Clariscan 0,5 mmol/ml Injektionsvätska, lösning i förfylld spruta

Sverige - svenska - Läkemedelsverket (Medical Products Agency)

Bipacksedel Bipacksedel (PIL)

20-04-2018

Produktens egenskaper Produktens egenskaper (SPC)

20-04-2018

Aktiva substanser:
gadoterinsyra
Tillgänglig från:
GE Healthcare AS
ATC-kod:
V08CA02
INN (International namn):
gadoteric acid
Dos:
0,5 mmol/ml
Läkemedelsform:
Injektionsvätska, lösning i förfylld spruta
Sammansättning:
gadoterinsyra 279,3 mg Aktiv substans
Receptbelagda typ:
Receptbelagt
Produktsammanfattning:
Förpacknings: Förfylld spruta, 10 ml; Förfylld spruta, 10 x 20 ml; Förfylld spruta, 15 ml; Förfylld spruta, 20 ml; Förfylld spruta, 10 x 10 ml; Förfylld spruta, 10 x 15 ml
Bemyndigande status:
Godkänd
Godkännandenummer:
54434
Tillstånd datum:
2017-02-20

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20-02-2017

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30-11-2020

Offentlig bedömningsrapport Offentlig bedömningsrapport - engelska

20-02-2017

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PACKAGE LEAFLET: INFORMATION FOR THE USER

Clariscan 0.5 mmol/mLsolution for injection

Clariscan 0.5 mmol/mL solution for injection in pre-filled syringe

Gadoteric acid

Read all of this leaflet carefully before you start using 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, ask your doctor or radiologist or pharmacist.

If you get any of the side effects, talk to your doctor, radiologist or pharmacist. This includes any

possible side effects not listed in this leaflet. See section 4.

In this leaflet

1. What Clariscan is and what it is used for

2. What you need to know before you are given Clariscan

3. How you will be given Clariscan

4. Possible side effects

5. How to store Clariscan

6. Contents of the pack and other information

1. What Clariscan is and what it is used for

What Clariscan is

Clariscan contains the active substance gadoteric acid. It belongs to a group called “contrast agents”

used for magnetic resonance imaging” (MRI).

What Clariscan is used for

Clariscan is used to enhance the contrast of the images obtained during MRI examinations.

In adults and in children and adolescents 0-18 years old:

- MRI of the CNS including of defects (lesions) in brain, spine, and surrounding tissues

In adults and in children and adolescents 6 months – 18 years old:

- Whole body MRI including defects (lesions)

In adults only:

MR angiography including defects (lesions) or narrowing (stenosis) in arteries, except in coronary

arteries.

This medicine is for diagnostic use only

How Clariscan works

Clariscan makes the pictures on an MRI scanner easier to see. It does this by increasing the contrast

between the part of the body being looked at and the rest of the body. This allows doctors or

radiologists to see different areas of the body better.

2. What you need to know before you are given Clariscan

You should not be given Clariscan :

if you are allergic to gadoteric acid or any of the other ingredients of this medicine (listed in

section 6)

if you are allergic to medicines which contain gadolinium or other contrast agents used for

MRI.

Warnings and precautions

Remove all metallic objects you may wear before the examination

Talk to your doctor or radiologist before being given Clariscan if:

you have previously reacted to a contrast agent during an examination

you have asthma

you have a history of allergy - such as a seafood allergy, hay fever, urticaria (severe itching)

you are being treated with a beta-blocker (medicine for heart and blood pressure disorders, such

as metoprolol

your kidneys do not work properly

you have recently had a liver transplant – or expect to have one soon

you have had fits (seizures or convulsions) or you are being treated for epilepsy

you have a severe heart problem.

you have a disease affecting your heart or your blood vessels

you have a heart pacemaker, an iron-based (ferromagnetic) clip, an implant or an insulin pump,

any suspected metallic foreign bodies, particularly in the eye. It is a condition where MRI is

not suitable

Talk to your doctor or radiologist if any of the above apply to you before being given Clariscan.

Risk of serious side effects

As with all MRI contrast agents, there is a risk of side effects. The side effects are usually minor and

temporary but cannot be predicted. However, there is a risk they could endanger your life:

possible serious side effects may happen immediately or within one hour of being given the

medicine

side effects may happen up to 7 days after treatment. Side effects are more likely if you have

ever had a reaction to an MRI contrast agent in the past (see section 4 “Possible side effects”)

Tell your doctor or radiologist before being given Clariscan if you have had a reaction in the

past. Your doctor or radiologist will only give you Clariscan if the benefits outweigh the risks.

