MACROCYLUX 0,5 MMOL/ML Roztwór do wstrzykiwań

Treść ulotki

1. Macrocylux 0.5 mmol/ml
   1. What is Macrocylux and what is it 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. Package Contents and Other Information
2. Macrocylux 0.5 mmol/ml
   1. What is Macrocylux and what is it used for
   2. What you need to know before you use Macrocylux
   3. How to use Macrocylux
   4. Possible side effects
   5. How to store Macrocylux
   6. Contents of the pack and other information

Macrocylux 0.5 mmol/ml

Injectable solution
Gadoteric acid
Equivalent medicine

Read this leaflet carefully before using this medicine as 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 any side effects occur, including those not listed in this leaflet, tell 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 you use 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 is Macrocylux and what is it used for

Macrocylux is a contrast agent containing gadoteric acid. It is for diagnostic use only.
Macrocylux is used to intensify the contrast in images obtained with 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 alterations (lesions) at the level of the brain, spinal cord and adjacent tissues;
• MRI of the whole body (so-called total body), including alterations (lesions) at the level of liver, kidneys, pancreas, pelvis, lungs, heart, breast and musculoskeletal system. Adult population
• MR angiography, including alterations (lesions) and narrowing (stenoses) of the arteries, with the exception of the 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 ingredient or to any of the other ingredients of this medicine (listed in section 6).
• if you are allergic to drugs containing gadolinium (like other contrast agents used for magnetic resonance imaging).

Warnings and precautions
Tell your doctor or radiologist if you fall into any of the following categories:

• you have developed reactions to a contrast agent during a previous examination
• you suffer from asthma
• you have a history of allergy (e.g., allergy to seafood, hives, hay fever)
• you are being treated with a beta-blocker (medicine for heart and blood pressure disorders, such as metoprolol)
• your kidneys are not functioning properly
• you have recently had, or will soon have, 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, the doctor or radiologist will assess the benefit/risk ratio and decide whether it is appropriate to
administer Macrocylux to you. If Macrocylux is administered to you, the doctor or radiologist will take the
necessary precautions and the administration of Macrocylux will be carefully monitored.
The 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
Because kidney function is immature in newborns up to 4 weeks of age and in infants up to 1 year of age,
Macrocylux will only be used in these patients after careful evaluation by the doctor.
Before the examination, remove any metal objects you are wearing. Tell 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)
• suspect the presence of any foreign metal body, especially in the eye. This is important because these devices can cause serious problems, as the machines used for magnetic resonance imaging use very powerful magnetic fields.

Other medicines and Macrocylux
Tell your doctor or radiologist if you are taking, have recently taken, or might take any other
medicines. In particular, tell your doctor, radiologist or pharmacist if you are taking or have recently taken
medicines for heart and blood pressure disorders, such as beta-blockers, vasoactive substances,
angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists.

Macrocylux with food and drink
No interactions between Macrocylux and food and drink are known. However, ask your doctor, radiologist or
pharmacist if you need to avoid eating or drinking before the examination.

Pregnancy and breastfeeding
If you are pregnant, suspect you are pregnant, or are planning a pregnancy, or if you are breastfeeding with breast milk
ask your doctor or radiologist for advice before taking this medicine.

Pregnancy
Gadoteric acid can cross the placenta. It is not known whether this can have effects on the baby. Macrocylux should not
be used during pregnancy unless strictly necessary.

Breastfeeding
The doctor or radiologist will assess whether you should continue or stop breastfeeding for 24 hours after
receiving Macrocylux.

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

3. How to use Macrocylux

Macrocylux will be administered to you by injection into a vein.

During the examinationyou will be under the supervision of a doctor or radiologist. A needle will be left in your vein to
allow the doctor or radiologist to inject you, if necessary, with appropriate emergency medications. If
you develop an allergic reaction, the administration of Macrocylux will be stopped.
Macrocylux can be administered manually or via 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 know what
precautions need to be taken for the examination. They are also aware of the possible complications that may
occur.

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

Dosage in particular patient groups
The use of Macrocylux is not recommended in patients with severe kidney problems and in patients who have
recently undergone, or will soon undergo, a liver transplant. However, if use is necessary, you should receive
a single dose of Macrocylux during a scan and should not receive a second injection for at least 7
days.

