Package leaflet: Information for the user

CYCLOLUX 0.5 mmol/ml Solution for injection

Gadoteric acid

Read all of this leaflet carefully before you start using 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 get any side effects, talk to your doctor, radiologist or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet:

1.    What Cyclolux is and what it is used for

2.    What you need to know before Cyclolux is used

3.    How Cyclolux is used

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 diagnostic agent. It belongs to the group of contrast agents used for magnetic resonance imaging (MRI).

Cyclolux is used to enhance the contrast of the images obtained during MRI examination techniques. This contrast enhancement improves the visualisation and delineation of:

•    MRI of the CNS including defects (lesions) in brain, spinal cord and adjacent tissue;

•    Whole body MRI including defects (lesions) in liver, kidneys, pancreas, pelvis, lungs, heart, breast and musculoskeletal system;

•    MR angiography including defects (lesions) and narrowing (stenosis) in arteries, except in coronary arteries.

This medicine is for diagnostic use only.

2.    WHAT YOU NEED TO KNOW BEFORE CYCLOLUX IS USED

The information in this section should be read carefully.

The information given should be taken into consideration by you and your doctor or radiologist before you are given Cyclolux.

You should NOT be given Cyclolux

•    if you are allergic to the active section 6).

•    if you are allergic to medicines resonance imaging).

Warnings and precautions

Inform your doctor or radiologist if the following applies to you:

•    you have previously reacted to a contrast agent during an examination

•    you have asthma

•    you have a history of allergy (such as seafood allergy, urticaria, hay fever)

•    you are being treated with a beta-blocker (medicine for heart and blood pressure disorders, such as metoprolol)

•    your kidneys do not work properly

•    you have recently had, or soon expect to have, a liver transplant

•    you have a disease affecting your heart or your blood vessels

•    you have had convulsions or you are being treated for epilepsy.

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

Your doctor or radiologist may decide to take a blood test to check how well your kidneys are working before making the decision to use Cyclolux, especially if you are 65 years of age or older.

Neonates and infants

As kidney function is immature in babies up to 4 weeks of age and infants up to 1 year of age, Cyclolux will only be used in these patients after careful consideration by the doctor.

Remove all metallic objects you may wear before the examination. Inform your doctor or radiologist if you have:

•    a pacemaker

•    a vascular clip

•    an infusion pump

•    a nerve stimulator

•    a cochlear implant (implant in the inner ear)

•    any suspected metallic foreign bodies, particularly in the eye.

This is important as these can result in serious problems, as magnetic resonance imaging devices use very strong magnetic fields.

Other medicines and Cyclolux

Tell your doctor or radiologist if you are taking or have recently taken any other medicines. In particular, please inform your doctor, radiologist or pharmacist if you are taking or have recently taken medicines for heart and blood pressure disorders such as beta-blocking agents (such as metoprolol), vasoactive substances (such as doxazosin), angiotensin-converting enzyme inhibitors (such as ramipril), angiontensin II receptor antagonists (such as valsartan).

Cyclolux with food, drink and alcohol

There are no known interactions between Cyclolux and food and drinks. However, please check with your doctor, radiologist or pharmacist if it is required not to eat or drink before the examination.

Pregnancy, breastfeeding and fertility

If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby, ask your doctor or radiologist for advice before taking this medicine.

Pregnancy

Cyclolux should not be used during pregnancy unless strictly necessary.

Breastfeeding

Your doctor or radiologist will discuss whether you should continue breast-feeding or interrupt breast-feeding for a period of 24 hours after you receive Cyclolux.

Driving and using machines

No data are available on the effects of Cyclolux on the ability to drive. If you feel unwell after the examination, you should not drive or use machines.

3. HOW CYCLOLUX IS USED

Cyclolux will be administered to you by intravenous injection.

During the examination, 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 you with appropriate emergency drugs if necessary. If you experience an allergic reaction, the administration of Cyclolux will be stopped.

Cyclolux can be administered by hand or by the mean of an automatic injector. In children, the product will only be administered by hand.

The procedure will be carried out in a hospital, clinic or private practice. The attending staff know what precautions have to be taken for the examination. They are also a ware of the possible complications that can occur.

Dosage

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

Dosage in special patient groups

The use of Cyclolux is not recommended in patients with severe kidney problems and patients who have recently had, or soon expect to have, a liver transplant. However if use is required you should only receive one dose of Cyclolux during a scan and you should not receive a second injection for at least 7 days.

Neonates, infants, children and adolescents

As kidney function is immature in babies up to 4 weeks of age and infants up to 1 year of age, Cyclolux will only be used in these patients after careful consideration by the doctor. Neonates and infants should only receive one dose of Cyclolux during a scan and should not receive a second injection for at least 7 days.

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

Use for whole body MRI is not recommended in children less than 6 months of age.

Elderly

It is not necessary to adjust your dose if you are 65 years of age or older but you may have a blood test to check how well your kidneys are working.

If too much Cyclolux has been administered to you

It is highly unlikely that you will be given an overdose. You will be given Cyclolux in a medical setting by a trained person. In the real case of overdose, Cyclolux can be removed from the body by haemodialysis (blood cleaning).

Additional information regarding the use and handling by the medical or healthcare professional is given at the end of this leaflet.

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

There is a small risk that you may have an allergic reaction to Cyclolux. Such reactions can be severe and result in shock (case of allergic reaction that could put your life in danger). The following symptoms may be the first signs of a shock. Inform immediately your doctor, radiologist or health professional if you feel any of them:

• swelling of the face, mouth or throat which may cause you difficulties in swallowing or breathing

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•    swelling of hands or feet

•    lightheadedness (hypotension)

•    breathing difficulties

•    whistling respiration

•    coughing

•    itching

•    runny nose

•    sneezing

•    eye irritation

•    hives

•    skin rash

Very common side effects (may affect more than 1 in 10 people)

•    headaches

•    tingling sensation

Common side effects (may affect up to 1 in 10 people)

•    sensation of warmth or cold and/or pain at the injection site

•    nausea (feeling sick)

•    vomiting (being sick)

•    redness of the skin, itching and rash

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

•    allergic reactions

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

•    unusual taste in the mouth

•    hives, increased perspiration

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

•    agitation, anxiety

•    coma, seizures, syncope (brief loss of consciousness), faintness (dizziness and feeling of imminent loss of consciousness), dizziness, disorder of smell (perception of often unpleasant odours), tremor

•    conjunctivitis, red eye, blurred vision, increased tear secretion, eye swelling

•    cardiac arrest, accelered or slow heart beat, irregular heart beat, palpitations, low or high blood pressure, vascular dilatation, pallor

•    respiratory arrest, pulmonary oedema, breathing difficulties, feeling of tight throat, wheezing, stuffy nose, sneezing, cough, dry throat

•    diarrhoea, stomach pain, increased saliva secretion

•    eczema

•    muscle contractures, muscle weakness, back pain

•    malaise, chest pain, chest discomfort, fever, chills, swelling of the face, fatigue, injection site discomfort, injection site reaction, injection site swelling, diffusion of the product outside of blood vessels that can lead to inflammation (redness and local pain) or tissue dying off at the injection site, inflammation of a vein

•    decrease in oxygen level in blood

There have been reports of nephrogenic systemic fibrosis (which causes hardening of the skin and may affect also soft tissue and internal organs), most of which were in patients who received Cyclolux together with other gadolinium-containing contrast agents. If, during the weeks following the MRI examination, you notice changes in the colour and/or thickness of your skin in any part of your body, inform the radiologist who performed the examination.

Reporting of side effects

If you get any side effects, talk to your radiologist, pharmacist, doctor or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard. By reporting side effects you can help provide more information on the safety of this medicine.

5. HOW TO STORE CYCLOLUX

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

This medicinal product does not require any special precaution for storage.

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

Do not use this medicine after the expiry date which is stated on the vial and on the carton, after the abbreviation “Exp”. The expiry date refers to the last day of that month.

6. CONTENTS OF THE PACK AND OTHER INFORMATION What Cyclolux contains

•    The active substance is gadoteric acid. One millilitre of solution for injection contains 279.32 mg of gadoteric acid (as meglumine salt), equivalent to 0.5 mmol of gadoteric acid (as meglumine salt).

•    The other ingredients are meglumine, DOTA and water for injection.

What Cyclolux looks like and contents of the pack

Cyclolux is a clear, colourless to yellow solution for intravenous injection.

The Cyclolux pack contains one or ten vials with 10, 15 and 20 ml of solution for injection.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Sanochemia Pharmazeutika AG Boltzmanngasse 11 1090 Vienna, Austria

Manufacturer

Sanochemia Pharmazeutika AG

Landeggerstrasse 7

2491 Neufeld/Leitha, Austria

This leaflet was last revised in June 2015.

The following information is intended for medical or healthcare professionals only:

Posology

•    Brain and spinal MRI: In neurological examinations, the dose can vary from 0.1 to 0.3 mmol/kg BW, corresponding to 0.2 to 0.6 ml/kg BW. After administration of 0.1 mmol/kg BW to patients with brain tumours, the additional dose of 0.2 mmol/kg BW may improve tumour characterisation and facilitate therapeutic decision- making.

•    MRI of other organs and Angiography: The recommended dose for intravenous injection is 0.1 mmol/kg (i.e. 0.2 ml/kg) to provide diagnostically adequate contrast.

•    Angiography: In exceptional circumstances (e.g. failure to gain satisfactory images of an extensive vascular territory) administration of a second consecutive injection of 0.1 mmol/kg BW, equivalent to 0.2 ml/kg BW may be justified. However, if the use of 2 consecutive doses of Cyclolux is anticipated prior to commencing angiography, use of 0.05 mmol/kg BW, equivalent to 0.1ml/kg BW for each dose may be of benefit, depending on the imaging equipment available.

•    Children: The 0.1 mmol/kg BW dose applies to all indications except angiography due to insufficient data on efficacy and safety in this indication.

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 at a dose not exceeding 0.1 mmol/kg body weight. More than one dose should not be used during a scan. Because of the lack of information on repeated administration, Cyclolux injections should not be repeated unless the interval between injections is at least 7 days.

In neonates and infants the required dose should be administered by hand.

•    Patients with renal impairment: The adult dose applies to patients with mild to moderate renal impairment (GFR > 30 ml/min/1.73m²). See also below “Impaired renal function”.

•    Patients with hepatic impairment: The adult dose applies to these patients. Caution is recommended, especially in the case of perioperative liver transplantation period.

Method of administration

Cyclolux is indicated for intravenous administration only. Cyclolux must not be administered by subarachnoid (or epidural) injection.

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 for angiographic procedures)

Optimal imaging: within 45 minutes after injection Optimal image sequence: T1-weighted

Intravascular administration of contrast media should, if possible, be done with the patient lying down. After the administration, the patient should be kept under observation for at least half an hour, since experience shows that the majority of undesirable effects occur within this time.

Prepare a syringe with a needle. Remove the plastic disk. After cleaning the stopper with a pad soaked in alcohol, puncture the stopper with the needle. Withdraw the quantity of product required for the examination and inject it intravenously.

For single use only, any unused solution should be discarded.

The solution for injection should be inspected visually prior to use. Only clear solutions free of visible particles should be used.

Impaired renal function

Prior to administration of Cyclolux, it is recommended that all patients are screened for renal dysfunction by obtaining laboratory tests:

There have been reports of nephrogenic systemic fibrosis (NSF) associated with use of some gadolinium-containing contrast agents in patients with acute or chronic severe renal impairment (GFR < 30ml/min/1.73m²). Patients undergoing liver transplantation are at particular risk since the incidence of acute renal failure is high in this group. As there is a possibility that NSF may occur with Cyclolux, it should therefore only be used in patients with severe renal impairment and in patients in the perioperative liver transplantation period after careful risk/benefit assessment and if the diagnostic information is essential and not available with non-contrast enhanced MRI. If it is necessary to use Cyclolux, the dose should not exceed 0.1 mmol/kg body weight. More than one dose should not be used during a scan. Because of the lack of information on repeated administration, Cyclolux injections should not be repeated unless the interval between injections is at least 7 days. Haemodialysis shortly after Cyclolux administration may be useful at removing Cyclolux from the body. There is no evidence to support the initiation of haemodialysis for prevention or treatment of NSF in patients not already undergoing haemodialysis.

Elderly

As the renal clearance of gadoteric acid may be impaired in the elderly, it is particularly important to screen patients aged 65 years and older for renal dysfunction.

Neonates and infants

See under Posology, Children Pregnancy and lactation

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

Continuing or discontinuing breast feeding for a period of 24 hours after administration of Cyclolux, should be at the discretion of the doctor and lactating mother.

Instructions on handling

The peel-off tracking label on the vials should be stuck onto the patient record to enable accurate recording of the gadolinium contrast agent used. The dose used should also be recorded. If electronic patient records are used, the name of the product, the batch number and the dose should be entered into the patient record.

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