Prohance

PATIENT INFORMATION LEAFLET: USER INFORMATION

ProHance, 279.3 mg/ml (0.5 mmol/ml), solution for injection
Gadoteridol

Read the leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• In case of any doubts, consult a doctor or nurse.
• This product has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including any not listed in this leaflet, they should inform their doctor or nurse. See section 4.

Table of contents of the leaflet:

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

1. What is ProHance and what is it used for

Product intended exclusively for diagnostic purposes.
The active substance of ProHance is gadoteridol - a non-ionic paramagnetic contrast agent
used in magnetic resonance imaging (MRI).
Gadoteridol does not pass through the intact blood-brain barrier and therefore does not accumulate in
normal brain structures or in lesions where the blood-brain barrier has not been damaged, e.g. cysts, mature postoperative scars, etc. However, disruption of the blood-brain barrier or the presence of blood vessels allows gadoteridol to reach such lesions as tumors, abscesses, or subacute strokes.
ProHance is used in MRI examinations of the central nervous system (brain and spinal cord) and surrounding tissues. The use of ProHance improves the visibility (compared to MRI without contrast agent) of pathological changes with abnormal vascularization or where blood-brain barrier damage is suspected.
ProHance is also indicated for whole-body MRI, including: head, neck, liver, breast, musculoskeletal system, and soft tissues, to improve the visibility of pathological changes in soft tissues and parenchymal organs.

2. Important information before using ProHance

ProHance should only be used in hospitals or medical facilities where means and personnel trained in the management of allergic reactions are available.

When not to use ProHance

Do not use ProHance:

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

Warnings and precautions

Inform your doctor that:

• the patient has or has had an allergy;
• the patient's kidneys do not work properly;
• the patient has recently undergone or is scheduled to undergo a liver transplant
• the patient has a history of epilepsy or brain changes.

Always consider the possibility of severe, life-threatening, or fatal anaphylactic reactions or idiosyncratic reactions (reactions specific to a given patient).
The possibility of these reactions should be particularly expected in patients with clinically confirmed hypersensitivity to the ingredients of the medicine, asthma, and other allergic reactions involving the respiratory system in their history.
When using contrast agents, appropriate medications and equipment for cardiopulmonary resuscitation must be available, and patients with a history of allergy, drug reactions, or other pseudo-allergic disorders should be closely monitored during the administration of the contrast agent, during the examination, and after its completion for a period considered necessary by the doctor.
In vitro studies have shown that under the influence of gadolinium chelates, deoxygenated sickle red blood cells align linearly and perpendicularly to the magnetic field, which in in vivo studies may cause complications resulting from the closure of blood vessels. No studies have been conducted in patients with sickle cell anemia, other hemoglobinopathies, or hemolytic anemias to rule out the possibility of exacerbating hemolysis. Therefore, caution is recommended when administering the contrast agent.
Repeating examinations: No studies have been conducted on the repeated performance of examinations. Only cases where two consecutive administrations were used in the same session for imaging of central nervous system structures have been studied.
When using ProHance, it is recommended to follow the generally accepted precautions during MRI examinations, especially in patients with a pacemaker or aneurysm clips and other elements with ferromagnetic properties. In such cases, the examination by this method (with or without contrast agent) may only be performed if the safety of using the metal element in the MRI examination has been previously proven.
To avoid extravasation of ProHance, it is essential to exercise particular caution when administering the contrast agent.
The doctor may decide to perform a blood test to check kidney function before deciding to use ProHance, especially in people over 65 years old.

Special patient groups

Elderly patients
Elderly patients should be cautious when using and after using the medicine.
Patients with renal impairment
Gadoteridol is excreted from the body by the kidneys, so caution should be exercised when using and after using the medicine in patients with impaired renal function.
Newborns and infants
Due to the not fully developed kidney function in children up to 4 weeks of age and infants up to 1 year of age, ProHance should only be used in these patients after careful consideration of the justification for such treatment by the doctor.

