Gadovist 1.0 mmol/ml solution for injection in prefilled syringe
*Company:
Bayer LimitedStatus:
No Recent UpdateLegal Category:
Product subject to restricted prescription (C)Active Ingredient(s):
*Additional information is available within the SPC or upon request to the company
Updated on 04 October 2024
File name
23043_PL_CC+cross_PFS_glass_20240910.pdf
Reasons for updating
- Change to section 2 - what you need to know - warnings and precautions
- Change to section 2 - pregnancy, breast feeding and fertility
- Change to section 4 - possible side effects
Free text change information supplied by the pharmaceutical company
2. What you need to know before you are given Gadovist
[…]
• Allergy-like or other unpredictable 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).
[…]
4. Possible side effects
[…]
The most serious side effects (which have been fatal or life-threatening in some cases) are:
• Heart stops beating (cardiac arrest), a severe lung disease (acute respiratory distress syndrome) / fluid in the lungs (pulmonary oedema) and severe allergy-like (anaphylactoid) reactions (including stop of breathing and shock).
[…]
Delayed allergy-like or other unpredictable 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.
[…]
Common: (may affect up to 1 in 10 people)
[…]
Uncommon: (may affect up to 1 in 100 people)
[…]
The frequency of the following allergy-like reactions is not known:
[…]
- fluid in the lungs
[…]
Rare: (may affect up to 1 in 1,000 people)
[…]
Updated on 26 September 2024
File name
23043_PL_CC+cross_PFS_glass_20240910.pdf
Reasons for updating
- Change to section 2 - what you need to know - warnings and precautions
- Change to section 2 - pregnancy, breast feeding and fertility
- Change to section 4 - possible side effects
Free text change information supplied by the pharmaceutical company
2. What you need to know before you are given Gadovist
[…]
• Allergy-like or other unpredictable 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).
[…]
4. Possible side effects
[…]
The most serious side effects (which have been fatal or life-threatening in some cases) are:
• Heart stops beating (cardiac arrest), a severe lung disease (acute respiratory distress syndrome) / fluid in the lungs (pulmonary oedema) and severe allergy-like (anaphylactoid) reactions (including stop of breathing and shock).
[…]
Delayed allergy-like or other unpredictable 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.
[…]
Common: (may affect up to 1 in 10 people)
[…]
Uncommon: (may affect up to 1 in 100 people)
[…]
The frequency of the following allergy-like reactions is not known:
[…]
- fluid in the lungs
[…]
Rare: (may affect up to 1 in 1,000 people)
[…]
Updated on 26 September 2024
File name
23043_SmPC_CC_GADS_20240910.pdf
Reasons for updating
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.8 - Undesirable effects
- Change to section 10 - Date of revision of the text
Legal category:Product subject to restricted prescription (C)
Free text change information supplied by the pharmaceutical company
4.4 Special warnings and precautions for use
...
Hypersensitivity reactions or other idiosyncratic reactions
As with other intravenous contrast agents, Gadovist can be associated with anaphylactoid/hypersensitivity or other idiosyncratic reactions (e.g., acute respiratory distress syndrome / pulmonary oedema with and without the context of hypersensitivity 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.
...
Medication for the treatment of hypersensitivity or other idiosyncratic reactions as well as preparedness for institution of emergency measures are necessary (see section 4.2).
...
4.8 Undesirable effects
...
The most serious adverse drug reactions in patients receiving Gadovist are cardiac arrest, acute respiratory distress syndrome / pulmonary oedema and severe anaphylactoid reactions (including respiratory arrest and anaphylactic shock).
Delayed anaphylactoid or other idiosyncratic reactions (hours later up to several days) have been rarely observed (see section 4.4).
...
Table 1: Adverse drug reactions reported in clinical trials or during post-marketing surveillance in patients treated with Gadovist
Uncommon: (...) pulmonary oedema, (...)
Not known: (...) Acute Respiratory Distress Syndrome (ARDS)*1 Pulmonary oedema*1 (...)
(...)
¹ These ADRs have been reported with and without the context of hypersensitivity reactions
10. DATE OF REVISION OF THE TEXT
September 20242
Updated on 13 September 2024
File name
24018_SmPC_CC_GADS_20240704.pdf
Reasons for updating
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.6 - Pregnancy and lactation
- Change to section 10 - Date of revision of the text
Legal category:Product subject to restricted prescription (C)
Free text change information supplied by the pharmaceutical company
BP24018, REC32748
Note
Text in blue = added text
Text in red strikethrough = deleted text
4.4 Special warnings and precautions for use
Gadobutrol must not be used intrathecally. Serious, life-threatening and fatal cases, primarily with neurological reactions (e.g. coma, encephalopathy, seizures), have been reported with intrathecal use.
