Dotagraf

Package Leaflet: Information for the User

Dotagraf, 0.5 mmol/ml

Solution for Injection

Gadoterenic acid

Read all of this leaflet carefully before using this medicine because it contains important information for you.

• You should keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or radiologist.
• If you get any side effects, talk to your doctor or radiologist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

• 1. What is Dotagraf and what is it used for
• 2. Before you are given 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 is Dotagraf and what is it used for

Dotagraf is a contrast agent containing gadoterenic acid. It is for diagnostic use only.
Dotagraf is used to increase the contrast of images obtained during magnetic resonance imaging (MRI) examinations.
This contrast enhancement improves the visibility and differentiation of the image:
Adults, children, and adolescents (0-18 years)

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

Adults

• in MR angiography, including disorders (pathological changes) and stenosis of arteries, with the exception of coronary arteries.

2. Before you are given Dotagraf

When must you not be given Dotagraf

• if you are allergic to the active substance or any of the other ingredients of this medicine (listed in section 6).
• if you are allergic to gadolinium-containing contrast agents (such as other MRI contrast agents).

Warnings and precautions

Before receiving Dotagraf, tell 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 have asthma.
• you have had an allergy (e.g., allergy to shellfish, hives, hay fever).
• you are being treated with a beta-blocker (a medicine used to treat heart and blood pressure disorders, such as metoprolol).
• your kidneys do not work properly.
• you have recently had or are expecting a liver transplant in the near future.
• you have heart or blood vessel disease.
• you have had seizures or are being treated for epilepsy.

In all these cases, your doctor or radiologist will assess the benefits and risks and decide whether you can be given Dotagraf. If you are given Dotagraf, your doctor or radiologist will take the necessary precautions and closely monitor the administration of Dotagraf.
Your doctor or radiologist may decide to perform a blood test to check your kidney function before deciding to use Dotagraf, especially in patients aged 65 and over.

Newborns and infants

Due to the immaturity of kidney function in newborns up to 4 weeks of age and infants up to 1 year of age, Dotagraf will only be used in these patients after careful consideration by the doctor.
Before the examination, remove any metal objects that the patient may be wearing. Inform your doctor or radiologist if the patient has:

• a pacemaker,
• a vascular clip,
• an infusion pump,
• a nerve stimulator,
• a cochlear implant (an implant in the inner ear),
• or if there is a suspicion of a metal foreign body, especially in the eye. This is very important because MRI equipment uses very strong magnetic fields.

Dotagraf with other medicines

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 currently taking or have recently taken medicines for heart or blood pressure disorders, such as beta-blockers, vasoactive agents, ACE inhibitors, or angiotensin II receptor antagonists.

Dotagraf with food and drink

No interactions with 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 or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or radiologist for advice before receiving this medicine.
Pregnancy
Gadoterenic acid may pass through the placenta. It is not known whether this affects the baby. Dotagraf should not be used during pregnancy unless absolutely necessary.
Breastfeeding
Your doctor or radiologist will discuss with you whether you can continue breastfeeding or should stop for 24 hours after receiving Dotagraf.

Driving and using machines

There is no available data on the effects of Dotagraf on the ability to drive or use machines.
If you feel unwell after the examination, you should not drive or operate machinery.

3. How Dotagraf is given

Dotagraf will be given as an intravenous injection.
During the examination, you will be under close observation by your doctor or radiologist. A needle will be left in your vein, so that if necessary, your doctor or radiologist can quickly inject emergency medication. If you have an allergic reaction, the administration of Dotagraf will be stopped.
Dotagraf may be given manually or using an automatic injector. In newborns and infants, it will only be given manually.
This procedure may be performed in a hospital, clinic, or private office. The personnel involved in performing the examination know what precautions to take during the examination and are also aware of potential complications that may occur.

Dosage

Your doctor or radiologist will determine the dose suitable for you and will supervise the administration of Dotagraf.

Dosage in special patient groups

Dotagraf is not recommended for use in patients with severe kidney function disorders or in patients who have recently had or are expecting a liver transplant in the near future. However, if Dotagraf needs to be used during an MRI examination, the patient should receive only one dose of Dotagraf and should not receive another dose for at least 7 days.
Newborns, infants, children, and adolescents
Due to the immaturity of kidney function in newborns up to 4 weeks of age and infants up to 1 year of age, Dotagraf will only be used in these patients after careful consideration by the doctor. Newborns and infants should receive only one dose of Dotagraf during the examination and should not receive another dose for at least 7 days.
MR 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 and over; however, it may be necessary to perform a blood test to check kidney function.

