Package Leaflet: Information for the User

Dotagraf 0.5 mmol/ml

Injectable solution
Gadoteric acid
Generic Medicine
Please 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, consult 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 package leaflet:

What Dotagraf is and what it is used for
What you need to know before being administered Dotagraf
How Dotagraf will be administered
Possible side effects
How to store Dotagraf
Contents of the pack and other information

1. What Dotagraf is and what it is used for

Dotagraf is a contrast agent containing gadoteric acid. The medicinal product is for diagnostic use only.
Dotagraf is used to enhance the contrast of images obtained in Magnetic Resonance (MR) examinations. This contrast enhancement improves the visualization and delineation of:
Adult and pediatric population (0-18 years)

MR of the Central Nervous System, including abnormalities (lesions) of the brain, spinal cord, and adjacent tissues;
MR of the whole body, including abnormalities (lesions) of the liver, kidneys, pancreas, pelvis, lungs, heart, breast, and the musculoskeletal system

Adult population

MR angiography, including abnormalities (lesions) and narrowing (stenosis) of arteries, except in the coronary arteries.

2. What you should know before being given Dotagraf

Dotagraf must NOT be administered to you if:

You are allergic to the active substance or to any of the other components of this medicine (listed in section 6).
You are allergic to medicines containing gadolinium (such as other contrast agents used in 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 examination.
You suffer from asthma.
You have a history of allergies (e.g. to shellfish, hives, hay fever).
You are currently being treated with a beta-blocking medicine (a medicine used for heart or blood pressure conditions, such as metoprolol).
You have impaired kidney function.
You have recently undergone or are scheduled to undergo a liver transplant in the near future.
You suffer from a disease affecting the heart or blood vessels.
You have had seizures or are currently being treated for epilepsy.

In all these cases, your doctor or radiologist will evaluate the benefit-risk ratio and decide whether administration of Dotagraf is necessary. If you are to be treated with Dotagraf, your doctor or radiologist will take the necessary precautions, and the administration of Dotagraf will be closely monitored. Your doctor or radiologist may decide to perform a blood test to check your kidney function before deciding to administer Dotagraf, 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, Dotagraf will be used in these patients only after the doctor has carefully considered the necessity of administration.

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 (in the inner ear)
Any suspected metallic foreign body, especially in the eye.

These details are important because the presence of such devices may cause serious problems due to the very strong magnetic fields used during magnetic resonance imaging.

Other medicines and Dotagraf
Inform your doctor or radiologist if you are taking, have recently taken, or might take any other medicines. In particular, please inform your doctor, radiologist, or pharmacist if you are taking or have recently taken medicines for heart or blood pressure conditions such as beta-blockers, vasoactive substances, angiotensin-converting enzyme inhibitors (such as ramipril), or angiotensin II receptor antagonists.

Dotagraf with food and drinks
No interactions between Dotagraf and food or drinks are known. However, please check with your doctor, radiologist, or pharmacist whether you are required to refrain from eating or drinking before the examination.

Pregnancy and breastfeeding

If you are pregnant, think you might be pregnant, are planning a pregnancy, or are breastfeeding, please consult your doctor or radiologist before receiving this medicine.

Pregnancy
Gadoteric acid may cross the placenta. It is not known whether it has effects on the unborn child. Dotagraf should not be used during pregnancy unless strictly necessary.

Breastfeeding
Your doctor or radiologist will decide whether you should continue breastfeeding or interrupt it for a period of 24 hours after administration of Dotagraf.

Driving and using machines
There are no available data on the effects of Dotagraf on the ability to drive vehicles. If you do not feel well after the examination, you must not drive or operate machinery.

3. How to use Dotagraf

Dotagraf will be administered to you by intravenous injection.
During the examination, you will be under the supervision of a doctor or radiologist. A venous needle will be left in place so that the doctor or radiologist can administer appropriate emergency medications if necessary. If an allergic reaction occurs, the administration of Dotagraf will be stopped.
Dotagraf may be administered manually or by using 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 facility. The staff performing the examination is aware of the precautions to take for this investigation and is also familiar with the possible complications that could occur.

Dosage
The doctor or radiologist will determine the dose to be administered and will supervise the injection.

