Ciclolux multidose

Package Leaflet: Information for the User

Cyclolux multidose, 0.5 mmol/ml, solution for injection

Gadoteric acid

Read the package leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this package 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 those not listed in this package leaflet, inform your doctor, radiologist, or pharmacist. See section 4.

Table of Contents of the Package Leaflet

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

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

Cyclolux multidose is a contrast agent containing gadoteric acid. It is for diagnostic use only.
Cyclolux multidose is used to increase the contrast of images obtained during magnetic resonance imaging (MRI) examinations. This contrast enhancement improves the visibility and definition of boundaries in:
Adults, children, and adolescents (0-18 years)

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

Adults

• MR angiography, including pathological changes and stenosis in arteries, with the exception of 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 any of the other ingredients of this medicine (listed in section 6).
• if the patient is allergic to gadolinium-containing contrast agents (such as other MRI contrast agents).

Warnings and precautions

Tell your doctor or radiologist if any of the following apply to the patient:

• the patient has had a reaction to a contrast agent during an examination;
• the patient has asthma;
• the patient has had an allergic reaction (e.g., to seafood, hives, hay fever);
• the patient is being treated with a beta-blocker (a medicine used to treat heart disorders and high blood pressure, such as metoprolol);
• the patient's kidneys do not work properly;
• the patient has recently undergone or is awaiting a liver transplant;
• the patient has a heart or blood vessel disease;
• the patient has had seizures or is being treated for epilepsy.

In all these cases, the doctor or radiologist will assess the benefit-risk ratio and decide whether the patient can be given Cyclolux multidose. If the patient is given Cyclolux multidose, the doctor or radiologist will take the necessary precautions, and the administration of Cyclolux multidose will be closely monitored.
The doctor or radiologist may decide to perform a blood test to check the patient's kidney function before using Cyclolux multidose, especially in patients over 65 years of age.

Newborns and infants

Due to the immaturity of kidney function in newborns up to 4 weeks of age and infants up to 1 year of age, Cyclolux multidose will only be used in these patients after careful consideration by the doctor.
Before the examination, all metal objects that the patient may be wearing should be removed. Inform the doctor or radiologist if the patient has:

• a pacemaker,
• a vascular clip,
• an infusion pump,
• a nerve stimulator,
• a cochlear implant (an implant in the inner ear),
• any suspected metal foreign body, especially in the eye. This is very important, as it can cause serious problems, since MRI equipment uses very strong magnetic fields.

Cyclolux multidose and other medicines

Tell your doctor or radiologist about all medicines the patient is taking or has recently taken, as well as any medicines the patient plans to take. In particular, inform your 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, vasodilators, ACE inhibitors, or angiotensin II receptor antagonists.

Using Cyclolux multidose with food and drink

No interactions between Cyclolux multidose and food or drink are known. However, ask your doctor, radiologist, or pharmacist if it is necessary to avoid eating or drinking before the examination.

Pregnancy and breastfeeding

If the patient is pregnant or breastfeeding, thinks she may be pregnant, or plans to have a child, she should consult her doctor or radiologist before using this medicine.
Pregnancy
Gadoteric acid may pass through the placenta. It is not known whether this affects the fetus. Cyclolux multidose should 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 stop for 24 hours after receiving Cyclolux multidose.

Driving and using machines

There is no available data on the effect of Cyclolux multidose on the ability to drive or use machines. 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 given as an intravenous injection.
During the examination, the patient will be closely monitored by the doctor or radiologist. A needle will be left in the patient's vein, so that if necessary, the doctor or radiologist can quickly inject life-saving medicines. If the patient has an allergic reaction, the administration of Cyclolux multidose will be stopped immediately.
Cyclolux multidose can be injected manually or using an automatic injector. In newborns and infants, this medicine is given manually only.
This procedure can be performed in a hospital, clinic, or private office. Medical personnel know what precautions to take during the examination and are also aware of potential complications that may occur.

Dosage

The doctor or radiologist will determine the dose suitable for the patient and will supervise the administration of Cyclolux multidose.