Newborns, infants, children and adolescents
Since kidney function is immature in newborns up to 4 weeks of age and in infants up to 1 year of age,
Macrocylux will only be used in these patients after careful evaluation by the doctor. Newborns and
infants should receive a single dose of Macrocylux during a scan and should not receive a second
injection for at least 7 days.
Use for angiography is not recommended in patients under the age of 18.

Elderly
It is not necessary to change the dose if you are 65 years of age or older, but you may undergo a blood test to check
kidney function.

If you have been given too much Macrocylux
It is highly unlikely that you will be given an excessive dose. Macrocylux will be administered to you in
a medical setting by an experienced person. In the actual case of overdose, Macrocylux can be eliminated
from the body by hemodialysis (blood cleaning).
Further information on use and handling by the doctor or healthcare professional is reported
If you have further questions about 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.
manifest.

After administrationYou will be kept under observation for at least half an hour. Most side
effects occur immediately or sometimes later. Some effects may occur up to
seven days after the injection of Macrocylux.

There is a minimal risk that you may have an allergic reaction to Macrocylux. Such reactions can
be serious and cause shock(an allergic reaction that could be life-threatening). The following
symptoms may be early signs of shock. Inform the doctor, radiologist or healthcare
professional immediately if you experience any of these symptoms:

• swelling of the face, mouth or throat that can 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
• urticaria (hives)
• skin rash

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

• hypersensitivity (allergic reaction)
• headache
• unusual taste in mouth
• dizziness
• drowsiness
• sensation of tingling, warmth/burning, cold and/or pain
• low or high blood pressure
• nausea (feeling sick)
• stomach pain
• skin rash
• feeling of warmth, feeling of cold
• asthenia (loss of energy; weakness)
• discomfort at the injection site, reaction at the injection site, coldness at the injection site, swelling at the injection site, extravasation of the product outside the blood vessels which can 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)
• swelling of the eyelids
• palpitations
• sneezing
• vomiting
• diarrhea
• increased saliva production
• urticaria (hives), itching, sweating
• chest pain, chills.

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

• anaphylactic or anaphylactoid reactions (a severe allergic reaction that is potentially life-threatening)
• agitation
• coma, seizures, syncope (brief loss of consciousness), olfactory disorders (perception of often unpleasant smells), tremor
• conjunctivitis, red eyes, blurred vision, increased tear production
• cardiac arrest, fast or slow heartbeat, irregular heartbeat, vasodilation, pallor
• respiratory arrest, pulmonary edema, difficulty breathing, wheezing, nasal congestion, dry throat, constriction of the throat with a feeling of suffocation, respiratory spasms, swelling of the throat
• eczema, skin redness, swelling of the lips and localized in the mouth
• muscle cramps, muscle weakness, back pain
• malaise, chest discomfort, fever, facial swelling, spread of the product outside the blood vessels which can lead to tissue death at the injection site, inflammation of a vein
• decrease in blood oxygen level.

Cases of nephrogenic systemic fibrosis (which causes hardening of the skin and can also affect
soft tissues and internal organs) have been reported, most of them in patients who received Macrocylux together
with other contrast agents containing gadolinium. If you notice changes in the color and/or thickness of the skin in any part of the body in the weeks following the magnetic resonance imaging, 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. You can also report side effects directly
through the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-
avverse . By reporting side effects 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 particular precautions for storage.
Chemical and physical stability in use has been demonstrated for 72 hours at room temperature. From a
microbiological point of view, the product must be used immediately. If not used immediately, the
storage times and conditions before use are the responsibility of the user and generally do not
exceed 24 hours at 2-8° C, unless the opening occurred under controlled and
validated aseptic conditions.
Do not use this medicine after the expiry date which is reported on the vial and on the package, after
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 ingredient 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 ingredients are meglumine, -1,4,7,10-Tetraazacyclododecane-1,4,7,10 tetraacetic acid (DOTA) and water for injection. Description of Macrocylux and Package ContentsMacrocylux is a transparent, colourless to yellow solution for intravenous injection. The Macrocylux pack contains one or ten vials containing 10, 15 and 20 ml of injectable solution.

It is possible that not all pack sizes are 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 Member States of the European Economic Area and in the United Kingdom
(Northern Ireland) under the following designations:
Germany: Cyclolux 0,5 mmol/ml Injektionslösung
Austria: Cyclolux 0,5 mmol/ml Injektionslösung im Einzeldosisbehältnis
Belgium: Macrocyclolux 0,5 mmol/ml solution for injection
Croatia: Cyclolux 0,5 mmol/ml otopina za injekciju
Cyprus: Macrocyclolux 0,5 mmol/ml ενέσιμο διάλυμα
Czech Republic: Cyclolux
Estonia: Cyclolux
Greece: Cyclolux 0,5 mmol ενέσιμο διάλυμα
Ireland: Cyclolux 279.32 mg/ml solution for injection
Italy: Macrocylux
Latvia: Cyclolux 0,5 mmol/ml injekcinis tirpalas
Lithuania: Cyclolux
Netherlands Cyclolux 0,5 mmol/ml, oplossing voor injectie
Poland: Cyclolux
Portugal: Cyclolux
Hungary: Cyclolux 0,5 mmol/ml oldatos injekció, egyadagos
Romania: Cyclolux 0,5 mmol/ml soluţie injectabilă
Spain: Cyclolux 0,5 mmol/ml solución inyectable EFG
Slovakia: Cyclolux 0,5 mmol/ml Injekčný roztok
Slovenia: Cyclolux 0,5 mmol/ml raztopina za injiciranje
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 allows sufficient improvement for diagnostic purposes should be used.
The dose must be calculated based on the patient's body weight and must not exceed the recommended dose per
kilogram of body weight indicated in this section.

• MRI of the brain and spinal cord:in neurological examinations, the dose may vary from 0.1 to 0.3 mmol/kg of 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, a further 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) the administration of a second consecutive injection of 0.1 mmol/kg of body weight, equivalent to 0.2 ml/kg BW, may be justified. However, if the use of 2 consecutive doses of Macrocylux is anticipated before starting angiography, the use of 0.05
mmol/kg BW, equivalent to 0.1 ml/kg BW for each dose, may be useful, depending on the diagnostic imaging equipment available.

• Paediatric population:MRI of the brain and spinal cord/Whole body MRI: the recommended and maximum dose of Macrocylux is 0.1 mmol/kg of body weight. Given the immaturity of renal function in neonates up to 4 weeks of age and in children up to 1 year of age, Macrocylux should be used in these patients only after careful evaluation and at a dose not exceeding 0.1 mmol/kg of body weight. More than one dose should not be used during a scan. Due to the lack of information 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 the lack of sufficient data on efficacy and safety in this indication.
• Patients with impaired renal function:the adult dose applies to patients with mild to moderate renal impairment (GFR ≥ 30 ml/min/1.73m ). See also below “Impaired renal function”.
• Patients with impaired hepatic function:the adult dose applies to these patients. Caution is recommended, especially in the perioperative period of a liver transplant.

Route of administration
Macrocylux is only indicated for intravenous administration. Do not use by the intrathecal route. Take care to strictly maintain the injection in the vein: extravasation may cause local intolerance reactions
that require usual topical treatment.
Infusion rate: 3-5 ml/min (for angiographic procedures, higher infusion rates of up to 120 ml/min, i.e. 2 ml/sec, can be used).
Optimal imaging: within 45 minutes of injection.
Optimal imaging sequence: T1-weighted
Intravascular administration of contrast agents should be carried out, if possible, with the patient lying down.
After administration, the patient should be monitored for at least half an hour, as
experience shows that most adverse reactions occur within this time frame.
Prepare a syringe with a needle. Remove the plastic disc. After cleaning the cap with an alcohol swab, puncture it with the needle. Draw the amount of product needed for the examination and inject it intravenously.
For single use only, unused solution must be discarded.
The injectable solution must 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 to the patient, it is preferable to use the vials of
Macrocylux with a single-use syringe of adequate volume for that amount to have better accuracy of
the volume injected.
In neonates and infants, the required dose must be administered manually.

Impaired renal function
Before administering Macrocylux, all patients are recommended to be screened for
renal dysfunction by laboratory tests.
Cases of nephrogenic systemic fibrosis (NSF) associated with the use of certain gadolinium-containing contrast agents have been reported in patients with severe acute or chronic renal insufficiency (GFR < 30 ml/min/1.73m ).
Patients undergoing liver transplantation are particularly at risk as the incidence of acute renal failure is high in this group. Since there is a possibility of developing NSF with Macrocylux, this
drug should be used in patients with severe renal insufficiency and in patients in the perioperative period
of a liver transplant only after careful evaluation of the risk/benefit ratio and when diagnostic information is essential and not obtainable with MRI without contrast. If Macrocylux is necessary, the
dose should not exceed 0.1 mmol/kg of body weight. More than one dose should not be used during a
scan. Due to the lack of information on repeated administration, Macrocylux
injections should not be repeated unless the interval between injections is at least 7 days.
Haemodialysis shortly after the administration of Macrocylux may be helpful in eliminating Macrocylux
from the body. There is no evidence to support the benefit of initiating haemodialysis for the
prevention or treatment of NSF in patients not yet undergoing haemodialysis.

