UROGRAFIN 150 INFUSION

Package Leaflet: information for the patient

Urografin

2. Before you are given Urografin
Do not use Urografin if: R you are, or suspect you are, allergic (hypersensitive) to iodine or iodine-containing contrast media or any of the other ingredients of Urografin (see Section 6: Further Information) R you have a condition caused by too much thyroid hormone (uncontrolled thyrotoxicosis) R you have severe heart insufficiency (causing oedema (swelling of areas of your body e.g. ankles) or shortness of breath) R you are pregnant or have inflammation of the pelvic cavity (symptoms include stomach pain and tenderness, fever and irregular menstrual periods): you must not have your uterus (womb) investigated with Urografin. Take special care with Urografin You must tell the X-ray department staff if you have any of the following: R reduced liver or kidney function R epilepsy or a history of seizures R disease of blood vessels in the brain (cerebral a arteriosclerosis) R diabetes mellitus requiring treatment and/or associated with diabetic complications R damaged lungs (pulmonary emphysema) R poor general health R overactive thyroid gland (hyperthyroidism) or a an swollen neck due to an enlarged thyroid gland (benign nodular goitre) R disease of the bone marrow (multiple myeloma) a R history of allergy or a tendency to develop a hypersensitivity reactions (for example if you have hay fever, asthma or eczema), especially if you have taken a medicine like Urografin (a contrast medium) before R poor heart function or blood circulation R previously had a reaction to any contrast media. If any of these apply to you, you may be at a higher risk of having an allergic reaction or becoming unconscious/fainting. If you have a phaeochromocytoma (tumour of the adrenal gland) you may be given a medicine called an alpha-receptor blocker before the investigation to prevent your blood pressure from rising. Urografin may affect the way the thyroid gland works for 6 weeks or more after being given it. If you are going to have an iodine test for thyroid disease, tell your doctor or the laboratory staff if you have been given Urografin recently.

Sodium amidotrizoate (sodium diatrizoate) and meglumine amidotrizoate (meglumine diatrizoate)

Read all of this leaflet carefully before you are given this medicine. R Keep this leaflet. You may need to read it again. R you have any further questions, ask the doctor If giving you Urografin (the radiologist) or the X-ray department staff. R any of the side effects gets serious, or if you If notice any side effects not listed in this leaflet, please tell your doctor or the X-ray department staff/radiologist. In this leaflet: 1. What Urografin is and what it is used for 2. Before you are given Urografin 3. How you will be given Urografin 4. Possible side effects 5. How to store Urografin 6. Further information

1. hat Urografin is and what it is W used for
Urografin 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. X-rays, like radio waves, can pass through objects and can be focused to make a picture. When you have an X-ray, the beam of rays goes through your body where it is absorbed to differing degrees by different tissues such as bones, muscles and organs. When the rays come out on the other side they make a pattern of light and shade on a film. Urografin helps to make this pattern clearer. The film is then examined by a specialist who will make a diagnosis. This medicine is for diagnostic use only.

Taking or using other medicines Please tell the radiologist or X-ray department staff if you are taking or have recently taken any other medicines, including medicines obtained without prescription. This is particularly important for: R beta-blockers (drugs used to treat heart or blood pressure), because they can make allergic reactions worse R you have been treated with a drug called if interleukin, because there is a higher chance of getting delayed reactions (e.g. fever flu-like symptoms, joint pain and pruritus (itching)) R you have kidney disease due to diabetes (diabetic if nephropathy) and are taking a type of medicine called biguanides (metformin). You should inform your doctor who will probably stop the biguanides 48 hours before the examination. Ask the X-ray department staff if you are not sure. Using with food and drink If the procedure is to look at your abdomen, kidneys or bladder you may be asked to avoid foods that cause flatulence (wind) for two days beforehand. These foods include: - peas, beans, lentils, salads, fruit - brown or granary bread - kinds of uncooked vegetables. all You will be told not to eat after 6pm on the day before the examination, but you can still drink. Babies and young children, however, must not fast. If you have a disorder of your body water and body salts balance this will be corrected before the examination. Do not reduce the amount you normally drink before the investigation, especially if you have any of the following: R multiple myeloma (disease of the bone marrow) R diabetes mellitus R polyuria (production of large amounts of urine which is pale in colour) R oliguria (production of small amounts of urine) R gout. Also, fluid intake must not be reduced in babies, young children, or in someone who is in a very poor general state of health where their body tissues are wasting away. Pregnancy and breast-feeding Tell the X-ray department staff if you are pregnant, think you may be pregnant, or are breast feeding. Driving and using machines You should not drive or operate machinery for 24 hours after the examination as you may have a delayed reaction to Urografin. Please turn over

------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------Information for Healthcare Professionals

Urografin

Contra-indications
Proven or suspected hypersensitivity to iodinecontaining contrast media, uncontrolled thyrotox icosis and decompensated cardiac insufficiency. Hysterosalpingography must not be carried out during pregnancy or in patients with acute inflammatory conditions in the pelvic cavity.

Pregnancy and lactation
X-ray examinations should if possible be avoided during pregnancy. It has not yet been proved beyond question that Urografin may be used without hesitation in pregnant patients. Therefore, an examination with a contrast medium during pregnancy should be carried out only if considered absolutely necessary by the physician. Renally eliminated contrast media such as Urografin enter the breast milk in only very small amounts. Limited data suggest that the risk to the suckling infant of administering salts of diatrizoic acid to its mother is low.

Warnings Composition, availability and viscosity
The Urografin range contains sodium and meglumine amidotrizoate in various ratios. The numerical suffix gives the approximate iodine concentration of each medium (see table 1). 1ml Urografin 150 contains 40mg sodium amidotrizoate and 260mg meglumine amidotrizoate. 1ml Urografin 370 contains 100mg sodium amidotrizoate and 660mg meglumine amidotrizoate. Excipients: Sodium calcium edetate (E Number 385), water for injection. Table 1
Medium Ratio of sodium: meglu mine amido trizoate 10:66 Exact Availability Iodine Viscosity Iodine content (cp) concen (g) per tration container mg/ml 20C 37C 146 10ml ampoule 20ml ampoule 1.46 2.92 2.2 1.4

Urografin 150

250ml infu- 36.5 sion bottle 500ml infu- 73.0 sion bottle Urografin 370 10:66 370 20ml ampoule 7.4 18.5 8.9

50ml bottle 18.5 100ml bottle 37.0

Package quantities
Urografin 150: Packs of 10x10ml ampoules and 10x20ml ampoules. Urografin 150 for infusion: Packs of 1x250ml bottles and 1x500ml bottles. Urografin 370: Packs of 10x20ml ampoules and 10x50ml bottles. In addition packs of 1x100ml bottles. Urografin is a contrast medium. The product licence is held by: Bayer plc Bayer House Strawberry Hill Newbury Berkshire, RG14 1JA Product licence numbers Urografin 150 (30%) 00010/0569 Urografin 150 (30%) 00010/0568 for infusion Urografin 370 (76%) 00010/0570 Urografin is manufactured by: BerliMed S.A., Madrid, Spain.

Uses
X-ray contrast media for the delineation of the vascular and renal systems.

For patients with severe impairment of hepatic or renal function, cerebral arteriosclerosis, epileptic conditions, diabetes mellitus requiring drug treatment and/or associated with diabetic complications, pulmonary emphysema, poor general health, latent hyperthyroidism, multiple myeloma or benign nodular goitre the need for examination with X-ray contrast media merits careful consideration. This also applies to patients with a history of allergy, atopy, bronchial asthma, endogenous eczema, cardiac or circulatory insufficiency or a previous adverse reaction with any contrast medium since experience shows that they may be at higher risk from developing anaphylaxis or cardiovascular collapse. Consideration should be given to the use of low osmolar radiocontrast media in such patients. The patient should be recumbent during the administration of Urografin. Thereafter, the patient must be kept under close observation for at least 30 minutes, since about 90% of all severe incidents occur within that time. If the administration does not take place on the X-ray table, any patient with a labile circulation should be brought to the X-ray machine sitting or lying down. Particular caution should be exercised in allergic persons who have previously tolerated an injectable iodine-containing contrast medium without any complication because they may have become sensitized to these substances in the meantime. As with any contrast medium, the possibility of hypersensitivity must always be considered. If marked sideeffects or suspected allergic reactions occur during injection and do not disappear, or even get worse, when the injection is briefly interrupted, it is probable that the patient is hypersensitive and the investigation must be abandoned. Even relatively minor symptoms such as itching of the skin, sneezing, violent yawns, tickling in the throat, hoarseness or attacks of coughing may be early signs of a severe reaction and, therefore, merit careful attention. Ionic iodinated contrast media inhibit blood coagulation in vitro more than non-ionic contrast media. Nevertheless medical personnel performing vascular catheterisation procedures should pay meticulous attention to the angiographic technique and catheter flushing so as to minimise the risk of procedurerelated thrombosis and embolisation. In patients with multiple myeloma, diabetes mellitus requiring drug treatment, polyuria, oliguria or gout, and in infants, young children and marasmic patients the fluid supply should not be restricted. Existing disturbances of the balance of water and electrolytes must be corrected before the administration of a hypertonic contrast-medium solution. Premedication with an alpha-blocker is recommended in patients with phaeochromocytoma, because of the risk of hypertensive crisis. If iodine isotopes are to be administered for the diagnosis of thyroid disease, it should be borne in mind that after the administration of iodinated contrast media which are excreted via the kidneys, the capacity of the thyroid tissue to take up iodine will be reduced for 2 weeks, and sometimes up to 6 weeks. Experience shows that pronounced states of excitement, anxiety and pain can be the cause of side effects or intensify contrast medium-related reactions. They can be counteracted by calm management of the patient and the use of suitable drugs.

