Cycloleux 0.5 mmol/ml solution for injection EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Cyclolux 0,5 mmol/ml injection solution EFG

Gadoteric acid

Read the entire leaflet carefully before you start using this 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 or radiologist.
• If you experience any adverse reactions, consult your doctor, radiologist or pharmacist, even if they are adverse reactions not listed in this leaflet. See section 4.

Leaflet contents:

1. What Cyclolux is and what it is used for
2. What you need to know before using Cyclolux
3. How to use Cyclolux
4. Possible side effects
5. How to store Cyclolux
6. Contents of the pack and other information

1. What Cyclolux is and what it is used for

Cyclolux is a contrast medium containing gadoteric acid. It is for diagnostic use only.

Cyclolux is used to enhance the contrast of images obtained by magnetic resonance imaging (MRI). Contrast enhancement improves visualization and delineation in:

Adults and pediatric population (0–18 years)

• MRI of the central nervous system, including abnormalities (lesions) of the brain, spinal cord, and adjacent tissues.
• Whole-body MRI, including abnormalities (lesions) of the liver, kidneys, pancreas, pelvis, lungs, heart, breasts, and the musculoskeletal system.

Adults

Magnetic resonance angiography (MRA), including abnormalities (lesions) and narrowing (stenosis) of arteries, except for coronary arteries.

2. What you need to know before using Cyclolux

Do not use Cyclolux

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

Warnings and precautions

Consult your doctor or radiologist before using Cyclolux if you:

• have previously had a reaction to contrast media during an earlier procedure.
• have asthma.
• have a history of allergies (such as to shellfish, hives, hay fever).
• are being treated with a beta-blocker (a medicine used for heart problems and blood pressure disorders; such as metoprolol).
• have impaired kidney function.
• have recently undergone, or are scheduled to undergo, a liver transplant.
• suffer from a disease affecting the heart or blood vessels.
• have had seizures or are being treated for epilepsy.

In all these cases, your doctor or radiologist will evaluate the benefit-risk balance and decide whether you should be given Cyclolux. If you are administered Cyclolux, your doctor or radiologist will take the necessary precautions and the administration will be closely supervised.

Your doctor or radiologist may decide to perform a blood test to check your kidney function before deciding to use Cyclolux, especially if you are 65 years of age or older.

Neonates and infants

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

You must remove all metallic objects you are carrying before the examination. Inform your doctor or radiologist if you have:

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

This information is extremely important, as these devices may cause serious problems due to the powerful magnetic fields used in magnetic resonance imaging.

Use of Cyclolux with other medicines

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

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

Use of Cyclolux with food and drink

There are no known interactions between Cyclolux and food or drink. However, please consult your doctor, radiologist, or pharmacist about whether you need to avoid eating or drinking before the procedure.

Pregnancy and breastfeeding

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

Pregnancy

Gadoteric acid may cross the placenta. It is unknown whether it affects the fetus. Cyclolux should not be used during pregnancy unless considered absolutely necessary.

Breastfeeding

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

Driving and using machines

There is no information available on the effects of Cyclolux on the ability to drive or operate machinery. If you feel unwell after the procedure, you should not drive or operate machinery.

3. How to use Cyclolux

Cyclolux will be administered to you via intravenous injection.

During the procedure, you will be under the supervision of a doctor or radiologist. A needle will remain in your vein; this will allow the doctor or radiologist to administer appropriate emergency medications if necessary. If you experience an allergic reaction, the administration of Cyclolux will be stopped.

Cyclolux may be administered manually or by 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 practice. Healthcare personnel are aware of the precautions that must be taken for the procedure. They are also aware of any possible complications that may occur.

Dosage

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

Dosage in special populations

The use of Cyclolux is not recommended in patients with severe renal impairment or in patients who have recently had, or are about to undergo, a liver transplant. However, if use is required, only one dose of Cyclolux should be given during the procedure, and a second injection must not be administered within 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 infants up to 1 year of age, Cyclolux will only be used in these patients after careful medical assessment. Neonates and infants should receive only one dose of Cyclolux during the procedure and must not receive a second dose within at least 7 days.

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

Elderly patients

If you are 65 years of age or older, dose adjustment is not necessary, but you may be given a blood test to check that your kidneys are functioning properly.

If you have been given too much Cyclolux

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

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

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

4. Possible adverse effects

Like all medicines, this medicine can have adverse effects, although not everyone will experience them.

After administration, you will remain under observation for at least half an hour. Most side effects occur immediately or sometimes take longer to appear. Some effects may occur up to 7 days after injection of Cyclolux.

There is a small risk that you may have an allergic reaction to Cyclolux. Such reactions can be serious and exceptionally may cause shock (a case of allergic reaction that could endanger your life). Any of the symptoms described below may be early signs of shock. Inform your doctor, radiologist, or healthcare professional immediately if you experience any of the following:

• swelling of the face, mouth, or throat, which may cause difficulty swallowing or breathing.
• swelling of the hands or feet.
• dizziness (drop in blood pressure).
• difficulty breathing.
• wheezing.
• cough.
• itching.
• runny nose.
• sneezing.
• eye irritation.
• hives.
• skin rash.

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

• hypersensitivity (allergic reaction).
• headache.
• unusual taste in the mouth.
• dizziness.
• somnolence (drowsiness).
• tingling, warmth, cold sensation, and/or pain.
• high or low blood pressure.
• nausea (feeling unwell).
• stomach pain.
• rash.
• sensation of warmth, sensation of cold.
• asthenia (loss of energy, weakness).
• discomfort at the injection site, cold sensation at the injection site, leakage of the product outside the blood vessels which may cause inflammation (local redness and pain).

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

• anxiety, fainting (dizziness and feeling of imminent loss of consciousness).
• eyelid swelling.
• palpitations.
• sneezing.
• vomiting (feeling unwell).
• diarrhea.
• increased salivary secretion.
• hives, itching, sweating.
• chest pain, chills.

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

• anaphylactic reactions or anaphylactoid-type reactions.
• agitation.
• coma, convulsions, syncope (brief loss of consciousness), altered sense of smell (perception of smells, often unpleasant), tremor.
• conjunctivitis, red eyes, blurred vision, increased lacrimation.
• cardiac arrest, rapid or slow heartbeat, irregular heartbeat, vascular dilation, pallor.
• respiratory arrest, pulmonary edema, difficulty breathing, wheezing, nasal congestion, cough, dry throat, throat tightness with sensation of suffocation, respiratory spasms, throat swelling.
• eczema, skin redness, swelling of the lips and localized in the mouth.
• muscle cramps, muscle weakness, back pain.
• malaise, chest discomfort, fever, facial swelling, leakage of the medicine outside blood vessels which may lead to tissue death at the injection site, inflammation of a vein.
• decreased blood oxygen levels.

Cases of nephrogenic systemic fibrosis (which causes hardening of the skin and may also affect soft tissues and internal organs) have been reported, most of which occurred in patients who had been administered Cyclolux together with other gadolinium-based contrast agents. If, during the weeks following the MRI study, you notice changes in the color and/or thickness of your skin anywhere on your body, inform the radiologist who performed the examination.

Reporting of adverse effects:

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if they are possible adverse effects not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Cyclolux

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

This medicine does not require any special storage conditions.

Chemical and physical in-use stability has been demonstrated for up to 72 hours at room temperature. From a microbiological standpoint, the product should be used immediately. If not used immediately, the times and conditions of storage prior to use are the responsibility of the user and normally should not exceed 24 hours at temperatures of 2º to 8ºC, unless reconstitution has taken place under strictly controlled and validated aseptic conditions.

Do not use this medicine after the expiry date stated on the vial and on the outer packaging following EXP. The expiry date refers to the last day of the month indicated.

6. Contents of the pack and other information

Composition of Cyclolux

• The active substance 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-tetrayl)tetraacetic acid (DOTA), and water for injections.

Appearance of the product and contents of the pack

Cyclolux is a clear, colourless to yellow, particle-free, injectable solution for intravenous use.

Cyclolux pack contents consist of 1 or 10 vials containing 10, 15 or 20 ml of injectable solution.

Only certain pack sizes may be commercially available.

Marketing Authorisation 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 authorised in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:

• Germany: Cyclolux 0.5 mmol/ml Injektionslösung
• Austria: Cyclolux 0.5 mmol/ml Injektionslösung im Einzeldosisbehältnis
• Belgium: Macrocyclolux 0.5 mmol/ml oplossing voor injectie
• Croatia: Cyclolux 0.5 mmol/ml otopina za injekciju
• Cyprus: Macrocyclolux 0.5 mmol/ml ενέσιμο διάλυμα
• Czech Republic: Cyclolux
• Estonia: Cyclolux
• Greece: Cyclolux 0.5 mmol ενέσιμο διάλυμα
• Ireland: Cyclolux 279.32 mg/ml solution for injection
• Italy: Macrocylux
• Latvia: Cyclolux 0.5 mmol/ml injekcinis tirpalas
• Lithuania: Cyclolux
• Netherlands: Cyclolux 0.5 mmol/ml, oplossing voor injectie
• Poland: Cyclolux
• Portugal: Cyclolux
• Hungary: Cyclolux 0.5 mmol/ml oldatos injekció, egyadagos
• Romania: Cyclolux 0.5 mmol/ml solutie injectabila
• Spain: Cyclolux 0.5 mmol/ml solución inyectable EFG
• Slovakia: Cyclolux 0.5 mmol/ml Injekcný roztok
• Slovenia: Cyclolux 0.5 mmol/ml raztopina za injiciranje
• United Kingdom (Northern Ireland): Cyclolux 0.5 mmol/ml solution for injection

Other sources of information

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

Date of the most recent review of this leaflet: May 2024

This information is intended for healthcare professionals only

Dosage

The lowest dose providing sufficient enhancement for diagnostic purposes should be used. The dose must be calculated according to the patient's body weight and must not exceed the recommended dose per kilogram of body weight indicated in this section.

