NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER
[To be completed nationally]
12.
MARKETING AUTHORISATION NUMBER(S)
[To be completed nationally]
13.
BATCH NUMBER
Lot
14.
GENERAL CLASSIFICATION FOR SUPPLY
[To be completed nationally]
15.
INSTRUCTIONS ON USE
<Sticky label detailing name of the product, volume presentation and batch number.>
[65 ml bottle:] Product name, batch number and dose should be recorded in the patient record.
16.
INFORMATION IN BRAILLE
<Justification for not including Braille accepted.>
21
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
Label of 2 ml, 7.5 ml and 15 ml Vial
1.
NAME OF THE MEDICINAL PRODUCT AND ROUTE OF ADMINISTRATION
Gadovist 1.0 mmol/ml solution for injection
Gadobutrol
Intravenous use
2.
METHOD OF ADMINISTRATION
Single use
Read the package leaflet before use.
3.
EXPIRY DATE
EXP {MM/YYYY}
Read the package leaflet for information on use after opening.
4.
BATCH NUMBER
Lot
5.
CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT
2 ml
7.5 ml
15 ml
6.
OTHER
<Sticky label detailing name of the product, volume presentation and batch number.>
22
PACKAGE LEAFLET
for
Gadovist 1.0 mmol/ml solution for injection
23
Package leaflet: Information for the patient
Gadovist 1.0 mmol/ml solution for injection
Gadobutrol
Read all of this leaflet carefully before you are given this medicine because it contains important
information for you.
Keep this leaflet. You may need to read it again.
If you have any further questions, please ask your doctor or the person giving you Gadovist (the
radiologist) or the hospital/MRI-centre personnel.
If you get any side effects talk to your doctor or radiologist. This includes any possible side effects not
listed in this leaflet. See section 4.
What is in this leaflet
1.
What Gadovist is and what it is used for
2.
What you need to know before you are given Gadovist
3.
How Gadovist will be given
4.
Possible side effects
5.
How to store Gadovist
6.
Contents of the pack and other information
1.
What Gadovist is and what it is used for
Gadovist is a contrast medium for magnetic resonance imaging (MRI) used for diagnostics of the brain,
spine and vessels. Gadovist can also help the doctor find out the kind (benign or malignant) of known or
suspected abnormalities in the liver and kidneys.
Gadovist can also be used for MRI of abnormalities of other body regions.
It facilitates visualisation of abnormal structures or lesions and helps in the differentiation between healthy
and diseased tissue.
It is for use in adults and children of all ages (including term newborn infants).
How Gadovist works
MRI is a form of medical diagnostic imaging that uses the behaviour of water molecules in normal and
abnormal tissues. This is done by a complex system of magnets and radio waves. Computers record the
activity and translate that into images.
Gadovist is given as an injection into your vein. This medicine is for diagnostic use only and will only be
administered by healthcare professionals experienced in the field of clinical MRI practice.
2.
What you need to know before you are given Gadovist
Do NOT use Gadovist if you
are allergic to gadobutrol or any of the other ingredients of this medicine (listed in section 6).
Warnings and precautions
Talk to your doctor before you are given Gadovist if you
suffer or have suffered from an allergy (e.g. hay fever, hives) or asthma
had a previous reaction to any contrast media
have very poor kidney function
suffer from brain conditions with seizures (fits) or from other diseases of the nervous system
have a heart pacemaker or if there are any implants or clips containing iron in your body.
24
Your doctor will decide whether the intended examination is possible or not.
Allergy-like reactions leading to heart problems, breathing difficulties or skin reactions may occur
after use of Gadovist. Severe reactions are possible. Most of these reactions occur within half an hour
after you are given Gadovist. Therefore, you will be observed after the examination. Delayed reactions
have been observed (after hours or days) (see section 4).
Kidneys/Liver
Tell your doctor if
your kidneys do not work properly
you have recently had, or soon expect to have, a liver transplant.
Your doctor may decide to take a blood test to check how well your kidneys are working before making the
decision to use Gadovist, especially if you are 65 years of age or older.