4.6 Fertility, pregnancy and lactation
Pregnancy
There are no dataData from the use of gadolinium-based contrast agents including gadobutrol in pregnant women is limited. Gadolinium can cross the placenta. It is unknown whether exposure to gadolinium is associated with adverse effects in the foetus. 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.
10. DATE OF REVISION OF THE TEXT
September2022September 2024
Updated on 13 September 2024
File name
24018_PL_CC+Cross_PFS_glass_20240704.pdf
Reasons for updating
- Change to section 2 - pregnancy, breast feeding and fertility
- Change to section 6 - manufacturer
- Change to section 6 - date of revision
Free text change information supplied by the pharmaceutical company
BP24018, REC32748
Note
Text in blue = added text
Text in red strikethrough = deleted text
2. What you need to know before you are given Gadovist
[...]
- Pregnancy
Gadobutrol can cross the placenta. It is not known whether it affects the baby. 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.
6. Contents of the pack and other information
[...]
This medicine is authorised in the Member States of the European Economic Area under the following names:
[...]
Iceland Gadovist 1,0 mmól/ml, stungulyf, lausn í áfylltum sprautum/rörlykjum
[...]
This leaflet was last revised in September 2022September 2024
Updated on 12 September 2024
File name
24018_SmPC_CC_GADS_20240704.pdf
Reasons for updating
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.6 - Pregnancy and lactation
- Change to section 10 - Date of revision of the text
Legal category:Product subject to restricted prescription (C)
Updated on 01 May 2024
File name
24018_PL_CC+Cross_PFS_glass_20240325.pdf
Reasons for updating
- Change to section 2 - pregnancy, breast feeding and fertility
- Change to section 6 - manufacturer
- Change to section 6 - date of revision
Free text change information supplied by the pharmaceutical company
BP24018, REC32748
Note
Text in blue = added text
Text in red strikethrough = deleted text
2. What you need to know before you are given Gadovist
[...]
- Pregnancy
Gadobutrol can cross the placenta. It is not known whether it affects the baby. 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.
6. Contents of the pack and other information
[...]
This medicine is authorised in the Member States of the European Economic Area under the following names:
[...]
Iceland Gadovist 1,0 mmól/ml, stungulyf, lausn í áfylltum sprautum/rörlykjum
[...]
This leaflet was last revised in SeptemberApril 20242
Updated on 01 May 2024
File name
24018_SmPC_CC_GADS_20240325.pdf
Reasons for updating
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.6 - Pregnancy and lactation
- Change to section 10 - Date of revision of the text
Legal category:Product subject to restricted prescription (C)
Free text change information supplied by the pharmaceutical company
BP24018, REC32748
Note
Text in blue = added text
Text in red strikethrough = deleted text
4.4 Special warnings and precautions for use
Gadobutrol must not be used intrathecally. Serious, life-threatening and fatal cases, primarily with neurological reactions (e.g. coma, encephalopathy, seizures), have been reported with intrathecal use.
4.6 Fertility, pregnancy and lactation
Pregnancy
There are no dataData from the use of gadolinium-based contrast agents including gadobutrol in pregnant women is limited. Gadolinium can cross the placenta. It is unknown whether exposure to gadolinium is associated with adverse effects in the foetus. 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.
10. DATE OF REVISION OF THE TEXT
SeptemberApril 20242
Updated on 06 October 2022
File name
22036_PL_CC+Cross_PFS_glass_20220830.pdf
Reasons for updating
- Change to section 3 - how to take/use
- Change to section 6 - marketing authorisation holder
- Change to section 6 - date of revision
Free text change information supplied by the pharmaceutical company
3. How Gadovist will be given
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 millilitres) for imaging of the central nervous system (CNS) and CE-MRA. A dose of 0.075 millilitres Gadovist per kg body weight may be given at minimum (this means for a person weighing 70 kg the dose would be 5.25 millilitres) for the CNS.
6, Marketing Auhtorisation Holder
Bayer Limited, 1st Floor, The Grange Offices, The Grange, Brewery Road, Stillorgan, Co. Dublin, A94 H2K7, Ireland
Updated on 06 October 2022
File name
22036_SmPC_CC_GADS_20220830.pdf
Reasons for updating
- Change to section 4.2 - Posology and method of administration
- Change to section 5.1 - Pharmacodynamic properties
- Change to section 7 - Marketing authorisation holder
- Change to section 10 - Date of revision of the text
Legal category:Product subject to restricted prescription (C)
Free text change information supplied by the pharmaceutical company
4.2 Posology and method of administration
Adults
CNS indications
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).