If you are given Clariscan, you will be carefully monitored by your doctor or radiologist.

Tests and checks

Your doctor or radiologist may decide to do a blood test before you are given Clariscan, especially if

you are over 65 years old. This is to check how well your kidneys are working.

Children and adolescents

Use for angiography is not recommended in children less than 18 years of age.

New borns and infants

Your doctor or radiologist will carefully consider whether your baby can be given Clariscan. This is

because the kidneys are immature in babies up to up to 4 weeks and infants up to 1 year

Use for whole body MRI is not recommended in children less than 6 months of age.

Other medicines and Clariscan

Tell your doctor or radiologist if you are taking, have recently taken or might take any other medicines.

In particular, tell your doctor or radiologist if you are taking or have recently taken any of these

medicines for heart and high blood pressure:

a beta-blocker medicine – Medicines that slow your heart rate (such as metoprolol)

medicinesthat enlarge (dilate) your blood vessels and decrease blood pressure: vasoactive

substances (such as doxazosin) ,, angiotensin-converting enzyme (ACE) inhibitors (such as

ramipril) angiotensin II receptor antagonist (such as valsartan).

Tell your doctor or radiologist if you are taking or have recently taken any of the medicines listed

above.

Clariscan with food and drink

Nausea and vomiting are known possible undesirable effects when using MRI contrast agents. The

patient should therefore refrain from eating for 2 hours prior to the investigation

Pregnancy and breast-feeding

Pregnancy

You must tell your doctor or radiologist if you are pregnant, think you may be pregnant or might

become pregnant. This is because Clariscan should not be given during pregnancy unless your doctor

decides it is necessary.

Breast-feeding

Tell your doctor or radiologist if you are breast-feeding or about to start breast-feeding. Your doctor or

radiologist will discuss with you whether you should continue breast-feeding. You may need to stop

breast-feeding for 24 hours after you have been given Clariscan.

Driving and using machines

No data are available on the effects of Clariscan on the ability to drive. However, while driving or

operating machines you should take into account dizziness (symptom of low blood pressure) and nausea.

If you feel unwell after

examination, you should not drive or use machines.

ow you will be

3. How you will be given Clariscan

How Clariscan is given

Clariscan will be given to you by intra-venous injection.

This will happen in a hospital, clinic or private practice.

Medical staff know the precautions that need to be taken.

They also know the possible complications that can happen.

During the examination, you will be supervised by your doctor or radiologist.

A needle will be left in your vein.

This will allow the doctor or radiologist inject you with emergency drugs if needed.

If you have an allergic reaction, the doctor or radiologist will stop giving you Clariscan.

How much you will be given

Your doctor or radiologist will decide how much Clariscan you will be given and supervise the

injection.

People with liver or kidney problems

The use of Clariscan is not recommended in patients with severe kidney problems or patients who have

recently had a liver transplant – or expect to have one soon.

However if your doctor or radiologist decides to give you Clariscan:

you must only be given one dose of Clariscan during an MRI and

you must not be given a second injection for at least 7 days.

New borns, infants, children and teenagers

Clariscan will only be used in these patients after careful consideration by the doctor or radiologist.

However, if your doctor or radiologist decides to give your child Clariscan:

they must only be given one dose of Clariscan during an MRI scan and

they must not be given a second injection for at least 7 days.

Use for whole body MRI is not recommended in children less than 6 months of age.

Use for angiography is not recommended in children less than 18 years of age.

The elderly

Your dose will not be changed if you are 65 years of age or older. However, you may have a blood test

first to check how well your kidneys are working.

If too much Clariscan has been given to you

It is very unlikely that you will be given an overdose. This is because you will be given Clariscan in a

medical setting by a trained person.

In a real case of overdose, Clariscan can be removed from the body by cleaning your blood

(“haemodialysis”).

Additional information regarding the use and handling by the medical or healthcare professional is

given at the end of this leaflet.

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.

After the administration

, you will be kept under observation for at least half an hour

Most side effects occur immediately or sometimes delayed. Some effects can occur up to several days

after being given the Clariscan injection.

There is a small risk (rare) that you may have an allergic reaction to Clariscan.

Such reactions can

be severe and

exceptionally result in “shock”

(a very rare case of allergic

reaction that could put your

life in danger).

Any of the symptoms listed below may be the first signs of shock.

Tell your doctor, radiologist or healthcare professional straight away if you have any of the

following signs

– you may

need urgent medical treatment:

swelling of the face, mouth or throat which may cause difficulties in swallowing or breathing

swelling of hands or feet

low blood pressure (hypotension- feeling faint)

breathing problems including breathing which sounds like a whistle

cough

itching

runny nose

sneezing or irritated eyes

patches of red skin, severe itching (urticaria)

Other side effects

Tell your doctor or radiologist if you notice any of the following side effects:

Very common: may affect more than 1 in 10 people

headaches

tingling sensation

Common: may affect up to 1 in 10 people

sensation of warmth or cold or pain where the injection was given

nausea (feeling sick)

vomiting (being sick)

redness of the skin, itching and rash

Uncommon: may affect up to 1 in 100 people

allergic reactions

Rare: may affect up to 1 in 1,000 people

unusual taste in the mouth

hives (patches of red skin, severe itching (urticaria)).

increased sweating

Very rare: may affect up to 1 in 10,000 people

feeling agitated or anxiety

coma, seizures, syncope (brief loss of consciousness), faintness (dizziness and feeling of

imminent loss of consciousness), dizziness, disorder of smell (perception of often unpleasant

odours), tremor

conjunctivitis, red eye, blurred vision,

increased tear secretion

,eye swelling

cardiac arrest, accelered or slow heart beat, irregular heart beat, palpitations, low or high blood

pressure, enlargement or relaxation of your blood vessels (vascular dilatation) leading to

lowering in your blood pressure and slow heart beat , pallor

breathing stops suddenly (respiratory arrest), fluid on the lungs (pulmonary oedema), breathing

difficulties, feeling of tight throat, wheezing, feeling of blocked nose, sneezing, cough, feeling

of dry throat

diarrhoea, stomach pain, producing more saliva

eczema, other skin reactions (for example red skin)

muscle contractures, muscle weakness, back pain

feeling tired (malaise or fatigue)

chest pain or discomfort

fever or rigors

swelling of the face

swelling or a reaction or discomfort around the injection site, redness and pain, oozing of the

medicine outside the veins can lead to inflammation or death of the skin cells (necrosis) at the

injection site, blood clot in the vein which causes inflammation (superficial phlebitis)

less oxygen in the blood

Unknown: it is not known how often these happen

Nephrogenic Systemic Fibrosis

This is a disease which hardens the skin and may affect soft tissue and internal organs. This has been

mostly in patients who were given Clariscan together with other gadolinium containing contrast agents.

Tell your doctor or radiologist if you notice any changes in the colour or thickness of your skin in any

part of your body as this may be a sign of the condition listed above

The following side effects have occurred with other similar contrast agents for MRI: destruction of your

red blood cells (haemolysis), confusion, temporary blindness, eye pain, ringing in the ears (tinnitus), ear

pain, asthma, dry mouth, blister- like eczema of the skin, inability to control urine (incontinence),

kidney damage, acute renal failure, Changes in electrocardiogram measurements of your heart, changes

in blood tests (increase in blood iron, increased bilirubin), abnormal liver tests.

Reporting of side effects

If you get any side effects, talk to your doctor or radiologist

This includes any possible 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 Clariscan

Keep this medicine out of the sight and reach of children.

The vials/bottles do not require any special storage conditions.

The pre-filled syringe must not be frozen.

Do not use this medicine after the expiry date which is stated on the vial or bottle or the pre-filled

syringe and on the carton, after the abbreviation “Exp”.

The expiry date refers to the last day of that month.

Chemical and physical in-use stability has been demonstrated for 48 hours at room temperature. 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.

Contents of the pack and other information

What Clariscan contains

The active substance is gadoteric acid. One mL of solution for injection contains 279.3mg of gadoteric

acid (as gadoterate meglumine), equivalent to 0.5 mmol of gadoteric acid.

The other ingredients are meglumine,tetraxetan (DOTA) and water for injection.

What Clariscan looks like and contents of the pack

Clariscan is a clear, colourless to slightly yellow solution for intravenous injection.

Clariscan is available in the following containers:

Glass vials (Type 1, colourless) filled to 5, 10, 15 and 20 mL

Polymer pre-filled syringes filled to 10, 15 and 20 mL.

Glass bottles (Type 1, colourless) and polypropylene bottles filled to 50 and 100 mL.

All containers are packed in an outer box of 1 and 10 units.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

GE Healthcare AS

Nycoveien 1-2

P.O. Box 4220 Nydalen

NO-0401 OSLO

NORWAY

This leaflet was last revised in February 2017

The following information is intended for medical or healthcare professionals only:

Posology

Adults

MRI of brain and spine

The recommended dose is 0.1 mmol/kg BW, i.e. 0.2 mL/kg BW. In patients with brain tumours, an

additional dose of 0.2 mmol/kg BW, i.e. 0.4 mL/kg BW, may improve tumor characterisation and

facilitate therapeutic decision making.