Overdose

It is very unlikely that you will receive too much Dotagraf. Dotagraf will be given in a medical facility by trained personnel. In the event of an 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, ask 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 observed for at least half an hour. Most side effects occur immediately or shortly after administration. Some side effects may occur up to seven days after injection of Dotagraf.

There is a small risk of an allergic reaction to Dotagraf. Such reactions can

be severe and may cause anaphylactic shock(a life-threatening allergic reaction). The following symptoms may be the first signs of anaphylactic shock. If you notice any of these symptoms, tell your doctor, radiologist, or other medical staff immediately:

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

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

• hypersensitivity (allergic reaction),
• headache,
• unusual taste in the mouth,
• dizziness,
• drowsiness,
• feeling of tingling, warmth/burning, cold, and/or pain,
• low or high blood pressure,
• nausea (vomiting),
• abdominal pain,
• rash,
• feeling of heat, feeling of cold,
• asthenia (loss of energy, weakness),
• discomfort at the injection site, injection site reactions, feeling of coolness at the injection site, swelling at the injection site, extravasation, which may lead to inflammation (redness and local 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,
• coughing,
• vomiting,
• diarrhea,
• increased salivation,
• hives, itching, increased sweating,
• chest pain, chills.

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

• anaphylactic or anaphylactoid reactions (severe, potentially life-threatening allergic reactions),
• agitation,
• coma, seizures, fainting (transient loss of consciousness), olfactory disorders (perception of unpleasant odors), muscle tremors,
• conjunctivitis, eye redness, blurred vision, increased tearing,
• cardiac arrest, accelerated or slowed heart rate, irregular heartbeat, vasodilation, pallor,
• respiratory arrest, pulmonary edema, breathing difficulties, wheezing, feeling of nasal congestion, coughing, throat dryness, throat spasm with a feeling of choking, respiratory spasms, throat swelling
• flushing, skin redness, swelling of the lips and inside the mouth,
• muscle spasms, muscle weakness, back pain,
• malaise, chest discomfort, fever, facial swelling, extravasation, which may lead to tissue necrosis at the injection site, phlebitis,
• decreased oxygen levels in the blood.

There have been reports of nephrogenic systemic fibrosis (NSF), which causes skin hardening and may also affect soft tissues and internal organs, predominantly in patients receiving Dotagraf along with other gadolinium-containing contrast agents. If, in the weeks following the MRI examination, the patient notices changes in skin color and/or thickness at any site on the body, they should inform the radiologist who performed the examination.

Reporting of side effects

If you get any side effects, talk to your doctor or radiologist. This includes any possible side effects not listed in this leaflet. Side effects can be reported to the Department of Adverse Reaction Monitoring 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.
Side effects can also be reported to the marketing authorization holder. 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.
No special precautions for storage are necessary.
The chemical and physical stability of the medicine after preparation has been demonstrated for at least 72 hours at room temperature. From a microbiological point of view, the medicine should be used immediately. If not used immediately, the user is responsible for the storage conditions and storage time before administration, which should not exceed 24 hours at 2°C – 8°C, unless the medicine has been opened in controlled and validated aseptic conditions.
Do not use this medicine after the expiry date which is stated on the vial and carton after “Exp”. The expiry date refers to the last day of that month.

6. Contents of the pack and other information

What Dotagraf contains

• The active substance is gadoterenic acid. One milliliter of the solution for injection contains 279.32 mg of gadoterenic acid (as meglumine salt), which corresponds to 0.5 mmol of gadoterenic acid (as meglumine salt).
• The other ingredients 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 colorless to yellowish, clear solution for intravenous injection.
The pack contains one or ten vials of 10, 15, or 20 ml of solution for injection.
Not all pack sizes may be marketed.

Marketing Authorization 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 authorized in the Member States of the EEA under the following names:

Date of last revision of the leaflet:November 2024
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Information intended for healthcare professionals only:

Dosage

Use the smallest dose that provides sufficient contrast enhancement for diagnostic purposes. The dose should be calculated based on the patient's body weight and should not exceed the recommended dose per kilogram of body weight specified in this section.