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

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

Pregnancy and breastfeeding
Macrocylux should not be used during pregnancy unless the clinical condition of the woman
requires the use of gadoteric acid.
Continuing or discontinuing breastfeeding for a period of 24 hours after the administration of
Macrocylux must be 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 allow correct recording of the gadolinium-based contrast agent used. The dose used must also be recorded. If an electronic medical record is used, the product name, batch number and dose must be entered into the
medical record.

Macrocylux 0.5 mmol/ml

Injectable solution
Gadoteric acid
Generic medicine

Read this leaflet carefully before using this medicine as 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 any side effects occur, including those not listed in this leaflet, tell 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 you use 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 is Macrocylux and what is it used for

Macrocylux is a contrast agent containing gadoteric acid. It is for diagnostic use only.
Macrocylux is used to intensify the contrast in images obtained with 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 alterations (lesions) at the level of the brain, spinal cord and adjacent tissues;
• MRI of the whole body (so-called total body), including alterations (lesions) at the level of liver, kidneys, pancreas, pelvis, lungs, heart, breast and musculoskeletal system. Adult population
• Angio-MRI, including alterations (lesions) and narrowing (stenoses) of the arteries, with the exception of the coronary arteries.

2. What you need to know before you use Macrocylux

Macrocyluxmust NOT be administered to you

• if you are allergic to the active ingredient or to any of the other ingredients of this medicine (listed in section 6).
• if you are allergic to drugs containing gadolinium (like other contrast agents used for magnetic resonance imaging).

Warnings and precautions
Tell your doctor or radiologist if you fall into any of the following categories:

• you have developed reactions to a contrast agent during a previous examination
• you suffer from asthma
• you have a history of allergy (for example, allergy to seafood, hives, hay fever)
• you are being treated with a beta-blocker (medicine for heart and blood pressure disorders, such as metoprolol)
• your kidneys are not functioning properly
• you have recently had, or will soon have, a liver transplant
• you have a disease that affects the heart or blood vessels
• you have had seizures or are being treated for epilepsy.

In all these cases, the doctor or radiologist will assess the benefit/risk ratio and decide whether it is appropriate to
administer you Macrocylux. If Macrocylux is administered to you, the doctor or radiologist will take the
necessary precautions and the administration of Macrocylux will be carefully monitored.
The 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
Because kidney function is immature in newborns up to 4 weeks of age and in infants up to 1 year of age,
Macrocylux will only be used in these patients after careful evaluation by the doctor.
Before the examination, remove any metal objects you are wearing. Tell 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)
• suspect the presence of any foreign metal body, especially in the eye. This is important because these devices can cause serious problems, as the machines used for magnetic resonance imaging use very powerful magnetic fields.

Other medicines and Macrocylux
Tell your doctor or radiologist if you are taking, have recently taken, or might take any other
medicines. In particular, tell your doctor, radiologist, or pharmacist if you are taking or have recently taken
medicines for heart and blood pressure disorders, such as beta-blockers, vasoactive substances,
angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists.

Macrocylux with food and drink
No interactions between Macrocylux and food and drinks are known. However, ask your doctor, radiologist, or
pharmacist if you need to avoid eating or drinking before the examination.

Pregnancy and breastfeeding
If you are pregnant, suspect you are pregnant, are planning a pregnancy, or are breastfeeding with breast milk
ask your doctor or radiologist for advice before taking this medicine.

Pregnancy
Gadoteric acid can cross the placenta. It is not known whether this may have effects on the baby. Macrocylux should not
be used during pregnancy unless strictly necessary.

Breastfeeding
The doctor or radiologist will assess whether you should continue or stop breastfeeding for 24 hours after
receiving Macrocylux.

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

3. How to use Macrocylux

Macrocylux will be administered to you by injection into a vein.