Dosage in special patient groups
The use of Dotagraf is not recommended in patients with severe kidney problems who have recently undergone, or are scheduled to undergo shortly, a liver transplant. However, if its use is necessary, you will receive only one dose of Dotagraf during the scan and should not receive a second dose within 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, Dotagraf will be used in these patients only after the doctor has carefully considered the need for administration.
Newborns and infants should receive only one dose of Dotagraf during a scan and should not receive a second injection within at least 7 days.
The use of angiography is not recommended in children under 18 years of age.

Elderly
Dose adjustment is not necessary if you are 65 years of age or older, but a blood test may be performed to check that your kidneys are functioning properly.

If you have been given too much Dotagraf
It is highly unlikely that you would be given an excessive dose of the medicine. Dotagraf will be administered in a medical facility by a trained specialist. In case of overdose, Dotagraf can be removed from your body by haemodialysis (blood purification).
Further information regarding use and management by the doctor or healthcare professional is provided at the end of this leaflet.
If you have any doubts about the use of this medicine, consult your doctor or radiologist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
After administration, you will be monitored for at least half an hour. Most side effects occur immediately or sometimes later. Some effects may appear up to seven days after injection of Dotagraf.
There is a slight risk of allergic reactions to Dotagraf. These reactions can be severe and cause
anaphylactic shock (a type of allergic reaction that may put the patient at risk of life-threatening complications). The following symptoms may be early signs of shock. Inform your doctor, radiologist, or healthcare professional immediately if you notice any of the effects listed below:

swelling of the face, mouth or throat, which may cause difficulty in swallowing or breathing
swelling of the hands or feet
feeling of light-headedness (low blood pressure)
breathing difficulties
wheezing
cough
itching
runny nose
sneezing
eye irritation
hives (urticaria)
skin rash

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

hypersensitivity (allergic reaction)
headache
unusual taste sensation in the mouth
dizziness
drowsiness (feeling sleepy)
sensation of tingling, warmth/burning, cold and/or pain
decrease or increase in blood pressure
nausea
stomach pain
skin rash
sensation of warmth, sensation of cold
fatigue (loss of energy; weakness)
discomfort at injection site, reaction at injection site, coldness at injection site, swelling at 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 edema
palpitations
sneezing
vomiting
diarrhea
increased salivary secretion
hives (urticaria), itching, sweating
chest pain, chills

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

anaphylactic or anaphylactoid reactions (a serious, potentially life-threatening allergic reaction)
agitation
coma, seizures, syncope (brief loss of consciousness), olfactory disturbance (frequent perception of unpleasant odors), tremor
conjunctivitis, red eyes, blurred vision, increased lacrimation
cardiac arrest, accelerated, delayed or irregular heartbeat, palpitations, vasodilation, pallor
respiratory arrest, pulmonary edema, breathing difficulties, wheezing, nasal congestion, sneezing, cough
dry throat, tightness in the throat with a sensation of suffocation, respiratory spasms, throat swelling
eczema, skin redness, swelling of the lips and local areas in the mouth
muscle cramps, myasthenia, back pain
malaise, chest discomfort, fever, facial edema, extravasation of the product outside blood vessels which may cause tissue necrosis at the injection site, inflammation of a vein
reduced levels of oxygen in the blood

Cases of nephrogenic systemic fibrosis (a condition causing hardening of the skin and possibly affecting soft tissues and internal organs) have been reported, most of them in patients treated with Dotagraf in combination with other gadolinium-containing contrast agents. If, in the weeks following your MRI, you notice changes in the colour and/or thickness of your skin anywhere on 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, talk to your radiologist, pharmacist, doctor or nurse. You can also report side effects directly via the national reporting system at the following website:
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Dotagraf

Keep this medicine out of the sight and reach of children.
This medicine does not require special storage precautions.
Chemical and physical stability has been demonstrated for 72 hours at room temperature during use. From a
microbiological standpoint, the product should be used immediately. Otherwise, the storage time during use and the
conditions prior to use are the responsibility of the user and normally should not exceed 24 hours at temperatures
between 2 and 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 packaging following the abbreviation “Exp”. The expiry date refers to the last day of that month.