Dosage in special patient groups

Cyclolux multidose is not recommended for use in patients with severe kidney function disorders or in patients who have recently undergone or are awaiting a liver transplant. However, if the use of Cyclolux multidose is necessary, the patient should receive only one dose of the medicine during the examination and should not receive another dose for at least 7 days.
Use in newborns, infants, children, and adolescents
Due to the immaturity of kidney function in newborns up to 4 weeks of age and infants up to 1 year of age, Cyclolux multidose will only be used in these patients after careful consideration by the doctor. Newborns and infants should receive only one dose of Cyclolux multidose during the examination and should not receive another dose for at least 7 days.
Cyclolux multidose is not recommended for use in angiography in children under 18 years of age.
Elderly patients
There is no need to adjust the dose in patients over 65 years of age; however, it may be necessary to perform a blood test to check kidney function.

Overdose of Cyclolux multidose

It is very unlikely that the patient will receive too much Cyclolux multidose. Cyclolux multidose will be given in a medical facility by properly trained personnel. In case of 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 package leaflet.
If you have any further questions about the use of this medicine, ask your doctor or radiologist.

4. Possible side effects

Like all medicines, Cyclolux multidose can cause side effects, although not everybody gets them.
After administration, the patient will be monitored for at least half an hour. Most side effects occur immediately or with some delay. Some side effects may occur even up to seven days after the injection of Cyclolux multidose.

There is a small risk of an allergic reaction to Cyclolux multidose.

Such reactions can be severe and cause anaphylactic shock(a type of allergic reaction that can be life-threatening). The following symptoms may be the first signs of anaphylactic shock. If the patient notices any of these symptoms, they should immediately inform their doctor, radiologist, or other medical personnel:

• swelling of the face, lips, and/or throat, which may cause difficulty swallowing or breathing,
• swelling of the hands or feet,
• feeling of dizziness (low blood pressure),
• shortness of breath (difficulty breathing),
• wheezing,
• coughing,
• itching of the skin,
• runny nose,
• sneezing,
• eye irritation,
• hives,
• skin rash.

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

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

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

• anxiety, presyncope (dizziness and feeling of impending loss of consciousness),
• eyelid swelling,
• palpitations,
• coughing,
• vomiting,
• diarrhea
• increased salivation,
• hives, itching, excessive sweating
• chest pain, chills.

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

• anaphylactic or anaphylactoid reactions (severe, potentially life-threatening allergic reactions),
• agitation,
• coma, seizures, fainting (short-term loss of consciousness), olfactory disorders (perception of unpleasant odors), muscle tremors,
• conjunctivitis, eye redness, blurred vision, increased tearing,
• cardiac arrest, accelerated or slowed heart rate, arrhythmia, vasodilation, pallor,
• respiratory arrest, pulmonary edema, breathing difficulties, wheezing, stuffy nose, coughing, throat dryness, throat constriction with a feeling of suffocation, respiratory spasms, throat swelling,
• flushing, skin redness, swelling of the lips and/or mouth,
• muscle spasms, muscle weakness, back pain,
• malaise, chest discomfort, fever, facial swelling, extravasation, which can lead to tissue necrosis (redness and local pain) at the injection site, phlebitis,
• decreased oxygen levels in the blood.

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

Reporting side effects

If you experience any side effects, including those not listed in this package leaflet, inform your radiologist, pharmacist, doctor, or nurse.
Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocidal Products – Al. Jerozolimskie 181C, 02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Cyclolux multidose

Keep the medicine out of the sight and reach of children.
No special precautions for storage are necessary.
Chemical and physical stability of the medicine has been demonstrated after the first use for 72 hours at room temperature. From a microbiological point of view, the medicine should be used immediately. If not used immediately, the responsibility for the storage time and conditions before use lies with the user. The storage time should not normally exceed 24 hours at 2 to 8°C, unless the opening is performed under controlled and validated aseptic conditions.
Do not use this medicine after the expiry date stated on the vial and carton after "EXP". The expiry date refers to the last day of the month stated.

6. Contents of the pack and other information

What Cyclolux multidose contains

• The active substance is gadoteric acid. One milliliter of the solution for injection contains 279.32 mg of gadoteric acid (as meglumine salt), which corresponds to 0.5 mmol of gadoteric acid (as meglumine salt).
• The other ingredients 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 solution for intravenous injection, colorless or in various shades of yellow, free from visible particles.
The pack contains one or ten vials; one vial contains 60 or 100 ml of the solution for injection.
Not all pack sizes may be marketed.

