Consumer medicine information

Optiray

Ioversol

BRAND INFORMATION

Brand name

Optiray

Active ingredient

Ioversol

Schedule

Unscheduled

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Optiray.

What is in this leaflet

This leaflet answers some common questions about OPTIRAY. It does not contain all the available information. It does not take the place of talking to your doctor.

All medicines have risks and benefits. Your doctor has weighed the risks of using OPTIRAY against the benefits it is expected to have for you.

If you have any concerns about receiving OPTIRAY, ask your doctor.

Keep this leaflet. You may need to read it again.

1. What is OPTIRAY and what it is used for

OPTIRAY is an injectable contrast medium containing iodine. The active ingredient is ioversol. It is used to make clearer diagnostic images of the brain and body in adults and children. The iodine blocks the X-rays, allowing vessels and the inner organs supplied with blood to be seen. As a result, it helps to clearly show abnormalities in the brain or body. OPTIRAY is for diagnostic examinations only.

2. Before you are given OPTIRAY

When you must not use it

Do not use OPTIRAY if you:

  • you are allergic (hypersensitive) to the active ingredient ioversol, or to any of the other ingredients in OPTIRAY
  • you have an overactive thyroid gland or high levels of thyroid hormones you are unable to pass urine or pass very little urine.

Before you start to use it

Tell your doctor if you:

  • suffer from asthma or allergies (e.g. medicinal products, seafood, hay fever, hives)
  • had previous reactions to injections of a contrast agent, including a previous history of reaction to iodine-based agents
  • have kidney or liver disease
  • have diabetes
  • have heart failure, high blood pressure, circulation disorders, or had a stroke, and if you are elderly
  • have brain disorders
  • have problems with bone marrow, such as blood cancers known as paraproteinaemia or multiple myeloma
  • have a red blood cell abnormality, known as sickle cell anaemia
  • have a tumour of the adrenal gland which affects your blood pressure, known as phaeochromocytoma
  • have a child who is under the age or 12 months and OPTIRAY is planned for the examination.
  • are pregnant, intend to become pregnant. If you receive this medicine whilst pregnant, your newborn should be tested to ensure they are producing the correct amount of thyroid hormone.
  • are breast-feeding or plan to breast-feed
  • are feeling thirst and/or you have only had small quantities or nothing to drink before the examination
  • have a cardiac pacemaker or any ferromagnetic implant (vascular clips, etc.) or a metallic stent in your body
  • are taking a antihypertensive medicine, known as a beta-blocker
  • you are or your child is on a controlled sodium diet

If any of these apply to you, your doctor will decide whether the intended examination is suitable for you.

Using other medicines

Please tell your doctor if you are taking or have recently taken any other medicines including medicines obtained without a prescription from your pharmacy, supermarket or health food shop.

Tell your doctor if you are taking any of the following medicines:

  • metformin, used to treat diabetes
  • interleukins, used to treat certain tumours
  • vasopressors, used to increase blood pressure
  • diuretics, used to help eliminate salt and water from your body.

Pregnancy and breast feeding

It is not known whether OPTIRAY is excreted in human milk. Tell your doctor if you are pregnant and ask your doctor for advice before you are given OPTIRAY.

Driving and using machines

Driving or operating machines is not advisable for up to 1 hour after injection. Symptoms such as dizziness, drowsiness, fatigue and visceral disturbances have been reported. If this affects you, do not attempt any activities which require concentration and the ability to react appropriately.

Children should be careful when riding bicycles or climbing trees.

3. How OPTIRAY is given

Diagnostic examinations involving the use of contrast agents should be conducted under the supervision of a doctor with the prerequisite training and a thorough knowledge of the examination to be performed.

Dosage

Your doctor will decide how much you will be given. The dose depends on your condition, the specific examination you are having and other factors, such as your health and age. The lowest possible dose will be given to produce adequate X-ray images.

You should be well hydrated prior to and following the administration of OPTIRAY.

If you are given more OPTIRAY than you should have been (overdose)

Overdosages are potentially life-threatening and may affect breathing, heart, and circulation system. Inform your doctor immediately if you notice any of these symptoms after receiving OPTIRAY.

4. Possible side effects

Like all medicines, this medicine can cause side effects, but not everybody will get them. Side effects with OPTIRAY in most cases are mild or moderate, they are very rarely serious or life-threatening.

Tell your doctor immediately if you develop any of the following signs of serious side effects:

  • heart or breathing irregular
  • heart vessel spasms or blood clots
  • stroke, blue lips, fainting
  • loss of memory
  • speech disorders
  • sudden movements
  • temporary blindness
  • acute kidney failure
  • skin rash, redness or blisters which may develop into life-threatening skin reactions including extensive peeling of the skin (toxic epidermal necrolysis), or a drug reaction which causes rash, fever, inflammation of internal organs, haemtological abnormalities and systemic illness (DRESS)
  • signs of allergic reactions, such as allergic shock, tightened airways, swelling of the throat, tongue, beathing difficulties, cough, sneezing, reddening and/or swelling of the face and eyes, itching, rash and hives.

Immediately tell the doctor or other healthcare professional who is giving you the injection, if you feel unwell, especially if you feel any tightness, pain or discomfort in your chest, face or throat, or you have difficulty breathing.

If you feel lightheaded, dizzy or faint when getting out of bed or standing up, get up slowly.

Standing up slowly, especially when you get up from bed or chairs, will help your body get used to the change in position and blood pressure. If this problem continues or gets worse, talk to your doctor.

Side-effects in Children

Some paediatric patients have a higher risk of adverse reactions to contrast media. Such patients may include those with sensitivity to allergens, including other medicines, those with asthma, congestive heart failure, a serum creatinine 1.5 mg/dL, or ages under 12 months.