6. Package contents and other information

What Dotagraf 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-tetra-azacyclododecane-1,4,7,10-tetra-acetic acid (DOTA), and water for injections.

Description of the appearance of Dotagraf and contents of the pack
Dotagraf is a clear, colourless to yellow solution for intravenous injection. The Dotagraf pack contains one or ten vials of 10, 15 and 20 ml of injectable solution. Not all pack sizes may be marketed.

Marketing Authorization Holder
Bayer S.p.A.
Viale Certosa, 130
20156 Milan, Italy

Manufacturer
Sanochemia Pharmazeutika GmbH
Landegger Straße 7
2491 Neufeld/Leitha, Austria

This medicinal product is authorized in the European Economic Area Member States under the following names

Belgium	Dotagraph 0.5 mmol/ml solution for injection / solution injectable / Injektionslösung
Bulgaria, Malta	Dotagraf 0.5 mmol/ml solution for injection
Croatia	Dotagraf 0.5 mmol/ml otopina za injekciju
Cyprus, Denmark, Estonia, Greece, Iceland, Italy, Poland, Portugal, Sweden	Dotagraf
Germany	Dotagraf 0.5 mmol/ml Injektionslösung
Hungary	Dotagraf 0.5 mmol/ml oldatos injekció, egyadagos
Ireland	Dotagraf 279.32 mg/ml solution for injection
Latvia	Dotagraf 0.5 mmol/ml šķīdums injekcijām
Lithuania	Dotagraf 0.5 mmol/ml injekcinis tirpalas
Luxembourg	Dotagraph 0.5 mmol/ml solution injectable
Netherlands	Dotagraf 0.5 mmol/ml, oplossing voor injectie
Romania	Dotagraf 0.5 mmol/ml soluţie injectabilă în flacon unidoză
Slovenia	Dotagraf 0.5 mmol/ml raztopina za injiciranje
Spain	Dotagraf 0.5 mmol/ml solución inyectable unidosis EFG

The following information is intended exclusively for medical or healthcare professionals:
Dosage
Use the lowest dose that provides sufficient diagnostic enhancement. The dose should be calculated according to the patient's body weight and must not exceed the recommended dose per kilogram of body weight stated in this section.

Brain and spinal MRI: In neurological examinations, the dose may range from 0.1 to 0.3 mmol/kg body weight, corresponding to 0.2–0.6 ml/kg body weight. After administration of 0.1 mmol/kg body weight in patients with brain tumors, an additional dose of 0.2 mmol/kg body weight may improve tumor characterization and assist in therapeutic decision-making.
Whole-body MRI and Angiography: The recommended dose for intravenous injection is 0.1 mmol/kg body weight (i.e., 0.2 ml/kg body weight) to provide diagnostically adequate contrast enhancement. Angiography: In specific circumstances (e.g., failure to obtain satisfactory images of a large vascular territory), administration of a second consecutive injection of 0.1 mmol/kg body weight, equivalent to 0.2 ml/kg body weight, may be justified. However, if two consecutive doses of Dotagraf are anticipated prior to the start of angiography, using 0.05 mmol/kg body weight (equivalent to 0.1 ml/kg body weight) for each dose may be beneficial, depending on the available imaging equipment.
Pediatric population: Brain and spinal cord MRI / Whole-body MRI: The recommended and maximum dose of Dotagraf is 0.1 mmol/kg body weight. More than one dose should not be used during a single scan. Due to immature renal function in neonates up to 4 weeks of age and infants up to 1 year of age, Dotagraf should be used in these patients only after careful consideration of the necessity of use and at a dose not exceeding 0.1 mmol/kg body weight. More than one dose should not be administered during a single scan. Due to lack of data on repeated administration, Dotagraf injections should not be repeated unless the interval between injections is at least 7 days. Dotagraf is not recommended for angiography in children under 18 years of age, as data on efficacy and safety for this indication are insufficient.
Patients with renal impairment: The dose used in adults applies to patients with mild to moderate renal impairment (GFR ≥ 30 ml/min/1.73m²). See also the section below “Renal function impairment”.
Patients with hepatic impairment: The dose used in adults applies to these patients. Caution is recommended, especially during the perioperative period of liver transplantation.