• Cranial and spinal magnetic resonance (MR) imaging: In neurological studies, the dose may range from 0.1 to 0.3 mmol per kilogram of body weight (mmol/kg b.w.), equivalent to 0.2 to 0.6 ml/kg b.w. In some cases, following administration of 0.1 mmol/kg b.w. to patients with brain tumours, an additional dose of 0.2 mmol/kg b.w. may improve tumour characterisation and assist in therapeutic decision-making.
• Whole-body MR and angiography: The recommended intravenous dose is 0.1 mmol/kg b.w. (i.e., 0.2 ml/kg b.w.) to provide adequate contrast for diagnosis. Angiography: In exceptional circumstances (e.g., when satisfactory imaging of a large vascular territory cannot be obtained), 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 Cyclolux are anticipated before starting angiography, using 0.05 mmol/kg b.w., equivalent to 0.1 ml/kg b.w., for each dose may be beneficial, depending on the MR equipment used for imaging.
• Paediatric population (0–18 years): Cranial MR and whole-body/spinal MR: the maximum and recommended dose of Cyclolux is 0.1 mmol/kg b.w.

Due to the immaturity of renal function in neonates up to 4 weeks of age and infants up to 1 year of age, Cyclolux should be used in these patients only after careful consideration, at a dose not exceeding 0.1 mmol/kg body weight. No more than one dose should be administered during a single examination. Due to the lack of data on repeated administration, Cyclolux should not be re-administered unless the interval between injections is at least 7 days.

Cyclolux is not recommended for angiography in children under 18 years of age, as safety and efficacy data for this indication are insufficient.

• Renal impairment: The adult dose applies to patients with mild to moderate renal impairment (GFR or glomerular filtration rate ≥30 ml/min/1.73 m²). See section “Renal impairment” below.
• Hepatic impairment: The adult dose applies to these patients. Caution should be exercised, especially during the perioperative period of liver transplantation.

Method of administration

Cyclolux is indicated only for intravenous administration. Do not use by intrathecal route. Care must be taken to ensure strictly intravenous injection: extravasation may lead to local intolerance reactions, requiring standard local management.

Infusion rate: 3–5 ml/min (for angiographic procedures, higher infusion rates up to 120 ml/min, i.e., 2 ml/sec, may be used).

Optimal imaging window: Approximately within 45 minutes after injection.

Optimal imaging sequence: T1-weighted sequences.

Intravascular administration of the contrast agent should be performed, if possible, with the patient lying down. After administration, the patient should remain under observation for at least 30 minutes, as experience shows that most adverse reactions occur during this period.

Prepare a syringe with a needle. Remove the plastic cap. After cleaning the stopper with an alcohol-soaked swab, pierce the stopper with the needle. Withdraw the required amount of product for the examination and administer intravenously.

This medicinal product is for single use only; any unused solution must be discarded.

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

Paediatric population

Depending on the amount of gadoteric acid to be administered to the child, it is preferable to use vials of gadoteric acid with a single-use syringe of an appropriate volume to ensure greater accuracy in the injected volume.

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

Renal impairment

Prior to administration of Cyclolux, it is recommended to evaluate all patients for potential renal dysfunction using laboratory tests.

Cases of nephrogenic systemic fibrosis (NSF) have been reported following the use of some gadolinium-based contrast agents in patients with severe acute or chronic renal impairment (GFR or glomerular filtration rate < 30 ml/min/1.73 m²). Patients undergoing liver transplantation are at particular risk, as the incidence of acute renal failure is high in this group. Since NSF may potentially occur with Cyclolux, it should only be used in patients with severe renal impairment and in patients during the perioperative period of liver transplantation after careful benefit-risk assessment and only if essential diagnostic information cannot be obtained by non-contrast MRI. If Cyclolux use is necessary, the dose must not exceed 0.1 mmol/kg body weight. No more than one dose should be administered during a single examination. Due to the lack of data on repeated administration, Cyclolux should not be re-administered unless at least 7 days have elapsed between injections. Haemodialysis shortly after Cyclolux administration may be helpful in eliminating the agent from the body. There is no evidence to support initiating haemodialysis for the prevention or treatment of NSF in patients not already undergoing haemodialysis.

Elderly patients

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

Paediatric population (neonates and infants)

See the sections "Dosage" and "Method of administration", "Paediatric population" above.

Pregnancy and lactation

Cyclolux must not be used during pregnancy unless the woman's clinical condition requires the use of gadoteric acid.

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

Handling instructions

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