Primovist

Package Leaflet: Information for the User

Primovist, 0.25 mmol/ml, solution for injection, pre-filled syringe
Sodium gadexetate

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

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

Table of Contents of the Package Leaflet:

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

1. What is Primovist and what is it used for

Primovist is a contrast agent used in liver imaging by magnetic resonance imaging (MRI). It is used to help diagnose and improve the detection of changes that may occur in the liver. It allows for a better assessment of abnormal changes in the liver, their number, size, and distribution. Primovist can also help the doctor determine the type of changes, increasing the reliability of the diagnosis.
Primovist is intended for intravenous injection. The product is for diagnostic use only.
MRI is a type of diagnostic test that uses differences in the distribution and amount of water molecules in healthy and abnormal tissues to create images. The basis of this technique is 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 has been diagnosed with an allergy to sodium gadexetate or any of the other ingredients of this product (listed in section 6).

Warnings and precautions

Before starting to use Primovist, discuss it with your doctor if the patient:

• has currently or has had asthma or an allergy (such as hay fever, hives);
• has had an allergic reaction after using a contrast agent;
• has impaired kidney function. The use of some contrast agents containing gadolinium in patients with this condition has been associated with the occurrence of nephrogenic systemic fibrosis (NSF). NSF is a disease that causes thickening of the skin and connective tissue. NSF can lead to disability due to joint stiffness, muscle weakness, or organ dysfunction, and can be life-threatening;
• has severe heart and blood vessel disease;
• has low potassium levels;
• or has a family history of abnormal heart rhythm recordings (ECG) called long QT syndrome;
• has had abnormal heart rhythm after taking medications;
• has a pacemaker or any implant or stent containing iron.

After using Primovist, delayed reactions similar to an allergy may occur. These reactions may appear after several hours or days. See section 4.
Tell your doctor if:

• the patient's kidneys do not work properly,
• the patient has recently undergone or is scheduled to undergo a liver transplant. The doctor may decide to perform a blood test to check kidney function before deciding to use Primovist, especially in people over 65 years of age.

Accumulation in the body

Primovist works because it contains a metal called gadolinium. Studies have shown that small amounts of gadolinium may accumulate in the body, including the brain. No adverse effects related to the accumulation of gadolinium 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 its use in this population. More information can be found at the end of this package leaflet.

Primovist and other medicines

Tell your 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:

• about beta-blockers, medicines used to treat high blood pressure or heart disease;
• about medicines that affect heart rhythm or frequency, such as amiodarone, sotalol;
• about rifampicin, a medicine used to treat tuberculosis or some other infections.

Pregnancy and breastfeeding Pregnancy

Gadexetate may pass through the placenta. It is not known whether this has an effect on the fetus. Women who think they are pregnant or may be pregnant should tell their doctor, as Primovist should not be used during pregnancy unless it is absolutely necessary.
Breastfeeding
Women who are breastfeeding or plan to breastfeed should tell their doctor. The doctor will discuss with the patient whether she should continue breastfeeding or stop breastfeeding for 24 hours after receiving Primovist.

Driving and using machines

Primovist does not affect the ability to drive and use machines.

Primovist contains sodium

The medicine contains 82 mg of sodium (the main component of common salt) in each dose unit based on the amount given to a person with a body weight of 70 kg. This corresponds to 4.1% of the maximum recommended daily intake of sodium in the diet for adults.

3. How to use Primovist

Primovist is administered through a small needle into a vein, just before the start of the MRI examination.
After injection of the contrast agent, the patient will remain under observation for at least 30 minutes.

Recommended dose

0.1 ml of Primovist per kilogram of body weight.

Dosing in special patient groups

It is not recommended to use Primovist in patients with severe kidney disease, as well as in patients who have recently undergone or are scheduled to undergo a liver transplant. However, if the 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 for at least 7 days.
Elderly patients
There is no need to adjust the dose in patients over 65 years of age, but a blood test should be performed to check kidney function.

Overdose of Primovist

The risk of overdose is very low. If symptoms of overdose occur, they will be monitored by the doctor and appropriate action will be taken.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Most of these side effects are mild or moderate.
If you experience any side effects, tell your doctor.
As with other contrast agents, allergic reactions may rarely occur. After using Primovist, delayed reactions may occur after several hours or days.
The most serious side effect in patients receiving Primovist is anaphylactoid shock (a severe allergic reaction).

If you experience any of the following symptoms or have difficulty breathing, tell your doctor immediately:

• low blood pressure
• swelling of the tongue, throat, or face
• runny nose, sneezing, coughing
• red, wet, and itchy eyes
• stomach pain
• hives
• reduced sensation or sensitivity of the skin, itching, pale skin

The following additional side effects may occur:
Common:may occur in 1 in 10 people

• headache
• nausea

Uncommon:may occur in 1 in 100 people

• dizziness
• numbness and tingling
• taste or smell disorders
• redness
• increased blood pressure
• breathing disorders
• vomiting
• dry mouth
• skin rash
• intensified itching of the whole body or eyes
• back pain, chest pain
• reactions at the injection site, such as
• burning, cold, irritation, or pain
• feeling of heat
• chills
• fatigue
• malaise

Rare:may occur in 1 in 1000 people

• inability to sit or stand for a long time
• uncontrolled shaking
• feeling of strong heartbeat
• irregular heartbeat (symptoms of heart block)
• discomfort in the mouth, increased salivation
• red rash with nodules or spots on the skin
• excessive sweating
• feeling of discomfort, general malaise

Unknown:frequency cannot be estimated from available data

• rapid heartbeat
• anxiety

After administration of the Primovist contrast agent, changes in laboratory test results have been observed. You should inform the medical staff performing blood or urine tests if you have recently used Primovist.
There have been reports of nephrogenic systemic fibrosis (a disease associated with skin thickening, which can also affect soft tissues and internal organs) in association with the use of other gadolinium-containing products.

Reporting side effects

If you experience any side effects, including those not listed in this package leaflet, tell your doctor or the MRI facility staff. Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, 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.
Side effects can also be reported to the marketing authorization holder.
Reporting side effects will help to gather 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 the carton. The expiry date refers to the last day of the month.
There are no special precautions for storage of the medicinal product.
The product should be used immediately after opening.
Before use, the appearance of the product should be visually evaluated. The product should not be used if there is significant discoloration, the presence of solid particles, or damage to the packaging.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the pack and other information

What Primovist contains

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

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

What Primovist looks like and contents of the pack

Primovist is a clear, colorless or pale yellow solution, free from solid particles. The pack sizes are 1, 5, or 10 pre-filled syringes containing:

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

Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder

Bayer AG
Kaiser-Wilhelm-Allee 1
51373 Leverkusen
Germany

Manufacturer

Bayer AG
Mullerstrasse 178
13353 Berlin
Germany
To obtain more detailed information, contact the representative of the marketing authorization holder:
Bayer Sp. z o.o.
Al. Jerozolimskie 158
02-326 Warsaw
tel. (0-22) 572 35 00
Date of last revision of the package leaflet:December 2024
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Information intended for healthcare professionals only.

Kidney problems

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

There have been reports of nephrogenic systemic fibrosis (NSF) associated with the use of some gadolinium-containing products in patients with acute or chronic severe kidney impairment (GFR <30 ml min 1.73 m).
Patients undergoing liver transplantation are particularly at risk, as the risk of acute kidney failure in this patient group is high. Due to the possibility of NSF during the use of Primovist, this medicinal product should be avoided in patients with severe kidney impairment and in patients in the perioperative period of liver transplantation, unless the diagnostic information is essential and not available for MRI without contrast enhancement. If the use of Primovist cannot be avoided, the dose should not exceed 0.025 mmol/kg body weight. No more than one administration should be performed during imaging. Due to the lack of data on repeated administration, injections of Primovist should not be repeated unless the intervals between injections are at least 7 days.
Since the renal clearance of gadexetate may be reduced in elderly patients, it is particularly important to monitor patients aged 65 and over for kidney problems.

Pregnancy and breastfeeding

Primovist should not be used during pregnancy unless the clinical condition of the woman requires the use of gadexetate.
The doctor and the breastfeeding mother should decide whether to continue breastfeeding or stop breastfeeding for 24 hours after administration of Primovist.

Children and adolescents

An observational study was conducted in 52 pediatric patients (aged over 2 months and under 18 years). Patients underwent liver MRI with Primovist to evaluate suspected or known focal liver lesions.
Additional diagnostic information was obtained by comparing superimposed liver images enhanced with contrast agent and not enhanced with contrast agent in MRI, compared to MRI images without contrast agent enhancement. No serious adverse reactions reported were considered related to the use of Primovist. Due to the retrospective nature and small sample size of this study, no definitive conclusion can be drawn regarding the efficacy and safety in this population.

Before administration

Primovist is a clear, colorless or pale yellow solution, free from solid particles. The appearance of the product should always be visually evaluated before use. In case of significant discoloration, presence of particles in the solution, or damage to the container, the contrast agents are not suitable for use.

Administration

Primovist should be administered undiluted by intravenous injection at a flow rate of approximately 2 ml/s. After injection, the cannula/catheter should be flushed with a saline solution (9 mg/ml).

• after injection, the patient should be observed for at least 30 minutes.
• Primovist should not be administered simultaneously with other medicinal products.
• Primovist should not be administered intramuscularly.

Preparation

Primovist is a solution ready for use.
The pre-filled syringe should be prepared for injection immediately before the examination.
The cap should be removed from the pre-filled syringe just before use.
Any unused contrast agent remaining after the examination should be discarded in accordance with the regulations in force in the country.
The torn label from the pre-filled syringe should be attached to the patient's card to allow proper registration of the gadolinium-containing medicinal product used. The dose used should also be documented. If electronic patient cards are used, the name of the medicinal product, batch number, and dose should be entered in the patient's register.
Glass pre-filled syringes:

• 1. Open the packaging
• 2. Screw the plunger into the syringe

• 3. Break the protective cap of the tip
• 4. Remove the tip cap

• 5. Remove the rubber plug
• 6. Remove air from the syringe

Plastic pre-filled syringes
Manual injection
Injection using an injector

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

• 2. Open the tip cap by turning it
• 2. Screw the plunger into the syringe in the direction of the arrow

• 3. Connect the syringe tip to the
• 3. Open the tip cap by turning it and follow the instructions

• 4. Remove air from the syringe