Route of administration
Dotagraf is intended exclusively for intravenous use. Do not use intrathecally. Particular care must be taken to ensure strictly intravenous injection: extravasation may cause local intolerance reactions requiring standard local 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 monitored for at least 30 minutes, as experience shows that most adverse reactions occur within this time frame.
Prepare a syringe with a needle. Remove the plastic disk. After cleaning the stopper with an alcohol swab, pierce the stopper with the needle. Withdraw the volume required for the examination and administer it intravenously.
The product is for single use; discard any unused solution.
The injectable solution should be visually inspected before use. Only clear solutions free from visible particles should be used.
Pediatric population
Depending on the amount of Dotagraf administered to the child, it is preferable to use vials of Dotagraf with a single-use syringe appropriate for the required volume to ensure greater accuracy in injected volume.
In neonates and children, the required dose should be administered manually.

Renal function impairment
Prior to administration of Dotagraf, 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 severe acute or chronic renal impairment (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. Because NSF may occur with Dotagraf, the product should be used in patients with severe renal impairment and in patients during the perioperative period of liver transplantation only after careful consideration of the risk-benefit ratio and when essential diagnostic information cannot be obtained by non-contrast MRI. If Dotagraf must be used, the dose should not exceed 0.1 mmol/kg body weight. More than one dose should not be administered during a single scan. Due to lack of data on repeated administration, Dotagraf injections should not be repeated unless the interval between injections is at least 7 days. Hemodialysis immediately after Dotagraf administration may be useful for eliminating this medicinal product from the body. There is no evidence supporting initiation of hemodialysis for the prevention or treatment of NSF in patients 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 under Dosage and method of administration, pediatric population.

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

Instructions for handling
The adhesive traceability label on the vials should be removed and affixed to the patient's documentation to allow accurate recording of the gadolinium-containing contrast agent used. The administered dose must also be recorded. If electronic patient records are used, the product name, batch number, and dose must be recorded in the electronic record.

Package Leaflet: Information for the User

Dotagraf 0.5 mmol/ml

Injectable solution
Gadoteric acid
Generic medicine
Please 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, consult 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 package leaflet:

What Dotagraf is and what it is used for
What you need to know before being administered Dotagraf
How Dotagraf will be administered
Possible side effects
How to store Dotagraf
Package contents and other information

1. What Dotagraf is and what it is used for

Dotagraf is a contrast agent containing gadoterate acid. The medicinal product is for diagnostic use only.
Dotagraf is used to enhance image contrast in Magnetic Resonance (MR) imaging. This contrast enhancement improves visualization and delineation in:

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, including abnormalities (lesions) of the liver, kidneys, pancreas, pelvis, lungs, heart, breast, and the musculoskeletal system;

Adult population

MR angiography, including abnormalities (lesions) and narrowing (stenosis) of arteries, except coronary arteries.

2. What you should know before being given Dotagraf

Dotagraf must NOT be administered to you if

You are allergic to the active substance or to any of the other components of this medicine (listed in section 6).
You are allergic to medicines containing gadolinium (such as other contrast agents used in magnetic resonance imaging).

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

you have previously had a reaction to a contrast agent during an examination
you suffer from asthma
you have a history of allergies (e.g. to shellfish, hives, hay fever)
you are currently being treated with a beta-blocking medicine (a medicine used for heart and blood pressure disorders, such as metoprolol)
you have impaired renal function
you have recently undergone or are scheduled to undergo a liver transplant in the near future
you suffer from a disease affecting the heart or blood vessels
you have had seizures or are currently being treated for epilepsy.

In all these cases, your doctor or radiologist will evaluate the benefit-risk ratio and decide whether administration of Dotagraf is necessary. If you are to be treated with Dotagraf, your doctor or radiologist will take the necessary precautions and the administration of Dotagraf will be closely monitored. Your doctor or radiologist may decide to perform a blood test to check your renal function before deciding to administer Dotagraf to you, especially if you are 65 years of age or older.

Newborns and infants
Since renal function is immature in newborns up to 4 weeks of age and in infants up to 1 year of age, Dotagraf will be used in these patients only after the doctor has carefully considered the need for administration.

