Package Insert: Information for the User

Primovist 0.25 mmol/mL, Injectable Solution in Pre-filled Syringe

Gadoxetate Sodium

Primovist is a contrast medium for magnetic resonance imaging (MRI) of the liver. It is used to contribute to the detection and diagnosis of alterations that may appear in the liver. Abnormal signs of the liver can be better evaluated in terms of number, size, and distribution. Primovist may also help the doctor determine the nature of any abnormality, thereby increasing confidence in the diagnosis. It is supplied as an injectable solution. This medication is solely for diagnostic use.

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

No usePrimovist

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

Warnings and precautions

Consult your doctor before starting to use Primovist if you have:

• or have had asthma or an allergy such as hay fever, urticaria.
• previously had a reaction to contrast media.
• reduced kidney function.

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

• severe heart or blood vessel disease.
• low blood potassium levels.
• or a family member has had a heart rhythm problem called long QT syndrome.
• had heart rhythm alterations due to some medication.
• has a pacemaker or has an implant or clip containing iron in the body.

After administration of Primovist, delayed allergic reactions may occur hours or days later. See section 4.

Inform your doctor if:

• your kidneys do not function correctly
• you have recently had, or are about to have, a liver transplant

Your doctor may decide to perform a blood test to check the proper functioning of your kidneys before deciding to use Primovist, especially if you are 65 years or older.

Accumulation in the body

Primovist works because it contains a metal called gadolinium. Studies have shown that small amounts of gadolinium can accumulate in the body, including the brain.

No adverse effects have been observed due to gadolinium accumulation in the brain.

Children and adolescents

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

Use of Primovist with other medications

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication. This includes especially:

• beta-blockers, medications for the treatment of high blood pressure or other heart diseases
• medications that alter heart rhythm or cadence, such as amiodarone, sotalol
• rifampicin, a medication used for the treatment of tuberculosis or other infections.

Pregnancy and breastfeeding

Pregnancy

Gadoxetate can cross the placenta. It is unknown if it affects the fetus. Inform your doctor if you believe you are pregnant or may 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. Your doctor will assess whether you should continue breastfeeding or interrupt it for 24 hours after Primovist administration.

Driving and operating machinery

Primovist has no influence on the ability to drive and operate machinery.

Primovist contains sodium

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

Primovistis injected into a vein using a small-gauge needle. You will be administered Primovist immediately before your MRI (magnetic resonance imaging) test.

You will be under observation for at least 30 minutes after the injection.

Recommended Dose

0.1 mL of Primovist per kilogram of body weight.

Posology in Special Populations

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

Patients Over 65 Years Old

If you are 65 years old or older, it is not necessary to adjust the dose, but you may undergo a blood test to check the proper functioning of your kidneys.

If You Take More Primovist Than You Should:

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

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

You can also call the Toxicology Information Service. Phone: 91 562 04 20.

Like all medicines, this medicine may cause side effects, although not everyone will experience them.

The majority of side effects are mild to moderate in nature.

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

Like other contrast agents, rare cases of allergic reactions may occur.Reactions may occur hours to days after the administration of Primovist.

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

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

• low blood pressure
• swelling in the tongue, throat, or face
• nasal secretion, sneezing, coughing
• red, watery, and itchy eyes
• stomach pain
• hives
• decreased sensation or sensitivity in the skin, itching, pale skin

The following additional side effects may occur:

Frequent side effects:may affect up to 1 in 10 people

• headache
• nausea

Infrequent side effects:may affect up to 1 in 100 people

• dizziness
• numbness and tingling
• alterations in the sense of taste or smell
• flushing
• increased blood pressure
• breathing difficulties
• vomiting
• dry mouth
• skin rash
• intense itching, affecting the entire body or eyes
• back pain, chest pain
• reactions at the injection site, such as burning, coldness, irritation, pain
• sensation of heat,
• chills
• fatigue
• abnormal sensitivity

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

• inability to sit or stand
• uncontrollable tremor
• abnormally intense or rapid heartbeats (palpitations)
• irregular heartbeats (signs of cardiac blockage)
• mouth discomfort
• increased saliva production
• skin redness with blisters and patches
• increased sweating
• sensation of discomfort, general malaise

Unknown frequency:the frequency cannot be estimated from available data

• rapid heart rate
• agitation

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

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

Reporting of side effectsIf you experience any type of side effect, consult your doctor, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the Spanish System of Pharmacovigilance of Medicines for Human Use:https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the syringe label or the container after CAD. The expiration date is the last day of the month indicated.

This medication does not require special storage conditions.

This medication must be used immediately after opening.

It should be visually inspected before use. This medication should not be used if it presents significant color changes, the appearance of particles, or if the packaging is defective.

Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications you no longer need. This will help protect the environment.

Composition of Primovist

• The active ingredient is gadoxetate disodium. Each milliliter of injection solution contains 0.25 mmol of gadoxetate disodium (equivalent to 181.43 mg of gadoxetate disodium).
• The other components are: calcium trioside, trometamol, sodium hydroxide, and hydrochloric acid (both for pH adjustment), and water for injection preparations.

1 preloaded syringe with 5.0 ml of solution contains 907 mg ofgadoxetate disodium,

1 preloaded syringe with 7.5 ml of solution contains 1361mg ofgadoxetate disodium, [only glass syringe]

1 preloaded syringe with 10.0 ml of solution contains 1814mg ofgadoxetate disodium.

Appearance of the product and contents of the package

Primovist is a clear, colorless to pale yellow solution free of particles. The contents of the packages are 1, 5, or 10 preloaded syringes with:

5.0 ml of injection solution (in a 10 ml preloaded syringe of glass or plastic)

7.5 ml of injection solution (in a 10 ml preloaded syringe of glass) [only glass syringe]

10.0 ml of injection solution (in a 10 ml preloaded syringe of glass or plastic)

Only some package sizes may be commercially available.

Marketing Authorization Holder:

Bayer Hispania, S.L.

Avda. Baix Llobregat, 3-5

08970 Sant Joan Despí (Barcelona)

Spain

Manufacturer:

Bayer AG

Müllerstrasse 178

13353 Berlin, Germany

Last review date of this leaflet: June 2024

The detailed information of this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es/

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This information is intended solely for healthcare professionals:

• Renal Insufficiency

Before administering Primovist, it is recommended to evaluate all patients to detect possible renal dysfunction by laboratory tests.

Cases of systemic fibrosis nephrogenic (FNS) have been reported associated with the use of some gadolinium-based contrast agents in patients with severe acute or chronic renal insufficiency (GFR <30). Patients undergoing liver transplantation have a special risk since the incidence of renal failure is high in this group. Since there is a possibility that FNS may occur with Primovist, it should be avoided:

• in patients with severe renal insufficiency
• in the perioperative period of a liver transplant

unless diagnostic information is essential and cannot be obtained by MRI without contrast. If the use of Primovist cannot be avoided, the dose should not exceed 0.025 mmol/kg of body weight. During an examination, no more than one dose should be administered. Due to the lack of information on repeated administration, the administration of Primovist should not be repeated 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 and over to detect possible renal dysfunction.

Hemodialysis shortly after administration of Primovist may be useful for the elimination of Primovist from the body. There is no evidence to support the initiation of hemodialysis for the prevention or treatment of FNS in patients not undergoing hemodialysis.

• Pregnancy and Lactation

Primovist should not be used during pregnancy unless the clinical situation of the woman requires treatment with gadoxetate.

The continuation or interruption of breastfeeding 24 hours after administration of Primovist will be at the discretion of the doctor and the breastfeeding mother.

• Pediatric Population

An observational study was conducted in 52 pediatric patients aged over 2 months and under 18 years. Patients were referred for a liver MRI with contrast enhancement using Primovist to evaluate known or suspected liver lesions. Additional diagnostic information was obtained when comparing the MRI liver combined with and without contrast enhancement, with MRI without contrast enhancement. Severe adverse events were reported, however none of them were 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, colorless to pale yellow solution free of visible particles. The contrast medium should be visually inspected before use. The contrast medium should not be used if it presents significant color changes, particle formation, or if the package is defective.

• Administration

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

• Patients should be observed for at least 30 minutes after injection.
• Primovist should not be mixed with other medications.
• Intramuscular injection should be avoided.

• Handling

Primovist is ready for use.

The preloaded syringe should be prepared for injection immediately before the examination. The cap of the preloaded syringe should be separated from the tip immediately before use.

All unused contrast medium should be disposed of in accordance with local regulations.

The detachable label of the preloaded syringes should be attached to the patient's medical history to allow for precise recording of the gadolinium-based contrast medium used. The dose used should also be recorded. In the case of electronic patient records, the product name, batch number, and administered dose should be entered into the records.

Glass syringe:

Plastic syringe: