Package Insert:Information for the Patient

Gadovist 1 mmol/ml injectable solution in pre-filled syringe/

pre-filled cartridge

Gadobutrol

Read the entire package insert carefully before starting to use this medication,because it contains important information for you.

-Keep this package insert, as you may need to read it again.

-If you have any questions, consult your doctor or the person administering Gadovist (the radiologist) or hospital staff where the MRI is performed.

• If you experience any adverse effects,consult your doctor or radiologist,even if they are not listed in this package insert. See section 4.

1.What is Gadovist and how it is used

2.What you need to knowbefore starting to use Gadovist

3.How to use Gadovist

4.Possible adverse effects

5.Storage of Gadovist

6.Contents of the package and additional information

Gadovist is a magnetic resonance (MR) contrast agent used for the diagnosis of the brain, spine, and blood vessels. Gadovist may also help the doctor determine the type of abnormalities (benign or malignant) known or suspected in the liver and kidneys.

Gadovist can also be used for MR imaging of abnormalities in other parts of the body. It facilitates the visualization of abnormal structures or lesions and helps in the differentiation of healthy tissue and diseased tissue.

It is indicated for adults and children of all ages (including full-term neonates).

How Gadovist works

MR is a diagnostic imaging method that uses the behavior of water molecules in normal and abnormal tissues. This is carried out through a complex system of magnets and radio waves. Computers record the activity and transform it into images.

Gadovist is administered through an injection into your vein. This medication is solely for diagnostic use and will only be administered by a healthcare professional with experience in clinical MR practice.

No use Gadovist if you

- are allergic to gadobutrol or any of the other components of this medication (listed in section 6).

Warnings and precautions

Consult your doctor before starting to use Gadovist if you

• have or have had an allergy (for example, hay fever, urticaria) or asthma

• have had a previous reaction to any contrast medium
• have severely impaired renal function
• have neurological disorders with seizures (attacks) or other nervous system diseases
• are wearing a pacemaker or any implant or clip containing iron in your body.

Your doctor will decide whether it is possible or not to perform the planned examination.

• Severe allergic reactions or other types of reactions that involve heart problems, difficulty breathing, or skin reactions may occur after using Gadovist. Severe reactions are possible. Most of these reactions occur 30 minutes after the administration of Gadovist. You will be observed after treatment. Delayed reactions (after hours or days) have been observed (see section 4).

Kidneys/Liver

Inform your doctor if

• your kidneys do not function correctly
• you have recently had, or are about to have, a liver transplant.

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

Newborns and infants

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

Other medications and Gadovist

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or think you may be pregnant, consult your doctor or pharmacist before using this medication.

• Pregnancy

Gadobutrol may cross the placenta. It is unknown whether it affects the fetus. Inform your doctor if you think you are pregnant or may be pregnant, as Gadovist should not be used during pregnancy unless absolutely necessary.

• Breastfeeding

Inform your doctor if you are breastfeeding or about to start. Your doctor will evaluate whether you should continue or interrupt breastfeeding 24 hours after the administration of Gadovist.

Gadovist contains sodium

This medication contains less than 23 mg of sodium per dose (based on the average amount administered to a 70 kg person); it is essentially "sodium-free".

Gadovist is injected by a healthcare professional through a small needle into a vein. Your MRI scan may start immediately.

After injection, you will be observed for at least 30 minutes.

Usual Dosage

The usual dose that is suitable for you will depend on your body weight and the region being examined by MRI:

In adults, a single injection of 0.1 milliliters of Gadovist per kilogram of body weight (this means that for a person weighing70 kg, the dose would be 7 milliliters), however, an additional injection of up to 0.2milliliters per kilogram of body weight may be administered within 30 minutes after the first injection. A maximum total dose of 0.3 milliliters of Gadovist per kilogram of body weight (this means that for a person weighing 70 kg, the dose would be 21 milliliters) may be administered for the acquisition of images of the central nervous system (CNS) and magnetic resonance angiography (MRA) with contrast. A minimum dose of 0.075 milliliters of Gadovist per kilogram of body weight (this means that for a person weighing 70 kg, the dose would be 5.25 milliliters) may be administered for the CNS.

Additional information on the administration and handling of Gadovist is included at the end of the leaflet.

Dosage in Special Populations

The use of Gadovist 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 a single dose of Gadovist should be administered during the examination, and a second injection should not be administered until at least 7 days have passed.

Use inneonates, infants,children and adolescents

The recommended dose in childrenof all ages (including full-term neonates)is a single injection of 0.1milliliters of Gadovist per kilogram of body weight for all indications (see section 1).

Due to the immaturity of the renal function of neonates up to 4 weeks and infants up to 1 year of age, Gadovist should only be used in these patients after careful evaluation by a doctor. Neonates and infants should only receive a single dose of Gadovist during an examination and should not receive a second injection until at least 7 days have passed.

