Claricyclic

PATIENT LEAFLET: INFORMATION FOR THE PATIENT

Claricyclic 0,5 mmol/mL injectable solution, 0,5 mmol/mL pre-filled syringe injectable solution

Gadoteridic acid
Generic medicine
Please read 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 questions, ask your doctor, radiologist, or pharmacist.
• If you experience any side effects, including those not listed in this leaflet, inform your doctor, radiologist, or pharmacist. See section 4. Contents of this leaflet:
  1. What Claricyclic is and what it is used for
  2. What you need to know before using Claricyclic
  3. How to use Claricyclic
  4. Possible side effects
  5. How to store Claricyclic
  6. Contents of the pack and other information

1. What Claricyclic is and what it is used for

What Claricyclic is
Claricyclic contains the active substance gadoteridic acid. It belongs to a group called "contrast agents" and is used for magnetic resonance imaging (MRI).
What Claricyclic is used for
Claricyclic is used to enhance the contrast of images obtained during MRI scans.
In adults and children and adolescents aged 0 to 18 years:

• MRI of the central nervous system (CNS), including brain, spinal and adjacent tissue abnormalities (lesions);
  In adults and children and adolescents aged 6 months to 18 years:

• Whole-body MRI, including abnormalities (lesions).

For adults only:

• MR angiography, including abnormalities (lesions) or narrowing (stenosis) of arteries, except coronary arteries. This medicine is for diagnostic use only.

How Claricyclic works
Claricyclic facilitates visualization of images on an MRI scanner by increasing the contrast between the area being examined and the rest of the body. This enables the doctor or radiologist to better observe different areas of the body.

2. What you need to know before using Claricyclic

Do not use Claricyclic:

• if you are allergic to gadoteric acid or to any of the other ingredients of this medicine (listed in section 6);
• if you are allergic to medicines containing gadolinium or to other contrast agents used for MRI.

Warnings and precautions
Before the examination, remove all metallic objects you may be wearing.
Consult your doctor or radiologist before receiving Claricyclic if:

• you have previously had a reaction to a contrast agent during an examination;
• you suffer from asthma;
• you have a history of allergies, such as allergy to shellfish, hay fever, or hives (severe itching);
• you are taking a beta-blocker (a medicine for heart problems or high blood pressure such as metoprolol);
• your kidneys are not functioning properly;
• you have recently undergone or are scheduled to undergo a liver transplant in the near future;
• you have suffered from seizures (epilepsy or convulsions) or are being treated for epilepsy;
• you suffer from severe heart disorders;
• you suffer from heart or blood vessel disorders;
• you have a cardiac pacemaker implant, a ferromagnetic clip, an insulin pump or device, or suspected metallic foreign bodies, particularly in the eye. These conditions make MRI unsuitable.

Inform your doctor or radiologist if any of the above apply to you before receiving Claricyclic.
Risk of serious side effects
As with all MRI contrast agents, there is a risk of adverse effects. These side effects are generally mild and temporary, but unpredictable. However, they may be life-threatening:

• serious possible side effects may occur immediately or within one hour after administration of the medicine;
• side effects may occur up to 7 days after treatment. Side effects are more likely if you have previously had a reaction to another contrast agent (see section 4 “Possible side effects”);
• Inform your doctor or radiologist before receiving Claricyclic if you have had a previous reaction. Your doctor or radiologist will administer Claricyclic only if the benefits outweigh the risks. If Claricyclic is administered, you will be closely monitored by the doctor or radiologist.

Tests and monitoring
Your doctor or radiologist may decide to perform a blood test before administering Claricyclic, especially if you are over 65 years of age. This is to check how well your kidneys are functioning.
Children and adolescents
Use in angiography is not recommended in children under 18 years of age.
Newborns and infants
Your doctor or radiologist will carefully assess whether your child can receive Claricyclic, as kidneys are immature in newborns up to 4 weeks of age and in children up to 1 year of age.
Use in whole-body MRI is not recommended in children under 6 months of age.
Other medicines and Claricyclic
Inform your doctor or radiologist if you are taking, have recently taken, or might take any other medicines.
In particular, inform your doctor or radiologist if you are currently taking or have recently taken any of the following medicines for heart conditions or high blood pressure:

• beta-blockers – medicines that slow heart rate (e.g. metoprolol), medicines that widen (dilate) blood vessels and reduce blood pressure: vasoactive substances (e.g. doxazosin), angiotensin-converting enzyme (ACE) inhibitors (e.g. ramipril), angiotensin II receptor antagonists (e.g. valsartan).

