Pixxoscan 1.0 mmol/ml solution for injection in pre-filled syringe EFG

Package leaflet: Information for the user

Introduction

Package leaflet: Information for the patient

Pixxoscan 1.0 mmol/ml injectable solution EFG

Pixxoscan 1.0 mmol/ml injectable solution in pre-filled syringe EFG

Gadobutrol

Read all of this 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 or the person who will administer Pixxoscan to you
  (the radiologist) or the hospital/centre staff where the magnetic resonance imaging will be performed.
• If you experience side effects, consult your doctor or radiologist, even if they are adverse effects not listed in this leaflet. See section 4.

What this leaflet contains

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

1. What Pixxoscan is and what it is used for

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

Pixxoscan may also be used for magnetic resonance imaging of 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, adolescents, and children of all ages (including full-term neonates).

How Pixxoscan works

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

Pixxoscan is administered by injection into your vein. This medicine is for diagnostic use only and will be given to you only by healthcare professionals experienced in clinical MRI practice.

2. What you need to know before using Pixxoscan

DO NOT use Pixxoscan 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 Pixxoscan if

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

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

Allergy-type reactions may occur after the use of Pixxoscan, which may lead to heart problems, difficulty breathing, or skin reactions. Severe reactions are possible. Most of these reactions occur within half an hour 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

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 Pixxoscan, especially if you are 65 years of age or older.

Newborns and infants

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

Other medicines and Pixxoscan

Inform your doctor 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 Pixxoscan 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 Pixxoscan.

Pixxoscan contains 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., essentially "sodium-free".

3. How to use Pixxoscan

Pixxoscan is administered by a healthcare professional as an intravenous injection using a small needle. Your MRI scan may begin immediately afterward.

After the injection, you will be kept under observation for at least 30 minutes.

Dosage

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

In adults, a single injection of 0.1 millilitres of Pixxoscan per kilogram 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 dose of up to 0.3 millilitres of Pixxoscan per kg of body weight (this means that for a person weighing 70 kg, the dose would be 21 millilitres) may be administered to obtain images of the central nervous system (CNS) and its blood vessels (contrast-enhanced MR angiography). A minimum dose of 0.075 millilitres of Pixxoscan 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 the administration and handling of Pixxoscan is provided at the end of this leaflet.

Dosage in special populations

The use of Pixxoscan 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 your doctor or radiologist decides to administer Pixxoscan, only one dose of Pixxoscan should be given per examination, and a second injection should not be administered 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 Pixxoscan 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 evaluation by the physician. Neonates and infants should receive only one dose of Pixxoscan per examination, and a second injection should not be administered until at least 7 days have passed.

Dosage in elderly patients

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

If you have been given more Pixxoscan than you should

Overdose is unlikely. If it occurs, the doctor will treat any symptoms and may use dialysis to remove Pixxoscan from your body.

In case of overdose, contact the Toxicology Information Service at telephone number: 91 562 04 20, indicating the medication and the amount administered.

There is no evidence indicating 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 will be monitored.

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 produce adverse effects, although not everyone experiences them.

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

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

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

• breathing difficulty (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 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
• cough and sneezing
• difficulty breathing
• itching
• nasal congestion
• hives (rash similar to that caused by nettles)

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

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

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

• headache, feeling of discomfort (nausea), and dizziness.

Most side effects are mild to moderate.

The following is a list of possible adverse effects observed in clinical trials before the approval of Pixxoscan, categorized by their likelihood:

Frequent (may affect up to 1 in 10 people)

• headache
• feeling of discomfort (nausea)

Uncommon (may affect up to 1 in 100 people)

• allergic-type reaction, for example:

• low blood pressure

• hives

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

The frequency of the following allergic reactions is unknown:

• severe allergic reaction (anaphylactoid shock)
• severe drop in blood pressure may lead to collapse (shock)
• respiratory arrest
• fluid in the lungs
• breathing difficulties (bronchospasm)
• blue lips
• swelling of the mouth and throat
• swelling of the throat
• increase in blood pressure
• chest pain
• swelling of the face, throat, mouth, lips and/or tongue (angioedema)

• conjunctivitis

• increased sweating

• Cough

• Sneezing

• Burning sensation

• pale skin (pallor)

• dizziness, taste disturbance, numbness and tingling
• difficulty breathing (dyspnea)
• vomiting
• skin redness (erythema)
• itching (pruritus, including generalized pruritus)
• skin rash (including generalized rash, flat red spots [macular rash], small raised and well-defined lesions [papular rash], and itchy rash [pruriginous rash])
• various types of injection site reactions (e.g., leakage into surrounding tissue, burning, cold sensation, warmth, redness, skin rash, pain or bruising)
• sensation of warmth

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

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

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

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

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

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor or radiologist, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse effects, you can help provide 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 expiry date stated on the label and packaging after EXP. The expiry date refers to the last day of the month indicated. This medicine does not require any special storage conditions.

