HEXABRIX 320 (320 MGI/ML) SOLUTION FOR INJECTION.
HEXABRIX 320 (320 mgI/ml)
PACKAGE LEAFLET: INFORMATION FOR THE USER
Solution for injection
Meglumine ioxaglate, Sodium ioxaglate
Read all of this leaflet carefully before you start using this medicine.
• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• 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 pharmacist.
What is in this leaflet:
1. What HEXABRIX 320 is and what it is used for
2. What you need to know before you are given HEXABRIX 320
3. How to use HEXABRIX 320
4. Possible side effects
5. How to store HEXABRIX 320
6. Content of the pack and other information
1. WHAT HEXABRIX 320 IS AND WHAT IT IS USED FOR
HEXABRIX 320 is a diagnostic agent. It belongs to the group of contrast agents used for radiological
HEXABRIX 320 is used to enhance the contrast of the images obtained during radiological examinations.
This contrast enhancement improves the visualisation and delineation of certain body parts.
This medicine is for diagnostic use only.
2. WHAT YOU NEED TO KNOW BEFORE YOU ARE GIVEN HEXABRIX 320
You should read the information in this section carefully.
You and your doctor should consider this information before you are given HEXABRIX 320.
Your doctor must never give you HEXABRIX 320 in the following cases:
• If you are allergic to the active substance (ioxaglic acid) or any of the other ingredients of HEXABRIX 320.
The list of these ingredients can be found in section 6. Content of the pack and other information.
• If you have already had an allergic reaction following the injection of a medicinal product containing the
same active ingredient (ioxaglic acid) (also refer to section 4. Possible side effects).
• If you suffer from excessively high levels of thyroid hormones (hyperthyroidism or thyrotoxicosis).
• If you are pregnant, if you think you are pregnant and you are to undergo an examination of the uterus
and fallopian tubes, which are ducts connecting the uterus and the ovaries (hysterosalpingography).
When special care is needed with HEXABRIX 320 (warning and precautions)
As with any iodinated contrast medium, no matter what the method of administration and the dose, there is
a possibility of side effects; which can be minor but can also be life-threatening. These reactions can occur
within an hour or, more rarely, up to 7 days after administration. They are often unexpected but the risk of
these is higher if you have already had a reaction following previous administration of an iodinated contrast
medium (see section 4. Possible side effects).
You should also report any other disease that you suffer from, so that the doctor who administers the product
can take the necessary precautions for use.
Before the examination, you must inform your doctor if one of the following situations
applies to you:
• If you have already had a reaction to an iodinated contrast medium during an examination.
• If you are to undergo an examination of the spinal cord (myelography).
• If you suffer from poor kidney function (renal impairment).
• If you suffer from both poor kidney function and poor liver function (renal and hepatic impairment).
• If your heart does not work properly (heart failure) or if you have any other heart or vascular disease
• If the level of sugar in your blood is high (diabetes).
• If you are asthmatic and you have had an asthma attack in the 8 days leading up to the examination.
• If you suffer from epilepsy.
• If you have had a stroke, if you recently experienced bleeding inside your skull (intracranial haemorrhage).
• If the quantity of liquid inside your brain is increased (cerebral oedema) .
• If your body produces an excess of hormones, leading to very high arterial pressure (pheochromocytoma).
• If you have a disease of the muscles (myasthenia gravis).
• If you have thyroid disease or a history of thyroid disease.
• if you are to have a thyroid examination or treatment with radioactive iodine in the near future.
• If you have a bone marrow disease (myeloma, monoclonal gammopathy, multiple myeloma or
• If you are anxious, nervous, or in pain (side effects can be increased in such cases).
• If you regularly drink large quantities of alcohol or if you use drugs.
• If you suffer from any other disease.
Other medicines and HEXABRIX 320
Tell your doctor or pharmacist if you are taking or have recently taken any other medicines, even ones obtained
without a prescription. Take particular care if you are taking :
• a medicinal product used to treat high levels of sugar in the blood (metformin).
• a medicinal product used to treat a heart disease or high blood pressure (diuretics and beta blockers).
• a medicinal product used, among others, to treat certain cancers (interleukin-2).
• any other radiopharmaceutical agent which has been used recently.
HEXABRIX 320 with food, drink and alcohol
Ask your doctor or pharmacist to know if you need to not eat or drink before the examination.
You should inform your doctor if you regularly drink large quantities of alcohol (see section 2. What you need
to know before you are given HEXABRIX 320).
Pregnancy, breast-feeding and fertility
You must never be given HEXABRIX 320 if you are pregnant or think you can be pregnant and you are to
undergo an examination of the uterus and the fallopian tubes (ducts connecting the uterus and the ovaries).
If you are pregnant or late with any of your periods, it is essential that you tell your doctor before you undergo
your radiological examination.
Ask your doctor or pharmacist for advice before taking any medicine.
HEXABRIX 320 may be secreted in breast milk.
You should stop breastfeeding for at least 24 hours after administration of HEXABRIX 320.
Ask your doctor or pharmacist for advice before taking any medicine.
Driving and using machines
There is no known effect on your ability to drive. However, because of the risk of early reactions, driving is
not advisable for 1 hour following the time of injection.
HEXABRIX 320 contains sodium:
This medicinal product contains 352 mg of sodium (salt) per 100 ml. Take this into account in case you are
on a low sodium diet.
3. HOW TO USE HEXABRIX 320
HEXABRIX 320 will be administered to you by injection.
Your doctor will determine the dose you will receive and supervise the injection.
Your doctor or health professional will make a decision as to how you will be given HEXABRIX 320, and how
much you will need for your examination. This will be based on the type of of X-ray examination that you
need and may also depend on how much you weigh. You will be given HEXABRIX 320 by injection into either
a blood vessel or a joint, or through the neck of your womb, depending upon the X-ray examination.
This product must never be injected into the spinal cord (myelography).
You will be supervised for at least 30 minutes following injection of HEXABRIX 320.
If too much HEXABRIX 320 has been administered to you
It is highly unlikely that you would receive too high a dose of HEXABRIX 320, as it will be given to you in a
medical setting by qualified staff. In the event of an overdose, HEXABRIX 320 can be eliminated from the
body by haemodialysis (blood-cleaning procedure).
If you have any questions or doubts, ask your doctor or pharmacist for more information.
4. POSSIBLE SIDE EFFECTS
Like all medicines, HEXABRIX 320 can cause side effects, although not everybody gets them.
Hypersensitivity reactions (allergic reactions) which are sometimes severe and which can take the form of:
• Reactions which appear very rapidly (often within an hour) with skin manifestations such as spots, redness
(erythema) and itching (localised or extensive urticaria), sudden swelling of the face and neck (Quincke’s
• Skin reactions which appear later with red spots (maculo-papular rash) and, exceptionally, serious and major
disorders of the skin such as blisters and bullae all over the body (Lyell’s syndrome or Stevens-Johnson’s
• Reactions affecting breathing: coughing, inflammation of the nose (rhinitis), sensation of throat tightness,
breathing difficulty, swelling of the throat (laryngeal oedema), breathing difficulties associated with coughing
(bronchial spasm), respiratory arrest.
• Effects on the heart and vessels: low blood pressure (hypotension), dizziness, fainting, acceleration of the
heart rhythm (tachycardia), cardiac arrest.
• Digestive reactions : nausea, vomiting, abdominal pain.
If you experience one of these reactions during or after the injection of HEXABRIX 320, you must immediately
inform your doctor.
Other side effects are possible, such as:
• Pain and/or redness and/or swelling at the injection site.
• Fever, shivering, warmth feeling.
• Effects on the thyroid.
• Effects on the heart and the blood vessels.
• Effects on the nervous and sensory systems.
• Digestive problems.
• Effects on the kidneys.
• Breathing problems.
• Effects affecting the part of the body where HEXABRIX 320 is injected:
- non-serious, transient pain and swelling.
- formation of a blood clot in a vein in the leg (thrombophlebitis).
- inflammation or even local destruction of the skin in case HEXABRIX 320 spreads outside the vessels
into which it is injected.
Effects connected with specific examinations:
• During the examination of the uterus and fallopian tubes in female patients (hysterosalpingography): pain
in the lower belly (pelvic pain).
• During the examination of joints (arthrography): moderate and transient pain and/or swelling of the joint.
Reporting of side effects
If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet.
You can also report side effects directly via the national reporting system:
Yellow Card Scheme
By reporting side effects, you can help provide more information on the safety of this medicine.