If you have any further questions or concerns on the use of this medicine, ask your doctor.

5. How to store OPTIRAY

As this is being given to you by your doctor, it is extremely unlikely that you will be expected to look after the injection. However, in the case that you may have to transport it from the pharmacy to your doctor, keep the container in the outer carton to protect from light. Do not store below 25°C.

Do not use this medicine if the packaging is torn or shows signs of tampering or after the expiry date which is stated on the label.

Do not use the solution if it is discoloured or particulate material is present. This medicine should only be used once. Discard unused contents.

Keep all medicines in a safe place where children cannot reach them.

6. Product Description

What it looks like and packs

OPTIRAY is a clear, colourless to pale yellow solution, available in glass vials or plastic pre-filled syringes.

OPTIRAY contains the active ingredient, ioversol, 509 to 791 mg/mL, depending on the concertation being administered. It also contains sodium calcium edetate, trometamol, trometamol hydrochloride, sodium hydroxide, and water for injections.

This medicine does not contain lactose, sucrose, gluten, tartrazine or any other azo dyes.

The following OPTIRAY packs are registered

The Australian Registration number is AUST R 34371.

OPTIRAY 240

  • 30 mL (AUST R 15326) and 50 mL (AUST R 49410) injection vials
  • 50 mL (AUST R 46639) and 125 mL (AUST R 46640) Ultraject® injection syringes

OPTIRAY 320

  • 20 mL (AUST R 20034), 30 mL (AUST R 49421), 50 mL (AUST R 49422), 100 mL (AUST R 49423), 150 mL (AUST R49424) and 200mL (AUST R 49425) injection vials
  • 50 mL (AUST R 46641), 75 mL (AUST R 73580) and 125 mL (AUST R 46642) Ultraject® injection syringes

OPTIRAY 350

  • 20 mL (AUST R 49610), 30 mL (AUST R 47856), 50 mL (AUST R 47996),75 mL (AUST R 47997), 100 mL (AUST R 47998), 150 mL (AUST R 49611),200 mL (AUST R 49612) and 500 mL (AUST R 320145) injection vials
  • 30 mL (AUST R51795), 50 mL (AUST R 51796), 75 mL (AUST R 70059), 100 mL (AUST R 61983) and 125 mL (AUST R 61984) Ultraject® injection syringes.

OPTIRAY vials are available in packs of 10 or 25 units.
OPTIRAY 350 in 500 mL vials are available in packs of 5, 6 or 10 units.
OPTIRAY prefilled syringes are available in packs of 10 or 20 units.
Note: Not all strengths and pack sizes may be available.

Sponsor

Guerbet Australia Pty Ltd
166 Epping Road, Level 2
Lane Cove, NSW, 2066
Australia

Telephone: 1800 859 436
Customer Service Email: [email protected]

This leaflet was revised in February 2023.

Published by MIMS May 2023

BRAND INFORMATION

Brand name

Optiray

Active ingredient

Ioversol

Schedule

Unscheduled

 

1 Name of Medicine

Ioversol.

2 Qualitative and Quantitative Composition

Optiray (ioversol injection) formulations are sterile, non-pyrogenic, aqueous solutions intended for intravascular administration as diagnostic radiopaque media.
Each millilitre of Optiray 240 (ioversol injection 51% w/v) provides 509 mg of ioversol with 3.6 mg of trometamol as a buffer and 0.2 mg of sodium calcium edetate as a stabiliser. Optiray 240 provides 24% (240 mg/mL) organically bound iodine.
Each millilitre of Optiray 320 (ioversol injection 68% w/v) provides 678 mg of ioversol with 3.6 mg of trometamol as a buffer and 0.2 mg of sodium calcium edetate as a stabiliser. Optiray 320 provides 32% (320 mg/mL) organically bound iodine.
Each millilitre of Optiray 350 (ioversol injection 74% w/v) provides 741 mg of ioversol with 3.6 mg of trometamol as a buffer and 0.2 mg of sodium calcium edetate as a stabiliser. Optiray 350 provides 35% (350 mg/mL) organically bound iodine.
The pH of the Optiray formulations has been adjusted to 6.0 to 7.4 with hydrochloric acid or sodium hydroxide.
Some physical and chemical properties of these formulations are listed in Table 1.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Solution for injection.
The Optiray formulations are clear, colourless to pale yellow solutions containing no undissolved solids. Crystallisation does not occur at temperatures above 15°C. The products are supplied in containers from which the air has been displaced by nitrogen. Optiray solutions have osmolalities 1.2 to 2.5 times that of plasma (285 mOsm/kg water) as shown in Table 1 and are hypertonic under conditions of use.

4 Clinical Particulars

4.1 Therapeutic Indications

Optiray is indicated in adults for angiography throughout the cardiovascular system by conventional or digital subtraction techniques. These include cerebral, coronary, peripheral, visceral and renal arteriography, aortography, left ventriculography and venography. Optiray may be used for intravenous excretory urography.
Optiray 320 is indicated in children (excluding neonates) for angiocardiography, contrast enhanced computed tomographic imaging of the head and body, and intravenous excretory urography.

4.2 Dose and Method of Administration

It is desirable that intravascular administered iodinated contrast media be at, or close to, body temperature when injected.
As with all radiopaque contrast media, only the lowest dose necessary to obtain adequate visualisation should be used.
Under no circumstances should any other therapy be mixed with the contrast media because of the potential for chemical incompatibility.
Withdrawal of contrast media from their containers should be accomplished under strict aseptic conditions using only sterile syringes and transfer devices. Contrast media which have been transferred into other delivery systems should be used immediately.
Parenteral products should be inspected visually for particulate matter and discolouration prior to administration and should not be used if particulates are observed or marked discolouration has occurred.
The Optiray formulations are supplied in single use containers. Discard unused portion.
Any contrast medium solution left over from the examination must be discarded.

