DOTAGRAF 0.5 mmol/ml INJECTABLE SOLUTION

2. What you need to know before you start using Dotagraf

Do not use Dotagraf

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

Warnings and precautions

Consult your doctor or radiologist before starting Dotagraf if you:

• have had a reaction to contrast agents during a previous test
• have asthma
• have a history of allergy (such as shellfish allergy, hives, hay fever)
• are being treated with a beta-blocker (medications used for heart problems and blood pressure disorders, such as metoprolol)

your kidneys do not function properly

• you have recently undergone or are about to undergo 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, your doctor or radiologist will assess the benefit-risk ratio and decide whether you should be given Dotagraf. If you are given Dotagraf, your doctor or radiologist will take the necessary precautions and the administration of Dotagraf will be carefully monitored.

Your doctor or radiologist may decide to perform a blood test to check the proper functioning of your kidneys before deciding to use Dotagraf, especially if you are 65 years or older.

Newborns and infants

Due to the immaturity of renal function in newborns up to 4 weeks of age and in infants up to 1 year of age, Dotagraf should only be used in these patients after careful evaluation by the doctor.

Remove all metal objects you may be wearing before the examination. Inform your doctor or radiologist if you have:

• a pacemaker
• a vascular clip
• an infusion pump
• a neurostimulator
• a cochlear implant (implant in the inner ear)
• any suspected metal foreign body, particularly in the eye.

This is important because they can cause serious problems due to the strong magnetic fields used in MRI equipment.

Using Dotagraf with other medications

Tell your doctor or radiologist if you are taking, have recently taken, or may need to take other medications.

In particular, please inform your doctor, radiologist, or pharmacist if you are taking or have recently taken medications for heart problems or blood pressure disorders, such as beta-blockers, vasoactive substances, angiotensin-converting enzyme inhibitors, or angiotensin II receptor antagonists.

Using Dotagraf with food and drinks

There are no known interactions between Dotagraf and food or drinks. However, please consult your doctor, radiologist, or pharmacist if you need to avoid eating or drinking before the test.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or radiologist before using this medicine.

Pregnancy

Gadoteric acid may cross the placenta. It is unknown whether it affects the fetus. Dotagraf should not be used during pregnancy unless it is absolutely necessary.

Breastfeeding

Your doctor or radiologist will assess whether you should continue or interrupt breastfeeding 24 hours after the administration of Dotagraf.

Driving and using machines

There is no information on the effects of Dotagraf on the ability to drive and use machines. If you feel unwell after the test, you should not drive or use machines.

3. How to use Dotagraf

Dotagraf will be administered by intravenous injection.

During the test, you will be under the supervision of a doctor or radiologist. A needle will be left in your vein; this will allow the doctor or radiologist to inject emergency medications if necessary. If you experience an allergic reaction, the administration of Dotagraf will be stopped.

Dotagraf can be administered manually or using an automatic injector. In newborns and infants, the product will only be administered manually.

The procedure will be performed in a hospital, clinic, or private clinic. The healthcare staff is aware of the precautions to be taken for the test. They are also aware of any possible complications that may occur.

Dosage

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

Dosage in special populations

The use of Dotagraf is not recommended in patients with severe kidney problems or in patients who have recently undergone or are about to undergo a liver transplant. However, if use is required, only one dose of Dotagraf should be administered during the procedure, and a second injection should not be administered until at least 7 days have passed.

Newborns, infants, children, and adolescents

Due to the immaturity of renal function in newborns up to 4 weeks of age and in infants up to 1 year of age, Dotagraf should only be used after careful evaluation by the doctor. Newborns and infants should only receive one dose of Dotagraf during the procedure, and a second injection should not be administered until at least 7 days have passed.

The use for angiography is not recommended in children under 18 years of age.

Elderly patients

If you are 65 years or older, it is not necessary to adjust the dose, but a blood test may be performed to check the proper functioning of your kidneys.

If you use more Dotagraf than you should

It is highly unlikely that you will be given an overdose. You will be administered Dotagraf in medical facilities by a trained person. In the event of an overdose, Dotagraf can be removed from the body by hemodialysis (blood cleansing).

At the end of this leaflet, you will find additional information on the use and handling of Dotagraf by the doctor or healthcare professional.

If you have any further questions on the use of this medicine, ask your doctor or radiologist.

In case of overdose or accidental ingestion, consult the Toxicology Information Service (telephone 915620420).

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

After administration, you will be kept under observation for at least half an hour. Most side effects occur immediately or, sometimes, with a delay. Some effects may occur up to seven days after the injection of Dotagraf.