Marketing authorization 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 medicine 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: 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

Date of last revision of the package leaflet: 08-05-2024

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Information intended for healthcare professionals only:

Dosage

Use the smallest dose that provides sufficient contrast enhancement for diagnostic purposes. The dose should be calculated based on the patient's body weight and should not exceed the recommended dose per kilogram of body weight.

• MRI of the brain and spinal cord: In CNS examinations, doses range from 0.1 to 0.3 mmol/kg body weight, which corresponds to 0.2 to 0.6 ml/kg body weight. After administration of 0.1 mmol/kg body weight to patients with brain tumors, administration of an additional dose of 0.2 mmol/kg body weight may improve tumor visibility and facilitate treatment decisions.
• MRI of the whole body and angiography: The recommended dose for intravenous injection, 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 images of satisfactory quality, covering an extensive vascular area, are not obtained), a second 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 Cyclolux multidose are planned before the start of angiography, it may be beneficial to administer 0.05 mmol/kg body weight (i.e., 0.1 ml/kg body weight) in each dose, depending on the available imaging equipment.
• Children and adolescents: MRI of the brain and spinal cord / whole-body MRI: the recommended and maximum dose of Cyclolux multidose is 0.1 mmol/kg body weight. Do not administer more than one dose during the imaging examination. Due to the immaturity of kidney function in newborns 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 by the doctor. Newborns and infants should receive only one dose of Cyclolux multidose during the examination and should not receive another dose for at least 7 days. Do not repeat injections of Cyclolux multidose unless the interval between injections is at least 7 days. Cyclolux multidose is not recommended for use in angiography in children under 18 years of age.
• Patients with kidney function disorders: Use the doses recommended for adults. See "Kidney function disorders" below.
• Patients with liver function disorders: Use the doses recommended for adults. Exercise caution, especially in the perioperative period of liver transplantation.

Method of administration

Cyclolux multidose is indicated for intravenous use only. Do not administer intraperitoneally.
Administer intravenously only: extravasation may cause local intolerance reactions, requiring local treatment.
Infusion rate: 3-5 ml/min (at angiographic examinations, a higher infusion rate of up to 120 ml/min, i.e., 2 ml/sec, can 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 half an hour, as experience shows that most side effects occur during this period.
The rubber stopper must be pierced only once using a suitable device (spike) for withdrawing the solution.
Generally, the device for withdrawing the solution must include the following elements: a trocar, a sterile air filter, a Luer connector, and a protective cap.

Kidney function disorders

It is recommended that all patients undergo laboratory tests to check kidney function before administration of 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 kidney function disorders (GFR <30 ml min 1.73 m2). patients who have undergone liver transplantation are particularly at risk due to the high frequency of acute kidney failure in this group. nsf associated with cyclolux multidose, medicine should only be used severe function disorders and perioperative period after careful benefit-risk assessment when diagnostic information is essential cannot obtained using mri without contrast enhancement. if use multidose necessary, dose not exceed 0.1 mmol kg body weight. do administer more than one during imaging examination. lack on repeated administration, repeat injections unless interval between least 7 days.
Hemodialysis performed shortly after administration of Cyclolux multidose may facilitate the elimination of Cyclolux multidose from the body. There is no evidence to support the initiation of hemodialysis as a prophylactic or therapeutic measure for NSF in patients who are not currently undergoing hemodialysis.

Elderly patients

As kidney clearance of gadoteric acid may be reduced in elderly patients, it is especially important to check kidney function in patients over 65 years of age.

Newborns and infants

See "Dosage and method of administration, Children and adolescents".

Pregnancy and breastfeeding

Cyclolux multidose should not be used during pregnancy unless the clinical condition of the woman requires the administration of gadoteric acid.
The decision to continue or stop breastfeeding for 24 hours after administration of Cyclolux multidose should be left to the doctor and the breastfeeding mother.

Handling of the medicinal product

The torn label from the vials should be attached to the patient's documentation to allow for accurate identification of the contrast agent used. The administered dose should also be recorded. If electronic patient cards are used, the name of the medicinal product, batch number, and dose should be entered in the patient's record.