Drug Interactions
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. Hypersensitivity reactions can be aggravated in patients on beta-blockers. 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.

Incompatibilities
Some radiologists give an antihistamine or a corticoid prophylactically to patients with a history of allergy. However, because of the possibility of precipitation, X-ray contrast media and prophylactic agents must not be administered mixed together.

Effects on ability to drive and to use machines
Delayed reactions following intravascular admin istration of iodinated contrast media are rare. Nevertheless, driving or operating machinery is not advisable for the first 24 hours.

Dosage and administration
1. Adults only Table 2 shows the medium/media that the licence holder suggests for each investigation. These media may be used at the discretion of the radiologist for other established permutations of medium and exam ination which, for the sake of simplicity, have been omitted from the table.

Urografin.indd 1

29.10.2008 10:14:04



3. How you will be given Urografin
The X-ray department staff will decide how much Urografin is needed for your particular investigation. They will explain how everything works and what position you should lie in on the X-ray table. The dose of Urografin varies depending on the investigation and your weight. The dose range is normally between 1 and 500ml. Once you lie down the Urografin will be injected into a vein. Sometimes, Urografin will be injected into your muscles or anus (back passage). The staff in the X-ray department will observe you for 30 minutes after the injection just in case you have any side effects. If you receive more Urografin than you should Overdosing is unlikely. If it does happen the radiologist will treat any symptoms that follow.

4. Possible side effects
Like all medicines, Urografin can cause side effects, although not everybody gets them. Side effects you may get after being given a contrast medium like Urografin are usually mild and do not last long. However, as with similar contrast media, severe and life-threatening reactions, as well as deaths, have been reported. If you notice: R itching of the skin, rash, wheals on the skin (urticaria) R difficulty breathing, gagging, feeling of suffocation R swelling of the face, neck or body R itchy or watery eyes, tickling in the throat or nose, hoarseness, coughing or sneezing R headache, dizziness, feeling faint R feeling particularly hot or cold, sweating R paleness or reddening of the skin R chest pain, cramp, tremor R feeling sick Tell the radiologist or X-ray staff immediately as these may be the first signs of allergic reaction or shock. Your investigation will need to be stopped, and you may need further treatment.

Apart from the symptoms listed above the other possible side effects of Urografin are: R feeling sick or being sick R sensation of pain and a general feeling of a warmth R rare cases your kidneys temporarily stop in working R reddening or other reactions at the injection site if Urografin is not injected properly. Very rarely severe or even life-threatening side-effects may occur and in some cases have been fatal. These include: R lowered blood pressure R fainting (collapse) R circulatory failure R irregular, rapid heart beat which may cause the an heart to suddenly stop beating altogether (cardiac arrest) R or other brain related symptoms fits R build-up of water in the air spaces of the lung a R anaphylactic shock (a very severe allergic reaction). If you are having a procedure where Urografin will reach the brain, you may have complications such as: R coma, temporary confusion and drowsiness R temporary weakness of the muscles R disturbed vision or weakness of the facial muscles R epileptic fits, especially in someone with epilepsy or brain damage. Delayed reactions can occasionally occur, if you are concerned you should contact your doctor. If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or the X-ray department staff/radiologist.

6. Further Information
What Urografin contains The active substances are sodium amidotrizoate and meglumine amidotrizoate. 1 ml Urografin 150 contains 40mg sodium amidotrizoate and 260mg meglumine amidotrizoate. 1 ml Urografin 150 for infusion contains 40mg sodium amidotrizoate and 260mg meglumine amidotrizoate. 1 ml Urografin 370 contains 100mg sodium amidotrizoate and 660 mg meglumine amidotrizoate. T he other ingredients are sodium calcium edetate (E 385) and water for injections. What Urografin looks like and contents of the pack Urografin 150 is available in packs of ten 10ml ampoules or packs of ten 20ml ampoules. Urografin 150 for infusion is available in 250ml or 500ml bottles. Urografin 370 is available in packs of ten 50 ml bottles or one 100ml bottle. Marketing Authorisation Holder and Manufacturer Marketing Authorisation Holder: Bayer plc Bayer House Strawberry Hill Newbury Berkshire, RG14 1JA Manufacturer: BerliMed S.A Madrid Spain This leaflet was last approved in May 2008 Urografin is a registered trademark of Bayer Schering Pharma AG (formerly Schering AG).

5. How to store Urografin
Keep out of the reach and sight of children. Do not use Urografin after the expiry date which is stated on the label. The expiry date refers to the last day of that month. Protect from light and secondary X-rays.

To listen to or request a copy of this leaflet in Braille, large print or audio please call, free of charge: Please be ready to give the following information: Product name Reference number Urografin 150 00010/0569 Urografin 150 for 00010/0568 Infusion Urografin 370 00010/0570 This is a service provided by the Royal National Institute of the Blind.

0800 198 5000 (UK only)

---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------Table 2 medium. The earlier time should be chosen for younger patients and the later time for older patients. Urografin 370 Examination 150 370 In babies and young children it is advisable to take the up to 1 year 7-10ml first film as early as about 2 minutes after the adminIntravenous urography Up to 1-2 years 10-12ml istration of the contrast medium. 70mla Insufficient contrast can necessitate later films. 2-6 years 12-15ml Drip-infusion urography 2-4ml/kg body wt up 6-12 years 15-20ml Overdosage to 250ml over 12 years adult dose Acute symptoms of poisoning are unlikely with intraRetrograde urography 5-10ml R Drip infusion urography vascular administration. On inadvertent overdosage Dosage of Urografin 150 should not exceed 4ml/kg Cystography Up to or in greatly impaired renal function, the contrast body weight. 500ml medium may be removed by dialysis, and the balance R Angiocardiography of water and electrolytes should be corrected. Angiocardiography 30-50ml In neonates up to 5kg body weight, 8ml Urografin Acute toxicity studies do not suggest a risk of acute Right heart 40-80ml 370; Infants over 5kg body weight, 1ml/kg body intoxication. catheterisation weight up to 25ml per injection. R Right and left heart catheterisation Left heart 40-60ml Side effects catheterisation 1-1.2ml/kg body weight of Urografin 370, with a Mild subjective symptoms, such as a feeling of heat maximum of 15ml per injection for right heart and Pulmonary 30-40ml and nausea, occur very seldom and disappear rapidly 25ml per injection for left heart. angiography when the injection is slowed down or briefly interR Pulmonary angiography rupted. Transient pain may occur, in particular during Coronary arteriography 4-8ml per the examination of peripheral vascular regions. 0.5-0.6ml/kg body weight up to 8ml Urografin 370 per arteryb injection. Other symptoms which may occur are: Renal arteriography 5-8ml 3. General Chills, fever, sweating, headache, dizziness, blanching, weakness, gagging and a feeling of suffocation, In the case of abdominal angiography and urography, Coeliac-axis 35-80ml gasping, a rise or fall of blood pressure, itching, urtic the diagnostic yield is increased if the bowels are arteriography aria, other kinds of skin eruption, oedema, cramp, emptied of faecal matter and gas. On the two days Thoracic aortography 30-60ml tremor, sneezing and lacrimation. These reactions, prior to the examination, patients should therefore which can occur irrespective of the amount adminisavoid flatulent food, in particular peas, beans and Pelvic aortography 20-25ml tered and the mode of administration, may be the first lentils, salads, fruit, brown or granary bread and all Translumbar 20-30ml signs of incipient shock. Administration of the kinds of uncooked vegetables. On the day before abdominal aortography contrast medium must be discontinued immediately examination, patients should refrain from eating after and - if necessary - specific therapy instituted intra 6pm. Moreover, it can be appropriate to administer a Placentography 25ml venously. It is therefore advisable to use a flexible laxative in the evening. Splenoportography 40-50ml indwelling cannula for intravenous contrast medium The patient must attend for examination fasting but administration. Hysterosalpingography 4-7ml adequately hydrated. Disorders of the water and eleca If patients with cardiac insufficiency are given 100ml Very rarely, severe or even life-threatening side-effects trolyte balance must be corrected. This applies in or more, an injection time of at least 20-30 minutes is such as severe hypotension and collapse, circulatory particular to patients who are predisposed to such recommended. failure, ventricular fibrillation, cardiac arrest, disturbances. b pulmonary oedema, anaphylactic shock or other 1 00ml vials are available for coronary arteriography. In babies and young children, however, prolonged allergic manifestations, convulsions, or other cerebral fasting and the administration of a laxative before the Other indications include: high dose urography, pelvic symptoms may occur. In some cases these have examination are contraindicated. venography, venacavography, arthrography, selective proved fatal. visceral angiography, limb venography, jugular Intravascular administration of contrast media To permit immediate countermeasures to be taken in venography, vesiculography, sialography, should, if possible, be done with the patient lying emergencies, appropriate drugs, an endotracheal tube sinusography, amniography, lymphangiography, down. After the administration, the patient should be and a ventilator should be ready to hand. intramuscular urography, operative and percutaneous kept under observation for at least 30 minutes, since cholangiography, fistulography, oesophageal and anal Experience shows that hypersensitivity reactions occur experience shows that the majority of all severe atresia. more frequently in patients with an allergic incidents occur within this time. If the administration disposition. does not take place on the X-ray table, any patient Urografin media are not suitable for myelography. with a labile circulation should be brought to the X-ray Paravascular administration of the contrast medium Urodynamic studies machine sitting or lying down. rarely leads to severe tissue reactions. Urografin 150 (a 30% solution) can be diluted with Experience shows that contrast medium is tolerated Delayed reactions can occasionally occur. normal saline to obtain the desired density. better if it is warmed to body temperature. Neurological complications such as coma, temporary The pH is not significantly affected by dilution. The contrast medium solution should not be drawn states of confusion and somnolence, transient paresis, R Retrograde urography into the syringe or the infusion bottle attached to the disturbed vision or facial muscle paresis and epileptic A 30% solution (Urografin 150) is generally sufficient infusion set until immediately before the examination. fits may occur after cerebral angiography and other for retrograde urography. It is advisable to warm the procedures in which the contrast medium reaches the Vials containing contrast medium solutions are not contrast medium to body temperature to avoid lowbrain with the arterial blood. In very rare cases the intended for the withdrawal of multiple doses. The temperature stimulus and resultant ureteric spasms. induction of fits has been observed after intravenous rubber stopper should never be pierced more than R Infusion urography administration of Urografin in epileptics and patients once. The use of cannulas with a long tip and a The rapid infusion of large amounts of a contrast with focal brain damage. However, a causal maximum diameter of 18G is recommended for piercmedium in low concentration produces increased relationship seems to be questionable. ing the stopper and drawing up the contrast medium urine formation while retaining a high concentration (dedicated withdrawal cannulas with a side hole, e.g. Temporary renal failure may occur in rare cases. of the contrast medium in the urine. Nocore-Admix cannulas, are particularly suitable). This method can provide complete visualisation of the Contrast media not used in one investigation must be Suggestions for the treatment of renal pelvis and calyces as well as the entire course of discarded. contrast medium incidents the ureters. The nephrographic effect is also intensiIf diagnostic clarification necessitates several high fied, and is prolonged for up to 15-30 minutes after It is very important in order to be able to take prompt single doses, the patient should be given the the termination of the infusion. action in the event of contrast medium incidents to opportunity between injections to compensate for the have all drugs and instruments for emergency therapy R Angiography increased serum osmolality by the influx of interstitial readily available and to be familiar with the practice fluid. Urografin 370 is suitable for angiographic of emergency measures. Please refer to the Royal investigations. It is preferred for those angiographic To achieve this, a period of 10-15 minutes is necessary College of Radiologists guidelines Advice on the investigations in which a high iodine concentration is in adequately hydrated patients. The intravascular management of reactions to intravenous contrast of special significance, e.g. aortography, administration of water and electrolytes is indicated if media. angiocardiography, coronary arteriography. more than 300ml contrast medium are required for a Expiry date: The expiry date is printed on the label. single examination. 2. Children and neonates The contrast medium should not be used after this R Filming times after injection R Intravenous Urography date. The renal parenchyma can be demonstrated best The fact that urograms of infants and young children Storage: Protect from light and X-rays. when the film is taken immediately after the end of generally show a lower contrast density than those of Date of last revision of this leaflet: 1 May 2008 the administration. adults is explained by the physiologically less effecUrografin is a registered trademark of Bayer Schering tive function of the immature nephron. Relatively For visualisation of the renal pelvis and urinary tract, Pharma AG (formerly Schering AG). high doses of media are therefore indicated. the first film is taken 3-5 and the second 10-12 minutes after the administration of the contrast

Urografin.indd 2

29.10.2008 10:14:04