Whole body MRI (including lesions of the liver, kidneys, pancreas, pelvis, lungs, heart, breast,

and musculoskeletal system)

The recommended dose is 0.1 mmol/kg BW, i.e. 0.2 mL/kg BW to provide diagnostically adequate

contrast.

For angiography: The recommended dose for intravenous injection is

0.1 mmol/kg BW, i.e. 0.2 mL/ kg

BW to provide diagnostically adequate contrast.

In exceptional circumstances (e.g. failure to gain satisfactory images of an extensive vascular territory)

administration of a second consecutive injection of 0.1 mmol/kg BW, i.e. 0.2 mL/kg BW may be

justified. However, if the use of 2 consecutive doses of Clariscan are anticipated prior to commencing

angiography, the use of 0.05 mmol/kg BW (i.e. 0.1 mL/kg) for each dose may be of benefit, depending

on the imaging equipment available.

Special populations

Impaired renal function

Clariscan should only be used in patients with severe renal impairment (GFR < 30 mL/min/1.73m

) 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 Clariscan 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, Clariscan 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.

Impaired hepatic function

The adult dose applies to these patients. Caution is recommended, especially in the case of perioperative

liver transplantation period (see above impaired renal function).

Paediatric population (aged 0-18 years)

Encephalic and Spinal MRI, Whole body MRI:

The recommended and maximum dose of Clariscan is 0.1 mmol/kg body weight. More than one dose

should not be used during a scan.

Use for whole body MRI is not recommended in children less than 6 months of age

Due to immature renal function in neonates up to 4 weeks of age and infants up to 1 year of age,

Clariscan 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, Clariscan injections should not be repeated unless the interval

between injections is at least 7 days.

Angiography:

Clariscan is not recommended for angiography in children under 18 years of age due to insufficient data

on its efficacy and safety in this indication.

Method of administration

The product is indicated for intravenous administration only.

Infusion rate: 3-5 mL/min (higher infusion rates up to 120 mL/min, i.e. 2 mL/sec, may be used for

angiographic procedures). For instructions on preparation and disposal see

Precautions for use and

handling

below.

Paediatric population (0-18 years). Depending on the amount of Clariscan to be given to the child, it is

preferable to use Clariscan vials with a single use syringe of a volume adapted to this amount in order to

have a better precision of the injected volume.

In neonates and infants the required dose should be administered by hand.

Special warnings and precautions for use

Impaired renal function

Prior to administration of Clariscan it is recommended that all patients are screened for renal

dysfunction by obtaining laboratory tests.

There have been reports of nephrogenic systemic fibrosis (NSF) associated with use of some

gadolinium-containing contrast agents in patients with acute or chronic severe renal impairment (GFR<

30mL/min /1.73 m

). 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 Clariscan

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.

As the renal clearance of Clariscan may be impaired in the elderly, it is particularly important to screen

patients aged 65 years and older for renal dysfunction.

Haemodialysis shortly after Clariscan administration may be useful at removing Clariscan 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 lactation

Clariscan should not be used during pregnancy unless the clinical condition of the woman requires use

of gadoteric acid.

Continuing or discontinuing breast feeding for a period of 24 hours after administration of Clariscan,

should be at the discretion of the doctor or radiologist and lactating mother.

Precautions for use and handling

For single use

The solution for injection should be inspected visually prior to use. Only clear solutions free of visible

particles should be used.

Vials and bottles:

- Prepare a syringe with a needle. For vials, remove the plastic disk. For

polypropylene bottles remove the plastic screw cap or top plastic lid by pulling the top ring. After

cleaning the stopper with a pad soaked in alcohol, puncture the stopper with the needle. Withdraw the

quantity of product required for the examination and inject it intravenously.

Prefilled syringes

: Inject intravenously the quantity of product required for the examination.

The remaining contrast medium in the vial/bottle, the connecting lines and all disposable components in

the injector system must be discarded after the examination

The peel-off tracking label: The peel-off tracking label on the syringes/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.

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

requirements.

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SUMMARY OF PRODUCT CHARACTERISTICS

1.

NAME OF THE MEDICINAL PRODUCT

Clariscan 0.5 mmol/ mL solution for injection

Clariscan 0.5 mmol/ mL solution for injection in pre-filled syringe

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

1 mL solution for injection contains 279.3 mg gadoteric acid*(as gadoterate meglumine) equivalent to 0.5

mmol

Tetraxetan (DOTA)

202.46 mg

Gadolinium oxide

90.62 mg

* Gadoteric acid: gadolinium complex with1,4,7,10 tetraazacyclododecane N,N’,N”,N’’’ tetraacetic acid

(tetraxetan (DOTA))

For the full list of excipients, see section 6.1

3.