Before the examination, remove all metallic objects being worn. Inform your doctor or radiologist if you have any of the following:

a pacemaker
a vascular clip
an infusion pump
a nerve stimulator
a cochlear implant (in the inner ear)
any suspected metallic foreign body, especially in the eye.

This information is important because the presence of these devices may cause serious problems, as very strong magnetic fields are used during magnetic resonance imaging.

Other medicines and Dotagraf
Inform your doctor or radiologist if you are taking, have recently taken, or might take any other medicine. 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-blockers, vasoactive substances, angiotensin-converting enzyme inhibitors, or angiotensin II receptor antagonists.

Dotagraf with food and drink
No interactions between Dotagraf and food or drink are known. However, please check with your doctor, radiologist, or pharmacist whether you are required to refrain from eating or drinking before the examination.

Pregnancy and breastfeeding

If you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding, please consult your doctor or radiologist before taking this medicine.

Pregnancy
Gadoteric acid may cross the placenta. It is not known whether it has effects on the unborn child. Dotagraf must not be used during pregnancy unless strictly necessary.

Breastfeeding
Your doctor or radiologist will decide whether you should continue breastfeeding or interrupt it for a period of 24 hours after administration of Dotagraf.

Driving and using machines
There are no available data on the effects of Dotagraf on the ability to drive or operate machinery. If you do not feel well after the examination, you must not drive or use machinery.

5. How to use Dotagraf

Dotagraf will be administered to you by intravenous injection.
During the examination, you will be under the supervision of a doctor or radiologist. An intravenous cannula will be left in place so that the doctor or radiologist can administer appropriate emergency medications if necessary. If an allergic reaction occurs, the administration of Dotagraf will be stopped.
Dotagraf 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 facility. The personnel performing the examination are aware of the precautions to take for this investigation and are also familiar with the possible complications that could occur.
Dosage
The doctor or radiologist will determine the dose to be administered and will supervise the injection.
Dosage in special patient groups
The use of Dotagraf is not recommended in patients with severe renal impairment who have recently undergone, or are scheduled to undergo shortly, a liver transplant. However, if its use is necessary, you will receive only one dose of Dotagraf during the scan and should not receive a second dose 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, Dotagraf will be used in these patients only after the doctor has carefully considered the necessity of administration.
Neonates and infants should receive only one dose of Dotagraf during a scan and should not receive a second injection within at least 7 days.
The use of angiography is not recommended in children under 18 years of age.
Elderly
Dose adjustment is not required if you are 65 years of age or older, but a blood test may be performed to check that your kidneys are functioning properly.
If you have been given too much Dotagraf
It is highly unlikely that an excessive dose of the medicine will be administered. Dotagraf will be given in a medical facility by a trained healthcare professional. In the event of overdose, Dotagraf can be removed from your body by haemodialysis (blood cleansing).
Further information regarding use and management by the doctor or healthcare professional is provided at the end of this leaflet.
If you have any doubts about the use of this medicine, consult your doctor or radiologist.

6. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
After administration, you will be kept under observation for at least half an hour. Most side effects occur immediately or sometimes later. Some effects may appear up to seven days after receiving Dotagraf.
There is a slight risk of allergic reactions to Dotagraf. These reactions can be severe and cause shock (a case of allergic reaction capable of exposing the patient to life-threatening risk). The following symptoms may be the first signs of shock. Inform your doctor, radiologist, or healthcare professional immediately if you notice any of the effects listed below:

swelling of the face, mouth, or throat, which may cause difficulty in swallowing or breathing
swelling of the hands or feet
feeling of light-headedness (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 sensation in the mouth
dizziness
somnolence (drowsiness)
tingling sensation, warmth/burning, cold, and/or pain
decrease or increase in blood pressure
nausea
stomach pain
skin rash
sensation of warmth, sensation of cold
discomfort at injection site, reaction at injection site, coldness at injection site, swelling at 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 edema
palpitations
sneezing
vomiting
diarrhea
increased salivary secretion
hives, itching, sweating
chest pain, chills