5.1 Pharmacodynamic properties
Clinical efficacy
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.
7. MARKETING AUTHORISATION HOLDER
Bayer Limited, 1st Floor The Grange Offices, The Grange, Brewery Road, Stillorgan, Co. Dublin, A94 H2K7, Ireland
Updated on 29 August 2022
File name
21038_PL_CC+Cross_PFS_glass_20220815.pdf
Reasons for updating
- Change to section 3 - dose and frequency
- Change to section 6 - date of revision
Free text change information supplied by the pharmaceutical company
3. How Gadovist will be given
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 millilitres) for imaging of the central nervous system (CNS) and CE-MRA. A dose of 0.075 millilitres Gadovist per kg body weight may be given at minimum (this means for a person weighing 70 kg the dose would be 5.25 millilitres) for the CNS.
The following information is intended for healthcare professionals only:
Posology
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.
Updated on 29 August 2022
File name
21038_SmPC_CC_GADS_20220815.pdf
Reasons for updating
- Change to section 4.2 - Posology and method of administration
- Change to section 5.1 - Pharmacodynamic properties
- Change to section 10 - Date of revision of the text
Legal category:Product subject to restricted prescription (C)
Free text change information supplied by the pharmaceutical company
4.2 Posology and method of administration
Adults
CNS indications
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).
5.1 Pharmacodynamic properties
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.
Updated on 10 November 2021
File name
20170913_PL_CC+Cross_PFS_glass_17194.pdf
Reasons for updating
- Change to section 6 - marketing authorisation number
Updated on 10 November 2021
File name
19115_SmPC_CC_GADS_20200806.pdf
Reasons for updating
- Change to section 8 - Marketing authorisation number(s)
Legal category:Product subject to restricted prescription (C)
Updated on 07 September 2020
File name
19115_SmPC_CC_GADS_20200806.pdf
Reasons for updating
- Change to section 5.1 - Pharmacodynamic properties
- Change to section 10 - Date of revision of the text
Legal category:Product subject to restricted prescription (C)
Updated on 10 January 2018
Reasons for updating
- New SPC for new product
Legal category:Product subject to restricted prescription (C)
Updated on 10 January 2018
Reasons for updating
- Change to section 4.1 - Therapeutic indications
- Change to section 4.2 - Posology and method of administration
Legal category:Product subject to restricted prescription (C)
Free text change information supplied by the pharmaceutical company
In Section 4.2 - Addition of "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."
Date of revision has been updated to November 2017.
Updated on 09 January 2018
File name
PIL_10490_831.pdf
Reasons for updating
- New PIL for new product
Updated on 09 January 2018
Reasons for updating
- Change to information for healthcare professionals
Updated on 24 May 2017
Reasons for updating
- Change to section 6 - manufacturer
- Change to section 6 - date of revision
Updated on 13 May 2016
Reasons for updating
- Change to section 5.1 - Pharmacodynamic properties
- Change to section 10 - Date of revision of the text
Legal category:Product subject to restricted prescription (C)
Free text change information supplied by the pharmaceutical company
Pharmacodynamic effects:
-
tissue or in lesions featuring an intact blood-brain barrier.
the T2 effect results in a lessening of signal intensity. -was removed.
In section 10. DATE OF REVISION OF THE TEXT:
Updated on 04 March 2016
Reasons for updating
- Correction of spelling/typing errors
Updated on 09 December 2015
Reasons for updating
- Change to packaging
- Change to dosage and administration
Updated on 02 November 2015
Reasons for updating
- Change to section 6.5 - Nature and contents of container
Legal category:Product subject to restricted prescription (C)
Free text change information supplied by the pharmaceutical company
Section 6.5 has been changed and now includes the following:
Plastic syringes:
One 10-ml prefilled syringe (cyclo-olefin polymer) with a plunger stopper (siliconized bromobutyl) and a tip seal (thermoplastic elastomer) contains 5 ml, 7.5 ml, 10 ml solution for injection.
One 20-ml prefilled syringe (cyclo-olefin polymer) with a plunger stopper (siliconized bromobutyl) and a tip seal (thermoplastic elastomer) contains 15 ml, 20 ml solution for injection.