PHARMACEUTICAL FORM

Solution for injection.

Solution for injection in prefilled syringe

Clear, colourless to slightly yellow solution

Contrast medium concentration

279.3 mg/mL

equivalent to 0.5 mmol/mL

Osmolality at 37 °C

1350 mOsm.kg

Viscosity at 20 °C

3.0 mPa.s

Viscosity at 37 °C

2.1 mPa.s

pH value

6.5 – 8.0

4.

CLINICAL PARTICULARS

4.1

Therapeutic indications

This medicinal product is for diagnostic use only.

Clariscan should be used only when diagnostic information is essential and not available with unenhanced

magnetic resonance imaging (MRI).

Clariscan is a contrast agent indicated for enhancement of the contrast in Magnetic Resonance Imaging for

a better visualization/delineation.

Adult population and paediatric population (0-18 years):

- lesions of the brain, spine, and surrounding tissues

- whole body MRI (see section 4.2)

Use for whole body is not recommended in children less than 6 months

In adults only:

- lesions or stenoses of the non-coronary arteries (MR Angiography).

4.2

Posology and method of administration

This medicinal product should only be administered by trained healthcare professionals with technical

expertise in performing and interpreting gadolinium enhanced MRI.

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

MRI of brain and spine

The recommended dose is 0.1 mmol/kg BW, i.e. 0.2 mL/kg BW.

In patients with brain tumors, an

additional dose of 0.2 mmol/kg BW, i.e. 0.4 mL/kg BW, may improve tumor characterisation and facilitate

therapeutic decision making.

Whole body MRI (including lesions of the liver, kidneys, pancreas, pelvis, lungs, heart, breast, and

musculoskeletal system)

The recommended dose is 0.1 mmol/kg BW, i.e. 0.2 mL/kg BW to provide diagnostically adequate

contrast.

For angiography: The recommended dose for intravenous injection is

0.1 mmol/kg BW, i.e. 0.2 mL/kg

BW to provide diagnostically adequate contrast.

In exceptional circumstances (e.g. failure to gain satisfactory images of an extensive vascular territory)

administration of a second consecutive injection of 0.1 mmol/kg BW, i.e. 0.2 mL/kg BW may be justified.

However, if the use of 2 consecutive doses of Clariscan are anticipated prior to commencing angiography,

the use of 0.05 mmol/kg BW (i.e. 0.1 mL/kg BW) for each dose may be of benefit, depending on the

imaging equipment available.

Special populations

Impaired renal function

Clariscan should only be used in patients with severe renal impairment (GFR < 30 mL /min/1.73m

) 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 Clariscan 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, Clariscan 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).

Impaired hepatic function

The adult dose applies to these patients. Caution is recommended, especially in the case of perioperative

liver transplantation period (see above impaired renal function).

Paediatric population (aged 0-18 years)

Encephalic and Spinal MRI, Whole body MRI:

The recommended and maximum dose of Clariscan is 0.1 mmol/kg body weight. More than one dose

should not be used during a scan.

Due to immature renal function in neonates up to 4 weeks of age and infants up to 1 year of age, Clariscan

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, Clariscan injections should not be repeated unless the interval between injections

is at least 7 days.

Use for whole body MRI is not recommended in children less than 6 months of age.

Angiography:

Clariscan is not recommended for angiography in children under 18 years of age due to

insufficient data on its efficacy and safety in this indication (see section 4.4).

Method of administration

The product is indicated for intravenous administration only.

Infusion rate: 3-5 mL/min (higher infusion rates up to 120 mL/min, i.e. 2 mL/sec, may be used for

angiographic procedures). For instructions on preparation and disposal, see section 6.6.

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.

For single patient use only, any unused solution should be discarded.

Paediatric population (0-18 years). Depending on the amount of Clariscan to be given to the child, it is

preferable to use Clariscan vials with a single use syringe of a volume adapted to this amount in order to

have a better precision of the injected volume.

In neonates and infants the required dose should be administered by hand.

Image acquisition

Contrast enhanced MRI may be initiated immediately after administration of the agent. Optimal imaging:

within 45 minutes after injection. Optimal image sequence: T1-weighted

4.3

Contraindications

Hypersensitivity to gadoteric acid, to meglumine or to any medicinal products containing gadolinium.

4.4

Special warnings and precautions for use

Clariscan is administered strictly by intravenous injection only. In the event of extravasation local

intolerance reactions may be observed, necessitating short term local treatment.

Clariscan must not be administered by subarachnoid (or epidural) injections.

Appropriate facilities should be readily available for coping with any complication of the procedure, as

well as for emergency treatment of severe reaction to the contrast agent itself (e.g. hypersensitivity,

seizures).

The usual precaution for MRI examination should be taken, such as exclusion of patients with pacemakers,

vascular clips, infusion pumps, nerve stimulators, cochlear implants, or suspected intracorporeal metallic

foreign bodies, particularly in the eye.

Hypersensitivity

Hypersensitivity reactions can occur, including life-threatening (see section 4.8). Hypersensitivity

reactions may be either allergic (described as anaphylactic reactions when serious) or non-allergic.

They can be either immediate (less than 60 minutes), or delayed (up to 7 days).Anaphylactic

reactions can occur immediately and can be fatal. Hypersensitivity reactions may be independent of

the dose, may occur after even the first dose of the product, and are often unpredictable.

There is always a risk of hypersensitivity regardless of the dose injected.

Patients who have already experienced a reaction during previous administration of a gadolinium-

containing MRI contrast agent present an increased risk of experiencing another reaction on

subsequent administration of the same product, or possibly other products, and are therefore

considered to be at high risk.

The injection of gadoteric acid may aggravate symptoms of an existing asthma. In patients with

asthma unbalanced by the treatment, the decision to use gadoteric acid must be made after careful

evaluation of the risk/benefit ratio.

As known from the use of iodinated contrast media, hypersensitivity reactions can be aggravated in

patients on beta-blockers, and particularly in the presence of bronchial asthma. These patients may

be refractory to standard treatment of hypersensitivity reactions with beta-agonists.

Before any contrast medium is injected, the patient should be questioned for a history of allergy (e.g.

fish and seafood allergy, hay fever, hives), sensitivity to contrast media and bronchial asthma as the

reported incidence of adverse reactions to contrast media is higher in patients with these conditions

and premedication with antihistamines and/or glucocorticoids may be considered.

During the examination, supervision by a physician is necessary. If hypersensitivity reactions occur,

administration of the contrast medium must be discontinued immediately and, if necessary, specific

therapy instituted. A venous access should thus be kept during the entire examination. To permit

immediate emergency countermeasures, appropriate drugs (e.g. adrenaline and antihistamines), an

endotracheal tube and a respirator should be ready at hand.

Impaired renal function

Prior to administration of Clariscan 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/1.73m

). Patients undergoing liver transplantation are at particular high risk since the incidence of

acute renal failure is high in this group. As there is a possibility that NSF may occur with

Clariscan

, 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.

Haemodialysis shortly after Clariscan administration may be useful at removing Clariscan 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 gadoteric acid may be impaired in the elderly, it is particularly important to screen

patients aged 65 years and older for renal dysfunction.

Paediatric population

Neonates and infants

Due to immature renal function in neonates up to 4 weeks of age and infants up to 1 year of age, Clariscan

should only be used in these patients after careful consideration.

In neonates and infants the required dose should be administered by hand.

CNS disorders

Like with other gadolinium containing contrast agents special precaution is necessary in patients with a low

threshold for seizures

Precautionary measures should be taken, e.g. close monitoring. All equipment and drugs necessary to

counter any convulsions, which may occur, must be made ready for use beforehand.

Cardiovascular disease

In patients with severe cardiovascular disease Clariscan should only be administered after careful benefit

assessment because only limited data are available so far.

Patient preparation

Nausea and vomiting are known possible undesirable effects when using MRI contrast agents. The patient

should therefore refrain from eating for 2 hours prior to the investigation.

4.5

Interaction with other medicinal products and other forms of interaction

No interactions with other medicinal products have been observed. Formal drug interaction studies have

not been carried out.

Beta-blockers, vasoactive substances, angiotensin-converting enzyme inhibitors, angiotensin receptor

antagonists: These medicinal products induce decreased efficacy of cardiovascular compensation

mechanisms of blood pressure changes. The application of contrast media may increase the incidence of

hypersensitivity reactions in patients taking beta-blockers (see section 4.4).

4.6

Fertility, pregnancy and lactation

Pregnancy

There are no data from the use of gadoteric acid in pregnant women. Animal studies do not indicate direct

or indirect harmful effects with respect to reproductive toxicity (see section 5.3). Clariscan should not be

used during pregnancy unless the clinical condition of the woman requires use of gadoteric acid.

Breastfeeding

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 absorption from the gut.

Continuing or discontinuing breast feeding for a period of 24 hours after administration of Clariscan,

should be at the discretion of the doctor and lactating mother.

Fertility

There are no clinical data available with regard to effects on fertility.

4.7

Effects on ability to drive and use machines

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

while driving vehicles or operating machinery should take into account that nausea may incidentally occur.

4.8

Undesirable effects

Side effects in association with the use of gadoteric acid are usually mild to moderate in intensity and

transient in nature. A sensation of heat, cold and/or pain at the injection site is the most frequently observed

reactions.

During clinical trials, headache and paresthesia were very commonly observed (>1/10), and nausea,

vomiting and skin reactions such as erythematous rash and pruritus were commonly observed (>1/100 to

<1/10).

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

acid are nausea, vomiting, pruritus and hypersensitivity reactions.

In hypersensitivity reactions, the reactions most frequently observed are skin reactions, which can be

localized, extended or generalized.

These reactions occur most often immediately (during the injection or within one hour after the start of

injection) or sometimes delayed (one hour to several days after injection), presenting as skin reactions in

this case.

Immediate reactions include one or more effects, which appear simultaneously or sequentially, which are

most often cutaneous, respiratory and/or cardiovascular reactions. Each sign may be a warning sign of a

starting shock and go very rarely to death.

Isolated cases of nephrogenic systemic fibrosis (NSF) have been reported with gadoteric acid, most of

which were in patients co-administered other gadolinium-containing contrast agents (see section 4.4).

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

following guidelines: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100),

rare (≥1/10 000 to <1/1 000), very rare (<1/10 000), not known (cannot be estimated from the available

data). The data presented are from clinical trials when available, or from an observational study involving

82,103 patients.

System Organ Class

Frequency : adverse reaction

Immune system

disorders

Uncommon: hypersensitivity, anaphylactic reaction, anaphylactoid reaction

Psychiatric disorders

Very rare: agitation, anxiety

Nervous system

disorders

Very common: paraesthesia, headache

Rare: dysgeusia

Very rare: coma, convulsion, syncope, presyncope, dizziness, parosmia,

tremor

Eye disorders

Very rare: conjunctivitis, ocular hyperaemia, vision blurred, lacrimation

increased, eyelid oedema

Cardiac disorders

Very rare: cardiac arrest, bradycardia, tachycardia, arrhythmia, palpitations

Vascular disorders

Very rare: hypotension, hypertension, vasodilatation, pallor

Respiratory, thoracic

and mediastinal

disorders

Very rare: respiratory arrest, pulmonary oedema, bronchospasm,

laryngospasm, pharyngeal oedema, dyspnoea, nasal congestion, sneezing,

cough, dry throat

Gastrointestinal

disorders

Common: nausea, vomiting

Very rare: diarrhoea, abdominal pain, salivary hypersecretion

Skin and subcutaneous

Common: pruritus, erythema, rash

tissue disorders

Rare: urticaria, hyperhidrosis

Very rare: eczema, angioedema

Not known: nephrogenic systemic fibrosis

Musculoskeletal and

connective tissue

disorders

Very rare: muscle contracture, muscular weakness, back pain

General disorders and

administration site

conditions

Common: feeling hot, feeling cold, injection site pain

Very rare : malaise, thoracic pain, chest discomfort, fever, chills, face

oedema, asthenia, injection site discomfort, injection site reaction, injection

site oedema, injection site extravasation, injection site inflammation (in

case of extravasation), injection site necrosis (in case of extravasation),

superficial phlebitis

Investigations

Very rare: decreased oxygen saturation

The following adverse reactions were reported with other intravenous contrast agents for MRI. It is

therefore possible that they also occur during examination with Clariscan

System Organ Class

Adverse reaction

Blood and lymphatic

system disorders

Haemolysis

Psychiatric disorders

Confusion

Eye disorders

Blindness transient, eye pain

Ear and labyrinth

disorders

Tinnitus, ear pain

Respiratory, thoracic

and mediastinal

disorders

Asthma

Gastrointestinal

disorders

Dry mouth

Skin and subcutaneous

tissue disorders

Dermatitis bullous

Renal and urinary

disorders

Urinary incontinence, renal tubular necrosis, renal failure acute

Investigations

Electrocardiogram PR prolongation, blood iron increased, blood bilirubin

increased, serum ferritin increased, liver function test abnormal

Adverse reaction in children

Adverse events related to gadoteric acid are uncommon in children. The expectedness of these events is

identical to that of the events reported 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*.

4.9

Overdose

Clariscan can be removed by haemodialysis. 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 for magnetic resonance imaging

ATC code: V08 CA 02

This product has no specific pharmacodynamic activity.

Gadoteric acid is a paramagnetic agent for Magnetic Resonance Imaging (MRI). The contrast-enhancing

effect is mediated by gadoteric acid which is an ionic gadolinium complex composed out of Gadolinium

oxide

1,4,7,10

tetraazacyclododecane-

N,N’,N’’,N’’’

tetraacetic

acid

(DOTA),

present

meglumine salt.

5.2

Pharmacokinetic Properties

Distribution

After intravenous injection, Clariscan is distributed in the extracellular fluids of the body. The distribution

volume was approx. 18 L which is approximately equal to the volume of extra-cellular fluid. Gadoteric acid

does not bind to proteins like serum albumin.

Gadoteric acid is poorly excreted in the milk and cross slowly

through the placenta barrier.

Biotransformation

No metabolites were detected.

Elimination

Gadoteric acid is eliminated rapidly (89% after 6 h, 95% after 24 h) in unchanged form through the kidneys

by glomerular filtration. Excretion via the feces is negligible. The elimination half-life amounts to about 1.6

hours in patients with a normal renal function.

Special characteristics in patients with renal impairment

In renally impaired patients, the elimination half-life was increased to approximately 5 hours for a

creatinine clearance between 30 and 60 mL/min and approximately 14 hours for a creatinine clearance

between 10 and 30 mL/min.

5.3

Preclinical Safety data

Non-clinical data reveal no special hazard for humans based on conventional studies of safety

pharmacology, repeated dose toxicity, genotoxicity or toxicity to reproduction.

Animal studies have shown negligible secretion (less than 1% of the dose) of gadoteric acid in maternal

milk.

6.

PHARMACEUTICAL PARTICULARS

6.1

List of Excipients

Meglumine

Tetraxetan (DOTA)

Water for injections

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

Bottles

Chemical and physical in-use stability has been demonstrated for 48 hours at room temperature. 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

Vials/bottles: This medicinal product does not require any special storage conditions

Pre-filled syringes: Do not freeze

6.5

Nature and Contents of Container

Clariscan is filled in the following containers:

Vials

Glass vials (type I, colourless) of 10 mL (filled to 5 or 10 mL) and 20 mL (filled to 15 or 20 mL), closed

with halobutyl rubber stopper sealed with caps of aluminium with coloured plastic top. Packed in outer box

of 1 and 10 units.

Pre-filled syringes

Polymer syringe: Poly-cycloolefin, Crystal Clear Polymer (CCP) syringe of 20 mL (filled to 10, 15, and 20

mL), label graduated per mL with tip cap and halobutyl plunger stopper attached to a plunger rod.

Packed in outer box of 1 and 10 units.

Bottles

Glass bottles (type I, colourless) of 50 mL (filled to 50 mL) and 100 mL(filled to 100 mL), closed with

halobutyl rubber stopper sealed with caps of aluminium with coloured plastic top.

Packed in outer box of 1 and 10 units.

Polypropylene bottles of 50 mL (filled to 50 mL) and 100 mL (filled to 100 mL), closed with halobutyl

rubber stopper held in place by a plastic screw cap with pull-off ring and tamper proof ring. Packed in outer

box of 1 and 10 units.

Not all pack sizes may be marketed.

6.6

Special precautions for disposal and other handling

For single use

The solution for injection should be inspected visually prior to use. Only clear solutions free of visible

particles should be used.

Vials and bottles:

- Prepare a syringe with a needle. For vials, remove the plastic

disk. For polypropylene bottles remove the plastic screw cap or top plastic lid by pulling the top ring. After

cleaning the stopper with a pad soaked in alcohol, puncture the stopper with the needle. Withdraw the

quantity of product required for the examination and inject it intravenously.

Prefilled syringes

: Inject intravenously the quantity of product required for the examination.

The remaining contrast medium in the vial/bottle, the connecting lines and all disposable components in the

injector system must be discarded after the examination

The peel-off tracking label on the syringes/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.

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

requirements.

7.

MARKETING AUTHORISATION HOLDER

GE Healthcare AS

Nycoveien 1-2

P.O. Box 4220 Nydalen

NO-0401 OSLO

NORWAY

8.

MARKETING AUTHORISATION NUMBER(S)

<[To be completed nationally]>

9.

DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

<[To be completed nationally]>

10.

DATE OF REVISION OF THE TEXT

2020-11-19

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