Consumer medicine information

ULTRAVIST

Iopromide

BRAND INFORMATION

Brand name

Ultravist

Active ingredient

Iopromide

Schedule

Unscheduled

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using ULTRAVIST.

SUMMARY CMI

ULTRAVIST®

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I given ULTRAVIST?

ULTRAVIST contains the active ingredient iopromide. ULTRAVIST is a contrast agent used during an X-ray examination.

For more information, see Section 1. Why am I given ULTRAVIST? in the full CMI.

2. What should I know before I am given ULTRAVIST?

Do not use if you have ever had an allergic reaction to ULTRAVIST or any of the ingredients listed at the end of the CMI.

Talk to your doctor, radiographer or nurse if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I am given ULTRAVIST? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with ULTRAVIST and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How am I given ULTRAVIST?

ULTRAVIST is injected by the doctor, radiographer or nurse into different parts of your body depending on the area of your body to be examined.

More instructions can be found in Section 4. How am I given ULTRAVIST? in the full CMI.

5. What should I know while receiving ULTRAVIST?

Things you should doTell your doctor, radiographer or nurse if you have:
  • experience any of the severe symptoms of loss of consciousness or heart attack, increase in heart rate, difficulty breathing, low blood pressure and swelling of the face, lips or tongue leading to severe breathing difficulties and shock
  • experience any asthma symptoms e.g. chest tightening.
Driving or using machinesAvoid driving a car or operating machinery for 24 hours after receiving ULTRAVIST
Laboratory testULTRAVIST can affect the results of some thyroid tests up to several weeks after receiving it.
Looking after your medicineThe X-Ray unit will store ULTRAVIST as required by the manufacturer.

For more information, see Section 5. What should I know while receiving ULTRAVIST? in the full CMI.

6. Are there any side effects?

All medicines can have side effects. If they do occur, they are usually minor and temporary. Do not be alarmed by this list. You may not experience any of them.

Serious side effects can include severe allergic reactions, severe asthma, neurological effects (stroke, coma, seizures) and heart attack. Common side effects can include headache, nausea and vasodilatation (feeling hot, flushed or faint).

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

ULTRAVIST® (UHL-tra-vist)

Active ingredient: iopromide


Consumer Medicine Information (CMI)

This leaflet provides important information about using ULTRAVIST. You should also speak to your doctor, radiographer, nurse or pharmacist if you would like further information or if you have any concerns or questions about using ULTRAVIST.

Where to find information in this leaflet:

1. Why am I given ULTRAVIST?
2. What should I know before I am given ULTRAVIST?
3. What if I am taking other medicines?
4. How am I given ULTRAVIST?
5. What should I know while receiving ULTRAVIST?
6. Are there any side effects?
7. Product details

1. Why am I given ULTRAVIST?

ULTRAVIST contains the active ingredient iopromide.

ULTRAVIST is an injectable contrast medium (a dye) which contains iodine. It is used to clearly show on X-rays the area of your body that your doctor wants to investigate, for example, your kidney, bladder, heart, vessels or spinal cord. It can also be used with sensitive computer-assisted X-ray machines (CT scanners) to investigate other parts of your body.

ULTRAVIST is also used during an angiogram in a cardiac catheterization procedure to help the doctor visualise the blood vessels in your heart and body using an X-ray machine.

ULTRAVIST can also be used in lumbar myelography to help the doctor visualise the spinal cord in your lower back using an X-ray machine.

2. What should I know before I am given ULTRAVIST?

Warnings

Do not use ULTRAVIST if:

  • you are allergic to iopromide, or any of the ingredients listed at the end of this leaflet.
  • Always check the ingredients to make sure you can use this medicine.

Check with your doctor, radiographer or nurse if you have:

  • any allergies to other iodine-containing contrast or any other allergies (e.g. shellfish, hay fever, hives, anaphylaxis)
  • asthma
  • underactive or overactive thyroid gland, goitre (swelling in the neck) or other thyroid conditions
  • a neurological condition including seizures, stroke or brain tumour
  • a drug or alcohol addiction
  • anxiety
  • heart or blood vessel disease or blood clots
  • kidney problems
  • diabetes
  • diseases such as multiple myeloma or paraproteinemia or myasthenia gravis
  • a rare tumour of the adrenal gland (pheochromocytoma)
  • are dehydrated and your body needs more fluids
  • very low blood pressure
  • take any medicines for any other condition.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

You may be asked to stay in the X-ray department for a period of time after your examination so that the medical staff can monitor you for side effects.

You will also be advised to take fluids before the examination to help protect your kidneys.

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

There is no need to stop breastfeeding if you have an examination involving ULTRAVIST.

Use in children

ULTRAVIST is approved for use in adults, adolescents and children including full-term newborns.

3. What if I am taking other medicines?

Tell your doctor, radiographer, nurse or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

  • are taking metformin used to treat diabetes
  • are taking beta-blockers used for high blood pressure or heart conditions
  • are taking interleukin-2 used to treat some cancers
  • are taking neuroleptic tranquilisers used to treat some psychiatric problems
  • are taking antidepressants used to treat depression
  • are taking diuretics used to treat high blood pressure or fluid buildup
  • any medicine that can have toxic effects on the kidneys

Some medicines may interfere with ULTRAVIST and affect how it works.

If you experience an allergy-like reaction to ULTRAVIST, any treatment given to you may be affected by these medicines.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect ULTRAVIST.

4. How am I given ULTRAVIST?

How much to be given

  • The dosage of ULTRAVIST is based on your weight and area of your body that will be examined. The doctor or radiographer will calculate the right dose for you.

When ULTRAVIST is given

  • ULTRAVIST will be given immediately before or during your examination.

