CYCLOLUX REP 0.5 mmol/ml INJECTABLE SOLUTION

2. What you need to know before starting to use Cyclolux Rep

Do not use Cyclolux Rep

• if you are allergic to the active substance or to any of the other components of this medicine (listed in section 6).
• if you are allergic to gadolinium-containing medications (such as other contrast agents used in MRI).

Warnings and precautions

Consult your doctor or radiologist before starting to use Cyclolux Rep if you:

• have had a reaction to contrast agents during a previous study.
• have asthma.
• have a history of allergy (such as shellfish allergy, hives, hay fever).
• are being treated with a beta-blocker (a medication used for heart problems and blood pressure disorders; such as metoprolol).
• have kidney problems.
• have recently undergone, or are scheduled to undergo, a liver transplant.
• have a condition that affects the heart or blood vessels.
• have had seizures or are being treated for epilepsy.

In all these cases, your doctor or radiologist will assess the benefit-risk ratio and decide whether you should be given Cyclolux Rep. If you are given Cyclolux Rep, your doctor or radiologist will take the necessary precautions and the administration of Cyclolux Rep will be carefully monitored.

Your doctor or radiologist may decide to perform a blood test to check the proper functioning of your kidneys before deciding to use Cyclolux Rep, especially if you are 65 years or older.

Neonates and infants

Due to the immaturity of renal function in newborns up to 4 weeks of age and in infants up to 1 year of age, Cyclolux Rep should only be used in these patients after careful evaluation by the doctor.

You should remove all metal objects you are wearing before the examination. Inform your doctor or radiologist if you have:

• a pacemaker.
• a vascular clip.
• an infusion pump.
• a neurostimulator.
• a cochlear implant (implant in the inner ear).
• any suspected metal foreign body, particularly in the eye.

This information is extremely important as these can cause serious problems due to the strong magnetic fields used in MRI machines.

Using Cyclolux Rep with other medicines

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

In particular, please inform your doctor, radiologist, or pharmacist if you are taking or have recently taken medications for heart problems or blood pressure disorders, such as beta-blockers, vasoactive substances, angiotensin-converting enzyme inhibitors, or angiotensin II receptor antagonists.

Using Cyclolux Rep with food and drinks

There are no known interactions between Cyclolux Rep and food or drinks. However, please consult your doctor, radiologist, or pharmacist if you need to avoid eating or drinking before the test.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or radiologist before using this medicine.

Pregnancy

Gadoteric acid can cross the placenta. It is not known if it affects the fetus. Cyclolux Rep should not be used during pregnancy unless it is considered absolutely necessary.

Breastfeeding

Your doctor or radiologist will assess whether you should continue or interrupt breastfeeding 24 hours after administration of Cyclolux Rep.

Driving and using machines

There is no information on the effects of Cyclolux Rep on the ability to drive and use machines. If you feel unwell after the test, you should not drive or use machines.

3. How to use Cyclolux Rep

Cyclolux Rep will be administered to you by intravenous injection.

During the test, you will be under the supervision of a doctor or radiologist. A needle will be left in your vein; this will allow the doctor or radiologist to inject emergency medications if necessary. If you experience an allergic reaction, the administration of Cyclolux Rep will be interrupted.

Cyclolux Rep can be administered manually or using an automatic injector. In newborns and infants, the product will only be administered manually.

The procedure will be performed in a hospital, clinic, or private clinic. The healthcare staff is aware of the precautions to be taken for the test. They are also aware of any possible complications that may occur.

Dosage

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

Dosage in special populations

The use of Cyclolux Rep is not recommended in patients with severe kidney problems or in patients who have recently undergone, or are scheduled to undergo, a liver transplant. However, if use is required, you should only receive one dose of Cyclolux Rep during the procedure and should not receive a second injection for at least 7 days.

Neonates, infants, children, and adolescents

Due to the immaturity of renal function in newborns up to 4 weeks of age and in infants up to 1 year of age, Cyclolux Rep will only be used in these patients after careful evaluation by the doctor. Neonates and infants should only receive one dose of Cyclolux Rep during the procedure and should not receive a second dose for at least 7 days.

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

Elderly patients

If you are 65 years or older, it is not necessary to adjust the dose, but you may undergo a blood test to check the proper functioning of your kidneys.

If you have been given too much Cyclolux Rep

It is highly unlikely that you will be given an overdose. You will be administered Cyclolux Rep in medical facilities and by a trained person. In the event of an overdose, Cyclolux Rep can be removed from the body by hemodialysis (blood cleansing).

At the end of this leaflet, you will find additional information on the use and handling of Cyclolux Rep by the doctor or healthcare professional.

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 administration, you will be kept under observation for at least half an hour. Most side effects occur immediately or, sometimes, may be delayed. Some effects may appear up to seven days after the injection of Cyclolux Rep.