General angiography.

Visualisation of the cardiovascular system may be accomplished by any accepted technique. Since intra-arterial digital subtraction angiography (IA-DSA) requires adjustments in the method of administration, this procedure is described separately.

Cerebral arteriography.

Additional precautions and adverse reactions.

Extreme caution is advised in patients with advanced arteriosclerosis, severe hypertension, cardiac decompensation, senility, recent cerebral thrombosis or embolism and migraine. Cardiovascular reaction that may occur with some frequency are bradycardia and either an increase or decrease in systemic blood pressure.

Dosage and administration (adults).

Either Optiray 240 or Optiray 320 is recommended for this procedure. The usual individual injection for visualisation of the carotid or vertebral arteries is 2 to 12 mL, repeated as necessary. Aortic arch injection for a simultaneous four vessel study requires 20 to 50 mL. Total procedural doses should not usually exceed 150 mL.

Peripheral arteriography.

Additional precautions.

Pulsation should be present in the artery to be injected. In thromboangiitis obliterans or ascending infection associated with severe ischaemia, angiography should be performed with extreme caution, if at all.

Dosage and administration (adults).

Optiray 320 or Optiray 350 is recommended for this procedure. The usual individual injection volumes for visualisation of various peripheral arteries are as follows: aorta-iliac runoff - 60 mL (range: 20 to 90 mL); common iliac, femoral - 40 mL (range: 10 to 50 mL); subclavian, brachial - 20 mL (range: 15 to 30 mL).
These doses may be repeated as necessary. Total procedural doses should not usually exceed 150 mL.

Selective visceral and renal arteriography and aortography.

Additional precautions and adverse effects.

In aortography, depending on the technique employed, the risks of this procedure also included the following: injury to the aorta and neighbouring organs, pleural puncture, renal damage including infarction and acute tubular necrosis with oliguria and anuria, accidental filling of the renal arteries in the presence of pre-existing renal disease, retroperitoneal haemorrhage, and spinal cord injury and pathology associated with the syndrome of transverse myelitis.

Dosage and administration (adults).

Optiray 320 or Optiray 350 is recommended for this procedure. The usual individual injection volumes for visualisation of the aorta and various visceral arteries are as follows: aorta - 45 mL (range: 10 to 80 mL); coeliac - 45 mL (range: 12 to 60 mL); superior mesenteric - 45 mL (range: 15 to 60 mL); renal or inferior mesenteric - 9 mL (range: 6 to 15 mL).
These doses may be repeated as necessary. Total procedural doses should not usually exceed 150 mL.

Coronary arteriography and ventriculography.

Additional precautions and adverse reactions.

Selective coronary arteriography should be performed only in selected patients and those in whom the expected benefits outweigh the procedural risk. The inherent risks of angiocardiography in patients with chronic pulmonary emphysema must be weighed against the necessity for performing this procedure.
Cardiac decompensation, serious arrhythmias, myocardial ischaemia, myocardial infarction may occur during coronary arteriography and ventriculography. However, electrocardiographic and haemodynamic changes occur with less frequency and severity with ioversol injection than with conventional ionic media.
Mandatory prerequisites to the procedure are specialised personnel, ECG monitoring apparatus and adequate facilities for immediate resuscitation and cardioversion. Electrocardiograms and vital signs should be routinely monitored throughout the procedure.
When large individual volumes are administered, as in ventriculography and aortography, it has been suggested that several minutes be permitted to elapse between each injection to allow for subsidence of possible hemodynamic disturbances.

Dosage and administration (adults).

Optiray 320 or Optiray 350 is recommended for this procedure. The usual individual injection volumes for visualisation of the coronary arteries and left ventricle are: left coronary - 8 mL (range: 2 to 10 mL); right coronary - 6 mL (range: 1 to 10 mL); left ventricle - 40 mL (range: 30 to 50 mL).
These doses may be repeated as necessary. Total procedural dose for the combined procedures should not usually exceed 150 mL.

Paediatric angiocardiography.

Additional precautions.

Mandatory prerequisites to the procedure are specialised personnel, ECG monitoring apparatus and adequate facilities for immediate resuscitation and cardioversion. Electrocardiograms and vital signs should be routinely monitored throughout the procedure. Paediatric patients are at higher risk of experiencing adverse events during contrast medium administration, these include children having asthma, a sensitivity to medication and/or allergens, congestive heart failure, a serum creatinine greater than 1.5 mg/dL, or those less than 12 months of age.

Dosage and administration.

Optiray 320 is recommended for this procedure. The usual single injection dose for Optiray 320 is 1.25 mL/kg of body weight with a range of 1 mL/kg to 1.5 mL/kg. When multiple injections are given, the total administered dose should not exceed 5 mL/kg up to a total volume of 75 mL.

Intra-arterial digital subtraction angiography (IA-DSA).

All of the arteriographic procedures described above can be performed using digital subtraction techniques.

Dosage and administration (adults).

The recommended doses are similar to those used for conventional arteriography. The flow rate of the vessel being injected should always be considered when selecting the concentration and dose. Total dosage should not usually exceed 150 mL.

Venography.

Additional precautions.

Special care is required when venography is performed in patients with suspected thrombosis, phlebitis, severe ischaemic disease, local infection or a totally obstructed venous system. In order to minimise extravasation during injection, fluoroscopy is recommended.

Dosage and administration (adults).

Either Optiray 240, Optiray 320 or Optiray 350 is recommended for this procedure. The usual dose is 50 to 100 mL per extremity. Total dosage should not usually exceed 150 mL.
Following the procedure, the venous system should be flushed with Sodium Chloride Injection USP or 5% glucose in water (D5W). Massage and elevation are also helpful in clearing the contrast media from the extremity.

Computed tomography.

Optiray 320 or Optiray 350 is recommended for these procedures in adults and Optiray 320 in children.
Head imaging.

Dosage and administration.

Adults: The usual dosage is 50 to 150 mL of Optiray 320 or Optiray 350. Scanning may be performed immediately after completion of the intravenous administration. Total dosage should not usually exceed 150 mL.
Children: The usual dosage for use in children is 1.9 mL/kg (range: 1.3 to 2.4 mL/kg) of Optiray 320.
Body imaging.

Dosage and administration.

Optiray 320 or Optiray 350 may be administered by bolus injection, by rapid infusion, or by a combination of both. The usual dose for bolus injection is 25 to 75 mL.
Adults: The usual dose for infusion is 50 to 150 mL. Total dosage should not usually exceed 150 mL.
Children: The usual dosage for use in children is 2 mL/kg (range: 1.7 to 2.4 mL/kg) of Optiray 320.

Intravenous urography.

Dosage and administration.

Optiray 320 or Optiray 350 is recommended for routine and high dose excretory urography.
Adults: The usual dose for routine excretory urography in adults is 50 to 75 mL of Optiray 320 or Optiray 350. Higher doses may be indicated to achieve optimum results where poor visualisation is anticipated (e.g. elderly patients or patients with impaired renal function). In these patients, high dose urography may be preferred, using Optiray 320 at a dose of 1.5 to 2 mL/kg (maximum 150 mL).
Children: Optiray 320 at doses of 0.5 mL/kg to 3 mL/kg of body weight has produced diagnostic opacification of the excretory tract. The usual dose for children is 1 mL/kg to 1.5 mL/kg of Optiray 320. Dosage for infants and children (on a mL/kg basis) gradually decreases with age. In one study, mean dose (mL/kg) decreased from 2.7 in infants to 1.0 in children 12-18 years of age. The total administered dose should not exceed 3 mL/kg.

4.3 Contraindications

Known hypersensitivity to ioversol (Optiray) or any of the excipients.
Manifest hyperthyroidism.
Thyrotoxicosis.
Anuria.
Decompensated cardiac insufficiency.
Certain specific procedures and situations, e.g. carotid artery angiography during the progressive period of stroke, coronary arteriography in the first four weeks after myocardial infarction, and the presence of infection or open injury in or near the region to be examined.

4.4 Special Warnings and Precautions for Use

(Precautions for specific procedures receive comment in Section 4.2 Dose and Method of Administration).
Serious or fatal reactions have been associated with the administration of iodine containing radiopaque media. It is of utmost importance to be completely prepared to treat any contrast medium reactions.
Diagnostic procedures which involve the use of iodinated intravascular contrast media should be carried out under the direction of personnel skilled and experienced in the particular procedure to be performed. A fully equipped emergency cart, or equivalent supplies and equipment, and personnel competent in recognising and treating adverse reactions of all types should always be available.
Since severe delayed reactions have been known to occur, emergency facilities and competent personnel should be available for at least 30 to 60 minutes after administration.
Preparatory dehydration is dangerous and may contribute to acute renal failure in patients with advanced vascular disease, diabetics and in susceptible nondiabetics (often elderly with pre-existing renal disease). Fluid intake should not be restricted before the use of Optiray, especially in patients with multiple myeloma, juvenile-type diabetes or diabetes of long standing, polyuria, oliguria, gout in babies or small children, elderly or in debilitated patients. Patients should be well hydrated prior to and following the administration of Optiray (see Section 4.4, Use in renal impairment).

Thyroid disorders.

Reports of thyroid storm following the intravascular use of iodinated radiopaque agents in patients with hyperthyroidism or with an autonomously functioning thyroid nodule, suggest that this additional risk be evaluated in such patients before use of any contrast media (see Section 4.3 Contraindications).

Thromboembolic events.

Serious thromboembolic events have been observed during catheterisation procedures with iodinated X-ray contrast media, and clotting has been reported when blood remains in contact with syringes containing non-ionic contrast media. Optiray, like all non-ionic compounds, does not have any significant anticoagulant effect. Serious, rarely fatal, thromboembolic events causing myocardial infarction and stroke have been reported during angiographic procedures with both ionic and non-ionic contrast media.
Therefore, meticulous intravascular administration technique is necessary, particularly during angiographic procedures, to minimise thromboembolic events. Numerous factors, including length of procedure, catheter and syringe material, underlying disease state, and concomitant medications may contribute to the development of thromboembolic events. For these reasons, meticulous angiographic techniques are recommended including close attention to guidewire and catheter manipulation, use of manifold systems and/or three-way stopcocks, frequent catheter flushing with heparinised saline solutions and minimising the length of the procedure. The use of plastic syringes in place of glass syringes has been reported to decrease but not eliminate the likelihood of in vitro clotting.

Central nervous system disorders.

As with any contrast media, serious neurologic sequelae, including permanent paralysis, can occur following cardiac catheterisation, cerebral arteriography, selective spinal arteriography and arteriography of vessels supplying the spinal cord. A cause effect relationship to the contrast media has not been established since the patients' pre-existing condition and procedural technique are causative factors in themselves. The arterial injection of a contrast media should never be made following the administration of vasopressor since they strongly potentiate neurologic effects (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Encephalopathy has been reported with the use of Optiray (see Section 4.8 Adverse Effects (Undesirable Effects)). Contrast-induced encephalopathy may manifest with symptoms and signs of neurological dysfunction such as headache, visual disturbance, cortical blindness, confusion, seizures, loss of coordination, hemiparesis, aphasia, unconsciousness, coma, and cerebral oedema. Symptoms usually occur within minutes to hours after administration of Optiray and generally resolved within days.
Factors which increase blood-brain barrier permeability facilitate the passage of the contrast medium into cerebral tissue, which can lead to central nervous system reactions, e.g. encephalopathy.
If contrast encephalopathy is suspected, appropriate medical management should be initiated, and administration of Optiray must not be repeated.
The potential risk of seizures may be increased under the following conditions: large dose of contrast medium, renal failure, blood-brain barrier disruption.

Phaeochromocytoma.

Administration of radiopaque materials to patients known or suspected of having pheochromocytoma should be performed with extreme caution. If, in the opinion of the physician, the possible benefits of such procedures outweigh the considered risks, the procedures may be performed, however, the amount of radiopaque medium injected should be kept to an absolute minimum. The blood pressure should be assessed throughout the procedure, and measures for treatment of a hypertensive crisis should be available.
Contrast media may promote sickling in individuals who are homozygous for sickle cell disease when administered intravascularly.

Hypersensitivity reactions.

The possibility that a reaction, including serious life-threatening, fatal, anaphylactoid or cardiovascular reactions, should always be considered (see Section 4.8 Adverse Effects (Undesirable Effects)).
Severe cutaneous adverse reactions (SCARs) may develop from 1 hour to several weeks after intravascular contrast agent administration. These reactions include Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), acute generalised exanthematous pustulosis (AGEP), and drug reaction with eosinophilia and systemic symptoms (DRESS). Reaction severity may increase and time to onset may decrease with repeat administration of a contrast agent; prophylactic medications may not prevent or mitigate severe cutaneous adverse reactions. Avoid administering Optiray to patients with a history of a severe cutaneous adverse reaction to Optiray.
The patient should be informed that allergic reactions may develop up to several days post administration; in such case, a physician should be consulted immediately.
Increased risk is associated with a history of previous reaction to contrast media, a known sensitivity to iodine and known allergies (including bronchial asthma, hay fever and food allergies) or hypersensitivities. However, while this implies the need for extra caution it does not necessarily contraindicate the use of the contrast media.
The occurrence of severe idiosyncratic reactions has prompted the use of several pretesting methods. However, pretesting cannot be relied upon to predict severe reactions and may itself be hazardous to the patient. It is suggested that a thorough medical history with emphasis on allergy and hypersensitivity, prior to the injection of any contrast media, may be more accurate than pretesting in predicting potential adverse reactions.
A positive history of allergies or hypersensitivity does not arbitrarily contraindicate the use of contrast media when a diagnostic procedure is thought essential, but caution should be exercised. Premedication with antihistamines or corticosteroids to avoid or minimise possible allergic reactions in such patients should be considered. Reports indicate that such pretreatment does not prevent serious life threatening reactions, but may reduce both their incidence and severity.
Administration of the contrast medium and the investigation must be interrupted if pronounced side effects or allergic reactions occur during the administration and appropriate treatment should be instituted. If, despite this, the reactions do not disappear, or even grow worse, the investigation must be terminated. Even relatively minor symptoms, such as itching of the skin, sneezing, violent yawning, tickling in the throat, hoarseness, coughing fits, may be initial signs of a severe reaction (including shock), so careful attention should be paid to them.

Anaesthetised patient.

General anaesthesia may be indicated in the performance of some procedures in selected patients, however, a higher incidence of adverse reactions has been reported in these patients, and may be attributed to the inability of the patient to identify untoward symptoms or to the hypotensive effect of anaesthesia which can prolong the circulation time and increase the duration of exposure to the contrast agent.

Cardiovascular diseases.

In angiographic procedures, the risk of dislodging plaques or damaging or perforating the vessel wall should be considered during catheter manipulations and contrast medium injection. Test injections to ensure proper catheter placement are suggested.
The inhibitory effects of non-ionic contrast media on mechanisms of haemostasis have been shown, in vitro, to be less than conventional ionic contrast media at comparable concentrations. For this reason, standard angiographic procedures should always be followed, e.g. angiographic catheters should be flushed frequently and prolonged contact of blood with the contrast medium in syringes and catheters should be avoided.
Angiography should be avoided whenever possible in patients with homocystinuria because of the risk of inducing thrombosis and embolism.
Patients with congestive heart failure should be observed for several hours following the procedure to detect delayed haemodynamic disturbances which may be associated with a transitory increase in the circulating osmotic load.

Extravasation.

Caution during injection of a contrast medium is necessary to avoid extravasation. This is especially important in patients with severe arterial or venous disease. Significant extravasation of Optiray may occur: generally, it is tolerated without substantial tissue injury applying conservative treatment. However, serious tissue damage (e.g. necrosis) has been reported in isolated cases requiring surgical treatment.

Optiray prefilled syringes.

Optiray in prefilled syringes must only be used with administration devices (e.g. infusion pumps or dual-head injectors), which are provided with reliable connecting tubes. The manufacturer's instructions for use for these devices must be followed.

Optiray 500 mL vials.

The transmission of viral infections and bacterial contamination are recognised but rare complications of multi-use vials and administration devices. The following measures should be strictly adhered to when using Optiray 500 mL vial.
The use of the specific automatic injector with Optiray 500 mL vial should only be carried out by the healthcare professionals who have received adequate training on the use of the device and aseptic technique.
The multiple withdrawal must be performed utilising an administration device approved for this use, such as dual-head injectors which are provided with reliable connecting tubes.
The rubber stopper of the vial can only be pierced once to prevent large amounts of microparticles from the stopper getting into the solution.
Optiray 500 mL vials must be administered by means of an automatic injector, or by other approved procedures which ensure sterility of the contrast medium.
Aseptic technique practices and routine checks for visible contamination with blood should be adhered to when changing connections.
The Instructions for Use from the device manufacturer must be followed, including connecting tubes and all disposable parts of the injector system.
Any Optiray injection solution in the 500 mL vial which is unused at the end of the day must be discarded.

