DOTAREM 0.5 MMOL/ML SOLUTION FOR INJECTION IN VIAL

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

DOTAREM 0.5 mmol/ml solution for injection in vial

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 questions, ask your doctor or pharmacist.
• If you experience any side effects, talk to your doctor or pharmacist, even if it is a side effect not listed in this leaflet. See section 4.

What this leaflet contains

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

1. What Dotarem is and what it is used for

This medicine 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 (MR) imaging scans to enhance image contrast. This enhancement improves the examination of certain areas of the body.

2. What you need to know before Dotarem is administered to you

Dotarem must not be given to you if:

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

Warnings and precautions

Inform your doctor or radiologist if any of the following apply to you:

• If you have previously had a reaction to contrast media during an examination.
• If you have asthma.
• If you have a history of allergies (such as seafood allergy, hives, hay fever).
• If you are being treated with a beta-blocker (medicines used for heart problems, high blood pressure, such as metoprolol).
• If your kidneys are not functioning properly.
• 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 receiving treatment for epilepsy.

In all of these cases, your doctor or radiologist will assess the benefit-risk balance and decide whether Dotarem should be administered.

If Dotarem is given to you, 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 that your kidneys are functioning properly before deciding to use Dotarem, especially if you are 65 years of age 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 evaluation by the doctor.

Remove all metallic 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 (an implant inside the ear)
• any suspected metallic foreign body, especially in the eye.

This is important because these may cause serious problems, as magnetic resonance imaging equipment uses very strong magnetic fields.

Use of Dotarem with other medicines

Inform your doctor or radiologist if you are taking, have recently taken, or might 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 conditions or blood pressure disorders such as beta-blockers, vasoactive substances, angiotensin-converting enzyme inhibitors, or angiotensin II receptor antagonists.

Use of Dotarem with food and drink

There are no known interactions between Dotarem and food or drink. However, please consult your doctor, radiologist, or pharmacist to find out whether you need to refrain from eating or drinking before the test.

Pregnancy and breastfeeding

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

Pregnancy:

Gadoteric acid can cross the placenta. It is unknown whether it affects the fetus. 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 a period of 24 hours after administration of Dotarem.

Driving and using machines

There are no available data on the effects of Dotarem on the ability to drive or operate machinery. If you feel unwell after the examination, or experience nausea (feeling of discomfort), you should not drive or operate machinery.

3. How Dotarem is administered

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 administer appropriate emergency medications, if necessary. If you experience an allergic reaction, the administration of Dotarem will be stopped.

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

The procedure will be performed in a hospital or clinic. Healthcare staff are aware of the precautions that must be taken for the examination, as well as any potential complications that may arise.

Dosage

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

Dosage in special populations

The use of Dotarem is not recommended in patients with severe renal impairment or in patients who have recently undergone, or are about to undergo, a liver transplant. However, if use is required, only a single dose of Dotarem should be administered during an examination, and a second injection must 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 careful medical evaluation.

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

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

Elderly patients

If you are 65 years of age or older, dose adjustment is not required, but a blood test may be performed to check that your kidneys are functioning properly.

If you have been given too much Dotarem

It is highly unlikely that you will be given an overdose. Dotarem will be administered by a trained person following medical guidelines. In the rare case of overdose, Dotarem can be removed from the body by haemodialysis (blood cleansing).

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

At the end of this leaflet, additional information on the use and handling of this medicine by doctors or healthcare professionals is provided.

Please consult your doctor or radiologist if you have any questions about the use of this medicine.

4. Possible adverse effects

Like all medicines, this medicine can produce adverse effects, although not everyone experiences them.

After administration, you will be under observation for at least half an hour. Most side effects occur immediately, although in some cases they may be delayed. Some effects may occur up to seven days after receiving Dotarem injection.