Updated on 11 August 2015
Reasons for updating
- Change to section 4.1 - Therapeutic indications
- Change to section 4.2 - Posology and method of administration
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.8 - Undesirable effects
- Change to section 5.1 - Pharmacodynamic properties
- Change to section 5.2 - Pharmacokinetic properties
- Change to section 5.3 - Preclinical safety data
- Change to section 6.6 - Special precautions for disposal and other handling
Legal category:Product subject to restricted prescription (C)
Free text change information supplied by the pharmaceutical company
'This medicinal product is for diagnostic use only. Gadovist is indicated in adults, adolescents and children aged 2 years and older for:.......'
to:'This medicinal product is for diagnostic use only. Gadovist is indicated in adults and children of all ages (including term neonates) for:.....'
Section 4.2 has been changed from:
'....
Paediatric population
For children aged 2 years and older and for adolescents the recommended dose is 0.1 mmol Gadovist per kg body weight (equivalent to 0.1 ml Gadovist per kg body weight) for all indications (see section 4.1).
Gadovist is not recommended for use in children below age 2 years due to a lack of data on efficacy and safety.....'
to:
'.....
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.....'
Section 4.4 has been changed to include:
'....
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....'
Section 4.8 has been changed from:'
The overall safety profile of Gadovist is based on data from more than 5,700 patients in clinical trials and from post-marketing surveillance...................................................
Paediatric population
Based on a single dose phase I/III study in 140 paediatric patients (see section 5.1) the frequency, type and severity of adverse reactions in children aged 2 years and older are expected to be comparable to the adverse event profile known in adults.........'
to:'The overall safety profile of Gadovist is based on data from more than 6,300 patients in clinical trials and from post-marketing surveillance......................
Paediatric population
Based on two single dose phase I/III studies in 138 paediatricsubjects 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.....'
Section 5.1 has been changed from:
'.............
Paediatric population
A single dose phase I/III study in 140 paediatric patients (aged 2 to 17 years) scheduled for CE-MRI of CNS, liver and kidneys or CE-MRA has been performed.
It was shown that the overall pharmacokinetic (PK) profile of gadobutrol in children over 2 is similar to that in adults. PK parameters such as total clearance (CLtot), area under the curve (AUC) and volume of distribution (V) increased with increasing body weight. Neither age nor gender was found to have an additional independent effect on PK. The amount of gadobutrol excreted into urine within 6 hours p.i. was 98.7 % (median) of the administered dose, confirming fast renal excretion of gadobutrol also in the paediatric population.....'
to:
'...........
Paediatric population
Two single dose phase I/III studies in 138 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.....'
Section 5.2 has been changed from:
'....
Characteristics in special patient populations
Paediatric population
A single dose phase I/III study in 140 paediatric patients (aged 2 to 17 years) scheduled for CE-MRI of CNS, liver and kidneys or CE-MRA has been performed.
It was shown that the overall pharmacokinetic (PK) profile of gadobutrol in children over 2 is similar to that in adults. PK parameters such as total clearance (CLtot), area under the curve (AUC) and volume of distribution (V) increased with increasing body weight. Neither age nor gender was found to have an additional independent effect on PK. The amount of gadobutrol excreted into urine within 6 hours p.i. was 98.7 % (median) of the administered dose, confirming fast renal excretion of gadobutrol also in the paediatric population....'
to:'...
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)....'
Section 5.3 has been changed to add:
'....
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....'
Section 6.5 has been changed to add:
'....
Hospital pack:
5 prefilled syringes with 5, 7.5, 10, 15, 20 ml solution for injection...'
Setion 6.6 has been changed from:
'.........
The peel-off tracking label on the pre-filled syringes should be stuck onto the patient record to enable accurate recording of the gadolinium contrast agent used. The dose used should also be recorded.'
to:'.....
The peel-off tracking label on the pre-filled syringes 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.'
Updated on 06 August 2015
Reasons for updating
- Change to warnings or special precautions for use
- Change to date of revision
- Change to dosage and administration
- Changes to therapeutic indications
Updated on 11 November 2014
Reasons for updating
- Change to section 4.2 - Posology and method of administration
- Change to section 4.8 - Undesirable effects
- Change to Section 4.8 – Undesirable effects - how to report a side effect
- Change to section 10 - Date of revision of the text
Legal category:Product subject to restricted prescription (C)
Free text change information supplied by the pharmaceutical company
4.2 Posology and method of administration
…
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).
…
4.8 Undesirable effects
…
Fluctuations of renal function parameters including increases of serum creatinine have been observed after administration of Gadovist.
…
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 details provided below HPRA Pharmacovigilance, Earlsfort Terrace, IRL – Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; E-mail: medsafety@hpra.ie.