Other.

Other precautions which apply to the various radiographic contrast procedures are the same for Optiray as they are for conventional ionic media. The risk of the procedure itself should be carefully evaluated in each patient. Such precautions include:

Cerebral angiography.

Used with caution in patients with extreme senility, advanced atherosclerosis or severe hypotension.
The procedure may be hazardous in subarachnoid haemorrhage and in migraine (because of ischaemic complications).

Peripheral angiography.

Pulsation should be present in the artery to be injected.
In thromboangiitis obliterans (Buerger's disease) or ischaemia associated with ascending infection, angiography should be performed with extreme caution, if at all.

Cardioangiography.

Caution is advised in the administration of large volumes to patients with incipient heart failure because of the possibility of aggravating the pre-existing condition. Hypotension should be corrected promptly since it may induce serious arrhythmias.
Caution is advised with dosage in patients with right ventricular failure, pulmonary hypertension or stenotic pulmonary vascular beds because of the haemodynamic changes which may occur after injection into the right heart outflow tract.

Urography.

It is advisable to allow an interval of at least 48 hours before repeating excretory urography.
Dehydration should be avoided in the elderly, particularly those with polyuria, oliguria, advanced vascular disease or pre-existing dehydration (see Section 4.4 Special Warnings and Precautions for Use).
Myelomatosis (see Section 4.4 Special Warnings and Precautions for Use).

Use in the elderly.

The tolerance of elderly patients to drugs in general is diminished. These patients may have reduced renal reserve, impaired general health and may be taking medication (e.g. adrenergic β-blockers) which make them more susceptible to the potentially harmful effects of procedures involving the use of contrast media. The need for and the expected benefits of the procedure have to be carefully evaluated and dosage should be very conservative.

Use in renal impairment.

Avoid administration of Optiray with nephrotoxic medicines. If this cannot be avoided, laboratory monitoring of renal function must be intensified.
Caution must be exercised in patients with severely impaired renal function, combined renal and hepatic disease, renal and hepatic disease, multiple myeloma or other paraproteinemia or anuria, particularly when large doses are administered. Myeloma occurs most commonly in persons over age 40. Although neither the contrast medium nor dehydration has been proved separately to be the cause of renal failure, it has been speculated that the combination of both may be causative.
The risk in patients with impaired renal function is not a contraindication to the procedure, however, special precautions, including maintenance of normal hydration and close monitoring are required. Partial dehydration in the preparation of these patients prior to injection maybe harmful and is not recommended, especially in myelomatous patients since this may predispose the patient to precipitation of the myeloma protein.
In patients with severe impairment of hepatic or renal function, cardiac and circulatory insufficiency, pulmonary emphysema, poor general health, cerebral arteriosclerosis, juvenile-type diabetes or diabetes of long standing, cerebral spasmodic conditions and latent thyroid hyperfunction the need for examination merits particularly careful consideration. Diabetics with serum creatinine above 500 micromol/L should not be examined unless the possibility of benefit clearly outweighs the additional risk.
In patients with renal impairment the maximum dose should not be exceeded (see Section 4.2 Dose and Method of Administration).

Use in hepatic impairment.

Patients with severe impairment of hepatic function should not be examined unless the possibility of benefit clearly outweighs the additional risk.

Paediatric use.

Some paediatric patients have a higher risk of adverse reactions to iodinated contrast media. Such patients may include those with sensitivity to allergens, including other medicines, those with asthma, congestive heart failure, a serum creatinine > 1.5 mg/dL, or ages under 12 months.

Hypothyroidism.

Hypothyroidism or transient thyroid suppression may be observed after exposure to iodinated contrast media. This adverse reaction should also be observed in newborns whose mothers have received an iodinated contrast medium during pregnancy (see Section 4.6 Fertility, Pregnancy and Lactation, Use in pregnancy).
Younger age, very low birth weight, prematurity, and the presence of other conditions, such as, admission to neonatal or paediatric intensive care units, and cardiac conditions are associated with an increased risk.
Paediatric patients with cardiac conditions may be at the greatest risk given that they often require high doses of contrast during invasive cardiac procedures, such as catheterisation, and computed tomography (CT).
Special attention should be paid to paediatric patients below 3 years of age because an incident underactive thyroid during early life may be harmful for motor, hearing, and cognitive development and may require transient thyroxin (T4) replacement therapy.
Thyroid function should be evaluated in all paediatric patients younger than 3 years of age, 7 to 10 days and 1 month after exposure to iodinated contrast media, especially in premature infants and neonates. If hypothyroidism is detected, thyroid function should be monitored as appropriate even when replacement treatment is given.

Effects on laboratory tests.

The results of protein-bound iodine (PBI) and radioactive iodine uptake studies, which depend on iodine estimation, will not accurately reflect thyroid function for up to sixteen (16) days following administration of iodinated contrast media. However, thyroid function tests not depending on iodine estimations e.g. T3 resin uptake and total or free thyroxine (T4) assays are not likely to be affected.

Information for patients.

Patients receiving iodinated intravascular contrast media should be instructed to:
1. Inform your physician if you are pregnant.
2. Inform your physician if you are diabetic or if you have multiple myeloma, pheochromocytoma, homozygous sickle cell disease or known thyroid disorder (see Section 4.4 Special Warnings and Precautions for Use).
3. Inform your physician if you are allergic to any medicines or food, or if you had any reactions to previous injections of dyes used for X-ray procedures (see Section 4.4 Special Warnings and Precautions for Use).

4.5 Interactions with Other Medicines and Other Forms of Interactions

No interaction studies have been performed.

Cholecystographic agents.

Renal toxicity has been reported in a few patients with liver dysfunction who were given oral cholecystographic agents followed by intravascular contrast media. Administration of any intravascular contrast medium should therefore be postponed in patients who have recently received a cholecystographic contrast agent.

Metformin.

Acute renal failure has been associated with lactic acidosis in patients receiving metformin at the time of an X-ray examination involving parenteral administration of iodinated contrast media. Therefore, in diabetic patients taking metformin, the examination should be performed, and intake of metformin stopped from the time of the examination. The use of metformin should not be resumed for 48 hours and should only be restarted if renal function/serum creatinine remains within the normal range.

Interleukin.

Literature reports show patients who have been treated with interleukin may develop a higher rate of adverse reactions, such as cutaneous eruption, hypotension, oliguria, and renal failure.

Diuretics.

In case of diuretic-induced dehydration, patients are at increased risk of acute renal failure, especially when using large doses of iodinated contrast media.

Vasopressors.

The arterial injection of a contrast media should not be made following the administration of vasopressors since they strongly potentiate neurologic effects.
Other medicines should not be mixed with Optiray injection.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Animal studies did not indicate direct or indirect harmful effects with respect to fertility in humans. There are, however, no adequate and well controlled clinical studies on fertility. However, animal studies suggest that Optiray is not mutagenic and does not affect fertility in males or females.
(Category B1)
No teratogenic effects attributable to ioversol have been observed in teratology studies performed on animals using doses up to 3.2 gL/kg. There are, however, no adequate and well controlled studies in pregnant women. Literature reports show that ioversol crosses the placenta, reaches foetal tissues in small amounts, and is visualised in the digestive tract of exposed infants after birth. Many injectable contrast media cross the placental barrier in humans and appears to enter foetal tissue passively. Because animal teratology studies are not always predictive of human response, Optiray should be used during pregnancy only if clearly needed. X-ray procedures involve a certain risk related to the exposure of the foetus.
Thyroid function of neonates should be closely monitored during the first week of life if iodinated contrast was administered to the mother during pregnancy. It is recommended that thyroid function be monitored again at 2 and 4 weeks of age. Some patients required treatment for hypothyroidism (see Section 4.4 Special Warnings and Precautions for Use, Paediatric use).
 It is not known whether ioversol is excreted in human milk. However, many injectable contrast agents are excreted unchanged in human milk. Although it has not been established that serious adverse reactions occur in nursing infants, caution should be exercised when intravascular contrast media are administered to nursing women because of potential adverse reactions, and considerations should be given to temporarily discontinuing nursing (see Section 4.4 Special Warnings and Precautions for Use, Paediatric use).

4.7 Effects on Ability to Drive and Use Machines

There is no known effect of Optiray on the ability to drive and operate machines, however, because of the risk of early reactions, driving or operating machinery is not advisable for 30 to 60 minutes following Optiray administration.

4.8 Adverse Effects (Undesirable Effects)

Adverse reactions following the use of Optiray formulations are generally independent of the dose administered. They are usually mild to moderate, of short duration and generally resolve spontaneously (without treatment). However, even mild adverse reactions may be the first indication of a serious, generalised reaction that can occur rarely after iodinated contrast media. Such serious reactions may be life-threatening and fatal and will mostly affect the cardiovascular system.
Most adverse drug reactions to Optiray occur within minutes after administration. However, contrast related hypersensitivity reactions may occur with a delay of some hours up to several days. Injections of contrast media are very commonly associated with sensations of warmth and commonly associated with pain, especially in peripheral arteriography. When compared with ionic contrast media, warmth and pain occurred less frequently and were less severe with ioversol injection.
Adverse drug reactions may be classified as follows:
Hypersensitivity or anaphylactoid reactions are mostly mild to moderate with symptoms like rash, pruritus, urticaria, rhinitis and blister. These symptoms may occur independent of dose and route of administration and may be the first signs of an evolving shock with symptoms like pronounced decrease in blood pressure, tachycardia, dyspnoea, pallor and decrease in consciousness. Fatal cases reported.
Vasovagal reactions with symptoms ranging from dizziness and hypotension to syncope. Vasovagal reactions may be caused either by the contrast media or by the procedure.
Cardiologic side effects during cardiac catheterisation may include ECG changes, arrhythmia, conductivity disorders as well as coronary spasm. Such reactions may be caused by the contrast media or by the procedure.
Nephrotoxic reactions with acute renal failure may occur in patients with pre-existing renal damage.
Neurotoxic reactions after intra-arterial injection of the contrast media like confusion, visual disorders, convulsions or fits. The symptoms are generally transient and abate spontaneously within several hours (contrast-induced encephalopathy).
Local reactions at the injection site may occur and include rashes, swelling, inflammation and oedema. Such reactions occur probably in most cases due to extravasation of the contrast media. Extended paravasation may necessitate surgical treatment.
Regardless of the contrast media employed, the overall incidence of serious adverse reaction is higher with coronary arteriography than with other procedures. Cardiac decompensation, serious arrhythmias, myocardial ischaemia or myocardial infarction may occur during coronary arteriography and left ventriculography. In coronary arteriography clinical studies with ioversol, the only adverse reaction with an incidence of greater than one percent was angina (1.6%).
Following coronary artery and left ventricular injection, electrocardiograms and cardiovascular and haemodynamic functions were affected less frequently with Optiray than with the comparative ionic contrast agents. These changes included the following parameters: bradycardia, tachycardia, T wave amplitude, ST depression and ST elevation.
Optiray has also been shown to cause fewer changes in cardiac function and systemic blood pressure. These include cardiac output, left ventricular systolic and end diastolic pressure, right ventricular systolic and pulmonary artery systolic pressures and decreases in systolic and diastolic blood pressure.
For adverse reactions for specific procedures and for serious or life-threatening reactions see Section 4.4 Special Warnings and Precautions for Use.

Clinical trial experience.

Table 2 incidence of reactions is based upon clinical trials with Optiray formulations in over 1000 adult patients. This listing includes all adverse reactions which were coincidental to the administration of ioversol regardless of their direct attributability to the drug or the procedure. Adverse reactions are listed by organ system and in decreasing order of occurrence. Significantly more severe reactions are listed before others in a system regardless of frequency.

Paediatrics.

In clinical trials involving 128 patients for paediatric angiocardiography, contrast enhanced computed tomographic imaging of the head and body, or intravenous excretory urography, adverse reactions following the use of Optiray 320 were generally similar to adults.

Post-marketing experience.

The following adverse reactions presented in Table 3 have been reported during the post-approval use of Optiray.

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 at www.tga.gov.au/reporting-problems.

4.9 Overdose

Activated charcoal may reduce absorption of Optiray if given within one or two hours after ingestion. In patients who are not fully conscious or have impaired gag reflex, consideration should be given to administering activated charcoal via a nasogastric tube, once the airway is protected.
Whole bowel irrigation (e.g. 1 or 2 litres of polyethylene glycol solution orally per hour until rectal effluent is clear) may be useful for gut decontamination.
The adverse effects of overdosage are life threatening and affect mainly the pulmonary and cardiovascular system. Treatment of an overdosage is directed toward the support of all vital functions, and prompt institution of symptomatic therapy.
Ioversol does not bind significantly to plasma or serum protein and is, therefore, dialyzable.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

No data available.

5.2 Pharmacokinetic Properties

The pharmacokinetics of ioversol in normal adult subjects conform to an open two compartment model with first order elimination (a rapid alpha phase for drug distribution and a slower beta phase for drug elimination). Based on the blood clearance curves for twelve healthy adult volunteers (six receiving 50 mL and six receiving 150 mL of Optiray 320), the biological half-life was 1.5 hours for both dose levels and there was no evidence of any dose related difference in the rate of elimination.
Ioversol is excreted mainly through the kidneys following intravascular administration. In patients with impaired renal function, the elimination half-life is prolonged. In the absence of renal dysfunction, the mean half-life for urinary excretion following a 50 mL dose was 118 minutes (105 to 156) and following a 150 mL dose was 105 minutes (74 to 141). Faecal elimination was negligible.
Ioversol is bound to serum or plasma proteins to the extent of 9 to 13% only and no significant metabolism or biotransformation occurs.
Intravascular injection of ioversol opacifies those vessels in the path of the flow of the contrast medium, permitting radiographic visualisation of the internal structures until significant haemodilution occurs.
Ioversol may be visualised in the renal parenchyma within 30 to 60 seconds following rapid intravenous injection. Opacification of the calyces and pelvis in patients with normal renal functions becomes apparent within 1 to 3 minutes, with optimum contrast occurring within 5 to 15 minutes.
Pharmacokinetics of ioversol in children has not been established.

5.3 Preclinical Safety Data

Genotoxicity.

Animal studies indicate that ioversol does not cross the blood-brain barrier or cause endothelial damage to any significant extent.

Carcinogenicity.

No long-term animal studies have been performed to evaluate carcinogenic potential.

6 Pharmaceutical Particulars

6.1 List of Excipients

Trometamol; trometamol hydrochloride; sodium hydroxide; hydrochloric acid; sodium calcium edetate; water for injections.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

Vials and pre-filled syringes: 36 months.
The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C, protect from light and secondary X-rays. Do not freeze.
Optiray in 500 mL vials is suitable for use over 24 hours in connection with a multi-dispensing device.

6.5 Nature and Contents of Container

Optiray vials are packaged in type I clear glass, closed with a bromobutyl stopper and sealed with an aluminium cap.
Optiray prefilled syringes are packaged in polypropylene syringes, coated with silicone. Pistons and tip caps are moulded from a natural/synthetic rubber blend, coated with silicon.

Optiray 240 (ioversol injection 51% w/v).

30 mL, 50 mL glass vial;
50 mL Ultraject prefilled plastic syringe hand-held;
125 mL Ultraject prefilled plastic syringe power injector.

Optiray 320 (ioversol injection 68% w/v).

20 mL, 30 mL, 50 mL, 100 mL, 150 mL, 200 mL glass vial;
50 mL Ultraject prefilled plastic syringe hand-held;
50 mL, 75 mL, 125 mL Ultraject prefilled plastic syringe power injector.

Optiray 350 (ioversol injection 74% w/v).

20 mL, 30 mL, 50 mL, 75 mL, 100 mL, 150 mL, 200 mL, 500 mL glass vial;
30 mL, 50 mL Ultraject prefilled plastic syringe hand-held;
50 mL, 75 mL, 100 mL, 125 mL Ultraject prefilled plastic syringe power injector.
Optiray prefilled syringes are packed in boxes of 1, 10 or 20 units.
Optiray glass vials are packed in boxes of 10, 12 or 25 units.
Optiray 350 in 500 mL glass vials are packed in boxes of 5, 6 or 10 units.

Note.

Not all presentations and pack sizes may be available.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Chemical structure.

Ioversol is designated chemically as N, N'-bis (2, 3-dihydroxypropyl)-5-[N-(2-hydroxyethyl) glycolamido]-2, 4, 6-triiodoisopthalamide and has the following structural formula:
Chemical formula: C18H24I3N3O9.
The molecular weight of ioversol is 807.13 and the organically bound iodine content is 47.2%. Ioversol is non-ionic and does not dissociate in solution.

CAS number.

87771-40-2.

7 Medicine Schedule (Poisons Standard)

Unscheduled.

Summary Table of Changes