DOTAREM 0.5 mmol/ml INJECTABLE SOLUTION IN PRE-FILLED SYRINGE

Introduction

Package Leaflet: Information for the User

DOTAREM 0.5 mmol/ml solution for injection in pre-filled syringe

Gadoteric Acid

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

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• If you experience any side effects, talk to your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

Contents of the pack

1. What Dotarem is and what it is used for
2. What you need to know before you are given Dotarem
3. How Dotarem is given
4. Possible side effects
5. Storing Dotarem
6. Contents of the pack and further information

1. What Dotarem is and what it is used for

This medicinal product is for diagnostic use only.

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

2. What you need to know before you are given Dotarem

Dotarem must not be given to you:

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

Warnings and precautions

Tell your doctor or radiologist if:

• You have had a reaction to contrast media during a previous examination.
• You have asthma
• You have a history of allergy (such as shellfish allergy, hives, hay fever)
• You are being treated with a beta-blocker (medicines used for heart problems, high blood pressure, such as metoprolol)
• Your kidneys are not working properly
• You have recently had, or are soon going to have, 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 weigh the benefits and risks and decide whether you should be given Dotarem.

If you are given 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 only be used after medical evaluation.

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

• a pacemaker
• a vascular clip
• an 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 they can cause serious problems due to the strong magnetic fields used in magnetic resonance imaging equipment.

Using Dotarem withother medicines

Tell your doctor or radiologist if you are taking, have recently taken, or may need to take any other medicines. In particular, please inform your doctor, radiologist, or pharmacist if you are taking or have recently taken medicines for heart problems or blood pressure problems, such as beta-blockers, vasoactive substances, angiotensin-converting enzyme inhibitors, and angiotensin II receptor antagonists.

Using Dotarem with food and drinks

There are no interactions between Dotarem 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 medicinal product.

Pregnancy:

Gadoteric acid can cross the placenta. It is not known whether it affects the fetus. Dotarem should not be used during pregnancy unless it is strictly necessary.

Breastfeeding:

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

Driving and using machines

There are no available data on the effects of Dotarem on the ability to drive or use machines. If you feel unwell after the test, such as nausea (feeling sick), you should not drive or use machines.

3. How Dotarem is given

Dotarem is given by intravenous injection.

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 medication if necessary. If you experience an allergic reaction, the administration of Dotarem will be stopped.

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

The procedure will be performed in a hospital or clinic. The healthcare staff knows the precautions that need to 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 will 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 are soon going to have, a liver transplant. However, if use is required, during an examination, only one dose of Dotarem should be administered, and a second injection should not be given until at least 7 days have passed.

Neonates, 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 only be used 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.

Elderly patients

If you are 65 years old 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 are given too much Dotarem

It is highly unlikely that you will be given an overdose. You will be given Dotarem after medical evaluation 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, consult the Toxicology Information Service. Phone 91 562 04 20.

At the end of this leaflet, there is further information on the use and handling of this medicinal product by the doctor or healthcare professional.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets 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 injection of Dotarem.

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

• swelling of the face, mouth, or throat that may cause difficulty swallowing or breathing
• swelling of hands and feet
• dizziness (hypotension)
• 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
• headache
• unusual taste in the mouth
• dizziness
• drowsiness
• tingling, heat, cold, and/or pain sensation
• increase or decrease in blood pressure
• nausea (feeling sick)
• stomach pain
• rash
• heat sensation, cold sensation
• asthenia
• discomfort at the injection site, reaction at the injection site, coldness at the injection site, inflammation at the injection site, diffusion of the medicinal product outside the blood vessel, which may cause inflammation (redness and local pain)

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

• anxiety, fainting (dizziness and feeling of impending loss of consciousness)
• eyelid inflammation
• palpitations
• sneezing
• vomiting (feeling sick)
• diarrhea
• increased salivation
• hives, itching, sweating
• chest pain, chills

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

• anaphylactic reactions or anaphylactoid reactions
• agitation
• coma, seizures, syncope (brief loss of consciousness), alteration of smell (perception of unpleasant odors), tremors
• conjunctivitis, red eyes, blurred vision, increased tear secretion
• cardiac arrest, rapid or slow heartbeat, irregular heartbeat, vasodilation, paleness
• respiratory arrest, pulmonary edema, difficulty breathing, wheezing, nasal congestion, coughing, dry throat, throat constriction with a feeling of choking, respiratory spasms, throat inflammation
• eczema, skin redness, inflammation of the lips and localized in the mouth
• muscle cramps, muscle weakness, back pain
• discomfort, chest discomfort, fever, facial inflammation, diffusion of the medicinal product outside the blood vessels, which may cause tissue death at the injection site, vein inflammation
• decrease in blood oxygen level.

Cases of nephrogenic systemic fibrosis (which causes skin hardening and may also affect soft tissues and internal organs) have been reported, most of which were in patients who were given Dotarem in combination with other gadolinium-containing contrast media.

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 scan.

If you experience side effects, talk to your doctor or pharmacist, even if they are not listed in this leaflet.

Reporting of side effects:

If you experience any side effects, talk to your doctor or radiologist, even if they are not listed in this leaflet. You can also report them directly through the national reporting system: Spanish Pharmacovigilance System for Human Use Medicines: www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicinal product.

5. Storing Dotarem

Keep this medicinal product out of the sight and reach of children.

Do not freeze the pre-filled syringes.

Do not use Dotarem after the expiry date stated on the syringe after "EXP". The expiry date is the last day of the month indicated.

Medicines should not be disposed of via wastewater or household waste. Dispose of the packaging and any unused medicinal products in the SIGRE collection point at the pharmacy. If you are unsure, ask your pharmacist how to dispose of the packaging and any unused medicinal products. This will help protect the environment.

6. Container Content and Additional Information

Composition of Dotarem

The active ingredient is gadoteric acid.

The excipients are meglumine and water for injectable preparations.

1 ml of injectable solution contains 376.4 mg of meglumine gadoterate (equivalent to 0.5 mmol) which contains 279.32 mg of gadoteric acid and contains 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 meglumine gadoterate (equivalent to 2.5 mmol) which contain 1,396.6 mg of gadoteric acid and contain 393 mg of gadolinium.

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

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

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

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

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

Product Appearance and Container Content

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

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

Only some package sizes may be marketed.

Marketing Authorization Holder

Guerbet

BP 57400

95943 Roissy CdG cedex

France

Tel.: +33 1 45 91 50 00

Manufacturer

Guerbet

16-24 rue Jean Chaptal

93600 Aulnay-sous-Bois

France

For any information about this medicinal product, please contact the local representative of the Marketing Authorization Holder:

Pharmaceutical Laboratories Guerbet, S.A.

Pº de la Castellana, 91, 3ª planta

28046 Madrid

+ (34) 91 504 50 00

This medicinal product is authorized in the Member States of the European Economic Area under the following name: Dotarem

Date of the last revision of this leaflet: May 2024

Other sources of information

Detailed and updated 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/.

_____________________________________________________________________________

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

Posology and Method of Administration:

The lowest dose that provides sufficient contrast for diagnostic purposes should be used. The dose must be calculated based on the patient's body weight and must 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 for 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: 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 MR angiography for arterial study (except 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 (e.g., when it is not possible to obtain satisfactory images 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 arteriography of certain regions (such as the lung or lower limbs), it is advisable to administer only 0.05 mmol/kg of body weight for each dose, depending on the MR equipment 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 for MR 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 be used in these patients only 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 the interval between injections is at least 7 days.
• Gadoteric acid is not recommended for MR angiography for arterial study in children under 18 years of age, as the safety and efficacy data for this indication are insufficient.

Elderly patients (population over 65 years of age)

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

Before administering Dotarem, it is recommended to evaluate all patients for possible renal dysfunction through 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 insufficiency (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 dotarem, it should only be used severe insufficiency and perioperative period after careful benefit assessment if diagnostic information essential cannot obtained through contrast-free mr. use dotarem necessary, dose not exceed 0.1 mmol kg body weight. during an examination, no more than one administered. due to lack on repeated administration, administration unless interval at least 7 days has passed between injections.< p>

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

Hemodialysis shortly after Dotarem administration may be useful for the elimination of Dotarem from the body. There is no evidence to support the initiation of hemodialysis for the prevention or treatment of NSF in patients who are not undergoing hemodialysis.

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

The continuation or interruption of breastfeeding 24 hours after the administration of gadoteric acid will be at the discretion of the doctor and the breastfeeding mother.

Methods of Administration:

When using Dotarem, the usual safety rules for MR should be observed.

Dotarem should not be administered by intrathecal (subarachnoid) or epidural injection. Route of administration: strictly intravenous.

During the examination, medical surveillance is necessary, as well as maintaining a venous access route for any symptomatic therapy that may be required, as well as other specific precautionary measures (see section "Before using Dotarem").

The patient should fast from 2 hours before the examination to avoid aspiration and should have the necessary equipment and medications to treat a possible anaphylactoid reaction. Additionally, the intravascular administration of the contrast agent should be performed, if possible, with the patient lying down. After administration, the patient should be kept under observation for at least 30 minutes, as experience shows that most adverse effects occur during this 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 a volume adapted to this amount so that the precision of the injected volume is greater.

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

Instructions for Use:

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

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

Preparation of the contrast agent requires lifting the plastic disc from the vial, cleaning the stopper with alcohol, and puncturing with a needle incorporated into a syringe, and extracting the necessary amount of product for the test.

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

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

The rubber stopper should be punctured only with a suitable extraction device (spike). In general, the extraction device should have the following characteristics: trocar, sterile air filter, luer lock with protective cap, and anti-reflux systems.

The patient tube of the injector should be changed after each examination. The contrast agent remaining in the bottle, connector tubes, and all 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.

Any solution for injection should be visually inspected before use. Only clear and particle-free solutions should be used.

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