SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Urografin® 150 for infusion

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

1ml contains 40 mg sodium amidotrizoate (sodium diatrizoate) and 260 mg meglumine amidotrizoate (meglumine diatrizoate).

Excipient with known effect

Sodium calcium edetate

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Aqueous solution for injection

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

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

4.2 Posology and method of administration

1. Adults only

The table below shows the medium the licence holder suggests for each investigation. This medium may be used at the discretion of the radiologist for other established permutations of medium and examination which, for the sake of simplicity, have been omitted from the table.

Examination_Dose regimen

Drip-infusion urography    2-4 ml/kg body

wt up to 250 ml

Retrograde urography    5-10 ml

Cystography    Up to 500 ml

(Other indications include: high dose urography, pelvic venography, venacavography, arthrography, selective visceral angiography, limb venography, jugular venography, vesiculography, sialography, sinusography, amniography,lymphangiography, intramuscular urography,operative cholangiography,percutaneous cholangiography, fistulography, oesophageal and anal atresia).

Urografin medium is not suitable for myelography 2. Children and neonates

Drip-infusion urography: Dosage of Urografin 150 should not exceed 4 ml/kg body weight.

• General Information

The patient should be recumbent during the administration of Urografin and kept under close observation for at least 30 minutes (see Special warnings and special precautions for use).

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

4.3 Contraindications

Proven or suspected hypersensitivity to iodine-containing contrast media, uncontrolled thyrotoxicosis and decompensated cardiac insufficiency.

Hysterosalpingography must not be carried out during pregnancy or in patients with acute inflammatory conditions in the pelvic cavity.

4.4 Special warnings and precautions for use

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 an X-ray contrast medium 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 sensitised to these substances in the meantime.

As with any contrast medium, the possibility of hypersensitivity must always be considered. If marked side-effects 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 procedure-related 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 an iodinated contrast medium which is 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.

4.5 Interaction with other medicinal products and other forms of interaction

Diabetic nephropathy may predispose to renal impairment following intravascular administration of contrast media. This may precipitate lactic acidosis in patients who are taking biguanides. As a precaution biguanides should be stopped 48 hours prior to the 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.

4.6 Fertility, pregnancy and lactation

Pregnancy

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.

Breast-feeding

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.

4.7 Effects on ability to drive and use machines

Delayed reactions following intravascular administration of iodinated contrast media are rare. Nevertheless, driving or operating machinery is not advisable for the first 24 hours.

4.8 Undesirable effects

Mild subjective symptoms, such as a feeling of heat and nausea, occur very seldom and disappear rapidly when the injection is slowed down or briefly interrupted. Transient pain may occur, in particular during the examination of peripheral vascular regions.

Other symptoms which may occur are:

Chills, fever, sweating, headache, dizziness, blanching, weakness, gagging and a feeling of suffocation, gasping, a rise or fall of blood pressure, itching, urticaria, other kinds of skin eruption, oedema, cramp, tremor, sneezing and lacrimation. These reactions, which can occur irrespective of the amount administered and the mode of administration, may be the first signs of incipient shock. Administration of the contrast medium must be discontinued immediately and - if necessary - specific therapy instituted intravenously. It is therefore advisable to use a flexible indwelling cannula for intravenous contrast medium administration.

Very rarely, severe or even life-threatening side-effects such as severe hypotension and collapse, circulatory failure, ventricular fibrillation, cardiac arrest, pulmonary oedema, anaphylactic shock or other allergic manifestations, convulsions, or other cerebral symptoms may occur. In some cases these have proved fatal.

To permit immediate countermeasures to be taken in emergencies, appropriate drugs, an endotracheal tube and a ventilator should be ready to hand.

Experience shows that hypersensitivity reactions occur more frequently in patients with an allergic disposition.

Paravascular administration of the contrast medium rarely leads to severe tissue reactions.

Delayed reactions can occasionally occur.

Neurological complications such as coma, temporary states of confusion and somnolence, transient paresis, disturbed vision or facial muscle paresis and epileptic fits may occur after cerebral angiography and other procedures in which the contrast medium reaches the brain with the arterial blood. In very rare cases the induction of fits has been observed after intravenous administration of Urografin in epileptics and patients with focal brain damage. However, a causal relationship seems to be questionable.

Temporary renal failure may occur in rare cases.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation 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 via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

4.9 Overdose

Acute symptoms of poisoning are unlikely with intravascular administration. On inadvertent overdosage or in greatly impaired renal function, the contrast medium may be removed by dialysis, and the balance of water and electrolytes should be corrected. Acute toxicity studies do not suggest a risk of acute intoxication.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: X-ray contrast medium, iodinated and watersoluble, ATC code: V08AA01

Urografin does not exert a pharmacological effect. It is an iodine - containing contrast medium, iodine being radio-opaque.

5.2 Pharmacokinetic properties

Absorption of amidotrizoic acid, the radiopaque component of Urografin, following oral administration is virtually nil. Plasma protein binding following intravenous injection amounts to less than 10%.

At diagnostic doses, amidotrizoic acid undergoes glomerular filtration. Approximately 15% of the dose is eliminated in chemically unchanged form with the urine within 30 minutes after the injection, and more than 50% within 3 hours; no metabolites could be demonstrated.

In impaired renal function amidotrizoate can also be eliminated extrarenally via the liver, although at a distinctly reduced rate. Renal contrast media can easily be removed from the body by extracorporeal haemodialysis.

It is very quickly distributed in the extracelluar space following intravascular administration, but is not able to Overcome an intact blood-brain barrier and is transmitted in only minimal amounts into breast milk.

5.3 Preclinical safety data

There are no pre-clinical safety data which could be of relevance to the prescriber and which are not already included in other relevant sections of the SPC.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

water for injection, sodium calcium edetate.

6.2 Incompatibilities

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

6.3    Shelf life

5 years

6.4    Special precautions for storage

Protect from light and X-rays.

6.5 Nature and contents of container

Packs of 1 x 250 ml infusion bottles.

Packs of 1 x 500 ml infusion bottles.

6.6 Special precautions for disposal

The infusion bottle should not be attached to the infusion set until immediately before the examination.

Bottles containing contrast medium solutions are not intended for the withdrawal of multiple doses. The rubber stopper should never be pierced more than once.

Contrast medium not used in one examination session must be discarded.

7    MARKETING AUTHORISATION HOLDER

Bayer plc Bayer House Strawberry Hill Newbury Berkshire RG14 1JA

8    MARKETING AUTHORISATION NUMBER(S)

PL 00010/0568

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION

12 December 1996

10 DATE OF REVISION OF THE TEXT

13/01/2016