Primovist 0.25 mmol/ml solution for injection in pre-filled syringe

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Primovist 0.25 mmol/ml, injectable solution in a pre-filled syringe

Gadoxetate disodium

Read the entire package leaflet carefully before you start using this medicine, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult the doctor administering Primovist to you.
• If you experience any adverse reactions, contact your doctor, even if they are not listed in this leaflet. See section 4.

Contents of the package leaflet:

1. What Primovist is and what it is used for
2. What you need to know before using Primovist
3. How to use Primovist
4. Possible adverse 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 help detect and diagnose abnormalities that may occur in the liver. Abnormal liver findings can be better assessed in terms of number, size, and distribution. Primovist may also help the physician determine the nature of any abnormality, thereby increasing diagnostic confidence. It is supplied as an injectable solution. This medicine is for diagnostic use only.

MRI (magnetic resonance imaging) is an imaging diagnostic method that creates images by detecting water molecules in normal and abnormal tissues. This is achieved using a complex system of magnets and radio waves.

2. What you need to know before using Primovist

Do not use Primovist

• If you are allergic to gadoxetate disodium or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor before using Primovist if you have:

• or have had asthma or an allergy such as hay fever, hives.
• previously experienced any reaction to contrast agents.
• reduced kidney function.

The use of some gadolinium-containing contrast agents in patients with this condition has been associated with a disease known as Nephrogenic Systemic Fibrosis (NSF). NSF is a disease that causes thickening of the skin and connective tissues. NSF may lead to reduced joint mobility, muscle weakness, or impairment of internal organ function, which can be life-threatening.

• severe heart or blood vessel disease.
• low blood potassium levels.
• or if a member of your family has had a heart rhythm problem called long QT syndrome.
• experienced heart rhythm disturbances due to any medication.
• have a cardiac pacemaker or if you have any implant or clip containing iron in your body.

Delayed allergic reactions may occur hours or days after administration of Primovist. See section 4.

Inform your doctor if:

• your kidneys do not function properly
• you have recently undergone, or are scheduled to undergo, a liver transplant

Your doctor may decide to perform a blood test to check your kidney function before deciding to use Primovist, especially if you are 65 years of age or older.

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 due to gadolinium accumulation in the brain have been observed.

Children and adolescents

The safety and efficacy of Primovist in patients under 18 years of age have not been established, as experience with its use is limited. Additional information is provided at the end of the leaflet.

Using Primovist with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines. This includes especially:

• beta-blockers, medicines used to treat high blood pressure or other heart conditions
• medicines that affect the rhythm or rate of your heartbeat, such as amiodarone, sotalol
• rifampicin, a medicine used to treat tuberculosis or other infections.

Pregnancy and breastfeeding

Pregnancy

Gadoxetate may cross the placenta. It is unknown whether it affects the fetus. You must inform your doctor if you think you are pregnant or could be pregnant, as Primovist should not be used during pregnancy unless strictly necessary.

Breastfeeding

Inform your doctor if you are breastfeeding or about to start breastfeeding. Your doctor will assess whether you should continue breastfeeding or interrupt it for a period of 24 hours after administration of Primovist.

Driving and use of machines

Primovist has no influence on the ability to drive and use machines.

Primovist contains sodium

This medicine contains 82 mg of sodium (the main component of table/cooking salt) per dose, based on the amount administered for a 70 kg person. This corresponds to 4.1% of the maximum daily sodium intake recommended for an adult.

3. How to use Primovist

Primovist is injected into a vein using a small needle. You will be given Primovist immediately before your MRI (magnetic resonance imaging) scan.

After the injection, you will be monitored for at least 30 minutes.

Recommended dose

0.1 ml of Primovist per kilogram of body weight.

Dosage in special populations

The use of Primovist is not recommended in patients with severe renal impairment or in patients who have recently undergone or are about to undergo liver transplantation. However, if use is required, only one dose of Primovist should be administered during an examination, and a second injection should not be given until at least 7 days have passed.

Elderly patients

If you are 65 years of age or older, dose adjustment is not necessary, but a blood test may be performed to check that your kidneys are functioning properly.

If you use more Primovist than you should:

Overdose is unlikely. If this occurs, your doctor will treat any symptoms that appear.

If you have any further questions about the use of this product, ask your doctor or pharmacist.

You may also call the Toxicology Information Service. Telephone: 91 562 04 20.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.

Most adverse effects are mild to moderate in nature.

If you experience any type of adverse effect, consult your doctor.

As with other contrast agents, rare cases of allergic reactions may occur. Delayed reactions may occur hours to days after administration of Primovist.

The most serious adverse effect in patients receiving Primovist is anaphylactic shock (a severe allergic reaction).

Contact your doctor immediately if you experience any of the following signs or if you have difficulty breathing:

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

The following additional adverse effects may occur:

Common adverse effects: may affect up to 1 in 10 people

• headache
• nausea

Uncommon adverse effects: may affect up to 1 in 100 people

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

Rare adverse effects: may affect up to 1 in 1000 people

• inability to sit or stand
• uncontrollable tremor
• abnormally strong or rapid heartbeat (palpitations)
• irregular heartbeat (signs of cardiac block)
• mouth discomfort
• increased saliva production
• red, blistered, and spotted skin
• increased sweating
• feeling of discomfort, general malaise

Frequency not known: frequency cannot be estimated from available data

• fast heart rate
• agitation

Some laboratory values may change shortly after administration of Primovist. Inform your healthcare professional if you have recently undergone a test with Primovist, in case you need to have a blood or urine test.

