Ultravist

Package leaflet: Information for the user

Ultravist 150 mg/ml injection solution, 240 mg/ml injection solution, 300 mg/ml injection solution, 370 mg/ml injection solution

iopromide
Please read this leaflet carefully before you are given this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, radiographer, or nurse.
• If you get any side effects, including those not listed in this leaflet, tell your doctor, pharmacist, radiographer, or nurse. See section 4.

Contents of this leaflet:

1. What Ultravist is and what it is used for
2. What you need to know before you are given Ultravist
3. How Ultravist will be administered to you
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 belongs to the class of water-soluble, nephrotropic, low-osmolar radiological contrast agents.
This medicinal product is for diagnostic use only.
Ultravist is used as a contrast medium for the following diagnostic procedures:
angiography, digital subtraction angiography (DSA) via venous and arterial routes, contrast enhancement in computed tomography, urography, imaging of body cavities (excluding myelography, ventriculography, and cisternography), and in adult women, contrast-enhanced mammography 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 unavailable.

2. What you should know before using Ultravist

Do not receive Ultravist

• if you are allergic to iopromide, water-soluble contrast media, and/or iodine or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Speak to your doctor, radiographer, or nurse before receiving Ultravist.
The use of organoiodinated products such as Ultravist should be limited to cases where there is a clear clinical indication for contrast imaging, which your doctor will assess based on your clinical condition, particularly with regard to any pre-existing diseases affecting the cardiovascular, urogenital, and hepatobiliary systems.
In the following cases, your doctor will carefully evaluate the risk/benefit ratio before administering Ultravist, as administration of the medicine may expose you to a high risk of serious adverse effects:

• if you suffer from Waldenström's macroglobulinemia (a disease characterized by the presence of abnormal proteins in the blood) and multiple myeloma (a tumor of the bone marrow),
• if you have liver and/or kidney disease,
• if you have a pheochromocytoma (a tumor of the adrenal gland),
• if you have homozygous sickle cell anemia,
• if you have acute pelvic inflammation,
• if you are elderly,
• if you have heart disease,
• if you have hypertension (high blood pressure),
• if you have advanced arteriosclerosis (a chronic inflammatory disease of the arteries),
• if you have tumors,
• if you have previously experienced reactions to contrast media,
• if you have allergies,
• if you have asthma,
• if you have diabetes,
• if you have recently had cerebral embolism or thrombosis (formation of a blood clot in a blood vessel of the brain),
• if you have hyperthyroidism (excessive activity of the thyroid gland),
• if you have hyperuricemia (elevated levels of uric acid in the blood),
• if you have cholangitis (inflammation of the bile ducts),
• if you abuse alcohol and/or smoke,
• if you have anxiety,
• if you have ever developed a severe skin rash or skin exfoliation, skin rash with blisters and/or mouth ulcers after using Ultravist.

Exercise particular caution with Ultravist:
Severe skin reactions, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and generalized acute exanthematous pustulosis (GEP) have been reported in association with the use of Ultravist. Consult a doctor immediately if you notice any of the signs described in section 4.
Hypersensitivity reactions
Ultravist may be associated with anaphylactoid/hypersensitivity reactions (severe allergic or allergy-like reactions) or other intolerance reactions, characterized by cardiovascular, respiratory, and cutaneous manifestations.
Allergy-like reactions of variable intensity, ranging from mild to shock, are possible (see "Possible side effects"). Most of these reactions occur within 30 minutes of administration. However, delayed reactions (after hours or days) are also possible.
The risk of allergic reactions is higher if:

• you have previously experienced reactions to contrast media;
• you have a history of bronchial asthma or other allergic disorders (e.g., allergy to seafood, hay fever, or urticaria).

If you have previously experienced a hypersensitivity reaction to any other iodinated or radiographic contrast medium (in the broad sense), your doctor will pay particular attention to evaluating the risk/benefit ratio due to an increased risk of allergic reactions and may decide to administer preventive therapy with corticosteroids alone or in combination with antihistamines. This therapy must not be administered concomitantly with contrast media. However, these reactions are irregular and unpredictable.
In patients with cardiovascular diseases, severe or even fatal outcomes are more likely in the event of a severe allergic reaction.
Due to the possibility of significant allergic reactions after administration of Ultravist, you will be kept under observation after the examination.
If you are at increased risk of acute allergy-like reactions or have previously experienced a moderate or severe acute reaction, asthma, or an allergy requiring treatment, your doctor may decide to administer corticosteroids.
If hypersensitivity reactions occur, administration of the contrast medium will be immediately discontinued. Regardless of the amount and type of administration, even mild allergy symptoms may be the first signs of severe anaphylactoid reactions.
Inform your doctor if you have a history of thyroid disease, including hypothyroidism (a condition in which the thyroid gland is underactive). After diagnostic tests performed with iodine-containing contrast agents, abnormal blood tests for thyroid function have been reported, which may suggest potential hypothyroidism or a transient (temporary) reduction in thyroid function that may require treatment.
Thyroid function alterations
Your doctor will carefully evaluate the risk/benefit ratio in patients with confirmed or suspected hyperthyroidism or goiter, as iodinated contrast media may induce hyperthyroidism (excessive activity of the thyroid gland) and thyrotoxic crisis (excess thyroid hormones in circulation) in these patients.
If you have or suspect you have hyperthyroidism, your doctor may perform tests to assess thyroid function and/or prescribe preventive antithyroid treatment.
Central nervous system disorders
Patients with central nervous system disorders may be at increased risk of neurological complications following administration of Ultravist. Neurological complications are more frequent in cerebral angiography and related procedures.
Particular attention must be paid in cases of: previous epilepsy, presence of blood in cerebrospinal fluid, concomitant therapy with antipsychotics, analgesics, sedative antihistamines (phenothiazines), and all other medicines that predispose to seizures.
If you are taking anticonvulsant medication, you should continue treatment prior to the radiological examination. If seizures occur during the examination, your doctor will administer diazepam or sodium phenobarbital intravenously.
Factors that increase the permeability of the blood-brain barrier (the structure separating brain nervous tissue from the bloodstream) facilitate the passage of the contrast medium into brain tissue, potentially leading to reactions affecting the central nervous system.
Nervous system disorders
During or shortly after the imaging procedure, you may experience a short-term brain disorder called encephalopathy. Inform your doctor immediately if you notice any of the signs and symptoms related to this condition described in section 4.
Hydration
Before and after intravascular administration of Ultravist, adequate hydration will be ensured, especially if you have multiple myeloma (a tumor of the bone marrow), diabetes (a disease characterized by high blood glucose levels due to reduced insulin production by the pancreas), polyuria (increased urine volume), oliguria (reduced urine volume), or hyperuricemia (elevated levels of uric acid in the blood), if you are elderly, or if the examination is to be performed on a child (see section "Intravascular use" – "Acute kidney injury").
In case of severe renal impairment (eGFR <30 mL/min/1.73 m²), intravenous fluids will be administered before and after the use of the contrast medium. If you have heart disease, your doctor will carefully evaluate the most appropriate hydration method for you.
Anxiety
Marked states of excitement, anxiety, and pain may increase the risk of adverse effects or intensify reactions related to the contrast medium.
Intravascular use

• Acute kidney injury After intravascular administration of Ultravist, acute kidney injury may occur, with transient impairment of kidney function, which will be monitored by blood tests. Risk factors include:
  • renal impairment (reduced kidney function),
  • dehydration,
  • diabetes,
  • multiple myeloma/paraproteinemia (elevated levels of certain proteins in the blood),
  • repeated and/or high doses of Ultravist.

Patients on dialysis without residual kidney function may receive Ultravist for radiological examinations, as iodinated contrast media are eliminated through dialysis.

• Cardiovascular diseases The incidence of serious adverse effects increases if you have: advanced arteriosclerosis (a chronic inflammatory disease of the arteries), hypertension (high blood pressure), heart failure (the heart's inability to pump sufficient blood), severe systemic disease (affecting the entire organism), recent pulmonary embolism or cerebral thrombosis (formation of a blood clot in a blood vessel of the lung or brain). In cases of severe heart disease, the risk of worsening pre-existing conditions and onset of heart rhythm disturbances (arrhythmias) is increased; therefore, you will be closely monitored.
• Pheochromocytoma Patients with pheochromocytoma (a tumor of the adrenal gland) may be at increased risk of developing hypertensive crises.
• Myasthenia gravis
  Administration of Ultravist may worsen symptoms of myasthenia gravis (an autoimmune disease characterized by muscle weakness).
  Contrast-Enhanced Mammography (CEM)
  Contrast-enhanced mammography exposes patients to higher levels of ionizing radiation compared to traditional mammography, but still falls within the range defined by international guidelines for mammography. The radiation dose depends on breast thickness and the type of mammography equipment used.
  Children, newborns, and infants
  Newborns may have been exposed to Ultravist through their mother during pregnancy.
  If your child is under 3 years of age: your doctor may monitor and check thyroid function, particularly in newborns.
  Adequate hydration must be ensured before and after intravascular administration of Ultravist to minimize the risk of contrast medium-induced renal toxicity (see also "Intravascular use" – "Impairment of renal function"). This is particularly important in newborns, infants, and young children.
  In pediatric practice, injection into the right heart requires particular caution in cyanotic newborns (those with bluish skin and mucous membranes) with pulmonary hypertension (increased pressure in the pulmonary circulation) and impaired cardiac function.
  Other medicines and Ultravist
  Inform your doctor, radiographer, or nurse if you are taking, have recently taken, or might take any other medicines.
  Biguanides (such as Metformin, a medicine for diabetes): in patients with acute renal impairment (rapid reduction in kidney function) or severe chronic kidney disease, elimination of biguanides may be reduced, leading to accumulation and development of lactic acidosis (accumulation of lactate in the body). Since administration of Ultravist may cause or worsen impaired kidney function, patients treated with metformin may be at increased risk of developing lactic acidosis, especially those with pre-existing impaired kidney function.
  Based on assessment of kidney function, your doctor will evaluate whether metformin administration needs to be discontinued.
  Interleukin-2 (a medicine that modulates the immune system): previous treatment (up to several weeks prior) with interleukin-2 is associated with an increased risk of delayed reactions to Ultravist.
  Radioactive iodine: for diagnosis and treatment of thyroid diseases using radioactive iodine, note that after administration of renally excreted iodinated contrast media, iodine uptake by thyroid tissue is reduced for a prolonged period of up to 2 weeks, and in individual cases, even longer.
  Pregnancy and breastfeeding
  If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, inform your doctor, radiographer, or nurse before receiving this medicine.
  Adequate and well-controlled studies in pregnant women have not been conducted.
  Animal studies are insufficient to demonstrate potential harmful effects on pregnancy, embryonic/fetal development, delivery, or postnatal development following administration of iopromide for diagnostic use in humans.
  The safety of Ultravist in infants has not been studied. Contrast media pass into human breast milk in small amounts, and it is unlikely that this would cause harm to the breastfed infant (see also "Children, newborns, and infants").
  Ultravist contains sodium
  This medicine contains less than 1 mmol (23 mg) of sodium per dose (based on the average dose administered to a 70 kg person), i.e., essentially 'sodium-free'.

3. How Ultravist will be administered to you

General information
At the time of the examination, you must have fasted for at least six to eight hours and be adequately hydrated.
The medicine will be administered while you are lying down, and you will then be kept under observation for at least half an hour after the administration is completed. Most serious reactions occur within this time frame.
In urography and abdominal angiography, image contrast will be better if there are no food residues or gas in the intestine. Therefore, during the 24 hours preceding the examination, avoid foods that produce residues or cause bloating.
The dose of Ultravist administered to you will depend on the following parameters: age, weight, cardiac output, general condition, diagnostic purpose, type and technique of examination, and extent of the area to be examined.

Contrast-enhanced mammography (CEM, Contrast-Enhanced Mammography)
Ultravist will be injected intravenously (a significant amount into a vein), preferably using an automatic injector.

Adults:
Ultravist 300/370: 1.5 ml/kg of body weight.

Use in neonates and early infancy
Laxatives must not be used in infants, and prolonged fasting should not be applied.
Infants under one year of age, and especially neonates, are particularly sensitive to electrolyte imbalances (salts) and circulatory disturbances. Care must be taken regarding the dose of contrast medium to be administered, the technical performance of the radiological procedure, and the patient's condition.

Use in patients with impaired liver function
Dosage adjustments are not required in this patient population.

Use in patients with impaired kidney function
Since iopromide is excreted almost entirely unchanged via the kidneys, its elimination is slower in patients with impaired renal function. In patients with pre-existing kidney dysfunction, to reduce the risk of further contrast-induced kidney damage, the smallest possible dose should be used (see also “Warnings and precautions”).

If you are given more Ultravist than you should have received
Intravascular overdose: symptoms may include fluid and electrolyte imbalance, kidney failure (reduced kidney function), and cardiovascular and pulmonary complications.
In case of accidental intravascular overdose, your doctor will monitor fluid balance, electrolytes, and kidney function (the latter for at least 3 days). Treatment of overdose should focus on maintaining vital functions.
Ultravist can be removed from the body by dialysis.

If you have any doubts about the use of this medicine, consult your doctor, radiographer, or nurse.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.
The adverse reactions most frequently observed (≥ 4%) in patients receiving Ultravist are:

• headache,
• nausea,
• vasodilation (dilation of blood vessels).

The most serious adverse reactions are: anaphylactic shock (a severe, rapidly developing allergic reaction that may be fatal), respiratory arrest, bronchospasm (contraction of the airway muscles, obstructing airflow), laryngeal edema (swelling of the larynx), pharyngeal edema (swelling of the pharynx), asthma, coma, cerebral infarction, stroke, cerebral edema (increased water content in brain tissue), convulsion, arrhythmia (irregular heartbeat), cardiac arrest, myocardial ischemia (inadequate blood supply to the heart muscle), myocardial infarction, heart failure (weak heart), bradycardia (slowed heartbeat), cyanosis (bluish discoloration of the skin and mucous membranes), hypotension (low blood pressure), shock (sudden drop in blood pressure), dyspnea (shortness of breath), pulmonary edema (fluid accumulation in the lungs), respiratory failure, and aspiration.

The adverse reactions observed with Ultravist are listed below.
Common adverse effects (may affect up to 1 in 10 people)

• dizziness,
• headache,
• altered taste,
• blurred/changed vision,
• chest pain/discomfort,
• hypertension (high blood pressure),
• vasodilation (dilation of blood vessels),
• vomiting,
• nausea,
• pain at injection site,
• injection site reactions (e.g., pain, sensation of warmth, swelling, inflammation, and soft tissue damage in case of extravasation),
• sensation of warmth.

Uncommon adverse effects (may affect up to 1 in 100 people)

• hypersensitivity/anaphylactoid reactions (anaphylactoid shock *,
• respiratory arrest *,
• bronchospasm* (contraction of the airway muscles, obstructing airflow),
• laryngeal*/pharyngeal*/facial edema* (swelling of the larynx/pharynx/face), tongue edema (swelling of the tongue),
• laryngeal/pharyngeal spasm (contraction of the larynx/pharynx),
• asthma *,
• conjunctivitis,
• lacrimation,
• sneezing,
• cough,
• edema (swelling) of mucous membranes,
• rhinitis (inflammation of the nasal mucosa),
• hoarseness,
• throat irritation,
• urticaria (itching and small skin spots),
• itching,
• angioedema (rapid swelling of the skin of the face and mucous membranes),
• vasovagal reactions (excessive nervous system responses leading to low blood pressure, pallor, dizziness, sweating, etc.),
• confusion,
• restlessness,
• paresthesia/hypoesthesia (altered/reduced skin sensitivity),
• somnolence,
• arrhythmia* (irregular heartbeat),
• hypotension* (low blood pressure),
• dyspnea* (shortness of breath),
• abdominal pain (stomach ache),
• edema (swelling) at injection site.

Rare adverse effects (may affect up to 1 in 1,000 people)

• anxiety,
• cardiac arrest*,
• myocardial ischemia* (inadequate blood supply to the heart muscle),
• palpitations (awareness of rapid heartbeat).

Adverse effects with unknown frequency (frequency cannot be estimated from the available data)

• thyrotoxic crisis (excess thyroid hormones in circulation),
• thyroid disorders,
• coma*,
• cerebral ischemia/infarction* (inadequate blood supply to part of the brain),
• stroke*,
• cerebral edema* (increased water content in brain tissue),
• convulsion*,
• transient cortical blindness (transient blindness due to damage to the cerebral cortex),
• loss of consciousness,
• agitation,
• amnesia (memory loss),
• tremor,
• speech disorders,
• paresis (partial loss of muscle movement)/paralysis,
• hearing disturbances,
• myocardial infarction*,
• heart failure*,
• bradycardia* (slowed heartbeat),
• tachycardia (rapid heartbeat),
• cyanosis* (bluish discoloration of the skin and mucous membranes),
• shock* (sudden drop in blood pressure),
• thromboembolic events (formation of blood clots in blood vessels),
• vasospasm (contraction of blood vessels),
• pulmonary edema* (fluid accumulation in the lungs),
• respiratory failure*,
• aspiration*,
• dysphagia (difficulty swallowing),
• salivary gland enlargement,
• diarrhea,
• bullous manifestations (e.g., Stevens-Johnson syndrome or Lyell’s syndrome),
• skin rash,
• erythema (skin irritation),
• hyperhidrosis (excessive sweating),
• compartment syndrome (increased pressure within a muscle compartment) in case of extravasation,
• impaired renal function,
• renal failure (reduced kidney function),
• acute renal failure (rapid decline in kidney function),
• malaise,
• chills,
• pallor,
• fluctuation in body temperature,
• transiently inactive thyroid in neonates.

Contact a doctor immediately if you notice any of the following signs and symptoms (frequency unknown):

• reddish patches on the trunk resembling a target or circular in shape, often with blisters in the center, skin peeling, mouth, throat, nose, genital, or eye ulcers. These severe skin rashes may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome, toxic epidermal necrolysis);
• widespread rash, high body temperature, and swollen lymph nodes (DRESS syndrome or drug hypersensitivity syndrome);
• widespread, red, scaly rash with subcutaneous pustules and blisters accompanied by fever after an imaging procedure (acute generalized exanthematous pustulosis);
• short-term brain disorder (encephalopathy) that may cause memory loss, confusion, hallucinations, vision problems, loss of vision, seizures, loss of coordination, hemiparesis (loss of movement on one side of the body), speech difficulties, and loss of consciousness.

The following adverse effects have also been reported:

• grand mal (epileptic seizure),
• aseptic meningitis (non-infectious inflammation of the meninges),
• vasculitis (inflammation of blood vessels),
• cold,
• intestinal necrosis (death of intestinal tissue),
• polyuria (increased urine volume),
• hematuria (blood in urine),
• urinary retention (inability to completely empty the bladder),
• renal infarction (occlusion of a renal artery),
• spinal cord injury,
• retroperitoneal hemorrhages (bleeding behind the abdominal cavity),
• increased levels of pancreatic enzymes and pancreatitis (when the medicine is used for endoscopic retrograde cholangiopancreatography - ERCP).

* Life-threatening and/or fatal cases have been reported
only for intravascular use
identified only during post-marketing surveillance (frequency not known)
Most reactions following use in body cavities occur several hours after administration.

Reporting of adverse effects
If you experience any adverse effect, including those not listed in this leaflet, talk to your doctor, pharmacist, radiology technician, or nurse. You may also report adverse effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. How to store Ultravist

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and label after Exp. The expiry date refers to the last day of that month. The expiry date applies to the product in its original, unopened packaging and properly stored.
Once opened, the vial must be used immediately. Any unused portion must not be retained.
Do not store above 30°C.
Keep the container in the outer packaging to protect the medicine from light.
Protect the medicine from ionizing radiation.
Caution
Any additional instructions provided by the respective manufacturer regarding equipment must be observed.
Contrast media must be visually inspected before use.
Do not use this medicine if you notice any change in colour, presence of particles (including crystals), or if the container is damaged. Since Ultravist is a highly concentrated solution, crystallization may very rarely occur (appearance of milky-turbid solution and/or deposit at the bottom, or floating crystals).
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Package contents and other information

What Ultravist contains

• The active substance is iopromide. Each vial contains:
  Ultravist 150 mg/ml – 311.7 mg/ml of iopromide (equivalent to 150.0 mg/ml of iodine).
  Ultravist 240 mg/ml – 498.7 mg/ml of iopromide (equivalent to 240.0 mg/ml of iodine).
  Ultravist 300 mg/ml – 623.4 mg/ml of iopromide (equivalent to 300.0 mg/ml of iodine).
  Ultravist 370 mg/ml – 768.9 mg/ml of iopromide (equivalent to 370.0 mg/ml of iodine).
• The other components are: trometamol, sodium calcium edetate, hydrochloric acid, sodium hydroxide (for pH adjustment), water for injections.

Description of the appearance of Ultravist and contents of the pack
Ultravist is a clear, particle-free injectable solution.
Pack sizes:

• Ultravist 150 mg/ml: 200 ml vials
• Ultravist 240 mg/ml: 50 ml vial
• Ultravist 300 mg/ml: 20-50-75-100-200-500 ml vials
• Ultravist 370 mg/ml: 50-100-200-500 ml vials

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
Bayer AG
Kaiser-Wilhelm-Allee 1
51373 Leverkusen (Germany)
Local representative:
Bayer S.p.A. – Viale Certosa, 130 – 20156 Milan, Italy
Manufacturer
The manufacturer can be identified by the batch number printed on the side of the package and on each vial.

• If the first and second characters are KT, the manufacturer is Bayer AG Muellerstrasse 178, 13353 Berlin, Germany
• If the first and second characters are MA, the manufacturer is Berlimed S.A., Francisco Alonso, 7, Poligono Industrial Santa Rosa, 28806 Alcalá de Henares, Madrid, Spain

The following information is intended exclusively for physicians or healthcare professionals:
General information
The use of contrast media (CM) must occur exclusively in hospitals, clinics, radiological outpatient facilities or specialist radiological practices where equipment and trained personnel are immediately available to manage emergencies.
However, for commonly performed contrast examinations, it may be sufficient that public or private radiology departments have appropriate equipment and medications immediately available for the treatment of potential emergencies (Ambu bag, oxygen, antihistamines, corticosteroids, vasoconstrictors, etc.).
In any case, prompt availability and activation of appropriate emergency measures are required for all patients.
Intravenous administrations must be performed with the patient lying down, and the patient must remain under observation for at least 30 minutes after completion of the injection or infusion. Most serious adverse events occur within this time frame. Vials should be opened only immediately before use, and unused CM solution must not be stored (see “Instructions for use”).
Intravascular administration of any CM should be postponed in subjects who have recently received a CM for cholecystography.

Preliminary test
Performing a sensitivity test using a small test dose of contrast medium is not recommended, as such a test has no predictive value. Moreover, the test itself has occasionally caused severe and even fatal hypersensitivity reactions.

Cardiovascular diseases
During angiocardiography, particular attention must be paid to the condition of the right heart and pulmonary circulation; in cases of cardiac insufficiency, additional volumes of CM may cause circulatory overload with bradycardia and decreased systemic blood pressure. During aortic arch imaging, special care must be taken regarding catheter tip positioning. Excessive pressure transmitted from the injector to the brachiocephalic vessels may cause hypotension, bradycardia, and central nervous system damage. Similarly, in abdominal aortography, excessive pressure delivered by an automatic pump may cause renal infarction, spinal cord injury, retroperitoneal hemorrhage, intestinal infarction, and necrosis.

Thromboembolic events
A property of non-ionic contrast media is their minimal interference with normal physiological functions. In vitro studies have shown that, at equal concentrations, the inhibitory effects of non-ionic CM on hemostatic mechanisms are less pronounced than those of ionic CM. Numerous factors, besides the contrast medium itself, may contribute to the development of thromboembolic events. These include duration of the procedure, number of injections, catheter and syringe material, underlying disease, and concomitant pharmacological therapies. Therefore, it is recommended that proper angiographic techniques be followed: catheters should be frequently flushed with heparinized saline solution, prolonged contact between blood and CM in catheters and syringes should be avoided, and the duration of the procedure should be minimized to reduce the risk of thrombosis and embolism.

Patients should be reassured through conversation or medication to prevent anxiety states, which increase the risk of serious adverse effects.
Patients scheduled to receive organoiodine contrast media via intravascular route should be interviewed regarding possible pregnancy, breastfeeding, allergies, current therapies (including self-medication), and any other conditions listed among contraindications and precautions for use.

Contrast media warmed prior to administration are better tolerated and can be injected more easily due to reduced viscosity.
For further information, see “Instructions for use”.

Recommendations for the management of contrast medium-related adverse effects
Immediate availability of all medications and equipment necessary for emergency treatment, as well as the presence of trained personnel, is essential for rapid intervention in case of contrast medium-related adverse effects (see section “Warnings and precautions”).
Patients receiving beta-blockers (medications that lower blood pressure) who experience hypersensitivity reactions may be resistant to the effects of beta-agonist treatment.
Adherence to the instructions provided in the package leaflet reduces the risk of adverse reactions.

Administration regimen
Dosage for intravascular use
The dose is determined based on age, body weight, cardiac output, patient's general condition, diagnostic question, examination technique, and extent of the area to be examined.

A NGIOGRAPHY
The following table suggests some dosages:

DIGITAL SUBTRACTION ANGIOGRAPHY (DSA)
INTRAVENOUS DSA
For visualization of large vessels and pulmonary arteries, neck, head, kidneys, and limbs, it is recommended to inject 30–60 ml of Ultravist 300 or 370 as an intravenous bolus (8–12 ml/sec via cubital vein; 10–20 ml/sec via catheter into the vena cava). An additional subsequent bolus injection of 20–40 ml of physiological saline solution may reduce the contact time of the contrast medium with the vascular endothelium.

INTRA-ARTERIAL DSA
In intra-arterial DSA, volumes of contrast solution and iodine concentrations lower than those used for intravenous administration are recommended.
The more selective the angiography, the lower the required dose of Ultravist. This technique is therefore recommended in patients with impaired renal function. In particular, for visualization of arteries of the head, neck, and limbs, several direct injections or catheter injections of 10–40 ml of Ultravist 150 or 240 are recommended, depending on the diameter of the vessels to be examined. Higher doses of Ultravist 150 (approximately 200 ml) may be necessary in some cases to visualize vessels of the lower limbs (e.g., during radiographic examination of both limbs).

DIALYSIS SHUNT FUNCTION
Ultravist 150 is also indicated for assessing dialysis shunt function. For this purpose, administration of approximately 10 ml of contrast medium is generally sufficient.

COMPUTED TOMOGRAPHY (CT)
CEREBRAL CT
For contrast enhancement of neoplasms and other lesions, the following dosages are recommended:
Ultravist 240: 1.5 – 2.5 ml/kg body weight
Ultravist 300: 1 – 2 ml/kg body weight
Ultravist 370: 1 – 1.5 ml/kg body weight
The following table suggests average times for initiation of scans.

The difference in the timing of scan initiation is due to the fact that the peak blood concentration of the contrast medium occurs immediately after administration, whereas in individual pathologically altered tissues, maximum concentration is reached at varying times.
With a slow scanner, a dose of 100 ml administered using a biphasic technique (50 ml over approximately 3 minutes and the remainder over approximately 7 minutes) allows maintenance of a relatively constant blood level for a certain period, although less elevated. Scans must begin after completion of the first phase of administration.

TOTAL BODY CT
The doses of Ultravist and the rate of administration depend on the organs to be examined, the diagnostic question, and particularly on the type of scanner available.

UROGRAPHY
ADULTS
The mild osmotic diuretic effect of Ultravist enables high urinary concentration of the contrast medium, allowing excellent visualization of the renal pelvis and calyceal system. If the diagnostic question also requires adequate filling of the ureters, the dose should not be less than 1 ml/kg of Ultravist 300 (0.8 ml/kg of Ultravist 370; 1.3 ml/kg of Ultravist 240). In special cases, for example in patients with unfavorable excretory conditions, the dose may be increased.

CHILDREN
The naturally reduced concentrating capacity of the infant kidney due to immature nephrons requires relatively high doses of contrast medium. When using Ultravist 300, the following dosages are recommended:
Neonates: 1.2 g iodine/kg body weight, corresponding to 4.0 ml/kg body weight
Infants: 1.0 g iodine/kg body weight, corresponding to approximately 3.0 ml/kg body weight
Young children: 0.5 g iodine/kg body weight, corresponding to approximately 1.5 ml/kg body weight

SCAN TIMING
When these dosages are followed and Ultravist 300–370 is injected over 1–2 minutes (3–5 minutes with Ultravist 240), in most cases the renal parenchyma is well enhanced 3–5 minutes after the start of administration (5–10 minutes with Ultravist 240), and the renal pelvis and urinary tract are visualized after 8–15 minutes (12–20 minutes with Ultravist 240). For younger patients, the shorter interval should be chosen; for older patients, the longer one. In infants and young children, it is recommended to perform the first scan early, approximately 2 minutes after contrast administration. If visualization is insufficient, subsequent scans are necessary.

VISUALIZATION OF BODY CAVITIES
The following doses are recommended:
Arthrography: Ultravist 240–300–370, 2–15 ml
Hysterosalpingography: Ultravist 240–300, 10–25 ml

CONTRAST-ENHANCED MAMMOGRAPHY (CEM)
Ultravist 300/370: for use in adult women undergoing contrast-enhanced mammography 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 unavailable.
Ultravist must be administered intravenously, preferably using an automatic injector. Image acquisition begins approximately 2 minutes after administration of the contrast medium.
Adults:
Ultravist 300/370: 1.5 ml/kg body weight.

Instructions for Use
Ultravist must be warmed to body temperature before use.
Contrast media must be visually inspected before use and must not be used if there is discoloration, presence of particles (including crystals), or if the container is damaged. Since Ultravist is a highly concentrated solution, crystallization may very rarely occur (milky-turbid appearance and/or deposit at the bottom, or floating crystals).
Vials should be opened only immediately before use, and unused contrast medium solution must not be stored.
The contrast medium solution should be withdrawn in a single step, so that the rubber stopper is punctured only once. For puncturing the rubber stopper and withdrawing the contrast medium solution, needles with long bevels and a maximum diameter of 18 G are recommended (needles with lateral openings are particularly suitable).

For the use of 500 ml Ultravist vials, the following guidelines are recommended. The contrast medium solution must be administered using an automatic injector. The tubing connecting the injector to the patient ("patient tubing") must be replaced after each examination because it becomes contaminated with blood. Unused contrast medium remaining in the vial, in the connecting tubes, and in any part of the injector must be discarded at the end of the day's examinations.

Plastic Cartridges
Administration of contrast media must be performed by qualified personnel using appropriate procedures and equipment.
Sterile technique must be used in all injections involving contrast media.
Follow the manufacturer's instructions for the device.
Unused contrast solution remaining after the procedure must be discarded in accordance with applicable regulations.

The table below provides information on contrast medium content, iodine content, and physicochemical characteristics for the various pack sizes: