Label: Information for the User

Ultravist 300 mg/ml injectable solution and for infusion in vial

Iopromida

6. Contents of the container and additional information

This medication is for diagnostic use only.

Ultravist belongs to a group of medications known as low osmolar, water-soluble, and nephrotropic contrast media for X-rays.

Ultravist is used to intensify contrast during visualization of different body areas using certain radiological techniques:

• computed tomography (CT, obtaining images of slices or sections of a specific body region)
• conventional arteriography (for visualization of arteries)
• conventional venography of extremities (for visualization of veins in the extremities) in adults and venography in children.
• digital subtraction angiography (DSA) intraarterial/intravenous
• intravenous urography (for visualization of urinary tracts)
• mammography (for visualization of the interior of the breasts) with contrast (CEM) in adult women to evaluate and detect known or suspected breast lesions, as a complement to mammography (with or without ultrasound) or as an alternative to magnetic resonance (MR) when MR is contraindicated or not available.
• arthrography (visualization of joints) and hysterosalpingography (visualization of the uterus and fallopian tubes).

No use Ultravist:

• If you are allergic (hypersensitive) to the active ingredient or to any of the other components of this medicine (listed in section 6)
• If you have clinical hyperthyroidism (your thyroid gland produces too much thyroid hormone)
• If you are pregnant or have acute pelvic cavity inflammation and are to undergo a hysterosalpingography (visualization of the uterus and fallopian tubes)

Warnings and Precautions

Consult your doctor or pharmacist before starting to use Ultravist:

• If you have ever experienced severe skin eruptions or skin peeling, blistering, and/or mouth ulcers after using Ultravist

Be especially careful with Ultravist

For all indications

• If you havehad an allergic reactionto another iodinated contrast medium, as there is an increased risk of hypersensitivity reactions (allergic reactions).

The risk of allergic reactions is also higher in patients with a history of asthma or other allergic disorders and in patients with known hypersensitivity to Ultravist or any of its excipients.

Your doctor may consider premedication with corticosteroids to minimize allergic reactions.

Patients who experience these reactions while on beta-blocker treatment may develop resistance to beta-agonist treatment (see Taking Other Medicines).

In the event of a severe hypersensitivity reaction, patients with cardiovascular disease are more susceptible to severe reactions and even fatal outcomes.

Due to the possibility of severe hypersensitivity reactions after administration, patients should be observed once the diagnostic procedure is completed.

• Severe skin reactions such as Stevens-Johnson syndrome (SSJ), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and generalized acute pustular psoriasis (AGEP) have been associated with the use of Ultravist. Seek medical assistance immediately if you notice any of the signs described in section 4.

• If you havethyroid dysfunction(alteration of thyroid function). Inform your doctor if you have hyperthyroidism (overactive thyroid) or goiter (enlargement of the thyroid gland), as iodinated contrast media may induce hyperthyroidism and thyroid crisis (a severe complication of an overactive thyroid). You may undergo blood tests for thyroid function and receive necessary medication. Your doctor will consider the need for thyroid function tests before administering Ultravist.

Inform your doctor if you have a history of thyroid disease, including hypothyroidism (underactive thyroid). Abnormal blood tests for thyroid function have been reported after imaging with iodinated contrast media that may suggest possible hypothyroidism or a temporary reduction in thyroid function, which may require treatment.

Newborns may also be exposed to Ultravist through the mother during pregnancy.

If your child is under 3 years:

Your doctor may monitor and check thyroid function, especially in newborns.

• If you havecentral nervous system (CNS) disorders:

Patients with CNS alterations may have a higher risk of CNS-related complications following Ultravist administration. CNS complications are more frequent with cerebral angiography (radiography of the brain vessels) and related procedures.

During or shortly after the imaging procedure, you may experience a short-term CNS disorder called encephalopathy. Inform your doctor immediately if you notice any of the signs and symptoms related to this disorder described in section 4.

