Ultravist 370

Ultravist 300, 623.40 mg/ml, solution for injection
Ultravist 370, 768.86 mg/ml, solution for injection
Iopromide
Please read this leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. 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 adverse reactions, including any not listed in this leaflet, inform the doctor or radiology staff immediately. See section 4.

Leaflet contents:

1. What Ultravist is and what it is 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 ULTRAVIST IS AND WHAT IT IS USED FOR

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

Indications
The medicine is intended for diagnostic use only.
Depending on the route of administration and the concentration of Ultravist, imaging of blood vessels (veins and arteries) is obtained, and abnormalities in the urinary system, kidneys, brain, heart, breasts, 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 components of this medicine (listed in section 6).

Warnings and precautions
Before administration, Ultravist should be warmed to body temperature, as it is then better tolerated and its viscosity is reduced, facilitating injection.
Before administering the contrast agent Ultravist, medical personnel will inspect it and, if discoloration, presence of solid particles in the solution (including crystals), or container damage are observed, will not administer the agent. Ultravist is a highly concentrated solution and, rarely, may crystallize (milky appearance and/or sediment at the bottom or floating crystals).
Due to the possibility of pharmaceutical incompatibility, the contrast agent Ultravist must not be mixed with other medicinal products.
Before administering Ultravist contrast agent, inform the doctor if the patient feels anxious. States of excessive excitement, anxiety, or pain may increase the risk of adverse reactions or intensify the severity of reactions to contrast agents (see section "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 the patient has taken adequate fluids before the examination (see section "Warnings and precautions").
Before starting Ultravist administration, discuss the following with the doctor or nurse:

• if the patient has asthma or any other type of allergy (e.g. allergy to seafood, hay fever, urticaria);
• if the patient is allergic to iodine-containing contrast agents, iopromide, or any excipient listed in the section on excipients;
• if the patient previously experienced a reaction to contrast agents;
• if the patient has impaired kidney function;
• if the patient has polyuria;
• if the patient has oliguria;
• if the patient has high blood uric acid levels (hyperuricaemia, gout);
• if the patient has heart or circulatory 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 enlarged thyroid (goitre);
• if the patient has multiple myeloma (bone marrow cancer) or increased production of specific proteins (paraproteinaemia), or has muscle weakness (myasthenia);
• if the patient has arterial hypertension caused by a chromaffin cell tumour of the adrenal gland (pheochromocytoma);
• if the patient is taking certain medications;
• if the patient ever experienced severe skin rash, skin peeling, blisters, and/or oral mucosal ulcers after receiving Ultravist.

This is particularly important for elderly patients, newborns, infants, and young children.
If any of the above conditions are present, the doctor will decide whether the examination can proceed.
Inform the doctor if the patient has kidney problems. The doctor will ensure the patient is well hydrated before the examination. However, intravenous fluid administration (fluids into veins) is not recommended if the patient has kidney problems.
Inform the doctor if the patient has severe kidney problems associated with heart disease. Intravenous fluid administration (fluids into veins) may be dangerous for the heart.
The doctor will not perform a sensitivity test (a small test dose of the contrast agent Ultravist), because such a test does not reliably predict hypersensitivity and itself has occasionally caused severe, even fatal, hypersensitivity reactions.
Exercise particular caution when using Ultravist:
Serious adverse skin reactions have been observed following the use of contrast agents such as Ultravist, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalised exanthematous pustulosis (AGEP). If any symptoms described in section 4 occur, seek immediate medical help.
Hypersensitivity and pseudoallergic reactions have been observed after administration of
radiological contrast agents such as Ultravist (see "Possible side effects").
Inform the doctor if allergic reactions to the contrast agent Ultravist, its excipients, or any other contrast agent have occurred in the past. If bronchial asthma or other allergic reactions have ever occurred, this may indicate an increased risk of allergic-type reactions (including severe reactions).
Allergic-type reactions are characterized by symptoms affecting the cardiovascular system (heart and blood vessels), respiratory system (lungs), and skin (skin reactions).
Reactions resembling allergic reactions may occur, ranging from mild to severe, including anaphylactic shock (see section "Possible side effects"). Such reactions are difficult to predict and may occur unpredictably. Most of these reactions occur within 30 minutes of administration, but delayed reactions (after several hours or days) may also occur.
Inform the doctor if the patient is taking beta-blockers (medications used to treat hypertension), due to the possibility of resistance to treatment with beta-adrenergic agonists (medications used in shock).
After administration of Ultravist, medical personnel will monitor the patient for possible severe hypersensitivity reactions and will have emergency equipment available.
Before the examination, the doctor may administer corticosteroids (medications used, among others, to treat inflammatory conditions) if there is a risk of an acute allergic reaction (e.g. if a previous moderate or severe acute reaction occurred, or if asthma or allergy requiring treatment is present).
Thyroid function disorders
Inform the doctor if hyperthyroidism or goitre is suspected or diagnosed in the patient, due to the risk of developing hyperthyroidism or thyroid storm after administration of iodine-containing contrast agents. In patients with suspected or diagnosed hyperthyroidism, thyroid function tests and/or prophylactic administration of thyroid-suppressing medications may be considered before administering Ultravist.
Inform the doctor if the patient has a history of thyroid disease, 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.
The doctor will assess thyroid function in newborns exposed to Ultravist due to an examination performed on the mother during pregnancy or during the neonatal period, as excess iodine may cause hypothyroidism potentially requiring treatment.
Nervous system disorders
Inform the doctor if the patient has had central nervous system (CNS) disorders (e.g. seizures).
In situations where the seizure threshold may be lowered or blood-brain barrier permeability increased (e.g. due to 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 procedures.
During or shortly after the imaging procedure, a transient brain dysfunction called encephalopathy may occur. If any subjective or objective symptoms related to this condition described in section 4 occur, seek immediate medical help.
Acute kidney injury
When Ultravist is administered intravascularly (into blood vessels), there is a risk of contrast-induced nephropathy (acute kidney injury after contrast administration). As a result, the kidneys may temporarily function improperly. Some patients may experience kidney failure.
This is especially likely if any of the following conditions are present:

• pre-existing kidney failure (kidneys not functioning properly). See also sections "How to use Ultravist" / "Patients with kidney impairment",
• diabetes,
• multiple myeloma (bone marrow cancer),
• paraproteinaemia (excessive production of specific proteins),
• dehydration;
• or if the patient has received repeated or large doses of Ultravist. Contrast-enhanced radiological examinations using Ultravist may be performed in patients with non-functioning kidneys undergoing dialysis.

Cardiovascular diseases
If the patient is to receive intravascular (into blood vessels) administration of Ultravist and has severe heart disease, including advanced coronary artery disease, there is an increased risk of arrhythmias (abnormal heart rhythm or rate) and significant hemodynamic disturbances (changes in blood circulation).
Intravascular administration of contrast agent in patients with heart failure may cause pulmonary edema (fluid accumulation in the lungs) (see sections "Important information before using Ultravist" / "Patients with kidney impairment").
Adrenal chromaffin cell tumour (pheochromocytoma)
If the patient is to receive intravascular (into blood vessels) administration of Ultravist and has an adrenal chromaffin cell tumour, there is an increased risk of hypertensive crisis (severe form of hypertension).
Myasthenia
If the patient is to receive intravascular (into blood vessels) administration of Ultravist and has myasthenia (a chronic muscle disease), administration of Ultravist may worsen the symptoms of the disease.
Contrast-enhanced mammography exposes the patient to a higher level of ionizing radiation than conventional mammography, but it still remains within the range defined by international mammography guidelines. The radiation dose depends on breast thickness and the type of mammography equipment used.
Ultravist and other medicines
Inform the doctor about all medicines currently or recently taken by the patient, as well as any medicines the patient plans to take, including those available without a prescription.
Some medicines may affect the action of Ultravist. These include:

• biguanides (a class of medicines used to treat diabetes);
• interleukin;
• radioactive substances used to treat the thyroid.

The doctor will advise how to use these medicines before the examination.
Using Ultravist with food and drink
The patient should not eat for 2 hours before the examination, but may drink. Further instructions will be provided by the doctor.
Pregnancy and breastfeeding
Pregnancy
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to become pregnant, she should consult a doctor before using this medicine.
Studies in pregnant women have not been conducted.
Animal studies did not show harmful effects of the contrast agent on pregnancy, embryonic or fetal development, course of delivery, or postnatal development of the newborn.
Breastfeeding
Studies on the safety of Ultravist in breastfeeding women have not been conducted. Iopromide, the active substance of the contrast agent, passes into breast milk in small amounts; therefore, the risk of harmful effects on the infant is low. (See section "Important information before using Ultravist" / " Warnings and precautions" / "Thyroid function disorders").
Ultravist contains sodium
The medicine contains less than 1 mmol (23 mg) of sodium per dose (calculated based on the average amount administered to a person weighing 70 kg), meaning the medicine is considered "sodium-free".

3. HOW TO USE ULTRAVIST

The Ultravist medication is administered by trained medical personnel.
Before intravascular (into blood vessels) injection of Ultravist, the physician will assess the patient's
health status and inquire about any medications being taken, as they may influence the risk of thromboembolic complications (blood clot formation).
Additionally, the physician will:

• pay particular attention to the angiography procedure technique;
• flush the catheter appropriately and frequently (if possible, with the addition of heparin – a blood-thinning agent);
• if feasible, shorten the duration of the procedure to minimize the risk of thrombosis and embolism (formation and movement of a blood clot causing vessel blockage).

Dosage – intravascular injection (into blood vessels)
The physician individually determines the appropriate dose of Ultravist for each patient based on age,
body weight, diagnostic purpose, and technique used.
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): dosage is determined according to
the diagnostic issue and size of the area being examined.
Others: dosage is determined according to the diagnostic issue and size of the area being examined.
Newborns (age: <1 month) and infants (age: 1 month–2 years)
The physician must exercise special caution when determining dosage, selecting radiological examination parameters, and evaluating the general condition of infants (under 1 year of age), particularly newborns, as these patients belong to a group at particularly high risk of electrolyte disturbances and hemodynamic instability.
Patients with renal impairment
Since iopromide, the active substance in Ultravist, is excreted almost entirely unchanged by the kidneys, elimination of iopromide is prolonged in patients with renal impairment. To reduce the risk of contrast-induced nephropathy in patients with pre-existing renal dysfunction, the physician will use the smallest possible dose (see “Important information before using Ultravist” / “ Warnings and precautions”).
Contrast-enhanced mammography (CEM)
Ultravist will be administered intravenously (large volume injected into a vein), preferably using an automatic injector if possible.
Adult women:
Ultravist 300/370: 1.5 ml/kg body weight.
Accidental overdose of Ultravist
If more Ultravist has been administered than prescribed and the patient's condition worsens, medical advice must be sought immediately. Symptoms may include disturbances in fluid and electrolyte balance, renal failure, and cardiovascular or pulmonary complications. The physician will monitor fluid and electrolyte balance and kidney function, and may recommend dialysis to remove the drug from the body.

4. POSSIBLE ADVERSE REACTIONS

Like any medicine, this medicinal product can cause adverse reactions, although not everyone will experience them.
The most severe adverse reactions (life-threatening and potentially leading to death)
in patients receiving Ultravist are: anaphylactoid shock (allergy-type reactions),
respiratory arrest, bronchospasm (difficulty breathing), laryngeal oedema, pharyngeal oedema, asthma,
coma, cerebral infarction (reduced blood flow through part of the brain), stroke, cerebral oedema,
seizures, cardiac arrhythmia, cardiac arrest (heart stops beating), myocardial ischaemia (heart disease
manifesting as pain due to lack of blood supply to the heart), myocardial infarction, heart failure,
bradycardia (slow heartbeat), cyanosis (bluish discoloration of the skin and mucous membranes due to lack of oxygen),
hypotension (low blood pressure), shock, dyspnoea (shortness of breath), pulmonary oedema (fluid accumulation
in the lungs), respiratory failure (insufficient oxygen reaches the lungs and carbon dioxide is not fully expelled),
and aspiration.

The most commonly observed adverse reactions in patients receiving Ultravist are:
headache, nausea, and vasodilation.

If any of the following subjective or objective symptoms occur (frequency unknown), seek immediate medical help:

• Reddish skin patches on the trunk, resembling a target or circular lesions, often with blisters in the centre, peeling skin, and oral, pharyngeal, nasal, genital, or ocular mucosal ulcers. These severe skin rashes may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome, toxic epidermal necrolysis).
• Widespread rash, high fever, and enlarged lymph nodes (DRESS syndrome or drug hypersensitivity syndrome).
• Widespread red, scaly rash with subcutaneous nodules and blisters, accompanied by fever, occurring after imaging procedures (acute generalised exanthematous pustulosis).
• Transient brain dysfunction (encephalopathy), which may cause memory loss, confusion, hallucinations, visual disturbances, vision loss, seizures, loss of coordination, hemiparesis, speech difficulties, and loss of consciousness.

Possible adverse reactions are listed below according to their likelihood of occurrence.
Common (may occur in 1 to 10 out of 100 patients):

• Dizziness
• Headache
• Taste disturbances
• Blurred vision / visual disturbances
• Chest pain, discomfort
• Hypertension (high blood pressure)
• Vasodilation
• Vomiting
• Nausea
• Pain
• Injection site reactions (e.g. pain, warmth, swelling, inflammation, and damage to surrounding soft tissues in case of extravasation)
• Feeling of warmth

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

• Hypersensitivity / anaphylactoid reactions (anaphylactoid shock, respiratory arrest, bronchospasm (difficulty breathing), laryngeal oedema, pharyngeal oedema, tongue or facial oedema, laryngospasm, pharyngospasm, asthma, conjunctivitis, lacrimation, sneezing, cough, mucosal oedema, rhinitis, hoarseness, throat irritation, urticaria, pruritus (intense itching), angioneurotic oedema
• Vasovagal reactions (loss of consciousness / fainting)
• Confusion
• Motor restlessness
• Paresthesia (skin sensation disturbances such as burning, stinging, itching, or tingling) / hypoesthesia (reduced sensitivity to touch)
• Somnolence
• Arrhythmia (irregularities in heart rhythm or rate)
• Hypotension (low blood pressure)
• Dyspnoea (shortness of breath)
• Abdominal pain
• Oedema (swelling of tissues)

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

• Anxiety
• Cardiac arrest (heart stops beating)
• Myocardial ischaemia (heart disease manifesting as pain due to lack of blood supply to the heart)
• Palpitations (irregular, rapid heartbeat or pulsation)

Unknown (frequency cannot be determined from available data):

• Thyroid storm (severe complications of hyperthyroidism)
• Thyroid dysfunction
• Coma
• Cerebral ischaemia, cerebral infarction (reduced blood flow through part of the brain)
• Stroke
• Cerebral oedema (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 ability to move)
• Hearing disturbances
• Myocardial infarction
• Heart failure
• Bradycardia (slow heartbeat)
• Tachycardia (rapid heartbeat)
• Cyanosis (bluish discoloration of the skin and mucous membranes due to lack of oxygen)
• Shock
• Thromboembolic complications (formation of blood clots in blood vessels leading to stroke) (reported only with intravascular administration)
• Vasoconstriction (reported only with intravascular administration)
• Pulmonary oedema (fluid accumulation in the lungs)
• Respiratory failure (insufficient oxygen reaches the lungs and carbon dioxide is not fully expelled)
• Aspiration
• Swallowing disorders
• Salivary gland enlargement
• Diarrhoea
• Bullous syndromes (e.g. Stevens-Johnson syndrome or Lyell's syndrome) (serious inflammatory skin and mucosal lesions)
• Rash
• Erythema (redness of the skin)
• Excessive sweating
• Compartment syndrome (in case of extravasation) (increased pressure within muscles leading to muscle, nerve, and blood flow problems) (reported only with intravascular administration)
• Renal function disorders (reported only with intravascular administration)
• Acute renal failure (reported only with intravascular administration)
• Malaise
• Chills
• Pallor
• Body temperature fluctuations

In addition to the adverse reactions listed above, following administration of the medicinal product during ERCP procedures, increased pancreatic enzyme activity and pancreatitis have been observed, with unknown frequency of occurrence.
If any adverse reaction worsens or if any adverse reactions not listed in this leaflet occur, inform your doctor or radiology department staff immediately.
Reporting of adverse reactions
If any adverse reactions occur, including those not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions, 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 .
Adverse reactions can also be reported to the marketing authorisation holder.
Reporting adverse reactions helps to provide more information on the safety of the medicinal product.

5. HOW TO STORE ULTRAVIST

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

6. CONTENTS OF THE PACKAGE AND OTHER INFORMATION

What Ultravist contains

• The active substance is iopromide.

Ultravist 300
1 ml of injection solution contains 623.40 mg of iopromide.
Ultravist 370
1 ml of injection solution contains 768.86 mg of iopromide.

• Other components of Ultravist are: edetate disodium calcium, trometamol, hydrochloric acid 10%, 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 Authorisation 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

For further information about this medicinal product, please contact the representative of the Marketing Authorisation Holder:
Bayer Sp. z o.o.
Al. Jerozolimskie 158
02-326 Warsaw
Phone: (0-22) 572 35 00

Information intended exclusively for medical professionals:

Indications
The medicinal product is intended for diagnostic use only.
Ultravist 300/370: for intravenous, intra-arterial and intracavitary administration.
A contrast agent for use in computed tomography (CT), arteriography, venography, intravenous and intra-arterial digital subtraction angiography (DSA), intravenous urography, endoscopic retrograde cholangiopancreatography (ERCP), arthrography and other body cavity examinations, and for use in contrast-enhanced mammography in adult women for evaluation and detection of known or suspected breast lesions, as an adjunct to mammography (with or without ultrasound) or as an alternative to magnetic resonance imaging (MRI) when MRI is contraindicated or unavailable.
Ultravist 370: a contrast agent recommended for use in angiocardiography.

Route of administration:
Prior to administration, Ultravist contrast agent should be warmed to body temperature.
Contrast agents should be inspected visually before administration. Do not use the contrast agent if significant discoloration, presence of particulate matter in the solution (including crystals), or container damage is observed. Ultravist is a highly concentrated solution and, rarely, may crystallize (appearing milky or turbid, and/or with sediment at the bottom or floating crystals).

Vials:
Any unused portion of the contrast agent solution remaining after a patient procedure must be discarded.

Large-volume containers:
The contrast agent must be administered exclusively using an automated injection system or another registered procedure ensuring sterility of the contrast solution. Follow the manufacturer's instructions for the device.
Any unused portion of Ultravist contrast agent remaining in an opened container must be discarded 10 hours after the first opening of the container.