Gadobutrol farmak

Gadobutrol Farmak, 1.0 mmol/mL, solution for injection in a prefilled syringe
Gadobutrolum
Please read this leaflet carefully before using the medicine, as it contains
important information for the patient.

• Keep this leaflet, so that you can read it again if necessary.
• If you have any questions, please consult your doctor (radiologist) or MRI facility staff.
• If you experience any adverse reactions, including any adverse reactions not listed in this leaflet, inform your doctor or MRI facility staff. See section 4.

Table of contents

1. What Gadobutrol Farmak is and what it is used for
2. Important information before using Gadobutrol Farmak
3. How to use Gadobutrol Farmak
4. Possible side effects
5. How to store Gadobutrol Farmak
6. Contents of the pack and other information

1. What Gadobutrol Farmak is and what it is used for

Gadobutrol Farmak is a contrast agent used during magnetic resonance imaging (MRI) of the brain, spine, and blood vessels. Gadobutrol Farmak may also help the doctor determine the nature (benign or malignant) of known or suspected abnormalities in the liver and kidneys.
Gadobutrol Farmak may also be used in MRI imaging of abnormalities in other parts of the body.
This medicine helps to visualize abnormal structures or lesions and assists in distinguishing between healthy and diseased tissue.
The medicine is used in adults and children of all ages (including full-term newborns).

How Gadobutrol Farmak works
Magnetic resonance imaging (MRI) is a type of medical diagnostic imaging that uses the different behavior of water molecules in healthy and diseased tissues. The examination is performed using powerful magnetic fields and radio waves. Signals are detected by computers and translated into images.
Gadobutrol Farmak is administered as an intravenous injection. This medicine is intended solely for diagnostic use and should be administered by trained healthcare professionals experienced in performing magnetic resonance imaging (MRI) procedures.

2. Important information before using Gadobutrol Farmak

Do not use Gadobutrol Farmak if:

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

Warnings and precautions
Before receiving Gadobutrol Farmak, consult a doctor if the patient:

• has or has had allergies (e.g. hay fever, hives) or asthma,
• has previously experienced a reaction to any contrast agent,
• has severely impaired kidney function,
• has a brain disorder with seizures or other neurological diseases,
• has a cardiac pacemaker implanted or any implants or clips containing iron in the body. The doctor will decide whether the requested examination can be performed.

After administration of Gadobutrol Farmak, allergic-type reactions or other types of reactions leading to disturbances in heart function, breathing difficulties, or skin reactions may occur. Severe reactions are possible. Most of these reactions occur within half an hour after administration of Gadobutrol Farmak. Therefore, the patient will be monitored after the examination. Delayed reactions (after several hours or days) have also 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 undergo liver transplantation.

The doctor may decide to perform blood tests to assess kidney function before deciding to administer Gadobutrol Farmak, especially in patients over 65 years of age.

Use in 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), Gadobutrol Farmak should be used in these patients only after careful consideration by the doctor.

Gadobutrol Farmak and other medicines
Tell the doctor about all medicines currently used or recently used by the patient, as well as any medicines the patient plans to take.

Pregnancy and breastfeeding

• Pregnancy Gadobutrol may cross the placenta. It is not known whether this affects the unborn child. Women who suspect they are pregnant or may be pregnant should inform their doctor, as Gadobutrol Farmak should not be used during pregnancy unless absolutely necessary.
• Breastfeeding Women who are breastfeeding or planning to start breastfeeding 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 Gadobutrol Farmak.

Gadobutrol Farmak contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per dose (calculated based on the average amount administered to a 70 kg person), meaning it is considered "sodium-free".

3. How to use Gadobutrol Farmak

Gadobutrol Farmak is administered intravenously via a fine needle by medical personnel.
The magnetic resonance imaging (MRI) examination may begin immediately.
After injection, the patient will be observed for at least 30 minutes.

Recommended dose
The actual dose of Gadobutrol Farmak appropriate for a given patient will depend on body weight and the body area being examined by magnetic resonance imaging.
In adults, a single injection dose of 0.1 millilitre of Gadobutrol Farmak per kg of body weight is recommended (meaning a 70 kg person would receive a 7 millilitre dose). However, within 30 minutes of the first injection, an additional injection may be given, up to 0.2 millilitres per kilogram of body weight. For central nervous system (CNS) imaging and CE-MRA (contrast enhancement in magnetic resonance angiography), the maximum total dose is 0.3 millilitres of Gadobutrol Farmak per kilogram of body weight (meaning a 70 kg person would receive a 21 millilitre dose). The minimum dose for CNS imaging is 0.075 millilitres of Gadobutrol Farmak per kilogram of body weight (meaning a 70 kg person would receive 5.25 millilitres).
Further information on administration and preparation for use of Gadobutrol Farmak can be found at the end of this leaflet.

Dosing in special patient groups
Gadobutrol Farmak is not recommended for patients with severe kidney disease, or for patients who have recently undergone or are awaiting liver transplantation. However, if administration is necessary, the patient should receive only a single dose of Gadobutrol Farmak during the examination and should not receive a second injection within at least 7 days.

Use in newborns, infants, children and adolescents
In children of all ages (including full-term newborns), a single injection dose of 0.1 millilitre of Gadobutrol Farmak per kg of body weight is recommended for all examinations (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), Gadobutrol Farmak should be used in these patients only after careful consideration by the physician. Newborns and infants should receive a single dose during the examination and should not receive a second injection within at least 7 days.

Elderly patients
Dose adjustment is not required for patients aged 65 years and older; however, a blood test should be performed to assess kidney function.

Use of a higher than recommended dose of Gadobutrol Farmak
Overdose is unlikely. However, if it occurs, the physician will treat any symptoms that appear and may perform kidney dialysis to remove Gadobutrol Farmak from the body.
There is no evidence that this prevents nephrogenic systemic fibrosis (NSF, see section 4), and it should not be used as a treatment for this condition. In some cases, a heart examination may be performed.

If you have any further doubts regarding the use of this medicine, please consult your doctor or the MRI facility staff.

4. Possible adverse reactions

Like all medicines, this medicinal product may cause adverse reactions, although not everybody will experience them.
Most of these reactions occur within half an hour after administration of gadobutrol. In rare
cases, delayed allergic reactions or other types of adverse reactions have been observed,
occurring from several hours to several days after administration of gadobutrol. If a patient notices
any symptoms of an allergic reaction, they should contact their doctor or radiologist immediately.
The most severe adverse reactions (in some cases life-threatening or fatal) are:

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

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

• shortness of breath (dyspnea), loss of consciousness, severe allergic-type reaction, significant drop in blood pressure which may lead to collapse, respiratory arrest, fluid in the lungs, swelling of the mouth and throat, and low blood pressure.

In rare cases, the following have been reported:

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

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), the MRI facility staff must be informed immediately. The above symptoms may be the first signs of a severe reaction. It may be necessary to discontinue the examination and initiate further treatment.

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

• headache, nausea (feeling of sickness), dizziness.

Most adverse reactions are mild to moderate in severity.
Possible adverse reactions observed in clinical trials prior to the marketing authorization of gadobutrol are listed below according to their likelihood of occurrence.
Common (may occur in up to 1 in 10 people):

• headache,
• nausea (feeling of sickness).

Uncommon (may occur in up to 1 in 100 people):

• hypersensitivity reactions, e.g.:
• low blood pressure,
• hives,
• facial swelling,
• eyelid swelling (periorbital edema),
• redness.

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

• severe hypersensitivity reaction (anaphylactic shock),
• serious drop in blood pressure which may lead to collapse (shock),
• respiratory arrest,
• breathing difficulties (bronchospasm),
• blue discoloration of the lips,
• swelling of the mouth and throat,
• laryngeal edema,
• increase in blood pressure,
• chest pain,
• swelling of the face, throat, lips, mouth and/or tongue (angioedema),
• conjunctivitis,
• excessive sweating,
• cough,
• sneezing,
• burning sensation,
• pale skin (pallor),
• dizziness, taste disturbances, tingling and numbness,
• shallow breathing (dyspnea),
• vomiting,
• skin redness (flushing),
• itching (including generalized itching),
• rash (including generalized rash, small flat red spots [macular rash], small raised localized lesions [papular rash], itchy rash [pruritic erythema]),
• various injection site reactions (e.g. leakage into surrounding tissues, burning sensation, cold sensation, warm sensation, redness, rash, pain or bruising),
• feeling of warmth.

