Consumer medicine information

Urografin

Amidotrizoate meglumine; Sodium amidotrizoate

BRAND INFORMATION

Brand name

Urografin

Active ingredient

Amidotrizoate meglumine; Sodium amidotrizoate

Schedule

Unscheduled

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Urografin.

WHAT IS IN THIS LEAFLET

This leaflet answers some common questions about Urografin. 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 using Urografin against the benefits they expect it will have for you.

If you have any concerns about using this diagnostic agent, ask your doctor or radiologist.

Keep this leaflet You may need to read it again.

Only the doctors conducting your X-Ray examination are able to weigh up all the relevant facts and you should consult them about all aspects of this medicine as it relates to you.

Should you have any questions on the use of Urografin in your X-ray examination, these should be discussed immediately with the staff at the X-ray unit performing the examination.

WHAT UROGRAFIN IS USED FOR

Urografin is an ionic X-ray contrast medium or X-ray dye that is injected directly into the bloodstream while X-rays are being taken. All injectable X-ray dyes, including Urografin, contain iodine. Just as X-rays are unable to pass through bones in your body and thus produce a ‘picture’, X-rays are unable to pass through the iodine in contrast dyes. When Urografin is injected into your body it is used by X-ray specialist doctors (radiologists) in one of the following ways, depending on the condition that is being investigated in your particular case:

  • following injection into an arm vein, Urografin travels with the bloodstream to every organ of the body. Using sensitive computer assisted X-ray machines known as Computed Tomography (CT or CAT) scanners, the radiologist can see the X-ray dye in your brain, abdomen or other areas of the body
  • following injection into an arm vein Urografin also travels in the bloodstream to your kidneys where it is excreted from the body in your urine. The radiologist can see the X-ray dye in the kidneys, urinary system and bladder
  • X-ray dye may also be introduced directly into the bladder or other body cavities via a catheter.

BEFORE YOU ARE GIVEN UROGRAFIN

When you must not be given it

Do not receive Urografin if you have an allergy to:

  • any medicine containing sodium amidotrizoate or amidotrizoate meglumine
  • 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 have heart failure or an overactive thyroid gland which are not being adequately treated.

X-ray examinations of the womb and tubes must not be performed during pregnancy or in the presence of acute inflammation of the internal female sex organs. Tell your doctor if this applies to you.

X-ray examinations of the pancreas and bile ducts must not be performed in case of acute inflammation of the pancreas. Tell your doctor if you think this might apply to you.

Urografin must not be injected into the space around your spinal cord because severe adverse reactions are possible.

If you are not sure whether you should be given this diagnostic agent, talk to your doctor or radiologist.

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 are pregnant or plan to become pregnant or are breastfeeding. Your doctor can discuss with you the risks and benefits involved. If you are breastfeeding, your doctor can advise you when to discontinue and resume.

Tell your doctor if you:

  • suffer from allergy (e.g. seafood allergy, hay fever, hives) or bronchial asthma
  • suffer from allergy to iodine-containing contrast media, or any other ingredients listed above
  • have severe disturbances of liver or kidney function
  • have heart and circulatory disease
  • have advanced cerebral arteriosclerosis (disease of the brain arterioles with thickening of the blood vessel walls)
  • have diabetes mellitus requiring treatment (condition where the body does not produce enough insulin or the body tissues are not able to use the insulin present)
  • take biguanides, one type of medicine used to treat diabetes
  • suffer from brain conditions and seizures
  • have cerebral spasmodic conditions
  • have a circulatory problem in the brain, e.g. history of stroke
  • have latent hyperthyroidism (overactive thyroid gland)
  • have very poor general condition
  • have bland nodular goitre (swelling of the neck caused by enlargement of the thyroid gland)
  • have multiple myeloma (cancer of blood cells), overproduction of special proteins (paraproteinaemia),
  • a condition of allergy against parts of your body, a condition in which the muscles become weak and tire easily (myasthenia gravis)
  • have a special kind of high blood pressure caused by a rare tumour of the adrenal gland which sits near the kidney (pheochromocytoma)
  • take special drugs daily or drink alcohol regularly
  • take beta blockers, medicines used to treat high blood pressure or other heart conditions.
  • take Interleukin
  • have pulmonary emphysema (serious lung disease that makes breathing difficult).

