Primovist

Package leaflet: Information for the user

Primovist, 0,25 mmol/ml, solution for injection, pre-filled syringe
Dinatrii gadoxetas
Please read all of this leaflet carefully before the patient is given this medicine, because it contains
important information for the patient.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask the doctor who prescribed Primovist.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor. See section 4.

Contents of the leaflet:

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

1. What Primovist is and what it is used for

Primovist is a contrast agent used in magnetic resonance imaging (MRI) of the liver. It is used to enable diagnosis and improve the detection of lesions that may be present in the liver. It allows better assessment of abnormal liver lesions, including their number, size, and location. Primovist may also help the doctor determine the nature of the lesions, thereby increasing diagnostic confidence.
Primovist is intended for intravenous injection. This product is intended for diagnostic use only.
MRI is a type of diagnostic examination that uses differences in the distribution and amount of water molecules in normal and abnormal tissues to create images. This technique is based on the use of a complex system of magnets and radio waves.

2. Important information before using Primovist

When not to use Primovist

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

Warnings and precautions
Before using Primovist, discuss with the doctor if the patient:

• currently has or has had asthma or allergies (such as hay fever, hives) in the past;
• previously experienced an allergic reaction after administration of a contrast agent;
• has impaired kidney function. Use of certain gadolinium-containing contrast agents in such patients has been associated with nephrogenic systemic fibrosis (NSF). NSF is a disease causing thickening of the skin and connective tissue. NSF may lead to disability due to joint immobilization, muscle weakness, or impaired function of internal organs, and thus may be life-threatening;
• has severe cardiovascular disease;
• has low potassium levels;
• or has a family history of heart rhythm abnormalities on electrocardiogram (ECG) known as long QT syndrome;
• has experienced irregular heart rhythm after taking medications;
• has a cardiac pacemaker or any implant or stent containing iron.

Delayed allergic-like reactions may occur after administration of Primovist. These reactions may appear several hours or days later. See section 4.
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 monitor kidney function before deciding to use Primovist, especially in patients over 65 years of age.

Retention in the body
Primovist works because it contains a metal called gadolinium. Studies have shown that small amounts of gadolinium may deposit in the body, including in the brain. No adverse effects related to gadolinium deposition in the brain have been observed.

Children and adolescents
The safety and efficacy of Primovist in children under 18 years of age have not been established due to limited experience with use in this population. More information can be found at the end of this leaflet.

Primovist 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. In particular:

• beta-blockers, medicines used to treat high blood pressure or heart diseases;
• medicines affecting heart rhythm or rate, such as amiodarone, sotalol;
• rifampicin, a medicine used to treat tuberculosis or certain other infections.

Pregnancy and breastfeeding
Pregnancy
Women who are pregnant or suspect they may be pregnant should inform their doctor, as Primovist 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 receiving Primovist.

Driving and using machines
Primovist has no influence on the ability to drive or operate machinery.

Primovist contains sodium
The medicine contains 82 mg of sodium (the main component of table salt) per dose unit based on the amount administered to a 70 kg body weight individual. This corresponds to 4.1% of the maximum recommended daily dietary sodium intake for adults.

3. How to use Primovist

Primovist is administered via a small needle into a vein, just before starting the magnetic resonance imaging (MRI) examination.
After injection of the contrast agent, the patient will remain under observation for at least 30 minutes.
The recommended dose is
0.1 ml of Primovist per kg of body weight.
Dosing in special patient groups
Primovist is not recommended for patients with severe kidney disease, and in patients who have recently undergone or are scheduled to undergo liver transplantation. However, if use of the product is necessary, the patient should receive only one dose of Primovist during the examination and should not receive a second injection within at least 7 days.
Elderly patients
Dose adjustment is not required for patients over 65 years of age; however, a blood test should be performed to monitor kidney function.
Administration of a higher than recommended dose of Primovist
The risk of overdose is very low. If symptoms of overdose occur, a doctor will monitor their course and take appropriate action.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
Most of these adverse reactions are mild or moderate.
If any adverse symptoms occur, inform your doctor.
As with other contrast agents, allergic-like reactions may rarely occur.
After administration of Primovist, delayed reactions may appear after several hours or days.
The most serious adverse reaction in patients receiving Primovist is anaphylactoid shock (severe allergic reaction).
If any of the following symptoms occur or if you experience difficulty breathing, inform your doctor immediately:

• low blood pressure
• swelling of the tongue, throat, or face
• runny nose, sneezing, cough
• red, watery, itchy eyes
• stomach pain
• urticaria (hives)
• decreased or altered skin sensation, itching, pale skin

The following additional adverse reactions may occur:
Common: may affect up to 1 in 10 people

• headache
• nausea

Uncommon: may affect up to 1 in 100 people

• dizziness
• numbness and tingling
• disturbances of taste or smell
• flushing
• increased blood pressure
• breathing difficulties
• vomiting
• dry mouth
• skin rash
• intense itching of the whole body or eyes
• back pain, chest pain
• injection site reactions such as
• burning, cold, irritation, or pain sensation
• feeling of warmth
• chills
• fatigue
• malaise

Rare: may affect up to 1 in 1000 people

• inability to sit or stand for long periods
• uncontrollable tremor
• sensation of strong heartbeat
• irregular heartbeat (symptoms of heart block)
• oral discomfort, increased salivation
• red rash with bumps or spots on the skin
• excessive sweating
• discomfort sensation, general malaise

Not known: frequency cannot be estimated from available data

• rapid heartbeat
• restlessness

Following administration of the contrast agent Primovist, altered laboratory test results have been observed. Inform the medical staff performing blood or urine tests if Primovist has recently been administered.
Cases of nephrogenic systemic fibrosis (a disease associated with skin hardening, which may also affect soft tissues and internal organs) have been reported in association with the use of other medicinal products containing gadolinium.

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor or the MRI facility staff. 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 medicine.

5. How to store Primovist

The product should be stored out of sight and reach of children.
Do not use this contrast agent after the expiry date stated on the label on the syringe and on the carton. The expiry date refers to the last day of the stated month.
No special precautions for storage of the medicinal product.
The product should be used immediately after opening.
Before use, visually inspect the solution. Do not use if significant discoloration or presence of particulate matter is observed, or if the packaging is damaged.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures will help protect the environment.

6. Contents of the pack and other information

What Primovist contains

• The active substance is gadoxetate disodium. 1 ml of injection solution contains 0.25 mmol of gadoxetate disodium (corresponding to 181.43 mg of gadoxetate disodium).
• Other components of the product are: trisodium caloxetate, trometamol, sodium hydroxide and diluted hydrochloric acid (both used for pH adjustment), water for injections.

1 pre-filled syringe with 5.0 ml contains 907 mg of gadoxetate disodium,
1 pre-filled syringe with 7.5 ml contains 1361 mg of gadoxetate disodium (glass syringe only),
1 pre-filled syringe with 10.0 ml contains 1814 mg of gadoxetate disodium.

What Primovist looks like and contents of the pack
Primovist is a clear, colourless or slightly yellow solution free from solid particles. Pack sizes consist of 1, 5 or 10 pre-filled syringes containing:

• 5 ml of injection solution (in a 10 ml glass or plastic pre-filled syringe)
• 7.5 ml of injection solution (in a 10 ml glass pre-filled syringe) (glass syringe only)
• 10 ml of injection solution (in a 10 ml glass or plastic pre-filled syringe)

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Bayer AG
Kaiser-Wilhelm-Allee 1
51373 Leverkusen
Germany

Manufacturer
Bayer AG
Mullerstrasse 178
13353 Berlin
Germany

For further information, contact the representative of the Marketing Authorisation Holder:
Bayer Sp. z o.o.
Al. Jerozolimskie 158
02-326 Warsaw
Phone: (0-22) 572 35 00

Information intended exclusively for medical professionals.

Renal function impairment
Prior to administration of Primovist, it is recommended that all patients be evaluated for renal function impairment, including laboratory tests.
Cases of nephrogenic systemic fibrosis (NSF) associated with the use of certain gadolinium-containing medicinal products have been reported in patients with acute or chronic severe renal impairment (GFR < 30 ml/min/1.73 m²). Patients undergoing liver transplantation are at particularly high risk, as the likelihood of acute renal failure in this patient group is elevated. Due to the risk of NSF with the use of Primovist, administration of this medicinal product should be avoided in patients with severe renal impairment and in patients during the perioperative period of liver transplantation, unless the diagnostic information is essential and cannot be obtained by non-contrast MRI. If administration of Primovist cannot be avoided, the dose should not exceed 0.025 mmol/kg body weight. No more than a single dose should be administered per imaging session. Due to lack of data on repeated administration, injections of Primovist should not be repeated unless the interval between doses is at least 7 days.

Since renal clearance of gadoxetate may be reduced in elderly patients, particularly careful monitoring of renal function is essential in patients aged 65 years and older.

Hemodialysis immediately after administration of Primovist may facilitate elimination of the product from the body. However, there is no evidence to support initiating hemodialysis for the prevention or treatment of NSF in patients not already undergoing hemodialysis.

Pregnancy and breastfeeding
Primovist should not be used during pregnancy unless the clinical condition of the woman necessitates the use of gadoxetate.

The physician and the breastfeeding mother should decide whether to continue breastfeeding or to discontinue it for a period of 24 hours following administration of Primovist.

Children and adolescents
An observational study was conducted in 52 pediatric patients (aged over 2 months and below 18 years) who underwent liver MRI with Primovist to evaluate suspected or known focal liver lesions. Additional diagnostic information was obtained by comparing contrast-enhanced and non-contrast-enhanced MRI images of the liver, in comparison to non-contrast MRI images. No reported serious adverse reactions were considered by the investigator to be related to the use of Primovist. Due to the retrospective nature and small sample size of this study, definitive conclusions regarding efficacy and safety in this population cannot be drawn.

Before administration
Primovist is a clear, colorless or slightly yellow solution, free from visible particles. The medicinal product should always be visually inspected before use. If significant discoloration, presence of particles in the solution, or container damage is observed, the contrast agent must not be used.

Administration
Primovist should be administered intravenously as an undiluted injection at a flow rate of approximately 2 ml/s. After injection, the cannula/line should be flushed with physiological saline (9 mg/ml).

• After injection, the patient should be observed for at least 30 minutes.
• Primovist must not be administered simultaneously with other medicinal products.
• Intramuscular administration of Primovist is not permitted.

Preparation
Primovist is a ready-to-use solution.
The pre-filled syringe should be prepared immediately before the injection.
The cap should be removed from the pre-filled syringe immediately before use.
Any unused contrast agent remaining after a single examination must be discarded in accordance with applicable national regulations.
The detached label from the pre-filled syringe should be attached to the patient's chart to ensure proper documentation of the gadolinium-containing medicinal product used. The administered dose should also be documented. If electronic patient records are used, the product name, batch number, and dose should be entered into the patient's record.

Glass pre-filled syringes:

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

3. Break the cap protection 4. Remove the cap from the tip

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

Plastic pre-filled syringes
Manual injection Injection using an injector

1. Remove the syringe and plunger 1. Remove the syringe

2. Screw the plunger into the syringe in a clockwise direction 2. Open the tip cap by twisting

3. Connect the syringe tip to the
4. Open the tip cap by twisting clockwise and proceed according to instructions. drain

4. Remove air from the syringe