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

• fainting,
• seizures,
• impaired sense of smell,
• rapid heartbeat,
• palpitations,
• dry mouth,
• malaise (weakness),
• feeling of cold.

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

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

After administration of gadobutrol, 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 adverse reactions not listed in this leaflet, inform your doctor or radiologist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 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 medicinal product.

5. How to store Gadobutrol Farmak

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 the outer carton after: EXP. The expiry date refers to the last day of the stated month.
There are no special storage instructions for this medicine.
Chemical, physical, and microbiological stability has been demonstrated for 24 hours at 20–25°C during use. From a microbiological standpoint, the medicine should be used immediately after opening.
This medicine is a clear, colourless to slightly yellow solution. Do not use this medicine if you notice significant discolouration or the presence of particulate matter, or if the container appears damaged.
Medicines must not be disposed of via the sewage system or household waste. Medical personnel will dispose of this medicine when it is no longer needed. This practice helps protect the environment.

6. Contents of the packaging and other information

What Gadobutrol Farmak contains

• The active substance is gadobutrol. 1 millilitre of injection solution contains 604.72 mg of gadobutrol (as monohydrate), equivalent to 1.0 mmol gadobutrol.
• The other ingredients are: sodium calcbutrol, trometamol, diluted hydrochloric acid, and water for injections.

What Gadobutrol Farmak looks like and contents of the pack
Gadobutrol Farmak is a clear, colourless to slightly yellow solution.
Available pack sizes for Gadobutrol Farmak:
5 mL, 7.5 mL and 10 mL in pre-filled syringes with a nominal capacity of 10 mL made of clear
Type I glass, closed with a bromobutyl rubber stopper and a syringe cap.
15 mL in pre-filled syringes with a nominal capacity of 20 mL made of clear Type I glass,
closed with a bromobutyl rubber stopper and a syringe cap.
1 pre-filled syringe per blister. The pack contains 1 or 5 blisters in a cardboard box.
Not all pack sizes may be marketed.
Marketing Authorisation Holder
Farmak International Sp. z o.o.
ul. Koszykowa 65
00-667 Warsaw
tel. +48 22 822 93 06
Importer
Farmak International Sp. z o.o.
ul. Chełmżyńska 249
04-458 Warsaw
This medicinal product is authorised for marketing in the European Economic Area countries under the following names:
Poland: Gadobutrol Farmak
Czech Republic: Gadobutrol FMK
Slovakia: Gadobutrol FMK 1,0 mmol/mL injekčný roztok v naplnenej injekčnej striekačke
Germany: Gadobutrol Farmak 1,0 mmol/mL Injektionslösung in einer Fertigspritze
Spain: Gadobutrol Farmak 1 mmol/mL solución inyectable en jeringa precargada

Information intended exclusively for healthcare professionals:

• Renal function disorders

All patients should be evaluated for renal function impairment prior to administration of Gadobutrol Farmak,
including laboratory testing.
Cases of nephrogenic systemic fibrosis (NSF) have been reported following the use of certain gadolinium-containing contrast agents 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 acute renal failure in this patient group is high. Due to the potential risk of NSF, Gadobutrol Farmak should be administered to patients with severe renal impairment and patients in the perioperative period of liver transplantation only after careful assessment of benefit-risk ratio and if the diagnostic information is essential and cannot be obtained by non-contrast MRI. If use of Gadobutrol Farmak is necessary, the dose should not exceed 0.1 mmol/kg body weight. More than one dose should not be administered during a single imaging session. Due to lack of data on repeated administration, injections of Gadobutrol Farmak should not be repeated unless the intervals between injections are at least 7 days.
Because renal clearance of gadobutrol may be reduced in elderly patients, monitoring for renal function impairment is particularly important in patients aged 65 years and older.
Hemodialysis performed shortly after administration of Gadobutrol Farmak may facilitate its elimination from the body.
There is no evidence to support initiating hemodialysis for the prevention or treatment of NSF in patients not already undergoing hemodialysis.

• Pregnancy and breastfeeding

Gadobutrol Farmak should not be used during pregnancy unless the clinical condition of the woman justifies the use of gadobutrol.
The physician and the breastfeeding mother should decide whether to continue breastfeeding or discontinue it for 24 hours after administration of Gadobutrol Farmak.

• Hypersensitivity reactions

As with other contrast agents, administration of Gadobutrol Farmak may carry a risk of anaphylactoid, hypersensitivity, or idiosyncratic reactions, presenting with cardiovascular, respiratory, or cutaneous symptoms, up to severe reactions including shock. In general, patients with cardiovascular diseases are more susceptible to serious adverse events, including death, due to severe hypersensitivity reactions.
The risk of hypersensitivity reactions may be increased in the following cases:

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

In patients with a predisposition to allergies, the decision to administer Gadobutrol Farmak must be made after particularly careful assessment of the benefit-risk ratio.
Most reactions occur within 30 minutes after administration. Therefore, patient monitoring after the examination is recommended.
Access to medications used in the treatment of hypersensitivity reactions and preparedness to implement emergency procedures should be ensured.
Delayed reactions (occurring several hours to several days after administration) have been observed rarely.

• Seizure disorders

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

• Overdose

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

• Before injection

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

• Instructions for use

The pre-filled syringe should be removed from the packaging and prepared for injection immediately before administration.
The cap should be removed from the pre-filled syringe immediately before use.
MANUAL INJECTION

1. Open the package 2. Screw the plunger into the syringe

3. Break the safety seal 4. Remove the cap from the tip

5. Remove the rubber stopper 6. Remove air from the syringe

Any unused solution remaining after a single examination must be discarded in accordance with local regulations.

• Stability after first opening

Any unused solution remaining after a single 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 after opening. If not used immediately, the storage time and conditions prior to use are the responsibility of the medical personnel.
The detachable identification label from the pre-filled syringe should be attached to the patient's records to allow accurate identification of the gadolinium-containing contrast agent used. The administered dose should also be documented. If electronic patient records are used, 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 should not exceed the recommended dose per kilogram of body weight specified in this section.

• Adults

CNS examination:
The recommended dose for 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, despite a negative MRI result, there remains a strong clinical suspicion of pathology or if additional information may influence patient management, a second injection may be administered, increasing the total dose to a maximum of 0.2 mL/kg b.w. within 30 minutes of the first administration. For CNS imaging, the minimum dose that may be administered is 0.075 mmol gadobutrol per kg body weight (equivalent to 0.075 mL of Gadobutrol Farmak per kg body weight).
Whole-body MRI (excluding MRA):
For diagnostic purposes, a dose of 0.1 mL/kg b.w. of Gadobutrol Farmak is usually sufficient.
Angiographic examination (CE-MRA):
Imaging of 1 field of view (FOV): 7.5 mL for body weight below 75 kg; 10 mL for body weight of 75 kg and above (corresponding to 0.1–0.15 mmol/kg b.w.)
Imaging of more than 1 field of view (FOV): 15 mL for body weight below 75 kg; 20 mL for body weight of 75 kg and above (corresponding to 0.2–0.3 mmol/kg b.w.)

• Children and adolescents

In children of all ages (including full-term newborns), the recommended dose is 0.1 mmol gadobutrol per kg body weight (equivalent to 0.1 mL of Gadobutrol Farmak per kg body weight) for all indications (see section 1).
Due to immature renal function in newborns up to 4 weeks of age and infants up to 1 year of age, Gadobutrol Farmak 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 multiple administrations, injections of Gadobutrol Farmak should not be repeated unless the intervals between injections are at least 7 days.

Imaging
The required dose is administered intravenously as a bolus. Contrast-enhanced magnetic resonance imaging may be initiated immediately after injection (shortly after injection, depending on the pulse sequences and imaging protocol used).
Optimal signal enhancement is observed during the first pass of blood through the arteries for CE-MRA and within approximately 15 minutes after injection of Gadobutrol Farmak for CNS indications (timing depends on the type of lesion/tissue).
T1-weighted sequences are particularly useful for contrast-enhanced examinations.
Further information on the use of Gadobutrol Farmak is provided in section 3 of the package leaflet.