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

This medicine is a clear, colourless to pale yellow solution. Do not use this medicine if you notice a marked change in colour, 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 medicine when it is no longer needed. This helps protect the environment.

6. Contents of the pack and other information

Composition of Pixxoscan

The active substance is gadobutrol.

1 ml of injectable solution contains 604.72 mg of gadobutrol (equivalent to 1.0 mmol of gadobutrol, which 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 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 components are sodium calcobutrol (see end of section 2), trometamol, hydrochloric acid, and water for injections.

Appearance of the product and contents of the pack

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

Pack contents are:

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

Only certain pack sizes may be marketed.

Detailed information on this medicinal product is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS) http://www.aemps.gob.es/.

Marketing Authorisation Holder

GE Healthcare Bio-Sciences, S.A.U.
Calle Gobelas, 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 impairment

Before administering Pixxoscan, it is recommended to assess all patients 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 renal failure is high in this group. Since there is a possibility that NSF may occur with Pixxoscan, 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 the diagnostic information is essential and cannot be obtained by non-contrast MRI. If Pixxoscan use 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 the lack of data on repeated administration, Pixxoscan should not be re-administered 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 assess renal function in patients aged 65 years and older.

Haemodialysis shortly after Pixxoscan administration may be helpful in eliminating Pixxoscan from the body. However, there is no evidence supporting the initiation of haemodialysis for the prevention or treatment of NSF in patients not already undergoing haemodialysis.

• Pregnancy and breastfeeding

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

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

• Hypersensitivity reactions

As with other intravenous contrast agents, Pixxoscan may be associated with hypersensitivity/anaphylactoid reactions or other idiosyncratic reactions, including cardiovascular, respiratory, or cutaneous manifestations, up to and including severe reactions such as shock. In general, patients with cardiovascular disease are more susceptible to severe or even fatal consequences from serious hypersensitivity reactions.

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

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

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

Most of these reactions occur within half an hour 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. Rarely, delayed reactions (occurring hours or several days later) have been observed.

• Seizure disorders

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

• Overdose

In the 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, Pixxoscan can be eliminated by haemodialysis. Approximately 98% of the contrast agent is removed from the body after three haemodialysis sessions. However, there is no evidence that haemodialysis is effective in preventing nephrogenic systemic fibrosis (NSF).

• Before injection

This medicinal product is for single use only.

This medicine is a transparent, colourless to pale yellow solution. The solution should be inspected visually before use. Pixxoscan must not be used if there are significant changes in colour, presence of particles, or if the container is damaged.

• Instructions for use

Pixxoscan must not be drawn into a syringe until immediately before use.

The rubber stopper must not be punctured more than once.

Any unused contrast agent from an examination must be discarded.

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

Any unused contrast agent must be disposed of in accordance with local regulations.

In-use shelf life after first opening of the container

Any injectable solution not used during an examination must be discarded.

Bottles

Chemical, physical, and microbiological in-use 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, the in-use storage times and conditions prior to use are the responsibility of the user.

Other handling

Vials/bottles

Pixxoscan must not be drawn into a syringe from the vial until immediately before use.

The rubber stopper must never be punctured more than once.

Pre-filled syringe

The tip cap of the pre-filled syringe must be removed immediately before use.

The detachable label from 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 patient record is used, the name of the medicinal product, batch number, and administered dose should be included.

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

If a strong clinical suspicion of a lesion persists despite a non-contrast MRI showing no findings, or if more precise information may influence patient management, an additional injection 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 Pixxoscan per kg of body weight) may be administered as a minimum for CNS imaging.

Whole-body MRI (except CE-MRA)

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

Contrast-enhanced MR angiography (CE-MRA)

Imaging of 1 field of view (FOV): 7.5 ml for body weight below 75 kg; 10 ml for body weight equal to or above 75 kg (corresponding to 0.1–0.15 mmol/kg b.w.).

Imaging of >1 field of view (FOV): 15 ml for body weight below 75 kg; 20 ml for body weight equal to or above 75 kg (corresponding to 0.2–0.3 mmol/kg b.w.).

• Paediatric 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 evaluation 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 the lack of data on repeated administration, Pixxoscan should not be re-administered unless at least 7 days have 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 CE-MRA and for approximately 15 minutes after Pixxoscan injection for CNS indications (timing depends on lesion/tissue type).

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

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