There is a small risk that you may have an allergic reaction to Dotagraf. Such reactions can be severe and exceptionally may cause shock(a life-threatening allergic reaction). Any of the symptoms described below may be the first signs of shock. Inform your doctor, radiologist, or healthcare professional immediately if you have any of them:

• swelling of the face, mouth, or throat that 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 patients)

• hypersensitivity (allergic reactions)
• headache
• unusual taste in the mouth
• dizziness
• drowsiness (sleepiness)
• tingling, warmth/burning, cold, and/or pain
• low or high blood pressure
• nausea (feeling sick)
• stomach pain
• 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, diffusion of the product outside the blood vessels that may cause inflammation (redness and pain locally)

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

• anxiety, fainting (dizziness and feeling of impending loss of consciousness)
  • eye swelling
  • palpitations
  • sneezing
  • vomiting (with nausea)
  • diarrhea
  • increased saliva production

• hives, itching, sweating
• chest pain, chills

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

• anaphylactic or anaphylactoid reactions (severe, life-threatening allergic reactions)
• agitation
• coma, seizures, syncope (brief loss of consciousness),

olfactory disorders (frequent perception of unpleasant odors), tremor

• conjunctivitis, red eyes, blurred vision, increased tear production
• cardiac arrest, rapid or slow heartbeat, irregular heartbeat, vasodilation, pallor
• respiratory arrest, pulmonary edema, difficulty breathing, wheezing, nasal congestion, cough, dry throat, constriction of the throat with a feeling of suffocation, respiratory spasms, inflammation of the throat
• eczema, skin redness, inflammation of the lips and localized in the mouth
• muscle cramps, muscle weakness, back pain
• general malaise, chest discomfort, fever, facial swelling, diffusion of the product outside the blood vessels that may cause tissue necrosis at the injection site, vein inflammation
• decrease in blood oxygen levels

There have been reports of nephrogenic systemic fibrosis (which causes skin hardening and may also affect soft tissues and internal organs), most of which were in patients who were administered Dotagraf in combination with other gadolinium-based contrast agents. If, during the weeks following the MRI study, you notice changes in the color and/or thickness of your skin in any part of your body, inform the radiologist who performed the examination.

Reporting side effects

If you experience any side effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Dotagraf

Keep this medicine out of the sight and reach of children.

This medicine does not require special storage conditions.

The chemical and physical stability has been demonstrated during use for a period of 72 hours at room temperature. From a microbiological point of view, the product should be used immediately. If not used immediately, the storage times and conditions before use are the responsibility of the user and normally should not exceed 24 hours at temperatures between 2°C and 8°C, unless the opening has taken place in controlled and validated aseptic conditions.

Do not use this medicine after the expiry date stated on the vial and carton after EXP. The expiry date is the last day of the month indicated.

6. Container Content and Additional Information

Composition of Dotagraf

• The active ingredient is gadoteric acid. 1 ml of injectable solution contains 279.32 mg of gadoteric acid (as meglumine salt), equivalent to 0.5 mmol of gadoteric acid (as meglumine salt).
• The other components are meglumine, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), and water for injectable preparations.

Appearance of the Product and Container Content

Dotagraf is a clear, colorless to yellow solution for intravenous injection.

The content of Dotagraf containers is 1 or 10 vials containing 60 ml or 100 ml of injectable solution.

Only some package sizes may be marketed.

Marketing Authorization Holder

Bayer Hispania, S.L.

Av. Baix Llobregat, 3-5

08970 Sant Joan Despí (Barcelona)

Manufacturer

Sanochemia Pharmazeutika GmbH

Landegger Strasse 7

2491 Neufeld/Leitha, Austria

This Medicinal Product is Authorized in the Member States of the European Economic Area under the following Names:

Other Sources of Information

Detailed information on this medicinal product is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es

Date of the Last Revision of this Leaflet: November 2024

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This Information is Intended Only for Healthcare Professionals

Posology

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

• Magnetic Resonance Imaging (MRI) of the Brain and Spine: In neurological studies, the dose may vary from 0.1 to 0.3 mmol per kilogram of body weight (mmol/kg bw), equivalent to 0.2 to 0.6 ml/kg bw. After administration of 0.1 mmol/kg bw to patients with brain tumors, an additional dose of 0.2 mmol/kg bw 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 (equivalent to 0.2 ml/kg body weight) to provide adequate contrast for diagnosis.

Angiography: In exceptional circumstances (e.g., when it is not possible to obtain satisfactory images with the first dose of an extensive vascular territory), a second consecutive injection of 0.1 mmol/kg bw, equivalent to 0.2 ml/kg bw, may be justified. However, if it is presumed that two consecutive doses of Dotagraf will be administered before starting angiography, it is advisable to administer only 0.05 mmol/kg bw, equivalent to 0.1 ml/kg bw, for each dose, depending on the MRI equipment used to obtain the images.

• Pediatric Population:

Magnetic Resonance Imaging (MRI) of the Brain and Spine / Whole-Body MRI: The recommended and maximum dose of Dotagraf is 0.1 mmol/kg body weight. No more than one dose should be used during the procedure.

Due to the immaturity of renal function in newborns up to 4 weeks of age and in infants up to 1 year of age, Dotagraf should only be used in these patients after careful consideration, with a dose that does not exceed 0.1 mmol/kg body weight. No more than one dose should be used during the procedure. Due to the lack of information on repeated administration, Dotagraf injections should not be repeated unless an interval of at least 7 days has elapsed between injections.

Dotagraf is not recommended for angiography in children under 18 years of age because the safety and efficacy data for this indication are insufficient.

• Patients with Renal Impairment: The adult dose applies to patients with mild to moderate renal impairment (GFR or glomerular filtration rate ≥ 30 ml/min/1.73 m2). See also the section "Renal Impairment" below.
• Patients with Hepatic Impairment: The adult dose applies to these patients. Caution should be exercised, especially in the perioperative period of a liver transplant.

Method of Administration

Dotagraf is administered exclusively by the intravenous route. Do not use by the intrathecal route. Care should be taken to maintain the injection strictly intravenous: extravasation can lead to local intolerance reactions, requiring usual local care.

Perfusion rate: 3-5 ml/min (perfusion rates greater than 120 ml/min, equivalent to 2 ml/s, can be used in angiographic procedures).

Optimal image acquisition: Approximately 45 minutes after injection.

Optimal image acquisition sequence: T1-weighted.

Whenever possible, intravenous administration of the contrast medium should be performed with the patient in a supine position. After injection, the patient should be kept under observation for at least 30 minutes, as experience shows that most adverse effects occur during this time interval.

The rubber stopper should be pierced only once with a suitable extraction device (spike).

In general, the extraction device should have the following characteristics: trocar, sterile air filter, luer connector, and protective sealing cap.

It can be used with a single-use manual syringe (sterile) filled for the purpose of performing a single-dose protocol or for injecting a second contrast bolus if clinically necessary.

The contrast medium can only be administered using an automatic injector for a single patient for the purpose of performing repeated administrations.

At the end of the examination session, the quantities of product remaining in the vial and in the disposable device should be discarded no later than 24 hours after piercing the rubber stopper. The specific instructions of the manufacturer of the equipment used should be carefully followed.

The injectable solution should be visually inspected before use. Only clear and particle-free solutions should be used.

Pediatric Population

Depending on the amount of Dotagraf to be administered to the child, it is preferable to use Dotagraf vials with a single-use syringe with a volume adapted to that amount, to have better precision of the injected volume.

In newborns and infants, the required dose should be administered manually.

Renal Impairment

Before administration of Dotagraf, it is recommended to evaluate all patients for possible renal dysfunction using laboratory tests.

Cases of nephrogenic systemic fibrosis (NSF) have been reported in association with the use of some gadolinium-based contrast agents in patients with severe acute or chronic renal impairment (GFR or glomerular filtration rate <30 ml min 1.73 m2). patients undergoing liver transplantation have a special risk since the incidence of acute renal failure is high in this group. there possibility that nsf may occur with dotagraf, it should only be used severe impairment and perioperative period transplant after careful benefit-risk assessment if diagnostic information essential cannot obtained using contrast-free mri. use dotagraf necessary, dose not exceed 0.1 mmol kg body weight. during an examination, no more than one administered. due to lack on repeated administration, administered again unless interval at least 7 days has elapsed between injections. hemodialysis shortly administration useful for elimination from body. evidence support initiation prevention or treatment who are hemodialysis.< p>

Elderly Patients

Since the renal elimination of gadoteric acid may be reduced in elderly patients, it is especially important to evaluate patients aged 65 years or older for possible renal dysfunction.

Newborns and Infants

See the section Posology and Method of Administration, Pediatric Population.

Pregnancy and Lactation

Dotagraf should not be used during pregnancy unless the clinical condition of the woman requires treatment with gadoteric acid.

Continuation or interruption of breastfeeding 24 hours after administration of Dotagraf will be at the discretion of the physician and the breastfeeding mother.

Handling Instructions

The detachable label of the vials should be stuck to the patient's medical record to allow accurate recording of the gadolinium-based contrast agent used. The dose used should also be recorded. If an electronic patient record is used, the name of the medicinal product, batch number, and dose should be included in the same.