PIXXOSCAN 1.0 mmol/mL Injectable Solution in Pre-filled Syringe

2. What you need to know before starting to use Pixxoscan

Do not use Pixxoscanif

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

Warnings and precautions

Consult your doctor before starting to use Pixxoscan if

• you have or have had an allergy (e.g., hay fever, hives) or asthma
• you have had a previous reaction to any contrast agent
• you have severely impaired kidney function
• you have cerebral disorders with seizures (attacks) or other nervous system diseases
• you have a cardiac pacemaker or any implant or clip containing iron in your body.

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

Allergic reactions may occur, which can cause cardiac problems, breathing difficulties, or skin reactions after using Pixxoscan. Severe reactions are possible. Most of these reactions occur within 30 minutes after administration of Pixxoscan. Therefore, you will be monitored after treatment. Delayed reactions (after hours or days) have been observed (see section 4).

Kidneys/Liver

Tell your doctor if

• your kidneys are not working properly
• a liver transplant has been recently performed or is scheduled to be performed soon.

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

Neonates and Infants

Due to the immaturity of kidney function in babies up to 4 weeks old and infants up to 1 year old, Pixxoscan should only be used in these patients after careful evaluation by the doctor.

Other medicines and Pixxoscan

Tell your doctor if you are using, have recently used, or may need to use any other medicine.

Pregnancy and breastfeeding

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

• Pregnancy

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

• Breastfeeding

Tell your doctor if you are breastfeeding or about to start. Your doctor will assess whether you should continue or interrupt breastfeeding 24 hours after administration of Pixxoscan.

Pixxoscancontains sodium

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

3. How to use Pixxoscan

Pixxoscan is injected by a healthcare professional through a small needle into a vein. Your MRI examination can start immediately.

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

Dosage

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

In adults, it isrecommended to administer a single injection of Pixxoscan of 0.1 milliliters per kilogram of body weight (this means that for a person weighing 70 kg, the dose would be 7 milliliters), however, an additional injection of up to 0.2 milliliters per kilogram of body weight may be administered within 30 minutes after the first injection. A total amount of 0.3 milliliters of Pixxoscan per kilogram of body weight may be administered as a maximum (this means that for a person weighing 70 kg, the dose would be 21 milliliters) to obtain images of the central nervous system (CNS) and its blood vessels (MRI angiography with contrast). A dose of 0.075 milliliters of Pixxoscan per kilogram of body weight may be administered as a minimum (this means that for a person weighing 70 kg, the dose would be 5.25 milliliters) for the CNS.

At the end of the leaflet, additional information on the administration and handling of Pixxoscan is included.

Dosage in special populations

The use of Pixxoscan is not recommended in patients with severe kidney problems or in patients who have recently undergone or are scheduled to undergo a liver transplant. However, if your doctor or radiologist decides to administer Pixxoscan, only one dose of Pixxoscan should be administered during an 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 newborns) is a single injection of 0.1 milliliters of Pixxoscan per kilogram of body weight for all indications (see section 1).

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

Dosage in 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 have been administered more Pixxoscanthan you should

Overdose is unlikely to occur. If it does, your doctor will treat all symptoms and may use dialysis to remove Pixxoscan from your body.

In case of overdose, call the Toxicology Information Service, phone: 91 562 04 20, indicating the medicine and the amount administered.

There is no evidence to suggest that hemodialysis is suitable for preventing the development of nephrogenic systemic fibrosis (NSF; see section 4), so it should not be used to treat this disease. In some cases, your heart will be monitored.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.

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

• heart stoppage (cardiac arrest) and severe allergic reactions (anaphylactoid) (including respiratory arrest and shock).

Additionally, the following life-threatening or fatal side effectshave been observed:

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

In rarecases:

• Allergic 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 like that caused by nettles)

inform the MRI department staff immediately.These may be the first signs of a severe reaction. Your examination may be suspended, and you may need further treatment.

Delayed allergic reactionshave been observed in rare cases, from a few hours to several days after receiving Pixxoscan. If this happens to you, inform your doctor or radiologist immediately.

The most common side effects(may affect up to 5 in 1,000 people) are:

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

Most side effects are mild to moderate.

The following possible side effectshave been observed in clinical trials before the approval of Pixxoscan, according to their probability:

Common(may affect up to 1 in 10 people)

• headache
• feeling unwell (nausea)

Uncommon(may affect up to 1 in 100 people)

• allergic reaction, for example:

• low blood pressure

-hives

• swelling of the face
• swelling (edema) of the eyelids
• flushing

The frequency of the following allergic reactions is unknown:

• severe allergic reaction (anaphylactoid shock)
• severe decrease in blood pressure that can lead to collapse (shock)
• respiratory arrest
• fluid in the lungs
• breathing difficulties (bronchospasm)
• blue-tinged 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

• pale skin (pallor)
• dizziness, altered taste, numbness, and tingling
• difficulty breathing (dyspnea)
• vomiting
• redness of the skin (erythema)
• itching (pruritus, including generalized pruritus)
• skin rash (including generalized rash, small flat red spots [macular rash], small elevated and circumscribed lesions [papular rash], and itchy skin rash [pruriginous rash])
• various reactions at the injection site (e.g., leakage into the surrounding tissue, burning, cold, heat, redness, skin rash, pain, or bruising)
• feeling of heat

Rare(may affect up to 1 in 1,000 people)

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

Additional side effectsreported after the approvalof Pixxoscanwith unknown frequency(the frequency cannot be estimated from the available data):

• heart stoppage (cardiac arrest)
• cases of nephrogenic systemic fibrosis (NSF) have been reported, which causes skin hardening and can also affect soft tissues and internal organs.

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

Reporting of side effects

If you experience any side effects, consult your doctor or radiologist, even if they are possible side effects not listed in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Pixxoscan

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

Do not use this medicine after the expiration date stated on the label and carton after EXP. The expiration date is the last day of the month indicated. This medicine does not require special storage conditions.

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

This medicine is a clear, colorless to pale yellow solution. Do not use this medicine if you notice a severe color change or the presence of particles, or if the container appears to be defective.

Medicines should not be disposed of via wastewater or household waste. The healthcare professional will dispose of this medicine when it is no longer needed. This will help protect the environment.

6. Container Contents and Additional Information

Pixxoscan Composition

The active ingredientis gadobutrol.

1 ml of injectable solution contains 604.72 mg of gadobutrol (equivalent to 1.0 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 bottle with 30 ml contains 18,141.6 mg of gadobutrol.

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

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.

The other componentsare meglumine, trometamol, hydrochloric acid, and water for injectable preparations.

Product Appearance and Container Contents

Pixxoscan is a clear, colorless to pale yellow injectable solution.

The container contents are:

• 1 or 10 vials with 2 ml, 7.5 ml, and 15 ml injectable solution
• 1 or 10 bottles with 30 ml and 65 ml injectable solution
• 1 or 10 pre-filled syringes with 5 ml, 7.5 ml, 10 ml, 15 ml, and 20 ml injectable solution

Only certain package sizes may be marketed.

Detailed 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/.

Marketing Authorization Holder

GE Healthcare Bio-Sciences, S.A.U.

Gobelas Street, 35-37, La Florida

28023 Madrid

Manufacturer

GE Healthcare AS

Nycoveien 1

NO-0485 Oslo

Norway

This leaflet was last revised in April 2024

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The following information is intended for healthcare professionals only:

• Renal Insufficiency

Before administering Pixxoscan, 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 minute 1.73m2). patients undergoing liver transplantation have a special risk since the incidence of renal failure is high in this group. there possibility that nsf may occur with pixxoscan, it should only be used severe insufficiency and perioperative period after careful risk-benefit assessment if diagnostic information essential cannot obtained through non-contrast mri. use pixxoscan 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 Pixxoscan may be reduced in elderly patients, it is especially important to evaluate patients aged 65 and older for possible renal dysfunction.

Hemodialysis shortly after the administration of Pixxoscan may be useful for the elimination of Pixxoscan 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 yet undergoing hemodialysis.

• Pregnancy and Lactation

Pixxoscan should not be used during pregnancy unless the clinical situation of the woman requires the use of Pixxoscan.