• MRI of the brain and spinal cord: In central nervous system examinations, doses range from 0.1 to 0.3 mmol/kg body weight, which corresponds to 0.2 to 0.6 ml/kg body weight. After administration of 0.1 mmol/kg body weight to patients with brain tumors, administration of an additional dose of 0.2 mmol/kg body weight may facilitate the determination of the nature of the tumor and the decision on treatment.
• MRI of the whole body and angiography: The recommended dose for intravenous injection, providing adequate contrast for diagnosis, is 0.1 mmol/kg body weight (i.e., 0.2 ml/kg body weight). Angiography: In exceptional circumstances (e.g., when images of satisfactory quality covering an extensive vascular area cannot be obtained), it may be justified to administer a second consecutive dose of 0.1 mmol/kg body weight (corresponding to 0.2 ml/kg body weight). However, if two consecutive doses of Dotagraf are planned before angiography, it may be beneficial to administer 0.05 mmol/kg body weight (i.e., 0.1 ml/kg body weight) in each dose, depending on the available imaging equipment.
• Children and adolescents: MRI of the brain and spinal cord/MRI of the whole body: The recommended and maximum dose of Dotagraf is 0.1 mmol/kg body weight. Do not administer more than one dose during the examination. Due to the immaturity of kidney function in newborns 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. Newborns and infants should receive only one dose of Dotagraf during the examination and should not receive another dose for at least 7 days. Dotagraf is not recommended for use in MR angiography in children under 18 years of age.
• 1. Due to the immaturity of kidney function in newborns 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, at a dose not exceeding 0.1 mmol/kg body weight. During one examination, do not administer more than one dose. Due to the lack of information on repeated administration, do not repeat injections of Dotagraf at intervals of less than 7 days.
• Patients with renal impairment: In patients with mild to moderate renal impairment (GFR ≥30 ml/min/1.73 m²), use the doses recommended for adults. See also "Renal impairment" below.
• Patients with hepatic impairment: In these patients, use the doses recommended for adults. Caution is advised, especially in the perioperative period related to liver transplantation.

Method of administration

Dotagraf is intended for intravenous use only. Do not administer intraperitoneally. Administer intravenously only: extravasation may cause local intolerance reactions requiring local treatment.
Infusion rate: 3-5 ml/min (during angiographic examinations, a higher infusion rate of up to 120 ml/min, i.e., 2 ml/s, may be used).
Optimal imaging: within 45 minutes of injection.
Optimal imaging sequence: T1-weighted images
Whenever possible, the contrast agent should be administered intravenously to the patient in a supine position. After administration, the patient should remain under observation for at least half an hour, as experience shows that most side effects occur during this period.
Prepare a syringe with a needle. Remove the plastic disc. After cleaning the stopper with an alcohol swab, puncture the stopper with the needle. Draw up the required amount of Dotagraf and administer it intravenously to the patient.
For single use only. Discard any unused solution.
The solution for injection should be inspected visually before use. Only use clear solutions free from visible particles.
Children and adolescents
Depending on the amount of Dotagraf to be administered to the child, it is recommended to use vials of Dotagraf with a single-use syringe of suitable capacity to maintain greater accuracy in the injected volume.
In newborns and infants, the required dose should be administered manually.

Renal impairment

It is recommended that all patients undergo screening laboratory tests for renal impairment before administration of Dotagraf.

There have been reports of nephrogenic systemic fibrosis (NSF) associated with the use of some gadolinium-containing contrast agents 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 group has a high developing acute renal impairment. since there is nsf after administration dotagraf, it should only be used in with severe impairment and the perioperative period related to careful assessment benefit-risk ratio when diagnostic information essential cannot obtained using mri without contrast enhancement. if use dotagraf necessary, dose not exceed 0.1 mmol kg body weight. during one examination, do administer more than dose. due lack on repeated administration, repeat injections intervals less 7 days.
Hemodialysis performed shortly after administration of Dotagraf may facilitate its removal from the body. There is no evidence to justify the initiation of hemodialysis to prevent NSF or to treat it in patients not already undergoing hemodialysis.

Elderly patients

Since the renal clearance of gadoterenic acid may be impaired in elderly patients, it is particularly important to check kidney function before administration in patients aged 65 and over.

Newborns and infants

See Dosage and Method of 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 gadoterenic acid.
The decision to continue breastfeeding or to stop for 24 hours after administration of Dotagraf should be made by the doctor and the breastfeeding mother.

Instructions for handling Dotagraf

The detachable label from the vial should be attached to the patient's file to allow accurate recording of the contrast agent used. The administered dose should also be recorded. If the patient's file is kept electronically, the product name, batch number, and administered dose should be entered into the file.