Cyclolux multidose

Package leaflet: Information for the user

Cyclolux multidose, 0.5 mmol/ml, solution for injection
Acidum gadotericum
Please read all of this leaflet carefully before this medicine is given to you, 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 get 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 multidose is and what it is used for
2. What you need to know before you are given Cyclolux multidose
3. How Cyclolux multidose is given
4. Possible side effects
5. How to store Cyclolux multidose
6. Contents of the pack and other information

1. What Cyclolux multidose is and what it is used for

Cyclolux multidose is a contrast agent containing gadoteric acid. It is intended
for diagnostic use only.
Cyclolux multidose is used to enhance the contrast of images obtained by
magnetic resonance imaging (MRI). This contrast enhancement improves the visibility and delineation of lesions in:
Adults, children and adolescents (0–18 years)

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

Adults

• MR angiography, including pathological lesions and stenoses in arteries, except coronary arteries.

2. Important information before using Cyclolux multidose

When NOT to use Cyclolux multidose

• 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 should inform your doctor or radiologist if any of the following apply to the patient:

• the patient has previously experienced a reaction to a contrast agent during an examination;
• the patient suffers from asthma;
• the patient has a history of allergies (e.g. to seafood, hives, hay fever);
• the patient is being treated with beta-blockers (medicines used to treat heart disorders and high 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 multidose can be administered to the patient. If Cyclolux multidose is administered, the doctor or radiologist will take necessary precautions and the administration will be closely monitored.
The doctor or radiologist may decide to perform a blood test to check kidney function before administering Cyclolux multidose, especially in patients aged 65 years and 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 multidose will be administered to such patients only after careful consideration by the doctor.
Before the examination, all metal objects the patient may be wearing should be removed. The patient should inform the doctor or radiologist if they have any of the following implanted:

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

Cyclolux multidose and other medicines
You should 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, inform the doctor, radiologist, or pharmacist if the patient is currently taking or has recently taken medicines for heart disorders or high blood pressure, such as beta-blockers, vasoactive agents, angiotensin-converting enzyme inhibitors, or angiotensin II receptor antagonists.
Use of Cyclolux multidose with food and drink
No interactions between Cyclolux multidose and food or drink are known. However, you should ask your doctor, radiologist, or pharmacist whether it is necessary to avoid 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 become pregnant, 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. Cyclolux multidose 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 whether she should interrupt breastfeeding for 24 hours after administration of Cyclolux multidose.
Driving and operating machinery
There are no available data on the effect of Cyclolux multidose on the ability to drive. If the patient feels unwell after the examination, they should not drive or operate machinery.

3. How to use Cyclolux multidose

Cyclolux multidose will be administered as an intravenous injection.
During the examination, the patient will be closely monitored by a physician or radiologist. An intravenous needle 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 multidose will be immediately stopped.
Cyclolux multidose may be injected manually or using an automated injector. In newborns and infants, this medicine must be administered manually only.
The procedure may be performed in a hospital, outpatient clinic, or private practice. Medical personnel are aware of the precautions necessary during the examination and are also 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 special patient groups
Cyclolux multidose is not recommended for patients with severe renal function impairment, or for patients who have recently undergone or are scheduled to undergo liver transplantation. However, if use of Cyclolux multidose 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 newborns, infants, children, and adolescents
Due to immature kidney function in newborns up to 4 weeks of age and infants up to 1 year of age, Cyclolux multidose will be used in such patients only after careful consideration by the physician. Newborns and infants should receive only a single dose of Cyclolux multidose 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
There is no need to adjust the dose in patients aged 65 years and older; however, blood tests may be necessary to assess kidney function.
Use of a higher than recommended dose of Cyclolux multidose
It is highly unlikely that a patient would receive an overdose of the medicine. Cyclolux multidose is administered in a medical facility by appropriately trained personnel. In the event of an actual overdose, Cyclolux multidose 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 any medicine, this medicinal product may cause adverse reactions, although not everybody experiences them.
After administration, the patient will be under observation for at least half an hour. Most adverse
reactions occur immediately or with some delay. Some adverse reactions may occur even up to seven days after injection of Cyclolux multidose.
There is a small risk that the patient may experience an allergic reaction to Cyclolux multidose.
Such 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 other healthcare professional:

• facial, lip and/or throat swelling, which may cause difficulty in swallowing or breathing,
• swelling of 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, reactions at injection site, feeling of cold at injection site, extravasation of the drug (leakage 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 feeling of impending loss of consciousness),
• eyelid swelling,
• palpitations,
• sneezing,
• vomiting,
• diarrhoea,
• increased salivation,
• urticaria, itching, excessive sweating,
• chest pain, chills.

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

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

There have been reports of systemic nephrogenic fibrosing dermopathy (which causes skin hardening and may also affect soft tissues and internal organs), occurring predominantly in patients who received Cyclolux multidose together with other contrast agents containing gadolinium. If, within weeks after an MRI examination, the patient notices changes in skin colour and/or thickness anywhere on the body, they should inform the radiologist who performed the examination.

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions 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, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products – Al. Jerozolimskie 181C, 02-222 Warsaw
Tel.: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions may 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 Cyclolux multidose

Keep this medicine out of the sight and reach of children.
No special precautions for 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 point of view, the medicine should be used immediately.
If not used immediately, the user is responsible for the duration and conditions of storage prior to use.
The storage period should not in general exceed 24 hours at a temperature of 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 package and other information

What Cyclolux multidose contains

• The active substance is gadoteric acid. One millilitre of injection solution contains 279.32 mg of gadoteric acid (as its meglumine salt), corresponding to 0.5 mmol of gadoteric acid (as its 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 multidose looks like and contents of the pack
Cyclolux multidose is a clear, colourless or yellowish intravenous injection solution, free from visible particles.
The Cyclolux multidose pack contains one or ten vials; one vial contains 60 or 100 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 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: Macrocylux
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 Injekčný roztok

Information intended exclusively for healthcare 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 diagnosis is 0.1 mmol/kg body weight (i.e., 0.2 ml/kg body weight). Angiography: In exceptional circumstances (e.g., when satisfactory image quality covering a large vascular area has not been 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 multidose 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) per dose, depending on the available imaging equipment.
• Children and adolescents: Brain and spinal cord MRI / Whole-body MRI: The recommended and maximum dose of the medicinal product Cyclolux multidose is 0.1 mmol/kg body weight. More than one dose should not be administered during a single imaging examination. Due to immature renal function in neonates up to 4 weeks of age and infants up to 1 year of age, Cyclolux multidose 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 examination. Due to lack of data on multiple administrations, repeat injections of the medicinal product Cyclolux multidose should not be given unless the interval between consecutive injections is at least 7 days. Cyclolux multidose 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: In patients with mild to moderate renal impairment (GFR ≥ 30 ml/min/1.73 m²), doses as recommended for adults should be used. See section “Renal impairment” below.
• Patients with hepatic impairment: In such patients, doses as recommended for adults should be used. Caution is advised, particularly in the perioperative period related to liver transplantation.

Route of administration
Cyclolux multidose is indicated for intravenous use only. Do not administer intrathecally.
Administration must be strictly intravenous: extravasation may cause local intolerance reactions requiring local treatment.
Infusion rate: 3–5 ml/min (in angiographic studies, higher infusion rates 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.
Whenever possible, the contrast agent should be administered intravenously to the patient in a supine position. After administration, the patient should be monitored for at least 30 minutes, as clinical experience shows that most adverse reactions occur during this period.
The rubber stopper must be punctured only once using an appropriate solution withdrawal device (spike applicator).
Generally, the solution withdrawal device should contain the following components: a trocar, a sterile air filter, a Luer connector, and a protective sealing cap.
It can be used with a single-use manual syringe (sterile) for single administration of the medicinal product or for bolus injection of a second contrast agent dose if clinically indicated.
An automated injection system may be used only for a single patient to administer the medicinal product multiple times.
Any remaining medicinal product in the vial and single-use device after completion of the examination must be discarded within 24 hours of puncturing the rubber stopper. Instructions provided by the device manufacturer must be strictly followed.
The injection 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 multidose to be administered to a child, it is recommended to use vials of Cyclolux multidose 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 multidose.
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 the use of the medicinal product Cyclolux multidose, this product should be used in patients with severe renal impairment and in patients in 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 use of the medicinal product Cyclolux multidose 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 examination. Due to lack of data on repeated administration, repeat injections of the medicinal product Cyclolux multidose should not be given unless the interval between consecutive injections is at least 7 days.
Hemodialysis shortly after administration of the medicinal product Cyclolux multidose may facilitate elimination of Cyclolux multidose from the body. There is no evidence to support initiating hemodialysis for prophylaxis or treatment of NSF in patients who are not currently undergoing hemodialysis.

Elderly patients
Since renal clearance of gadoterate acid may be reduced in elderly patients, it is particularly important to assess renal function in patients aged 65 years and older prior to administration.

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

Pregnancy and breastfeeding
The medicinal product Cyclolux multidose should not be used during pregnancy unless the clinical condition of the woman necessitates administration of gadoterate acid.
Continuation or interruption of breastfeeding for 24 hours after administration of the medicinal product Cyclolux multidose 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 vials should be attached to the patient’s medical record to allow accurate identification of the contrast agent used. The administered dose should also be recorded. If electronic patient records are used, the name of the medicinal product, batch number, and dose should be entered into the patient’s registry.