Label: Information for the Patient

Pixxoscan 1.0 mmol/ml Injectable Solution EFG

Pixxoscan 1.0 mmol/ml Injectable Solution in Preloaded Syringe EFG

Gadobutrol

Read this label carefully before starting to use this medication, as it contains important information for you.

• Keep this label, as you may need to read it again.
• If you have any questions, consult your doctor or the person administering Pixxoscan.Pixxoscan.

(the radiologist) or hospital/center staff where the magnetic resonance imaging will be performed.

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

What this label contains

1. What Pixxoscan is and how it is used

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

3. How to use Pixxoscan

4. Possible side effects

5. Storage of Pixxoscan

6. Contents of the package and additional information

Pixxoscanis a contrast medium for magnetic resonance (MR) used for the diagnosis of the brain, spinal column, and blood vessels. Pixxoscanalso may help the doctor to determine the type of anomalies (benign or malignant) known or suspected in the liver and kidneys.

Pixxoscanalso can be used for magnetic resonance 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 in adults, adolescents, and children of all ages (including full-term newborns).

How Pixxoscan works

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

Pixxoscan is administered through an injection into your vein. This medication is solely for diagnostic use and will only be administered by experienced healthcare professionals in clinical practice of MR.

Do not use Pixxoscanif

• 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 usePixxoscanif

• you have or have had an allergy (for example, hay fever, urticaria) or asthma
• you have had a previous reaction to any contrast medium
• you have severely impaired renal function
• you have brain disorders with seizures (attacks) or other nervous system diseases
• you have 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.

Allergic reactions that can cause heart problems, breathing difficulties, or skin reactions may occur after using Pixxoscan. Severe reactions are possible. Most of these reactions occur 30 minutes after the administration of Pixxoscan. 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 Pixxoscan, especially if you are 65 years old or older.

Newborns and infants

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

Other medications and Pixxoscan

Inform your doctor 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 can 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 Pixxoscan should not be used during pregnancy unless absolutely necessary.

• Breastfeeding

Inform 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 ofPixxoscan.

Pixxoscancontains sodium

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

Pixxoscanis injected by a healthcare professional through a small needle into a vein. Your MRI scan can start immediately.

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

Dosage

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

In adults, it is recommended 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 maximum total dose of 0.3 milliliters of Pixxoscan per kilogram of body weight (this means that for a person weighing 70 kg, the dose would be 21 milliliters) may be administered 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 (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 Pixxoscan is included at the end of the prospectus.

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 will soon undergo a liver transplant. However, if your doctor or radiologist decides to administer Pixxoscan to you, only a single dose of Pixxoscan should be administered during the examination and you should not receive a second injection 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 milliliters of Pixxoscan 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 of age and infants up to 1 year of age, Pixxoscan should only be used in these patients after careful evaluation by a doctor. Neonates and infants should only receive a single 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 you may undergo blood tests to check the proper functioning of your kidneys.

If you have been administered more Pixxoscan than you should

It is unlikely that an overdose will occur. If it does, the doctor will treat all symptoms and may use dialysis to remove Pixxoscan from your body.

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

There is no evidence to indicate that hemodialysis is suitable for the prevention of systemic fibrosis nephrogenica (FNS; see section 4) and should not be used for the treatment of this disease. In some cases, your heart will be monitored.

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

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

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

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

Additionally, in some cases, thefollowing 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:

• Severe allergic reactions (hypersensitivityand anaphylaxis) may occur, including severe reactions (shock) that may require immediate medical intervention.

If you notice:

• inflammation of the face, lips, tongue, or throat
• cough and sneezing
• difficulty breathing
• itching
• nasal congestion
• hives (like those caused by nettle rash)

Inform the radiology department staff immediately.These may be the first signs of aserious reaction.Your examination may be suspended, and you may require further treatment.