Ireland
Pharmacovigilance Section
Irish Medicines Board
Kevin O’Malley House
Earlsfort Centre
Earlsfort Terrace
IRL – Dublin 2
Tel: +353 1 6764971
Fax: +353 1 6762517
Website: www.imb.ie
e-mail: imbpharmacovigilance@imb.ie
10. DATE OF REVISION OF THE TEXT
September 2013November 2014
Updated on 10 November 2014
Reasons for updating
- Change to side-effects
- Change to date of revision
- Addition of information on reporting a side effect.
Updated on 08 November 2013
Reasons for updating
- Change to section 10 - Date of revision of the text
- Correction of spelling/typing errors
Legal category:Product subject to restricted prescription (C)
Free text change information supplied by the pharmaceutical company
Also in section 4.8, the spelling of hematoma has been updated to haematoma
The date of revision of the text has been updated from July to September 2013
Updated on 06 November 2013
Reasons for updating
- Change to date of revision
Updated on 12 August 2013
Reasons for updating
- Change to Section 4.8 – Undesirable effects - how to report a side effect
- Change to section 6.3 - Shelf life
- Change to section 10 - Date of revision of the text
Legal category:Product subject to restricted prescription (C)
Free text change information supplied by the pharmaceutical company
4.8 Undesirable effects
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 details provided below. the national reporting system listed in Appendix V.
Ireland
Pharmacovigilance Section
Irish Medicines Board
Kevin O’Malley House
Earlsfort Centre
Earlsfort Terrace
IRL – Dublin 2
Tel: +353 1 6764971
Fax: +353 1 6762517
Website: www.imb.ie
e-mail: imbpharmacovigilance@imb.ie
6.3 Shelf life
3 years (prefilled syringe)
Shelf life after first opening of the container:
Any solution for injection not used in one examination must be discarded. Chemical, and 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. and would normally not be longer than 24 hours at 2 to 8 °C, unless opening has taken place in controlled and validated aseptic conditions.
10. DATE OF REVISION OF THE TEXT
Julyne 2013
Updated on 07 August 2013
Reasons for updating
- Change to storage instructions
- Change to date of revision
- Addition of information on reporting a side effect.
Updated on 12 July 2013
Reasons for updating
- Change to section 2 - Qualitative and quantitative composition
- Change to section 4.2 - Posology and method of administration
- Change to section 4.3 - Contraindications
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.6 - Pregnancy and lactation
- Change to section 4.8 - Undesirable effects
- Change to section 5.1 - Pharmacodynamic properties
- Change to section 5.2 - Pharmacokinetic properties
- Change to section 5.3 - Preclinical safety data
- Change to section 6.1 - List of excipients
- Change to section 6.3 - Shelf life
- Change to section 6.4 - Special precautions for storage
- Change to section 6.6 - Special precautions for disposal and other handling
- Change to section 10 - Date of revision of the text
Legal category:Product subject to restricted prescription (C)
Free text change information supplied by the pharmaceutical company
Red text = deleted text
Blue text = inserted text
Section 2 Qualitative and Quantitative Composition
……………………………
Excipient with known effect: 1 ml contains 0.00056 mmol (equivalent to 0.013 mg) of sodium (see section 4.4).
For a the full list of excipients, see section 6.1.
Section 4.2 Posology and method of administration
……………………………
The following sentence has been underlined: “Method of administration”
……………………………
• DosagePosology
……………………………
The following changed from bold, underlined to italics “Adults”; “Special Populations”
……………………………
Impaired renal function Renal impairment
……………………………
Section 4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Section 4.4 Special warnings and precautions for use
……………………………
The following has been underlined “Hypersensitivity reactions”
……………………………
Hypersensitivity reactions
Hypersensitivity reactions, including anaphylactoid reactions ranging to shock, have been observed after administration of Gadovist. To be able to react immediately to an emergency, medicinal products and equipment (e.g. endotracheal tube and respirator) should be within hand reach.
Hypersensitivity reactions are not predictable, however in patients with an allergic disposition hypersensitivity may occur more often than in patients without such a disposition. In rare cases delayed anaphylactoid reactions (after hours to days) have been observed.
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 (see section 4.2).
Delayed reactions (after hours up to several days) have been rarely observed (see section 4.8).
……………………………
The following text has been underlined “Impaired renal function”; “Seizure disorders”; ”Excipients”
……………………………
Section 4.6 Fertility, pPregnancy and lactation
……………………………
LactationBreast-feeding
……………………………
Fertility
Animal studies do not indicate impairment of fertility.