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

• swelling of the face, mouth, or throat, which may cause difficulty swallowing or breathing
• swelling of hands and feet
• dizziness (hypotension)
• difficulty breathing
• wheezing
• cough
• itching
• runny nose
• sneezing
• eye irritation
• hives
• skin rash

Uncommon adverse effects (may affect up to 1 in 100 patients):

• hypersensitivity
• headache
• unusual taste in mouth
• dizziness
• somnolence
• sensation of tingling, warmth, cold, and/or pain
• increase or decrease in blood pressure
• nausea (feeling unwell)
• stomach pain
• rash
• sensation of warmth, sensation of cold
• asthenia
• discomfort at injection site, reaction at injection site, cold sensation at injection site, swelling at injection site, leakage of medication from the blood vessel, which may cause inflammation (local redness and pain)

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

• anxiety, fainting (dizziness and feeling of imminent loss of consciousness)
• eyelid swelling
• palpitations
• sneezing
• vomiting (feeling unwell)
• diarrhea
• increased salivary secretion
• hives, itching, sweating
• chest pain, chills

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

• anaphylactic reactions or anaphylactoid-type reactions
• agitation
• coma, seizures, syncope (brief loss of consciousness), disturbance of smell (perception of smells, often unpleasant), tremor
• conjunctivitis, red eyes, blurred vision, increased lacrimation
• cardiac arrest, fast or slow heartbeat, irregular heartbeat, vasodilation, pallor
• respiratory arrest, pulmonary edema, difficulty breathing, wheezing, nasal congestion, cough, dry throat, throat constriction with sensation of suffocation, respiratory spasms, throat swelling
• eczema, skin redness, swelling of the lips and localized in the mouth
• muscle cramps, muscle weakness, back pain
• malaise, chest discomfort, fever, facial swelling, leakage of medication from blood vessels which may lead to tissue death at the injection site, inflammation of a vein
• decreased blood oxygen levels

Cases of nephrogenic systemic fibrosis (a condition causing skin hardening and potentially affecting soft tissues and internal organs) have been reported, most of which occurred in patients who received Dotarem together with other gadolinium-based contrast agents.

If, during the weeks following the magnetic resonance imaging (MRI) procedure, you notice changes in the color and/or thickness of your skin anywhere on your body, inform the radiologist who performed the scan.

If you experience any adverse effects, consult your doctor or pharmacist, even if they are adverse effects not listed in this leaflet.

Reporting of adverse effects:

If you experience any type of adverse effect, consult your doctor or radiologist, even if they are possible adverse effects not listed in this leaflet. You may also report them directly through the national reporting system: Spanish Pharmacovigilance System for Human Medicines: www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Dotarem

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

Vials do not require special storage conditions.

Do not use Dotarem after the expiry date stated on the vial 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 containers and unused medicines at the SIGRE collection point at your pharmacy. If you have any doubts, ask your pharmacist how to dispose of unused containers and medicines. This will help protect the environment.

6. Contents of the pack and other information

Composition of Dotarem

The active substance is gadoteric acid.

The excipients are meglumine and water for injectable preparations.

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

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 1,396.6 mg of gadoteric acid and 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 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 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 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 4,716 mg of gadolinium.

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

Presentation of the product and contents of the pack

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

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

Only certain pack sizes may be commercially available.

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:

Laboratorios Farmacéuticos Guerbet, S.A.

Pº de la Castellana, 91, 3rd floor

28046 Madrid

• (34) 91 504 50 00

This medicinal product is authorized in the member states of the European Economic Area under the name: Dotarem

Date of the most recent review of this leaflet: May 2024

Other sources of information

Detailed and up-to-date information on this medicinal product is available on the website of the Spanish Agency of Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es/.

_____________________________________________________________________________

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

Dosage and method of administration:

The lowest dose providing sufficient enhancement for diagnostic purposes should be used. The dose must be calculated according to 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 body weight (i.e., 0.2 ml/kg body weight) for all approved indications.

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

• For detection and/or characterization of primary and secondary brain tumors (known or suspected), a dose of 0.3 mmol/kg body weight (i.e., 0.6 ml/kg body weight) may be administered as two consecutive intravenous bolus injections: a first injection of 0.1 mmol/kg body weight, followed 20 minutes later by a second injection of 0.2 mmol/kg body weight.
• In MR angiography for arterial study (except coronary arteries), a second consecutive injection of 0.1 mmol/kg body weight administered under the same conditions as the first may be justified only in exceptional circumstances (e.g., if satisfactory images cannot be obtained with the first dose due to suboptimal timing of image acquisition, excessively extensive vascular territory, or hemodynamic alterations in bilateral vascular territories). However, if two consecutive doses of DOTAREM are expected to be administered before starting angiography of certain regions (such as the lungs or lower limbs), it is advisable to administer only 0.05 mmol/kg 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 body weight (i.e., 0.2 ml/kg body weight) for all approved 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 neonates up to 4 weeks of age and infants up to 1 year of age, Dotarem should only be used in these patients after careful consideration, with a dose not exceeding 0.1 mmol/kg body weight. No more than one dose should be administered during the scan. Due to the lack of data on repeated 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 safety and efficacy data for this indication are insufficient.

Elderly patients (population over 65 years of age)

Dose adjustment is not considered necessary. Caution should be exercised in elderly patients.

Prior to administration of Dotarem, all patients should be evaluated for potential renal dysfunction using laboratory tests.

Cases of nephrogenic systemic fibrosis (NSF) have been reported following 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 are at particular risk, as the incidence of acute renal failure is high in this group. Since NSF may occur with Dotarem, it should only be used in patients with severe renal impairment and in patients during the perioperative period of liver transplantation after careful risk/benefit assessment and only if essential diagnostic information cannot be obtained by non-contrast MRI. If Dotarem use is necessary, the dose must not exceed 0.1 mmol/kg body weight. No more than one dose should be administered during an examination. Due to the lack of data on repeated administration, Dotarem should not be re-administered unless at least 7 days have elapsed between injections.

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

Hemodialysis shortly after Dotarem administration may be helpful for eliminating Dotarem from the body. There is no evidence supporting initiation of hemodialysis for the prevention or treatment of NSF in patients not already undergoing hemodialysis.

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

The decision to continue or interrupt breastfeeding 24 hours after administration of gadoteric acid will be at the discretion of the physician and the breastfeeding mother.

Method of administration:

Standard MRI safety procedures must be followed when using Dotarem.

Dotarem must not be administered via intrathecal (subarachnoid) or epidural routes. Route of administration: strictly intravenous.

Medical supervision is required during the examination, along with maintenance of venous access for symptomatic therapy if needed, as well as other specific precautions (see section “Before using Dotarem”).

The patient should fast for at least 2 hours before the examination to prevent aspiration. Appropriate equipment and medications for managing potential anaphylactoid reactions should be readily available. Furthermore, intravascular contrast administration should be performed, if possible, with the patient lying down. After administration, the patient should remain under observation for at least 30 minutes, as experience shows that most adverse reactions occur within this period.

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

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

Instructions for use:

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

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

Preparation of the contrast agent requires lifting the plastic cap, disinfecting the stopper with alcohol, and puncturing it with a needle attached to a syringe to withdraw the required amount of product.

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

The contrast agent must be administered using an automated injector. The use of an injector is contraindicated in children under 2 years of age.

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

The injector-to-patient tubing (patient tubing) must be changed after each examination. Any remaining contrast agent in the bottle, connecting tubes, and all disposable parts of the injection system must be discarded at the end of each examination session. Any specific instructions from the equipment manufacturer must also be followed.

Each solution for injection must be visually inspected before use. Only clear, particle-free solutions should be used.

The detachable label from the vials/bottles should be affixed to the patient's medical record to allow accurate documentation of the gadolinium contrast agent used. The administered dose should also be recorded. If an electronic medical record is used, the drug name, batch number, and dose should be included.