During the examinationyou will be under the supervision of a doctor or radiologist. A needle will be left in your vein to
allow the doctor or radiologist to inject you, if necessary, with appropriate emergency medications. If
you develop an allergic reaction, the administration of Macrocylux will be stopped.
Macrocylux can be administered manually or via 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 know what
precautions must be taken for the examination. They are also aware of the possible complications that may
occur.

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

Dosage in particular patient groups
The use of Macrocylux is not recommended in patients with severe kidney problems and in patients who have
recently undergone, or will soon undergo, a liver transplant. However, if use is necessary,
you should receive only one dose of Macrocylux during a scan and should not receive a second injection
for at least 7 days.

Newborns, infants, children and adolescents
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. Newborns and
infants should receive only one dose of Macrocylux during a scan and should not receive a second
injection for at least 7 days.
Use for angiography is not recommended in patients under the age of 18 years.

Elderly
It is not necessary to modify the dose if you are 65 years of age or older, but you may undergo a blood test to check
kidney function.

If you have been given too much Macrocylux
It is highly unlikely that you will be given an excessive dose. Macrocylux will be administered to you in
a medical setting by an experienced person. In the actual case of overdose, Macrocylux can be eliminated
from the body by hemodialysis (blood cleansing).
Further information on use and handling by the doctor or healthcare professional is reported
If you have further questions about 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 everyone will experience them.
manifest.

After administrationYou will be kept under observation for at least half an hour. Most side
effects occur immediately or sometimes later. Some effects may occur up to
seven days after the injection of Macrocylux.

There is a minimal risk that you may have an allergic reaction to Macrocylux. Such reactions can
be serious 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 that can 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
• urticaria
• skin rash

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

• hypersensitivity (allergic reaction)
• headache
• unusual taste in mouth
• dizziness
• drowsiness
• sensation of tingling, warmth/burning, cold and/or pain
• low or high blood pressure
• nausea (feeling unwell)
• stomach pain
• skin rash
• feeling of warmth, feeling of cold
• asthenia (loss of energy; weakness)
• discomfort at the injection site, reaction at the injection site, coldness at the injection site, swelling at the injection site, extravasation of the product outside the 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)
• swelling of the eyelids
• palpitations
• sneezing
• vomiting
• diarrhea
• increased saliva production
• urticaria, itching, sweating
• chest pain, chills

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

• anaphylactic or anaphylactoid reactions (a severe allergic reaction that is potentially life-threatening)
• agitation
• coma, seizures, syncope (brief loss of consciousness), smell disorders (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, throat

dry, throat constriction with a feeling of suffocation, respiratory spasms, swelling of the throat

• eczema, skin redness, swelling of the lips and localized in the mouth
• muscle cramps, muscle weakness, back pain
• malaise, chest discomfort, fever, facial swelling, extravasation of the product outside the blood vessels which can lead to tissue death at the injection site, inflammation of a vein
• decreased blood oxygen level

Cases of nephrogenic systemic fibrosis (which causes hardening of the skin and can also affect
soft tissues and internal organs) have been reported, most of which in patients who have received Macrocylux together
with other contrast agents containing gadolinium. If you notice changes in the color and/or thickness of the skin in any part of the body in the weeks following the magnetic resonance imaging, 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. You can also report side effects directly
through the national reporting system at, https://www.aifa.gov.it/content/segnalazioni-reazioni-
avverse . By reporting side effects 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 particular precautions for storage.
Chemical and physical stability in use has been demonstrated for 72 hours at room temperature. From a
microbiological point of view, the product must be used immediately. If not used immediately, the
storage times and conditions before use are the responsibility of the user and generally do not
exceed 24 hours at 2-8° C, unless the opening occurred under controlled and
validated aseptic conditions.
Do not use this medicine after the expiry date which is reported on the vial and on the packaging, after
the abbreviation “Exp”. The expiry date refers to the last day of that month.

6. Contents of the pack 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 ingredients 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 packMacrocylux is a transparent, colourless to yellow solution, free from visible particles, for intravenous injection. The pack of Macrocylux contains one or ten vials containing 60 and 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 Member States of the European Economic Area with the following
denominations:
Germany:Cyclolux 0.5 mmol/ml Injektionslösung

Austria:Cyclolux 0.5 mmol/ml Injektionslösung

Belgium:Macrocyclolux 0.5 mmol/ml solution for injection

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:

Posology
The lowest possible dose that allows sufficient enhancement for diagnostic purposes should be used.
The dose must be calculated based on the patient's body weight and must not exceed the recommended dose per
kilogram of body weight indicated 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 of 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, a further 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 of body weight, equivalent to 0.2 ml/kg BW, may be justified. However, if the use of 2 consecutive doses of Macrocylux is anticipated before starting angiography, the use of 0.05 mmol/kg BW, equivalent to 0.1 ml/kg BW for each dose, may be useful, depending on the diagnostic imaging equipment available.
• Paediatric population:MRI of the brain and spinal cord/Whole-body MRI: the recommended and maximum dose of Macrocylux is 0.1 mmol/kg of body weight. Given the immaturity of renal function in neonates up to 4 weeks of age and in children up to 1 year of age, Macrocylux should be used in these patients only after careful evaluation and at a dose not exceeding 0.1 mmol/kg of body weight. More than one dose should not be used during a scan. Due to the lack of information on repeated administration, injections of Macrocylux 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 the lack of sufficient data on efficacy and safety in this indication.
• Patients with impaired renal function:the adult dose applies to patients with mild to moderate renal impairment (GFR ≥ 30 ml/min/1.73m ). See also below “Renal impairment”.
• Patients with impaired hepatic function:the adult dose applies to these patients. Caution is recommended, especially in the perioperative period of a liver transplant.

Route of administration
Macrocylux is only indicated for intravenous administration. Do not use intrathecally. Take care to
strictly maintain intravenous injection: extravasation can cause local intolerance reactions that require
usual topical treatment.
Infusion rate: 3-5 ml/min (for angiographic procedures, higher infusion rates of up to 120 ml/min, i.e. 2 ml/sec, can be used).
Optimal images: within 45 minutes of the injection.
Optimal image sequence: T1-weighted
Intravascular administration of contrast agents should be performed, if possible, with the patient in a supine position.
After administration, the patient should be observed for at least half an hour, as experience shows that most
adverse reactions occur within this time frame.
The rubber stopper must be punctured only once with a suitable drawing device (spike).
In general, the drawing device should have the following characteristics: trocar needle, sterile air filter,
luer adapter and protective seal.
It can be used with a manual (sterile) single-use syringe filled with a sufficient amount to perform
a protocol with single-dose administration or to inject a second bolus of contrast if clinically required.
An automatic injector may only be used for one patient for the purpose of performing multiple administrations.
At the conclusion of the examination session, any remaining product in the vial and the single-use device
must be disposed of within a maximum of 24 hours after puncturing the rubber stopper. Strictly adhere to
the instructions provided by the manufacturer of the device used.
The injectable solution must be visually inspected before use. Only clear and particle-free solutions should be used.

Paediatric population
Depending on the amount of Macrocylux to be administered to the patient, it is preferable to use the vials of
Macrocylux with a single-use syringe of adequate volume for that amount to have better accuracy of the
volume injected.
In neonates and infants, the required dose must be administered manually.

Renal impairment
Before administering Macrocylux, all patients are recommended to be screened for
renal dysfunction by laboratory tests.
Cases of nephrogenic systemic fibrosis (NSF) have been reported in association with the use of certain gadolinium-containing contrast agents in patients with severe acute or chronic renal insufficiency (GFR < 30 ml/min/1.73m ).
Patients undergoing liver transplantation are particularly at risk as the incidence of acute renal insufficiency is high in this group. Because there is a possibility of developing NSF with Macrocylux, this
drug should be used in patients with severe renal insufficiency and in patients in the perioperative period
of a liver transplant only after careful evaluation of the risk/benefit ratio and when diagnostic information is essential and not obtainable with MRI without contrast. If Macrocylux is necessary, the
dose should not exceed 0.1 mmol/kg of body weight. More than one dose should not be used during a
scan. Due to the lack of information on repeated administration, injections of Macrocylux
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 to demonstrate the benefit of initiating haemodialysis for the
prevention or treatment of NSF in patients not yet undergoing haemodialysis.

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

Neonates and infants
See section Posology and mode 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.
Continuation or discontinuation of breastfeeding for a period of 24 hours after administration of
Macrocylux, must be 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 allow
correctly noting the gadolinium-based contrast agent used. The dose used must also be recorded. If an electronic medical record is used, the product name, batch number and dose must be entered into the
medical record.