Gadobutrol farmak

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

• Keep this leaflet for future reference.
• If you have any questions, please consult your doctor (radiologist) or MRI facility staff.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or MRI facility staff immediately. See section 4.

Table of contents

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

Gadobutrol Farmak is a contrast agent used during magnetic resonance imaging (MRI) of the brain, spinal cord, and blood vessels. Gadobutrol Farmak may also help the physician 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 visualize abnormal structures or lesions and assists in differentiating between healthy and diseased tissue.
The medicine is used in adults as well as in children of all ages (including full-term newborns).

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

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,
• previously experienced a reaction to any contrast agent,
• has severely impaired kidney function,
• has a brain disorder with seizures or other neurological disorders,
• has a cardiac pacemaker implanted or any implants or clips containing iron in the body. The doctor will decide whether the planned examination can be performed.
• After administration of Gadobutrol Farmak, allergic-type reactions or other types of reactions causing heart disturbances, 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 do not function 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 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 the patient is currently taking or has recently taken, as well as any medicines the patient plans to take.
Pregnancy and breastfeeding
Before using any medicine, consult a doctor.

• Pregnancy Gadobutrol may cross the placenta. It is not known whether this affects the unborn child. Women who suspect they are pregnant or who could 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 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 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 thin needle by medical personnel.
Magnetic resonance imaging (MRI) may begin immediately.
After injection, the patient will be observed for at least 30 minutes.
Typical 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 will 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 kg 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 kg of body weight (meaning a 70 kg person will receive a 21 millilitre dose). The minimum dose for CNS imaging is 0.075 millilitres of Gadobutrol Farmak per kg of body weight (meaning a 70 kg person will receive a 5.25 millilitre dose).
More 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 scheduled to undergo liver transplantation. However, if administration of the drug is necessary, the patient should receive only one dose of Gadobutrol Farmak during the examination and should not receive a second injection for 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 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.
Use of a higher than recommended dose of Gadobutrol Farmak
Overdose is unlikely. However, if it occurs, the physician will treat any symptoms that arise and may perform kidney dialysis to remove Gadobutrol Farmak from the body.
There is no evidence that this will prevent 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 medicine can cause adverse reactions, although they do not occur in everyone.
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 within several hours to several days after administration of gadobutrol. If a patient
notices any symptoms of an allergic reaction, they should immediately contact a doctor or
radiologist.
The most serious 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, the following adverse reactions have been observed with life-threatening or fatal outcomes:

• 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-type reactions (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), immediately inform the MRI facility staff. The above symptoms may be the first signs of a severe reaction. It may be necessary to stop 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 nausea), 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 no more than 1 in 10 people):

• headache,
• nausea (feeling of nausea).

Uncommon (may occur in no more than 1 in 100 people):

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

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

• severe hypersensitivity reaction (anaphylactic shock),
• severe 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,
• increased blood pressure,
• chest pain,
• swelling of the face, throat, lips, 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 no more than 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 involving 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, the patient should inform their doctor or radiologist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the 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 gather more information on the safety of the medicine.

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 cardboard box after: EXP. The expiry date refers to the last day of the stated month.
No special storage conditions are required for this medicine.
Chemical, physical, and microbiological stability has been demonstrated for up to 24 hours during use at a temperature of 20–25°C. 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 any 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 will help 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 of gadobutrol.
• The other components are: sodium calcobutrol, 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 for injection.
Available pack sizes for Gadobutrol Farmak:
2 mL, 7.5 mL, 10 mL, 15 mL, 30 mL and 65 mL solution for injection in transparent glass
vials sealed with a bromobutyl rubber stopper and an aluminium seal with a plastic cap.
The pack contains 1 or 10 vials 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 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
Germany: Gadobutrol Farmak 1,0 mmol/mL Injektionslösung
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 disorders, including laboratory tests, prior to administration of Gadobutrol Farmak.
Cases of nephrogenic systemic fibrosis (NSF) associated with the use of certain gadolinium-containing contrast 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 particularly at risk due to the high likelihood of acute renal failure in this patient group. Because of 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 benefit-risk assessment 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 disorders 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 supporting initiation of hemodialysis for the prevention or treatment of NSF in patients not previously undergoing hemodialysis.

• Pregnancy and breastfeeding

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

• Hypersensitivity reactions

As with other contrast agents, administration of Gadobutrol Farmak may be associated with a risk of anaphylactoid, hypersensitivity, or idiosyncratic reactions, manifesting as 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 patients with:

• 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 benefit-risk assessment.
Most reactions occur within 30 minutes after administration. Therefore, it is recommended to observe the patient after the procedure.
Access to medications for treating hypersensitivity reactions and preparedness to implement emergency procedures should be ensured.
Delayed reactions (occurring several hours to several days after administration) have been rarely observed.

• 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 impairment, Gadobutrol Farmak can be removed from the body by hemodialysis. Approximately 98% of the agent is eliminated 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, colorless to slightly yellow solution. The solution should be inspected visually before use.
Gadobutrol Farmak should not be used if significant discoloration, presence of particulate matter, or container damage is observed.

• Instructions for use

Gadobutrol Farmak should be drawn into a syringe from the vial immediately before use.
The rubber stopper should never be punctured more than once.
Any unused contrast agent from a single examination should be discarded.
If this medicinal product is to be used with an automated injection system, its suitability for the intended use must be confirmed by the manufacturer of the medical device. All additional instructions provided by the device manufacturer must also be strictly followed.
Any unused injectable solution remaining after a single examination should be disposed of according to local regulations.

• Stability after first opening

Any unused injectable solution should be discarded after a single use. Chemical, physical, and microbiological stability has been demonstrated for up to 24 hours at 20–25°C. From a microbiological point of view, the product should be used immediately after opening. If not used immediately, the responsibility for storage conditions and duration prior to use lies with the medical personnel.
The detachable identification label from the vial should be attached to the patient's medical record to allow accurate identification of the gadolinium-containing contrast agent used. The administered dose should also be recorded. If electronic patient records are used, the drug name, batch number, and dose should be entered into the patient's record.

• Dosage

The smallest 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 imaging:
The recommended dose for adults is 0.1 mmol per kilogram of body weight (mmol/kg).
This corresponds to 0.1 mL/kg of the 1.0 M solution.
If, despite a negative MRI result, there remains a strong clinical suspicion of pathology or if more detailed information may influence patient management, a second injection may be administered, bringing the total dose up to a maximum of 0.2 mL/kg body weight 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 (corresponding to 0.075 mL of Gadobutrol Farmak per kg body weight).
Whole-body MRI (excluding MRA):
For diagnosis, a dose of 0.1 mL/kg body weight of Gadobutrol Farmak 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 body weight).
Imaging of more than 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 body weight).

• Children and adolescents

In children of all ages (including full-term newborns), the recommended dose is 0.1 mmol gadobutrol per kg body weight (corresponding 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. Magnetic resonance imaging with contrast enhancement 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 arterial pass for CE-MRA and 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.