Section 4.8 Undesirable effects
The overall safety profile of Gadovist is based on data from more than 4,5005,700 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, injection site reactions, dysgeusia and dizzinessfeeling hot.
The most serious adverse drug reactions in patients receiving Gadovist are cardiac arrest, respiratory arrest and severe anaphylactoid reactions shock(including respiratory arrest and anaphylactic shock).
……………………………
|
Frequency |
||||
System Organ Class |
Common |
Uncommon |
Rare |
Not known |
|
Immune system disorders |
|
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§) |
|
|
|
……………………………
Nervous system disorders |
Headache |
Dizziness, Dysgeusia Paresthesia |
Loss of consciousness*, Convulsion, Parosmia |
|
§ Hypersensitivity / anaphylactoid reactions identified only during post-marketing surveillance (frequency not known)
* There have been reports of life-threatening and/or fatal cases have been reported 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)
§ Hypersensitivity / anaphylactoid reactions identified only during post-marketing surveillance (frequency not known)
……………………………
Paediatric population
Based on a single dose phase I/III study in 140 paediatric patients (see section 5.1) the frequency, type and severity of adverse reactions in children aged 2 years and older are expected to be comparable to the adverse event profile known in adults.
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.
Section 5.1 Pharmacodynamic properties
Underline the following terms “Mechanism of action”; “Pharmacodynamic effects”; “Clinical efficacy”
……………………………
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
In clinical doses, gadobutrol leads to shortening of the relaxation times of protons in tissue water. At 0.47 T (20 MHz), pH 7 and 40 °C the paramagnetic effect (relaxivity), as determined from the effect on spin-lattice relaxation time (T1) measured in plasma - is about 5.6 l mmol-1 sec-1 and the spin-spin relaxation time (T2) is about 6.5 l mmol-1 sec-1. Within the range 0.47 to 2.0 Tesla, the relaxivity displays only slight dependency on the strength of the magnetic field.
Gadobutrol does not cross an intact blood-brain barrier and therefore does not accumulate in healthy brain tissue or in lesions featuring an intact blood-brain barrier. With high local tissue concentrations of gadobutrol the T2 effect results in a lessening of signal intensity.
Clinical efficacy
In a pivotal phase III liver study average sensitivity in combined pre and postcontrast MRI for Gadovist-treated patients was 79 % and specificity was 81 % for lesion detection and classification of suspected malignant liver lesions (patientbased analysis).
……………………………
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.
Paediatric population
A single dose phase I/III study in 140 paediatric patients (aged 2 to 17 years) scheduled for CE-MRI of CNS, liver and kidneys or CE-MRA has been performed. Diagnostic efficacy and an increase in diagnostic confidence was demonstrated for all parameters evaluated in the study and there was no difference among the age groups. Gadovist was well tolerated in this study with the same safety profile of gadobutrol as in adults.
Section 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
The pharmacokinetics of gadobutrol in humans are dose proportional. After doses up to 0.4 mmol gadobutrol/kg body weight, the plasma level declines after an early distribution phase 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 0.59 mmol gadobutrol/l plasma was measured 2 minutes after the injection and 0.3 mmol gadobutrol/l plasma 60 minutes post injection. Within two hours more than 50 % and within 12 hours more than 90 % of the given dose is eliminated via the 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 the faeces. No metabolites are detected in plasma or urine.
Characteristics in special patient populations
Paediatric population
……………………………
Elderly population (aged 65 years and above)
……………………………
Section 5.3 Preclinical safety data
……………………………
Radioactivelyity labelled gadobutrol administered intravenously to lactating rats was transferred to the neonates via milk at less than 0.1 % of the administered dose.
……………………………
Section 6.1 List of excipients
Calcobutrol sodium
Trometamol
Hydrochloric acid 1N (pH-adjustment)
Water for injections
Section 6.3 Shelf life
Shelf life of the medicinal product as packaged for sale:
3 years (prefilled syringe)
Section 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.
Section 6.6 Special precautions for disposal and other handling
Any contrast medium solution not used in one examination must be discarded.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
……………………………
Section 10 Date of revision of the text
September 2012 June 2013
Updated on 02 July 2013
Reasons for updating
- Change to warnings or special precautions for use
- Change to storage instructions
- Change to side-effects
- Change to how the medicine works
- Change to further information section
- Change to dosage and administration
- Change to improve clarity and readability
Updated on 31 October 2012
Reasons for updating
- Change to section 4.1 - Therapeutic indications
- Change to section 4.2 - Posology and method of administration
- Change to section 10 - Date of revision of the text
Legal category:Product subject to restricted prescription (C)
Free text change information supplied by the pharmaceutical company
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.
4.2 Posology and method of administration
Adults
CNS Indications
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-MRI of liver and kidneys:
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.
10 Date of revision of text
September 2012
Updated on 27 September 2012
Reasons for updating
- Change to section 4.1 - Therapeutic indications
- Change to section 10 - Date of revision of the text
Legal category:Product subject to restricted prescription (C)
Free text change information supplied by the pharmaceutical company
In section 4.1 therapeutic indication added as follows:
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.
In section 4.2 method of administration was updated in accordance with the change in section 4.1 as follows:
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-MRI of liver and kidneys:
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.
In section 10 Date of revision of text was changed from June 2012 to August 2012
Updated on 27 September 2012
Reasons for updating
- Change to, or new use for medicine
- Change to date of revision
Updated on 05 September 2012
Reasons for updating
- Change to further information section
- Change to date of revision
Updated on 30 August 2012
Reasons for updating
- Change to date of revision
- Changes to therapeutic indications
Updated on 20 July 2012
Reasons for updating
- Change to paediatric information
- Change to section 10 - Date of revision of the text
Legal category:Product subject to restricted prescription (C)
Free text change information supplied by the pharmaceutical company
- section 4.1 - change from indicated for use in children 7 years and older, to indicated for use in children 2 years and older.
- section 4.2, also updated in the paediatric population subsection, with regards to the above change in indication.
- section 5.2, updated in subsection Characteristics in special patient populations - Paediatric populations - to reflect further information with regards to the indication change above.
Updated on 25 June 2012
Reasons for updating
- Change to warnings or special precautions for use
- Change to drug interactions
- Change to how the medicine works
- Change to date of revision
- Change to dosage and administration
Updated on 07 December 2011
Reasons for updating
- Change to section 4.2 - Posology and method of administration
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.8 - Undesirable effects
- Change to section 4.9 - Overdose
- Change to section 5.1 - Pharmacodynamic properties
- Change to section 5.2 - Pharmacokinetic properties
- Change to section 5.3 - Preclinical safety data
- Change to section 10 - Date of revision of the text
Legal category:Product subject to restricted prescription (C)
Free text change information supplied by the pharmaceutical company
Updated on 05 December 2011
Reasons for updating
- Change to warnings or special precautions for use
- Change to side-effects
- Change to further information section
- Change to date of revision
- Change to name of manufacturer
Updated on 27 January 2011
Reasons for updating
- Change to section 2 - Qualitative and quantitative composition
- Change to section 3 - Pharmaceutical form
- Change to section 4.2 - Posology and method of administration
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.6 - Pregnancy and lactation
- Change to section 4.8 - Undesirable effects
- Change to section 4.9 - Overdose
- Change to section 5.1 - Pharmacodynamic properties
- Change to section 6.1 - List of excipients
- Change to section 6.3 - Shelf life
- Change to section 6.4 - Special precautions for storage
- Change to section 6.6 - Special precautions for disposal and other handling
- Change to section 9 - Date of renewal of authorisation
- Change to section 10 - Date of revision of the text
Legal category:Product subject to restricted prescription (C)
Free text change information supplied by the pharmaceutical company
Sections Updated: The following additional text was added.
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 prefilled syringe with 5.0 ml contains 3023.6 mg gadobutrol,
1 prefilled syringe with 7.5 ml contains 4535.4 mg gadobutrol,
1 prefilled syringe with 10 ml contains 6047.2 mg gadobutrol,
1 prefilled syringe with 15 ml contains 9070.8 mg gadobutrol,
1 prefilled syringe with 20 ml contains 12094.4 mg gadobutrol.
1 ml contains 0.00056 mmol (equivalent to 0.013 mg) of sodium (see section 4.4).
For a full list of excipients, see section 6.1.
3. PHARMACEUTICAL form
Physico-chemical properties:
Osmolality at 37°C: 1603 mOsm/kg H2O
Viscosity at 37°C: 4.96 mPa·s
4.2 Posology and method of administration
Gadovist should only be administered by healthcare professionals experienced in the field of clinical MRI practice.
This product is intended for single use only
Adults
Special Populations
Impaired renal function
Gadovist should only be used in patients with severe renal impairment (GFR < 30 ml/min/1.73m2) 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 aged 7 years and older and for adolescents the recommended dose is 0.1 mmol Gadovist per kg body weight (equivalent to 0.1 ml Gadovist per kg body weight) for all indications (see section 4.1).
Elderly (aged 65 years and above)
No dosage adjustment is considered necessary. Caution should be exercised in elderly patients (see section 4.4).
4.4 Special warnings and precautions for use
The possibility that Gadovist may cause torsade de pointes arrhythmias in an individual patient cannot be excluded (see section 5.3).
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 gadolinium-containing contrast agents in patients with acute or chronic severe renal impairment (GFR < 30 ml/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 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.
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.
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’.
4.6 Pregnancy and lactation
PregnancyThere 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.
LactationGadolinium 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 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.
4.8 Undesirable effects
|
Adverse reactions from clinical trial data (experience in more than 2900 patients) |
Additional adverse reactions from postmarketing spontaneous reporting |
|
System Organ Class |
Uncommon |
Rare |
Rare |
Immune system disorders |
|
Anaphylactoid reaction |
Anaphylactoid shock |
|
|
|
|
Nervous system disorders |
Headache, Dizziness, Dysgeusia, Paresthesia, |
Parosmia |
Loss of consciousness, Convulsion |
Eye disorders |
|
|
Conjunctivitis, Eyelid oedema |
Cardiac disorders |
|
|
Cardiac arrest, Tachycardia |
Vascular disorders |
Vasodilatation |
Hypotension |
Circulatory collapse, |
Respiratory, thoracic and mediastinal disorders |
|
Dyspnoea |
Respiratory arrest, Bronchospasm, Cyanosis, Oropharyngeal swelling, Cough, Sneezing |
Gastrointestinal disorders |
Nausea |
Vomiting |
|
Skin and subcutaneous tissue disorders |
|
Urticaria, Rash |
Face edema, Hyperhidrosis, Pruritus, Erythema |
|
|
|
|
General disorders and administration site conditions |
Injection site pain, Injection site reaction |
|
Nephrogenic Systemic Fibrosis (NSF), Feeling hot, Malaise, |
|
|
|
|
Isolated cases of renal impairment or renal impairment aggravation have been reported.
Isolated cases of nephrogenic systemic fibrosis (NSF) have been reported with Gadovist (see section 4.4).
4.9 Overdose
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).
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Paramagnetic contrast media
ATC – Code: V08C A09
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).
5.3 Preclinical safety data
Repeated treatment in reproductive toxicology studies caused a retardation of embryonal development in rats and an increase in embryolethality in monkeys and in rabbits at maternally toxic dose levels (8 to 17 times the diagnostic dose) only. It is not known whether these effects can also be induced by a single administration.
6.1 List of excipients
Hydrochloric acid 1N
6.3 Shelf life
Shelf life after first opening of the container:
Any solution for injection not used in one examination must be discarded. Chemical and physical in-use stability has been demonstrated for 24 hours at 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 and would normally not be longer than 24 hours at 2 to 8 °C, unless opening has taken place in controlled and validated aseptic conditions.
6.4 Special precautions for storage
This medicinal product does not require any special storage conditions.
For storage conditions after first opening, see section 6.3.
6.6 Special precautions for disposal and other handling
The peel-off tracking label on the pre-filled syringes/cartridges should be stuck onto the patient record to enable accurate recording of the gadolinium contrast agent used. The dose used should also be recorded.
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
Date of last renewal: 24 January 2010
10. DATE OF REVISION OF THE TEXT
January 2011
Updated on 26 January 2011
Reasons for updating
- Change to warnings or special precautions for use
- Change to instructions about overdose
- Change to storage instructions
- Change to side-effects
- Change to information about pregnancy or lactation
- Change to further information section
- Change to dosage and administration
- Change to date of revision
Updated on 25 January 2010
Reasons for updating
- Change to section 4.1 - Therapeutic indications
- Change to section 4.2 - Posology and method of administration
- Change to section 5.1 - Pharmacodynamic properties
- Change to section 5.2 - Pharmacokinetic properties
- Change to section 10 - Date of revision of the text
Legal category:Product subject to restricted prescription (C)
Free text change information supplied by the pharmaceutical company
4.1 Therapeutic indications
Additional Text:
· . Gadovist is indicated in adults, adolescents, and children aged 7 years and older for:
4.2 Posology and method of administration
Additional Text:
Paediatric patients
For children aged 7 years and older and for adolescents the recommended dose is 0.1 mmol Gadovist per kg body weight (equivalent to 0.1 ml Gadovist per kg body weight) for all indications (see section 4.1 Therapeutic indications).
Gadovist is not recommended for use in children below age 7 years due to a lack of sufficien