For any information about this medicine, please contact the local representative of the Marketing Authorisation
Avon House - 435 Stratford Road – Shirley - Solihull B90 4AA - UK
Phone: + 44 1217 338 542
This leaflet was last revised in November 2015
INFORMATION FOR THE HEALTHCARE PROFESSIONAL
The following information is intended for medical or healthcare professionals only. For full prescribing
information please consult the Summary of Product Characteristics.
POSOLOGY AND METHOD OF ADMINISTRATION
5. HOW TO STORE HEXABRIX 320
Keep out of the reach and sight of children.
This medicinal product should be stored in its outer packaging.
Do not use HEXABRIX 320 after the expiry date which is stated on the vial and on the carton, after the
The expiry date refers to the last day of that month.
It is unlikely that you will be asked to dispose of any left over HEXABRIX 320. If this happens ask your
pharmacist what you should do. These measures will help to protect the environment.
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
(carotid and vertebral)
Average adult dose: 6 - 8 ml for each (carotid and vertebral)
Up to 10 injections each of 8 ml may be required.
Multiple small test injections may be used for positioning catheter
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
6. CONTENT OF THE PACK AND OTHER INFORMATION
What HEXABRIX 320 contains
• The active substance is ioxaglic acid. 100 millilitres of solution for injection of HEXABRIX 320 contains
ioxaglic acid under the form of meglumine ioxaglate (39.30 g) and sodium ioxaglate (19.65 g),
corresponding to a quantity of 32 g of iodine.
• The other ingredients are: meglumine, sodium calcium edetate, water for injections, sodium hydroxide (for pH
What HEXABRIX 320 looks like and content of the pack
HEXABRIX 320, solution for injection, is packaged in a glass vial closed with a rubber stopper and 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 and
100 ml filled in a 100 ml or 125 ml vial.
Pack size : 10
Not all pack sizes may be marketed.
Marketing Authorisation Holder:
BP 57400 - 95943 Roissy CdG cedex - FRANCE
16-24, rue Jean Chaptal - 93600 AULNAY-SOUS-BOIS - FRANCE
Dosage and Administration
Femoral and other
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.
(direct puncture or
Adults: 20- 30 ml.
Up to 50 ml may be used particularly if films of the legs are also
taken following the same injection.
Adults and children: 0.5 - 1.0 ml per kg body weight, up to
40 ml per injection. This may be repeated if necessary.
Adults: 20 - 40 ml.
Children: 0.5-1 ml per kg body weight.
Total dosage should not normally exceed 4 ml per kg body weight.
Special care should be exercised in patients with pulmonary artery
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Dosage and Administration
Hexabrix 320 to The appropriate volume of diluted medium (depending on the part
be diluted 50% of the body to be visualised) should be injected into a suitable
with water for artery.
injection BP or
injection BP to
160 mg of
iodine per ml.
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
Adults: 20 - 50 ml.
Particular attention should be paid to the injection sites of neonates and infants. The administered dose should
be reduced to the minimum.
Impaired renal function
In patients with severe renal insufficiency or diabetes, HEXABRIX should be administered with caution in well
hydrated patients, and the administered dose should be reduced to the minimum.
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 watersoluble contrast media are unknown, the information detailed under precautions and resuscitation should be
After the examination:
- Hypersensitivity to ioxaglic acid or to any of the excipients.
- Manifest hyperthyroidism or thyrotoxicosis.
- Hysterosalpingography during pregnancy or in the presence of acute inflammation or infection in the pelvic region.
- Epidural and intrathecal administration (can cause convulsions and result in death).
After contrast agent administration, the patient must be monitored for at least 30 minutes.
The patient must be informed of the possibility of delayed reactions (for up to seven days).
20 - 50 ml injected into a vein in the foot.
SPECIAL WARNINGS AND PRECAUTIONS FOR USE
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.
• There is a risk of allergic reactions whatever the administration route or dose.
• The risk of intolerance is not completely ascertainable with products administered locally to enhance contrast
in body cavities:
o Administration via particular routes (articular, biliary, intra-uterine, etc.) results in appreciable systemic
absorption, i.e. systemic effects may be observed.
o However, the allergic immune mechanism is not dose-dependent and immuno-allergic reactions may be
observed at any time, whatever the administration route.
Adults: 20 - 40 ml by splenic puncture.
By injection into the knee joint.
Adults: 4.5 ml together with injections of air before and after the
positive contrast medium.
About 10 ml are usually required. Administered by slow injection
into uterine cervical canal via a syringe or suitable cannula.
Since a decline in physiological functions is common in the elderly, the clinical condition of the patient should
be carefully monitored. HEXABRIX should be administered with caution, in well hydrated patients, and the
administered dose reduced to the minimum.
Corticosteroids and H1-type antihistamines have been suggested as premedication in patients at risk for
intolerance reactions (history of intolerance to an iodinated contrast agent). However, they do not prevent
the occurrence of serious or fatal anaphylactic shock.
Identify subjects at risk by a precise interview on their history.
An indwelling intravenous catheter.
1.2 Precautions for use
1.2.1 Intolerance to iodinated contrast agents
Before the examination:
Overdose usually manifests as cardiorespiratory failure and renal insufficiency. Appropriate treatment must be
directed at maintaining vital functions, quickly initiating symptomatic therapy. In the event of accidental
intravascular overdose in humans, the water and electrolytes losses must be compensated by infusion. Renal
function must be monitored for at least three days. Haemodialysis may be carried out if necessary.
and/ or inferior vena
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.
Before administering an iodinated contrast agent, make sure that the patient is not scheduled for a scintigraphic
examination or laboratory tests related to the thyroid or for administration of radioactive iodine for therapeutic
Administration of contrast agents via any route affects hormone tests and iodine uptake by the thyroid or by
metastases of thyroid cancer, until urinary excretion of iodine returns to normal.
1. General comments for all iodinated contrast agents
Myelography is not an indication for Hexabrix.
The examination should only be initiated after insertion of an indwelling venous catheter.
All iodinated contrast agents may cause minor or major reactions that may be life-threatening or even fatal.
They may be immediate (within 60 minutes) or delayed (up to 7 days). They are often unpredictable but
they occur more frequently in patients with a history of hypersensitivity reactions to earlier examinations with
iodinated contrast media. Premedication is recommended for these patients.
The risk of a major reaction implies that emergency measures must be immediately available especially in
patients on beta blockers in whom adrenaline and vascular perfusion would be insufficiently effective.
Sufficient fluid intake (no dehydration) and normal electrolyte balance must be ensure in elderly patients,
infants, small children, patients with renal damage (oliguria, polyuria) or hyperuricaemia, multiple myeloma,
patients with plasmacytoma or diabetes mellitus, particularly if it is longstanding.
Iodinated contrast agents and the thyroid (see also section 1.2.5)
Throughout the examination, maintain:
1.2.2 Renal failure
Iodinated contrast agents can induce a transient deterioration of renal function or exacerbate pre-existing
renal failure. The preventive measures are as follows:
Identify patients at risk, i.e. patients who are dehydrated or who have renal failure, diabetes, severe heart
failure, monoclonal gammopathy (multiple myeloma, Waldenstrom's macroglobulinemia), hyperuricemia, a
history of renal failure after administration of iodinated contrast agents, children under one year of age and
elderly atheromatous subjects.
Hydrate with appropriate water and sodium replenishment if necessary.
Avoid combinations with nephrotoxic medicines (if such a combination is necessary, laboratory monitoring of
renal function must be intensified. The medicines concerned are in particular the aminoglycosides,
organoplatinums, high doses of methotrexate, pentamidine, foscarnet and certain antiviral agents [aciclovir,
ganciclovir, valaciclovir, adefovir, cidofovir, tenofovir], vancomycin, amphotericin B, immunosuppressors such
as cyclosporine or tacrolimus, ifosfamide).
Allow at least 48 hours between radiological examinations with contrast agent injections, or delay further
examinations until renal function returns to baseline.
Check for lactic acidosis in diabetics treated with metformin, by monitoring serum creatinine. Normal renal
function: discontinue metformin for at least 48 hours after contrast agent administration or until renal function
returns to normal. Abnormal renal function: metformin is contraindicated. In emergencies, if the examination
is required, precautions must be taken, i.e. discontinue metformin, hydrate the patient, monitor renal function
and test for signs of lactic acidosis.
Iodinated contrast agents can be used in haemodialysed patients as the agents are removed by dialysis. Prior
approval should be obtained from the haemodialysis department.
1.2.3 Hepatic failure
Particular attention is required if the patient has both hepatic and renal failure, which increases the risk of
contrast agent retention.
Asthma should be stabilised before injecting the iodinated contrast agent.
Particular attention is required if an asthmatic attack has occurred within eight days prior to the examination,
because of the increased risk of bronchospasm.
INTERACTION WITH OTHER MEDICINAL PRODUCTS AND OTHER FORMS OF
Following injection of an iodinated contrast agent, particularly in patients with goitre or a history of
dysthyroidism, there is a risk of either an episode of hyperthyroidism or induction of hypothyroidism. There is
also a risk of hypothyroidism in neonates who have received, or whose mother has received, an iodinated
contrast agent. In such population, screening for hypothyroidism should be performed systematically after
administration of the product to neonates and particularly to premature babies by assaying TSH and possibly
free T4, 7 to 10 days and 1 month after iodine overload.
1. Medicinal products
1.2.6 Severe cardiovascular diseases
In patients with manifest or incipient heart failure, coronary disease, pulmonary hypertension, or valvular
heart disease, the risks of pulmonary oedema, myocardial ischaemia and arrhythmia, and severe
haemodynamic disturbances is increased after administration of an iodinated contrast agent.
Post-marketing cases of Torsade de Pointes have been reported in patients using sodium and meglumine
ioxaglate, hence Hexabrix should be administered with caution to patients who have or may develop
prolongation of QTc, including patients taking other medicinal products that lead to QT prolongation.
1.2.7 Central nervous system disorders
The benefit-to-risk ratio must be evaluated for each case:
- due to the increased risk of neurological symptoms in patients manifesting a transient ischemic attack,
stroke, recent intracranial bleeding, cerebral oedema or idiopathic or secondary epilepsy (tumour, scar).
- if the intra-arterial route is used in patients who are alcoholic (acute or chronic alcoholism) or addicted to
Patients with phaeochromocytoma may suddenly develop hypertension after intravascular administration of
a contrast agent, which may require appropriate management before the examination.
1.2.9 Myasthenia gravis
Administration of a contrast agent may exacerbate the symptoms of myasthenia gravis.
1.2.10 Exacerbation of side effects
Adverse reactions related to administration of iodinated contrast agents may be exacerbated in patients
showing agitation, anxiety and pain. Appropriate management may be needed, which may even involve
Hexabrix 320 contains 352 mg of sodium per 100 ml.
This should be taken into account in patients on a strict low sodium diet.
Metformin in diabetics (see above precautions for use - renal failure)
Radiopharmaceuticals (see above warnings)
Iodinated contrast agents may disturb the uptake of radioactive iodine by thyroid tissue for several weeks,
which may result in an uptake deficit in thyroid scintigraphy and a reduction of the therapeutic efficacy of
If renal scintigraphy involving the injection of a radiopharmaceutical excreted by the renal tubules is scheduled,
it is preferable to perform it before injecting the iodinated contrast agent.
Beta blockers, vasoactive substances, angiotensin-converting enzyme inhibitors,
angiotensin receptor antagonists
These medicinal products reduce the efficacy of cardiovascular compensation mechanisms for blood pressure
disorders. The physician must be aware of this before injecting the iodinated contrast agent and emergency
measures must be available.
Because of the risk of dehydration due to diuretics, rehydration with water and electrolytes must be carried
out before contrast agent injection, to limit the risk of acute renal failure, particularly if high doses of iodinated
contrast agent were used.
Reactions to contrast agents may be increased if the patient has recently been treated with interleukin-2
(intravenous route), i.e. skin eruptions or more rarely hypotension, oliguria, or renal failure.
2. Other forms of interaction
High concentrations of iodinated contrast agents in plasma and urine may interfere with in vitro tests for
bilirubin, proteins and inorganic substances (iron, copper, calcium and phosphate). These tests should not be
carried out within 24 hours following the examination.
Thyroid tests (PBI, labelled iodine) are affected for several weeks after administration of iodinated contrast
agents. To avoid confusion, thyroid hormones (thyroxine, triiodothyronine) should be assayed directly.
Shelf-life: 3 years unopened.
Once opened, use immediately.
Keep container in the outer carton.
2. Special warnings and precautions for the use specific to certain administration routes
with appreciable systemic diffusion
Products administered via the intra-uterine route
Pregnancy for hysterosalpingography.
Precautions for use
In the interview and with appropriate tests, systematically check for possible pregnancy in women of
childbearing age. Exposure of the female genital tract to x-rays calls for a careful evaluation of the benefit-torisk ratio.
In the event of inflammation or acute pelvic infection, hysterosalpingography can only be performed after a
careful assessment of the benefit-to-risk ratio.