Geriatric Patients

If you are 65 years or older, it is not necessary to adjust the dose, but you may be required to have a blood test to check that your kidneys are functioning properly.

If you use more Gadovist than you should

It is unlikely that an overdose will occur. If it does, the doctor will treat all symptoms, and it may be possible to use dialysis to remove Gadovist from your body. There is no evidence to indicate that hemodialysis is suitable for the prevention of systemic fibrosis nephrogenica (FNS; see section 4), so it should not be used for the treatment of this condition. In some cases, your heart may be monitored.

In the event of an overdose or accidental ingestion, contact the Toxicology Information Service (telephone 91 562 04 20).

If you have any other questions about the use of this medication, ask your doctor or radiologist.

Like all medications, this medication may cause side effects, although not everyone will experience them. Most of these reactions occur within 30 minutes after administration of Gadovist. Rarely, delayed allergic reactions or other types of reactions have been observed, occurring from a few hours to several days after receiving Gadovist. If this happens to you, inform your doctor or radiologist immediately.

Themost serious side effects(which have been fatal or have put lives at risk in some cases) are:

• heart arrest (cardiac arrest)a severe lung disease(acute respiratory distress syndrome)/ fluid in the lungs(pulmonary edema) and severe allergic reactions (anaphylactoid) (including respiratory arrest and shock).

In addition, in some cases, the following life-threatening or fatal side effects have been observed:

• shortness of breath (breathlessness), loss of consciousness, severe allergic reactions, severe drop in blood pressure that can lead to collapse, respiratory arrest, fluid in the lungs, inflammation of the mouth and throat, and low blood pressure.

Inrare cases:

• allergic reactions of the type (hypersensitivity) and anaphylaxis, including severe reactions (shock) that may require immediate medical intervention, may occur.

If you notice:

- inflammation of the face, lips, tongue, or throat

- coughing and sneezing

- difficulty breathing

- itching

- nasal congestion

- urticaria (hives like those caused by nettle)

inform your department of RM staff immediately.Thesemay be the first signs of aserious reaction. Your examination may be suspended, and you may need further treatment.

Themost frequent side effects observed(may affect 5 or more out of every 1,000 people) are:

• headaches, feeling unwell (nausea), and dizziness.

Most side effects are mild to moderate.

The following possible side effects have been observed inclinical trialsbefore the approval of Gadovist, according to their probability:

Frequent:may affect up to 1 in 10 people

- headache

- feeling unwell (nausea)

Rare:may affect up to 1 in 100 people

• allergic reaction, for example:

- low blood pressure

- urticaria

- inflammation of the face

- inflammation (swelling) of the eyelids

- flushing

The frequency of the following allergic reactions is unknown:

- a severe allergic reaction (anaphylactic shock)

- severe drop in blood pressure that can lead to collapse (shock)

- respiratory arrest

- difficulty breathing (bronchospasm)

- blue lips

- inflammation of the mouth and throat

- inflammation of the throat

- increased blood pressure

- chest pain

- inflammation of the face, throat, mouth, lips, and/or tongue (angioedema)

- conjunctivitis

- increased sweating

- coughing

- sneezing

-burning sensation

- paleness (pale skin)

- dizziness, alteration of taste, numbness, and tingling

- shortness of breath (breathlessness)

- vomiting

- redness of the skin (erythema)

- itching (pruritus, including generalized pruritus)

- rash (including generalized rash, small flat red spots (macular rash), small elevated circumscribed lesions (papular rash), pruritic rash (pruritic rash))

- different types of reactions at the injection site (for example, leakage into adjacent tissue, burning, coldness, heat, redness, rash, pain, or hematoma)

- feeling of heat

Rare:may affect up to 1 in 1,000 people

• syncope
• seizure
• alteration of smell
• rapid heart rate
• palpitations
• dry mouth
• general feeling of illness
• feeling of cold

Additional side effects that have been reported after the approval of Gadovist of unknown frequency(the frequency cannot be estimated from the available data):

- heart arrest (cardiac arrest)

- A severe lung disease(acute respiratory distress syndrome)

- Fluid in the lungs(pulmonary edema)

- cases of systemic nephrogenic fibrosis – FNS (which causes skin hardening and may also affect soft tissues and internal organs) have been reported.

After administration of Gadovist, variations in renal function test results (e.g., increased serum creatinine) have been observed.

Reporting of side effects

If you experience any type of side effect, consult your doctor or radiologist, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the Spanish System of Pharmacovigilance of Medicinal Products for Human Usehttps://www.notificaram.es.By reporting side effects, you can contribute to providing more information on the safety of this medication.

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

Do not use this medication after the expiration date that appears on the label and the packaging after CAD. The expiration date is the last day of the month indicated. This medication does not require special storage conditions.

Chemical, physical, and microbiological stability has been demonstrated during use for a period of 24 hours at 20-25°C. From a microbiological standpoint, the product should be used immediately after opening.

This medication is a clear, colorless to pale yellow solution. Do not use this medication if you observe a severe color alteration, or the presence of particles, or if the packaging appears defective.

Medications should not be disposed of through drains or in the trash.The healthcare professional will dispose of this medication whenit is no longer needed. This will help protect the environment.

Composition of Gadovist

The active ingredient is gadobutrol.

1 ml of injectable solution contains 604.72 mg of gadobutrol (equivalent to 1 mmol of gadobutrol containing 157.25 mg of gadolinium).

1 pre-filled syringe with 5.0 ml contains 3,023.6 mg of gadobutrol.

1 pre-filled syringe with 7.5 ml contains 4,535.4 mg of gadobutrol.

1 pre-filled syringe with 10 ml contains 6,047.2 mg of gadobutrol.

1 pre-filled syringe with 15 ml contains 9,070.8 mg of gadobutrol.

1 pre-filled syringe with 20 ml contains 12,094.4 mg of gadobutrol.

1 pre-filled cartridge with 15 ml contains 9,070.8 mg of gadobutrol.

1 pre-filled cartridge with 20 ml contains 12,094.4 mg of gadobutrol.

1 pre-filled cartridge with 30 ml contains 18,141.6 mg of gadobutrol.

The other components are sodium calcobutrol (see final section 2), trometamol, hydrochloric acid 1N, and water for injectable preparations.

Appearance of the product and contents of the package

Gadovist is a transparent, colorless to pale yellow injectable solution.

The contents of the packages are:

- 1 or 5 pre-filled syringes containing 5, 7.5, and 10 ml of injectable solution (in a 10 ml glass or plastic syringe).

- 1 or 5 pre-filled syringes containing 15 ml of injectable solution (in a 17 ml glass syringe or a 20 ml plastic syringe).

- 1 or 5 pre-filled syringes containing 20 ml of injectable solution (in a 20 ml glass or plastic syringe).

- 1 or 5 pre-filled cartridges containing 15, 20, and 30 ml of injectable solution (in a 65 ml cartridge).

Clinical packaging:

• 5 pre-filled syringes containing 5, 7.5, 10, 15, 20 ml of injectable solution
• 5 pre-filled cartridges containing 15, 20, 30 ml of injectable solution

Only some package sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder

Bayer Hispania, S.L.

Av. Baix Llobregat, 3-5

08970 Sant Joan Despí (Barcelona)

Spain

Manufacturer

Bayer AG

Müllerstrasse 178

13353 Berlin

Germany

This medicinal product is authorized in the member states of the European Economic Area with the following names:

Last review date of this leaflet: 09/2024.

Other sources of information

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

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This information is intended solely for healthcare professionals:

• Renal insufficiency

Before administering Gadovist, it is recommended to evaluate all patients to detect possible renal dysfunction through laboratory tests.

Cases of systemic fibrosis nephrogenica (FNS) have been reported associated with the use of some gadolinium-containing contrast agents in patients with severe acute or chronic renal insufficiency (TFG or glomerular filtration rate <30ml/min). Patients undergoing liver transplantation have a special risk since the incidence of renal failure is high in this group. Since there is a possibility that FNS may occur with Gadovist, it should only be used in patients with severe renal insufficiency and in patients in the perioperative period of liver transplantation after careful evaluation of the risk/benefit ratio and if the diagnostic information is essential and cannot be available through MRI without contrast. If necessary, the dose should not exceed 0.1 mmol/kg of body weight. During an examination, no more than one dose should be administered. Due to the lack of information on repeated administration, the administration of Gadovist should not be repeated unless at least 7 days have elapsed between injections.

Since renal elimination of Gadovist may be reduced in elderly patients, it is especially important to evaluate patients aged 65 and over to detect possible renal dysfunction.

Haemodialysis shortly after administration of Gadovist may be useful for the elimination of Gadovist from the body. There is no evidence to support the initiation of haemodialysis for the prevention or treatment of FNS in patients who are not yet undergoing haemodialysis.

• Pregnancy and Lactation

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

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

• Hypersensitivity reactions

Like other intravenous contrast media, Gadovist may be associated with hypersensitivity/anaphylactoid reactions or other idiosyncratic reactions characterized by cardiovascular, respiratory, or cutaneous manifestations, including severe reactions such as shock. In general, patients with cardiovascular disease are more susceptible to severe or even fatal consequences of severe hypersensitivity reactions.