Cases of nephrogenic systemic fibrosis (which causes hardening of the skin and may also affect soft tissues and internal organs) have been reported in association with the use of other gadolinium-based contrast agents.

Reporting of adverse effects If you experience any adverse effect, consult your doctor, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Primovist

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the syringe label or carton after EXP. The expiry date refers to the last day of the month indicated.

This medicine does not require any special storage conditions.

This medicine must be used immediately after opening.

It should be inspected visually before use. This medicine must not be used if there are significant changes in colour, if particles are present, or if the container is damaged.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to properly dispose of unused medicines and their packaging. This will help protect the environment.

6. Contents of the container and other information

Composition of Primovist

• The active substance is disodium gadoxetate. Each ml of solution for injection contains 0.25 mmol of disodium gadoxetate (equivalent to 181.43 mg of disodium gadoxetate).
• The other components are: trisodium caloxetate, trometamol, sodium hydroxide and hydrochloric acid (both used to adjust pH), and water for injections.

One pre-filled syringe containing 5.0 ml of solution contains 907 mg of disodium gadoxetate,

One pre-filled syringe containing 7.5 ml of solution contains 1361 mg of disodium gadoxetate, [glass syringe only]

One pre-filled syringe containing 10.0 ml of solution contains 1814 mg of disodium gadoxetate.

Appearance of the product and contents of the container

Primovist is a clear, particle-free solution ranging from colourless to pale yellow. The container contents consist of 1, 5 or 10 pre-filled syringes with:

5.0 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]

10.0 ml of injection solution (in a 10 ml glass or plastic pre-filled syringe)

Only certain pack sizes may be marketed.

Marketing Authorisation Holder:

Bayer Hispania, S.L.
Avda. Baix Llobregat, 3-5
08970 Sant Joan Despí (Barcelona)
Spain

Manufacturer:

Bayer AG
Müllerstrasse 178
13353 Berlin, Germany

Date of the most recent review of this summary: December 2024

Detailed information on this medicinal product is available on the website of the Spanish Agency of Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es/

This information is intended for healthcare professionals only:

• Renal impairment

Prior to administration of Primovist, it is recommended to assess all patients for potential renal dysfunction by laboratory tests.

Cases of nephrogenic systemic fibrosis (NSF) have been reported following the use of some gadolinium-based contrast agents in patients with severe acute or chronic renal impairment (GFR or glomerular filtration rate < 30 ml/min/1.73 m²). Patients undergoing liver transplantation are at particular risk, as renal failure is common in this group. Since there is a possibility that NSF may occur with Primovist, its use should be avoided:

• in patients with severe renal impairment
• during the perioperative period of liver transplantation

unless the diagnostic information is essential and cannot be obtained by non-contrast magnetic resonance imaging (MRI). If use of Primovist cannot be avoided, the dose must not exceed 0.025 mmol/kg body weight. Only one dose should be administered during an examination. Due to the lack of data on repeated administration, Primovist should not be re-administered unless an interval of at least 7 days has elapsed between injections.

Since renal elimination of gadoxetate may be reduced in elderly patients, it is especially important to evaluate patients aged 65 years and older for potential renal dysfunction.

Haemodialysis shortly after administration of Primovist may be helpful in eliminating Primovist from the body. There is no evidence supporting initiation of haemodialysis for the prevention or treatment of NSF in patients not already undergoing haemodialysis.

• Pregnancy and Lactation

Primovist should not be used during pregnancy unless the woman's clinical condition requires treatment with gadoxetate.

The decision to continue or interrupt breastfeeding 24 hours after administration of Primovist will be at the discretion of the physician and the breastfeeding mother.

• Paediatric population

An observational study was conducted in 52 paediatric patients aged over 2 months and under 18 years. Patients were referred for contrast-enhanced hepatic magnetic resonance imaging (MRI) with Primovist to evaluate known or suspected focal liver lesions. Additional diagnostic information was obtained when contrast-enhanced and non-contrast MRI were compared. Serious adverse events were reported, but none were considered related to Primovist by the investigator. Due to the retrospective nature and small sample size of this study, no definitive conclusions can be drawn regarding efficacy and safety in this population.

• Before injection

Primovist is a clear, particle-free liquid ranging from colourless to pale yellow. The contrast agent should be inspected visually before use. The contrast agent must not be used if there are significant changes in colour, presence of particles, or if the container is defective.

• Administration

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

• Patients should be kept under observation for at least 30 minutes after injection.

• Primovist must not be mixed with other medicinal products.

• Intramuscular injection must be strictly avoided.

• Handling

Primovist is ready for use.

The pre-filled syringe should be prepared for injection immediately before the procedure. The cap at the end of the pre-filled syringe should be removed immediately before use.

Any unused contrast agent must be disposed of according to local regulations.

The detachable label from the pre-filled syringes should be affixed to the patient's medical record to allow accurate documentation of the gadolinium-based contrast agent used. The administered dose should also be recorded. In cases where electronic patient records are used, the product name, batch number and administered dose should be entered.

Glass syringe:

Plastic syringe: