Pixxoscan

Package leaflet: Information for the user

Pixxoscan, 1.0 mmol/ml, solution for injection
Pixxoscan, 1.0 mmol/ml, solution for injection in pre-filled syringe
Gadobutrol
Please read all of this leaflet carefully before the medicine is administered, because it contains
important information for the patient.

• Keep this leaflet as you may need to read it again.
• If you have any further questions, please ask your doctor (radiologist) or the MRI facility staff.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or the MRI facility staff. See section 4.

Leaflet contents

1. What Pixxoscan is and what it is used for
2. Important information before using 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 used during magnetic resonance imaging (MRI) for the diagnosis of the brain, spinal cord, and blood vessels. Pixxoscan helps in assessing the nature (benign or malignant characteristics) of detected or suspected abnormalities in the liver and kidneys.
Pixxoscan may also be used in MRI imaging of abnormalities in other body regions.
The medicine facilitates visualization of abnormal structures or lesions and helps differentiate between healthy and diseased tissue.
Pixxoscan is used in adults, adolescents, and children of all ages (including full-term newborns).

How Pixxoscan works
MRI is a type of diagnostic imaging in medicine that exploits the different behavior of water molecules in healthy and diseased tissues. The examination is performed using complex magnetic systems and radio waves. The resulting signals are recorded by computers and converted into images.
Pixxoscan is administered as an intravenous injection. This medicine is intended solely for diagnostic use and must be administered by qualified healthcare professionals experienced in performing magnetic resonance imaging (MRI).

2. Important information before using Pixxoscan

When not to use Pixxoscan

• if the patient is allergic to gadobutrol or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Before starting treatment with Pixxoscan, consult a doctor if the patient:

• has or has had allergies (e.g. hay fever, hives) or asthma,
• previously experienced a reaction to a contrast agent,
• has severely impaired kidney function,
• has brain disorders with seizures or other nervous system disorders,
• has a cardiac pacemaker or any implants containing iron.

The doctor will decide whether the ordered examination can be performed.
After administration of Pixxoscan, allergic-type reactions may occur, leading to
heart problems, breathing difficulties, or skin reactions. Severe reactions are possible. Most
reactions occur within half an hour after administration. Therefore, patient monitoring after the examination is recommended. Delayed reactions (after several hours or days) have been observed (see section 4).
Kidney and/or liver function disorders
Inform the doctor if:

• the patient's kidneys are not functioning properly,
• the patient has recently undergone or is scheduled to receive a liver transplant.

The doctor may decide to perform blood tests to assess kidney function before deciding to use Pixxoscan, especially in patients over 65 years of age.
Newborns and infants
Due to immature kidney function in newborns (children up to 4 weeks of age) and infants (children up to 1 year of age), Pixxoscan should be used in these patients only after careful consideration by the doctor.
Pixxoscan and other medicines
Inform the doctor about all medicines currently or recently used by the patient, as well as any medicines the patient plans to take.
Pregnancy and breastfeeding
Consult a doctor before using any medicine.

• Pregnancy Gadobutrol may cross the placenta. It is not known whether this affects the unborn child. Women who think they are pregnant or suspect they may be pregnant should inform their doctor, as Pixxoscan should not be used during pregnancy unless absolutely necessary.
• Breastfeeding Women who are breastfeeding or planning to breastfeed should inform their doctor. The doctor will discuss with the patient whether she should continue breastfeeding or interrupt breastfeeding for 24 hours after administration of Pixxoscan.

Pixxoscan contains sodium
This medicine contains less than 23 mg per dose (calculated based on the average amount administered to a person weighing 70 kg), which means it is considered "sodium-free".

3. How to use Pixxoscan

Pixxoscan is administered by injection through a thin needle into a vein by medical personnel. Pixxoscan
will be given shortly before the magnetic resonance imaging (MRI) examination.
After injection, the patient will be monitored for at least 30 minutes.
Typical dose
The actual dose of Pixxoscan appropriate for a given patient will depend on body weight
and the area of the body being examined by magnetic resonance imaging (MRI).
In adults, a single intravenous dose of 0.1 millilitre of Pixxoscan per kg of body weight is recommended
(meaning that a person weighing 70 kg will receive a dose of 7 millilitres). However, an additional
injection of up to 0.2 millilitres per kg of body weight may be administered within 30 minutes of the first
injection. For central nervous system (CNS) imaging and CE-MRA (contrast enhancement in magnetic
resonance angiography) procedures, a total dose of up to 0.3 millilitres of Pixxoscan per kg of body
weight may be administered (meaning that a person weighing 70 kg will receive a dose of 21 millilitres).
For CNS imaging, the lowest dose that may be administered is 0.075 millilitres of Pixxoscan per kg of
body weight (meaning that a person weighing 70 kg will receive a dose of 5.25 millilitres).
Further information on administration and handling of Pixxoscan is provided at the end of this leaflet.
Dosing in specific patient groups
Pixxoscan is not recommended for use in patients with severe kidney disease, or in patients who have
recently undergone or are scheduled to undergo liver transplantation.
However, if use of the medicine is necessary, the patient should receive only one dose of Pixxoscan
during the examination and should not receive a second injection for at least 7 days.
Use in children and adolescents
In children of all ages (including full-term newborns), a single intravenous dose of 0.1 millilitre of
Pixxoscan per kg of body weight is recommended (see section 1).
Due to immature kidney function in newborns (children up to 4 weeks of age) and infants (children up
to 1 year of age), Pixxoscan should be used in these patients only after careful consideration by the
physician. Newborns and infants should receive a single dose of Pixxoscan during the examination and
should not receive a second injection for at least 7 days.
Elderly patients
There is no need to adjust the dose in patients aged 65 years and older; however, a blood test should
be performed to assess kidney function.
Administration of a higher than recommended dose of Pixxoscan
Overdose is unlikely. However, if it occurs, the physician will treat any symptoms and may use kidney
dialysis to remove Pixxoscan from the body.
There is no evidence that kidney dialysis prevents the development of nephrogenic systemic fibrosis
(NSF; see section 4) and it should not be used as a treatment for this condition. In some cases, heart
function may be monitored.
If you have any further questions about the use of this medicine, consult your doctor or MRI facility staff.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
The most severe adverse reactions (in some cases life-threatening or
fatal) are:

• cardiac arrest (heart stops beating) and severe allergic-type reactions (anaphylactoid reactions), including respiratory arrest and shock.

Additionally, in some cases the following adverse reactions have been observed that are life-threatening or may lead to death:

• difficulty breathing, loss of consciousness, severe allergic-type reaction, significant drop in blood pressure that may lead to circulatory collapse, respiratory arrest, pulmonary edema (fluid in the lungs), swelling of the mouth and throat, and low blood pressure.

Rarely, cases may occur of:

• hypersensitivity reactions (hypersensitivity and anaphylaxis), including severe reactions (shock), which may require immediate medical intervention.

The patient should immediately inform the MRI facility staff if any of the following occur:

• swelling of the face, lips, tongue or throat,
• coughing and sneezing,
• difficulty breathing,
• itching,
• runny nose,
• hives (a specific type of rash).

These symptoms may be the first signs of a severe reaction, meaning that the examination may need to be stopped and appropriate treatment initiated.
Rarely, delayed hypersensitivity-type reactions have been observed, occurring from hours to several days after administration of Pixxoscan. If such reactions occur, the patient should contact a physician or MRI facility staff.

The most commonly observed adverse reactions (may occur in 5 or more out of 1,000 people) are:

• headache, nausea, dizziness.

Most adverse reactions are mild to moderate in severity.
Below are listed possible adverse reactions observed during clinical trials prior to the marketing authorization of Pixxoscan, classified by frequency of occurrence.

Frequent (may occur in up to 1 in 10 people):

• headache
• nausea (feeling of sickness)

Uncommon (may occur in up to 1 in 00 people):

• allergic-type reactions, e.g.:
• hypotension (low blood pressure)
• urticaria (hives)
• facial swelling (facial edema)
• eyelid swelling (periorbital edema)
• erythema (redness)

The frequency of the following allergic-type reactions is unknown:

• severe allergic-type reaction (anaphylactic shock)
• significant drop in blood pressure that may lead to shock
• respiratory arrest
• pulmonary edema (fluid in the lungs)
• bronchospasm (difficulty breathing)
• cyanosis (bluish discoloration of the lips)
• swelling of the mouth and throat (edema of the oral cavity and pharynx)
• laryngeal edema (swelling of the larynx)
• increased blood pressure
• chest pain
• swelling (edema) of the face, throat, lips, mouth and/or tongue
• conjunctivitis
• excessive sweating (increased perspiration)
• cough
• sneezing
• burning sensation
• pallor (pale skin)
• dizziness, taste disturbances (altered sense of taste), numbness and tingling
• dyspnea (shortness of breath)
• vomiting
• erythema (redness of the skin)
• pruritus (itching, including generalized itching)
• rash (including generalized rash, macular rash [small, flat red spots], papular rash [small, raised, localized lesions], pruritic erythema [itchy rash])
• various injection site reactions (e.g., extravasation into surrounding tissues, burning sensation, cold sensation, warm sensation, redness, itching, pain or bruising)
• feeling of warmth

Rare (may occur in up to 1 in 1,000 people):

• loss of consciousness (fainting)
• seizures
• olfactory hallucinations (disturbed sense of smell)
• rapid heartbeat
• palpitations (pounding heart)
• dry mouth
• malaise
• feeling of cold

Additional adverse reactions reported after marketing authorization of Pixxoscan
with unknown frequency (cannot be estimated from available data):

• cardiac arrest (heart stops beating)
• cases of nephrogenic systemic fibrosis (a disease associated with skin hardening, which may also affect soft tissues and internal organs) have been reported.

After administration of Pixxoscan, changes in blood tests related to kidney function (e.g., increased serum creatinine concentration) have been observed.

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, the patient should inform their doctor. Adverse reactions can be reported directly to the Department of Monitoring of Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181 C
02-222 Warsaw
Tel.: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl.
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Pixxoscan

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the vial, bottle, or syringe-vial (EXP). The expiry date refers to the last day of the stated month. This medicine does not require any special storage conditions.
Bottles
Chemical, physical and microbiological stability has been demonstrated for 24 hours at temperatures between 20 and 25 ºC.
From a microbiological standpoint, this medicine should be used immediately after opening.
This medicine is a clear, colourless to pale yellow solution. Do not use this medicine if significant discolouration or the presence of particulate matter is observed, or if the container appears damaged.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the package and other information

What Pixxoscan contains

• The active substance is gadobutrol. One millilitre of injection solution contains 604.72 mg gadobutrol (equivalent to 1.0 mmol gadobutrol, which contains 157.25 mg gadolinium).
• The other ingredients are: sodium calcbutrol (see section 2), trometamol, hydrochloric acid and water for injections.

One 2 ml vial contains 1209.44 mg gadobutrol.
One 7.5 ml vial contains 4535.4 mg gadobutrol.
One 15 ml vial contains 9070.8 mg gadobutrol.
One 30 ml bottle contains 18141.6 mg gadobutrol.
One 65 ml bottle contains 39306.8 mg gadobutrol.
One 5 ml prefilled syringe contains 3023.6 mg gadobutrol.
One 7.5 ml prefilled syringe contains 4535.4 mg gadobutrol.
One 10 ml prefilled syringe contains 6047.2 mg gadobutrol.
One 15 ml prefilled syringe contains 9070.8 mg gadobutrol.
One 20 ml prefilled syringe contains 12094.4 mg gadobutrol.

What Pixxoscan looks like and contents of the pack
Pixxoscan is a clear, colourless to slightly yellowish injection solution.

Pack contents:

• 1 or 10 vials, each containing 2 ml, 7.5 ml or 15 ml of injection solution.
• 1 or 10 bottles, each containing 30 ml or 65 ml of injection solution.
• 1 or 10 prefilled syringes, each containing 5 ml, 7.5 ml, 10 ml, 15 ml or 20 ml of injection solution.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
GE Healthcare AS
Nycoveien 1
0485 Oslo
Norway

For further information, contact the representative of the Marketing Authorisation Holder:
GE Medical Systems Polska Sp. z o.o.
Wołoska 9
02-583 Warsaw
Tel: +48 22 330 83 00

This medicinal product is authorised in the European Economic Area member states under the following names:
France: Pixcyclic
Austria, Spain, Germany, Norway, Portugal, Sweden, Italy: Pixxoscan

Information intended exclusively for healthcare professionals:

• Renal function disorders

All patients should be evaluated for renal function disorders, including laboratory tests, prior to administration of Pixxoscan.
Cases of nephrogenic systemic fibrosis (NSF) associated with administration of some gadolinium-containing agents have been reported in patients with acute or severe chronic renal impairment (glomerular filtration rate [GFR] < 30 mL/min/1.73 m²). Patients undergoing liver transplantation are at particular risk, as the likelihood of developing acute renal failure in this patient population is high. Due to the potential risk of NSF with Pixxoscan, the agent should be used in patients with severe renal impairment and in patients during the perioperative period of liver transplantation only after careful benefit-risk assessment and if essential diagnostic information cannot be obtained by non-contrast MRI. If use of Pixxoscan is considered necessary, the dose should not exceed 0.1 mmol/kg body weight. Only a single dose should be administered per imaging session. Due to lack of data on repeated administration, injections of Pixxoscan should not be repeated unless intervals between injections are at least 7 days.

As renal clearance of Pixxoscan may be reduced in elderly patients, monitoring for renal function impairment is particularly important in patients aged 65 years and older.
Hemodialysis shortly after Pixxoscan administration may facilitate elimination of the agent from the body. However, there is no evidence to support initiating hemodialysis for the prevention or treatment of NSF in patients not already on dialysis.

• Pregnancy and breastfeeding

Pixxoscan should not be used during pregnancy unless the clinical condition of the woman necessitates its use.
The physician and the breastfeeding mother should decide whether to discontinue breastfeeding or to interrupt it for 24 hours after administration of Pixxoscan.

