Label: information for the user

DOTAREM 0.5 mmol/ml injectable solution in pre-filled syringe

Gadoteric Acid

Read this label carefully before starting to use this medicine, because it contains important information for you.

• Keep this label, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this label. See section 4.

1. What is Dotarem and how it is used

2. What you need to know before Dotarem is administered

3. How Dotarem will be administered

4. Possible adverse effects

5. Storage of Dotarem

6. Contents of the package and additional information

This medication is for diagnostic use only.

Dotarem is a contrast agent used in adults and children. It belongs to the group of contrast agents used for magnetic resonance imaging (MRI). Dotarem is used in magnetic resonance imaging (MRI) examinations to enhance image contrast. The enhancement improves the examination of certain body areas.

You should not be administered Dotarem:

Warnings and precautions

Inform your doctor or radiologist in the following cases:

• If you have had a reaction to a contrast medium during a previous examination.
• If you have asthma
• If you have a history of allergy (such as shellfish allergy, urticaria, hay fever)
• If you are being treated with a beta-blocker (medications used for heart problems, high blood pressure, such as metoprolol)
• If your kidneys do not function correctly
• If you have recently undergone, or are about to undergo, a liver transplant
• If you have a disease affecting the heart or blood vessels
• If you have had seizures or are being treated for epilepsy.

Your doctor or radiologist will assess the benefit-risk balance and decide whether you should be administered Dotarem.

If you are administered Dotarem, your doctor or radiologist will take the necessary precautions and the administration of Dotarem will be carefully supervised.

Your doctor or radiologist may decide to perform a blood test to check the proper functioning of your kidneys before deciding to use Dotarem, especially if you are 65 years old 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, gadoteric acid should be used only after medical evaluation.

Remove all metal objects you are wearing before the examination. Inform your doctor if you have:

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

This is important because MRI equipment uses very strong magnetic fields, which can cause serious problems.

Use of Dotarem withother medications

Inform your doctor or radiologist if you are taking, have taken recently, or may need to take any other medication. In particular, please inform your doctor, radiologist, or pharmacist if you are taking or have taken recently medications for the heart or blood pressure alterations such as beta-blockers, vasodilators, angiotensin-converting enzyme inhibitors, and angiotensin II receptor antagonists.

Use of Dotarem with food and drinks

There are no interactions between Dotarem and food or drink. 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 medication.

Pregnancy:

Gadoteric acid may cross the placenta. Its effects on the fetus are unknown. Dotarem should not be used during pregnancy unless strictly necessary.

Breastfeeding:

Your doctor or radiologist will assess whether you should continue breastfeeding or interrupt it for 24 hours after Dotarem administration.

Driving and operating machinery

No data are available on the effects of Dotarem on driving or operating machinery. If you feel unwell after the test, experience nausea (feeling of discomfort), you should not drive or operate machinery.

Dotarem is administered intravenously.

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

Dotarem can be administered manually or using an automatic injector.In newborns and infants, the medication must be administered manually.

The procedure will be performed in a hospital or clinic. The healthcare staff knows the precautions that must be taken for the examination. They also know any possible complications that may arise.

Dose

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

Posology in special populations

The use of Dotarem is not recommended in patients with severe kidney problems or in patients who have recently had or will soon have a liver transplant. However, if use is required, only one dose of Dotarem should be administered during an examination, 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, gadoteric acid should be used only after medical evaluation.

Children should only receive one dose of Dotarem during the scan and should not receive a second dose until at least 7 days have passed.

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

Older adults

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

If too much Dotarem has been administered

It is highly unlikely that you will receive an overdose. Dotarem will be administered after medical adjustment by a trained person. In the event of an overdose, Dotarem can be removed from the body by hemodialysis (blood cleansing).

In case of overdose or accidental ingestion, contact the Toxicological Information Service. Phone 91 562 04 20.

Additional information on the use and management of this medication by the doctor or healthcare professional can be found at the end of this prospectus.

Consult your doctor or radiologist if you have any doubts about the use of this medication.

Like all medicines, this medicine may cause side effects, although not everyone will experience them.

After administration, you will be under observation for at least half an hour. Most side effects occur immediately or may be delayed. Some effects may occur up to seven days after the Dotarem injection.

There is a small risk that you may have an allergic reaction to Dotarem. Such reactions can be severe and may cause anaphylactic shock (a reaction that could put your life in danger). The following symptoms may be the first signs of anaphylactic shock. Immediately inform your doctor, radiologist, or healthcare professional if you experience any of them:

• Swelling of the face, mouth, or throat that may cause difficulty swallowing or breathing
• Swelling of the hands and feet
• Dizziness (hypotension)
• Difficulty breathing
• Wheezing
• Cough
• Itching
• Runny nose
• Stuffy nose
• Irritation of the eyes
• Hoarseness
• Skin rash

Less common side effects (may affect up to 1 in 100 patients)

• Hypersensitivity
• Headache
• Unusual taste in the mouth
• Dizziness
• Drowsiness
• Sensation of tingling, warmth, coldness, and/or pain
• Changes in blood pressure
• Nausea (feeling unwell)
• Abdominal pain
• Rash
• Sensation of heat, sensation of cold
• Weakness
• Discomfort at the injection site, reaction at the injection site, coldness at the injection site, inflammation at the injection site, diffusion of the medication outside the blood vessels, which may cause inflammation (redness and pain at the local site)

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

• Anxiety, fainting (dizziness and sensation of impending loss of consciousness)
• Inflammation of the eyelids
• Palpitations
• Runny nose
• Vomiting (feeling unwell)
• Diarrhea
• Increased salivation
• Hoarseness, itching, sweating
• Chest pain, chills

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

• Anaphylactic reactions or anaphylactoid-like reactions
• Agitation
• Coma, convulsions, syncope (brief loss of consciousness), alteration of the sense of smell (perception of unpleasant odors), tremors
• Conjunctivitis, red eyes, blurred vision, increased tear production
• Cardiac arrest, rapid or slow heart rate, irregular heartbeat, vasodilation, pallor
• Respiratory arrest, pulmonary edema, difficulty breathing, wheezing, nasal congestion, cough, dry throat, constriction of the throat with a sensation of choking, respiratory spasms, inflammation of the throat
• Eczema, redness of the skin, inflammation of the lips and localized in the mouth
• Muscle cramps, muscle weakness, back pain
• Discomfort, chest discomfort, fever, inflammation of the face, diffusion of the medication outside the blood vessels, which may cause death of the tissue at the injection site, inflammation of a vein
• Decreased oxygen levels in the blood

Cases of systemic fibrosis nephrogenica (which causes skin hardening and may also affect soft tissues and internal organs) have been reported, most of which were in patients who received Dotarem together with other gadolinium-based contrast agents.

If, during the weeks after the MRI scan, you notice changes in the color and/or thickness of your skin in any part of your body, inform the radiologist who performed the test.

If you experience side effects, consult your doctor or pharmacist, even if they are side effects that do not appear in this prospectus.

Reporting of side effects:

If you experience any type of side effect, consult your doctor or radiologist, even if it is possible side effects that do not appear in this prospectus. You can also report them directly through the national notification system: Spanish System of Pharmacovigilance of Medicines for Human Use:www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keepthis medicationout of the sight and reach of children.

Do not freeze preloaded syringes.

Do not use Dotarem after the expiration date that appears on the syringe after “CAD”. The expiration date is the last day of the month indicated.

Medicines should not be disposed of through drains or in the trash. Dispose of containers and medicines you no longer need at the SIGRE collection pointat the pharmacy. If in doubt, ask your pharmacist how to dispose of containers and medicines you no longer need. By doing so, you will help protect the environment.

Composition of Dotarem

The active principle is gadoteric acid.

The excipients are meglumine and water for injection preparation.

1 ml of injectable solution contains 376.4 mg of gadoterate meglumine (equivalent to 0.5 mmol) which contain 279.32 mg of gadoteric acid and which contain 78.6 mg of gadolinium.

The other components are meglumine and water for injectable preparations.

5 ml of injectable solution contain 1,882 mg of gadoterate meglumine (equivalent to 2.5 mmol) which contain 1396.6 mg of gadoteric acid and which contain 393 mg of gadolinium

10 ml of injectable solution contain 3,764 mg of gadoterate meglumine (equivalent to 5 mmol) which contain 2,793.2 mg of gadoteric acid and which contain 786 mg of gadolinium

15 ml of injectable solution contain 5,646 mg of gadoterate meglumine (equivalent to 7.5 mmol) which contain 4,189.8 mg of gadoteric acid and which contain 1,179 mg of gadolinium

20 ml of injectable solution contain 7,528 mg of gadoterate meglumine (equivalent to 10 mmol) which contain 5,586.4 mg of gadoteric acid and which contain 1,572 mg of gadolinium

60 ml of injectable solution contain 22,583 mg of gadoterate meglumine (equivalent to 30 mmol) which contain 16,759.2 mg of gadoteric acid and which contain 4,716 mg of gadolinium

100ml of injectable solution contain 37,639 mg of gadoterate meglumine (equivalent to 50 mmol) which contain 27,932 mg of gadoteric acid and which contain 7,860 mg of gadolinium

Aspect of the product and content of the packaging

Dotarem is a transparent, colorless to yellowish solution for intravenous injection.

The packaging of Dotarem contains a vial of 5, 10, 15, 20, single-dose format, a bottle of 60 or 100, multi-dose format.

Only some sizes of packaging may be commercially available.

Marketing Authorization Holder

Guerbet

BP 57400

95943 Roissy CdG cedex

France

Tel.: +33 1 45 91 50 00

Responsible for manufacturing

Guerbet

16-24 rue Jean Chaptal

93600 Aulnay-sous-Bois

France

Please contact the local representative of the Marketing Authorization Holder for any information about this medicine:

Laboratorios Farmacéuticos Guerbet, S.A.

Pº de la Castellana, 91, 3ª planta

28046 Madrid

+ (34) 91 504 50 00

This medicine is authorized in the member states of the European Economic Area with the following name: Dotarem

Last review date of this leaflet: May 2024

Other sources of information

The detailed and updated information about this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/.

_____________________________________________________________________________

This information is intended solely for the doctor or healthcare professional:

Dosage and administration:

Use the lowest dose that provides sufficient 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 indicated in this section.

The recommended dose is 0.1 mmol/kg of body weight (i.e. 0.2 ml/kg of body weight) for all authorized indications.

Only if necessary, a higher dose may be administered exclusively in the following indications:

- For the detection and/or characterization of primary and secondary brain tumors (known or suspected) a dose of 0.3 mmol/kg of body weight (i.e. 0.6 ml/kg of body weight) may be administered, in the form of two consecutive intravenous injections in bolus: a first injection of 0.1 mmol/kg of body weight, followed 20 minutes later by a second injection of 0.2 mmol/kg of body weight.

-In magnetic resonance angiography for arterial study (except for coronary arteries) a second consecutive injection of 0.1 mmol/kg of body weight may be justified, administered under the same conditions as the first, only in exceptional circumstances (for example, if satisfactory images cannot be obtained with the first dose because the moment of image acquisition was not perfect, the vascular territory is too extensive or there is lateralization of hemodynamic alterations in bilateral vascular territories). However, if it is presumed that two consecutive doses of DOTAREM will be administered before starting the arteriography of certain regions (such as the lungs or lower extremities), it is advisable to administer only 0.05 mmol/kg of body weight for each dose, depending on the MRI equipment to be used to obtain the images.

Pediatric population (0-18 years)

The maximum recommended dose is 0.1 mmol/kg of body weight (i.e. 0.2 ml/kg of body weight) for all authorized indications, except formagnetic resonance angiography for arterial study. No more than one dose should be used during the scan.

