Cyclolux

Package leaflet: Information for the user

Cyclolux, 0.5 mmol/ml, solution for injection
Acidum gadotericum
Please read all of this leaflet carefully before you are given this medicine, because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or radiologist.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor, radiologist, or pharmacist. See section 4.

Contents of the leaflet

1. What Cyclolux is and what it is used for
2. What you need to know before being given Cyclolux
3. How Cyclolux is given
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 agent containing gadoteric acid. It is intended
for diagnostic use only.
Cyclolux is used to enhance the contrast of images obtained by
magnetic resonance imaging (MRI). This contrast enhancement improves the visibility and delineation of abnormalities in:
Adults, children and adolescents (0–18 years of age)

• MRI of the central nervous system (CNS), including pathological lesions in the brain, spinal cord and surrounding tissues;
• MRI of the whole body, including pathological lesions in the liver, kidneys, pancreas, pelvis, lungs, heart, breast and musculoskeletal system.

Adults

• MR angiography (MRA) of pathological lesions and stenoses in arteries, excluding coronary arteries.

2. Important information before using Cyclolux

When NOT to use Cyclolux

• if the patient is allergic to the active substance or to any of the other ingredients of this medicine (listed in section 6).
• if the patient is allergic to drugs containing gadolinium (such as other contrast agents used in magnetic resonance imaging).

Warnings and precautions
You must inform your doctor or radiologist if any of the following apply to you:

• the patient has previously experienced a reaction to a contrast agent during an examination;
• the patient suffers from asthma;
• the patient has had allergies in the past (e.g. allergy to seafood, hives, hay fever);
• the patient is being treated with beta-blockers (a medicine used to treat heart conditions 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;
• the patient has a disease affecting the heart or blood vessels;
• the patient has had seizures or is being treated for epilepsy.

In all such cases, the doctor or radiologist will assess the benefit-risk ratio and determine whether Cyclolux can be administered to the patient. If Cyclolux is administered, the doctor or radiologist will take necessary precautions, and administration of Cyclolux will be closely monitored.
The doctor or radiologist may decide to perform blood tests to check kidney function before administering Cyclolux, especially in patients aged 65 years or older.
Newborns and infants
Due to immature kidney function in newborns up to 4 weeks of age and infants up to 1 year of age, Cyclolux will be administered to such patients only after careful consideration by the doctor.
Before the examination, all metallic objects that the patient may be wearing should be removed. You must inform the doctor or radiologist if the patient has any of the following implanted:

• a cardiac pacemaker,
• a vascular clip,
• an infusion pump,
• a nerve stimulator,
• a cochlear implant (an implant in the inner ear),
• any suspected metallic foreign body, especially in the eye. This is very important, as it may cause serious problems due to the very strong magnetic fields used in magnetic resonance imaging equipment.

Cyclolux and other medicines
You must tell your doctor or radiologist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take. In particular, you must inform the doctor, radiologist, or pharmacist if the patient is currently taking or has recently taken medicines for heart conditions or blood pressure, such as beta-blockers, vasoactive agents, angiotensin-converting enzyme inhibitors, or angiotensin II receptor antagonists.
Taking Cyclolux with food and drink
No interactions between Cyclolux and food or drink are known. However, you should ask your doctor, radiologist, or pharmacist whether you need to refrain from eating or drinking 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 unknown whether this affects the unborn child. Cyclolux must not be used during pregnancy unless absolutely necessary.
Breastfeeding
The doctor or radiologist will discuss with the patient whether she can continue breastfeeding or should interrupt it for 24 hours after administration of Cyclolux.
Driving and operating machinery
There are no available data on the effect of Cyclolux on the ability to drive. If the patient feels unwell after the examination, she should not drive or operate machinery.

3. How to use Cyclolux

Cyclolux will be administered as an intravenous injection.
During the examination, the patient will be closely monitored by the physician or radiologist. An intravenous catheter will remain in place so that, in case of an emergency, the physician or radiologist can quickly administer life-saving medications. If the patient experiences an allergic reaction, administration of Cyclolux will be immediately stopped.
Cyclolux may be injected manually or using an automated injector.
In neonates and infants, this medicine must be administered manually only.
The procedure may be performed in a hospital, outpatient clinic, or private office. Medical personnel are aware of the precautions to be taken during the examination and are familiar with potential complications that may occur.
Dosage
The physician or radiologist will determine the appropriate dose for the patient and will supervise the injection of the medicine.
Dosage in specific patient groups
Cyclolux is not recommended for patients with severe renal impairment, or for patients who have recently undergone or are scheduled to undergo liver transplantation.
However, if use of Cyclolux is necessary, the patient should receive only a single dose during the examination and should not receive another dose within at least 7 days.
Use in neonates, infants, children, and adolescents
Due to immature kidney 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 by the physician. Neonates and infants should receive only a single dose of Cyclolux during the examination and should not receive another injection within at least 7 days.
The use of this medicine for angiography is not recommended in children under 18 years of age.
Elderly patients
Dosage 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 Cyclolux
It is highly unlikely that a patient would receive an overdose of the medicine. Cyclolux is administered in a medical facility by appropriately trained personnel. In the event of an actual overdose, Cyclolux can be removed from the body by hemodialysis (blood purification).
Additional information on the use and handling of this medicine by medical personnel is provided 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 adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone experiences them.
After administration, the patient will be under observation for at least 30 minutes. Most adverse
reactions occur immediately or with some delay. Some adverse reactions may occur even up to seven days after administration of Cyclolux.
There is a small risk that the patient may experience an allergic reaction to Cyclolux. These
reactions may be severe and lead to shock (a type of allergic reaction which 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 doctor, radiologist, or another healthcare professional:

• swelling of the face, lips and/or throat, which may cause difficulty swallowing or breathing,
• swelling of the hands or feet,
• dizziness (low blood pressure),
• shortness of breath (difficulty breathing),
• wheezing,
• cough,
• skin itching,
• watery nasal discharge,
• sneezing,
• eye irritation,
• urticaria,
• skin rash.

Uncommon adverse reactions (may occur in up to 1 in 100 patients)

• hypersensitivity (allergic reactions),
• headache,
• unusual taste in the mouth,
• dizziness,
• drowsiness,
• tingling sensation, warmth and/or burning, cold and/or pain,
• low or high blood pressure,
• nausea,
• abdominal pain,
• rash,
• feeling of warmth, feeling of cold,
• asthenia (loss of energy, weakness),
• discomfort at injection site, injection site reactions, feeling of cold at injection site, extravasation (leakage of the drug outside blood vessels), which may lead to inflammation (redness and local pain).

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

• anxiety, pre-syncope (dizziness and sensation of impending loss of consciousness),
• eyelid swelling,
• palpitations,
• sneezing,
• vomiting,
• diarrhea,
• increased salivation,
• unusual taste in the mouth,
• urticaria, itching, excessive sweating,
• chest pain, chills.

Very rare adverse reactions (may occur in up to 1 in 10,000 patients)

• anaphylactic or anaphylactoid reactions (severe, potentially life-threatening allergic reactions),
• agitation,
• coma, seizures, fainting (transient loss of consciousness), olfactory disturbances (perception of often unpleasant odors), muscle tremor,
• conjunctivitis, eye redness, blurred vision, excessive tearing,
• cardiac arrest, rapid or slow heartbeat, arrhythmia, vasodilation, pallor,
• respiratory arrest, pulmonary edema, breathing difficulties, wheezing, nasal congestion, cough, dry throat, throat tightness with sensation of suffocation, bronchospasm, throat swelling,
• rash, skin redness, swelling of lips and inside the mouth,
• muscle spasms, muscle weakness, back pain,
• malaise, chest discomfort, fever, facial swelling, extravasation which may lead to tissue necrosis at the injection site, phlebitis,
• decreased oxygen levels in blood.