The risk of hypersensitivity reactions may be higher in the following cases:

- previous reaction to contrast media

- history of asthma

- history of allergic disorders

In patients with allergic predisposition, the decision to use Gadovist should be made after careful evaluation of the benefit/risk ratio.

Most of these reactions occur within 30 minutes after administration. Therefore, it is recommended to observe the patient after treatment.

It is necessary to have the appropriate medication available for the treatment of hypersensitivity reactions, as well as to prepare emergency measures.

Rarely, delayed reactions (after hours or several days) have been observed.

• Convulsive disorders

As with other contrast media containing gadolinium, special caution should be taken in patients with a low convulsive threshold.

• Overdose

In the event of an accidental overdose, cardiovascular monitoring (including ECG) and renal function surveillance are recommended as precautionary measures.

In the case of overdose in patients with renal insufficiency, Gadovist may be eliminated by haemodialysis.After 3 haemodialysis sessions, approximately 98% of the contrast agent is eliminated from the body. However, there is no evidence that haemodialysis is suitable for the prevention of systemic fibrosis nephrogenica (FNS).

• Before injection

This medicinal product is intended for single use.

This medicinal product is a transparent, colorless to pale yellow injectable solution. The solution should be visually inspected before use.

Gadovist should not be used if it presents significant color changes, the appearance of particles, or if the package is defective.

• Instructions for use

Pre-filled syringes

The pre-filled syringe should be removed from the package and prepared for injection immediately before administration.

The tip of the stopper should be removed from the pre-filled syringe immediately before use.

Glass syringe:

Plastic syringe:

Pre-filled cartridges

The administration of contrast media should be performed by qualified personnel using the appropriate procedures and equipment.

The administration of contrast media should be performed using a sterile technique.

The contrast medium should be administered using a MEDRAD Spectris®injector.

Follow the instructions provided by the manufacturers of the devices used.

Any unused contrast medium should be disposed of in accordance with local regulations.

Validity period after the first opening of the package

Any injectable solution that has not been used in an examination should be discarded. Chemical, physical, and microbiological stability has been demonstrated in use for 24 hours at 20-25°C. From a microbiological point of view, the product should be used immediately. If not used immediately, the storage times during use and the conditions prior to use are the responsibility of the user.

The detachable label of the pre-filled syringes/cartridges should be attached to the patient's medical history to allow for precise recording of the gadolinium-containing contrast medium used. The dose used should also be recorded. In the case of electronic patient records, the product name, batch number, and administered dose should be entered into them.

Dosage

The lowest dose that provides sufficient enhancement 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.

• Adults

Indications in the CNS

The recommended dose in adults is 0.1 mmol per kilogram of body weight (mmol/kg b.w.), equivalent to 0.1 ml/kg b.w. of the 1.0 M solution.

If clinical suspicion persists despite negative MRI findings or when more precise information may influence patient treatment, an additional dose of up to 0.2 ml/kg b.w. may be administered within 30 minutes after the first injection.A minimum dose of 0.075 mmol of gadobutrol per kg of body weight (equivalent to 0.075 ml of Gadovist per kg of body weight) should be administered for CNS imaging.

Whole-body MRI (except ARM)

Generally, administration of 0.1 ml of Gadovist per kg of body weight is sufficient to respond to the clinical question.

Magnetic Resonance Angiography (ARM) with contrast

Obtaining images of 1 field of view (FOV): 7.5 ml for body weights less than 75 kg; 10 ml for body weights equal to or greater than 75 kg (equivalent to 0.1-0.15 mmol/kg b.w.).

Obtaining images of more than 1 field of view (FOV): 15 ml for body weights less than 75 kg; 20 ml for body weights equal to or greater than 75 kg (equivalent to 0.2-0.3 mmol/kg b.w.).

• Pediatric population

The recommended dose in children of all ages (including term neonates) is 0.1 mmol of gadobutrol per kilogram of body weight (equivalent to 0.1 ml of Gadovist per kilogram of body weight) for all indications (see section 1).

Due to the immaturity of renal function in neonates up to 4 weeks and infants up to 1 year of age, Gadovist should only be used in these patients after careful evaluation at a dose not exceeding 0.1 mmol/kg of body weight. During an examination, no more than one dose should be administered. Due to the lack of information on repeated administration, the administration of Gadovist should not be repeated unless at least 7 days have elapsed between injections.

Images

The required dose is administered intravenously as a bolus injection. MRI with contrast may begin immediately after (shortly after injection, depending on the pulse sequences used and the study protocol).

Optimal signal enhancement is observed during the first arterial pass for ARM with contrast and during a period of approximately 15 minutes after Gadovist injection for CNS indications (the time depends on the type of lesion/tissue).

Weighted imaging sequences in T1 are particularly suitable for contrast-enhanced examinations.

Further information on the use of Gadovist is provided in section 3 of the leaflet.