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

Theside effects observed most frequently(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 followingpossible side effectshave been observed in clinical trials before Pixxoscan was approved, according to their probability:

Frequent(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

- inflammation of the face

- swelling (edema) of the eyelids

- flushing

The frequency of the following allergic reactions is unknown:

- severe allergic reaction (anaphylactic shock)

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

- respiratory arrest

- fluid in the lungs

- breathing difficulties (bronchospasm)

- blue lips

- inflammation of the mouth and throat

- inflammation of the throat

- high blood pressure

- chest pain

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

- conjunctivitis

- excessive sweating

- cough

- sneezing

- burning sensation

- pale skin (pallor)

• dizziness, altered taste, numbness, and tingling
• difficulty breathing (breathlessness)
• vomiting
• skin redness (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 skin rash with itching (pruritic rash))
• different types of reactions at the injection site (e.g., swelling in the surrounding tissue, burning, coldness, redness, rash, pain, or hematomas)
• sensation of heat

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

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

Additional side effectsreported after approval of Pixxoscanof unknown frequency(the frequency cannot be estimated from the available data):

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

After administration of Pixxoscan, variations in the results of kidney function tests (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 not listed in this leaflet. You can also report them directly through the Spanish System for the Vigilance 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 medicine.

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 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 when it is no longer needed. This will help protect the environment.

Composition of Pixxoscan

The active principle is gadobutrol.

1 ml of injectable solution contains 604.72 mg of gadobutrol (equivalent to 1.0 mmol of gadobutrol that contains 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 preloaded syringe with 5.0 ml contains 3,023.6 mg of gadobutrol,

1 preloaded syringe with 7.5 ml contains 4,535.4 mg of gadobutrol,

1 preloaded syringe with 10 ml contains 6,047.2 mg of gadobutrol,

1 preloaded syringe with 15 ml contains 9,070.8 mg of gadobutrol,

1 preloaded syringe with 20 ml contains 12,094.4 mg of gadobutrol.

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

Appearance of the product and contents of the package

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

The contents of the packages are:

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

Only some package sizes may be marketed.

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

Marketing Authorization Holder

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

Calle Gobelas, 35-37, La Florida

28023 Madrid

Responsible for manufacturing

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 only for healthcare professionals:

• Renal insufficiency

Before administering Pixxoscan, it is recommended to evaluate all patients to detect possible renal dysfunction by 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 Pixxoscan, 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 by MRI without contrast. If Pixxoscan is 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 Pixxoscan should not be repeated unless at least 7 days have elapsed between injections.

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

Hemodialysis shortly after 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 FNS in patients who are not yet undergoing hemodialysis.

• Pregnancy and lactation

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

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

• Hypersensitivity reactions

Like other intravenous contrast media, Pixxoscan 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 case 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 careful evaluation of the benefit/risk ratio.

Most of these reactions occur 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 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, Pixxoscan may be eliminated by hemodialysis. After 3 hemodialysis sessions, approximately 98% of the contrast agent is eliminated from the body. However, there is no evidence that hemodialysis is suitable for the prevention of systemic fibrosis nephrogenica (FNS).

• Before injection

This medicine is indicated for single use.

This medicine is a transparent, colorless to pale yellow injectable solution. The solution should be visually inspected before use. Pixxoscan should not be used if it presents significant color changes, the appearance of particles, or if the package 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 should be discarded.

If this medicine is intended to be used with an automated 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 be strictly followed.

Any unused contrast medium should be discarded 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.

Bottles

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 in use and the conditions prior to use are the responsibility of the user.

Other manipulations

Vials/bottles

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

The rubber stopper should never be pierced more than once.

Preloaded syringe

The tip cap should be removed from the preloaded syringe immediately before use.

The detachable label of the vials/bottles should be stuck to the patient's history to allow for precise recording of the gadolinium-containing contrast medium used. The dose used should also be recorded. If the patient's electronic history is used, the name of the medicine, batch number, and dose administered should be included in it.

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.). This is equivalent to 0.1 ml/kg b.w. of the 1.0 M solution.

If a firm clinical suspicion persists despite a normal MRI or if having more precise information may influence the patient's treatment, an additional injection of up to 0.2 ml/kg b.w. may be administered within 30 minutes after the first injection. A dose of at least 0.075 mmol of gadobutrol per kilogram of body weight (equivalent to 0.075 ml of Pixxoscan per kilogram of body weight) should be administered for the CNS imaging.

Whole-body MRI (except for ARM)

Generally, the administration of 0.1 ml of Pixxoscan per kilogram of body weight is sufficient to respond to 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 b.w.).

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 b.w.).

• Pediatric population

For children of all ages (including neonates at term) the recommended dose is 0.1 mmol of gadobutrol per kilogram of body weight (equivalent to 0.1 ml of gadobutrol 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, Pixxoscan should only be used in these patients after careful evaluation at a dose not exceeding 0.1 mmol/kg of 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 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 the 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 Pixxoscan injection for CNS indications (the time depends on the type of lesion/tissue).

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

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