Dotagraf

Package leaflet: Information for the user

Dotagraf, 0.5 mmol/ml
Injection solution
Gadoterinic acid
Please read all of this leaflet carefully before this medicine is administered, because it contains
important information for you.

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

Table of contents of the leaflet

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

1. What Dotagraf is and what it is used for

Dotagraf is a contrast agent containing gadoterinic acid. It is intended
for diagnostic use only.
Dotagraf is used to enhance image contrast in magnetic resonance imaging (MRI) procedures. This contrast enhancement improves the visibility and differentiation of images:
Adults, children and adolescents (0–18 years)

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

Adults

• in MR angiography, including abnormalities (pathological changes) and narrowing (stenosis) of arteries, excluding coronary arteries.

2. Important information before using Dotagraf

When NOT to use Dotagraf

• if the patient is allergic to the active substance or to any of the other ingredients of this medicine (listed in section 6.).
• if the patient is allergic to gadolinium-containing medicines (such as other contrast agents used in magnetic resonance imaging).

Warnings and precautions
Before starting treatment with Dotagraf, inform your doctor or radiologist if any of the following apply to the patient:

• the patient has previously experienced a reaction to a contrast agent during an examination.
• the patient suffers from asthma.
• the patient has previously experienced allergies (e.g. allergy to seafood, hives, hay fever).
• the patient is being treated with beta-blockers (a medicine used to treat heart disorders and high blood pressure, such as metoprolol).
• the patient's kidneys are not working properly.
• the patient has recently undergone or is scheduled to undergo liver transplantation in the near future.
• the patient suffers from heart or blood vessel disease.
• the patient has experienced seizures or is being treated for epilepsy.

In all these cases, the doctor or radiologist will assess the benefit-risk ratio and decide whether Dotagraf can be administered to the patient. If Dotagraf is administered, the doctor or radiologist will take necessary precautions and the administration of Dotagraf will be closely monitored.
The doctor or radiologist may decide to perform a blood test to check the patient's kidney function before deciding to administer Dotagraf, especially in patients aged 65 years and older.
Newborns and infants
Due to immature kidney function in newborns up to 4 weeks of age and infants up to 1 year of age, Dotagraf will be administered to these patients only after careful consideration by the doctor.
Before the examination, all metallic objects the patient may be wearing should be removed. Inform the doctor or radiologist if the patient has implanted:

• a cardiac pacemaker,
• a vascular clip,
• an infusion pump,
• a nerve stimulator,
• a cochlear implant (an inner ear implant),
• or if there is suspicion of any metallic foreign body, especially in the eye. This is very important, as imaging devices using magnetic resonance employ very strong magnetic fields, which may cause serious problems.

Dotagraf and other medicines
Inform the doctor or radiologist if the patient is taking, has recently taken, or might take any other medicines. In particular, inform the doctor, radiologist, or pharmacist if the patient is currently taking or has recently taken medicines for heart disorders or high blood pressure, such as beta-blockers, vasoactive agents, angiotensin-converting enzyme inhibitors, or angiotensin II receptor antagonists.
Dotagraf with food and drink
No interactions between Dotagraf and food or beverages are known. However, ask your doctor, radiologist, or pharmacist whether it is necessary to refrain from eating or drinking before the examination.
Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor or radiologist before using this medicine.
Pregnancy
Gadoterinic acid may cross the placenta. It is unknown whether this affects the unborn child. Dotagraf should not be used during pregnancy unless absolutely necessary.
Breastfeeding
The treating doctor or radiologist will discuss with the patient and explain whether she can continue breastfeeding or should interrupt it for 24 hours after administration of Dotagraf.
Driving and using machines
There are no available data regarding the effect of Dotagraf on the ability to drive. If the patient feels unwell after the examination, he or she should not drive or operate machinery.

3. How to use Dotagraf

Dotagraf will be administered as an intravenous injection.
During the examination, the patient will be under close supervision by a physician or radiologist. An intravenous needle will remain in place so that, if necessary, the physician or radiologist can quickly administer life-saving medications. If the patient experiences an allergic reaction, administration of Dotagraf will be stopped immediately.
Dotagraf may be administered manually or using an automated injector. In newborns and infants, this medicine must be administered only manually.
This procedure may be performed in a hospital, outpatient clinic, or private office. The medical staff involved in the examination are aware of the precautions to be taken during the procedure and are familiar with potential complications that may occur.
Dosage
The physician or radiologist will determine the appropriate dose for the patient and will supervise the injection of the medicine.
Dosage in special patient groups
Dotagraf is not recommended for patients with severe renal function impairment or for patients who have recently undergone or are scheduled to undergo liver transplantation in the near future. However, if Dotagraf is required during an MRI examination, the patient should receive only a single dose and should not receive another dose within at least 7 days.
Newborns, infants, children, and adolescents
Due to immature kidney function in newborns 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 by the physician. Newborns and infants should receive only a single dose of Dotagraf during the examination and should not receive another dose within at least 7 days.
Angiography is not recommended in children under 18 years of age.
Elderly patients
There is no need to adjust the dose in patients aged 65 years and older; however, a blood test to assess kidney function may be necessary.
Administration of a higher than recommended dose of Dotagraf
It is highly unlikely that a patient would receive an excessive dose of the medicine. Dotagraf is administered in a medical facility by trained personnel. In the event of actual overdose, Dotagraf can be removed from the body by hemodialysis (blood purification).
Additional information on the use and handling of this medicine by medical personnel is provided at the end of this leaflet.
If you have any further questions about the use of this medicine, consult your physician or radiologist.

4. Possible adverse reactions

Like any medicine, this medicine can cause adverse reactions, although not everyone experiences them.
After receiving the medicine, the patient will be monitored for at least 30 minutes. Most adverse
reactions occur immediately or shortly after administration of the medicine. Some adverse
reactions may occur up to seven days after injection of Dotagraf.
There is a small risk of an allergic reaction to Dotagraf. Such reactions may be severe and may
cause anaphylactic shock (a type of allergic reaction that may be life-threatening). The following
symptoms may be early signs of shock. If the patient notices any of the symptoms listed below, they
should immediately inform the doctor, radiologist, or another healthcare professional:

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

Uncommon adverse reactions (may occur in no more than 1 in 100 patients)

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

Rare adverse reactions (may occur in no more than 1 in 1000 patients)

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

Very rare adverse reactions (may occur in no more than 1 in 10,000 patients)

• anaphylactic or anaphylactoid reactions (severe, potentially life-threatening allergic reactions),
• restlessness,
• coma, seizures, fainting (short-term loss of consciousness), disturbances of smell (perception of often unpleasant odours), muscle tremor,
• conjunctivitis, redness of the eyes, blurred vision, excessive tearing,
• circulatory arrest, rapid or slow heartbeat, irregular heartbeat, blood vessel dilation, pallor,
• respiratory arrest, pulmonary oedema, breathing difficulties, wheezing, nasal congestion, cough, dry throat, throat spasm with sensation of suffocation, respiratory spasms, throat swelling,
• rash, skin redness, swelling of lips and inside the mouth,
• muscle spasms, muscle weakness, back pain,
• malaise, chest discomfort, fever, facial swelling, extravasation (leakage of medicine outside blood vessels), which may lead to inflammation or necrosis of tissue at injection site, phlebitis,
• decreased oxygen levels in the blood.

There have been reports of systemic nephrogenic fibrosis (which causes hardening of the skin and may also affect soft tissues and internal organs), which usually occurred in patients receiving Dotagraf together with other contrast agents containing gadolinium. If, in the weeks following an MRI examination, the patient notices changes in colour and (or) thickness of the skin anywhere on the body, they should inform the radiologist who performed the examination.
Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, tell your doctor or radiologist. Adverse reactions can be reported directly to the Department of Monitoring of Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl .
Adverse reactions can also be reported to the marketing authorization holder. By reporting adverse reactions, additional information on the safety of the medicine can be collected.

5. How to store Dotagraf

Keep this medicine out of the sight and reach of children.
No special storage conditions are required.
Chemical and physical stability of the medicine has been demonstrated for at least 72 hours after preparation at room temperature. From a microbiological standpoint, the medicine should be used immediately. If the medicine is not used immediately, the user is responsible for ensuring appropriate storage conditions and storage time prior to administration, provided that this time does not exceed 24 hours at 2°C – 8°C, unless the medicine was opened 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 the specified month.

6. Contents of the pack and other information

What Dotagraf contains

• The active substance in Dotagraf is gadoterinic acid. One millilitre of injection solution contains 279.32 mg of gadoterinic acid (as meglumine salt), equivalent to 0.5 mmol of gadoterinic acid (as meglumine salt).
• The other components are meglumine, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), and water for injections.

