SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Hexabrix 320 (320 mgl/mL), solution for injection.

2    QUALITATIVE AND QUANTITATIVE COMPOSITION

Ioxaglic Acid    HSE    53.3%    w/v

For a full list of excipients, see section 6.1.

3    PHARMACEUTICAL FORM

Solution for injection

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Low osmolar X-ray contrast medium for the opacification of the vascular system, urinary tract and joints and female genital tract, the indications for which are given under doses and dosage schedules.

4.2 Posology and method of administration

There are no specific dosage recommendations for the elderly.

Procedure	Product	Dosage and Administration
Femoral and other peripheral arteriographies	Hexabrix 320	15 - 20 ml injected into the femoral or iliac artery will provide excellent visualisation of the arterial tree of the leg. A similar or smaller dose is indicated for smaller arteries.
Cerebral angiography Carotid and vertebral	Hexabrix 320	Average adult dose: 6 - 8 ml for each (carotid and vertebral) injection. Up to 10 injections each of 8 ml may be required.
Angiocardiography	Hexabrix 320	Multiple small test injections may be used for positioning catheter tip. Adults and children over 14 years: 30 -50 ml per injection. Children (14 years and under) and

		infants: 1-1.5 ml per kg body weight. Multiple injections may be required. Total dosage should not normally exceed 4 ml per kg body weight. In exceptional circumstances this total may be exceeded according to the clinical condition.
Abdominal aortography (direct puncture or catheterisation)	Hexabrix 320	Adults: 20 - 30 ml. up to 50 ml may be used particularly if films of the legs are also taken following the same injection.
Thoracic aortography (including arch aortography)	Hexabrix 320	Adults and children: 0.5 ml - 1.0 per kg body weight, up to 40 ml per injection. This may be repeated if necessary. Total dosage should not normally exceed 4 ml per kg body weight.
Pulmonary angiography	Hexabrix 320	Adults: 20 - 40 ml. Children. 0.5 - 1 ml per kg body weight. Special care should be exercised in patients with pulmonary artery hypertension.
Coronary arteriography	Hexabrix 320 to be diluted 50% with water for injection BP or sodium chloride and dextrose injection BP to produce a solution containing 160 mg of iodine per ml.	The appropriate volume of diluted medium (depending on the part of the body to be visualised) should be injected into a suitable artery.
Intravenous aortography	Hexabrix 320	Adults and children: 1 - 1.5 ml per kg body weight. In adults 100 ml is often used; frequently this amount is subdivided equally and given by simultaneous rapid bilateral injection.
Femoral venography and/ or	Hexabrix 320	Adults: 20 - 50 ml.

inferior vena
Cavography
Leg phlebography	Hexabrix 320	20 - 50 ml injected into a vein in the foot.
Intravenous urography	Hexabrix 320	Adults: 20 - 80 ml; 60 - 100 ml may be used, provided the patient is not dehydrated. Children: under 12 kg - 2 ml per kg body weight; over 12 kg - 1.5 ml per kg body weight (with a minimum of 24 ml). Over 10 years of age: lower range of adult dose.
		Patients with several renal disease or diabetes should be well hydrated. Particular care is necessary in these patients as temporary deterioration in renal function has been reported.
Splenography portal venography	Hexabrix 320	Adults: 20 - 40 ml by splenic puncture.
Knee arthrography	Hexabrix 320	By injection into the knee joint.
(double contrast)		Adults: 4.5 ml together with injections of air before and after the positive contrast medium.
Hysterosalpingography	Hexabrix 320	About 10 ml are usually required. Administered by slow injection into uterine cervical canal via a syringe or suitable cannula.

4.3 Contraindications

1)    Use by subarachnoid or epidural route.

2)    Use in myelography.

3)    Use in proven or suspected hypersensitivity to Iodine containing contrast media.

4.4 Special warnings and precautions for use

Since the causes of severe reactions to iodinated water-soluble contrast media are unknown and preliminary testing is unreliable as an indication that a patient will react unfavourably, the only other safeguards are physical examination and a careful evaluation of the patient’s history to screen out subjects known to suffer from allergy, asthma, atopy, or severe cardiovascular disease. The provision of facilities for resuscitation and the training of staff members in their prompt use is mandatory.

Patients must be kept under close observation for 15 minutes following the last injection as the majority of severe reactions occur at this time.

The patient should remain in the hospital environment for one hour after time of injection. The patient should return to the appropriate department if any symptoms develop.

Like all iodinated contrast agents, Hexabrix 320 can induce mild, serious or even fatal reactions. These reactions are always unpredictable, but are more frequent in patients with a history of allergy, or atopy or who have demonstrated hypersensitivity during a previous examination with an iodinated contrast agent.

A positive history of allergy, atopy, asthma, cardiac disease or of untoward reactions during previous similar investigations does not necessarily contraindicate the use of the contrast agent. However since these patients are at increased risk of developing anaphylaxis or cardiovascular collapse, there is need for extra caution, possibly steroid cover. Consideration should be given to the use of non-ionic low osmolar radio contrast media in such patients.

Extra caution should be exercised in carrying out radiographic procedures with contrast media in patients with severe systemic disease, asthma, and in allergic subjects. In patients with advanced renal disease and inadequate renal function as reflected by a raised blood urea, and in diabetics, the normally rapid excretion of the contrast medium may be markedly impaired. Even in patients with kidney disease substantial deterioration of renal function is minimised if the patient is well hydrated. Urine output must be carefully checked in these patients after the procedure.

Patients with hepatorenal insufficiency should not be examined unless the possibility of benefit clearly outweighs the additional risk. Re-examination should be delayed for five to seven days.

Because of the possibility, remote though it may be, of a delayed reaction to the contrast agent, the patient should never be left unsupervised for the thirty minutes immediately after the injection.

Rare cases of hypothyroidism due to iodine overload have been reported in new born and in particular, premature babies, following opacification via central catheters.

4.5 Interaction with other medicinal products and other forms of interaction

Special care should be exercised in patients being treated with a calcium ion antagonist (e.g. verapamil) and who are to undergo coronary angiography, in such circumstances a few instances of serious arrhythmias have been reported.

4.6 Pregnancy and lactation

There is no evidence that this product is safe during pregnancy, nor is there evidence in animal work that it is free from hazard. The product should not be used during pregnancy unless the benefits outweigh the risks and the physician considers it essential. The ten day rule in women of childbearing age should be observed.

4.7 Effects on ability to drive and use machines

There is no known effect on the ability to drive and operate machines. However, because of the risk of early reactions driving or operating machinery is not advisable for 1 hour following the time of the injection.

4.8 Undesirable effects

In cerebral arteriography, the only frequent side-effect is facial heat, usually of mild degree.

In femoral and iliac arteriography a warm feeling is usually experienced and very rarely slight pain may be felt but leg movement and/or vocal protests are unusual.

After the rapid injection of Hexabrix for angiocardiography or aortography, patients may experience a wave of mild warmth, associated with flushing passing over the body. Slight coughing may occur after right heart or pulmonary artery injections. Other transient reactions reported rarely are nausea, vomiting, hypotension, headache and a metallic taste.

In very rare instances, fever and rigors could occur in association with these symptoms or alone.

Following an arthrography, pain and/or joint swelling, both transient and of moderate intensity can occur.

A few ventricular extrasystoles are common after any rapid intra-ventricular injection and the injection flow should not exceed 12 ml/sec in the adult ventricle. Ventricular fibrillation may occur very infrequently after intra-cardiac or intra-coronary injection and a D.C. defibrillator and other equipment necessary for defibrillation must always be available during these studies.

Following intracardiac, ascending aortic or coronary artery injection, the QRST complex of the ECG may be altered briefly. After prolonged cardiac catheterisation (with or without injection of a contrast medium), 5 to 10 per cent of patients may develop some degree of shivering or shock.

In intravenous urography, nausea, vomiting, dizziness and urticaria have been reported occasionally but have been of little consequence.

Severe and life threatening side effects including cardiovascular collapse and anaphylactic shock have occurred; in some cases, these have proved fatal.

Delayed reactions may occasionally occur and the most common delayed reactions are pruritus and urticaria.

4.9 Overdose

In laboratory animals the main signs of toxicity are convulsions, pulmonary congestion and oedema, respiratory depression, prostration, darkening of the eyes and hypersalivation; it is most unlikely that such toxic signs would occur in man, as it would be necessary to inject far greater doses than the maximum recommended. In man, overdosage as such should not arise but, since the causes of severe reactions to iodinated water-soluble contrast media are unknown, the information detailed under precautions and resuscitation should be carefully studied.

5    PHARMACOLOGICAL PROPERTIES

5.1    Pharmacodynamic properties

Hexabrix produces opacification of the vascular system and the urinary tract.

Pharmacological effects on the central nervous system, cardiovascular system and respiratory system are generally minor and of short duration.

No other pharmacological activity of note has been demonstrated.

5.2 Pharmacokinetic properties

Hexabrix is rapidly eliminated by the kidneys with a half-life of about 90 minutes. 99% of the dose is eliminated in 24 hours. Biliary excretion may be of some importance in kidney impairment. The compound is not metabolised.

5.3 Preclinical safety data

None stated.

PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Meglumine	EP	QS	5.41	w/v
Sodium hydroxide (Pronalys)	EP	QS	0.63	w/v
Sodium calcium edetate	EP	QS	0.01	w/v
Water for injections	EP	TO	100.0

6.2 Incompatibilities

Apart from water for injections and dextrose saline, Hexabrix should not be mixed with any other substance.

6.3 Shelf life

3 years, unopened.

6.4 Special precautions for storage

Protect from light.

6.5 Nature and contents of container

Hexabrix 320, solution for injection, is packaged in a glass vial closed with a rubber stopper. Hexabrix 320 is presented in the following containers sizes :

-    20 mL filled in a 20 mL or 30 mL vial,

-    50 mL filled in a 60 mL vial,

-    100 mL filled in a 100 mL or 125 mL vial,

Pack size : 10

6.6 Special precautions for disposal

None stated.

7. MARKETING AUTHORISATION HOLDER

GUERBET BP 57400

95943 Roissy CdG cedex