Patient Information Leaflet

Clariscan 0.5 mmol/mL Injectable Solution EFG

Clariscan 0.5 mmol/mL Injectable Solution in Pre-filled Syringe EFG

Gadoteric Acid

Read this leaflet carefully before you start using the medicine because it contains important information for you.

? Keep this leaflet, as you may need to read it again.

? If you have any questions, consult your doctor, radiologist or pharmacist.

? If you experience any side effects, consult your doctor, radiologist or pharmacist, even if they are not listed in this leaflet. See section 4.

1. What is Clariscan and what it is used for

2. What you need to know before starting to use Clariscan

3. How to use Clariscan

4. Possible side effects

5. Storage of Clariscan

6. Contents of the pack and additional information

What is Clariscan

Clariscan contains gadoteric acid as the active ingredient. It belongs to the group called “contrast media” used in magnetic resonance imaging (MRI) studies.

What is Clariscan used for

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

For adults and children and adolescents from 0 to 18 years:

• MRI of the central nervous system (CNS) including defects (lesions) of the brain, spinal cord, and surrounding tissues

For adults and children and adolescents from 6 months to 18 years:

• MRI of the entire body including defects (lesions)

For adults only:

• MRI angiography including defects (lesions) or narrowing (stenosis) of arteries, except for coronary arteries.

This medication is solely for diagnostic use.

How Clariscan works

Clariscan makes it easier to see images obtained through MRI. This is achieved by increasing the contrast between the body part to be seen and the rest of the body. In this way, doctors or radiologists can see better the different parts of the body.

You should not be given Clariscan:

• if you are allergic to gadoteric acid or any of the other components of this medication (listed in section 6).
• if you are allergic to any medication that contains gadolinium or other contrast agents used in MRI studies.

Warnings and precautions

Remove all metal objects you may be wearing before the examination.

Consult your doctor or radiologist before using Clariscan if:

• you have previously had a reaction to a contrast agent during an examination.
• you have asthma.
• you have a history of allergies, such as shellfish allergy, hay fever, urticaria (intense itching).
• you are being treated with a beta-blocker (a medication used for heart or blood pressure problems such as metoprolol).
• your kidneys do not function properly.
• you have recently had or will soon have a liver transplant.
• you have had seizures or are being treated for epilepsy.
• you have a serious heart problem.
• you have a heart or blood vessel disease.
• you have a pacemaker, iron clip (ferromagnetic), implant, or insulin pump, or suspect having any metal foreign body, especially in the eye. In these cases, MRI is not suitable.

Speak with your doctor or radiologist if you are in any of the above cases before using Clariscan.

Risk of severe adverse effects

As with any contrast agent used for MRI, there is a risk of adverse effects. Adverse effects are usually mild and temporary, but cannot be predicted. However, there is a risk that could put your life in danger:

• adverse effects may appear immediately after or within an hour of using this medication.
• some adverse effects may appear up to 7 days after treatment. Adverse effects are more likely if you have ever had a reaction to a contrast agent used for MRI in the past (see section 4 “Possible adverse effects”).
• inform your doctor or radiologist before using Clariscan if you have had a reaction in the past. Your doctor or radiologist will only administer Clariscan if the benefits outweigh the risks. If they administer Clariscan, your doctor or radiologist will closely monitor you.

Analysis and controls

Your doctor or radiologist may decide to perform a blood test before you receive Clariscan, especially if you are over 65 years old. This test is to check the proper functioning of your kidneys.

Children and adolescents

Clariscan is not recommended for use in children under 18 years old for angiography.

Newborns and breastfeeding women

Your doctor or radiologist will carefully consider whether your baby can receive Clariscan. This is due to the immaturity of the kidneys in newborns up to 4 weeks and in breastfeeding women up to 1 year.

Clariscan is not recommended for use in children under 6 months old for whole-body MRI.

Use of Clariscan with other medications

Inform your doctor or radiologist if you are taking, have taken recently, or may need to take any other medication.

Particularly, inform your doctor, radiologist, or pharmacist if you are taking or have taken recently medications for the heart and blood pressure, such as beta-blockers, angiotensin-converting enzyme inhibitors, or angiotensin II receptor antagonists.

Use of Clariscan with food and drinks

The administration of contrast agents for MRI may cause nausea and vomiting as adverse effects. Therefore, the patient should remain fasting for 2 hours before the examination.

Pregnancy and breastfeeding

Pregnancy

Gadoteric acid can cross the placenta. Its effect on the fetus is unknown. Clariscan should not be used during pregnancy unless strictly necessary. If you are pregnant or breastfeeding, or suspect you may be pregnant, consult your doctor or radiologist before using this medication.

Breastfeeding

Inform your doctor or radiologist if you are breastfeeding or planning to start. Your doctor or radiologist will assess with you whether you should continue or interrupt breastfeeding for 24 hours after administering Clariscan.

Driving and operating machinery

There are no available data on the effects of Clariscan on driving ability. However, if you drive or operate machinery, be aware of the possible appearance of dizziness (low blood pressure symptom) and nausea. If you feel unwell after the examination, do not drive or operate machinery.

How Clariscan is administered

Clariscan will be administered to you through an intravenous injection.

The administration will take place in a hospital, clinic or private clinic.

The medical staff knows the precautions that must be taken.

They also know the possible complications that may occur.

During the test, you will be under the supervision of your doctor or radiologist.

• You will be left with a needle in the vein,
• This will allow the doctor or radiologist to inject emergency medications if necessary.

If you experience an allergic reaction, the doctor or radiologist will stop the administration of Clariscan.

Dosage

Your doctor or radiologist will determine the dose of Clariscan you will receive and supervise the injection.

Patients with liver or kidney problems

The use of Clariscan is not recommended in patients with severe renal problems or in patients who have recently undergone or will soon undergo a liver transplant.

However, if your doctor or radiologist decides to administer Clariscan:

• You should receive a single dose of Clariscan during the MRI and
• You should not receive a second injection until at least 7 days have passed.

Newborns, infants, children and adolescents

Clariscan should only be used in these patients after careful consideration by the doctor or radiologist. However, if your doctor or radiologist decides to administer Clariscan to your child:

• You should receive a single dose of Clariscan in an MRI examination and
• You should not receive a second injection until at least 7 days have passed.

In children under 6 months of age, its use for whole-body MRI is not recommended.

Its use for angiography is not recommended in children under 18 years old.

Older patients

If you are 65 years old or older, it is not necessary to adjust the dose. However, it is possible that you will have a blood test first to check the proper functioning of your kidneys.

If too much Clariscan has been administered

It is highly unlikely that you will receive an overdose, as you will receive Clariscan in a medical center by a trained person.

In a real case of overdose, Clariscan can be removed from the body by hemodialysis (blood cleansing).

At the end of this prospectus, additional information is provided regarding use and management for doctors and healthcare professionals.

If you have any other questions about the use of this medication, ask your doctor or radiologist.

Like all medicines, this one may cause side effects, although not everyone will experience them.

After administration, you will be under observation for at least half an hour. Most side effects occur immediately or may be delayed. Some effects may occur up to seven days after the Clariscan injection.

There is a small risk (rare) that you may have an allergic reaction to Clariscan.These reactions can be severe andmay cause shock(an allergic reaction that could put your life in danger).

Any of the following symptoms may be the first signs of shock. Inform your doctor, radiologist, or healthcare professional immediately if you experience any of them.

• Swelling of the face, mouth, or throat that may cause difficulty swallowing or breathing
• Swelling of the hands or feet
• Dizziness (hypotension)
• Difficulty breathing
• Wheezing while breathing
• Coughing
• Itching
• Runny nose
• Stuffy nose
• Irritation of the eyes
• Tickling in the throat
• Rash

Less common side effects: may affect up to 1 in 100 people

• Hyper-sensitivity
• Headaches
• Unusual taste in the mouth
• Dizziness
• Drowsiness
• Sensation of tingling, heat, cold, and/or pain
• High or low blood pressure
• Nausea (feeling unwell)
• Abdominal pain
• Rashes
• Sensation of heat, sensation of cold
• Weakness
• Discomfort at the injection site, reaction at the injection site, cold at the injection site, inflammation at the injection site, diffusion of the product outside the blood vessels that may cause inflammation (redness and pain at the local site).

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

• Anxiety, fainting (dizziness and sensation of impending loss of consciousness)
• Swelling of the eyelids
• Palpitations
• Runny nose
• Vomiting (feeling unwell)
• Diarrhea
• Increased salivation
• Tickling, itching, sweating
• Chest pain, chills

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

• Anaphylactic or anaphylactoid reactions
• Agitation
• Coma, convulsions, syncope (brief loss of consciousness), alteration of the sense of smell (perception of unpleasant odors), tremors
• Conjunctivitis, red eyes, blurred vision, increased tear secretion
• Cardiac arrest, rapid or slow heartbeat, irregular heartbeat,
  vascular dilation, pallor
• Respiratory arrest, pulmonary edema, difficulty breathing, , wheezing, nasal congestion, coughing, dry throat, constriction of the throat with sensation of choking, respiratory spasms, inflammation of the throat
• Eczema, redness of the skin, inflammation of the lips and localized in the mouth
• Muscle cramps, muscle weakness, back pain
• Uncomfortable feeling
• Uncomfortable feeling in the chest
• Fever
• Swelling of the face
• , diffusion of the product outside the blood vessels that may cause inflammation or destruction of skin cells at the injection site
• Decreased oxygen in the blood

Systemic nephrogenic fibrosis (which causes skin hardening and may also affect soft tissues and internal organs) has been reported, most of which occurred in patients who received gadoteric acid along with other contrast agents containing gadolinium. If, during the weeks following the MRI, you notice changes in the color and/or thickness of your skin anywhere on your body, inform the radiologist who performed the exam.

Reporting of side effects

If you experience side effects, consult your doctor or radiologist, even if they are side effects that do not appear in this prospectus.

You can also report them directly through the Spanish System of Pharmacovigilance of Medicines for Human Use:https://www.notificaram.es.By reporting side effects, you can contribute to providing more information on the safety of this medication.

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

The vials/bottles do not require special storage conditions.

The pre-filled syringe should not be frozen.

Do not use this medication after the expiration date that appears on the vial, in the bottle, on the pre-filled syringe, or on the box, after “CAD”.

The expiration date is the last day of the month indicated.

Chemical and physical stability has been demonstrated for use over a period of 48 hours at 30°C. From a microbiological standpoint, the product should be used immediately. If not used immediately, storage times and conditions before use are the responsibility of the user and should normally not exceed 24 hours at 2 to 8°C, unless the opening has taken place in controlled and validated aseptic conditions.

Composition of Clariscan

• The active principle is gadoteric acid. One mL of injectable solution contains 279.32 mg of gadoteric acid (in the form of meglumine gadoterate), equivalent to 0.5 mmol of gadoteric acid.

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

Appearance of the product and contents of the package

Clariscan is a transparent, colorless to yellowish solution for intravenous injection.

Clariscan is available in the following packages:

Glass vials (Type 1, colorless) filled with 5, 10, 15, and 20 mL.

Pre-filled syringes made of polymer filled with 10, 15, and 20 mL.

Colorless glass vials (Type 1) and polypropylene vials filled with 50 and 100 mL.

All packages are packaged in an outer box of 1 and 10 units.

Only some package sizes may be marketed.

Marketing Authorization Holder

GE Healthcare Bio-Sciences, S.A.U.

Calle Gobelas, 35-37, La Florida

28023 Madrid

Responsible for manufacturing

GE Healthcare AS

Nycoveien 1-2

P.O. P.O. Box 4220 Nydalen

NO-0401 Oslo

Norway

or

GE Healthcare Ireland Limited

IDA Business Park

Carrigtwohill, Cork

Ireland

This leaflet was last revised in: May 2024

This information is intended solely for medical professionals or healthcare professionals:

Dosage

Adults

Brain and spinal cord MRI

The recommended dose is 0.1 mmol/kg of body weight (b.w.), equivalent to 0.2 mL/kg b.w. In patients with brain tumors, an additional dose of 0.2 mmol/kg b.w. (equivalent to 0.4 mL/kg b.w.) may improve tumor characterization and facilitate therapeutic decision-making.

Whole-body MRI (including liver, kidney, pancreas, pelvis, lung, heart, breast, and musculoskeletal system MRI)

The recommended dose is 0.1 mmol/kg b.w. (equivalent to 0.2 mL/kg b.w.) to provide adequate contrast for diagnosis.

Angiography:The recommended dose for intravenous injection is 0.1 mmol/kg b.w. (equivalent to 0.2 mL/kg b.w.) to provide adequate contrast for diagnosis.

In exceptional circumstances (e.g., when obtaining satisfactory images of an extensive vascular territory is impossible), a second consecutive injection of 0.1 mmol/kg b.w. (equivalent to 0.2 mL/kg b.w.) may be justified. However, if two consecutive doses of Clariscan are to be administered before starting angiography, it may be advisable to administer only 0.05 mmol/kg b.w. (equivalent to 0.1 mL/kg) for each dose, depending on the MRI equipment to be used to obtain the images.

Special populations

Renal insufficiency

The adult doses apply to patients with mild to moderate renal insufficiency(GFR ≥ 30 ml/min/1.73m2).

Clariscan should only be used in patients with severe renal insufficiency (TFG or glomerular filtration rate <30)2) and in patients in the perioperative period of a liver transplant, after a careful assessment of the risk-benefit ratio and if the diagnostic information is essential and cannot be obtained by MRI without contrast. If Clariscan is necessary, the dose should not exceed 0.1 mmol/kg of body weight.

During an examination, no more than one dose should be administered. Due to the lack of information on repeated administration, the administration of Clariscan should not be repeated unless at least 7 days have elapsed between injections.

Geriatric population (population aged 65 years and older)

No dose adjustment is considered necessary. Caution should be exercised in elderly patients.

Liver insufficiency:

The adult dose applies to these patients. Caution is recommended, especially in the perioperative period of a liver transplant (see above renal insufficiency).

Pediatric population (population aged 0 to 18 years)

Brain and spinal cord MRI, whole-body MRI:

The maximum recommended dose of Clariscan is 0.1 mmol/kg of body weight. No more than one dose should be used in a single examination.

In children under 6 months of age, its use is not recommended for whole-body MRI.

Due to the immaturity of renal function in newborns up to 4 weeks and in infants up to 1 year of age, Clariscan should only be used in these patients after careful consideration, with a dose not exceeding 0.1 mmol/kg of body weight. No more than one dose should be administered in a single examination. Due to the lack of information on repeated administration, the administration of Clariscan should not be repeated unless at least 7 days have elapsed between injections.

Angiography:

Clariscan is not recommended for angiography in children under 18 years of age because the data on safety and efficacy in this indication are insufficient.

Administration

This product is administered only by intravenous injection.

Infusion rate: 3-5 mL/min (infusion rates greater than 120 mL/min, equivalent to 2 mL/sec, may be used in angiographic procedures).

To consult the instructions on preparation and disposal, see the sectionPrecautions for use and handlingbelow.

Pediatric population (population aged 0 to 18 years). Depending on the amount of Clariscan administered to the child, it is preferable to use Clariscan vials with a single-use syringe and a volume adapted to that amount to control the injected volume more precisely.

In newborns and infants, the required dose should be administered manually.

Special warnings and precautions for use

Renal insufficiency

Before administering Clariscan, it is recommended to evaluate all patients to detect possible renal dysfunction by laboratory tests.

Cases of systemic fibrosis nephrogenica (FNS) associated with the use of some gadolinium-based contrast media in patients with severe acute or chronic renal insufficiency (TFG or glomerular filtration rate <30)2) have been reported. Patients undergoing liver transplantation have a special risk since the incidence of acute renal failure is high in this group. Since there is a possibility that FNS may occur with Clariscan, it should only be used in patients with severe renal insufficiency and in patients in the perioperative period of a liver transplant after a careful assessment of the risk-benefit ratio and if the diagnostic information is essential and cannot be obtained by MRI without contrast.

Since renal elimination of Clariscan may be reduced in elderly patients, it is especially important to evaluate patients aged 65 or older to detect possible renal dysfunction.

Haemodialysis shortly after administration of Clariscan may be useful for the elimination of Clariscan from the body. There is no evidence to support the initiation of haemodialysis for the prevention or treatment of FNS in patients not undergoing haemodialysis.

Pregnancy and lactation

Clariscan should not be used during pregnancy unless the woman's clinical condition requires treatment with gadoteric acid.

The decision to continue or discontinue breastfeeding 24 hours after administration of Clariscan will be at the discretion of the doctor and the breastfeeding woman.

Precautions for use and handling

For single use

The injectable solution should be visually inspected before use. Only solutions without visible particles should be used.

Vials and vials:Prepare a syringe with a needle. In vials, remove the plastic disk. In polypropylene vials, remove the plastic screw cap or the upper plastic cap. After cleaning the cap with a dampened cotton swab in alcohol, pierce the cap with the needle. Extract the required amount of product for the examination and inject intravenously.

Pre-filled syringes:Inject the required amount of product for the examination intravenously.

The contrast medium remaining in the vial/vial, the connection lines, and all disposable components of the injector system should be disposed of after the examination.

The detachable label on the vials, vials, or syringes should be stuck to the patient's medical history to allow for precise recording of the gadolinium-based contrast medium used. The dose used should also be recorded. If electronic patient history is used, the name of the drug, batch number, and dose should be included in the same.

The unused medication or excess materials should be disposed of in accordance with local regulations.