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

Marketing Authorisation Holder
Bayer AG
Kaiser-Wilhelm-Allee 1
51373 Leverkusen
Germany

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

This medicinal product is authorised in the EEA countries under the following names:

Information intended exclusively for healthcare professionals:

Dosage
The lowest dose providing sufficient contrast enhancement for diagnostic purposes should be used. The dose should be calculated based on 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 imaging, doses range from 0.1 to 0.3 mmol/kg body weight, corresponding to 0.2 to 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 facilitate characterization of the tumor and support treatment decisions.
• Whole-body MRI and angiography: The recommended intravenous dose providing diagnostically adequate contrast enhancement is 0.1 mmol/kg body weight (i.e., 0.2 ml/kg body weight). Angiography: In exceptional circumstances (e.g., when satisfactory image quality covering a large vascular area has not been achieved), administration of a second consecutive dose of 0.1 mmol/kg body weight (corresponding to 0.2 ml/kg body weight) may be justified. However, if two consecutive doses of Dotagraf are anticipated prior to initiating angiography, administering 0.05 mmol/kg body weight (i.e., 0.1 ml/kg body weight) per dose may be beneficial, depending on the available imaging equipment.
• Children and adolescents: Brain and spine 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 administered during a single examination. Due to immature renal function in neonates up to 4 weeks of age and infants up to 1 year of age, Dotagraf should only be used in these patients after careful consideration and at a dose not exceeding 0.1 mmol/kg body weight. More than one dose should not be administered during a single examination. Due to lack of data on repeated administration, injections of Dotagraf should not be repeated at intervals shorter than 7 days. Dotagraf is not recommended for use in angiography in children under 18 years of age due to insufficient data on efficacy and safety for this indication.
• Patients with renal impairment: In patients with mild to moderate renal impairment (GFR ≥30 ml/min/1.73 m²), the standard adult doses are used. See also section "Renal function impairment" below.
• Patients with hepatic impairment: In such patients, the standard adult doses are used. Caution is advised, particularly in the perioperative period related to liver transplantation.

Administration
Dotagraf is indicated exclusively for intravenous use. Do not administer intrathecally. Intravenous administration only: extravasation may cause local intolerance reactions requiring local treatment.
Infusion rate: 3–5 ml/min (higher infusion rates up to 120 ml/min, i.e., 2 ml/s, may be used during angiographic procedures).
Optimal imaging: within 45 minutes after injection.
Optimal imaging sequence: T1-weighted images.
Whenever possible, the contrast agent should be administered intravenously while the patient is in a supine position. After administration, the patient should remain under observation for at least 30 minutes, as clinical experience shows that most adverse reactions occur during this period.
Prepare a syringe with a needle. Remove the plastic disk. After disinfecting the stopper with an alcohol swab, pierce the stopper with the needle. Draw up the required volume of Dotagraf and administer intravenously.
For single use only. Any unused solution must be discarded.
The injectable solution should be inspected visually before use. Only clear, particle-free solutions should be used.

Children and adolescents
Depending on the volume of Dotagraf to be administered to a child, it is recommended to use vials of Dotagraf together with a single-use syringe of appropriate capacity to ensure greater accuracy of the injected volume.
In neonates and infants, the required dose should be administered manually.

Renal function impairment
All patients should undergo screening laboratory tests for renal function impairment prior to administration of Dotagraf.
Cases of nephrogenic systemic fibrosis (NSF) associated with the use of certain gadolinium-containing contrast agents have been reported in patients with acute or chronic severe renal impairment (GFR < 30 ml/min/1.73 m²). Patients undergoing liver transplantation are particularly at risk of this complication, as this group has a high risk of developing acute renal failure. Because of the risk of NSF following administration of Dotagraf, the product should be used in patients with severe renal impairment and in patients in the perioperative period of liver transplantation only after careful benefit-risk assessment and only when essential diagnostic information cannot be obtained by non-contrast MRI. If use of Dotagraf is necessary, the dose should not exceed 0.1 mmol/kg body weight. More than one dose should not be administered during a single examination. Due to lack of data on repeated administration, injections of Dotagraf should not be repeated at intervals shorter than 7 days.
Hemodialysis performed shortly after administration of Dotagraf may facilitate elimination of the agent from the body. There is no evidence to support initiating hemodialysis for the prevention or treatment of NSF in patients not already undergoing dialysis.

Elderly patients
Since renal clearance of gadoterate acid may be reduced in elderly patients, assessment of renal function is particularly important in patients aged 65 years and older.

Neonates and infants
See Dosage and Administration, Children and adolescents.

Pregnancy and lactation
Dotagraf should not be used during pregnancy unless the clinical condition of the woman requires the use of gadoterate acid.
The decision on whether to continue or interrupt breastfeeding for 24 hours after administration of Dotagraf should be made jointly by the physician and the breastfeeding mother.

Instructions for handling Dotagraf
The detachable identification label from the vial should be attached to the patient's medical record to allow accurate documentation of the gadolinium-containing contrast agent used. The administered dose should also be recorded. If the patient's record is maintained electronically, the product name, batch number, and administered dose should be entered into the electronic record.