There have been reports of nephrogenic systemic fibrosis (which causes skin hardening and may also affect soft tissues and internal organs), occurring predominantly in patients who received Cyclolux together with other contrast agents containing gadolinium. If, in the weeks following an MRI examination, the patient notices changes in color and/or thickness of the skin anywhere on the body, they should inform the radiologist who performed the examination.
Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, the patient should inform the radiologist, pharmacist, doctor, or nurse.
Adverse reactions can be reported directly to the Department of Monitoring of Adverse Drug Reactions at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products – Al. Jerozolimskie 181C, 02-222 Warsaw
Tel.: +48 22 49 21 301
Faks: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store the medicine Cyclolux

The medicine should be stored in a place out of sight and reach of children.
No special precautions regarding storage of this medicine are required.
Chemical and physical stability of the medicine has been demonstrated for 72 hours after first use
at room temperature. From a microbiological standpoint, the medicine should be used immediately. If
it is not used immediately, the responsibility for the duration and conditions of storage prior
to use lies with the user. The storage period should in general not exceed 24 hours
at 2 to 8°C, unless the container is opened under controlled and validated
aseptic conditions.
Do not use this medicine after the expiry date stated on the vial and on the outer
carton after "EXP". The expiry date refers to the last day of the stated month.

6. Contents of the pack and other information

What Cyclolux contains

• The active substance is gadoterinic acid. One millilitre of injection solution contains 279.32 mg of gadoterinic acid (as meglumine salt), corresponding to 0.5 mmol of gadoterinic acid (as meglumine salt).
• The other components are meglumine, 2,2',2'',2'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid (DOTA), and water for injections.

What Cyclolux looks like and contents of the pack
Cyclolux is a clear, colourless or yellowish solution for intravenous injection, free from visible particles.
The Cyclolux pack contains one or ten vials; one vial contains 10, 15 or 20 ml of injection solution.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Sanochemia Pharmazeutika GmbH
Landegger Straße 7
2491 Neufeld an der Leitha
Austria

Manufacturer
Sanochemia Pharmazeutika GmbH
Landegger Straße 7
2491 Neufeld an der Leitha, Austria

This medicinal product is authorised in the European Economic Area and 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 soluţie injectabilă
Spain: Cyclolux 0,5 mmol/ml solución inyectable EFG
Slovakia: Cyclolux 0,5 mmol/ml Injekčný roztok
Slovenia: Cyclolux 0,5 mmol/ml raztopina za injiciranje
United Kingdom (Northern Ireland): Cyclolux 0.5 mmol/ml solution for injection

Information intended exclusively for medical professionals:

Dosage
The lowest dose providing sufficient contrast enhancement for diagnostic purposes should be used. The dose should be calculated based on the patient's body weight and must not exceed the recommended dose per kilogram of body weight specified in this section.

• Brain and spinal cord MRI: In neurological imaging, doses range from 0.1 to 0.3 mmol/kg body weight, corresponding to 0.2 to 0.6 ml/kg body weight. After administering 0.1 mmol/kg body weight to patients with brain tumors, an additional dose of 0.2 mmol/kg body weight may improve tumor visibility and facilitate treatment decisions.
• Whole-body MRI and angiography: The recommended intravenous dose providing adequate radiological contrast for diagnostic purposes is 0.1 mmol/kg body weight (i.e., 0.2 ml/kg body weight). Angiography: In exceptional circumstances (e.g., if images of satisfactory quality covering a large vascular area are not achieved), administration of a second consecutive dose of 0.1 mmol/kg body weight (corresponding to 0.2 ml/kg body weight) may be justified. However, if two consecutive doses of the medicinal product Cyclolux are anticipated before starting angiography, it may be beneficial to administer 0.05 mmol/kg body weight (i.e., 0.1 ml/kg body weight) for each dose, depending on the available imaging equipment.
• Children and adolescents: Brain and spine MRI / Whole-body MRI: The recommended and maximum dose of Cyclolux is 0.1 mmol/kg body weight. More than one dose should not be administered during a single imaging procedure. Due to immature renal function in neonates up to 4 weeks of age and infants up to 1 year of age, Cyclolux should only be used in these patients after careful consideration and at a dose not exceeding 0.1 mmol/kg body weight. More than one dose should not be administered during a single imaging procedure. Due to lack of data on multiple administrations, repeated injections of the medicinal product Cyclolux should not be performed unless the interval between consecutive injections is at least 7 days. Cyclolux is not recommended for use in angiography in children under 18 years of age due to insufficient data on efficacy and safety for this indication.
• Patients with renal impairment: For patients with mild to moderate renal impairment (GFR ≥ 30 ml/min/1.73 m²), doses recommended for adults are used. See section "Renal impairment" below.
• Patients with hepatic impairment: In such patients, doses recommended for adults are used. Caution is advised, especially in the perioperative period related to liver transplantation.

Route of administration
Cyclolux is indicated for intravenous use only. Do not administer intrathecally. Administer intravenously only: extravasation may cause local intolerance reactions requiring local treatment.
Infusion rate: 3–5 ml/min (in angiographic procedures, a higher infusion rate up to 120 ml/min, i.e., 2 ml/sec, may be used).
Optimal imaging: within 45 minutes after injection.
Optimal imaging sequence: T1-weighted images.
The contrast agent should be administered intravenously to the patient in a lying position whenever possible. After administration, the patient should be observed for at least 30 minutes, as clinical experience indicates that most adverse reactions occur during this period.
Prepare a syringe with a needle. Remove the plastic cap. Disinfect the stopper with an alcohol swab or gauze pad soaked in alcohol, then pierce the stopper with the needle. Draw up the volume of medicinal product required for the examination and inject it intravenously to the patient.
For single use only; any unused portions of the solution must be discarded.
The injectable solution should be visually inspected before use. Only clear solutions free from visible particles should be used.

Children and adolescents
Depending on the amount of Cyclolux to be administered to a child, it is recommended to use vials of Cyclolux product together with a single-use syringe of appropriate capacity to ensure greater accuracy of the injected volume.
In neonates and infants, the required dose should be administered manually.

Renal impairment
It is recommended that all patients undergo laboratory tests to assess renal function before administration of the medicinal product Cyclolux.
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. Due to the risk of NSF associated with the use of the medicinal product Cyclolux, this product should be used in patients with severe renal impairment and in patients in the perioperative period of liver transplantation only after careful assessment of benefit-risk ratio and only when diagnostic information is essential and cannot be obtained by non-contrast MRI. If use of the medicinal product Cyclolux is necessary, the dose should not exceed 0.1 mmol/kg body weight. More than one dose should not be administered during a single imaging procedure. Due to lack of data on repeated administration, repeated injections of the medicinal product Cyclolux should not be performed unless the interval between consecutive injections is at least 7 days.
Hemodialysis applied shortly after administration of the medicinal product Cyclolux may facilitate elimination of Cyclolux from the body. There is no evidence supporting initiation of hemodialysis for prophylaxis or treatment of NSF in patients who are not currently undergoing hemodialysis.

Elderly patients
Since renal clearance of gadoterinic acid may be reduced in elderly patients, prior assessment of renal function is particularly important in patients aged 65 years and older.

Neonates and infants
See section "Dosage and method of administration, Children and adolescents".

Pregnancy and breastfeeding
The medicinal product Cyclolux should not be used during pregnancy unless the woman's clinical condition requires administration of gadoterinic acid.
Continuation or interruption of breastfeeding for 24 hours after administration of the medicinal product Cyclolux should be decided at the discretion of the physician and the breastfeeding mother.

Instructions for handling the medicinal product
The detachable identification label from the vial should be attached to the patient's records to allow accurate identification of the contrast agent used. The administered dose should also be documented. If electronic patient records are used, the name of the medicinal product, batch number, and dose should be entered into the patient's record.