Macrocylux

Package leaflet: Information for the user

Macrocylux 0,5 mmol/ml

Injection solution
Gadoteric acid
Generic medicine
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 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.

Contents of this leaflet:

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

1. What Macrocylux is and what it is used for

Macrocylux is a contrast agent containing gadoteric acid. It is for diagnostic use only.
Macrocylux is used to enhance contrast in images obtained by magnetic resonance imaging (MRI), in order to improve visualization and delineation in:
Adult 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 (so-called total body), including abnormalities (lesions) of the liver, kidneys, pancreas, pelvis, lungs, heart, breast, and the musculoskeletal system. Adult population
• MR angiography (MRA), including abnormalities (lesions) and narrowing (stenosis) of arteries, except coronary arteries.

2. What you need to know before using Macrocylux

Macrocylux must NOT be administered to you

• 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 for magnetic resonance imaging).

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

• you have previously experienced reactions to a contrast agent during an earlier examination
• you suffer from asthma
• you have a history of allergies (for example, allergy to shellfish, hives, hay fever)
• you are being treated with a beta-blocker (a medicine for heart conditions and blood pressure, such as metoprolol)
• your kidneys do not function properly
• you have recently undergone, or are scheduled to undergo, a liver transplant
• you have a disease affecting the heart or blood vessels
• you have had seizures or are being treated for epilepsy.

In all these cases, your doctor or radiologist will evaluate the benefit-risk ratio and decide whether it is appropriate to administer Macrocylux to you. If Macrocylux is administered to you, your doctor or radiologist will take the necessary precautions and the administration of Macrocylux will be closely monitored.
Your doctor or radiologist may decide to perform a blood test to check kidney function before deciding to use Macrocylux, especially if you are 65 years of age or older.
Newborns and infants
Since kidney function is immature in newborns up to 4 weeks of age and in infants up to 1 year of age, Macrocylux will be used in these patients only after careful evaluation by the doctor.
Before the examination, remove all metallic objects you may be wearing. Inform your doctor or radiologist if you have:

• a pacemaker
• a vascular clip
• an infusion pump
• a nerve stimulator
• a cochlear implant (an implant in the inner ear)
• suspected presence of any metallic foreign body, particularly in the eye. This is important because these devices may cause serious problems, as the machines used for magnetic resonance imaging employ very powerful magnetic fields.

Other medicines and Macrocylux
Inform your doctor or radiologist if you are taking, have recently taken, or might take any other medicines. In particular, inform your doctor, radiologist, or pharmacist if you are taking or have recently taken medicines for heart conditions and blood pressure, such as beta-blocking agents, vasoactive substances, angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists.
Macrocylux with food and drink
Interactions between Macrocylux and food or drink are not known. However, please consult your doctor, radiologist, or pharmacist to find out whether you need to refrain from eating or drinking before the examination.
Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or are breastfeeding, ask your doctor or radiologist for advice before taking this medicine.
Pregnancy
Gadoteric acid may cross the placenta. It is not known whether this could affect the unborn child. Macrocylux should not be used during pregnancy unless strictly necessary.
Breastfeeding
Your doctor or radiologist will assess whether you should continue or interrupt breastfeeding for 24 hours after receiving Macrocylux.
Driving and using machines
There are no data available on the effects of Macrocylux on the ability to drive. If you feel unwell after the examination, you must not drive or operate machinery.

3. How to use Macrocylux

Macrocylux will be administered to you as an intravenous injection.
During the examination, you will be under the supervision of a physician or radiologist. An intravenous cannula will be left in place to allow the physician or radiologist to administer appropriate emergency medications if needed. If you develop an allergic reaction, administration of Macrocylux will be stopped.
Macrocylux may be administered manually or by using an automatic injector. In neonates and infants, the product will be administered only manually.
The procedure will be performed in a hospital, clinic, or private practice. The staff are aware of the precautions required for the examination and are also familiar with potential complications that may occur.
Dosage
Your physician or radiologist will determine the dose you will receive and will supervise the injection.
Dosage in specific patient groups
The use of Macrocylux is not recommended in patients with severe renal impairment and in patients who have recently undergone or will shortly undergo liver transplantation. However, if use is necessary, you should receive only one dose of Macrocylux per scan, and a second injection must not be given within at least 7 days.
Neonates, infants, children, and adolescents
Since renal function is immature in neonates up to 4 weeks of age and in infants up to 1 year of age, Macrocylux should be used in these patients only after careful medical evaluation. Neonates and infants should receive only one dose of Macrocylux per scan, and a second injection must not be given within at least 7 days.
Use for angiography is not recommended in patients under 18 years of age.
Elderly
Dose adjustment is not required if you are 65 years of age or older, but you may undergo a blood test to assess kidney function.
If you have been given too high a dose of Macrocylux
It is highly unlikely that you will receive an overdose. Macrocylux will be administered by an experienced healthcare professional in a medical setting. In the event of an actual overdose, Macrocylux can be removed from the body by haemodialysis (blood purification).
Additional information on use and handling by the physician or healthcare provider is provided at the end of this leaflet.
If you have further questions about the use of this medicine, please consult your physician or radiologist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
After administration, you will be monitored for at least half an hour. Most side effects occur immediately, but sometimes they may appear later. Some effects may occur up to seven days after injection of Macrocylux.
There is a minimal risk that you may have an allergic reaction to Macrocylux. These reactions can be severe and
cause shock (an allergic reaction that could be life-threatening). The following symptoms may be early signs of shock. Inform your doctor, radiologist, or healthcare professional immediately if you experience any of these symptoms:

• swelling of the face, mouth, or throat causing difficulty swallowing or breathing
• swelling of the hands or feet
• dizziness (low blood pressure)
• difficulty breathing
• wheezing
• cough
• itching
• runny nose
• sneezing
• eye irritation
• hives
• skin rash

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

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

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

• anxiety, fainting (dizziness and feeling of impending loss of consciousness)
• eyelid swelling
• palpitations
• sneezing
• vomiting
• diarrhoea
• increased salivation
• hives, itching, 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, convulsions, syncope (brief loss of consciousness), disturbances in smell (perception of often unpleasant odours), tremor
• conjunctivitis, red eyes, blurred vision, increased tear production
• cardiac arrest, accelerated or slowed heartbeat, irregular heartbeat, vasodilation, pallor
• respiratory arrest, pulmonary oedema, breathing difficulties, 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, diffusion of the product 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 (causing skin hardening and potentially affecting soft tissues and internal organs) have been reported, most of them in patients who received Macrocylux together with other contrast agents containing gadolinium. If in the weeks following the MRI scan you notice changes in the colour and/or thickness of the skin in any part of your body, inform the radiologist who performed the examination.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please contact your radiologist, pharmacist, doctor, or nurse. You may also report side effects directly through the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse . Reporting side effects helps provide more information on the safety of this medicine.

5. How to store Macrocylux

Keep this medicine out of the sight and reach of children.
This medicine requires no special storage conditions.
Chemical and physical in-use stability has been demonstrated for 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 2-8°C,
unless reconstitution has taken place under controlled and validated aseptic conditions.
Do not use this medicine after the expiry date stated on the vial and the outer carton, following the abbreviation “Exp”. The expiry date refers to the last day of that month.

6. Package contents and other information

What Macrocylux contains

• The active substance is gadoteric acid. One millilitre 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 are meglumine, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), and water for injection.

Description of the appearance of Macrocylux and contents of the package
Macrocylux is a clear, colourless to yellow solution for intravenous injection. The Macrocylux packaging contains one or ten vials containing 10, 15, and 20 ml of injectable 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 European Economic Area (EEA) Member States 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 šķīdums
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
Northern Ireland: Cyclolux 0.5 mmol/ml solution for injection

The following information is intended exclusively for physicians and healthcare professionals:
Dosage
The lowest dose that provides sufficient diagnostic enhancement 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 specified in this section.

• Brain and spinal cord MRI: In neurological examinations, the dose may range from 0.1 to 0.3 mmol/kg body weight (BW), corresponding to 0.2–0.6 ml/kg BW. In patients with brain tumours, after administration of 0.1 mmol/kg BW, an additional dose of 0.2 mmol/kg BW may improve tumour characterisation and facilitate therapeutic decision-making.

• Whole-body MRI and angiography: The recommended dose for intravenous injection is 0.1 mmol/kg BW (i.e., 0.2 ml/kg BW) to ensure adequate diagnostic contrast. Angiography: In exceptional circumstances (e.g., inability to obtain satisfactory images of a large vascular area), administration of a second consecutive injection of 0.1 mmol/kg BW, equivalent to 0.2 ml/kg BW, may be justified. However, if two consecutive doses of Macrocylux are expected to be used before starting angiography, using 0.05 mmol/kg BW (equivalent to 0.1 ml/kg BW) for each dose may be beneficial, depending on the available diagnostic imaging equipment.

• Paediatric population: Brain and spinal cord MRI/whole-body MRI: The recommended and maximum dose of Macrocylux is 0.1 mmol/kg body weight. Due to immature renal function in neonates up to 4 weeks of age and children up to 1 year of age, Macrocylux should be used in these patients only after careful assessment and at a dose not exceeding 0.1 mmol/kg body weight. No more than one dose should be used during a single scan. Due to lack of data on repeated administration, Macrocylux injections should not be repeated unless the interval between injections is at least 7 days. Macrocylux is not recommended for angiography in patients under 18 years of age due to insufficient data on efficacy and safety for this indication.

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

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

Method of administration
Macrocylux is intended for intravenous use only. Do not use intrathecally. Care must be taken to ensure strict intravenous injection: extravasation may cause local intolerance reactions requiring conventional topical treatment.
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: within 45 minutes after injection.
Optimal imaging sequence: T1-weighted.
Intravascular administration of contrast agents should be performed, if possible, with the patient lying down.
After administration, the patient should be observed for at least 30 minutes, as experience shows that most adverse reactions occur within this period.
Prepare a syringe with a needle. Remove the plastic cap. After cleaning the stopper with an alcohol swab, pierce it with the needle. Withdraw the required amount of product for the examination and inject it intravenously.
For single use only; any unused solution must be discarded.
The injectable solution should be inspected visually before use. Only clear solutions free from visible particles should be used.
Paediatric population
Depending on the amount of Macrocylux to be administered, it is preferable to use Macrocylux vials with a single-use syringe of appropriate volume to ensure accurate dosing.
In neonates and infants, the required dose must be administered manually.

Renal impairment
Before administering Macrocylux, it is recommended that all patients be screened for renal dysfunction through laboratory tests.
Cases of nephrogenic systemic fibrosis (NSF) have been reported following the use of certain gadolinium-containing contrast agents in patients with acute or severe chronic renal failure (GFR < 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 occur with Macrocylux, this medicinal product should be used in patients with severe renal insufficiency and in patients in the perioperative period of liver transplantation only after careful assessment of the risk-benefit ratio and when essential diagnostic information cannot be obtained by non-contrast MRI. If Macrocylux must be used, the dose should not exceed 0.1 mmol/kg body weight. No more than one dose should be used during a single scan. Due to lack of data on repeated administration, Macrocylux injections should not be repeated unless the interval between injections is at least 7 days.
Haemodialysis shortly after administration of Macrocylux may be helpful in eliminating Macrocylux from the body. There is no evidence demonstrating benefit from initiating haemodialysis for the prevention or treatment of NSF in patients not already undergoing dialysis.

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

Neonates and infants
See the section "Dosage and method of administration", Paediatric population.

Pregnancy and breastfeeding
Macrocylux should not be used during pregnancy unless the clinical condition of the woman requires the use of gadoteric acid.
The decision to continue or interrupt breastfeeding for 24 hours after administration of Macrocylux should be made at the discretion of the physician and the breastfeeding mother.

Instructions for handling
The removable tracking label on the vials should be affixed to the patient's medical record to ensure correct documentation of the gadolinium-based contrast agent used. The administered dose must also be recorded. If an electronic medical record is used, the product name, batch number, and dose must be entered into the patient's record.

Patient Information Leaflet: Information for the user

Macrocylux 0.5 mmol/ml

Injection solution
Gadoteric acid
Equivalent medicine
Please read this leaflet carefully before using this medicine because it contains important information for you.

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

Contents of this leaflet:

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

1. What Macrocylux is and what it is used for

Macrocylux is a contrast agent containing gadoteric acid. It is for diagnostic use only.
Macrocylux is used to enhance contrast in magnetic resonance (MR) images in order to improve the visualization and delineation of:
Adult and pediatric population (0–18 years)

• MR imaging of the central nervous system, including abnormalities (lesions) of the brain, spinal cord, and adjacent tissues;
• Whole-body MR imaging (so-called total body), including abnormalities (lesions) of the liver, kidneys, pancreas, pelvis, lungs, heart, breast, and the musculoskeletal system. Adult population
• MR angiography (MRA), including abnormalities (lesions) and narrowing (stenosis) of arteries, except for coronary arteries.

2. What you need to know before using Macrocylux

Macrocylux must NOT be administered to you

• 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 for magnetic resonance imaging).

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

• you have previously experienced reactions to a contrast agent during an earlier examination
• you suffer from asthma
• you have a history of allergies (for example, allergy to shellfish, hives, hay fever)
• you are being treated with a beta-blocker (a medicine for heart conditions and high blood pressure, such as metoprolol)
• your kidneys do not function properly
• you have recently undergone, or are scheduled to undergo, a liver transplant
• you have a disease affecting the heart or blood vessels
• you have had seizures or are being treated for epilepsy.

In all these cases, your doctor or radiologist will evaluate the benefit-risk ratio and decide whether it is appropriate to administer Macrocylux to you. If Macrocylux is administered to you, your doctor or radiologist will take the necessary precautions and the administration of Macrocylux will be closely monitored.
Your doctor or radiologist may decide to perform a blood test to check kidney function before deciding to use Macrocylux, especially if you are 65 years of age or older.
Newborns and infants
Since kidney function is immature in newborns up to 4 weeks of age and in infants up to 1 year of age, Macrocylux will be used in these patients only after careful evaluation by the doctor.
Before the examination, remove all metallic objects you may be wearing. Inform your doctor or radiologist if you have:

• a pacemaker
• a vascular clip
• an infusion pump
• a nerve stimulator
• a cochlear implant (an implant in the inner ear)
• suspected presence of any metallic foreign body, particularly in the eye. This is important because these devices may cause serious problems, as the machines used for magnetic resonance imaging employ very strong magnetic fields.

Other medicines and Macrocylux
Inform your doctor or radiologist if you are taking, have recently taken, or might take any other medicines. In particular, inform your doctor, radiologist, or pharmacist if you are taking or have recently taken medicines for heart conditions and high blood pressure, such as beta-blocking agents, vasoactive substances, angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists.
Macrocylux with food and drink
No interactions between Macrocylux and food or drink are known. However, please consult your doctor, radiologist, or pharmacist to find out whether you need to avoid eating or drinking before the examination.
Pregnancy and breastfeeding
If you are pregnant, think you might be pregnant, planning to become pregnant, or are breastfeeding, ask your doctor or radiologist for advice before taking this medicine.
Pregnancy
Gadoteric acid may cross the placenta. It is not known whether this may affect the unborn child. Macrocylux must not be used during pregnancy unless strictly necessary.
Breastfeeding
Your doctor or radiologist will assess whether you should continue or interrupt breastfeeding for 24 hours after receiving Macrocylux.
Driving and using machines
There are no data available on the effects of Macrocylux on the ability to drive. If you feel unwell after the examination, you must not drive or operate machinery.

3. How to use Macrocylux

Macrocylux will be administered to you as an intravenous injection.
During the examination, you will be under the supervision of a physician or radiologist. A venous needle will remain in place to allow the physician or radiologist to inject appropriate emergency medications, if needed. If you develop an allergic reaction, administration of Macrocylux will be stopped.
Macrocylux may be administered manually or by means of an automatic injector. In newborns and infants, the product will be administered only manually.
The procedure will be performed in a hospital, clinic, or private practice. The staff are aware of the precautions required for the examination and are also aware of potential complications that may occur.

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

Dosage in specific patient groups
The use of Macrocylux is not recommended in patients with severe renal impairment and in patients who have recently undergone, are undergoing, or will undergo liver transplantation. However, if use is necessary, you must receive only one dose of Macrocylux per scan and must not receive a second injection within at least 7 days.

Newborns, infants, children, and adolescents
Since renal function is immature in newborns up to 4 weeks of age and in infants up to 1 year of age, Macrocylux should be used in these patients only after careful physician evaluation. Newborns and infants must receive only one dose of Macrocylux per scan and must not receive a second injection within at least 7 days.
The use of Macrocylux for angiography is not recommended in patients under 18 years of age.

Elderly
Dose adjustment is not necessary if you are 65 years of age or older, but you may undergo a blood test to assess kidney function.

If you have been administered an overdose of Macrocylux
It is highly unlikely that you will receive an excessive dose. Macrocylux will be administered in a medical setting by an experienced professional. In the event of actual overdose, Macrocylux can be removed from the body by haemodialysis (blood cleansing).

Further information on use and handling by the physician or healthcare provider is provided at the end of this leaflet.
If you have further questions about the use of this medicinal product, please consult your physician or radiologist.

4. Possible adverse reactions

Like all medicines, this medicine may cause adverse reactions, although not everybody gets them.
After administration, you will be kept under observation for at least 30 minutes. Most adverse reactions occur immediately, but sometimes they may appear later. Some reactions may occur up to seven days after injection of Macrocylux.
There is a minimal risk that you may have an allergic reaction to Macrocylux. These reactions can be severe and may cause anaphylactic shock (an allergic reaction that could be life-threatening). The following symptoms 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 (low blood pressure)
• difficulty breathing
• wheezing
• cough
• itching
• runny nose
• sneezing
• eye irritation
• hives
• skin rash

Uncommon adverse reactions (may affect up to 1 in 100 people)

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

Rare adverse reactions (may affect up to 1 in 1,000 people)

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

Very rare adverse reactions (may affect up to 1 in 10,000 people)

• anaphylactic or anaphylactoid reactions (severe, potentially life-threatening allergic reactions)

• agitation

• coma, convulsions, syncope (brief loss of consciousness), disturbances in smell (perception of often unpleasant odors), tremor

• conjunctivitis, red eyes, blurred vision, increased tear production

• cardiac arrest, accelerated or slowed heartbeat, irregular heartbeat, vasodilation, 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 swelling in the mouth

• muscle cramps, muscle weakness, back pain

• malaise, chest discomfort, fever, facial swelling, extravasation of the product outside blood vessels which may lead to tissue death at the injection site, inflammation of a vein

• decreased oxygen levels in the blood

Cases of nephrogenic systemic fibrosis (causing skin hardening and potentially affecting soft tissues and internal organs) have been reported, most of them in patients who received Macrocylux together with other gadolinium-containing contrast agents. If in the weeks following the MRI scan you notice changes in the color and/or thickness of the skin in any part of your body, inform the radiologist who performed the examination.
Reporting of adverse reactions
If you experience any adverse reaction, including those not listed in this leaflet, talk to the radiologist, pharmacist, doctor, or nurse. You can also report adverse reactions directly via the national reporting system at the following website: https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse . By reporting adverse reactions, you can help provide more information on the safety of this medicine.

5. How to store Macrocylux

Keep this medicine out of the sight and reach of children.
This medicine does not require any special storage precautions.
Chemical and physical in-use stability has been demonstrated for 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 2-8°C, unless the container was opened under controlled and validated aseptic conditions.
Do not use this medicine after the expiry date stated on the vial and carton, following the abbreviation “Scad”. The expiry date refers to the last day of that month.

6. Package contents and other information

What Macrocylux contains

• The active substance is gadoteric acid. One millilitre 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 are meglumine, 2,2’,2’’,2’’’-(1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid (DOTA), and water for injection.

Description of the appearance of Macrocylux and contents of the pack
Macrocylux is a clear, particle-free solution, ranging from colourless to yellow, for intravenous injection. The Macrocylux pack contains either one or ten vials containing 60 ml or 100 ml of injectable 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 (EEA) 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
Slovak Republic: Cyclolux Multi 0.5 mmol/ml Injekčný roztok

The following information is intended exclusively for physicians and healthcare professionals:

Dosage
The lowest dose providing sufficient diagnostic enhancement 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 specified in this section.

• MRI of the brain and spinal cord: In neurological examinations, the dose may range from 0.1 to 0.3 mmol/kg body weight (BW), corresponding to 0.2–0.6 ml/kg BW. In patients with brain tumours, following administration of 0.1 mmol/kg BW, an additional dose of 0.2 mmol/kg BW may improve tumour characterisation and facilitate therapeutic decision-making.
• Whole-body MRI and angiography: The recommended dose for intravenous injection is 0.1 mmol/kg BW (i.e., 0.2 ml/kg BW) to ensure adequate diagnostic contrast. Angiography: under exceptional circumstances (e.g., inability to obtain satisfactory images of a large vascular area), administration of a second consecutive injection of 0.1 mmol/kg BW, equivalent to 0.2 ml/kg BW, may be justified. However, if two consecutive doses of Macrocylux are expected to be used prior to starting angiography, using 0.05 mmol/kg BW (equivalent to 0.1 ml/kg BW) for each dose may be beneficial, depending on the available diagnostic imaging equipment.
• Paediatric population: MRI of the brain and spinal cord/whole-body MRI: The recommended and maximum dose of Macrocylux is 0.1 mmol/kg body weight. Due to immature renal function in neonates up to 4 weeks of age and children up to 1 year of age, Macrocylux should be used in these patients only after careful consideration and at a dose not exceeding 0.1 mmol/kg body weight. No more than one dose should be administered during a single scan. Due to lack of data on repeated administration, Macrocylux injections should not be repeated unless the interval between injections is at least 7 days. Macrocylux is not recommended for angiography in patients under 18 years of age due to insufficient data on efficacy and safety for this indication.
• 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 “Renal function impairment”.
• Patients with hepatic impairment: The adult dose applies to these patients. Caution is recommended, particularly during the perioperative period of liver transplantation.

Method of administration
Macrocylux is indicated only for intravenous administration. Do not use intrathecally. Care must be taken to ensure strict intravenous injection: extravasation may cause local intolerance reactions requiring standard topical treatment.
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: within 45 minutes after injection.
Optimal imaging sequence: T1-weighted.
Intravascular administration of contrast agents should be performed, whenever possible, with the patient in the supine position. After administration, the patient should be monitored for at least 30 minutes, as clinical experience shows that most adverse reactions occur within this time frame.
The rubber stopper should be punctured only once using an appropriate withdrawal device (spike).
In general, the withdrawal device should have the following characteristics: trocar needle, sterile air filter, Luer adapter, and protective seal.
The product may be used with a single-use (sterile) manual syringe filled with sufficient volume to perform a single-dose protocol or to inject a second contrast bolus, if clinically required.
An automatic injector may be used only for a single patient to perform multiple administrations.
At the end of the examination session, any remaining product in the vial and in the single-use device must be discarded within 24 hours of piercing the rubber stopper. Strictly follow the instructions provided by the manufacturer of the device used.
The injectable solution should be visually inspected before use. Only clear solutions free from visible particles should be used.

Paediatric population
Depending on the amount of Macrocylux to be administered, it is preferable to use Macrocylux vials with a single-use syringe of appropriate volume to ensure accurate dosing.
In neonates and infants, the required dose should be administered manually.

Renal function impairment
Before administering Macrocylux, it is recommended to screen all patients for renal dysfunction through laboratory tests.
Cases of nephrogenic systemic fibrosis (NSF) have been reported following the use of certain gadolinium-containing contrast agents in patients with acute or severe chronic renal failure (GFR < 30 ml/min/1.73m²). Patients undergoing liver transplantation are at particular risk, as the incidence of acute renal failure is high in this group. Since there is a potential risk of NSF with Macrocylux, this medicinal product should be used in patients with severe renal impairment and in patients during the perioperative period of liver transplantation only after careful assessment of the risk-benefit ratio and when essential diagnostic information cannot be obtained by non-contrast MRI. If Macrocylux must be used, the dose should not exceed 0.1 mmol/kg body weight. No more than one dose should be administered during a single scan. Due to lack of data on repeated administration, Macrocylux injections should not be repeated unless the interval between injections is at least 7 days.
Haemodialysis shortly after Macrocylux administration may help eliminate Macrocylux from the body. However, there is no evidence that initiating haemodialysis prevents or treats NSF in patients not already undergoing dialysis.

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

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

Pregnancy and breastfeeding
Macrocylux should not be used during pregnancy unless the clinical condition of the woman requires the use of gadoteric acid.
The decision to continue or interrupt breastfeeding for 24 hours after administration of Macrocylux should be made at the discretion of the physician and the breastfeeding mother.

Instructions for handling
The removable tracking label on the vials should be affixed to the patient's medical record to ensure correct documentation of the gadolinium-based contrast agent used. The administered dose must also be recorded. If an electronic medical record is used, the product name, batch number, and dose must be entered into the patient's electronic record.