Ultravist 300

PATIENT INFORMATION LEAFLET: INFORMATION FOR THE USER

Ultravist 300, 623.40 mg/ml, solution for injection

Ultravist 370, 768.86 mg/ml, solution for injection

Iopromide

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

• Keep this leaflet, you may need to read it again.
• In case of any doubts, consult a doctor or pharmacist.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor or radiology staff. See section 4.

Table of contents of the leaflet:

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

1. WHAT IS ULTRAVIST AND WHAT IS IT USED FOR

Ultravist is a contrast agent in the form of a solution for injection, intended for use in X-ray diagnostics.
All contrast agents used in X-ray diagnostics, including Ultravist, contain iodine. X-rays do not pass through contrast agents because they are absorbed by iodine. Areas of the body where Ultravist accumulates after injection into the bloodstream or body cavities become visible during X-ray examination.

Indications for use

The drug is intended exclusively for diagnostic purposes.
Depending on the route of administration and the concentration of the Ultravist drug, an image of the veins and arteries is obtained, and changes in the urinary system, kidneys, brain, heart, chest, and body cavities are detected.

2. IMPORTANT INFORMATION BEFORE USING ULTRAVIST

When not to use Ultravist

• if the patient is allergic to iodine, iopromide, or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Before administering Ultravist, the doctor will warm it up to body temperature, as it is better tolerated and its viscosity is reduced, making it easier to inject.
Before administering the contrast agent Ultravist, medical personnel will inspect it, and if they notice discoloration, the presence of solid particles in the solution (including crystals), or damage to the container, they will not administer the agent. Ultravist is a high-concentration solution and, therefore, may rarely crystallize (milky turbid appearance and/or sediment at the bottom or floating crystals).
Due to the possibility of pharmaceutical incompatibilities of the contrast agent Ultravist, it must not be mixed with other medicines.
Before using the contrast agent Ultravist, the patient should inform their doctor if they feel anxious. States of excessive excitement and anxiety, as well as painful conditions, may increase the risk of side effects or enhance the severity of reactions to contrast agents (see "Possible side effects").
Ultravist should not be administered if the patient is dehydrated (has not taken sufficient fluids). To avoid this, the doctor will ensure that the patient has taken sufficient fluids before the examination (see "Warnings and precautions").
Before starting Ultravist, the patient should discuss the following with their doctor or nurse:

• if the patient has asthma or another type of allergy (e.g., seafood allergy, hay fever, hives);
• if the patient is allergic to iodine-containing contrast agents, iopromide, or any of the excipients listed in the section on excipients;
• if the patient has had a reaction to contrast agents in the past;
• if the patient has kidney function disorders;
• if the patient has polyuria;
• if the patient has oliguria;
• if the patient has a high level of uric acid in the blood (hyperuricemia, gout);
• if the patient has heart and circulatory system diseases;
• if the patient has diabetes;
• if the patient has epilepsy or other nervous system disorders;
• if the patient has hyperthyroidism or suspected hyperthyroidism;
• if the patient has neck swelling due to thyroid enlargement (goiter);
• if the patient has multiple myeloma (bone marrow cancer) or increased production of specific proteins (paraproteinemia), or muscle weakness (myasthenia);
• if the patient has hypertension caused by a pheochromocytoma (adrenal gland tumor);
• if the patient is taking certain medications;
• if the patient has ever experienced a severe skin rash or skin peeling after using Ultravist.

This is especially important for elderly patients, newborns, infants, and young children.
If any of the above conditions occur, the doctor will decide whether the examination can be performed.
The patient should inform their doctor if they have kidney problems. The doctor will ensure that the patient is well-hydrated before the examination. However, administering intravenous fluids is not recommended if the patient has kidney problems.
The patient should inform their doctor if they have severe kidney problems accompanied by heart disease. Administering intravenous fluids may be dangerous for the heart.
The doctor will not perform a test for hypersensitivity (administering a small dose of the contrast agent Ultravist), as the test does not provide reliable information about hypersensitivity and has sometimes been the cause of severe, even fatal, hypersensitivity reactions.
Particular caution should be exercised when using Ultravist:
severe skin reactions, such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP), have been reported in association with Ultravist. If any of the symptoms described in section 4 occur, medical help should be sought immediately.

Observed hypersensitivity reactions and pseudoallergic reactions after administration of X-ray contrast agents, such as Ultravist (see "Possible side effects").

The patient should inform their doctor if they have had allergic reactions to the contrast agent Ultravist, its excipients, or any other contrast agent in the past. If the patient has had asthma or other allergic reactions, this may indicate an increased risk of an allergic reaction (including severe reactions).
Allergic reactions are characterized by symptoms from the cardiovascular system (heart and blood vessels), respiratory system (lungs), and skin (skin reactions).
Reactions resembling allergies, with a severity ranging from mild to severe to shock, may occur (see "Possible side effects"). These reactions are difficult to predict and may occur irregularly. Most of these reactions occur within 30 minutes of administration, but sometimes delayed reactions (after several hours or days) may occur.
The patient should inform their doctor about taking beta-blockers (medicines used to treat high blood pressure), as they may affect the treatment with beta-adrenergic agonists (medicines used in case of shock).
After administering Ultravist, medical personnel will monitor the patient's condition, as there is a possibility of severe hypersensitivity reactions, and have a first-aid kit available.
Before the examination, the doctor may administer corticosteroids (medicines used, among other things, to treat inflammatory conditions), if they consider that there is a risk of an acute allergic reaction (e.g., if there has been a moderate or severe acute reaction in the past or if the patient has asthma or an allergy requiring treatment).

Thyroid function disorders

The patient should inform their doctor if they suspect or have been diagnosed with a goiter or hyperthyroidism, as there is a risk of hyperthyroidism and thyroid crisis after administration of iodine-containing contrast agents. In patients suspected of having hyperthyroidism, the doctor may consider performing thyroid function tests and/or preventive administration of medicines that inhibit thyroid function before administering Ultravist.
The patient should inform their doctor if they have had thyroid disease in the past, including hypothyroidism (underactive thyroid gland), as the use of iodine-containing contrast agents may result in abnormal blood test results suggesting potential hypothyroidism or transient (temporary) worsening of thyroid function, which may require treatment.
Newborn babies may also be exposed to the effects of Ultravist through their mother during pregnancy.
If the child is less than 3 years old:
The doctor may monitor and examine thyroid function, especially in newborns.

Nervous system disorders

The patient should inform their doctor if they have had nervous system disorders (e.g., seizures).
In situations where there may be a lowered seizure threshold or increased blood-brain barrier permeability (e.g., when taking certain medications), the patient may be at increased risk of neurological complications. Neurological complications occur more frequently in association with cerebral angiography and similar diagnostic tests.
A temporary brain function disorder called encephalopathy may occur during or shortly after the imaging procedure. If any of the subjective and objective symptoms associated with this condition, as described in section 4, occur, medical help should be sought immediately.

Acute kidney failure

In the case of intravascular administration of Ultravist (administration into blood vessels), there is a risk of contrast-induced nephropathy (acute kidney injury). As a result, the kidneys may not function properly for a short time. Some patients may experience kidney failure.
This is especially true if any of the following conditions occur:

• pre-existing kidney failure (kidneys do not function properly). See also "How to use Ultravist" / "Patients with kidney failure",
• diabetes,
• multiple myeloma (bone marrow cancer),
• paraproteinemia (excessive production of specific proteins),
• dehydration;
• or if the patient receives multiple or large doses of Ultravist. In patients with non-functioning kidneys undergoing dialysis, contrast-enhanced radiological examinations with Ultravist can be performed.

Cardiovascular diseases

If the patient is to receive Ultravist intravascularly (into blood vessels) and has severe heart disease, including advanced coronary artery disease, there is an increased risk of arrhythmias (disorders of heart rhythm or frequency) and significant hemodynamic disturbances (changes in blood circulation).
Intravascular administration of the contrast agent to patients with heart failure may cause pulmonary edema (fluid accumulation in the lungs) (see "Important information before using Ultravist" / "Patients with kidney failure").

Pheochromocytoma

If the patient is to receive Ultravist intravascularly (into blood vessels) and has a pheochromocytoma, they may be at increased risk of a hypertensive crisis (severe high blood pressure).

Myasthenia

If the patient is to receive Ultravist intravascularly (into blood vessels) and has myasthenia (a chronic muscle disease), the administration of Ultravist may exacerbate the symptoms of the disease.
Contrast-enhanced mammography exposes the patient to a higher level of ionizing radiation than traditional mammography, but it is still within the limits set by international mammography guidelines. The radiation dose depends on breast thickness and the type of mammography device used.

Ultravist and other medicines

The patient should tell their doctor about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take, even those that are available without a prescription.
Some medicines may affect the action of Ultravist. These include:

• biguanides (a type of medicine used to treat diabetes);
• interleukin;
• radioactive substances used to treat the thyroid gland.

The doctor will inform the patient how to use these medicines before the examination.

Using Ultravist with food and drink

Before the examination, the patient should not eat for 2 hours, but they can drink. The doctor will provide further instructions.

Pregnancy and breastfeeding

Pregnancy

If the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a child, they should consult their doctor before using this medicine.
No studies have been conducted in pregnant women.
Animal studies have not shown a harmful effect of the contrast agent on pregnancy, embryonic development, fetal development, the course of labor, or postpartum development.

Breastfeeding

No studies have been conducted on the safety of using Ultravist in breastfeeding women. Iopromide, the active substance of the contrast agent, is excreted in small amounts into the breast milk of breastfeeding women, so the risk of harmful effects on the baby is small. (See "Important information before using Ultravist" / "Warnings and precautions" / "Thyroid function disorders").

Ultravist contains sodium

The medicine contains 0.255 mg of sodium (the main component of common salt) per 1 mL. This corresponds to 0.013% of the maximum recommended daily intake of sodium in the diet for adults.

3. HOW TO USE ULTRAVIST

Ultravist is administered by medical personnel.
Before intravascular administration (into blood vessels) of Ultravist, the doctor will check the patient's health and ask about any medications they are taking, as they may affect the development of thromboembolic complications (blood clot formation).
Additionally, the doctor:

• will pay particular attention to the technique of performing angiography;
• will flush the catheter (if possible, with the addition of heparin - a blood-thinning medicine) as often as necessary;
• will shorten the examination time, if possible, to minimize the risk associated with the occurrence of thrombosis and embolism (formation and migration of a blood clot, blocking blood vessels).

Dosage - intravascular administration (into blood vessels)

The doctor will determine the appropriate dose of Ultravist for each patient individually, based on age, body weight, and the purpose and technique of the diagnostic examination.
Generally, doses not exceeding 1.5 g of iodine per kg of body weight are well tolerated.
This corresponds to:

• 5 mL of Ultravist 300 per kg of body weight;
• 4.05 mL of Ultravist 370 per kg of body weight.

Dosage - administration into body cavities

Arthrography: 5-15 mL of Ultravist 300/370

Endoscopic retrograde cholangiopancreatography (ERCP): the dose is selected based on the diagnostic problem and the size of the area being examined.

Others: the dose is selected based on the diagnostic problem and the size of the area being examined.

Newborns (age: <1 month) and infants (age: 1 month-2 years)< h4>

The doctor will exercise particular caution when determining the dose, selecting the parameters of the radiological examination, and assessing the overall condition of the infant (under 1 year of age), especially newborns, as these patients are at increased risk of developing electrolyte disturbances and variable hemodynamic conditions.

Patients with kidney failure

Since iopromide, the active substance of Ultravist, is excreted almost exclusively by the kidneys, the elimination of iopromide is prolonged in patients with kidney failure. To reduce the risk of additional kidney failure caused by contrast agents in patients with pre-existing kidney function disorders, the doctor will use the smallest possible dose (see "Important information before using Ultravist" / "Warnings and precautions").
Contrast-enhanced mammography (CEM)
Ultravist will be administered intravenously (into a vein), if possible using an automatic injector.
Adult women:
Ultravist 300/370: 1.5 mL/kg body weight.

Overdose

In case of overdose, the patient should immediately inform their doctor. Symptoms may include disturbances in water and electrolyte balance, kidney failure, and complications from the cardiovascular and respiratory systems. The doctor will monitor the parameters of water and electrolyte balance and kidney function and may order the removal of the medicine from the body by dialysis.

4. POSSIBLE SIDE EFFECTS

Like all medicines, Ultravist can cause side effects, although not everybody gets them.
The most severe side effects (life-threatening and potentially leading to death) in patients receiving Ultravist are: anaphylactoid shock (allergic reactions), respiratory arrest, bronchospasm (difficulty breathing), laryngeal edema, pharyngeal edema, asthma, coma, cerebral infarction (reduced blood flow to a part of the brain), stroke, cerebral edema, seizures, cardiac arrhythmias, cardiac arrest (heart stops beating), myocardial ischemia (heart disease characterized by pain due to lack of blood flow to the heart), myocardial infarction, heart failure, bradycardia (slow heart rate), sinica (bluish discoloration of the skin and mucous membranes due to lack of oxygen), hypotension (low blood pressure), shock, dyspnea (shortness of breath), pulmonary edema (fluid accumulation in the lungs), and respiratory failure (insufficient oxygen supply to the lungs, and carbon dioxide is not fully exhaled).
The most commonly observed side effects in patients receiving Ultravist are: headache, nausea, and vasodilation.
If any of the following subjective and objective symptoms (whose frequency is unknown) occur, the patient should seek medical help immediately:

• Red spots on the torso, resembling a target or circle, often with blisters in the center, skin peeling, ulcers of the mouth, throat, nose, genitals, and eyes. These severe skin rashes may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome, toxic epidermal necrolysis).
• Widespread rash, high fever, and swollen lymph nodes (DRESS or drug hypersensitivity syndrome).
• Red, peeling, widespread rash with nodules under the skin and blisters, with fever, occurring after imaging (acute generalized exanthematous pustulosis).
• Temporary brain function disorder (encephalopathy), which may cause memory loss, confusion, hallucinations, vision problems, loss of vision, seizures, loss of coordination, weakness on one side of the body, speech difficulties, and loss of consciousness.

Possible side effects are listed below by frequency of occurrence.

Frequent(may occur in 1 to 10 patients out of 100):

• Dizziness
• Headache
• Taste disorders
• Blurred vision / vision disturbances
• Chest pain or discomfort
• Hypertension (high blood pressure)
• Vasodilation
• Vomiting
• Nausea
• Pain
• Reactions at the injection site (e.g., pain, heat, swelling, inflammation, and damage to surrounding soft tissues in case of extravasation)
• Feeling of heat

Infrequent(may occur in 1 to 10 patients out of 1,000):

• Hypersensitivity reactions / anaphylactoid reactions (anaphylactoid shock, respiratory arrest, bronchospasm, laryngeal edema, pharyngeal edema, angioedema, asthma, conjunctivitis, tearing, sneezing, coughing, nasal congestion, rhinitis, hoarseness, throat irritation, urticaria, pruritus, angioedema)
• Vasovagal reactions (loss of consciousness / fainting)
• Confusion
• Restlessness
• Paresthesia (skin sensation disorders such as burning, tingling, itching, or numbness)
• Somnolence
• Arrhythmia (heart rhythm or frequency disorders)
• Hypotension (low blood pressure)
• Dyspnea (shortness of breath)
• Abdominal pain
• Edema (swelling of tissues)

Rare(may occur in 1 to 10 patients out of 10,000):

• Anxiety
• Cardiac arrest (heart stops beating)
• Myocardial ischemia (heart disease characterized by pain due to lack of blood flow to the heart)
• Palpitations (irregular, rapid, or pounding heartbeat)

Unknown(frequency cannot be estimated from available data):

• Thyroid crisis (severe hyperthyroidism complications)
• Thyroid function disorders
• Coma
• Ischemia, cerebral infarction (reduced blood flow to a part of the brain)
• Stroke
• Cerebral edema (reported only with intravascular administration)
• Seizures
• Transient cortical blindness (reported only with intravascular administration)
• Loss of consciousness
• Agitation
• Amnesia (memory loss)
• Tremors
• Speech disorders
• Paresis, paralysis (partial or complete loss of movement ability)
• Hearing disorders
• Myocardial infarction
• Heart failure
• Bradycardia (slow heart rate)
• Tachycardia (rapid heart rate)
• Sinica (bluish discoloration of the skin and mucous membranes due to lack of oxygen)
• Shock
• Thromboembolic complications (blood clot formation in blood vessels leading to stroke) (reported only with intravascular administration)
• Vasospasm (reported only with intravascular administration)
• Pulmonary edema (fluid accumulation in the lungs)
• Respiratory failure (insufficient oxygen supply to the lungs, and carbon dioxide is not fully exhaled)
• Aspiration (choking)
• Swallowing disorders
• Salivary gland enlargement
• Diarrhea
• Bullous syndromes (e.g., Stevens-Johnson syndrome or Lyell syndrome) (severe, inflammatory skin and mucous membrane rashes)
• Rash
• Flushing
• Excessive sweating
• Compartment syndrome (increased pressure in muscles leading to muscle, nerve, and blood flow problems) (reported only with intravascular administration)
• Kidney function disorders (reported only with intravascular administration)
• Acute kidney failure (reported only with intravascular administration)
• Malaise
• Chills
• Pallor
• Body temperature fluctuations

In addition to the side effects listed above, an increase in pancreatic enzyme activity and pancreatitis have been observed after administration of Ultravist during ERCP, with an unknown frequency of occurrence.
If any of the side effects worsen or any side effects not listed in this leaflet occur, the patient should tell their doctor or radiology staff.

Reporting side effects

If side effects occur, including any side effects not listed in this leaflet, the patient should tell their doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety Monitoring of 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 ULTRAVIST

Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the month.
Keep out of the sight and reach of children.
Store in a temperature below 30°C, protected from light and X-ray radiation.

6. CONTENTS OF THE PACK AND OTHER INFORMATION

What Ultravist contains

• The active substance of the medicine is iopromide.

Ultravist 300
1 mL of the solution for injection contains 623.40 mg of iopromide.
Ultravist 370
1 mL of the solution for injection contains 768.86 mg of iopromide.

• Ultravist also contains: calcium sodium edetate, trometamol, hydrochloric acid 10%, sodium hydroxide (to adjust pH), water for injections.

What Ultravist looks like and contents of the pack:

Ultravist 300:
10 vials of 5 mL, 5 vials of 10 mL, 10 vials of 10 mL, 1 vial of 20 mL, 10 vials of 20 mL, 1 bottle of 50 mL, 10 bottles of 50 mL, 1 bottle of 75 mL, 10 bottles of 75 mL, 1 bottle of 100 mL, 10 bottles of 100 mL, 1 bottle of 150 mL, 10 bottles of 150 mL, 1 bottle of 200 mL, 10 bottles of 200 mL, 1 bottle of 500 mL, 8 bottles of 500 mL
Ultravist 370:
1 vial of 20 mL, 10 vials of 20 mL, 1 vial of 30 mL, 10 vials of 30 mL, 1 bottle of 50 mL, 10 bottles of 50 mL, 10 bottles of 75 mL, 1 bottle of 100 mL, 10 bottles of 100 mL, 1 bottle of 150 mL, 10 bottles of 150 mL, 1 bottle of 200 mL, 10 bottles of 200 mL, 1 bottle of 500 mL, 8 bottles of 500 mL
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 Berlin
Müllerstrasse 178
13353 Berlin
Germany
Berlimed S.A., Madrid
Francisco Alonso, 7
Poligono Industrial Santa Rosa
28806 Alcalá de Henares, Madrid
Spain
To obtain more detailed information about this medicine, please 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 leaflet approval: September 2023