Label: information for the user

Ultravist 240 mg/ml injectable solution and for infusion in vial

Iopromida

This medication is for diagnostic use only.

Ultravist belongs to a group of medications called 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)
• phlebography of extremities (for visualization of veins in the extremities) in adults and phlebography in children.
• digital subtraction angiography (DSA) intraarterial/intravenous
• intravenous urography (for visualization of the urinary tract)
• lumbar, thoracic, and cervical myelography (visualization of structures within the spine) using intrathecal administration (administration in the space surrounding the spinal cord)

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 inflammation in the pelvic cavity and are to undergo a hysterosalpingography (visualization of the uterus and fallopian tubes)

The use of intrathecal Ultravist should not be performed in patients:

• with a history of epilepsy
• on anticonvulsant treatment (taking medications to combat, prevent, or interrupt seizures or epileptic attacks, for example, barbiturates, benzodiazepines, bromides, carbamates, and hydantoins)
• with convulsive cerebral disease
• with renal dysfunction (serum creatinine > 1.3 mg/dl)

Warnings and precautions

Consult your doctor or pharmacist before starting to use Ultravist:

• If you have ever suffered from severe skin eruptions or skin peeling, blistering, and/or oral 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 be resistant to standard beta-agonist treatment.

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 be required to 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 transient (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 disorders:

Patients with central nervous system disorders may have a higher risk of neurological complications related to Ultravist administration. Neurological 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 cerebral 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 concomitant 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 anadequate hydration statein all patientsbefore administering Ultravist by intraarterial, intravenous, or intrathecal 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), as well as 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.

• If you areelderly,as vascular pathology and neurological 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 ofintravenous or intraarterial injectionof Ultravist,you should also be cautious 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,
• deshidratación,
• 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,combined kidney and liver disordersor are to undergo a liver 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 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 (alterations in heart rhythm) in patients with significant cardiac pathology or severe coronary artery disease.

Intravenous or intraarterial injection 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 have anyautoimmune disease(diseases of the immune system that recognize their 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 become weakened and fatigued 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 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.

Additionally, in the case ofintrathecal useyou should also be cautious with Ultravist in the following situations:

• Intrathecal use of Ultravist is not indicated for cerebral ventriculography (radiography of the brain ventricles) and cisternography (radiography of the cisterns at the base of the skull).

• There are no data on the use of Ultravist by the intrathecal route in pediatric populations or in patients with renal dysfunction (serum creatinine > 1.3 mg/dl).

• If you have any type ofcerebral disease that is characterized by seizuressdo not administer Ultravist without first conducting a thorough evaluation. Additionally, have the necessary equipment and medications available to counteract any seizures that may occur.

• Most adverse reactions after myelography occur several hours after contrast medium administration. During this period, the patient should be observed.

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

• Exclude any possibility of pregnancy.

• Inflammation of the fallopian tubes 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 medications

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

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

• Metformin (biguanide: a medication 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, consider the need to discontinue metformin administration.

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

• Beta-blockers, as hypersensitivity reactions may be exacerbated, especially in cases of allergic predisposition, asthma, or history of 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 rehydration salts to minimize the risk of acute kidney injury before administering the iodinated contrast medium.

• Interference with analytical tests: Iodinated contrast media may interfere with thyroid function tests, as the thyroid'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, they should be delayed for several weeks after Ultravist administration, due to reduced uptake of the radioisotope.

Use of Ultravist with food and drinks

You may maintain a normal diet until two hours before the examination. During the two hours prior to 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 intend to become pregnant, consult your doctor or pharmacist before using this medication.

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 sensitivity of the fetal thyroid to iodine, as acute iodine overload after administration of an iodinated contrast medium to the mother may cause fetal thyroid dysfunction.

No safety studies have been conducted in women who were breastfeeding their infants. Iodinated contrast media are excreted in breast milk in minimal amounts. No harm to the infant is anticipated.

Driving and operating machinery

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

Ultravist contains Sodium

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

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

Ultravist is a contrast medium used for diagnostic testing, which should 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, intravenous, or intrathecal route, your doctor must rule out possible renal dysfunction through medical history and/or laboratory tests.

Adult Dosage

The recommended doses inadultsare as follows:

Special Populations Dosage

Geriatric Population (65 years of age and older):

No dose adjustment is necessary.

Pediatric Population (under 18 years of age):

The recommended doses in children are shown in the table below.

Infant kidneys, still immature, require administering 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 blood dynamics and electrolyte content in the body. Caution should be exercised when administering the contrast medium dose, the technical performance of the radiological procedure, and their general condition.