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

anaphylactic or anaphylactoid reactions (a serious, potentially life-threatening allergic reaction)
agitation
coma, convulsions, syncope (brief loss of consciousness), olfactory disturbance (frequent perception of unpleasant odors), tremor
conjunctivitis, red eyes, blurred vision, increased lacrimation
cardiac arrest, accelerated, delayed, or irregular heartbeat, palpitations, vasodilation, pallor
respiratory arrest, pulmonary edema, difficulty breathing, wheezing, nasal congestion, sneezing, cough, dry throat, throat tightness with sensation of suffocation, respiratory spasms, throat swelling
eczema, skin redness, swelling of the lips and local swelling in the mouth
muscle cramps, myasthenia, back pain
malaise, chest discomfort, fever, facial edema, extravasation of the product outside blood vessels which may cause tissue necrosis at the injection site, inflammation of a vein
reduced levels of oxygen in the blood

Cases of nephrogenic systemic fibrosis (which causes hardening of the skin and may also affect soft tissues and internal organs) have been reported, most of them in patients treated with Dotagraf in combination with other gadolinium-containing contrast agents. If, in the weeks following your MRI, you notice changes in the colour and/or thickness of your skin anywhere on 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, talk to the radiologist, pharmacist, doctor, or nurse. You can also report side effects directly via the following website: 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.

7. How to store Dotagraf

Keep this medicine out of the sight and reach of children.
This medicine requires no special storage conditions.
Chemical and physical stability has been demonstrated for 72 hours during use at room temperature. From a
microbiological standpoint, the product should be used immediately. Otherwise, the storage times during use and
conditions prior to use are the responsibility of the user and normally should not exceed 24 hours at temperatures
between 2 and 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 outer packaging following the abbreviation “Exp”. The expiry date refers to the last day of that month.

8. Contents of the pack and other information

What Dotagraf 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-tetra-azacyclododecane-1,4,7,10-tetra-acetic acid (DOTA), and water for injections.

Description of the appearance of Dotagraf and contents of the pack
Dotagraf is a clear, colourless to yellow solution for intravenous injection. Dotagraf is available in packs containing one or ten vials of 60 and 100 ml of injectable solution. Not all pack sizes may be marketed.

Marketing Authorisation Holder
Bayer S.p.A.
Viale Certosa, 130
20156 Milan, Italy

Manufacturer
Sanochemia Pharmazeutika GmbH
Landegger Straße 7
2491 Neufeld/Leitha, Austria

This medicinal product is authorised in the European Economic Area under the following names:

Austria, Germany	Dotagraf 0.5 mmol/ml solution for injection
Belgium	Dotagraph 0.5 mmol/ml solution for injection / injectable solution / Injektionslösung
Bulgaria	Dotagraf 0.5 mmol/ml solution for injection
Denmark, Estonia, Iceland, Italy, Portugal	Dotagraf
Hungary	Dotagraf 0.5 mmol/ml multi-dose injection solution
Ireland	Dotagraf 279.32 mg/ml solution for injection
Latvia	Dotagraf 0.5 mmol/ml solution for injection (multi-dose)
Lithuania	Dotagraf 0.5 mmol/ml injection solution
Luxembourg	Dotagraph 0.5 mmol/ml solution injectable
Netherlands	Dotagraf 0.5 mmol/ml (for multiple use), solution for injection
Poland	Dotagraf multidose
Romania	Dotagraf 0.5 mmol/ml injectable solution in multi-dose vial
Spain	Dotagraf 0.5 mmol/ml solution for injection EFG
Sweden	Dotagraf (large injection bottle)

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

Dosage

Use the lowest dose that provides sufficient diagnostic enhancement. The dose should be calculated according to the patient's body weight and must not exceed the recommended dose per kilogram of body weight stated in this section.

Brain and spinal MRI: In neurological examinations, the dose may range from 0.1 to 0.3 mmol/kg body weight, corresponding to 0.2–0.6 ml/kg body weight. After administration of 0.1 mmol/kg body weight in patients with brain tumors, an additional dose of 0.2 mmol/kg body weight may improve tumor characterization and facilitate therapeutic decision-making.
Whole-body MRI and angiography: The recommended dose for intravenous injection is 0.1 mmol/kg body weight (i.e., 0.2 ml/kg body weight) to provide diagnostically adequate contrast.
Angiography: In special circumstances (e.g., failure to obtain satisfactory images of a large vascular territory), administration of a second consecutive injection of 0.1 mmol/kg body weight (equivalent to 0.2 ml/kg body weight) may be justified. However, if the use of two consecutive doses of Dotagraf is anticipated prior to the start of angiography, using 0.05 mmol/kg body weight (equivalent to 0.1 ml/kg body weight) for each dose may be beneficial, depending on the available imaging equipment.
Paediatric population: Brain and spinal cord MRI / Whole-body MRI: The recommended and maximum dose of Dotagraf is 0.1 mmol/kg body weight. More than one dose should not be used during a single scan.
Due to immature renal function in neonates up to 4 weeks of age and infants up to 1 year of age, Dotagraf should be used in these patients only after careful consideration of the necessity of use, at a dose not exceeding 0.1 mmol/kg body weight. More than one

dose should not be administered during a single scan. Due to lack of data on repeated administration, Dotagraf injections should not be repeated unless the interval between injections is at least 7 days. Dotagraf is not recommended for angiography in children under 18 years of age, as data on efficacy and safety for this indication are insufficient.

Patients with renal impairment: The dose used in adults applies to patients with mild to moderate renal impairment (GFR ≥ 30 ml/min/1.73 m²). See also the section below “Renal function impairment”.
Patients with hepatic impairment: The adult dose applies to these patients. Caution is recommended, especially during the perioperative period of liver transplantation.

Route of administration

Dotagraf is indicated exclusively for intravenous administration. Do not use intrathecally. Particular care must be taken to ensure strictly intravenous injection: extravasation may cause local intolerance reactions, which require standard local 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 monitored for at least 30 minutes, as experience shows that most adverse reactions occur within this time frame.

The rubber stopper should be punctured only once with an appropriate withdrawal device (needle).

In general, the withdrawal device should have the following characteristics: trocar, sterile air filter, luer, and a closure with protective seal.

Dotagraf may be used with a single-use (sterile) pre-filled syringe to perform a single-dose protocol or to inject a second contrast bolus if clinically necessary.

An automated injection system may be used only for a single patient to perform repeated injections.

At the end of the examination, any remaining product in the vial or single-use device must be discarded within a maximum of 24 hours after puncturing the rubber stopper. Follow carefully the manufacturer's instructions for 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 Dotagraf administered to the child, it is preferable to use Dotagraf vials with a single-use syringe appropriate for that volume to ensure greater accuracy of the injected volume.

In neonates and children, the required dose should be administered manually.

Renal function impairment

Before administering Dotagraf, it is recommended that all patients be screened for renal dysfunction by laboratory tests:

Cases of nephrogenic systemic fibrosis (NSF) have been reported following the use of certain gadolinium-containing contrast agents in patients with severe acute or chronic renal impairment (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 potentially occur with Dotagraf, the product should be used in patients with severe renal impairment and in those in the perioperative phase of liver transplantation only after careful consideration of the risk-benefit ratio and when essential diagnostic information cannot be obtained by non-contrast MRI. If Dotagraf must be used, the dose should not exceed 0.1 mmol/kg body weight. More than one dose should not be administered during a single scan. Due to lack of data on repeated administration, Dotagraf injections should not be repeated unless the interval between injections is at least 7 days. Haemodialysis immediately after Dotagraf administration may be helpful in eliminating this medicinal product from the body. There is no evidence supporting initiation of haemodialysis for the prevention or treatment of NSF in patients 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 above under Dosage and Method of administration, paediatric population.

Pregnancy and lactation

Dotagraf must not be used during pregnancy unless the clinical condition of the woman necessitates the use of gadoteric acid.

The decision to continue or interrupt breastfeeding for a period of 24 hours after administration of Dotagraf should be at the discretion of the physician and the breastfeeding mother.

Instructions for handling

The traceability adhesive label on the vials should be removed and affixed to the patient's medical record to allow accurate documentation of the gadolinium-containing contrast agent used. The dose administered must also be recorded. If electronic patient records are used, the product name, batch number, and dose must be recorded in the electronic file.