• Hypersensitivity reactions

As with other contrast agents, administration of Pixxoscan may be associated with risk of pseudoallergic, hypersensitivity, or idiosyncratic reactions, presenting with cardiovascular, respiratory, or cutaneous symptoms, up to severe reactions including anaphylactoid shock. In general, patients with cardiovascular disease are more susceptible to serious complications and even death due to severe hypersensitivity reactions. Risk factors for hypersensitivity reactions include:

• previous reactions to contrast agents,
• history of bronchial asthma,
• history of allergic diseases.

In patients with a predisposition to allergies, the decision to administer Pixxoscan must be made after careful benefit-risk assessment.
Most reactions occur within 30 minutes after administration. Therefore, patients should be monitored after the procedure. Access to medications for treating hypersensitivity reactions and readiness to initiate emergency interventions should be ensured. Delayed reactions (occurring hours to several days after administration) have been rarely observed.

• Seizures

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

• Overdose

In case of overdose, monitoring of cardiovascular function (including ECG) and renal function is recommended as a precautionary measure.
In patients with renal insufficiency, Pixxoscan can be removed from the body by hemodialysis. Approximately 98% of the contrast agent is eliminated after three hemodialysis sessions. However, there is no evidence that hemodialysis is effective in preventing nephrogenic systemic fibrosis (NSF).

• Before administration

This medicinal product is intended for single use only.
The product is a clear, colourless to slightly yellow solution for injection. The solution should be inspected visually before use.
Pixxoscan should not be used if significant discoloration, presence of particulate matter, or package damage is observed.

• Method of administration

Any unused portion of the medicinal product remaining after one examination should be discarded.
If this medicinal product is to be used with an automated injection system, compatibility must be confirmed by the manufacturer of the medical device. All additional instructions provided by the equipment manufacturer must also be strictly followed.
Any unused medicinal product and waste material should be disposed of in accordance with local regulations.
Shelf-life after first opening of the container
Any unused portion of the injection solution remaining after one examination should be discarded.
Vials
Chemical, physical, and microbiological stability has been demonstrated for 24 hours at temperatures from 20 to 25°C.
From a microbiological point of view, the product should be used immediately. If not used immediately, the person administering the product is responsible for the duration and conditions of storage.
Preparation for administration
Vials / bottles
Pixxoscan should be drawn into a syringe immediately before use.
The stopper should not be punctured more than once.
Prefilled syringes
The prefilled syringe should be removed from its packaging immediately before use.
The label removed from the vial, bottle, or syringe should be attached to the patient's record to ensure proper documentation of the gadolinium-containing agent used. The administered dose should also be recorded. In case of electronic patient records, the name of the medicinal product, batch number, and dose should be entered into the patient's record.
Dosage
The lowest dose providing sufficient contrast 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 imaging
The recommended dose for adults is 0.1 mmol per kg body weight (0.1 mmol/kg b.w.), corresponding to 0.1 mL/kg b.w. of a 1.0 M solution.
If, despite a negative MRI result, there remains a strong clinical suspicion of a pathological lesion or if additional information may influence patient management, a second injection may be administered, bringing the total dose up to 0.2 mL/kg b.w. within 30 minutes of the first dose. For CNS MRI, the minimum dose that may be administered is 0.075 mmol gadobutrol per kg body weight (corresponding to 0.075 mL of Pixxoscan per kg body weight).
Whole-body MRI (except MRA)
For diagnostic purposes, a dose of 0.1 mL/kg b.w. of Pixxoscan is usually sufficient.
Angiographic imaging (CE-MRA)
Imaging of 1 field of view (FOV): 7.5 mL for body weight below 75 kg; 10 mL for body weight ≥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 ≥75 kg (corresponding to 0.2–0.3 mmol/kg b.w.).

• Children and adolescents

In children of all ages (including term neonates), the recommended dose is 0.1 mmol gadobutrol per kg body weight (corresponding to 0.1 mL of Pixxoscan per kg body weight) for all indications (see section 1).
Due to immature renal function in neonates up to 4 weeks of age and infants up to 1 year of age, Pixxoscan should be used in these patients only after careful consideration 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, injections of Pixxoscan should not be repeated unless intervals between injections are at least 7 days.

Imaging
The required dose should be administered as a single, rapid intravenous bolus injection. MRI with contrast agent may be initiated immediately after injection (shortly after injection, depending on the pulse sequences and imaging protocol used).
Optimal contrast effect occurs during the first arterial pass in angiographic imaging (CE-MRA) and within approximately 15 minutes after Pixxoscan injection in central nervous system (CNS) imaging (timing depends on the type of pathological lesion and tissue involved).
T1-weighted sequences are particularly useful for contrast-enhanced MRI examinations.
Additional information on the use of Pixxoscan is provided in section 3 of the package leaflet.