Gadovist 1 mmol/ml solution for injection in vial

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Gadovist 1 mmol/ml solution for injection in vial

Gadobutrol

Read the entire leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor, the person administering Gadovist (the radiologist), or hospital staff or personnel at the imaging center where the MRI (magnetic resonance imaging) will be performed.
  • If you experience any adverse effects, consult your doctor or radiologist, even if they are effects not listed in this leaflet. See section 4.

Leaflet contents

1. What Gadovist is and what it is used for

2. What you need to know before receiving Gadovist

3. How to use Gadovist

4. Possible side effects

   1. Storage of Gadovist

5. Contents of the pack and other information

1. What Gadovist is and what it is used for

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

Gadovist may also be used in MRI for abnormalities in other parts of the body. It enhances the visualization of abnormal structures or lesions and helps differentiate between healthy and diseased tissue.

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

How Gadovist works

MRI is an imaging diagnostic method that uses the behavior of water molecules in normal and abnormal tissues. This is performed using a complex system of magnets and radio waves. Computers record the activity and convert it into images.

Gadovist is administered by injection into your vein. This medicine is for diagnostic use only and will be given to you only by a healthcare professional experienced in the clinical practice of MRI.

2. What you need to know before using Gadovist

Do not use Gadovist if you

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

Warnings and precautions

Talk to your doctor before using Gadovist if you

• have or have had allergies (for example, hay fever, hives) or asthma
• have previously experienced a reaction to any contrast agent
• have severely impaired kidney function
• have brain disorders with seizures (attacks) or other diseases of the nervous system
• have a pacemaker or any implant or clip containing iron in your body.

Your doctor will decide whether or not the planned examination can be performed.

• Allergic-type reactions or other types of reactions involving heart problems, difficulty breathing, or skin reactions may occur after using Gadovist. Serious reactions are possible. Most of these reactions occur within 30 minutes after administration of Gadovist. Therefore, you will be monitored after treatment. Delayed reactions (after hours or days) have also been observed (see section 4).

Kidneys/Liver

Inform your doctor if

• your kidneys are not functioning properly
• you have recently had, or are about to have, a liver transplant.

Your doctor may decide to perform a blood test to check your kidney function before deciding to use Gadovist, especially if you are 65 years of age or older.

Newborns and infants

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

Other medicines and Gadovist

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines.

Pregnancy and breastfeeding

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

• Pregnancy

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

• Breastfeeding

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

Gadovist contains sodium

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

3. How to use Gadovist

Gadovist is administered by a healthcare professional through a small needle inserted into a vein. Your MRI scan may begin immediately afterward.

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

Recommended dosage

The usual dose appropriate for you will depend on your body weight and the area being examined by MRI:

In adults, a single injection of 0.1 millilitres of Gadovist per kg of body weight is recommended (this means that for a person weighing 70 kg, the dose would be 7 millilitres). However, an additional injection of up to 0.2 millilitres per kg of body weight may be given within 30 minutes after the first injection. A total amount of up to 0.3 millilitres of Gadovist per kg of body weight (this means that for a person weighing 70 kg, the dose would be 21 millilitres) may be administered for imaging of the central nervous system (CNS) and contrast-enhanced magnetic resonance angiography (MRA). A minimum dose of 0.075 millilitres of Gadovist per kg of body weight (this means that for a person weighing 70 kg, the dose would be 5.25 millilitres) may be used for CNS imaging.

Additional information on administration and handling of Gadovist is included at the end of this 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 one dose of Gadovist should be administered during a single examination, and a second injection should not be given until at least 7 days have passed.

Use in neonates, infants, children, and adolescents

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

Due to the immature renal function in neonates up to 4 weeks of age and infants up to 1 year of age, Gadovist should only be used in these patients after careful medical evaluation. Neonates and infants should receive only one dose of Gadovist per examination, and a second injection should not be administered until at least 7 days have passed.

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 use more Gadovist than you should

An overdose is unlikely. If it does occur, the doctor will treat all symptoms and may use dialysis to remove Gadovist from your body. There is no evidence that haemodialysis is effective in preventing the development of nephrogenic systemic fibrosis (NSF; see section 4), and therefore it should not be used for the treatment of this condition. In some cases, your heart may be monitored.

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

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them. Most of these reactions occur within the first half hour after administration of Gadovist. In rare cases, delayed allergic-type or other reactions have been observed, occurring from several hours to several days after receiving Gadovist. If this happens to you, inform your doctor or radiologist immediately.

The most serious adverse effects (which have been fatal or life-threatening in some cases) are:

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

Additionally, in some cases the following life-threatening or fatal adverse effects have been observed:

• difficulty breathing (dyspnea), loss of consciousness, severe allergic reactions, severe drop in blood pressure that may lead to collapse, respiratory arrest, fluid in the lungs, swelling of the mouth and throat, and low blood pressure.

In rare cases:

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

If you notice:

• swelling of the face, lips, tongue, or throat
• coughing and sneezing
• difficulty breathing
• itching
• nasal congestion
• hives (rash similar to nettle rash)

inform the MRI department staff immediately. These may be the first signs of a serious reaction. Your examination may be stopped and you may require further treatment.

The most commonly observed adverse effects (may affect 5 or more out of 1,000 people) are:

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

Most adverse effects are mild to moderate.

Listed below are possible adverse effects observed in clinical trials before approval of Gadovist, categorized by their likelihood:

Frequent: may affect up to 1 in 10 people

• headache
• feeling unwell (nausea)

Uncommon: may affect up to 1 in 100 people

• allergic-type reactions, for example:

• low blood pressure

• hives

• facial swelling

• eyelid swelling (edema)

• flushing

The frequency of the following allergic reactions is unknown:

• severe allergic reaction (anaphylactoid shock)
• severe drop in blood pressure that may lead to collapse (shock)
• respiratory arrest
• difficulty breathing (bronchospasm)
• blue lips
• swelling of the mouth and throat
• swelling of the throat
• increased blood pressure
• chest pain
• swelling of the face, throat, mouth, lips and/or tongue (angioedema)
• conjunctivitis
• increased sweating
• cough
• sneezing
• burning sensation
• paleness (pale skin)
• dizziness, taste disturbances, numbness, and tingling
• difficulty breathing (dyspnea)
• vomiting
• redness of the skin (erythema)
• itching (pruritus, including generalized pruritus)
• rash (including generalized rash, flat red spots (macular rash), small raised localized lesions (papular rash), itchy rash (pruritic rash))
• various types of injection site reactions (e.g., leakage into surrounding tissue, burning, cold sensation, warmth, redness, rash, pain, or bruising)
• sensation of warmth

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

• fainting
• seizure
• altered sense of smell
• rapid heartbeat
• palpitations
• dry mouth
• general malaise
• sensation of cold

Additional adverse effects reported after approval of Gadovist, with unknown frequency (frequency cannot be estimated from available data):

• cardiac arrest (cardiac arrest)
• severe lung disease (acute respiratory distress syndrome)
• fluid in the lungs (pulmonary edema)
• cases of nephrogenic systemic fibrosis (NSF) have been reported (which causes skin hardening and may also affect soft tissues and internal organs).

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

Reporting of adverse effects

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

5. Storage of Gadovist

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

Do not use this medicinal product after the expiry date which is stated on the label and container after EXP. The expiry date refers to the last day of the month indicated. This medicinal product does not require any special storage conditions.

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

This medicinal product is a clear solution, colourless to pale yellow. Do not use this medicinal product if you observe a marked change in colour, or the presence of particles, or if the container appears damaged.

Medicines must not be disposed of via wastewater or household waste. Healthcare professionals will dispose of this medicinal product when it is no longer required. This will help protect the environment.

6. Contents of the pack and other information

Composition of Gadovist

The active substance 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 vial with 2 ml contains 1,209.44 mg of gadobutrol.

1 vial with 7.5 ml contains 4,535.4 mg of gadobutrol.

1 vial with 15 ml contains 9,070.8 mg of gadobutrol.

1 vial with 30 ml contains 18,141.6 mg of gadobutrol.

1 bottle with 65 ml contains 39,306.8 mg of gadobutrol.

The other components are sodium calcobutrol (see end of section 2), trometamol, 1N hydrochloric acid and water for injections.

Appearance of the product and contents of the pack

Gadovist is a clear, colourless to pale yellow injectable solution.

Pack contents:

• 1 or 3 vials containing 2 ml of injectable solution
• 1 or 10 vials containing 7.5, 15 or 30 ml of injectable solution
• 1 or 10 bottles containing 65 ml of injectable solution (in a 100 ml bottle)

Hospital packs:

• 3 vials containing 2 ml of injectable solution
• 10 vials containing 7.5, 15 or 30 ml of injectable solution
• 10 bottles containing 65 ml of injectable solution

Only certain pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation 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 authorised in the Member States of the European Economic Area under the following names:

Austria, Germany	Gadovist 1.0 mmol/ml solution for injection
Belgium, Bulgaria, Cyprus, Denmark, Estonia, Finland, Greece, Italy, Luxembourg, Norway, Portugal, Sweden	Gadovist
Croatia	Gadovist 1.0 mmol/ml otopina za injekciju
France	GADOVIST 1.0 mmol/ml, solution injectable
Iceland	Gadovist 1.0 mmol/ml, stungulyf, lausn
Ireland	Gadovist 1.0 mmol/ml solution for injection
Netherlands	Gadovist 1.0 mmol/ml, oplossing voor injectie
Slovenia	Gadovist 1.0 mmol/ml raztopina za injiciranje
Slovakia	Gadovist 1.0 mmol/ml injekčný roztok
Spain	Gadovist 1 mmol/ml solution for injection in vial
Malta	Gadovist 1.0 mmol/ml solution for injection

Date of the most recent review of this leaflet: 09/2024.

Other sources of information

Detailed 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)

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This information is intended solely for healthcare professionals:

• Renal impairment

Before administration of Gadovist, it is recommended to assess all patients for potential renal dysfunction through laboratory tests.

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

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

Hemodialysis shortly after administration of Gadovist may be helpful in removing the agent from the body. However, there is no evidence supporting initiation of hemodialysis for the prevention or treatment of NSF in patients not already undergoing hemodialysis.

• Pregnancy and Lactation

Gadovist must not be used during pregnancy unless the woman's clinical condition requires treatment with Gadovist.

The decision to continue or interrupt breastfeeding 24 hours after administration of Gadovist remains at the discretion of the physician and the breastfeeding mother.

• Hypersensitivity reactions

As with 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 serious or even fatal consequences from severe hypersensitivity reactions.

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

• previous reaction to contrast media
• history of bronchial asthma
• history of allergic disorders

In patients with a predisposition to allergies, the decision to use Gadovist should be made only after careful assessment of the benefit-risk ratio.

Most of these reactions occur within 30 minutes of administration. Therefore, patient monitoring after administration is recommended.

Appropriate medication for the treatment of hypersensitivity reactions must be available, and emergency measures should be prepared.

Delayed reactions (occurring hours or several days later) have been observed rarely.

• Seizure disorders

As with other gadolinium-containing contrast agents, special caution should be exercised in patients with a low seizure threshold.

• Overdose

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

In cases of overdose in patients with renal impairment, Gadovist can be removed by hemodialysis. Approximately 98% of the contrast agent is eliminated from the body after three hemodialysis sessions. However, there is no evidence that hemodialysis is adequate for the prevention of nephrogenic systemic fibrosis (NSF).

• Before injection

This medicinal product is for single use only.

This medicine is a clear, colorless to pale yellow solution. The solution should be inspected visually before use. Gadovist must not be used if significant discoloration, presence of particles, or container defects are observed.

• Instructions for use

Gadovist should not be drawn into the syringe until immediately before use.

The rubber stopper must not be punctured more than once.

Any unused contrast medium from an examination must be discarded.

If this medicine is intended for use with an automated delivery system, the suitability of the system for the intended use must be demonstrated by the manufacturer. Any additional instructions from the manufacturer must also be strictly followed.

Any unused contrast medium from an examination must be discarded according to local regulations.

Shelf-life after first opening of the container

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

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. In cases where electronic patient records are used, the product name, batch number, and administered dose should be entered.

Dosage

The lowest dose providing sufficient enhancement for diagnostic purposes should be used. The dose should be calculated based on the patient's body weight and must not exceed the recommended dose per kilogram of body weight specified in this section.

• Adults

CNS indications

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 there remains a strong clinical suspicion of a lesion despite unremarkable MRI findings, or when obtaining more precise information could influence patient management, an additional dose of up to 0.2 mL/kg b.w. may be administered within 30 minutes of the first injection. A dose of 0.075 mmol of gadobutrol per kg of body weight (equivalent to 0.075 mL of Gadovist per kg of body weight) may be administered as a minimum for CNS imaging.

Whole-body MRI (excluding MRA)

In general, administration of 0.1 mL of Gadovist per kg of body weight is sufficient to address the clinical question.

Contrast-enhanced Magnetic Resonance Angiography (MRA)

Imaging of 1 field of view (FOV): 7.5 mL for body weights below 75 kg; 10 mL for body weights equal to or greater than 75 kg (equivalent to 0.1–0.15 mmol/kg b.w.).

Imaging of more than 1 field of view (FOV): 15 mL for body weights below 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 of age and infants up to 1 year of age, Gadovist should only be used in these patients after careful assessment and at a dose not exceeding 0.1 mmol/kg body weight. No more than one dose should be administered during a single examination. Due to lack of data on repeated administration, Gadovist should not be re-administered unless an interval of at least 7 days has elapsed between injections.

Imaging

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

Optimal signal enhancement is observed during the first arterial pass for contrast-enhanced MRA and within approximately 15 minutes after Gadovist injection for central nervous system (CNS) indications (timing depends on lesion/tissue type).

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

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