Neonates and infants
As kidney function is immature in babies up to 4 weeks of age and infants up to 1 year of age, Gadovist will
only be used in these patients after careful consideration by the doctor.
Other medicines and Gadovist
Tell your doctor if you are taking or have recently taken or might take any other medicines.
Pregnancy and breast-feeding
Ask your doctor for advice before taking any medicine.
Pregnancy
You must tell your doctor if you think you are, or might become, pregnant as Gadovist should not be used
during pregnancy unless strictly necessary.
Breast-feeding
Tell your doctor if you are breast-feeding or about to start breast-feeding. Your doctor will discuss whether
you should continue or interrupt breast-feeding for a period of 24 hours after you receive Gadovist.
Gadovist contains sodium
This medicinal product contains less than 23 mg sodium per dose (based on the average amount given to a
70 kg person), i.e. essentially ‘sodium-free’.
3.
How Gadovist will be given
Gadovist is injected into your vein using a small needle by a healthcare professional. Your MRI examination
can start immediately.
After the injection you will be observed for at least 30 minutes.
The usual dose
The actual dose that is right for you will depend on your body weight and on the region being examined by
MRI:
In adults a single injection of 0.1 millilitre Gadovist per kg body weight is recommended (this means for a
person weighing 70 kg the dose would be 7 millilitre), however a further injection of up to 0.2 millilitre per
kg body weight within 30 minutes of the first injection may be given. A total amount of 0.3 millilitre
Gadovist per kg body weight may be given at maximum (this means for a person weighing 70 kg the dose
would be 21 millilitre) for imaging of the central nervous system (CNS) and CE-MRA. A dose of 0.075
millilitre Gadovist per kg body weight may be given at minimum (this means for a person weighing 70 kg
the dose would be 5.25 millilitre) for the CNS.
25
Further information regarding the administration and handling of Gadovist is given at the end of the leaflet.
Dosage in special patient groups
The use of Gadovist is not recommended in patients with severe kidney problems and patients who have
recently had, or soon expect to have, a liver transplant. However if use is required you should only receive
one dose of Gadovist during a scan and you should not receive a second injection for at least 7 days.
Neonates, infants, children and adolescents
In children of all ages (including term newborn infants) a single dose of 0.1 millilitre Gadovist per kg body
weight is recommended for all examinations (see section 1).
As kidney function is immature in babies up to 4 weeks of age and infants up to 1 year of age, Gadovist will
only be used in these patients after careful consideration by the doctor. Neonates and infants should only
receive one dose of Gadovist during a scan and should not receive a second injection for at least 7 days.
Elderly
It is not necessary to adjust your dose if you are 65 years of age or older but you may have a blood test to
check how well your kidneys are working.
If you receive more Gadovist than you should
Overdosing is unlikely. If it does happen, the doctor will treat any symptoms and may use kidney dialysis to
remove Gadovist from your body.
There is no evidence to suggest that this will prevent the development of Nephrogenic Systemic Fibrosis
(NSF; see section 4) and it should not be used as treatment for the condition. In some cases your heart will be
checked.
If you have any further questions on the use of this medicine, ask your doctor or radiologist.
4.
Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody gets them.
The most serious side effects (which have been fatal or life-threatening in some cases) are:
heart stops beating (cardiac arrest) and severe allergy-like (anaphylactoid) reactions (including stop
of breathing and shock).
In addition for the following side effects life-threatening or fatal outcomes have been observed in some
cases:
shortness of breath (dyspnoea), loss of consciousness, severe allergy-like reaction, severe decrease of
blood pressure may lead to collapse, stop of breathing, fluid in the lungs, swelling of mouth and throat
and low blood pressure.
In rare cases:
allergy-like reactions (hypersensitivity and anaphylaxis) may occur, including severe reactions
(shock) that may need immediate medical intervention.
If you notice:
swelling of the face, lips, tongue or throat
coughing and sneezing
difficulty breathing
itching
runny nose
hives (nettle-type rash)
tell the MRI department staff immediately. These may be the first signs that a severe reaction is
happening. Your investigation may need to be stopped and you may need further treatment.
26
Delayed allergy-like reactions, hours to several days after you have received Gadovist, have been observed
in rare cases. If this should happen to you, tell your doctor or radiologist immediately.
The most frequently observed side effects (may affect 5 or more in 1,000 people) are:
headache, feeling sick (nausea) and dizziness.
Most of the side effects are mild to moderate.
Possible side effects which have been observed in clinical trials before the approval of Gadovist are listed
below by how likely they are.
Common (may affect up to 1 in 10 people)
headache
feeling sick (nausea)
Uncommon (may affect up to 1 in 100 people)
allergy-like reaction, e.g.
- low blood pressure
- hives
- swelling of the face
- swelling (oedema) of the eyelid
- flushing
The frequency of the following allergy-like reactions is not known:
- severe allergy-like reaction (anaphylactoid shock)
- severe decrease of blood pressure may lead to collapse (shock)
- breathing stops
- fluid in the lungs
- breathing difficulties (bronchospasm)
- blueness of the lips
- swelling of the mouth and throat
- swelling of the throat
- increased blood pressure
- chest pain
- swelling of the face, throat, mouth, lips and/or tongue (angioedema)
- conjunctivitis
- increased sweating
- cough
- sneezing
- burning sensation
- pale skin (pallor)
dizziness, disturbed sense of taste, numbness and tingling
shortness of breath (dyspnoea)
vomiting
redness of the skin (erythema)
itching (pruritus including generalized pruritus)
rash (including generalized rash, small flat red spots [macular rash], small, raised, circumscribed
lesions [papular rash] and itchy rash [pruritic rash])
various kinds of injection site reactions (e.g. leakage into the surrounding tissue, burning, coldness,
warmth, reddening, rash, pain or bruising)
feeling hot
Rare (may affect up to 1 in 1,000 people)
fainting
convulsion
disturbed sense of smell
rapid heart beat
27
palpitations
dry mouth
generally feeling unwell (malaise)
feeling cold
Additional side effects which have been reported after the approval of Gadovist with unknown
frequency (frequency cannot be estimated from the available data):
Heart stops beating (cardiac arrest)
There have been reports of nephrogenic systemic fibrosis - NSF (which causes hardening of the skin
and may affect also soft tissue and internal organs).
Variations in blood tests of the kidney function (e.g. increase of serum creatinine) have been observed after
administration of Gadovist.
Reporting of side effects
If you get any side effects talk to your doctor or radiologist. This includes any side effects not listed in this
leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By
reporting side effects you can help provide more information on the safety of this medicine.
5.
How to store Gadovist
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the label and the carton after EXP. The
expiry date refers to the last day of that month. This medicinal product does not require any special storage
conditions.
Chemical, physical and microbiological in-use stability has been demonstrated for 24 hours at 20-25°C.
From a microbiological point of view, the product should be used immediately after opening.
This medicinal product is a clear, colorless to pale yellow solution. Do not use this medicine if you notice
severe discoloration or the presence of particulate matter or if the container appears defective.
Medicines should not be disposed of via wastewater or household waste. The healthcare professional will
dispose of this medicine when no longer required. These measures will help to protect the environment.
6.
Contents of the pack and other information
What Gadovist contains
The active substance is gadobutrol.
1 ml of solution for injection contains 604.72 mg gadobutrol (equivalent to 1.0 mmol gadobutrol containing
157.25 mg gadolinium).
1 vial with 2 ml contains 1209.44 mg gadobutrol,
1 vial with 7.5 ml contains 4535.4 mg gadobutrol,
1 vial with 15 ml contains 9070.8 mg gadobutrol,
1 vial with 30 ml contains 18141.6 mg gadobutrol.
1 bottle with 65 ml contains 39306.8 mg gadobutrol.
The other ingredients are calcobutrol sodium (see end of section 2), trometamol, hydrochloric acid 1N and
water for injections.
28
What Gadovist looks like and contents of the pack
Gadovist is a clear, colourless to pale yellow solution for injection.
The contents of the packs are:
1 or 3 vials with 2 ml solution for injection
1 or 10 vials with 7.5, 15 or 30 ml solution for injection
1 or 10 bottles with 65 ml solution for injection (in 100-ml bottle)
Hospital pack:
3 vials with 2 ml solution for injection
10 vials with 7.5, 15 or 30 ml solution for injection
10 bottles with 65 ml solution for injection
Not all pack sizes may be marketed.
Marketing Authorisation Holder
[To be completed nationally]
Manufacturer
[To be completed nationally]
This medicine is authorised in the Member States of the E uropean Economic Area under the
following names:
Austria, Germany
Gadovist 1,0 mmol/ml Injektionslösung
Belgium, Bulgaria, Cyprus, Denmark, Estonia,
Finland, Greece, Italy, Luxembourg, Norway,
Portugal, Sweden
Croatia
Gadovist
France
GADOVIST 1,0 mmol/mL, solution injectable
Ireland
Gadovist 1.0 mmol/ml solution for injection
Netherlands
Gadovist 1,0 mmol/ml, oplossing voor injectie
Slovenia
Gadovist 1,0 mmol/ml raztopina za injiciranje
Slovakia
Gadovist 1,0 mmol/ ml injekčný roztok
Spain
Gadovist 1 mmol/ml solución inyectable en vial
Malta
Gadovist 1.0 mmol/ml solution for injection
Gadovist 1,0 mmol/ml otopina za injekciju
This leaflet was last revised in {month YYYY}. [To be completed nationally]
----------------------------------------------------------------------------------------------------------------------------The following information is intended for healthcare professionals only:
Renal impairment
Prior to administration of Gadovist, 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 gadoliniumcontaining contrast agents in patients with acute or chronic severe renal impairment
(GFR < 30 ml/min/1.73 m2). 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
29
Gadovist, it should therefore only be used in patients with severe renal impairment and in patients in the
perioperative liver transplantation period after careful risk/benefit assessment and if the diagnostic
information is essential and not available with non-contrast enhanced MRI. If it is necessary to use Gadovist,
the dose should not exceed 0.1 mmol/kg body weight. More than one dose should not be used during a scan.
Because of the lack of information on repeated administration, Gadovist injections should not be repeated
unless the interval between injections is at least 7 days.
As the renal clearance of Gadovist may be impaired in the elderly, it is particularly important to screen
patients aged 65 years and older for renal dysfunction.
Haemodialysis shortly after Gadovist administration may be useful at removing Gadovist from the body.
There is no evidence to support the initiation of haemodialysis for prevention or treatment of NSF in patients
not already undergoing haemodialysis.
Pregnancy and breast-feeding
Gadovist should not be used during pregnancy unless the clinical condition of the woman requires use of
Gadovist.
Continuing or discontinuing of breast-feeding for a period of 24 hours after administration of Gadovist,
should be at the discretion of the doctor and lactating mother.
Hypersensitivity reactions
As with other intravenous contrast agents, Gadovist can be associated with anaphylactoid/hypersensitivity or
other idiosyncratic reactions, characterized by cardiovascular, respiratory or cutaneous manifestations, and
ranging to severe reactions including shock. In general, patients with cardiovascular disease are more
susceptible to serious or even fatal outcomes of severe hypersensitivity reactions.
The risk of hypersensitivity reactions may be higher in case of:
previous reaction to contrast media
history of bronchial asthma
history of allergic disorders
In patients with an allergic disposition the decision to use Gadovist must be made after particularly careful
evaluation of the risk-benefit ratio.
Most of these reactions occur within half an hour of administration. Therefore, post-procedure
observation of the patient is recommended.
Medication for the treatment of hypersensitivity reactions as well as preparedness for institution of
emergency measures are necessary.
Delayed reactions (after hours up to several days) have been rarely observed.
Seizure disorders
Like with other gadolinium containing contrast agents special precaution is necessary in patients with a low
threshold for seizures.
Overdose
In case of inadvertent overdosage, cardiovascular monitoring (including ECG) and control of renal function
are recommended as a measure of precaution.
In case of overdose in patients with renal insufficiency, Gadovist can be removed by haemodialysis. After
3 haemodialysis sessions approx. 98 % of the agent are removed from the body. However, there is no
evidence that haemodialysis is suitable for prevention of nephrogenic systemic fibrosis (NSF).
30
Before injection
This product is intended for single use only.
This medicinal product is a clear, colourless to pale yellow solution. It should be visually inspected before
use.
Gadovist should not be used in case of severe discoloration, the occurrence of particulate matter or a
defective container.
Instructions for use
Gadovist should not be drawn up into the syringe from the vial until immediately before use.
The rubber stopper should never be pierced more than once.
Contrast medium not used in one examination must be discarded
If this medicinal product is intended to be used with an automatic application system, its suitability for the
intended use has to be demonstrated by the manufacturer of the medicinal device. Any additional instructions
from the respective equipment manufacturer must also be strictly adhered to.
Any solution not used in one examination is to be discarded in accordance with local requirements.
Shelf life after first opening of the container
Any solution for injection not used in one examination must be discarded. Chemical, physical and
microbiological in-use stability has been demonstrated for 24 hours at 20-25°C. From a microbiological
point of view, the product should be used immediately. If not used immediately, in-use storage times and
conditions prior to use are the responsibility of the user.
The peel-off tracking label on the vials/bottles should be stuck onto the patient record to enable accurate
recording of the gadolinium contrast agent used. The dose used should also be recorded. If electronic patient
records are used, the name of the product, the batch number and the dose should be entered into the patient
record.
Posology
The lowest dose that provides sufficient enhancement for diagnostic purposes should be used. The dose
should be calculated based on the patient’s body weight, and should not exceed the recommended dose per
kilogram of body weight detailed in this section.
Adults
CNS indications
The recommended dose for adults is 0.1 mmol per kilogram body weight (mmol/kg BW). This is equivalent
to 0.1 ml/kg BW of the 1.0 M solution.
If a strong clinical suspicion of a lesion persists despite an unremarkable MRI or when more accurate
information might influence therapy of the patient, a further injection of up to 0.2 ml/kg BW within
30 minutes of the first injection may be performed. A dose of 0.075 mmol gadobutrol per kg body weight
(equivalent to 0.075 ml Gadovist per kg body weight) may be given at minimum for imaging of the CNS.
Whole Body MRI (except MRA)
In general, the administration of 0.1 ml Gadovist per kg body weight is sufficient to answer the clinical
question.
CE-MRA
Imaging of 1 field of view (FOV): 7.5 ml for body weight below 75 kg; 10 ml for body weight of 75 kg and
higher (corresponding to 0.1-0.15 mmol/kg BW).
Imaging of > 1 field of view (FOV): 15 ml for body weight below 75 kg; 20 ml for body weight of 75 kg and
higher (corresponding to 0.2-0.3 mmol/kg BW).
31
Paediatric population
For children of all ages (including term neonates) the recommended dose is 0.1 mmol gadobutrol per kg
body weight (equivalent to 0.1 ml Gadovist per kg body weight) for all indications (see section 1).
Due to immature renal function in neonates up to 4 weeks of age and infants up to 1 year of age, Gadovist
should only be used in these patients after careful consideration at a dose not exceeding 0.1 mmol/kg body
weight. More than one dose should not be used during a scan. Because of the lack of information on repeated
administration, Gadovist injections should not be repeated unless the interval between injections is at least 7
days.
Imaging
The dose required is administered intravenously as a bolus injection. Contrast-enhanced MRI can commence
immediately afterwards (shortly after the injection depending on the pulse sequences used and the protocol
for the examination).
Optimal signal enhancement is observed during arterial first pass for CE-MRA and within a period of about
15 minutes after injection of Gadovist for CNS indications (time depending on type of lesion/tissue).
T1 -weighted scanning sequences are particularly suitable for contrast-enhanced examinations.
Further information regarding the use of Gadovist is given in section 3 of the leaflet.
32