• 1. The doctor should carefully consider the justification for using ProHance in newborns and infants.

Pregnancy, breastfeeding, and fertility

Before using any medicine, consult a doctor.
Pregnancy
Gadoteridol may pass through the placenta. It is not known whether this affects the fetus. Women who think they are pregnant or may be pregnant should inform their doctor,
as ProHance should not be used during pregnancy unless absolutely necessary.
Breastfeeding
Breastfeeding women or those planning to breastfeed should inform their doctor.
The doctor will discuss with the patient whether she should continue breastfeeding or stop breastfeeding for 24 hours after using ProHance.

Driving and using machines

There is no information on the effect of ProHance on the ability to drive vehicles, use tools, or operate machines.
Ask your doctor if you can drive and use machines safely.

ProHance and other medicines

There are no reports of interactions between ProHance and other medicines.
Inform your doctor about all medicines you are currently taking or have recently taken, including those available without a prescription.

ProHance contains sodium

This medicine contains less than 1 mmol (23 mg) of sodium per dose, which means the medicine is considered "sodium-free".

3. How to use ProHance

Use the lowest effective dose for examinations.
Adults:
MRI examinations of the musculoskeletal system: the recommended dose of ProHance is 0.2 ml/kg body weight (0.1 mmol/kg body weight).
MRI examinations of the brain, spinal cord, liver, breast, and pelvis: from 0.2 ml/kg body weight to 0.6 ml/kg body weight (0.1 mmol/kg body weight to 0.3 mmol/kg body weight).
In most applications, the standard dose of 0.2 ml/kg body weight (0.1 mmol/kg body weight) is sufficient.
A dose of 0.6 ml/kg body weight (0.3 mmol/kg body weight) is intended for patients suspected of having brain metastases or other poorly contrasting lesions.
In patients suspected of having poorly contrasting lesions, or in cases of unclear or absent examination results, a second dose of 0.4 ml/kg body weight (0.2 mmol/kg body weight) may be administered 30 minutes after the first dose.
The medicine should be administered as a rapid intravenous injection or bolus.
To minimize the potential risk of extravasation of ProHance, it is essential to ensure that the needle for intravenous injections or the cannula is properly inserted into the vein.
After injecting the medicine, the remaining cannula or needle should be flushed with 5 ml of physiological saline solution intravenously to ensure complete injection of the contrast agent. The examination should be completed within 1 hour of administering ProHance.
Additional dose
The use of an additional dose during the same examination has been analyzed only in the diagnostic procedure for the central nervous system in adults. If the doctor considers it necessary to repeat the dose, a second dose can be administered 30 minutes after the first dose.
Re-examination
Repeat contrast-enhanced MRI examinations should not be performed earlier than 6 hours after the first examination, which allows for the elimination of the contrast agent from the body.

Dosing in special patient groups

ProHance is not recommended for patients with severe kidney disease or those who have recently undergone or are scheduled to undergo a liver transplant.
If the use of ProHance is necessary, the patient should receive only one dose of ProHance during the examination and should not receive a second injection for at least 7 days.
Newborns, infants, children
Children
MRI examinations of the brain and spine: the recommended dose of ProHance is 0.2 ml/kg body weight (0.1 mmol/kg body weight).
The safety and efficacy of using doses greater than 0.2 ml/kg body weight and repeated doses have not been evaluated in children. Therefore, doses greater than 0.2 ml/kg body weight should not be used in children, and repeat examinations should not be performed.
Due to the not fully developed kidney function in children up to 4 weeks of age and infants up to 1 year of age, ProHance should only be used in these patients after careful consideration of the justification for such treatment by the doctor. Newborns and infants should receive only one dose of ProHance during the examination and should not receive a second injection for at least 7 days.

• 1. The doctor should carefully consider the justification for using ProHance in newborns and infants.

ProHance is not recommended for use in whole-body MRI examinations in children under 18 years of age.
Elderly patients
There is no need to adjust the dose in patients over 65 years old, but a blood test should be performed to check kidney function.

Instructions for using ProHance

ProHance must not be diluted. It should be drawn into a syringe immediately before use.
Before use, the medicine and packaging should be inspected to ensure that they are not damaged, have not changed color, or have not precipitated.
ProHance must not be mixed or administered through the same access to the vessel as other medicines or parenteral nutrition products due to the possibility of chemical incompatibilities.
Any unused product or waste material should be disposed of in accordance with local regulations.

Using more than the recommended dose of ProHance

No cases of ProHance overdose have been reported. In case of overdose, supportive measures should be initiated, and symptomatic treatment should be started.
ProHance can be removed by dialysis.

4. Possible side effects

Like all medicines, ProHance can cause side effects, although not everybody gets them.
Frequent (more than 1 in 100 and less than 1 in 10 patients)

• Nausea

Uncommon (more than 1 in 1,000 and less than 1 in 100 patients)

• Headache, sensation disturbances, dizziness, taste disturbances
• Lacrimation
• Flushing, low blood pressure
• Dry mouth, vomiting
• Pruritus, rash, itching
• Pain at the injection site
• Increased heart rate
• Fatigue
• Reactions at the injection site

Rare (more than 1 in 10,000 and less than 1 in 1,000 patients)

• Hypersensitivity reactions (most commonly reported symptoms include feeling of constriction in the throat, throat irritation, difficulty breathing, discomfort in the chest, feeling of heat, difficulty swallowing, burning sensation, throat edema, and low blood pressure)
• Anxiety
• Disorientation, lack of coordination, seizures
• Tinnitus
• Changes in heart rhythm
• Laryngospasm, shallow breathing, rhinorrhea, cough, transient apnea, wheezing
• Abdominal pain, tongue edema, oral itching, gingivitis, diarrhea
• Facial edema
• Muscle stiffness
• Chest pain, fever

Frequency not known (cannot be estimated from the available data)

• Loss of consciousness
• Coma
• Cardiac arrest
• Respiratory arrest, pulmonary edema
• Kidney function disorders
• Vasovagal reaction - the most common symptoms are drowsiness, dizziness, and excessive sweating. In the most severe cases, pallor, excessive sweating, bradycardia, and potential loss of consciousness may occur. Additional symptoms may include anxiety, restlessness, feeling of fainting, and excessive salivation.

As with other gadolinium chelates, anaphylactic reactions, pseudo-anaphylactic reactions, and hypersensitivity reactions have been reported. These reactions had varying degrees of severity, including anaphylactic shock and death. They involved one or more systems, primarily the respiratory, cardiovascular, and (or) skin and mucous membranes.
Cases of nephrogenic systemic fibrosis (NSF) have been reported in association with the use of some gadolinium-containing products in patients with acute or chronic severe kidney function impairment (GFR <30 ml min 1.73 m). patients undergoing liver transplantation are particularly at risk, as the risk of acute kidney injury in this patient group is high. due to possibility nsf during use prohance, its with severe function impairment and perioperative period only possible after careful evaluation benefit-risk ratio if diagnostic information essential not available for mri without contrast enhancement. prohance necessary, dose should exceed 0.1 mmol kg body weight. no more than one be administered imaging. lack data on repeated administrations it unless intervals between injections least 7 days.
Children
The safety profile of ProHance is similar in children and adults.
If any side effects worsen or any side effects not listed in this leaflet occur, inform your doctor or pharmacist.

Reporting side effects

If side effects occur, including any not listed in this leaflet, inform your doctor or pharmacist.
Side effects can be reported directly to the Department of Drug Safety Monitoring of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, tel.:

• (22) 49 21 301, fax: (22) 49 21 309, website: https://smz.ezdrowie.gov.pl Side effects can also be reported to the marketing authorization holder. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store ProHance

Store at a temperature not exceeding 25°C. Protect from light. Do not freeze.
Vials or prefilled syringes that have been frozen should be destroyed.
Store in a place inaccessible to children.
Do not use the medicine after the expiry date stated on the carton or vial. The expiry date refers to the last day of the specified month.

6. Contents of the pack and other information

What ProHance contains

The active substance is gadoteridol.
ProHance also contains: calcium calteridol salt, trometamine, hydrochloric acid or sodium hydroxide to adjust the pH, water for injections.

What ProHance looks like and contents of the pack

ProHance is a colorless or slightly yellowish aqueous solution.
ProHance is available in vials, prefilled syringes:
1 or 5 vials of 5, 10, 15, or 20 ml; 1 vial of 50 ml; 10 vials of 50 ml.
1 or 5 prefilled syringes of 10, 15, or 17 ml.
Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder:

Bracco Imaging Deutschland GmbH
Max-Stromeyer-Strasse 116
D-78467 Konstanz, Germany

Manufacturer:

vial:
BIPSO GmbH - Robert-Gerwig-Str. 4, 78224 Singen. Germany
Bracco Imaging S.p.A.- Bioindustry Park - Via Ribes 5, 10010 Colleretto Giacosa. Italy
Prefilled syringe:
Bracco Imaging S.p.A.- Bioindustry Park - Via Ribes 5, 10010 Colleretto Giacosa. Italy

For more information, contact the representative of the marketing authorization holder:

Bracco Imaging Polska Sp. z o.o.
ul. Domaniewska 39 A
02-672 Warsaw
tel: + 48 22 208 24 20

Date of last revision of the leaflet: 05/2024 ---------------------------------------------------------------------------------------------------------------

Information intended exclusively for healthcare professionals:

Before administering ProHance, it is recommended to perform a kidney function test in all patients.

Cases of nephrogenic systemic fibrosis (NSF) have been reported in association with the use of some gadolinium-containing products in patients with acute or chronic severe kidney function impairment (GFR <30 ml min 1.73 m). patients undergoing liver transplantation are particularly at risk, as the risk of acute kidney injury in this patient group is high. due to possibility nsf during use prohance, its with severe function impairment and perioperative period only possible after careful evaluation benefit-risk ratio if diagnostic information essential not available for mri without contrast enhancement. prohance necessary, dose should exceed 0.1 mmol kg body weight. no more than one be administered imaging. lack data on repeated administrations it unless intervals between injections least 7 days.
Due to the not fully developed kidney function in children up to 4 weeks of age and infants up to 1 year of age, ProHance should only be used in these patients after careful consideration of the benefit-risk ratio in this patient group, at a dose not exceeding 0.1 mmol/kg body weight. No more than one dose should be administered during imaging. Due to the lack of data on repeated administrations, ProHance injections should not be repeated unless the intervals between injections are at least 7 days.

• 1. The doctor should carefully consider the justification for using ProHance in newborns and infants.

Because the renal clearance of gadoteridol may be decreased in elderly patients, particularly in those over 65 years old, it is essential to monitor these patients for kidney function disorders.
Hemodialysis immediately after administering ProHance may facilitate the removal of ProHance from the body. There is no evidence to support the initiation of hemodialysis to prevent or treat NSF in patients not yet undergoing hemodialysis.
ProHance should not be used during pregnancy unless the clinical condition of the woman indicates the need for gadoteridol.
The doctor and the breastfeeding mother should decide whether to continue breastfeeding or stop breastfeeding for 24 hours after administering ProHance.
The label torn from the vial or prefilled syringe should be attached to the patient's card to enable proper registration of the administered gadolinium-containing product.
The dose should also be recorded.
The name of the medicinal product, batch number, and dose should be entered into the patient's electronic medical record.
The osmolality of ProHance is 2.2 times higher than the osmolality of blood serum (285 mOsmol/kg water). ProHance is a hypertonic solution under conditions of use.
Osmolality at 37°C: 630 mOsm/kg water
Viscosity at 20°C: 2.0 cP
Viscosity at 37°C: 1.3 cP
Specific gravity at 25°C: 1.140
Density at 25°C: 1.137 g/cm
Octanol: water partition coefficient: -3.68 ± 0.02