You should be cautious in situations where the seizure threshold is lowered, such as a history of previous seizures or concurrent use of certain medications.

• Do not administer Ultravist if you are dehydrated (have not taken enough fluids). To avoid this, your doctor will ensure that you have taken enough fluids before your examination (see section "Be especially careful with Ultravist").You must ensure adequate hydration in all patients before administering Ultravist by the intraarterial or intravenous route.

This is especially important if you have multiple myeloma (a type of blood cancer), diabetes mellitus, polyuria (excessive urine production), oliguria (reduced urine production), hyperuricemia (elevated blood uric acid), and in newborns, infants, young children, and elderly patients.

Inform your doctor if you have kidney problems. Your doctor will ensure that you are well-hydrated before your examination. However, it is not recommended to administer fluids intravenously (fluids in the veins) if you have kidney problems.

Inform your doctor if you have severe kidney problems accompanied by heart disease. Administering fluids intravenously (fluids in the veins) may be hazardous to the heart.

• If you haveanxiety:

States of excitement, anxiety, and intense pain may increase the risk of adverse reactions or the intensity of reactions associated with contrast media. In these cases, inform your doctor, who will attempt to minimize your anxiety level.

• If you areelderly,as the vascular pathology and CNS disorders that are commonly seen in these patients increase the risk of adverse reactions.

• If you havea significant deterioration in your health, your doctor will evaluate the need for the examination.

Additionally, in the case ofintraarterial or intravenousUltravist administration, you should also be especially careful in the following situations:

• If you receive Ultravist, there is a risk that you may develop acute kidney injury after injection(Contrast-Induced Nephropathy(CIN)). As a result, your kidneys may not function properly for a short period. Some patients experience renal insufficiency. This is especially relevant if you have any of the following conditions:

• Pre-existing renal insufficiency (your kidneys do not function properly). For more information, see section 3: "How to use Ultravist”, subsection “Patients with renal insufficiency",
• Diabetes mellitus,
• Dehydration,
• Multiple myeloma (blood cancer of the bone marrow),
• Paraproteinemia (a disease in which an excessive amount of certain proteins is produced),
• Patients receiving high or repeated doses of Ultravist.

• If you havesevere kidney or liver dysfunction, or combinedrenal and liver dysfunctionor are to undergo aliver transplant, Ultravist will only be administered if absolutely necessary. In these cases, adequate hydration is essential before administering the contrast medium.

• If you havediabetes mellitus, as the administration of iodinated contrast media in diabetic patients with pre-existing renal damage predisposes to renal dysfunction.

• If you haveany cardiovascular disease.

There is a higher risk of clinically relevant cardiovascular changes and arrhythmias (abnormal heart rhythms) in patients with significant cardiac pathology or severe coronary artery disease.

The intraarterial or intravenous administration of the contrast medium may precipitate the onset of pulmonary edema in patients with heart failure. (See section 3: "How to use Ultravist”, subsection “Patients with renal insufficiency").

• If you have been diagnosed withpheochromocytoma(a type of tumor) as you may have a higher risk of developing a hypertensive crisis.

• If you haveautoimmune disease(diseases of the immune system that recognize the body's own tissues as foreign and attack them) as severe vasculitis (inflammation of blood vessels) and Stevens-Johnson syndrome (a condition characterized by polymorphic erythema and cutaneous, mucosal, and ocular manifestations) have been described.

• If you havemyasthenia gravis(a disease in which muscles weaken and fatigue easily), as symptoms may worsen.

• Be cautious if you havehomocystinuria(a disorder of amino acid metabolism) due to the risk of inducing thrombosis and embolism.

• If you havemultiple myeloma(a type of blood cancer) orWaldestrom's paraproteinemia(a disease in which an excessive amount of certain proteins is produced), as you are more prone to develop transient renal insufficiency after contrast medium administration.

• Mammography with contrast exposes you to higher levels of ionizing radiation than traditional mammography, although they remain within the limits defined by international guidelines on mammography. The radiation dose depends on the breast thickness and the type of mammography device used.

Additionally, in the case ofhysterosalpingographyusing Ultravist, the following considerations should be taken into account:

• It is essential to exclude any possibility of pregnancy.

• Uterine tube inflammation may increase the risk of reactions after hysterosalpingography.

Consult your doctor, even if any of the circumstances mentioned above have occurred at any time.

Use of Ultravist with other medicines

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medicine, including those purchased without a prescription.

Certain medicines may interact, in which case you may need to change the dose or discontinue treatment with one of the medicines. It is especially important to inform your doctor if you are using any of the following medicines:

• Metformin (biguanide: a medicine used to treat certain forms of diabetes mellitus): in patients with renal insufficiency, the elimination of biguanides may be reduced, leading to accumulation and development of lactic acidosis (accumulation of lactic acid in the body). As the use of Ultravist may lead to renal insufficiency or worsening of the same, patients treated with metformin may have a higher risk of developing lactic acidosis, especially those with pre-existing renal insufficiency.Based on renal function measurements, your doctor should consider the need to discontinue metformin administration.

• Neuroleptics (medicines commonly used to treat psychosis), analgesics (pain-relieving medicines), antiemetics (medicines that prevent vomiting or nausea), antihistamines (medicines for the treatment of allergic rhinitis or dermatitis), and sedatives (tranquilizers). With the use of these medicines, your susceptibility to seizures may be reduced, and you have a higher risk of reactions related to the contrast medium. Therapy with these drugs should be suspended 48 hours before contrast medium administration and not resumed before 12 hours after recognition.

• Beta-blockers, as allergic reactions may be exacerbated, especially in cases of predisposition to allergy, asthma, or previous allergy to other contrast media. Additionally, you may not respond to standard beta-agonist treatment.

• Interleukin-2, as previous treatments (of up to several weeks) with interleukin-2 have been associated with an increased risk of delayed reactions to Ultravist.

• Oral cholecystographic contrast media: There is no evidence of interaction with contrast media eliminated by the kidneys.

• Diuretics: Due to the risk of dehydration caused by diuretics, your doctor should administer you saline solutions to minimize the risk of acute renal insufficiency before administering the iodinated contrast medium.

• Interference with analytical tests: Iodinated contrast media may interfere with thyroid function tests, as the thyroid gland's ability to bind iodine may be reduced for several weeks.

• Radioisotopes: If you are to undergo diagnostic and therapeutic tests for thyroid diseases with radioisotopes, these should be delayed for several weeks after Ultravist administration, due to a decrease in radioisotope uptake.

Use of Ultravist with food and drinks

You may maintain a normal diet until two hours before the examination. During the two hours preceding the study, you should abstain from eating.

Pregnancy and Lactation

If you are pregnant or breastfeeding, or if you think you may be pregnant or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

No well-controlled studies have been conducted in pregnant women.

After diagnostic application of Ultravist in humans, animal studies do not indicate harmful effects on pregnancy, embryonic/fetal development, parturition, or postnatal development.

The risk-benefit ratio should be evaluated before administering an iodinated contrast medium, taking into account the fetal thyroid sensitivity to iodine, as acute iodine overload after administration of an iodinated contrast medium to the mother may cause fetal thyroid dysfunction.

The safety of Ultravist in lactating women has not been investigated. Contrast media are eliminated in breast milk in minimal amounts. No harm to the infant is expected.

Driving and operating machinery

No studies have been conducted on the effects on the ability to drive and operate machinery.

Ultravist contains Sodium

This medicine contains less than 23 mg of sodium (1 mmol) per dose (based on the average dose administered to a 70 kg person); it is essentially "sodium-free".

Follow exactly the administration instructions of this medication as indicated by your doctor. If in doubt, consult your doctor or pharmacist again.

Ultravist is a contrast medium used for diagnostic testing, which must be performed in the presence of qualified personnel, preferably under the supervision of a doctor, who will indicate the instructions to follow at each moment.

Before administering the contrast medium via intraarterial or intravenous route, your doctor must rule out possible renal dysfunction through medical history and/or laboratory tests.

Mammography with contrast (CEM):Ultravist will be injected intravenously (a large amount in the vein) if possible using an automatic injector.

Adult dosage

The recommended doses inadultsare as follows:

Special populations dosage

Geriatric population (population over 65 years of age):

No dose adjustment is necessary.

Pediatric population (less than 18 years of age):

The recommended doses inchildrenare shown in the table below.

The immature kidneys of infants require relatively high doses of contrast mediumfor intravenous urography in relation to the rest of the indications,as indicated in the table below:

Infants under 1 year, especially newborns, are susceptible to alterations in both blood dynamics and electrolyte content in the body. Caution should be exercised with the dose of contrast medium to be administered, the technical performance of the radiological procedure, and their general condition.

The recommended doses in newborns, infants, small children, and pediatric population of 11 to 18 years should not be exceeded.

Patients with liver insufficiency:

No dose adjustment is necessary (see section 2).

Patients with renal insufficiency:

Since Ultravist is excreted almost exclusively unchanged by the kidneys, the elimination of Ultravist is prolonged in patients with renal insufficiency. In order to reduce the risk of additional renal damage induced by the contrast medium, in patients with pre-existing renal insufficiency, the lowest diagnostic dose should be used (see section 2).

If you estimate that the action of Ultravist is too strong or too weak, inform your doctor or pharmacist.

Your doctor will inform you about all the characteristics related to the administration of Ultravist.

If you use more Ultravist than you should

The symptoms may include electrolyte imbalance (increase or decrease in total volume of water and electrolytes in the body), renal failure, and cardiovascular and pulmonary complications.

In case of accidental intraarterial or intravenous overdose, it is recommended to monitor the electrolyte balance and renal function. The treatment of overdose should be directed to ensure the support of vital functions. The loss of water and electrolytes should be compensated by perfusion. Renal function should be monitored for at least 3 days after the procedure. If necessary, hemodialysis can be used to eliminate most of the contrast medium from the body.

Ultravist is dialyzable.

In the case of overdose or accidental ingestion, consult the Toxicology Information Service; Telephone 91 562 04 20

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

Like all medications, this medication may cause side effects, although not everyone will experience them.

The global safety profile of Ultravist is based on data from pre-marketing studies in more than 3,900 patients and post-authorization studies in more than 74,000 patients, as well as spontaneous reporting data and literature.

The most frequently observed side effects in patients receiving Ultravist are headache, nausea, and vasodilation.

The most serious side effects observed in patients receiving Ultravist are anaphylactic shock, respiratory arrest, bronchospasm or bronchial obstruction, laryngeal or pharyngeal edema, asthma, coma, cerebral infarction, stroke, cerebral edema, convulsions, abnormal heart rhythms, cardiac arrest, myocardial ischemia, myocardial infarction, heart failure, bradycardia, blue discoloration of the skin and mucous membranes, hypotension, shock, dyspnea, pulmonary edema, respiratory insufficiency, and aspiration.

All indications

Frequent side effects(may affect between 1 and 10 in 100 patients):

-dizziness, headache, altered taste

-blurred vision, visual disturbances

• chest pain or discomfort
• hypertension, vasodilation
• nausea, vomiting
• dyspnea, pain, reactions at the injection site (e.g., pain, and unknown frequency, sensation of heat, edema, inflammation, and injury) and sensation of heat.

Rare side effects(may affect between 1 and 10 in 10,000 patients):

-anxiety

-cardiac arrest (*), myocardial ischemia (*), palpitations

Side effects of unknown frequency(the frequencycannot be estimated from the available data)

-thyroid crisis (acute worsening of thyroid function), thyroid disorder

-coma (*), cerebral hypoperfusion or cerebral infarction (*), stroke (*), cerebral edema (*, only with intravenous or intraarterial administration), convulsions (*), loss of vision in one or both eyes (only with intravenous or intraarterial administration), loss of consciousness, agitation, memory loss, tremor, speech disorders, paresis/paralysis, encephalopathy due to contrast

-hearing disturbances

-myocardial infarction (*), heart failure (*), bradycardia (*), tachycardia, blue discoloration of the skin and mucous membranes (*)

-shock (*), decreased perfusion due to arterial obstruction (only with intravenous or intraarterial administration), arterial contraction (only with intravenous or intraarterial administration)

-pulmonary edema (*), respiratory insufficiency (*), aspiration (*)

-dyspnea, sialadenitis, diarrhea

-bullous skin reactions (e.g., Stevens-Johnson syndrome or Lyell syndrome), skin discoloration and appearance, skin rash, excessive sweating, generalized acute pustular exanthema, drug-induced hypersensitivity syndrome with eosinophilia and systemic symptoms

-compartment syndrome in case of extravasation (only with intravenous or intraarterial administration)

-renal insufficiency (only with intravenous or intraarterial administration), acute renal failure (only with intravenous or intraarterial administration)

-general malaise, chills, pallor

-body temperature fluctuations

*Cases that have put lives at risk have been reported.

If you consider that any of the side effects you are experiencing are severe or if you notice any side effects not mentioned in this leaflet, inform your doctor or pharmacist.

Seek immediate medical attention if you notice any of the following signs and symptoms (whose frequency is unknown):

• Plaques with a reddish color on the trunk, which are macules with a target or circular shape, often with central vesicles, skin peeling, and ulcers in the mouth, throat, nose, genitals, and eyes. These severe skin eruptions may be preceded by fever and pseudogripal symptoms (Stevens-Johnson syndrome, toxic epidermal necrolysis).
• Generalized rash, elevated body temperature, and enlarged lymph nodes (DRESS syndrome or drug hypersensitivity syndrome).
• Generalized exfoliative rash with subcutaneous nodules and vesicles that is accompanied by fever after imaging technique (generalized acute pustular exanthema).

Short-term cerebral disorder (encephalopathy) that may cause memory loss, confusion, hallucinations, visual disturbances, loss of vision, convulsions, loss of coordination, loss of mobility in one side of the body, speech disorders, and syncope.

Class effects

The contrast agent is administered under general anesthesia in some selected patients. However, a high incidence of side effects has been described in these patients, which is attributed to the patient's inability to distinguish between true side effects and the effects of low blood pressure caused by anesthesia, which prolongs circulation time and increases exposure to the contrast agent.

Reporting of side effects

If you experience any type of side effect, consult your doctor or radiologist, even if it is not mentioned in this leaflet. You can also report them directly through the Spanish System for the 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 medication.

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

Store in the original packaging to protect it from light and X-rays.

Do not store at a temperature above 30°C.

Do not use this medication after the expiration date that appears on the packaging after CAD.

Ultravist is supplied as a clear, colorless to pale yellow solution ready for use. Do not use Ultravist if you observe significant color changes, the appearance of particles in suspension, 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 packaging and unused medications. This will help protect the environment.

Composition of Ultravist 300

The active ingredient is iopromide. 1 ml of injectable solution contains 623 mg of iopromide, equivalent to 300 mg of iodine.

• 1 vial with 50 ml of injectable solution contains 31.15 g of iopromide, equivalent to 15 g of iodine.
• 1 vial with 75 ml of injectable solution contains 46.73 g of iopromide, equivalent to 22.5 g of iodine.
• 1 vial with 100 ml of injectable solution contains 62.3 g of iopromide, equivalent to 30 g of iodine.
• 1 vial with 500 ml of injectable solution contains 311.5 g of iopromide, equivalent to 150 g of iodine.

The other components are: calcium and sodium edetate, trometamol, hydrochloric acid (diluted to 10%) (to adjust the pH), sodium hydroxide (to adjust the pH) and water for injectable preparations.

Appearance of the product and contents of the package

Ultravist 300 is supplied as a clear, colorless to pale yellow injectable solution and for perfusion, ready for use. Each package contains: vials of 50, 75, 100 ml (single-dose) or 500 ml (multi-dose).

Package sizes: 1 vial.

Only some package sizes may be commercially available.

Marketing authorization holder and manufacturer

Marketing authorization holder

Bayer Hispania, S.L.

Avda. Baix Llobregat 3-5

08970 Sant Joan Despí (Barcelona)

Spain

Manufacturer

The manufacturer can be identified by the batch number printed on the box, and on the label of each vial:

• If the first and second characters are MA, the manufacturer is:

Berlimed S.A.

Polígono Industrial Santa Rosa

C/ Francisco Alonso, s/n

28806 Alcalá de Henares (Madrid) – Spain

• If the first and second characters are KT, the manufacturer is:

Bayer AG

Müllerstrasse 178

13353 Berlin, Germany

Last review date of this leaflet: September 2023

The detailed information on 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 doctors or healthcare professionals (see also section 3: How to use Ultravist)

Indications

This medicine is only for diagnostic use

Ultravist 300 mg/ml is indicated in adults for contrast enhancement in computed tomography (CT), conventional arteriography, conventional venography of extremities, digital subtraction angiography (DSA), intravenous urography, arthrography, hysterosalpingography, and mammography with contrast in adult women to evaluate and detect known or suspected breast lesions as a complement to mammography (with or without ultrasound) or as an alternative to magnetic resonance imaging (MRI) when MRI is contraindicated or not available

Ultravist 300 mg/ml is indicated in pediatric population of 0-18 years for contrast enhancement in computed tomography (CT), digital subtraction angiography (DSA), intravenous urography, conventional arteriography, and venography

Before injection

Ultravist must be warmed to body temperature before administration.

The contrast medium must be visually inspected before use and should not be administered if there has been a change in its color, the appearance of particles in suspension (including crystals), or if the package is defective.

Handling

• Vials (≤ 100 ml)

The contrast medium solution should not be drawn into the syringe, nor the vial connected to the infusion equipment, until immediately before the examination.

The rubber stopper should not be pierced more than once, to prevent large amounts of microparticles from the stopper passing into the solution. It is recommended to use long-tip cannulas with a maximum diameter of 18 G to pierce the stopper and withdraw the contrast medium (special extraction cannulas with a lateral opening are particularly suitable).

The unused contrast medium solution administered to a patient and not used in an examination, must be discarded. The disposal of unused medication and all materials that have come into contact with it, will be carried out in accordance with local regulations.

• Large-volume containers (500 ml, only for intra-arterial or intravenous administration)

Multiple extraction of the contrast medium must be performed with an authorized multiple administration device. Autoinjectors/pumps should not be used in small children.

The rubber stopper of the vial should not be pierced more than once, to prevent large amounts of microparticles from the stopper passing into the solution.

The contrast medium must be administered through an automatic injector, or by another approved means, that ensures the sterility of the contrast medium.

The patient's tube (patient tube) must be replaced with each patient, in order to prevent any possible contamination.

The connection tubes and all disposable parts of the injection system must be discarded when the perfusion vial is empty.

Any remaining contrast medium solution in the vial, connection tubes, or any other part of the disposable injection system, must be discarded 10 hours after the first opening of the package.

It is essential to follow the additional instructions provided by the manufacturers of the respective materials used.

The contrast medium remaining in the opened Ultravist package must be discarded 10 hours after the package has been opened. The disposal of unused medication and all materials that have come into contact with it, will be carried out in accordance with local regulations.