How ULTRAVIST is given

  • ULTRAVIST is injected by the doctor or radiographer into different parts of your body depending on the area of your body to be examined.

If you are given too much ULTRAVIST

If you think that you have been given too much ULTRAVIST, ask the doctor, radiographer or nurse. As ULTRAVIST is given by the doctor, radiographer or nurse, overdose is unlikely. If it does happen, a doctor will treat any symptoms that follow.

You should immediately:

  • phone the Poisons Information Centre (by calling Australia: 13 11 26 or New Zealand 0800 POISON or 0800 764 766), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

You must not be given a second injection of ULTRAVIST less than 48 hours after a first injection into the spine because there is a risk of overdose.

5. What should I know while receiving ULTRAVIST?

Things you should do

Follow carefully the directions given to you by your doctor and other medical staff.

Call your doctor straight away if you:

  • experience any of the severe symptoms of loss of consciousness or heart attack, increase in heart rate, difficulty breathing, low blood pressure and swelling of the face, lips or tongue leading to severe breathing difficulties and shock
  • experience any asthma symptoms e.g. chest tightening.

Remind any doctor, dentist or pharmacist you visit that you have been given ULTRAVIST.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how ULTRAVIST affects you.

Avoid driving a car or operating machinery for 24 hours after receiving ULTRAVIST.

Laboratory tests

  • ULTRAVIST can affect the results of some thyroid tests up to several weeks after receiving it
  • Remind your doctor or medical staff after you have received ULTRAVIST.

Looking after your medicine

  • The X-ray unit will store ULTRAVIST under the conditions advised by the manufacturer.
  • Shelf life and storage conditions are printed on the vial or bottle.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

A high level of excitement, anxiety and pain may increase the risk of side effects or make contrast agent related reactions more intense.

Allergic reaction

Some people may experience symptoms of an allergic reaction such as loss of consciousness or heart attack, increase in heart rate, difficulty breathing, low blood pressure and swelling of the face, lips or tongue leading to severe breathing difficulties and shock.

Allergic reactions occur more frequently in people with a history of allergies to other contrast agents, to foods (e.g. seafood) or those who suffer from anaphylaxis, hay fever or bronchial asthma.

Most of these reactions occur within one (1) hour of receiving ULTRAVIST. Rarely, some of these reactions may be delayed (up to several days after receiving ULTRAVIST).

Less serious side effects

Less serious side effectsWhat to do
Gastrointestinal disorders
  • Nausea
  • Vomiting
  • Stomach pain
  • Diarrhoea
Nervous system disorders
  • Headache
  • Dizziness
  • Distaste in mouth
  • Pins and needles sensation or numbness
  • Restless
  • Feeling drowsy
  • Confused
General disorders
  • Injection site pain
  • Feeling hot
  • Flushing
Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
Immune system disorders
  • Experience swelling of the face, eyelids, lips, tongue or other parts of the body
  • Coughing or throat irritation
  • Itching or hives
  • Wheezing, shortness of breath, difficulty breathing, gasping
  • Gagging, feeling of suffocation
  • Low blood pressure
Nervous system disorders
  • Seizure or convulsion (fit)
  • Paralysis, weakness, problems with speech
  • Vasovagal reaction (fainting)
Cardiac disorders
  • Heart attack
  • Chest pain or discomfort
  • Irregular heartbeat
  • Abnormal heartbeat (maybe faster)
Eye disorders
  • Blurred vision
Psychiatric disorders
  • Anxiety
Respiratory disorders
  • Difficulty breathing
Skin disorders
  • Severe skin reaction including reddening, itchy, blistering or painful progressive rash
  • Rash
  • Itchy skin
General disorders
  • Injection site reaction
  • Fluid under skin at injection site
  • Little, no or very dark urine
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Tell your doctor, radiographer, nurse or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration in Australia online at www.tga.gov.au/reporting-problems or in New Zealand nzphvc.otago.ac.nz/reporting. By reporting side effects, you can help provide more information on the safety of this medicine.

7. Product details

This medicine is only available in an X-ray unit.

What ULTRAVIST contains

Active ingredient
(main ingredient)
Iopromide
(contains iodine)
Other ingredients
(inactive ingredients)
Trometamol
Sodium calcium edetate
Dilute hydrochloric acid
Water for injections

Do not take this medicine if you are allergic to any of these ingredients.

What ULTRAVIST looks like

ULTRAVIST is a clear, colourless to slightly yellow solution for injection and is supplied in glass vials or glass bottles of various sizes.

ULTRAVIST 150:
10 x 50 mL glass bottles – AUST R 15728
10 x 100 mL glass bottles – AUST R 48502
1 x 200 mL glass bottle – AUST R 48503

ULTRAVIST 240:
10 x 10 mL glass vials – AUST R 76434
10 x 50 mL glass bottles – AUST R 15709
10 x 100 mL glass bottles – AUST R 76908

ULTRAVIST 300:
10 x 10 mL glass vials – AUST R 47381
10 x 20 mL glass vial – AUST R 47382
10 x 50 mL glass bottles – AUST R 15757
10 x 75 mL glass bottles – AUST R 48506
10 x 100 mL glass bottles – AUST R 48507
1 x 150 mL glass bottle – AUST R 48508

ULTRAVIST 370:
10 x 20 mL glass vials – AUST R 47383
10 x 30 mL glass vials – AUST R 47384
10 x 50 mL glass bottles – AUST R 15681
10 x 75 mL glass bottles – AUST R 48498
10 x 100 mL glass bottles – AUST R 48499
1 x 150 mL glass bottle – AUST R 48500
1 x 200 mL glass bottle – AUST R 48501
8 x 500 mL glass bottles – AUST R 321040

Not all presentations may be marketed in Australia or New Zealand.

Who distributes ULTRAVIST

Bayer Australia Limited
ABN 22 000 138 714
875 Pacific Highway
Pymble NSW 2073
www.bayer.com.au

Bayer New Zealand Limited
PO Box 2825
Shortland Street
Auckland 1140
Free phone 0800 229 376

This leaflet was prepared in November 2021.

See TGA website (www.ebs.tga.gov.au) for latest Australian Consumer Medicine Information or on the Medsafe website (www.medsafe.govt.nz) for New Zealand.

® Registered trademark

Published by MIMS February 2022

BRAND INFORMATION

Brand name

Ultravist

Active ingredient

Iopromide

Schedule

Unscheduled

 

1 Name of Medicine

Iopromide.

2 Qualitative and Quantitative Composition

Ultravist 150 injection contains 312 mg of iopromide per mL, equivalent to 150 mg iodine per mL.
Ultravist 240 injection contains 499 mg of iopromide per mL, equivalent to 240 mg iodine per mL.
Ultravist 300 injection contains 623 mg of iopromide per mL, equivalent to 300 mg iodine per mL.
Ultravist 370 injection contains 769 mg of iopromide per mL, equivalent to 370 mg iodine per mL.
Iopromide is a triiodinated, non-ionic, water-soluble X-ray contrast medium.

Physicochemical properties.

The iodine concentrations (mg I/mL) available have the following physicochemical properties (See Table 1):
Solutions of Ultravist injection 150 mg I/mL, 240 mg I/mL, 300 mg I/mL and 370 mg I/mL have osmolalities from approximately 1.1 to 2.7 times that of plasma (285 mOsmol/kg water).
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Ultravist solution for injection/infusion is a clear, colourless to pale yellow solution, free of particles and has a pH of 6.5-8.0.

4 Clinical Particulars

4.1 Therapeutic Indications

Ultravist is indicated for all angiographic and urographic examinations and for contrast enhancement in computerised tomography.
Ultravist 240 is additionally indicated for lumbar myelography in adults.

4.2 Dose and Method of Administration

Administration technique.

Contrast media should be visually inspected prior to use and must not be used, if discoloured, nor in the presence of particulate matter (including crystals) or defective containers. As Ultravist is a highly concentrated solution, crystallisation (milky cloudy appearance and/or sediment at the bottom, or floating crystals) may occur very rarely.
Avoid rapid dispersion of the medium. (Extreme caution during injection of a contrast medium is necessary to avoid extravasation. This is especially important in patients with severe arterial or venous disease).
Do not mix with other medicines (i.e. such as agents for the prophylactic treatment of hypersensitivity reactions).
Avoid immediate repeat myelography with Ultravist.
Unused Ultravist in opened containers must be discarded ten hours after first opening the container.

Use of Ultravist in a single-use setting.

Vials or bottles containing contrast medium solutions are not intended for the withdrawal of multiple doses.
The rubber stopper of the vial or bottle should never be pierced more than once.
Each vial or bottle should be used in one patient on one occasion only and any residue should be discarded. Ultravist contains no preservatives.
If a single-use injector system is used, Instructions For Use (IFU) of the device manufacturer must be followed, including connecting tubes and all disposable parts. Ensure the single-use disposables are replaced after each patient.

Use of Ultravist with a multi-patient use injector system and/or large volume containers (200 mL or more).

The multiple withdrawal and administration of contrast medium must be done utilising a device and disposables system validated and approved for multiple-patient use, such as an automatic injector system.
The rubber stopper of the bottle should never be pierced more than once.
Instructions For Use (IFU) of the device manufacturer must be followed, including connecting tubes and all disposable parts of the injector system. Ensure the single-use disposables are replaced after each patient.

General information.

Newborns (< 1 month) and infants (1 month to 2 years).

Young infants (age < 1 year) and especially newborns are susceptible to electrolyte imbalance and hemodynamic alterations. Care should be taken regarding the dose of contrast medium to be given, the technical performance of the radiological procedure and the patient status.

Patients with renal impairment.

Since iopromide is excreted almost exclusively in an unchanged form via the kidneys, the elimination of iopromide is prolonged in patients with renal impairment. In order to reduce the risk of additional contrast media induced kidney injury in patients with pre-existing renal impairment, the minimum possible dose should be used in these patients (also see Section 4.4 Special Warnings and Precautions for Use; Section 5.2 Pharmacokinetic Properties).

Warming prior to use.

Contrast media which are warmed to body temperature (37°C) before administration are better tolerated and can be injected more easily because of reduced viscosity.

Dosage for intravascular use.

Dosage should be adapted to age, weight, clinical question and examination technique.
The dosages given below are recommendations only and represent common doses for an average normal adult weighing 70 kg. Doses are given for single injections or per kilogram (kg) body weight (BW) as indicated below.
Generally, doses of up to 1.5 g iodine per kg body weight are well tolerated.

Intravenous urography.

Adults.

The dose should be 300 mg I/kg body weight (1 mL Ultravist 300, 0.8 mL Ultravist 370, 1.3 mL Ultravist 240/kg body weight) if the clinical problem also requires adequate filling of the ureters. Increasing the dose is possible if this is considered necessary in special indications.

Children.

The physiologically poor concentrating ability of the still immature nephron of infantile kidneys demands relatively high doses of contrast medium.

Newborns (< 1 month).

1.2 g I/kg body weight = 5.0 mL/kg body weight Ultravist 240;
= 4.0 mL/kg body weight Ultravist 300;
= 3.2 mL/kg body weight Ultravist 370.

Infants (1 month to 2 years).

1.0 g I/kg body weight = 4.2 mL/kg body weight Ultravist 240;
= 3.0 mL/kg body weight Ultravist 300;
= 2.7 mL/kg body weight Ultravist 370.

Children (2 to 11 years).

0.5 g I/kg body weight = 2.1 mL/kg body weight Ultravist 240;
= 1.5 mL/kg body weight Ultravist 300;
= 1.4 mL/kg body weight Ultravist 370.

Filming times.

When the above dosage guidelines are observed and Ultravist 300/370 is injected over one to two minutes (3-5 minutes in the case of Ultravist 240), the renal parenchyma is usually highly opacified three to five minutes (5-10 minutes for Ultravist 240) and the renal pelvis with the urinary tract 8 to 15 minutes (12-20 minutes for Ultravist 240) after the start of administration. The earlier time should be chosen for younger patients and the later time for older patients.
Normally, it is advisable to take the first film as early as 2-3 minutes after administration of the contrast medium. In neonates, infants and patients with impaired renal function later films may improve visualisation of the urinary tract.
Insufficient contrast necessitates late films.

Computerized tomography (CT).

Whenever possible, Ultravist should be injected as an i.v. bolus, preferably using a power injector. Only for slow scanners about half of the total dosage should be administered as a bolus and the rest within 2-6 minutes to guarantee a relatively constant, though not maximum, blood level.
Spiral CT in single but especially in multi-slice technique allows the rapid acquisition of a volume of data during a single breath hold. To optimise the effect of the i.v. administered bolus dose (80-150 mL Ultravist 300) in the region of interest (peak, time and duration of enhancement), the use of an automatic power injector and bolus tracking is strongly recommended.

Whole body CT.

Ultravist 300: 0.5-1.5 mL/kg body weight.
In whole body computerized tomography, the necessary doses of contrast medium and the rates of administration depend on the organs under investigation, the diagnostic problem and in particular, the different scan and image reconstruction times of the scanners in use.

Cranial CT.

The following dosages are recommended for cranial CT:
Ultravist 300: up to 1.0-2.0 mL/kg body weight;
Ultravist 370: up to 1.0-1.5 mL/kg body weight.

Paediatric contrast enhanced CT (CECT, head and body).

Ultravist 300 mg I/mL is indicated for intravenous administration for CECT of the head and body. Paediatric dosing is suggested proportional to body weight. The suggested dose is 1-2 mL/kg. Total dose for the procedure should not usually exceed 3 mL/kg.

Conventional angiography.

The dosage depends on the age, weight, cardiac output and general condition of the patient, the clinical problem, examination technique and the nature and volume of the vascular region to be investigated. (See Table 2).

Paediatric angiocardiography.

Ultravist 370 mg I/mL is indicated for intra-arterial and intra-cardiac administration in the radiographic contrast evaluation of the heart cavities and of the major arteries. Paediatric dosing is suggested proportional to body weight. The suggested dose is 1-3 mL/kg. Total dose for the procedure should not usually exceed 5 mL/kg.

Intravenous digital subtraction angiography (DSA).

The i.v. injection of 30-60 mL Ultravist 300 or 370 as a bolus (flow rate: 8-12 mL/second into the cubital vein; 10-20 mL/second into the vena cava) is only recommended for contrast demonstrations of the great vessels of the pulmonary arteries and of the arteries of the neck, head, kidneys and extremities. The period of time for which the contrast medium is in contact with the wall of the veins can be reduced by flushing with 20 to 40 mL isotonic sodium chloride solution as a bolus immediately afterwards.

Intra-arterial digital subtraction angiography (DSA).

Intra-arterial digital subtraction angiography requires small volumes and lower iodine concentrations than the intravenous technique. The more selective the angiography is, the lower the dose of contrast medium can be. The values used in conventional angiography for bolus concentration, bolus volume can be reduced for intra-arterial DSA.

Dosage for intrathecal use.

The dosage may vary depending on the clinical problem, examination technique and the region to be investigated.
If equipment is available which allows films in all necessary projections without the patient having to move and with which the instillation can be performed under fluoroscopic control, then often lower volumes are sufficient.

Recommended dose for single examinations.

Myelography.

Up to 12.5 mL Ultravist 240.
The maximum dose of 12.5 mL Ultravist 240 corresponds to a total iodine dose of 3 g and should not be exceeded.

Please note.

The more the patient moves or exerts themselves after the administration, the quicker the contrast medium will mix with the fluid of other regions of no interest. As a consequence, the contrast density decreases more quickly than usual.
After the examination the contrast medium should be directed to the lumbar region. This is achieved by placing the patient in an upright sitting position or by elevating the head of the bed by 15° for at least 6 hours. Thereafter, the patient should rest for about 18 hours to minimize any discomfort caused by leakage of cerebrospinal fluid. During this period, observation for adverse reactions is advisable. Patients suspected of having a reduced seizure threshold must be kept under particularly careful observation for some hours.

Repeat procedure.

An interval of at least 48 hours should be allowed before repeat examination.

4.3 Contraindications

Ultravist (iopromide) should not be administered to patients with known hypersensitivity or previous reaction to iodinated contrast media or any excipients. Immediate repeat myelography, in the event of technical failure, is contraindicated because of overdosage considerations (see Section 4.2 Dose and Method of Administration for recommendation).

4.4 Special Warnings and Precautions for Use

For all indications.

Evaluate the risk before use of iopromide when any of the following medical problems exist:

Hypersensitivity reactions.

Ultravist can be associated with anaphylactoid/hypersensitivity or other idiosyncratic reactions characterised by cardiovascular, respiratory and cutaneous manifestations.
Allergy-like reactions ranging from mild to severe reactions, including shock, are possible (see Section 4.8 Adverse Effects (Undesirable Effects)). Most of these reactions occur within one hour of administration. However, delayed reactions (after hours to days) may occur.
The risk of hypersensitivity reactions is higher in case of:
previous reaction to contrast media;
history of bronchial asthma or other allergic disorders.
However, such reactions are irregular and unpredictable in nature.
Patients who experience such reactions while taking beta-blockers may be resistant to treatment effects of beta-agonists.
In the event of a severe hypersensitivity reaction, patients with cardiovascular disease are more susceptible to serious or even fatal outcomes.
Due to the possibility of severe hypersensitivity reactions after administration, post-procedure observation of the patient is recommended.
Preparedness for institution of emergency measures is necessary for all patients. To permit immediate countermeasures to be taken in emergencies, appropriate medicines, an endotracheal tube and respirator should be ready at hand.
In patients with an increased risk of acute allergy-like reactions, patients with a previous moderate or severe acute reaction, asthma or allergy requiring medical treatment, premedication with a corticosteroid regimen may be considered.

Pretesting.

Sensitivity testing using a small test dose of contrast medium is not recommended as it has no predictive value. Furthermore, sensitivity testing itself has occasionally led to serious and even fatal hypersensitivity reactions.

Thyroid dysfunction.

Particularly careful risk/benefit judgement is required in patients with known or suspected hyperthyroidism or goitre, as iodinated contrast media may induce hyperthyroidism or thyreotoxic crisis in these patients. Iodinated contrast media should not be given to patients with manifest hyperthyroidism. Testing of thyroid function prior to Ultravist administration and preventive thyreostatic medication may be considered in patients with known or suspected hyperthyroidism.
Thyroid function tests indicative of hypothyroidism or transient thyroid suppression have been reported following iodinated contrast media administration to adult and paediatric patients. Evaluate the potential risk of hypothyroidism in patients with known or suspected thyroid diseases before use of iodinated contrast media.
In neonates, especially preterm infants, who have been exposed to Ultravist, either through the mother during pregnancy or in the neonatal period, it is recommended to monitor thyroid function, as an exposure to excess iodine may cause hypothyroidism, possibly requiring treatment.

CNS disorders.

Patients with CNS disorders may be at increased risk to have seizures and neurological complications in relationship to Ultravist administration. Neurological complications are more frequent in cerebral angiography and related procedures.
Caution should be exercised in situations in which there may be a reduced seizure threshold, such as a previous history of seizures, intrathecal administration, alcoholism, drug addiction and the use of certain concomitant medication.
Factors such as brain tumours and acute cerebrovascular ischaemia, which increase blood brain barrier permeability, facilitate the passage of the contrast medium into cerebral tissue, possibly leading to CNS reactions.

Anxiety.

Pronounced states of excitement, anxiety and pain may increase the risk of side effects or intensify contrast medium related reactions. Care should be taken to minimize the state of anxiety in such patients.

Cardiovascular disease.

Patients with significant cardiac disease or severe coronary artery disease are at an increased risk of developing clinically relevant haemodynamic changes and arrhythmia.
In patients with valvular disease and pulmonary hypertension contrast medium administration may lead to pronounced haemodynamic changes. Reactions involving ischaemic ECG changes and major arrhythmia are more common in older patients and in those with pre-existing cardiac disease.
Patients with congestive heart failure receiving concurrent diuretic therapy may have relative intravascular volume depletion, which may affect the renal response to the contrast agent osmotic load. Such patients should be observed for several hours following the procedure to detect delayed haemodynamic renal function disturbances.
The intravascular injection of Ultravist may precipitate pulmonary oedema in patients with heart failure.

Thromboembolic events.

Serious, rarely fatal, thromboembolic events causing myocardial infarction and stroke have been reported during angiographic procedures with both non-ionic and ionic contrast media. Therefore, meticulous intravascular administration technique is necessary, particularly during angiographic procedures to minimise thromboembolic events.
Exercise care when performing venography in patients with suspected thrombosis, phlebitis, severe ischaemic disease, local infection, venous thrombosis or a totally obstructed venous system.
Clotting may occur when blood remains in contact with syringes containing iodinated contrast agents.
Avoid angiography whenever possible in patients with homocystinuria because of the risk of inducing thrombosis and embolism.

Hydration.

Adequate hydration status must be assured in all patients before intravascular or intrathecal Ultravist administration in order to minimize the risk of Post-Contrast Acute Kidney Injury (PC-AKI) (see also subsection Use in renal impairment). This applies especially to patients with multiple myeloma, diabetes mellitus, polyuria, oliguria, hyperuricemia, as well as to newborns, infants, small children and elderly patients.
Adequate hydration status must be assured in renally impaired patients. However, prophylactic IV hydration in patients with moderate renal impairment (eGFR 30-59 mL/min/1.73 m2) is not recommended as additional renal safety benefits have not been established. In patients with severe renal impairment (eGFR < 30 mL/min/1.73 m2) and concomitant cardiac conditions, prophylactic IV hydration can lead to increased serious cardiac complications. See Section 4.2 Dose and Method of Administration, Patients with renal impairment; Section 4.4 Special Warnings and Precautions for Use, Use in renal impairment, Cardiovascular disease; Section 4.8 Adverse Effects (Undesirable Effects), Adverse drug reactions from post-marketing spontaneous reports.

Pheochromocytoma.

Administration of radiopaque materials to patients with known or suspected of having pheochromocytoma should be performed with extreme caution. If, in the opinion of the physician, the possible benefits of such a procedure outweigh the considered risks, the procedure may be performed; however, the amount of radiopaque medium injected should be kept to an absolute minimum. The blood pressure should be assessed throughout the procedure, and measures for treatment of a hypertensive crisis should be available. These patients should be monitored very closely during contrast enhanced procedures. Premedication with alpha-receptor blockers is recommended.

Intravascular use.

Patients with autoimmune disorders.

Cases of severe vasculitis or Stevens-Johnson-like syndrome have been reported in patients with pre-existing autoimmune disorders.

Myasthenia gravis.

The administration of Ultravist may aggravate the symptoms of myasthenia gravis.

Cerebral angiography.

Use caution in patients with extreme senility, advanced atherosclerosis or severe hypotension; the procedure may be hazardous in subarachnoid haemorrhage and in migraine (because of ischaemic complications).

Peripheral angiography.

Pulsation should be present in the artery to be injected; in thromboangitis obliterans (Buerger's Disease) or ischaemia associated with ascending infection, angiography should be performed with extreme caution, if at all.

Intrathecal use.

Care is needed in patients with a seizure history due to an increased risk for seizures in relationship to intrathecal Ultravist administration. Preparedness for institution of anti-convulsive measures is recommended.
The majority of adverse events after myelography occur some hours after administration. During this period observation is advisable.
Patients with a history of epilepsy and receiving anticonvulsant therapy should be maintained on this therapy when receiving the contrast medium intrathecally.
Ultravist injection is not indicated for use in thoracic, cervical or total columnar myelography, nor for cerebral ventriculography and cisternography as there are insufficient data to support its use in these indications.

Children.

The safety and effectiveness of Ultravist have not been established in children for intrathecal use.

Use in renal impairment.

In patients with impaired renal function, the plasma half-life of iopromide is prolonged according to the reduced glomerular filtration rate. Therefore, caution must be exercised in patients with severely impaired renal function, combined renal and hepatic disease, combined renal and cardiac disease, or anuria, particularly when large doses are administered.
Post-contrast acute kidney injury (PC-AKI), presenting as a transient impairment of renal function, may occur after intravascular administration of Ultravist. Acute renal failure may occur in some cases.
Risk factors include, for example:
pre-existing renal insufficiency (see Section 4.2 Dose and Method of Administration, Patients with renal impairment);
dehydration (see Section 4.4 Special Warnings and Precautions for Use, Hydration);
diabetes mellitus;
multiple myeloma/paraproteinaemia;
gout;
age over 70 years;
concurrent administration of nephrotoxic drugs;
repetitive and/or large doses of Ultravist.
Patients with moderate to severe (eGFR 44-30 mL/min/1.73 m2) or severe renal impairment (eGFR < 30 mL/min/1.73 m2) are at increased risk of PC-AKI with intra-arterial contrast administration and first pass renal exposure.
Patients with severe renal impairment (eGFR < 30 mL/min/1.73 m2) are at increased risk of PC-AKI with intra-venous or intra-arterial contrast administration with second pass renal exposure (see Section 4.4 Special Warnings and Precautions for Use, Hydration).
Patients on dialysis, if without residual renal function, may receive Ultravist for radiological procedures as iodinated contrast media are cleared by the dialysis process.
In the case of severe renal insufficiency the coexistence of severe hepatic dysfunction can seriously delay contrast medium excretion. Haemodialysis should be used only if clinically indicated.

Paediatric use.

Paediatric patients at higher risk of experiencing an adverse reaction during and after administration of any contrast agent may include those with asthma, a sensitivity to medication and/or allergens, cyanotic and acyanotic heart disease, congestive heart failure, or a serum creatinine greater than 1.5 mg/dL. The injection rates in small vascular beds, and the relationship of the dose by volume or concentration in small paediatric patients have not been established. Caution should be exercised in selecting the dose.

Effects on laboratory tests.

Radioisotopes.

Diagnosis and treatment of thyroid disorders with thyrotropic radioisotopes may be impeded for up to several weeks after administration of Ultravist due to reduced radioisotope uptake.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Metformin.

In patients with acute kidney failure or severe chronic kidney disease metformin elimination can be reduced leading to accumulation and the development of lactic acidosis. As the application of Ultravist can lead to renal impairment or an aggravation of renal impairment, patients treated with metformin may be at an increased risk of developing lactic acidosis, especially those with prior renal impairment (see Section 4.4 Special Warnings and Precautions for Use, Use in renal impairment).

Neuroleptics and antidepressants.

Concomitant use of neuroleptics and antidepressants may reduce the seizure threshold, thus increasing the risk of a contrast medium related reaction.

Beta-blockers.

Patients who experience hypersensitivity reactions while taking a beta-blocker may be resistant to treatment effects of beta-agonists (also see Section 4.4 Special Warnings and Precautions for Use).
Patients on beta-blockers may be unresponsive to the usual doses of adrenaline used to treat allergic reactions. Because of the risk of hypersensitivity reactions, use caution when administering iodinated contrast agents to patients taking beta-blockers.

Interleukin-2.

Previous treatment (up to several weeks) with interleukin-2 is associated with an increased risk for delayed reactions to Ultravist.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Long term animal studies have not been performed to evaluate effects on fertility.
(Category B2)
Adequate and well-controlled studies in pregnant women have not been conducted. Embryotoxicity including teratogenicity studies have been performed in rats and rabbits at doses up to 3.7 g I/kg bw. These studies did not indicate an increased risk of adverse effects to the foetus following the intended diagnostic use in humans.
Before administration to women during pregnancy, the benefit to the patient should be carefully weighed against the possible risk to the foetus. Ultravist should be used only if, in the judgement of the clinician, its use is deemed essential to the welfare of the patient. Generally, radiography of the abdomen is considered to be contraindicated during pregnancy.
The safety of Ultravist for nursed infants has not been investigated. Contrast media are poorly excreted in human breast milk. Harm to the nursed infant is not likely. Also see Section 4.4 Special Warnings and Precautions for Use, Thyroid dysfunction, Paediatric use.

4.7 Effects on Ability to Drive and Use Machines

Because of the risk of delayed adverse reactions, as a precaution, driving or operating machinery should be avoided for the first 24 hours after intrathecal as well as after intravascular administration of contrast media.

4.8 Adverse Effects (Undesirable Effects)

Summary of the safety profile.

The overall safety profile of Ultravist is based on data obtained in pre-marketing studies in more than 3900 patients and post-marketing studies in more than 74,000 patients, as well as data from spontaneous reporting and the literature.
The most frequently observed adverse drug reactions (≥ 4%) in patients receiving Ultravist are headache, nausea and vasodilatation.
The most serious adverse drug reactions in patients receiving Ultravist are anaphylactoid shock, respiratory arrest, bronchospasm, laryngeal oedema, pharyngeal oedema, asthma, coma, cerebral infarction, stroke, brain oedema, convulsion, arrhythmia, cardiac arrest, myocardial ischaemia, myocardial infarction, cardiac failure, bradycardia, cyanosis, hypotension, shock, dyspnoea, pulmonary oedema, respiratory insufficiency and aspiration.

Tabulated lists of adverse reactions.

The adverse drug reactions observed with Ultravist are represented in Tables 3 and 4. They are classified according to System Organ Class (MedDRA version 13.0). The most appropriate MedDRA term is used to describe a certain reaction and its synonyms and related conditions. Adverse drug reactions are classified according to their frequencies. Frequency groupings are defined according to the following convention: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000).
The above additional adverse drug reactions were reported in a post-marketing surveillance study conducted in over 74,000 patients from 25 countries.

Adverse drug reactions from post-marketing spontaneous reports.

Endocrine disorders.

Thyrotoxic crisis, thyroid disorder.

Nervous system disorders.

Coma*, cerebral ischaemia/ infarction*, stroke*, brain oedemaa *, convulsion*, transient cortical blindnessa, loss of consciousness, agitation, amnesia, tremor, speech disorders, paresis/ paralysis.

Ear and labyrinth disorders.

Hearing disorders.

Cardiac disorders.

Myocardial infarction*, cardiac failure*, bradycardia*, tachycardia, cyanosis*.

Vascular disorders.

Shock*, thromboembolic eventsa, vasospasma.

Respiratory, thoracic and mediastinal disorders.

Pulmonary oedema*, respiratory insufficiency*, aspiration*.

Gastrointestinal disorders.

Dysphagia, salivary gland enlargement, diarrhoea.

Skin and subcutaneous tissue disorders.

Severe cutaneous reactions: toxic epidermal necrolysis (TEN)/Lyell syndrome*, Stevens-Johnson syndrome (SJS)*, drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalised exanthematous pustulosis (AGEP), rash, erythema, hyperhydrosis.

Musculoskeletal, connective tissue and bone disorders.

Compartment syndrome in case of extravasationa.

Renal and urinary disorders.

Renal impairmenta, acute renal failurea.

General disorders and administration site conditions.

Malaise, chills, pallor.

Investigations.

Body temperature fluctuation.
* Life threatening and/or fatal cases have been reported.
a Intravascular use only.
In addition to the adverse drug reactions (ADRs) listed above, the following ADRs have been reported with:

Intrathecal use.

Chemical meningitis and meningism at an unknown frequency.

Use for ERCP.

Elevation of pancreatic enzyme levels and pancreatitis at an unknown frequency.
The majority of the reactions after myelography or use in body cavities occur some hours after the administration.

Description of selected adverse reactions.

Based on experience with other non-ionic contrast media, the following undesirable effects may occur with intrathecal use in addition to the undesirable effects listed above: psychosis, neuralgia, paraplegia, aseptic meningitis, back pain, pain in extremities, micturition disorder, EEG abnormal.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions:
In Australia: http://www.tga.gov.au/reporting-problems.
In New Zealand: https://nzphvc.otago.ac.nz/reporting/.

4.9 Overdose

Results from acute toxicity studies in animals do not indicate a risk of acute intoxication following use of Ultravist.

Intravascular overdose.

Symptoms may include fluid and electrolyte imbalance, renal failure, cardiovascular and pulmonary complications.
In case of inadvertent intravascular overdosage, it is recommended to monitor fluids, electrolytes and renal function. Treatment of overdose should be directed toward the support of vital functions.
Ultravist is dialysable.

Intrathecal overdose.

Serious neurological complications may occur. Close monitoring is recommended in case of inadvertent intrathecal overdosage.
For information on the management of overdose, contact:
Australia: The Poison Information Centre on 131126 (Australia).
New Zealand: The National Poisons Centre on 0800 POISON (0800 764766).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

The contrast giving substance in the Ultravist formulation is iopromide, a non-ionic, water soluble derivative of tri-iodinated isophthalic acid with a molecular weight of 791.12 in which the firmly bound iodine absorbs the X-rays.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption and distribution.

Following intravenous administration, plasma concentrations of iopromide decline rapidly due to distribution into the extracellular space and subsequent elimination. The total distribution volume at steady state is about 16 L corresponding roughly to the volume of the extracellular space. Protein binding is very low (about 1%). There is no indication that iopromide crosses the intact blood brain barrier. A small amount crossed the placental barrier in animal studies (≤ 0.3% of the dose were found in rabbit foetuses).
Following intravenous administration (infusion over 15 minutes), maximum serum concentrations of total iodine following a low dose of about 15 g iodine (118 mmol) were about 1.39 ± 0.242 g/L (10.9 ± 1.90 mmol/L) and following a high dose of 80 g iodine (630 mmol), were about 7.06 ± 1.13 g/L (55.6 ± 8.89 mmol/L), at 15 min after start of infusion.
Following intrathecal administration, maximum iodine concentrations of 4.5% of the administered dose per total plasma volume were observed after 3.8 hours.
Following administration in the biliary and/or pancreatic duct during Endoscopic Retrograde Cholangiopancreaticography (ERCP), iodinated contrast agents are systemically absorbed and reach peak plasma concentrations between 1 and 4 h post administration. Maximum serum concentrations of total iodine following a mean dose of about 7.3 g iodine (57.4 ± 22.8 mmol) were about 85.2 micromol/L 4 hours after administration of Ultravist 300. This value is about factor 40 lower than the maximum serum concentrations reached after the respective intravenous dose. During the same time period, free serum iodine levels rose to about 5.42 micromol/L.

Metabolism.

Iopromide is not metabolised.

Excretion.

The terminal elimination half-life of iopromide in patients with normal kidney function is approximately 2 hours, irrespective of the dose.
In the dose range tested, the mean total clearance of iopromide following intravenous administration of a low (15 g iodine) and a high (80 g iodine) dose amounts to mean values between 109.5 ± 11.0 mL/min and 103 ± 13.3 mL/min, respectively. Total clearance is very similar to the renal clearance of 104 ± 12.7 mL/min (low dose) and 100 ± 17.8 mL/min (high dose). Thus, excretion of iopromide is almost exclusively renal. Only about 2% of the dose administered is excreted via the faecal route within 3 days.
Approximately 60% of the dose are excreted within 3 hours after intravenous administration via urine. In the mean ≥ 93% of dose were recovered within 12 hours. Excretion is essentially complete within 24 hours.
After intrathecal administration for lumbar myelography, elimination of iopromide from plasma is prolonged with a terminal elimination half-life of 14.9 ± 17 hours. Approximately 78 ± 15% of iopromide is excreted renally within 72 hours.
Following administration into the biliary and/or the pancreatic duct for ERCP urinary iodine serum concentrations returned to pre-dose levels within 7 days.

Linearity/non-linearity.

The pharmacokinetic parameters of iopromide in humans change dose proportionally (e.g. Cmax, AUC) or are dose independent (e.g. Vss, t1/2).

Characteristics in special patient populations.

Patients with renal impairment.

In patients with impaired renal function, the plasma half-life of iopromide is prolonged according to the reduced glomerular filtration rate.
The plasma clearance was reduced to 49.4 mL/min/1.73 m2 (CV = 53%) in mildly and moderately impaired patients (80 > CLCR > 30 mL/min/1.73 m2) and to 18.1 mL/min/1.73 m2 (CV = 30%) in severely impaired patients not depending on dialysis (CLCR = 30-10 mL/min/1.73 m2).
The mean terminal half-life is 6.1 hours (CV = 43%) in mildly and moderately impaired patients (80 ≥ CLCR > 30 mL/min/1.73 m2) and 11.6 hours (CV = 49%) in severely impaired patients not depending on dialysis (CLCR = 30-10 mL/min/1.73 m2).
The amount recovered in urine within 6 h post dose was 38% in mildly to moderately impaired patients and 26% in severely impaired patients, compared to more than 83% in healthy volunteers. Within 24 h post dose the recovery was 60% in mildly to moderately and 51% in severely impaired patients, compared to more than 95% in healthy volunteers.
Iopromide can be eliminated by haemodialysis. Approximately 60% of the iopromide dose is removed during a 3 hours dialysis.

Patients with hepatic impairment.

Excretion is not affected by impaired liver function because iopromide is not metabolised and only about 2% of dose are excreted in faeces.

5.3 Preclinical Safety Data

Genotoxicity.

Iopromide was not genotoxic in a series of studies for gene mutations (Ames test) and chromosomal damage (in vivo mouse micronucleus assay and in an in vivo mouse dominant lethal assay).

Carcinogenicity.

Long term animal studies have not been performed to evaluate carcinogenic potential.

6 Pharmaceutical Particulars

6.1 List of Excipients

Ultravist also contains small amounts of trometamol, sodium calcium edetate, dilute hydrochloric acid (10%) (for pH adjustment) and water for injections. It contains no antimicrobial preservatives.

6.2 Incompatibilities

Ultravist must not be mixed with any other medicinal products to avoid the risk of possible incompatibilities.

6.3 Shelf Life

3 years.

6.4 Special Precautions for Storage

Store below 30°C. Protect from light and secondary X-rays.
In-use: It is recommended to warm Ultravist to body temperature (37°C) prior to administration. Unused Ultravist in opened containers must be discarded ten hours after first opening the container.

6.5 Nature and Contents of Container

Injection solutions of Ultravist (iopromide) are registered in 4 strengths. Iodine and iopromide content are given in Table 5:

Container type.

Vials: type I clear glass.
Bottles: type II clear glass.

6.6 Special Precautions for Disposal

Any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Chemical structure.

Chemically, iopromide is N,N'-Bis(2,3-dihydroxypropyl)-2,4,6-tri-iodo-5-(2-methoxyacetamido)-N-methylisophthalamide and has the following structural formula.
Molecular weight: 791.12.

CAS number.

73334-07-3.
Chemical formula: C18H24I3N3O8.

7 Medicine Schedule (Poisons Standard)

Australia: Not Scheduled.
New Zealand: General Sales Medicine.

Summary Table of Changes