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

• Hypersensitivity Reactions

As with other intravenous contrast media, Pixxoscan may be associated with hypersensitivity/anaphylactoid reactions or other idiosyncratic reactions characterized by cardiovascular, respiratory, or cutaneous manifestations, which can range from mild to severe reactions, including shock. In general, patients with cardiovascular diseases are more susceptible to serious or even fatal consequences from severe hypersensitivity reactions.

The risk of hypersensitivity reactions may be greater in cases of:

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

In patients with allergic predisposition, the decision to use Pixxoscan should be made after a careful risk-benefit assessment.

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 for the application of emergency measures. In rare cases, delayed reactions (after hours or several days) have been observed.

• Seizure Disorders

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

• Overdose

In case of accidental overdose, it is recommended to monitor cardiovascular function (including ECG) and renal function as precautionary measures.

In the case of overdose in patients with renal insufficiency, Pixxoscan can be eliminated from the body through hemodialysis. After 3 sessions of hemodialysis, approximately 98% of the contrast agent is eliminated from the body. However, there is no evidence to support the use of hemodialysis for the prevention of nephrogenic systemic fibrosis (NSF).

• Before Injection

This medicinal product is intended for single use.

This medicinal product is a clear, colorless to pale yellow solution. The solution should be visually inspected before use. Pixxoscan should not be used if it shows significant color changes, particle formation, or if the container is defective.

• Instructions for Use

Pixxoscan should not be placed in the syringe until immediately before use.

The rubber stopper should not be pierced more than once.

Unused contrast medium in an examination should be discarded.

If this medicinal product is intended to be used with an automatic application system, the suitability of this system for the intended use must be demonstrated by the manufacturer of the system. Any additional instructions from the manufacturer must also be strictly followed.

Any unused contrast medium in an examination should be disposed of according to local regulations.

Shelf Life after First Opening of the Container

Any unused injectable solution in an examination should be discarded.

Bottles

Chemical, physical, and microbiological stability has been demonstrated for 24 hours at 20-25 °C.

From a microbiological point of view, the product should be used immediately. If not used immediately, the in-use storage times and conditions prior to use are the responsibility of the user.

Other Handling

Vials/bottles

Pixxoscan should not be introduced into the syringe from the vial until just before use.

The rubber stopper should never be pierced more than once.

Pre-filled syringe

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

The detachable label from the vials/bottles should be attached to the patient's medical history to allow for accurate recording of the gadolinium-based contrast agent used. The dose used should also be recorded. If an electronic patient record is used, it should include the name of the medicinal product, batch number, and the dose administered.

Posology

The lowest dose that provides sufficient contrast 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 bw). This is equivalent to 0.1 ml/kg bw of the 1.0 M solution.

If a strong clinical suspicion of injury persists despite an MRI without findings or if having more precise information can influence patient treatment, an additional injection of up to 0.2 ml/kg bw may be administered within 30 minutes after the first injection. A dose of 0.075 mmol of gadobutrol per kg of body weight (equivalent to 0.075 ml of Pixxoscan per kg of body weight) may be administered as a minimum for CNS imaging.

Whole-body MRI (except for ARM)

In general, the administration of 0.1 ml of Pixxoscan per kg of body weight is sufficient to answer the clinical question.

Contrast-enhanced MRI angiography

Images of 1 field of view (FOV): 7.5 ml for body weight less than 75 kg; 10 ml for body weight equal to or greater than 75 kg (corresponding to 0.1-0.15 mmol/kg bw).

Images of >1 field of view (FOV): 15 ml for body weight less than 75 kg; 20 ml for body weight equal to or greater than 75 kg (corresponding to 0.2-0.3 mmol/kg bw).

• Pediatric Population

For children of all ages (including term neonates) the recommended dose is 0.1 mmol of gadobutrol per kg of body weight (equivalent to 0.1 ml of gadobutrol per kg 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, Pixxoscan should only be used in these patients after careful assessment at a dose not exceeding 0.1 mmol/kg body weight. No more than one dose should be administered during an examination. Due to the lack of information on repeated administration, the administration of Pixxoscan should not be repeated unless an interval of at least 7 days has passed between injections.

Imaging

The required dose is administered intravenously as a bolus injection. Contrast-enhanced MRI can 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 contrast-enhanced ARM and during a period of approximately 15 minutes after the injection of Pixxoscan for CNS indications (time depends on the type of lesion/tissue).

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

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