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

Patients with Hepatic 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. To reduce the risk of additional renal damage induced by the contrast medium, patients with pre-existing renal insufficiency should be given the lowest diagnostic dose. Do not administer via intrathecal route in patients with renal dysfunction (serum creatinine > 1.3 mg/dl); 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.

Using more Ultravist than you should

Intraarterial or intravenous use(in an artery or vein)

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

In case of accidental intraarterial or intravenous overdose, it is recommended to monitor the balance of electrolytes and renal function. 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 remove most of the contrast medium from the body.

Ultravist is dialyzable.

Intrathecal use(in the space surrounding the spinal cord)

Severe neurological complications may occur. In case of accidental intrathecal overdose, it is recommended to monitor closely.

You should be closely monitored for the first 12 hours to detect signs indicative of severe central nervous system alteration. These signs may include ascending hyperreflexia, tonic-clonic spasms, and, in severe cases, encephalopathy with generalized seizures, hyperthermia, stupor, and respiratory depression. To prevent large amounts of Ultravist from reaching the cerebral cisterns, the aspiration of the contrast medium should be performed as completely as possible.

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

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

Like all medicines, this medicine can 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, respiratory difficulty, 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
• vomiting, nausea
• dizziness, pain, or reactions at the injection site (e.g., pain, and unknown frequency, warmth, edema, inflammation, and injury) and warmth.

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, contrast-induced encephalopathy

-hearing disorders

-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 constriction (only with intravenous or intraarterial administration)

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

-respiratory difficulty, salivary gland enlargement, diarrhea

-bullous skin reactions (e.g., Stevens-Johnson syndrome or Lyell syndrome), skin color and appearance changes, skin rash, excessive sweating, generalized acute pustular exanthema, drug reaction 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.

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 blisters under the skin and vesicles that is accompanied by fever after imaging (generalized acute pustular exanthema).

A transient 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 fainting.

Intrathecal administration

In addition to the side effects listed above, the following side effects have been reported with intrathecal administration: chemical meningitis and meningeal syndrome of unknown frequency.

Most reactions after myelography or use of the contrast medium in body cavities appear several hours after administration.

Based on experience with other non-ionic contrast media, the following side effects may appear with intrathecal administration along with the side effects listed above: psychosis, neuralgia, paraplegia, aseptic meningitis, back pain, limb pain, urinary difficulties, abnormal electroencephalogram.

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

Class effects

The contrast medium is used with general anesthesia in some selected patients. However, a high incidence of side effects has been described in these patients, which is attributed to the lack of the patient's ability 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 medium.

Reporting of side effects

If you experience any type of side effect, consult your doctor or radiologist, even if it is a side effect not listed 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 medicine.

Keep this medicationout 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 86°F (30°C).

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

Ultravistis 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.

Medicines should not be disposed of through the drains or in the trash. Ask your pharmacist how to dispose of the packaging and unused medicines.This will help protect the environment..

Composition of Ultravist 240

• The active ingredient is iopromide. 1 ml of injectable solution contains 499 mg of iopromide, equivalent to

240 mg of iodine.

1 vial with 10 ml of injectable solution contains 4.99 g of iopromide, equivalent to 2.4 g of iodine.

1 bottle with 50 ml of injectable solution contains 24.95 g of iopromide, equivalent to 12 g of iodine.

1 bottle with 500 ml of injectable solution contains 249.5 g of iopromide, equivalent to 120 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 packaging

Ultravist 240 is supplied as a clear, colorless to pale yellow injectable solution and for perfusion, ready to use. Each package contains: vials of 10 ml (single-dose) or bottles of 50 ml (single-dose) or bottles of 500 ml (multi-dose).

Packaging sizes: 1 vial or 1 bottle.

Only some packaging sizes may be marketed.

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/bottle:

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

---------------------------------------------------------------------------------------------------------------------------

This information is intended solely for doctors or healthcare professionals (see also section 3: How to use Ultravist)

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 packaging is defective.

Handling

• Vials/Bottles (≤ 50 ml)

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

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

The 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 intraarterial or intravenous administration)

The multiple extraction of the contrast medium must be carried out with an authorized multiple administration device. Syringe pumps should not be used in small children.

The rubber stopper of the bottle should not be pierced more than once, to avoid 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 must be replaced with each patient, in order to avoid any possible contamination.

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

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

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

The contrast medium remaining in the opened Ultravist packaging must be discarded 10 hours after the packaging 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.