Clariscan

Patient Information Leaflet: Read this leaflet carefully before the administration of this medicine because it contains important information for you.

Clariscan, 0.5 mmol/ml, solution for injection
Clariscan, 0.5 mmol/ml, solution for injection in ampoule-syringe
Acidum gadotericum

• Keep this leaflet for future reference.
• If you have any questions, please consult your doctor, radiologist, or pharmacist.
• If you experience any adverse reactions, including those not listed in this leaflet, inform your doctor, radiologist, or pharmacist. See section 4.

Table of Contents

1. What Clariscan is and what it is used for
2. Important information before receiving Clariscan
3. How to use 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 of contrast agents used in magnetic resonance imaging (MRI).

What Clariscan is used for
Clariscan is used to enhance the contrast of images obtained during MRI scans.

Adults, children, and adolescents (from 0 to 18 years of age):

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

Adults, children, and adolescents (from 6 months to 18 years of age):

• Whole-body MRI, including pathological lesions.

Adults:

• Magnetic resonance angiography (MRA) including pathological lesions and stenosis in non-coronary arteries.

This product is intended for diagnostic use only.

How Clariscan works
Clariscan improves the readability of MRI images by enhancing the contrast between the areas being examined and the surrounding tissues. This allows doctors or radiologists to better visualize different parts of the body.

2. Important information before using Clariscan

When not to use Clariscan:

• if the patient is allergic to gadoteric acid or any of the other ingredients of this medicine (listed in section 6).
• if the patient is allergic to medicines containing gadolinium or other contrast agents used in magnetic resonance imaging.

Warnings and precautions
Before the examination, all metallic objects the patient may have on their person must be removed.
The doctor or radiologist should be informed before administering Clariscan if:

• the patient has previously experienced a reaction to a contrast agent during an examination;
• the patient has asthma;
• the patient has previously had an allergic reaction – e.g. to shellfish, hay fever, urticaria (severe itching);
• the patient is being treated with beta-blockers (medicines used to treat heart disorders and blood pressure, such as metoprolol);
• the patient's kidneys are not functioning properly;
• the patient has recently undergone or is scheduled to undergo a liver transplant in the near future;
• the patient has experienced seizures or convulsions, or is being treated for epilepsy;
• the patient has a serious heart disease;
• the patient has a disease affecting the heart or blood vessels;
• the patient has an implanted: cardiac pacemaker, ferromagnetic vascular clip, implant or insulin pump, or if there is any suspicion of the presence of a metallic foreign body, especially in the eye. In all of the above cases, MRI is not recommended.

Before administering Clariscan, inform the doctor or radiologist if any of the above conditions apply to the patient.
Risk of serious adverse reactions
As with other contrast agents used in magnetic resonance imaging (MRI), there is a risk of adverse reactions.
Adverse reactions are usually mild and transient, but they cannot be predicted. However, there is a risk that they may be life-threatening.

• Serious adverse reactions may occur immediately or within 60 minutes after administration of the medicine.
• Adverse reactions may also occur within 7 days after administration of the medicine. The likelihood of an adverse reaction is higher in patients who have previously experienced a hypersensitivity reaction following administration of a contrast agent used in MRI. (See section 4 "Possible adverse effects").
• Before administering Clariscan, inform the doctor or radiologist if a hypersensitivity reaction has occurred in the past. In all such cases, the doctor or radiologist will evaluate the benefit-risk ratio and decide whether Clariscan can be administered to the patient. Administration of Clariscan will be closely monitored by the doctor or radiologist.
  Tests and monitoring
  The referring physician or radiologist may decide to perform a blood test to assess kidney function before administering Clariscan, especially in patients aged 65 years and older.
  Children and adolescents
  Angiography is not recommended in children under 18 years of age.
  Newborns and infants
  Due to immature kidney function in newborns up to 4 weeks of age and infants up to 1 year of age, Clariscan will be administered to such patients only after careful consideration by the physician.
  Use of Clariscan is not recommended during whole-body MRI examinations in children under 6 months of age.
  Clariscan and other medicines
  Inform the referring physician or radiologist about all medicines currently or recently taken by the patient, as well as any medicines the patient plans to take.
  Specifically, inform the referring physician, radiologist, or pharmacist if the patient is currently taking or has recently taken medicines for heart disorders or blood pressure, such as beta-blockers, vasoactive substances, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists.
  Clariscan with food and drink
  Possible adverse effects following administration of agents used to enhance MRI image contrast include nausea and vomiting. The patient should refrain from eating for 2 hours before the examination.
  Pregnancy and breastfeeding
  If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor or radiologist before using this medicine.
  Pregnancy
  Gadoteric acid may cross the placenta. It is not known whether this affects the unborn child. Clariscan must not be used during pregnancy unless the doctor decides it is absolutely necessary.
  Breastfeeding
  The referring physician or radiologist will discuss with the patient whether she can continue breastfeeding or should interrupt it for 24 hours after administration of Clariscan.
  Driving and operating machinery
  There are no available data on the effects of Clariscan on the ability to drive. The possibility of dizziness (a symptom of low blood pressure) and nausea should be considered. If the patient feels unwell after the examination, they should not drive or operate machinery.

3. How to use Clariscan

Administration of Clariscan
Clariscan will be administered as an intravenous injection.
This procedure may be performed in a hospital, outpatient clinic, or private office.
Medical personnel are aware of the precautions to be taken during the procedure
and are also familiar with potential complications that may occur.
Throughout the examination, the patient will be closely monitored by a physician.

• A needle will remain in the patient's vein.
• This allows the physician to rapidly administer life-saving medications if necessary. If the patient experiences an allergic reaction, administration of Clariscan will be immediately stopped.

Recommended dose
The radiologist will determine the appropriate dose for the patient and will supervise the injection of the medication.
Patients with impaired kidney or liver function
Use of Clariscan is not recommended in patients with severe kidney dysfunction, or
in patients who have recently undergone or are scheduled to undergo liver transplantation.
However, if the referring physician or radiologist decides to administer Clariscan:

• the patient should receive only a single dose during the MRI examination,
• the patient should not receive another dose of the medication for at least 7 days.

Use in newborns, infants, children, and adolescents
Use of Clariscan in these patients may be considered after careful evaluation by the referring physician or radiologist.
However, if the referring physician or radiologist decides to administer Clariscan to such patients:

• the patient should receive only a single dose during the MRI examination,
• the patient should not receive another dose of the medication for at least 7 days. Whole-body MRI scanning with Clariscan is not recommended in children under 6 months of age. Use in angiography is not recommended in children under 18 years of age.

Elderly patients
Dose adjustment is not required for patients aged 65 years and older; however, blood tests to assess kidney function may be necessary.
Administration of a higher than recommended dose of Clariscan
It is highly unlikely that a patient would receive an excessive dose of the medication.
Clariscan will be administered in a medical facility by appropriately trained personnel.
In the event of actual overdose, Clariscan may be removed from the body by hemodialysis (blood purification).
Additional information on the use and handling of this medication by medical personnel is provided at the end of this leaflet.
If you have any further questions regarding the use of this medication, please consult your referring physician or radiologist.

4. Possible adverse reactions

Like any medicine, this medicine can cause adverse reactions, although not everyone will experience them.
After administration, the patient will be monitored for at least half an hour.
Most adverse reactions occur immediately or with some delay. Some adverse reactions may even occur several days after injection of Clariscan.

There is a small risk that the patient may experience an allergic reaction following administration of Clariscan.
Such reactions may be severe and may lead to shock (a type of allergic reaction that may be life-threatening).

The following symptoms may be early signs of shock. If the patient notices any of the symptoms listed below, they should immediately inform the referring physician, radiologist, or other medical personnel:

• swelling of the face, lips and/or throat, which may cause difficulty in swallowing or breathing,
• swelling of hands or feet,
• dizziness (hypotension),
• difficulty breathing,
• wheezing,
• coughing,
• itching,
• runny nose,
• sneezing,
• eye irritation,
• hives,
• skin rash.

Uncommon adverse reactions (may occur in 1 to 10 patients in 1000)

• hypersensitivity,
• headache,
• unusual taste in the mouth,
• dizziness,
• drowsiness,
• tingling sensation, feeling of warmth, cold and/or pain,
• low or high blood pressure,
• nausea,
• abdominal pain,
• rash,
• feeling of warmth, feeling of cold,
• asthenia (chronic fatigue),
• discomfort at injection site, reaction at injection site, feeling of cold at injection site, swelling at injection site, extravasation (leakage of medicine outside blood vessels), which may lead to inflammation (redness and local pain).

Rare adverse reactions (may occur in 1 to 10 patients in 10,000)

• anxiety, fainting (dizziness and feeling of impending loss of consciousness),
• eyelid swelling,
• palpitations,
• sneezing,
• vomiting,
• diarrhoea,
• increased salivation,
• hives, itching, sweating,
• chest pain, chills.

Very rare adverse reactions (may occur in fewer than 1 in 10,000 patients)

• anaphylactic or anaphylactoid reactions,
• restlessness,
• coma, seizures, fainting (short-term loss of consciousness), disturbances of smell (often perceiving unpleasant odours), tremor,
• conjunctivitis, eye redness, blurred vision, increased tear production,
• cardiac arrest, rapid or slow heartbeat, irregular heartbeat, blood vessel dilation, pale skin,
• respiratory arrest, pulmonary oedema, breathing difficulties, wheezing, nasal congestion, cough, dry throat, throat tightness with sensation of suffocation, bronchospasm, throat swelling,
• rash, skin redness, lip swelling and localized swelling in the oral cavity,
• muscle spasms, muscle weakness, back pain,
• malaise, chest discomfort, fever, facial swelling, extravasation of product outside blood vessels, which may lead to tissue necrosis at the injection site, phlebitis,
• decreased oxygen level in the blood.

There have been reports of nephrogenic systemic fibrosis (NSF), which causes hardening of the skin and may also affect soft tissues and internal organs. Most cases have occurred in patients who received gadoteric acid together with other contrast agents containing gadolinium. You should inform the radiologist who performed the examination if, within several weeks after the MRI scan, you notice changes in skin colour and/or thickness anywhere on the body.

Reporting of adverse reactions

If any adverse reactions occur, including any not listed in this leaflet, you should inform your doctor, pharmacist, or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:

Al. Jerozolimskie 181C
02-222 Warsaw
Tel: 22 49-21-301
Fax: 22 49-21-309
Website: https://smz.ezdrowie.gov.pl

Adverse reactions may also be reported to the marketing authorization holder.

By reporting adverse reactions, additional information on the safety of this medicine can be collected.

5. How to store Clariscan

Keep this medicine out of the sight and reach of children.
Vials and bottles: No special requirements for storage of the medicinal product.
Prefilled syringe: Do not freeze.
Do not use this medicine after the expiry date stated on the vial, bottle, prefilled syringe, or carton after "EXP". The expiry date refers to the last day of the month indicated. The batch number is indicated after "Lot".
Chemical and physical in-use stability of the medicinal product has been demonstrated for 48 hours at 30°C. From a microbiological point of view, the medicinal product should be used immediately. If the medicinal product is not used immediately, the user is responsible for ensuring appropriate storage time and conditions prior to administration; typically this should not exceed 24 hours at 2°C – 8°C, unless the medicinal product has been opened under controlled and validated aseptic conditions.
Medicines must not be disposed of via the sewage system or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

What Clariscan contains

• The active substance is gadoteric acid. Each millilitre of injection solution contains 279.32 mg of gadoteric acid (as the meglumine salt), equivalent to 0.5 mmol of gadoteric acid.
• The other components are: meglumine, tetraxetan (DOTA), and water for injections.

What Clariscan looks like and contents of the pack
Clariscan is a clear, colourless to pale yellow solution for intravenous injection.
Clariscan is available in the following pack sizes:
Vials made of colourless type I glass containing 5, 10, 15 or 20 ml of medicinal product,
Polymer vial-syringes containing 10, 15 or 20 ml of medicinal product,
Bottles made of colourless type I glass or polypropylene bottles containing 50 or 100 ml of medicinal product,
Packed in units of 1 or 10 in individual cardboard cartons.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
GE Healthcare AS
Nycoveien 1
0485 Oslo
Norway

Manufacturer
GE Healthcare Ireland Limited
IDA Business Park
Carrigtwohill
Cork
Ireland

Information intended exclusively for healthcare professionals:

Dosage

Adults

MRI of the brain and spinal cord
The recommended dose is 0.1 mmol/kg body weight, equivalent to 0.2 ml/kg body weight. In patients with brain tumours, administration of an additional dose of 0.2 mmol/kg body weight (equivalent to 0.4 ml/kg body weight) may improve tumour visibility and facilitate treatment decisions.

Whole-body MRI (lesions in the liver, kidneys, pancreas, pelvis, lungs, heart, breast, and musculoskeletal system)
The recommended dose providing contrast suitable for diagnosis is 0.1 mmol/kg body weight, equivalent to 0.2 ml/kg body weight.

Angiography: The recommended intravenous dose providing contrast suitable for diagnosis is 0.1 mmol/kg body weight, equivalent to 0.2 ml/kg body weight.

In exceptional circumstances (e.g., when satisfactory image quality covering a large vascular area is not achieved), administration of a second, sequential dose of 0.1 mmol/kg body weight (equivalent to 0.2 ml/kg body weight) may be justified. However, if two sequential doses of Clariscan are anticipated before starting the angiography, it may be beneficial to administer 0.05 mmol/kg body weight (equivalent to 0.1 ml/kg body weight) per dose, depending on the available imaging equipment.

Special patient populations

Renal impairment
The adult dose applies to patients with mild to moderate renal impairment (GFR ≥ 30 ml/min/1.73 m²).

Clariscan should be used in patients with severe renal impairment (GFR < 30 ml/min/1.73 m²) and in patients during the perioperative period of liver transplantation only after careful benefit-risk assessment and only when diagnostic information is essential and cannot be obtained by non-contrast MRI. If Clariscan must be used, the dose should not exceed 0.1 mmol/kg body weight. No more than one dose should be administered during a single imaging procedure. Due to lack of data on repeated administration, Clariscan injections should not be repeated unless the interval between doses is at least 7 days.

Elderly patients (aged 65 years and above)
Dose adjustment is not considered necessary. Caution should be exercised in elderly patients.

Hepatic impairment
The adult dose is recommended for patients with hepatic impairment. Caution is advised, particularly during the perioperative period of liver transplantation (see also section "Renal impairment" above).

Children and adolescents (aged 0 to 18 years)

MRI of the brain and spinal cord / Whole-body MRI:
The recommended and maximum dose of Clariscan is 0.1 mmol/kg body weight.

No more than one dose should be administered during a single scanning session. Whole-body scanning is not recommended in children under 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 be used in these patients only after careful physician evaluation, at a dose not exceeding 0.1 mmol/kg body weight. No more than one dose should be administered during a single scanning session. Due to lack of data on repeated administration, Clariscan injections should not be repeated unless the interval between doses is at least 7 days.

Angiography:
Clariscan is not indicated for use in angiography in children under 18 years of age due to insufficient data on efficacy and safety for this indication.

Administration method
This product is indicated for intravenous use only.

Infusion rate: 3–5 ml/min (in angiographic procedures, higher infusion rates up to 120 ml/min, i.e., 2 ml/sec, may be used). For instructions on preparation and disposal of the medicinal product, see warnings and precautions for use below.

Children and adolescents (0–18 years)
Depending on the volume of Clariscan to be administered to a child, it is recommended to use vials of Clariscan in combination with a single-use syringe of appropriate capacity to ensure higher precision of the administered dose.

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

Warnings and precautions for use

Renal impairment
All patients should undergo laboratory tests to assess renal function before administration of Clariscan.

There have been reports of nephrogenic systemic fibrosis (NSF) associated with the use of gadolinium-containing contrast agents in patients with acute or chronic renal impairment (GFR < 30 ml/min/1.73 m²). Patients undergoing liver transplantation are at particular risk due to the high incidence of acute renal failure in this group. Because of the risk of NSF associated with Clariscan, its use in patients with severe renal impairment and in patients during the perioperative period of liver transplantation should be restricted to cases where a careful benefit-risk assessment has been performed and when diagnostic information is essential and cannot be obtained by non-contrast MRI.

Since renal clearance of Clariscan may be reduced in elderly patients, assessment of renal function prior to administration is particularly important in patients aged 65 years and above.

Haemodialysis shortly after administration of Clariscan may facilitate elimination of the agent from the body. There is no evidence to support initiating haemodialysis for prophylaxis or treatment of NSF in patients not currently undergoing haemodialysis.

Pregnancy and breastfeeding

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

Continuation or interruption of breastfeeding for 24 hours after administration of Clariscan should be decided by the physician or radiologist and the breastfeeding mother.

Instructions for use of the product

For single use only.

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

Vials and bottles:

• Prepare a syringe with a needle. Remove the plastic disc from the vial.
• On the polypropylene bottle, unscrew the plastic cap or remove the top plastic overcap. After cleaning the stopper with an alcohol swab, pierce it with a needle. Withdraw the volume of medicinal product required for the examination and administer it intravenously to the patient.

Prefilled syringes: Administer intravenously the volume of product required for the examination.

Any unused remnants of the medicinal product remaining in the vial/bottle, materials used during administration, and components of the prefilled syringe must be discarded after the examination.

Removable identification labels:
Removable identification labels from prefilled syringes, vials, and bottles should be attached to the patient's medical record to allow accurate identification of the gadolinium-containing contrast agent used. The administered dose should also be recorded. When using an electronic patient record, the product name, batch number, and administered dose should be entered.

Any unused medicinal product or waste material must be disposed of in accordance with local regulations.