• Due to the immaturity of renal function in newborns up to 4 weeks of age and in infants up to 1 year of age, Dotarem should only be used in these patients after careful consideration, with a dose that does not exceed 0.1 mmol/kg of body weight. No more than one dose should be used during the scan. Due to the lack of information on consecutive administration, Dotarem injections should not be repeated unless an interval of at least 7 days has elapsed between injections.
• Gadoteric acid is not recommended formagnetic resonance angiography for arterial studyin children under 18 years of age, because the safety and efficacy data in this indication are insufficient.

Geriatric population (population over 65 years of age)

No adjustment of the dose is considered necessary. Caution should be exercised in elderly patients.

Before administeringDotarem, it is recommended to evaluate all patients to detect possible renal dysfunction by laboratory tests.

Cases of systemic fibrosis nephrogenica (FNS) have been reported associated with the use of some gadolinium-based contrast media in patients with severe acute or chronic renal insufficiency (TFG or glomerular filtration rate <30>2). Patients undergoing liver transplantation have a special risk since the incidence of acute renal failure is high in this group. Since there is a possibility that FNS may occur with Dotarem, it should only be used in patients with severe renal insufficiency and in patients in the perioperative period of liver transplantation after careful assessment of the risk/benefit ratio and si the diagnostic information is essential and cannot be obtained without contrast MRI. If necessary, the dose should not exceed0.1 mmol/kg of body weight. During the examination, no more than one dose should be administered. Due to the absence of information on repeated administration, the administration of Dotarem should not be repeated unless an interval of at least 7 days has elapsed between injections.

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

Hemodialysis shortly after administration of Dotaremmay be useful for the elimination ofDotaremfrom the body. There is no evidence to support the initiation of hemodialysis for the prevention or treatment of FNS in patients not undergoing hemodialysis.

Dotarem should not be used during pregnancy unless the woman's clinical situation requires treatment with gadoteric acid.

The continuation or interruption of breastfeeding 24 hours after administration of gadoteric acid will be at the discretion of the doctorand the mother in the breastfeeding period.

Administration forms:

When using Dotarem, the usual safety precautions in MRI should be observed.

Dotarem should not be administered by intrathecal (subarachnoid) or epidural injection. Administration route: strictly intravenous.

During the examination, medical supervision and maintenance of a venous access for any symptomatic therapy that may be required, as well as other specific precautions (see“Before using Dotarem”)

The patient should remain fasting for 2 hours before the examination to avoid aspiration, and the equipment and medications necessary for treating anaphylactic reactions should be available. Additionally, the intravascular administration of the contrast medium should be performed, if possible, with the patient lying down. After administration, the patient should remain under observation for at least half an hour, since most adverse effects occur during that time.

Depending on the amount of gadoteric acid administered to the child, it is preferable to use vials of gadoteric acid with a single-use syringe with an adapted volume to ensure greater accuracy of the injected volume.

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

Instructions for use:

Dotarem is an injectable solution that is presented in vials with a rubber stopper of 5, 10, 15, 20 ml and in bottles of 60 and 100 ml for use with an injector.

Use of vials of 5, 10, 15 and 20 ml:

The preparation of the contrast medium requires lifting the plastic disc from the bottle, cleaning the stopper with alcohol and piercing with a needle incorporated in a syringe, and extracting the amount of product necessary for the test.

Use of bottles of 60 ml and 100 ml for use with injector:

The contrast medium should be administered through an automatic injector, the use of which is prohibited in children under 2 years of age.

The rubber stopper should be pierced only with a suitable extraction device (spike). In general, the extraction device should have the following characteristics: trocar, sterile air filter, luer closure with protective cap and antireflux system.

The patient tube should be changed after each examination. The contrast medium remaining in the bottle, the connecting tubes and all the disposable parts of the injection system should be discarded at the end of each examination session. Any specific instructions from the equipment manufacturer should also be followed.

All injection solutions should be visually inspected before use. Only transparent and particle-free solutions should be used.

The detachable label of the vials/bottles should be stuck to the patient's history to allow for precise recording of the gadolinium-based contrast medium used. The dose used should also be recorded. If electronic patient history is used, the name of the medicine, batch number and dose should be included in the same.