Inform your doctor or radiologist if you are taking or have recently taken any of the medicines listed above.
Claricyclic with food and drink
Nausea and vomiting are known possible side effects associated with the use of MRI contrast agents. Therefore, patients should refrain from eating food within the 2 hours preceding the examination.
Pregnancy and breastfeeding
Pregnancy
Inform your doctor or radiologist if you are pregnant, suspect you may be pregnant, or are planning a pregnancy.
Claricyclic should not be administered during pregnancy unless your doctor considers it necessary.
Breastfeeding
Inform your doctor or radiologist if you are breastfeeding or about to start breastfeeding. Your doctor or radiologist will discuss with you whether or not to continue breastfeeding. You may need to interrupt breastfeeding for 24 hours after receiving Claricyclic.
Driving and using machines
There are no data available on the ability to drive vehicles. However, when driving or using machinery, consider the possible occurrence of dizziness (a symptom of low blood pressure) and nausea. If you do not feel well after the examination, do not drive vehicles and do not operate tools or machines.

3. How to use Claricyclic

How Claricyclic is administered
Claricyclic is administered via intravenous injection.
The injection is given in a hospital, clinic, or private practice setting.
Medical personnel are aware of the precautions that must be taken.
They are also familiar with potential complications that may occur.
During the procedure, you will remain under the supervision of the physician or radiologist.

• A venous needle will be left in place.
• This will allow the physician or radiologist to administer emergency medications if necessary.

In the event of an allergic reaction, the physician or radiologist will discontinue the administration of Claricyclic.
Dose administered
The physician or radiologist will determine the dose of Claricyclic to be administered and will monitor the injection.
Patients with liver or kidney problems
The use of Claricyclic is not recommended in patients with severe kidney problems or in patients who have recently undergone or are scheduled to undergo liver transplantation in the near future.
However, if the physician or radiologist decides to administer Claricyclic:

• you will receive only one dose of Claricyclic during the MRI examination, and
• you must not receive a second injection until at least 7 days have passed.

Newborns, infants, children, and adolescents
Claricyclic will be used in these patients only after careful evaluation by the physician or radiologist. If the physician or radiologist decides to administer Claricyclic to your child:

• your child will receive only one dose of Claricyclic during the MRI examination, and
• your child must not receive a second injection until at least 7 days have passed.

Use in whole-body MRI is not recommended in children under 6 months of age.
Use for angiography is not recommended in children under 18 years of age.
Elderly patients
The dosage does not change if you are 65 years of age or older. However, a blood test may be performed to assess whether the patient's kidneys are functioning properly.
What to do if you have received an overdose of Claricyclic
It is highly unlikely that an overdose would occur, as Claricyclic is administered in a medical setting by a qualified person.
In the event of an actual overdose, Claricyclic can be removed from the body by blood washing ("hemodialysis").
Further information on use and management by the specialist or healthcare professional can be found at the end of this leaflet.
If you have any further questions about the use of this medicine, please consult your physician or radiologist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
After administration, you will be monitored for at least half an hour.
Most side effects occur immediately or shortly after administration of the medicine. Some effects may appear up to several days after injection of Claricyclic.
There is a modest (rare) risk of developing an allergic reaction to Claricyclic. These reactions can be serious and very rarely cause "shock" (a very rare type of allergic reaction that may be life-threatening). The symptoms listed below may be the first signs of shock.
Inform the radiologist or healthcare professional immediately if you experience any of the following signs – urgent medical treatment may be required:

• swelling of the face, mouth or throat, which may cause difficulty in swallowing or breathing
• swelling of the hands or feet
• low blood pressure (hypotension - feeling of weakness)
• breathing problems, including wheezing
• cough
• itching
• runny nose
• sneezing and irritated eyes
• red spots on the skin, severe itching (urticaria)

Other side effects
Inform your doctor or radiologist if you notice any of the following side effects:
Very common: may affect more than 1 in 10 people

• headache
• tingling sensation

Common: may affect up to 1 in 10 people

• sensation of heat, cold or pain at the injection site
• nausea (feeling unwell), vomiting (feeling sick)
• skin redness, 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
• urticaria (red spots on the skin, severe itching (urticaria))
• increased sweating

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

• feeling agitated or anxious
• coma, convulsions, syncope (brief loss of consciousness), weakness (dizziness and feeling faint), dizziness, changes in smell (frequent perception of unpleasant odours), tremor
• conjunctivitis, red eyes, blurred vision, increased tear production, eye swelling
• cardiac arrest, fast or slow heartbeat, irregular heartbeat, palpitations, low or high blood pressure, widening or relaxation of blood vessels (vasodilation) leading to a drop in blood pressure and a slowed heartbeat, pallor
• sudden cessation of breathing (respiratory arrest), fluid accumulation in the lungs (pulmonary edema), breathing difficulties, sensation of a lump in the throat, laboured breathing, sensation of a blocked nose, sneezing, cough, sensation of dry throat
• diarrhoea, stomach pain, increased salivation
• eczema, other skin reactions (e.g., skin redness)
• muscle cramps, muscle weakness, back pain
• feeling tired (malaise or fatigue)
• chest pain or discomfort
• fever or chills
• swelling of the face
• swelling, reaction or discomfort at the injection site, redness and pain, leakage of medicine from the veins which may lead to inflammation or death of skin cells (necrosis) at the injection site, blood clot in the vein causing inflammation (superficial phlebitis)
• decreased oxygen in the blood

Not known: frequency not established
Nephrogenic systemic fibrosis
This is a disease that causes hardening of the skin and may affect soft tissues and internal organs. It has been observed mainly in patients who have received Claricyclic together with other gadolinium-containing contrast agents.
Inform your doctor or radiologist if you notice any changes in the colour or thickness of your skin anywhere on the body, as this may be a sign of the conditions listed above.
The following side effects have been reported with other MRI contrast agents similar to Claricyclic: destruction of red blood cells (haemolysis), confusion, temporary blindness, eye pain, ringing in the ears (tinnitus), ear pain, asthma, dry mouth, bullous-type skin eczema, inability to retain urine (incontinence), kidney damage, acute renal failure, changes in electrocardiogram (ECG) pattern, changes in blood tests (increased iron, increased bilirubin), altered liver function tests.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please consult your doctor or radiologist.
You can also report side effects directly via the national reporting system at www.agenziafarmaco.gov.it/it/responsabili. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Claricyclic

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 stated on the vial, bottle, or pre-filled syringe after "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 administered immediately. If not used immediately,
the responsibility for the storage times and conditions prior to use lies with the user and should normally not exceed 24 hours at 2-8 °C, unless the container is opened under controlled and validated aseptic conditions.

6. Package Contents and Other Information

What Claricyclic Contains

• The active substance is gadoteric acid. One mL of injectable solution contains 279.3 mg of gadoteric acid (as gadoterate meglumine), equivalent to 0.5 mmol of gadoteric acid.
• The other components are meglumine, tetraxetan (DOTA), and water for injections.

Presentation of Claricyclic and Contents of the Package
Claricyclic is a clear, colourless or slightly yellow solution for intravenous injection.
Claricyclic is available in the following containers:
Glass vials (Type 1, colourless) filled with 5, 10, 15, or 20 mL.
Pre-filled polymer syringes of 10, 15, or 20 mL.
Glass vials (Type 1, colourless) and polypropylene vials filled with 50 and 100 mL.
All containers are packaged in outer cartons containing 1 or 10 units.
It is possible that not all pack sizes will be marketed.

Marketing Authorisation Holder and Manufacturer
GE Healthcare AS
Nycoveien 1-2
P.O. Box 4220 Nydalen
NO-0401 OSLO
NORWAY

The following information is intended for healthcare professionals only:

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, an additional dose of 0.2 mmol/kg body weight, equivalent to 0.4 mL/kg body weight, may improve tumour characterisation and aid 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 body weight, equivalent to 0.2 mL/kg body weight, to ensure diagnostically adequate contrast enhancement.

For angiography: The recommended dose for intravenous injection is 0.1 mmol/kg body weight, i.e., 0.2 mL/kg body weight, to ensure diagnostically adequate contrast enhancement. In exceptional circumstances (e.g., inability to obtain satisfactory images of a large vascular area), administration of a second consecutive injection of 0.1 mmol/kg body weight, i.e., 0.2 mL/kg, may be justified. However, if two consecutive doses of Claricyclic are expected to be used prior to starting angiography, using 0.05 mmol/kg body weight (i.e., 0.1 mL/kg) per dose may be beneficial, depending on the available diagnostic imaging equipment.

Special Populations

Renal impairment
Claricyclic should be used in patients with severe renal impairment (GFR <30 mL/min/1.73m²) and during the perioperative period of liver transplantation only after careful assessment of the risk-benefit ratio and when diagnostic information is essential and not available with non-contrast MRI. If Claricyclic 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 scan. Repeated administration data are not available; therefore, Claricyclic should not be repeated unless at least 7 days have elapsed between injections.

Elderly (aged 65 years or older)
No dose adjustment is considered necessary. Caution is advised in elderly patients.

Hepatic impairment
The adult dose applies to these patients. Caution is recommended, especially during the perioperative period of liver transplantation (see above, renal impairment).

Paediatric population (0–18 years of age)

Brain and spinal cord MRI, whole-body MRI:
The maximum recommended dose of Claricyclic is 0.1 mmol/kg body weight. No more than one dose should be administered during a single scan.
Use in whole-body MRI is not recommended in children under 6 months of age.
Due to immature renal function in neonates up to 4 weeks of age and in children up to 1 year of age, Claricyclic should be used in these patients only after careful assessment and at a dose not exceeding 0.1 mmol/kg body weight. No more than one dose should be administered during a single scan. Repeated administration data are not available; therefore, Claricyclic should not be repeated unless at least 7 days have elapsed between injections.

Angiography: Claricyclic is not recommended for angiography in children under 18 years of age due to lack of efficacy and safety data for this indication.

Method of Administration
This product is intended for intravenous use 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 the section Precautions for Use and Handling below.

Paediatric population (0–18 years of age): Depending on the amount of Claricyclic to be administered to the child, it is preferable to use Claricyclic vials with a single-use syringe of appropriate volume to ensure accurate dosing.
In neonates and children, the required dose should be administered manually.

Special Warnings and Precautions for Use

Renal impairment
Prior to administration of Claricyclic, screening for renal dysfunction via laboratory tests is recommended in all patients.
Cases of nephrogenic systemic fibrosis (NSF) have been reported following the use of some gadolinium-containing contrast agents in patients with severe acute or chronic renal impairment (GFR <30 mL/min/1.73m²). Patients undergoing liver transplantation are at particular risk due to the high incidence of acute renal failure in this group. Since NSF may occur with Claricyclic, this medicinal product should be used in patients with severe renal impairment and during the perioperative period of liver transplantation only after careful risk-benefit assessment and when essential diagnostic information is not obtainable with non-contrast MRI.

As renal clearance of gadoteric acid may be reduced in elderly patients, screening for renal dysfunction is particularly important in patients aged 65 years or older.

Haemodialysis shortly after administration of Claricyclic may be helpful in removing Claricyclic from the body. However, there is no evidence supporting the use of haemodialysis for the prevention or treatment of NSF in patients not already undergoing dialysis.

Pregnancy and Breastfeeding

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

The decision to continue or interrupt breastfeeding for a period of 24 hours after administration of Claricyclic should be at the discretion of the physician or radiologist and the mother.

Precautions for Use and Handling

Single use
The injectable solution should be inspected visually before use. Only clear solutions free from visible particles should be used.

Vials and Bottles: Prepare a syringe with a needle. Vials: remove the plastic cap. Polypropylene bottles: remove the plastic screw cap or plastic cover by lifting the upper ring. After cleaning the stopper with an alcohol swab, pierce the stopper with the needle. Withdraw the required amount of product for the examination and administer intravenously.

Pre-filled syringes: Administer the required amount of product intravenously.

Any unused contrast medium remaining in vials/bottles, connecting materials, and all disposable components of the system must be discarded after the examination.

Removable traceability label: The removable traceability label on syringes/vials/bottles must be affixed to the patient’s medical record to allow accurate documentation of the gadolinium-based contrast agent used. The administered dose must be recorded. If electronic medical records are used, the product name, batch number, and dose must be entered into the patient’s medical record.

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