Consumer medicine information

ULTRAVIST

Iopromide

BRAND INFORMATION

Brand name

Ultravist 370 Solution for injection

Active ingredient

Iopromide

Schedule

Unscheduled

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using ULTRAVIST.

WHAT IS IN THIS LEAFLET

This leaflet answers some common questions about Ultravist. It does not contain all the available information. It does not take the place of talking to your doctor.

All diagnostic agents have risks and benefits. Your doctor has weighed the risks of you being given Ultravist against the benefits he/she expects it will have for you.

If you have any concerns about being given Ultravist, ask your doctor.

Keep this leaflet.

You may need to read it again.

WHAT ULTRAVIST IS USED FOR

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 only available in Xray departments and Xray practices.

Ask your doctor or the staff at the X-ray department if you have any questions about why Ultravist is being given to you.

It may be given to you for another reason.

BEFORE YOU ARE GIVEN ULTRAVIST

When you must not be given it

You must not be given Ultravist if you have an allergy to:

  • iopromide, the active ingredient in Ultravist
  • other iodine-containing contrast media (dyes)
  • any of the ingredients listed at the end of this leaflet

Some of the symptoms of an allergic reaction may include:

  • shortness of breath
  • wheezing or difficulty breathing
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching or hives on the skin

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.

You must not be given Ultravist after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering.

The staff at the X-ray department will check this for you.

If you are not sure whether you should be given Ultravist, talk to your doctor.

Before you are given it

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you have, or have had, any medical conditions, especially the following:

  • overactive thyroid gland or goitre (swelling of the neck caused by enlargement of the thyroid gland)
  • asthma
  • kidney problems
  • heart or blood vessel disease
  • diabetes
  • any condition affecting your brain or nervous system, particularly if you have ever had a seizure (‘fit’), stroke or brain tumour
  • cancer of the blood cells (multiple myeloma) or an overproduction of special proteins (paraproteinemia)
  • a condition of allergy against parts of your body (autoimmune disease) or a condition in which the muscles become weak and tire easily (myasthenia gravis)
  • a rare tumour of the adrenal gland which sits near the kidney and causes high blood pressure (pheochromocytoma)
  • dehydration, where your body does not have as much water and fluids as it should; you might feel thirsty, have a dry mouth or your urine might be darker than usual
  • blood clots
  • anxiety
  • very low blood pressure

Also tell your doctor if you are or have ever been addicted to drugs or alcohol.

Your doctor will use this information to decide whether special precautions or a different procedure are needed.

Tell your doctor if you are pregnant, or think you may be pregnant, or if you are breastfeeding.

Your doctor can discuss with you the risks and benefits involved.

If you have not told your doctor about any of the above, tell him/her before you are given Ultravist.

Taking other medicines

Tell your doctor if you are taking any medicines, including any that you buy without a prescription from your pharmacy, supermarket, naturopath or health food shop.

Some medicines and Ultravist may interfere with each other. These include:

  • beta-blockers, medicines used to treat high blood pressure or other heart conditions
  • interleukin-2, a medicine used to treat some forms of cancer
  • neuroleptic tranquilisers, medicines used to treat some psychiatric problems
  • antidepressants, medicines used to treat depression (low mood)
  • metformin, a medicine used to treat diabetes
  • diuretics, medicines used to treat high blood pressure and fluid buildup
  • any medicine that can have toxic effects on the kidneys

These medicines may be affected by Ultravist or may affect how well it works. You may need to use different amounts of your medicine or to take different medicines. Your doctor will advise you.

Your doctor has more information on medicines to be careful with or to avoid while receiving Ultravist.

HOW ULTRAVIST IS GIVEN

Follow all directions given to you by your doctor carefully.

They may differ from the information contained in this leaflet.

If you do not understand the instructions given, ask your doctor.

How much is given

The actual dose of Ultravist that is right for you will be worked out by the radiologist and will depend on your general health, age, weight and the type of X-ray that is being done.