If you suffer from any of these, your doctor will decide whether the intended examination is possible or not.

Inform your doctor if you are a diabetic because among other things he needs to check your medication especially if you are suffering from diabetic kidney disease.

If you are at all concerned, you should feel free to discuss the necessity of using Urografin with the radiologist.

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

HOW UROGRAFIN 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 for help.

Urografin is only available in X-ray departments and X-ray practices for use in conjunction with taking X-rays.

The radiologist will advise the use of Urografin if he/she feels that it is likely to assist the X-ray examination in finding out more about your medical condition.

You should attend for the examination fasted but you may drink as usual. Further directions on this will be given by your doctor. Do not restrict your fluid intake.

In the case of abdominal and kidney X-rays, the X-ray picture is improved if the bowels are emptied of faecal matter and gas. On the two days prior to the examination you should therefore avoid flatulent food, in particular peas, beans and lentils, salads, fruit, dark and fresh bread and all kinds of uncooked vegetables. On the day before the examination, you should refrain from eating after 6 p.m. Moreover, it can be appropriate to administer a laxative (medicines which assist in bowel motion) in the evening, which will be advised by your doctor if necessary.

How much is given

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

How it is given

Urografin will be injected by the radiologist, assisted by nursing or other X-ray staff.

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

You will be observed for about 30 minutes after your examination to ensure that you do not suffer a severe reaction to Urografin.

If you are given too much (overdose)

As Urografin is administered by a doctor, overdosage is unlikely. If it does happen, the doctor will treat symptoms that follow. The rare and severe side effects noted above can occur regardless of the dosage that is administered.

If in doubt telephone the Poisons Information Centre (Australia: 13 11 26 or New Zealand: 0800 POISON or 0800 764 766) for advice if you think that you or anyone else may have been given too much Urografin. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

SIDE EFFECTS

Tell your doctor or radiologist as soon as possible if you do not feel well while you are being given Urografin.

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:

  • nausea
  • vomiting
  • erythema (areas of skin redness)
  • a sensation of pain
  • a general feeling of warmth
  • mild swelling of the face, lips, tongue or throat
  • conjunctivitis
  • coughing
  • itching
  • running nose
  • sneezing
  • hives
  • headache
  • disturbance in breathing
  • difficulty in breathing
  • local pain which occurs mainly in the examination of blood vessels, especially if the contrast medium is not injected exactly into the blood vessel.
  • swelling of the tissue is also possible

The above list includes the more common side effects of your medicine.

Side effects in association with the intravascular use of iodinated contrast media are usually mild to moderate and temporary. However, severe and life-threatening reactions, even fatal ones, have been observed.

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

  • low blood pressure
  • difficulty in breathing
  • swelling of the throat
  • generally feeling unwell
  • chills or sweating
  • dizziness and fainting
  • disturbance in heart beat and heart function, fast heart beat
  • heart attack
  • agitation
  • confusion
  • stomach pain
  • swelling and redness along a vein and a blood clot in a vein.

The above list includes the less common side effects of your medicine.

Transient complications relating to the nervous system are uncommon. Tell your doctor if you notice any of the following and they worry you:

  • dizziness
  • headache
  • agitation or confusion
  • loss of memory
  • disturbed vision speech and hearing
  • seizures
  • tremor
  • weakness causing loss of movement/paralysis
  • unpleasant sensitivity to light
  • temporary blindness
  • coma
  • sleepiness

The above list includes the less common side effects of your medicine.

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

  • delayed contrast medium reactions
  • changes in body temperature
  • swelling of salivary glands
  • breathing arrest and build-up of fluids in the lungs
  • severe skin disease (pain, reddening, large blisters, peeling of layers of skin)
  • damage to part of the brain caused by an interruption to its blood supply has been reported on rare occasions
  • temporary kidney failure

The above list includes the rare and rarely reported side effects of your diagnostic agent.

Other unwanted effects which may occur are: fever, whitening, gagging and a feeling of suffocation, allergic rash, other kinds of skin rash, cramp and whitening eyes.

These reactions, which can occur irrespective of the amount injected and the method of injection may be the first signs of severe allergic circulatory reaction. Severe reactions requiring emergency treatment can occur in the form of a circulatory reaction accompanied by blood vessel dilation and subsequent low blood pressure, increase in heart rate, difficulty in breathing, agitation, confusion and ‘turning blue’, possibly leading to unconsciousness.

Allergic reactions occur more frequently in patients with an allergic disposition. These reactions can be aggravated in patients taking a type of blood pressure medication known as beta blockers.

Failure to inject Urografin directly into a vein or artery rarely leads to severe reactions around the site of injection.

Delayed reactions (e.g. fever, rash, flu-like symptoms, joint pain and itchiness) can occasionally occur. Such reactions are more likely to occur if you are receiving the medication interleukin.

If you experience a delayed reaction avoid driving because Urografin could prevent you from driving safely. Your ability to operate any tools or machines may be impaired. You may not be able to react rapidly and purposefully in the case of unexpected and suddenly occurring events.

Allergy like reactions have been observed after use of X-ray contrast media such as Urografin. Mild swelling of the face, lips, tongue, or throat, conjunctivitis, coughing, itching, running nose, sneezing and hives may be the first signs of incipient state of a severe reaction. (See also ‘Side effects’ above). Tell the doctor immediately if you experience any of these.

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

Other side effects not listed above may also occur in some people.

AFTER USING UROGRAFIN

Storage

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

PRODUCT DESCRIPTION

What it looks like

Urografin is the brand name for an agent containing the substances sodium amidotrizoateand amidotrizoate meglumine.

Ingredients

Active ingredients:

  • Urografin 30% - contains 40 mg of sodium diatrizoate and 260 mg of meglumine diatrizoate per mL
  • Urografin 76% - contains 100 mg of sodium diatrizoate and 660 mg of meglumine diatrizoate per mL .

Inactive ingredients:

  • sodium calcium edetate
  • water for injections

Supplier

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

Urografin 30% 10 mL ampoule - AUST R 42161

Urografin 30% 250 mL bottle - AUST R 42163

Urografin 76% 50 mL bottle - AUST R 42157

Urografin 76% 100 mL bottle - AUST R 48496

Not all presentations may be marketed.

Date of preparation

February 2020

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.

® Registered Trademark of Bayer AG, Germany

© Bayer Australia Ltd

All rights reserved.

Published by MIMS April 2020

BRAND INFORMATION

Brand name

Urografin

Active ingredient

Amidotrizoate meglumine; Sodium amidotrizoate

Schedule

Unscheduled

 

1 Name of Medicine

Sodium amidotrizoate/ amidotrizoate meglumine.

6.7 Physicochemical Properties

Sodium amidotrizoate.

Molecular formula: C11H8I3N2NaO4. Chemical name: sodium 3,5-diacetamido -2,4,6-triiodobenzoate. Molecular weight: 635.90. Solubility in water: freely soluble.

Amidotrizoate meglumine.

Molecular formula: C18H26I3N3O9. Chemical name: N-methylglucamine 3,5-diacetamido- 2,4,6-triiodobenzoate. Molecular weight: 809.13. Solubility in water: freely soluble. See Table 1.

Chemical structure.


CAS number.

Sodium amidotrizoate.

CAS No. 737-31-5.

Amidotrizoate meglumine.

CAS No. 131-49-7.

2 Qualitative and Quantitative Composition

Urografin 30% contains 40 mg/mL sodium amidotrizoate and 260 mg/mL amidotrizoate meglumine in aqueous solution.
Urografin 76% contains 100 mg/mL sodium amidotrizoate and 660 mg/mL amidotrizoate meglumine in aqueous solution.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Presentation.

Urografin is a clear, colourless to faintly yellowish aqueous solution for injection or infusion.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

No data available.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

No data available.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

4 Clinical Particulars

4.1 Therapeutic Indications

Intravenous and retrograde urography. Computerized tomography.
Also for all angiographic examinations as well as for amniography, arthrography, intraoperative cholangiography, fistulography, hysterosalpingography, splenoportography, vesiculography and others.
Urografin is not to be used for myelography, ventriculography or cisternography, since it is likely to provoke neurotoxic symptoms in these examinations.

4.3 Contraindications

Manifest hyperthyroidism, decompensated cardiac insufficiency.
Hysterosalpingography must not be performed during pregnancy or in the presence of acute inflammatory processes in the pelvic cavity.
Endoscopic retrograde cholangiopancreatography (ERCP) is contraindicated in acute pancreatitis.
Urografin is not to be used for myelography, ventriculography or cisternography, since it is likely to provoke neurotoxic symptoms (pain, convulsions and coma, often with lethal outcome) in these examinations.

4.4 Special Warnings and Precautions for Use

The need for examination merits particularly careful consideration in hypersensitivity to iodinated contrast media, severe impairment of hepatic or renal function, cardiac and circulatory insufficiency, pulmonary emphysema, poor general health, cerebral arteriosclerosis, diabetes mellitus requiring treatment, cerebral spasmodic conditions, latent hyperthyroidism, bland nodular goitre and multiple myeloma.
Fluid intake should not be restricted before the use of hypertonic contrast media in patients with multiple myeloma, diabetes mellitus requiring treatment, polyuria, oliguria or gout and in babies, young children and patients in a very poor general state of health.
The following precautions apply to any mode of administration, however the risks mentioned are higher in intravascular administration.

Hypersensitivity.

Occasionally, allergy-like hypersensitivity reactions have been observed after use of X-ray contrast media, such as Urografin (see Section 4.8 Adverse Effects (Undesirable Effects)). These reactions are usually manifest as non-serious respiratory or cutaneous symptoms, as mild respiratory distress, reddening of the skin (erythema), urticaria, itching or facial oedema. Serious events, such as angioedema, subglottic edema, bronchospasm and allergic shock are possible. Generally these reactions occur within one hour after administration of contrast media. However, in rare cases delayed reactions may occur (after hours to days).
Patients with hypersensitivity or a previous reaction to iodinated contrast media are at increased risk of having a severe reaction.
Before any contrast medium is injected, the patient should be questioned for a history of allergy (e.g. seafood allergy, hay fever, hives), sensitivity to iodine or to radiographic media and bronchial asthma as the reported incidence of adverse reactions to contrast media is higher in patients with these conditions and premedication with antihistamines and/or glucocorticoids may be considered. However contrast media and prophylactic agents should not be administered together.
Patients with bronchial asthma are at special risk of having bronchospasms or a hypersensitivity reaction.
If hypersensitivity reactions occur (see Section 4.8 Adverse Effects (Undesirable Effects)), administration of the contrast medium must be discontinued immediately and if necessary specific therapy instituted via a venous access. It is therefore advisable to use a flexible indwelling cannula for intravenous contrast medium administration. To permit immediate countermeasures to be taken in emergencies, appropriate drugs, an endotracheal tube and a respirator should be ready at hand.

Thyroid dysfunction.

Particularly careful risk-benefit assessment is required in patients with known or suspected hyperthyroidism or goiter, as iodinated contrast media may interfere with thyroid function, aggravate or induce hyperthyroidism and thyreotoxic crisis.
Testing of thyroid function prior to Urografin administration and/or preventive thyreostatic medication may be considered in patients with known or suspected hyperthyroidism.
In neonates, especially preterm infants, who have been exposed to Urografin, 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.

Cardiovascular disease.

There is an increased risk of severe reactions in individuals with severe cardiac disease and particularly in those with heart failure and coronary artery disease.

Very poor state of health.

The need for examination merits particularly careful consideration in patients with very poor general state of health.

Intravascular use.

Renal failure.

Temporary renal failure may occur in rare cases. Preventative measures against acute renal failure following contrast medium administration include:
Identification of high risk patients, e.g. patients with: a history of renal disease, pre-existing renal insufficiency, previous renal failure after contrast medium administration, diabetes mellitus and nephropathy, volume depletion, multiple myeloma, age greater than 60 years, advanced vascular disease, paraproteinemia, severe and chronic hypertension, gout, patients receiving large or repeated doses.
Ensuring adequate hydration in risk patients before contrast medium administration preferably by maintaining intravascular infusion before and after the procedure and until the contrast medium has been cleared by the kidneys.
Avoiding additional strain on the kidneys in the form of nephrotoxic drugs, oral cholecystographic agents, arterial clamping, renal arterial angioplasty, major surgery etc., until the contrast medium has been cleared.
Postponing a new contrast medium examination until renal function returns to pre-examination levels.

Metformin therapy.

The use of renally excreted intravascular X-ray contrast media can lead to transient impairment of kidney function. This may result in lactic acidosis in patients who are taking biguanides. (As a precaution, biguanides should be stopped 48 hours before until at least 48 hours after contrast medium administration and reinstated only after normal renal function has been regained).

Cardiovascular disease.

In patients with valvular disease and pulmonary hypertension, contrast medium administration may lead to pronounced hemodynamic changes. Reactions involving ischemic ECG changes and major arrhythmia are more common in older patients and in those with pre-existing cardiac disease.
The intravascular injection of contrast media may precipitate pulmonary edema in patients with heart failure.

CNS disorders.

Particular care should be paid to the intravascular administration of contrast media in patients with acute cerebral infarction, acute intracranial hemorrhage, and other conditions involving blood-brain barrier damage, cerebral edema or acute demyelination. Intracranial tumours or metastases and a history of epilepsy may increase the incidence of convulsive seizures after administration of iodinated contrast media. Neurological symptoms due to cerebrovascular diseases, intracranial tumours or metastases, degenerative or inflammatory pathologies may be exacerbated by contrast medium administration. Vasospasm and subsequent cerebral ischemic phenomena may be caused by intra-arterial injections of contrast media. Patients with symptomatic cerebrovascular diseases, recent stroke or frequent transient ischemic attacks have an increased risk of neurological complications.

Severe liver dysfunction.

In the case of severe renal insufficiency the coexistence of severe hepatic dysfunction can seriously delay contrast medium excretion, possibly necessitating haemodialysis.

Myeloma and paraproteinemia.

Myeloma or paraproteinemia may predispose to renal impairment following contrast medium administration. Adequate hydration is mandatory.

Pheochromocytoma.

Patients with pheochromocytoma may develop a severe (occasionally uncontrollable) hypertensive crisis following intravascular contrast medium use. Premedication with alpha-receptor blockers is recommended because of the risk of blood pressure crises.

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 iodinated contrast media may aggravate the symptoms of myasthenia gravis.

Alcoholism.

Acute or chronic alcoholism may increase blood-brain barrier permeability. This facilitates the passage of the contrast medium into cerebral tissue, possibly leading to CNS reactions. Caution must also be exercised in alcoholics and drug addicts because of the possibility of a reduced seizure threshold.

Coagulation.

Ionic iodinated contrast media inhibit blood coagulation in vitro, more than non-ionic contrast media. Nevertheless medical personnel performing vascular catheterization procedures should consider that numerous factors in addition to the contrast medium, including length of procedure, number of injections, catheter and syringe material, underlying disease state and concomitant medication may contribute to the development of thromboembolic events. Therefore, when performing vascular catheterization procedure one should be aware of this and pay meticulous attention to the angiographic technique and flush the catheter frequently with physiological saline (if possible with the addition of heparin) and minimize the length of the procedure so as to minimize the risk of procedure related thrombosis and embolism.
The use of plastic syringes in place of glass syringes has been reported to decrease but not eliminate the likelihood of in vitro clotting.
Caution is advised in patients with homocystinuria because of the risk of inducing thrombosis and embolism.

Use in body cavities.

The possibility of pregnancy must be excluded before performing hysterosalpingography.
Inflammation of the bile ducts or salpinx may increase the risk of reactions following cholangiography, ERCP or hysterosalpingography procedures.

Use in the elderly.

Underlying vascular pathology and neurological disorders often seen in the elderly constitute an increased risk of adverse reactions to iodinated contrast media.

Paediatric use.

See Section 4.6 Fertility, Pregnancy and Lactation, Use in paediatrics.

Effects on laboratory tests.

Interference with diagnostic tests.

Following the administration of iodinated renal contrast media, the capacity of the thyroid tissue to take up radioisotopes for diagnosing disorders of the thyroid is reduced for up to 2 weeks, and even longer in individual cases.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Hypersensitivity reactions can be aggravated in patients on beta-blockers particularly in the presence of bronchial asthma. Moreover, it should be considered that patients on beta-blockers may be refractory to standard treatment of hypersensitivity reactions with beta-agonists.
The prevalence of delayed reactions (e.g. fever, rash, flu-like symptoms, joint pain and pruritus) to contrast media is higher in patients who have received interleukin.
Diabetic nephropathy may predispose to renal impairment following intravascular contrast medium administration. This may precipitate lactic acidosis in patients who are taking biguanides. As a precaution, biguanides should be stopped 48 hours prior to the contrast medium examination and reinstated only after adequate renal function has been regained.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
It has not yet been demonstrated that Urografin is safe for use in pregnant patients. Since, wherever possible, radiation stress should be avoided during pregnancy, the benefits of any X-ray examination, with or without contrast material, should be carefully weighed against the possible risk.
Caution should be exercised when using Urografin in pregnant women. See Section 4.4 Special Warnings and Precautions for Use, Thyroid dysfunction, Paediatric use.
It is not known whether Urografin enters the breast milk. See Section 4.4 Special Warnings and Precautions for Use, Thyroid dysfunction, Paediatric use.

Use in paediatrics.

In neonates, especially preterm infants, who have been exposed to Urografin, 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. See Section 4.4 Special Warnings and Precautions for Use, Thyroid dysfunction.

4.8 Adverse Effects (Undesirable Effects)

In order to give an approximate indication of incidence of the following definitions apply when the words "common", "uncommon" and "rare" appear in the text. Common: incidence ≥ 1:100; uncommon: incidence < 1:100, but ≥ 1:1000; rare: incidence < 1:1000.

Intravascular use.

Side effects in association with the intravascular use of iodinated contrast media are usually mild to moderate and transient in nature. However, severe and life threatening reactions, even fatal ones, have been reported.
Nausea, vomiting, erythema, a sensation of pain and a general feeling of warmth are the most frequently recorded reactions on intravascular administration. Subjective complaints such as sensations of warmth or nausea can usually be alleviated quickly by reducing the rate of administration or interrupting the administration briefly.

Anaphylactoid reactions/ hypersensitivity.

Mild angioedema, conjunctivitis, coughing, pruritus, rhinitis, sneezing and urticaria have been reported commonly. These reactions, which can occur irrespective of the amount administered and the mode of administration, may be the first signs of incipient state of shock (see Section 4.4 Special Warnings and Precautions for Use).
Experience shows that hypersensitivity reactions occur more frequently in patients with an allergic disposition.
Severe reactions requiring emergency treatment can occur in the form of a circulatory reaction accompanied by peripheral vasodilatation and subsequent hypotension, reflex tachycardia, dyspnoea, agitation, confusion and cyanosis and possibly leading to unconsciousness.
Hypotension, bronchospasm and laryngeal spasm or oedema occurs uncommonly.
Delayed reactions can occasionally occur.
Paravascular administration of the contrast medium rarely leads to severe tissue reactions.

Body as a whole.

Heat sensations and headache have been reported as being common. Malaise, chills or sweating and vasovagal reactions are uncommon.
In rare cases alterations in body temperature and swelling of salivary glands are possible.

Respiratory.

Transient disturbances in respiratory rate, dyspnea and respiratory distress and coughing are common.
Respiratory arrest and pulmonary edema are rare reactions.

Cardiovascular.

Clinically relevant transient disturbance in heart rate, blood pressure, disturbance in cardiac rhythm or function and cardiac arrest are uncommon.
Severe reactions requiring emergency treatment can occur in the form of a circulatory reaction accompanied by peripheral vasodilatation and subsequent hypotension, reflex tachycardia, dyspnea, agitation, confusion and cyanosis possibly leading to unconsciousness.
Serious thromboembolic events causing myocardial infarction have been reported in rare cases.

Gastrointestinal.

Nausea and vomiting are common reactions. Abdominal pain has been reported as being uncommon.

Cerebrovascular.

It is known that cerebral angiography and other procedures in which the contrast medium reaches the brain with the arterial blood can be accompanied uncommonly by transient neurological complications. These include dizziness, headache, coma, amnesia, photophobia, temporary states, agitation or confusion and somnolence, convulsions, transient paresis/paralysis, tremor, disturbed speech, hearing, temporary blindness, vision or slack facial muscles and - particularly in epileptics and patients with focal brain damage - epileptic fits.
Serious, in isolated cases fatal, thromboembolic events causing stroke have been reported on rare occasions.

Renal.

Temporary renal failure may occur in rare cases.

Skin.

Mild angioedema, flush reaction with vasodilatation, urticaria, pruritus and erythema have been commonly observed.
Toxic skin reactions such as the mucocutaneous syndrome (e.g. Stevens-Johnson's or Lyell syndrome) may develop in rare cases.

Local irritation (injection site).

Local pain occurs commonly mainly in peripheral angiography. Extravasation of contrast media including Urografin gives rise to local pain and edema, but usually recedes without sequela. However inflammation and even tissue necrosis have been seen on very rare occasions. Thrombophlebitis and venous thrombosis are uncommon.

Use in body cavities.

Reactions after the administration into body cavities are rare. The majority of them occur some hours after the administration due to the slow absorption from the area of administration and distribution in the whole organism primarily through diffusion controlled processes.
Some elevation of amylase levels is common following ERCP. Acinar opacification following ERCP has been shown to be associated with an increased risk of post-ERCP pancreatitis. Rare cases of necrotizing pancreatitis have been described.
In connection with hysterosalpingography, cases of vasovagal reactions are uncommon.

Anaphylactoid reactions/ hypersensitivity.

Systemic hypersensitivity is rare, mostly mild and occurs generally in the form of skin reactions. However, the possibility of a severe hypersensitivity reaction cannot be totally excluded. For corresponding section on intravascular use, see Section 4.8 Adverse Effects (Undesirable Effects) for full information on anaphylactoid reactions.

Adverse drug reactions from post-marketing spontaneous reports.

Endocrine disorders.

Thyroid function tests indicative of hypothyroidism or transient thyroid suppression have been reported with unknown frequency following iodinated contrast media administration to adult and paediatric patients, including infants. Some patients were treated for hypothyroidism.

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/.

4.2 Dose and Method of Administration

General information.

Dietary suggestions.

In the case of abdominal angiography and urography, the diagnostic yield is increased if the bowels are emptied of faecal matter and gas. On the two days prior to the examination patients should therefore avoid flatulent food, in particular peas, beans and lentils, salads, fruit, dark and fresh bread and all kinds of uncooked vegetables. On the day before the examination, patients should refrain from eating after 6 p.m. Moreover, it can be appropriate to administer a laxative in the evening. In babies and young children, however, prolonged fasting and the administration of a laxative before the examination are contraindicated.

Hydration.

Adequate hydration must be assured before and after contrast medium administration. This applies especially to patients with multiple myeloma, diabetes mellitus and nephropathy, polyuria, oliguria, hyperuricaemia, as well as to newborns, infants, small children and elderly patients. Disturbances of the water and electrolyte balance must be corrected before the examination.

Newborns (< 1 month) and infants (1 month-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.

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.

Instructions for use/handling.

The contrast medium solution should not be drawn into the syringe or the infusion bottle attached to the infusion set until immediately before the examination. Contrast media should not be used in case of severe discoloration, the occurrence of particulate matter or defective container.
Vials containing contrast medium solutions are not intended for the withdrawal of multiple doses. The rubber stopper should never be pierced more than once to prevent large amounts of microparticles from the stopper getting into the solution. 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 cannulas, are particularly suitable).
Contrast medium solution not used in one examination session must be discarded.
The patient must attend for examination fasting but adequately hydrated. Disorders of the water and electrolyte balance must be corrected. This applies in particularly to patients who are predisposed to such disturbances.

Anxiety.

Pronounced states of excitement and anxiety may increase the risk of side effects or intensify contrast medium related reactions. They can be counteracted by calm management and the use of suitable drugs.

Warming prior to use.

Experience shows that contrast medium is tolerated better if it is warmed to body temperature.

Dosage for intravascular use.

Intravascular administration of contrast media should, if possible, be done with the patient lying down. After the administration, the patient should be kept under observation for at least 30 minutes, since experience shows that the majority of all severe incidents occur within this time.
The dosage may vary depending on the age, weight, cardiac output and general condition of the patient.
In patients suffering from marked renal or cardiovascular insufficiency and in patients in a poor general condition, the contrast medium dose must be kept as low as possible. In these patients it is advisable to monitor renal function for at least 3 days following the examination.
Should diagnostic clarification necessitate several high single doses, the opportunity should be given between injections to compensate for the increased serum osmolarity by the influx of interstitial fluid.
To achieve this, a period of 10-15 minutes is necessary in adequately hydrated patients. The intravascular administration of water and electrolytes is indicated if more than 300 mL contrast medium are required for a single examination.

Recommended doses.

Intravenous urography.

Injection.

Urografin 76% is used for intravenous urography. In general, the rate of injection is 20 mL/minute. If patients with cardiac insufficiency are given 100 mL or more, an injection time of 20-30 minutes is recommended.

Adults.

The dose is 20 mL Urografin 76%. Increasing the dose to 50 mL considerably increases the diagnostic yield. The dose may be increased yet again if this is considered necessary in special indications.

Children.

The physiologically weak concentrating ability of the still immature nephron of infantile kidneys necessitates relatively high doses of Urografin 76%. Up to 1 year: 7-10 mL; 1-2 years: 10-12 mL; 2-6 years: 12-15 mL; 6-12 years: 15-20 mL; above 12 years: adult dose.

Filming times.

The renal parenchyma can be demonstrated best when the film is taken immediately after the end of the administration.
For visualization of the renal pelvis and urinary tract, the first film is taken 3-5 minutes and the second 10-12 minutes after the administration of the contrast medium. In young patients one should generally choose the earlier and in older patients the later times.
In babies and young children it is advisable to take the first film as soon as about 2 minutes after the administration of the contrast medium.
Insufficient contrast can necessitate later films.

Infusion.

Adults and adolescents.

1 bottle of 100 mL Urografin 76% or 1 bottle of 250 mL Urografin 30%.
In general, the infusion time should not be less than 5 minutes nor much more than 10 minutes. Infusion times of 20-30 minutes are indicated in patients with cardiac insufficiency.

Children.

1 bottle of 250 mL Urografin 30% for infusion. 3-12 months: 6 mL/kg body weight; 1-8 years: 4 mL/kg body weight; over 8 years: 3 mL/kg body weight.
Infusion time: 8-10 minutes.
Compression is contraindicated in babies and is also inadvisable during the infusion of large amounts of contrast medium in children, adolescents and adults, since, if drainage is obstructed, the increased diuresis can lead to rupture of the fornix as a result of the high pressure. Compression may, however, be applied about 10 minutes after the end of the infusion to demarcate organic from functional filling defects.

Filming times.

The first film should be taken towards the end of the infusion. Further films may be taken within the next 20 minutes (or later in case of excretory disturbances).

Administration into body cavities.

Retrograde urography.

Because of its good tissue tolerance Urografin 30% is especially well suited for retrograde urography. It is advisable to warm the contrast medium to body temperature to avoid low-temperature stimulus and resultant ureteral spasms.
Urografin 76% solution may also be used if greater opacification is desirable for special examinations. Signs of irritation are observed extremely rarely despite the high concentration.

Angiography.

Urografin 76% is also suitable for angiographic examinations, preferably for those which require a particularly high iodine concentration, e.g. aortography, angiocardiography, coronary arteriography. The dosage depends on age, weight, cardiac output, general state of health, the clinical problem, examination technique, kind and volume of the region to be examined.

Other body cavities.

During arthrography, hysterosalpingography and especially ERCP, injections of contrast medium should be monitored by fluoroscopy. Consult special literature for further indications.

4.7 Effects on Ability to Drive and Use Machines

As with all iodinated contrast media, in rare cases there is a possibility of delayed reactions following contrast medium administration that could impair the ability to drive and use machines.

4.9 Overdose

In the event of accidental intravascular overdose in humans, the water and electrolyte losses must be compensated by infusion. Renal function needs monitoring for at least the next 3 days.
If needed, hemodialysis can be used to eliminate the bulk of the contrast medium from the patient's system.
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).

7 Medicine Schedule (Poisons Standard)

Unscheduled.

6 Pharmaceutical Particulars

6.1 List of Excipients

Urografin also contains sodium calcium edetate and water for injections.

6.2 Incompatibilities

Contrast media must not be mixed with any other drugs to avoid the risk of possible incompatibilities.

6.3 Shelf Life

5 years.
One day after first opening the container and without withdrawal of any contrast medium.

6.4 Special Precautions for Storage

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

6.5 Nature and Contents of Container

Urografin 30%.

10 x 10 mL in clear type I glass ampoule with rubber stopper closures; 1 x 250 mL in clear type II glass bottle with rubber stopper closures.

Urografin 76%.

10 x 50 mL in clear type II glass bottle with rubber stopper closures; 10 x 100 mL in clear type II glass bottle with rubber stopper closures.
Not all presentations are marketed in Australia or New Zealand.

6.6 Special Precautions for Disposal

In Australia and New Zealand, any unused medicine or waste material should be disposed of in accordance with local requirements.

Summary Table of Changes