There is a small risk that you may have an allergic reaction to Cyclolux Rep. Such reactions can be severe and exceptionally may cause anaphylactic shock(a life-threatening allergic reaction). Any of the symptoms described below may be the first signs of shock. Inform your doctor, radiologist, or healthcare professional immediately if you have any of them:

• swelling of the face, mouth, or throat that may cause difficulty swallowing or breathing.
• swelling of the hands or feet.
• drooping (low blood pressure).
• difficulty breathing.
• wheezing.
• coughing.
• itching.
• runny nose.
• sneezing.
• eye irritation.
• hives.
• skin rash.

Uncommon side effects (may affect up to 1 in 100 patients)

• hypersensitivity (allergic reaction).
• headache.
• unusual taste in the mouth.
• dizziness.
• drowsiness (sleepiness)
• tingling sensation, heat, cold, and/or pain.
• low or high blood pressure
• nausea (feeling unwell).
• stomach pain.
• rash.
• feeling of heat, feeling of cold.
• asthenia (lack of energy, weakness)
• discomfort at the injection site, reaction at the injection site, coldness at the injection site, diffusion of the product outside the blood vessels that can cause inflammation (redness and local pain).

Rare side effects (may affect up to 1 in 1,000 patients)

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

Very rare side effects (may affect up to 1 in 10,000 patients)

• anaphylactic reactions or anaphylactoid reaction
• agitation
• coma, seizures, syncope (brief loss of consciousness), alteration of smell (perception of unpleasant odors), tremor
• conjunctivitis, red eyes, blurred vision, increased tear secretion
• cardiac arrest, rapid or slow heartbeat, irregular heartbeat, vasodilation, paleness
• respiratory arrest, pulmonary edema, difficulty breathing, wheezing, nasal congestion, cough, dry throat, throat constriction with feeling of choking, respiratory spasms, throat inflammation
• eczema, skin redness, inflammation of the lips and localized in the mouth
• muscle cramps, muscle weakness, back pain
• discomfort, chest discomfort, fever, facial inflammation, diffusion of the medication outside the blood vessels that can cause tissue death at the injection site, vein inflammation
• decrease in blood oxygen level.

There have been reports of nephrogenic systemic fibrosis (which causes skin hardening and may also affect soft tissues and internal organs), most of which were in patients who were administered Cyclolux Rep in combination with other gadolinium-based contrast agents. If, during the weeks after the MRI study, you notice changes in the color and/or thickness of your skin in any part of your body, inform the radiologist who performed the examination.

Reporting side effects:

If you experience any side effects, consult your doctor, pharmacist, or nurse, even if they are side effects not listed in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Cyclolux Rep

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

This medicine does not require special storage conditions.

Chemical and physical stability has been demonstrated for a period of 72 hours at room temperature. From a microbiological point of view, the product should be used immediately. If not used immediately, the storage times and conditions before use are the responsibility of the user and should not normally exceed 24 hours at temperatures between 2°C and 8°C, unless the opening has taken place in controlled and validated aseptic conditions.

Do not use this medicine after the expiration date stated on the vial and on the packaging after EXP. The expiration date is the last day of the month indicated.

6. Container Content and Additional Information

Composition of Cyclolux Rep

• The active ingredient is gadoteric acid. 1 ml of injectable solution contains 279.32 mg of gadoteric acid (as meglumine salt), equivalent to 0.5 mmol of gadoteric acid (as meglumine salt).
• The other components (excipients) are meglumine, 2, 2’, 2’’, 2’’’-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) (DOTA), and water for injectable preparations.

Appearance of the Product and Container Content

Cyclolux Rep is a clear, colorless to yellow, particle-free solution for intravenous injection.

The content of Cyclolux Rep containers is 1 or 10 vials containing 60 ml or 100 ml of injectable solution.

Only certain package sizes may be marketed.

Marketing Authorization Holder and Manufacturer:

Sanochemia Pharmazeutika GmbH

Landegger Straße 7

2491 Neufeld an der Leitha, Austria

Local Representative:

Juste Farma S.L.U

Avda. de San Pablo, 27

28823 Coslada (Madrid), Spain

This Medicinal Product is Authorized in the Member States of the European Economic Area under the following Names:

• Germany: Cyclolux 0.5 mmol/ml Injektionslösung
• Austria: Cyclolux 0.5 mmol/ml Injektionslösung
• Belgium: Macrocyclolux 0.5 mmol/ml oplossing voor injectie
• Italy: Macrocyclolux
• Poland: Cyclolux multidose
• Hungary: Cyclolux 0.5 mmol/ml oldatos injekció, többadagos
• Spain: Cyclolux REP 0.5 mmol/ml solución inyectable EFG
• Slovakia: Cyclolux Multi 0.5 mmol/ml Injekcný roztok

Other Sources of Information

Detailed information on this medicinal product is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es

Date of the Last Revision of this Leaflet: May 2024

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This Information is Intended Only for Healthcare Professionals

Dosage

The lowest dose that provides sufficient contrast 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 indicated in this section.

• Magnetic Resonance Imaging (MRI) of the Brain and Spine: In neurological studies, the dose may vary from 0.1 to 0.3 mmol per kilogram of body weight (mmol/kg bw), equivalent to 0.2 to 0.6 ml/kg bw. In some cases, after administration of 0.1 mmol/kg bw to patients with brain tumors, an additional dose of 0.2 mmol/kg bw may improve tumor characterization and facilitate therapeutic decision-making.
• Whole-Body MRI and Angiography: The recommended dose for intravenous injection is 0.1 mmol/kg bw (equivalent to 0.2 ml/kg bw) to provide adequate contrast for diagnosis. Angiography: In exceptional circumstances (e.g., when it is not possible to obtain satisfactory images of an extensive vascular territory), a second consecutive injection of 0.1 mmol/kg bw, equivalent to 0.2 ml/kg bw, may be justified. However, if it is anticipated that two consecutive doses of Cyclolux Rep will be administered before starting angiography, it may be beneficial to use 0.05 mmol/kg bw, equivalent to 0.1 ml/kg bw, for each dose, depending on the MRI equipment used to obtain the images.
• Pediatric Population (0-18 years): (MRI) brain and (MRI) spine/whole body: The maximum and recommended dose of Cyclolux Rep is 0.1 mmol/kg bw.

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

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

• Patient with renal insufficiency: The adult dose applies to patients with mild to moderate renal insufficiency (GFR or glomerular filtration rate ≥ 30 ml/min/1.73 m2). See the section "Renal Insufficiency" below.
• Patient with hepatic insufficiency: The adult dose applies to these patients. Caution should be exercised, especially in the perioperative period of a liver transplant.

Method of Administration

Cyclolux Rep is indicated only for intravenous administration. Do not use intrathecally. Ensure that the injection is strictly intravenous: extravasation can lead to local intolerance reactions, requiring usual local measures.

Perfusion rate: 3-5 ml/min (for angiographic procedures, perfusion rates of up to 120 ml/min, equivalent to 2 ml/s, can be used).

Optimal Image Acquisition: Approximately 45 minutes after injection.

Optimal Image Acquisition Sequence: T1-weighted.

The intravascular administration of the contrast medium should be performed, if possible, with the patient lying down. After administration, the patient should be kept under observation for at least half an hour, as experience shows that most adverse effects occur during this time.

The rubber stopper should be pierced only once with a suitable extraction device (spike).

In general, the extraction device should have the following characteristics: trocar, sterile air filter, luer connection, and protective sealing cap.

A single-use manual syringe (sterile) can be used to perform a single-dose protocol or to inject a second contrast bolus if clinically necessary.

An automatic injector can be used for a single patient only, for repeated administrations.

At the end of the examination session, the contrast medium remaining in the vial, as well as that remaining in the disposable device, should be discarded within 24 hours after piercing the rubber stopper. The manufacturer's specific instructions for the equipment used should be carefully followed.

The injectable solution should be visually inspected before use. Only clear and particle-free solutions should be used.

Pediatric Population

Depending on the amount of gadoteric acid administered to the child, it is preferable to use vials of gadoteric acid with a single-use syringe of a volume adapted to this amount to ensure greater precision of the injected volume.

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

Renal Insufficiency

Before administering Cyclolux Rep, it is recommended to evaluate all patients for possible renal dysfunction using laboratory tests.

Cases of nephrogenic systemic fibrosis (NSF) associated with the use of some gadolinium-based contrast agents have been reported in patients with severe acute or chronic renal insufficiency (GFR or glomerular filtration rate <30 ml min 1.73 m2). patients undergoing liver transplantation have a special risk since the incidence of acute renal failure is high in this group. there possibility that nsf may occur with cyclolux rep, it should only be used severe insufficiency and perioperative period transplant after careful benefit-risk assessment if diagnostic information essential cannot obtained by mri without contrast. use rep necessary, dose not exceed 0.1 mmol kg body weight. during an examination, no more than one administered. due to lack on repeated administration, administration unless interval at least 7 days has elapsed between injections. hemodialysis shortly useful for elimination from body. evidence support initiation prevention or treatment who are hemodialysis.< p>

Elderly Patients

Since the renal elimination of gadoteric acid may be reduced in elderly patients, it is especially important to evaluate patients aged 65 years or older for possible renal dysfunction.

Pediatric Population (Newborns and Infants)

See above, under "Dosage" and "Method of Administration", "Pediatric Population".

Pregnancy and Lactation

Cyclolux Rep should not be used during pregnancy unless the clinical situation of the woman requires the use of gadoteric acid.

The continuation or interruption of breastfeeding during a period of 24 hours after administration of Cyclolux Rep will be at the discretion of the physician and the breastfeeding mother.

Handling Instructions

The detachable label of the vials should be stuck to the patient's medical record to allow accurate recording of the gadolinium-based contrast agent used. The dose used should also be recorded. If an electronic patient record is used, the name of the medicinal product, batch number, and dose should be included in the same.