For most types of X-ray, only a single dose of Ultravist will be required.

How it is given

Ultravist will be injected by the radiologist, assisted by nursing or other X-ray staff. It can be injected into different parts of your body, veins or arteries, depending on the area that needs to be examined.

The speed at which Ultravist is injected, and the length of time until the X-rays are taken will depend on the type of X-ray being done.

If you are given too much (overdose)

As Ultravist is administered by a doctor, overdose is unlikely. The possible outcomes of overdose include effects on the kidneys, heart and lungs.

Immediately tell your doctor or other medical staff if you think that you or anyone else may have been given too much Ultravist. Do this even if there are no signs of discomfort or poisoning.

You may need urgent medical attention.

AFTER HAVING ULTRAVIST

Things you must do

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

Usually you will need to stay in the X-ray facility for a period of time after receiving Ultravist so that the medical staff can monitor you for side effects.

You will also be advised to take fluids before and after the procedure to help protect your kidneys.

If you are going to have a test on your thyroid, remind your doctor and the medical staff that you have received Ultravist. Ultravist can affect some thyroid tests up to several weeks after receiving it.

Things to be careful of

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

This is recommended as a precaution in case you have a delayed reaction to Ultravist.

SIDE EFFECTS

Tell your doctor as soon as possible if you do not feel well whilst receiving or after being given Ultravist.

All diagnostic agents can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

Do not be alarmed by the following lists of side effects. You may not experience any of them.

Ask your doctor to answer any questions you may have.

Tell your doctor if you notice any of the following and they worry you:

  • headache
  • nausea
  • vomiting
  • dizziness
  • flushing
  • pain
  • reactions at the injection site
  • feeling hot
  • taste disturbance or loss of taste
  • blurry or disturbed vision

The above list includes the more common side effects of Ultravist.

Tell your doctor immediately if you notice any of the following:

  • shortness of breath
  • wheezing, gasping or difficulty breathing
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching or hives on the skin
  • sneezing, coughing or throat irritation
  • watering, sore or inflamed eyes
  • seizure (‘fit’) or loss of consciousness
  • paralysis, weakness, problems with speech
  • abnormal heart beat
  • chest pain or discomfort
  • sharp back pain, little or no urine.

The above list includes very serious side effects. You may need urgent medical attention or hospitalisation.

Some of these symptoms could be the first signs of a severe allergic reaction. Allergic reactions occur more frequently in patients with an allergic disposition.

Severe reactions requiring emergency treatment can occur, causing low blood pressure, increase in heart rate, difficulty breathing, agitation, confusion and "turning blue", possibly leading to unconsciousness.

Your doctor may ask you to stay for observation after your examination so you can be treated immediately if you suffer a severe reaction to Ultravist.

Tell your doctor if you notice anything else that is making you feel unwell

Other side effects not listed above may also occur in some people. Delayed reactions can occasionally occur.

STORING ULTRAVIST

Storage

The X-ray department or X-ray practice will store Ultravist under conditions advised by the manufacturer. Shelf-life and storage conditions are printed on the packaging and the bottle or vial.

PRODUCT DESCRIPTION

Ingredients

Active ingredients:

  • Ultravist 240: 499 mg iopromide per mL
  • Ultravist 300: 623 mg iopromide per mL
  • Ultravist 370: 769 mg iopromide per mL

Inactive ingredients:

  • trometamol
  • sodium calcium edetate
  • dilute hydrochloric acid
  • water for injections

Supplier

Made in Germany for:
Bayer Australia Ltd
ABN 22 000 138 714
875 Pacific Highway
Pymble NSW 2073

Bayer New Zealand Limited,
3 Argus Place
Hillcrest, North Shore
Auckland 0627

Australian Registration Numbers

Ultravist 240:

  • 50 mL - AUST R 15709

Ultravist 300:

  • 20 mL - AUST R 47382
  • 50 mL - AUST R 15757
  • 75 mL - AUST R 48506
  • 100 mL - AUST R 48507
  • 150 mL* - AUST R 48508

Ultravist 370:

  • 20 mL* - AUST R 47383
  • 30 mL - AUST R 47384
  • 50 mL - AUST R 15681
  • 75 mL - AUST R 48498
  • 100 mL - AUST R 48499
  • 200 mL - AUST R 48501

Date of Preparation

September 2012

See TGA website (www.ebs.tga.gov.au) for latest Australian Consumer Medicine Information.

See MEDSAFE website (www.medsafe.govt.nz) for latest New Zealand Consumer Medicine Information.

* Pack sizes marked with an asterisk are not registered in New Zealand

® Registered Trademark of the Bayer group, Germany

© Bayer Australia Ltd All rights reserved.

BRAND INFORMATION

Brand name

Ultravist 370 Solution for injection

Active ingredient

Iopromide

Schedule

Unscheduled

 

Name of the medicine

Iopromide.

Excipients

Trometamol, sodium calcium edetate, dilute hydrochloric acid (10%) (for pH adjustment) in water for injections.
It contains no antimicrobial preservatives.

Description

Chemical name: N,N'-bis (2,3-dihydroxypropyl) -2,4,6-tri-iodo-5 -(2-methoxyacetamido) -N-methylisophthalamide. Molecular formula: C18H24I3N3O8. MW: 791.12. CAS: 73334-07-3. Iopromide is a tri-iodinated, nonionic, water soluble X-ray contrast medium. Ultravist injection has a pH of 6.5 to 8.0.
The iodine concentrations (mg I/mL) available have the following physicochemical properties (see Table 1).
Solutions of Ultravist injection 150, 240, 300 and 370 mg I/mL have osmolalities from approximately 1.1 to 2.7 times that of plasma (285 mOsmol/kg water).

Pharmacology

Pharmacodynamic properties.

The contrast giving substance in the Ultravist formulation is iopromide, a nonionic, 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.

Pharmacokinetics.

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 postadministration. 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 is 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 predose levels within 7 days.

Linearity/ nonlinearity.

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 postdose 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 postdose 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.

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.

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 recommendation under Dosage and Administration).

Precautions

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 Adverse 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 β-blockers may be resistant to treatment effects of β-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, postprocedure 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 judgment 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.
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 nonionic 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.

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.
Contrast media induced nephrotoxicity, 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, dehydration, diabetes mellitus, multiple myeloma/ paraproteinaemia, gout, age over 70 years, concurrent administration of nephrotoxic drugs, repetitive and/or large doses of Ultravist.
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.

Hydration.

Adequate hydration must be assured before and after intravascular and intrathecal Ultravist administration in order to minimize the risk of contrast media induced nephrotoxicity (see also 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.

Phaeochromocytoma.

Administration of radiopaque materials to patients with known or suspected of having phaeochromocytoma 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 α-receptor blockers is recommended.

Paediatrics.

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.

Carcinogenicity, genotoxicity and impairment of fertility.

Long-term animal studies have not been performed to evaluate carcinogenic potential or effects on fertility. 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).

Use in pregnancy.

(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.

Use in lactation.

The safety of Ultravist for nursed infants has not been investigated. Contrast media are poorly excreted in human breast milk. Harm to the breastfed infant is not likely. See also Precautions, Thyroid dysfunction.

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 anticonvulsive 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.

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.

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.

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 Precautions, 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 β-blocker may be resistant to treatment effects of β-agonists (also see Precautions).
Patients on β-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 β-blockers.

Interleukin-2.

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

Adverse Effects

Summary of the safety profile.

The overall safety profile of Ultravist is based on data obtained in premarketing studies in more than 3900 patients and postmarketing 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.

Adverse drug reactions (ADRs) reported in clinical trials.

The adverse drug reactions observed with Ultravist are represented below. 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).

Immune system disorders.

Uncommon: hypersensitivity/ anaphylactoid reactions (anaphylactoid shock*, respiratory arrest*, bronchospasm*, laryngeal*/ pharyngeal*/ face oedema, tongue oedema, laryngeal/ pharyngeal spasm, asthma*, conjunctivitis, lacrimation, sneezing, cough, mucosal oedema, rhinitis, hoarseness, throat irritation, urticaria, pruritus, angioedema).

Psychiatric disorders.

Rare: anxiety.

Nervous system disorders.

Common: dizziness, headache, dysgeusia. Uncommon: vasovagal reactions, confusional state, restlessness, paraesthesia/ hypoaesthesia, somnolence.

Eye disorders.

Common: blurred/ disturbed vision.

Cardiac disorders.

Common: chest pain/ discomfort. Uncommon: arrhythmia*. Rare: cardiac arrest*, myocardial ischaemia*.

Vascular disorders.

Common: hypertension, vasodilatation. Uncommon: hypotension*.

Respiratory, thoracic and mediastinal disorders.

Uncommon: dyspnoea*.

Gastrointestinal disorders.

Common: vomiting, nausea. Uncommon: abdominal pain.

General disorders and administration site conditions.

Common: pain, injection site reactions (various kinds, e.g. pain, warmth, oedema, inflammation and soft tissue injury in case of extravasation).
* Life threatening and/or fatal cases have been reported.

Adverse drug reactions reported in a postmarketing surveillance study.

Cardiac disorders.

Rare: palpitations.

General disorders and administration site conditions.

Common: feeling hot. Uncommon: oedema.
The above additional adverse drug reactions were reported in a postmarketing surveillance study conducted in over 74,000 patients from 25 countries.

Adverse drug reactions from postmarketing 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.

Bullous conditions (e.g. Stevens-Johnson or Lyell syndrome), 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.

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 nonionic 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.

Dosage and 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.
Each vial or bottle should be used in one patient on one occasion only and any residue should be discarded. Ultravist contains no preservatives.
Vials/ bottles containing contrast medium solutions are not intended for the withdrawal of multiple doses. The rubber stopper should never be pierced more than once. The use of cannulas with a long tip and a diameter of maximally 18 G is recommended for piercing the stopper and drawing up the contrast medium (dedicated withdrawal cannulas with a side hole, e.g. Nocore-Admix cannulae, are particularly suitable).

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 haemodynamic 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 renal impairment in patients with pre-existing renal impairment, the minimum possible dose should be used in these patients (see also Precautions and Pharmacology, Pharmacokinetics).

Warming prior to use.

Contrast media which are warmed to body temperature 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) bodyweight (BW) as indicated below.
Generally, doses of up to 1.5 g iodine/kg bodyweight are well tolerated.

Intravenous urography.

Adults.

The dose should be 300 mg I/kg bodyweight (1 mL Ultravist 300, 0.8 mL Ultravist 370, 1.3 mL Ultravist 240/kg bodyweight) 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 bodyweight = 5.0 mL Ultravist 240, 4.0 mL Ultravist 300, 3.2 mL Ultravist 370/kg bodyweight.

Infants (1 month to 2 years).

1.0 g I/kg bodyweight = 4.2 mL Ultravist 240, 3.0 mL Ultravist 300, 2.7 mL Ultravist 370/kg bodyweight.

Children (2 to 11 years).

0.5 g I/kg bodyweight = 2.1 mL Ultravist 240, 1.5 mL Ultravist 300, 1.4 mL Ultravist 370/kg bodyweight.

Filming times.

When the above dosage guidelines are observed and Ultravist 300/370 is injected over one to two minutes (three to five minutes in the case of Ultravist 240), the renal parenchyma is usually highly opacified three to five minutes (five to ten minutes for Ultravist 240) and the renal pelvis with the urinary tract 8 to 15 minutes (12 to 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 two to three 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.

Computerised tomography.

Whenever possible, Ultravist should be injected as an intravenous (IV) 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 two to six minutes to guarantee a relatively constant, though not maximum, blood level.
Spiral computerised tomography (CT) in single but especially in multislice technique allows the rapid acquisition of a volume of data during a single breath hold. To optimise the effect of the IV administered bolus dose (80 to 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 computerised tomography.

Ultravist 300: 0.5 to 1.5 mL/kg bodyweight.
In whole body CT, 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 computerised tomography.

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

Paediatric contrast enhanced computerised tomography (head and body).

Ultravist 300 mg I/mL is indicated for intravenous administration for contrast enhanced computerised tomography (CECT) of the head and body. Paediatric dosing is suggested proportional to bodyweight. The suggested dose is 1 to 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 intracardiac administration in the radiographic contrast evaluation of the heart cavities and of the major arteries. Paediatric dosing is suggested proportional to bodyweight. The suggested dose is 1 to 3 mL/kg. Total dose for the procedure should not usually exceed 5 mL/kg.

Intravenous digital subtraction angiography (DSA).

The IV injection of 30 to 60 mL Ultravist 300 or 370 as a bolus (flow rate: 8 to 12 mL/second into the cubital vein; 10 to 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.

Note.

The more the patient moves or exerts themself 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 six hours. Thereafter, the patient should rest for about 18 hours to minimise 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.

Incompatibilities.

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

Overdosage

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.
In cases of overdose, it is advisable to contact the Poisons Information Centre (131 126) for recommendations on the management and treatment of overdosage.

Presentation

Ultravist 150*.

Solution for injection (clear, colourless to pale yellow, free of particles), iopromide 0.312 g/mL (≡ iodine 0.150 g/mL): 50 mL (10's), 100 mL (10's), 200 mL (1's) (glass bottle). Bottles of 50 mL, 100 mL and 200 mL have an iodine content of 7.5 g, 15 g and 30 g, respectively and an iopromide content of 15.6 g, 31.2 g and 62.4 g, respectively.

Ultravist 240.

Solution for injection (clear, colourless to pale yellow, free of particles), iopromide 0.499 g/mL (≡ iodine 0.240 g/mL): 10 mL (10's) (glass vial)*, 50 mL (10's), 100 mL (10's)* (glass bottle). Vials of 10 mL and bottles of 50 mL and 100 mL have an iodine content of 2.4 g, 12 g and 24 g, respectively and an iopromide content of 5 g, 25 g and 49.9 g, respectively.

Ultravist 300.

Solution for injection (clear, colourless to pale yellow, free of particles), iopromide 0.623 g/mL (≡ iodine 0.300 g/mL): 10 mL (10's)*, 20 mL (10's) (glass vial), 50 mL (10's), 75 mL (10's), 100 mL (10's), 150 mL (1's) (glass bottle). Vials of 10 mL and 20 mL, and bottles of 50 mL, 75 mL, 100 mL and 150 mL have an iodine content of 3 g, 6 g, 15 g, 22.5 g, 30 g and 45 g, respectively and an iopromide content of 6.2 g, 12.5 g, 31.2 g, 46.7 g, 62.3 g and 93.5 g, respectively.

Ultravist 370.

Solution for injection (clear, colourless to pale yellow, free of particles), iopromide 0.769 g/mL (≡ iodine 0.370 g/mL): 20 mL (10's), 30 mL (10's) (glass vial), 50 mL (10's), 75 mL (10's), 100 mL (10's); 150 mL (1's)*, 200 mL (1's) (glass bottle). Vials of 20 mL and 30 mL, and bottles of 50 mL, 75 mL, 100 mL, 150 mL and 200 mL have an iodine content of 7.4 g, 11.1 g, 18.5 g, 27.8 g, 37 g, 55.5 g and 74 g, respectively and an iopromide content of 15.4 g, 23.1 g, 38.5 g, 57.7 g, 76.9 g, 115.4 g and 153.8 g, respectively.
*Not currently marketed in Australia.

Storage

Store below 30°C. Protect from light and secondary X-rays.

Poison Schedule

Unscheduled.