Guerbet South Africa (Pty) Ltd
Optiray 350 (50, 75, 100, 125, 200 & 500 ml) Solution for Injection
Optiray 320 (50, 100 ml) Solution for Injection
Optiray 300 (30, 50, 100, 125 ml) Solution for Injection

PROFESSIONAL INFORMATIONSCHEDULING STATUS
S4

1. NAME OF THE MEDICINE
Optiray 350 - 50 ml Solution for Injection
Optiray 350 - 75 ml Solution for Injection
Optiray 350 - 100 ml Solution for Injection
Optiray 350 - 125 ml Solution for Injection
Optiray 350 Solution for Injection
Optiray 320 - 50 ml Solution for Injection
Optiray 320 - 100 ml Solution for Injection
Optiray 300 - 30 ml Solution for Injection
Optiray 300 - 50 ml Solution for Injection
Optiray 300 - 100 ml Solution for Injection
Optiray 300 - 125 ml Solution for Injection

2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Optiray 350:

Each millilitre solution contains 741 mg of ioversol equivalent to 350 mg

organically bound iodine.
Osmolality: 740 mOsm/kg
Viscosity: 8,3 mPa.s (at 37 °C)
Optiray 320: Each millilitre solution contains 678 mg of ioversol equivalent to 320 mg
organically bound iodine.
Osmolality: 680 mOsm/kg
Viscosity: 6,1 mPa.s (at 37 °C)
Optiray 300: Each millilitre solution contains 636 mg of ioversol equivalent to 300 mg
Version: 10.0
Submission date: 20 March 2023
Approved/Implemented: 31 October 2023

Page 1 of 28

Guerbet South Africa (Pty) Ltd
Optiray 350 (50, 75, 100, 125, 200 & 500 ml) Solution for Injection
Optiray 320 (50, 100 ml) Solution for Injection
Optiray 300 (30, 50, 100, 125 ml) Solution for Injection

organically bound iodine.
Osmolality: 643 mOsm/kg
Viscosity: 5,0 mPa.s (at 37 °C)

For the full list of excipients, see section 6.1
Sugar free.

3. PHARMACEUTICAL FORM
Solution for injection
Clear, colourless to pale yellow solution containing no solids.

4. CLINICAL PARTICULARS
4.1 Therapeutic indications
Optiray is for diagnostic use only.
Optiray 350 is indicated in adults for angiography throughout the cardiovascular system. The
uses include coronary, peripheral, visceral and renal angiography, aortography and left
ventriculography. Optiray 350 is also indicated for contrast enhanced computed tomographyof the head and body, intravenous urography, intravenous digital subtraction angiography andvenography.

Optiray 320 is indicated in adults for angiography throughout the cardiovascular system. The
uses include cerebral, coronary, peripheral, visceral and renal angiography, in aortography,
left ventriculography and intravenous urography. Optiray 320 is also indicated for contrast
enhanced computed tomography of the head and body
Optiray 320 is indicated in children for angiocardiography, contrast enhanced computed
tomography of the head and body, and intravenous urography.

Optiray 300 is indicated in adults for cerebral, peripheral and visceral angiography, intravenous
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Guerbet South Africa (Pty) Ltd
Optiray 350 (50, 75, 100, 125, 200 & 500 ml) Solution for Injection
Optiray 320 (50, 100 ml) Solution for Injection
Optiray 300 (30, 50, 100, 125 ml) Solution for Injection

urography, intravenous digital subtraction angiography and venography. Optiray 300 is also
indicated for contrast enhanced computed tomography of the head and body
Optiray 300 is indicated in children for cerebral, peripheral and visceral angiography, and for
intravenous urography.

4.2 Posology and method of administration
Please refer to table.
Adult dose:
Procedure

Product

Dosage andMaximum total

administrationdose

2 - 12 ml

200 ml20 - 50 ml

200 ml

Cerebralangiography
Carotid or vertebral

Optiray 320 orarteryOptiray 300

Aortic arch

Optiray 320 or
Optiray 300

Peripheral
angiography
Aortic-iliac runoff

250 mlOptiray 350 or

10 - 90 ml

Optiray 320 or

60 ml (range 20 to 90 ml)

Optiray 300
Optiray 350 or
Common iliac, femoral

40 ml (range 10 to 50 ml)

Optiray 320 or
Optiray 300

Subclavian, brachial

Optiray 350 or

20 ml (range 15 to 30 ml)

Optiray 320 orThese doses may be

Optiray 300

repeated as necessary.

Version: 10.0
Submission date: 20 March 2023
Approved/Implemented: 31 October 2023

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Guerbet South Africa (Pty) Ltd
Optiray 350 (50, 75, 100, 125, 200 & 500 ml) Solution for Injection
Optiray 320 (50, 100 ml) Solution for Injection
Optiray 300 (30, 50, 100, 125 ml) Solution for Injection

Adult dose:
Procedure

Venography

Product

Dosage andMaximum total

administration

dose

Optiray 350 or

50 – 100 ml per extremity.

250 mlOptiray 300

Following the procedure,
the venous system should
be flushed with Sodium
Chloride Injection USP(United States
Pharmacopeia) or 5 %Dextrose in water.
Massage and elevation
are also helpful for
clearing the extremities.

Left

Optiray 350 or

30 – 50 ml

ventriculography

Optiray 320

Left ventricle: 40 ml.

250 mlMay be repeated asnecessary. Several
minutes should bepermitted to elapse
between each injection toallow for subsidence ofpossible haemodynamic
disturbance.

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Approved/Implemented: 31 October 2023

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Guerbet South Africa (Pty) Ltd
Optiray 350 (50, 75, 100, 125, 200 & 500 ml) Solution for Injection
Optiray 320 (50, 100 ml) Solution for Injection
Optiray 300 (30, 50, 100, 125 ml) Solution for Injection

Adult dose:
Procedure

Product

Dosage andMaximum total

administrationdose
250 mlCoronary

Optiray 350 or

1 - 10 ml

arteriography

Optiray 320

Left coronary artery:

8 ml(range 2 to 10 ml)
Right coronary artery: 6
ml (range 1 to 10 ml)
May be repeated asnecessary. Several
minutes should bepermitted to elapse
between each injection toallow for subsidence ofpossible haemodynamic
disturbances.
Visceral

Optiray 350 or

12 - 60 ml

angiography

Optiray 320 or

Celiac: 45 ml (range 12 toOptiray 300

60 ml)

250 mlSuperior mesenteric: 45 ml(range 15 to 60 ml)
These doses may berepeated as necessary.
Aortography

Optiray 350 or

10 - 80 ml

Optiray 320

Aorta: 45 ml (range 10 to

250 ml80 ml)
These doses may berepeated as necessary.
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Approved/Implemented: 31 October 2023

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Guerbet South Africa (Pty) Ltd
Optiray 350 (50, 75, 100, 125, 200 & 500 ml) Solution for Injection
Optiray 320 (50, 100 ml) Solution for Injection
Optiray 300 (30, 50, 100, 125 ml) Solution for Injection

Adult dose:
Procedure

Renal angiography

Product

Dosage andMaximum total

administration

dose

Optiray 350 or

6 - 15 ml

250 mlOptiray 320

Renal or inferior
mesenteric: 9 ml (range 6
to 15 ml)
These doses may berepeated as necessary.

Urography

Optiray 350 or

50 - 75 ml

150 mlOptiray 320 or

50 - 75 ml

150 mlOptiray 300

50 - 75 ml

150 mlHead imaging

Optiray 350 or

50 - 150 ml

150 ml(Head CT)

Optiray 320 or

50 - 150 ml

150 mlOptiray 300

50 - 150 ml

150 mlComputed
tomography

Scanning may be
performed immediately
after I.V. administration.
Body imaging (Body

Optiray 350 or

25 - 150 ml

150 ml

CT)

Optiray 320 or

25 - 150 ml

150 mlOptiray 300

25 - 150 ml

150 mlVersion: 10.0
Submission date: 20 March 2023
Approved/Implemented: 31 October 2023

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Guerbet South Africa (Pty) Ltd
Optiray 350 (50, 75, 100, 125, 200 & 500 ml) Solution for Injection
Optiray 320 (50, 100 ml) Solution for Injection
Optiray 300 (30, 50, 100, 125 ml) Solution for Injection

Adult dose:
Procedure

Product

Dosage andMaximum total

administrationdose

5 - 80 ml

250 ml

250 mlDigital subtraction
angiography
Intra-arterial

Optiray 350 or(IA DSA)

Optiray 300

Intravenous

Optiray 350 or

30 - 50 ml(IV DSA)

Optiray 300

Injections may berepeated as necessary.

Children (older than four weeks):
Optiray 300 Recommended dosage schedule
Procedure

DosageMaximum total dose

Cerebral angiography

1 – 3 ml/kg

100 mlPeripheral angiogrpahy

1 – 3 ml/kg

100 mlVisceral and renal

1 – 3 ml/kg

100 ml2 ml/kg (>1 year of age)

100 mlangiography andaortography
Intravenous urography

3 ml/kg (<1 year of age)Children (older than four weeks):
Optiray 320 Recommended dosage schedule
Procedure

DosageMaximum total dose

Computed tomography:

1 – 3 ml/kg

100 mlHeadimagingor

Body

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Approved/Implemented: 31 October 2023

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Guerbet South Africa (Pty) Ltd
Optiray 350 (50, 75, 100, 125, 200 & 500 ml) Solution for Injection
Optiray 320 (50, 100 ml) Solution for Injection
Optiray 300 (30, 50, 100, 125 ml) Solution for Injection

Children (older than four weeks):
Optiray 320 Recommended dosage schedule
Procedure

DosageMaximum total dose

0,5 – 3 ml/kg

100 mlimaging
Intravenous urography

Paediatric: doses of 0,5 to 3
ml/kg

have

produced

diagnostic opacification of
the excretory tract. The usual
dose is 1 to 1,5 ml/kg.
Dosageforchildreninfants
shouldandbeadministered in proportion toage and body mass. The
total

administereddoseshould not exceed 3 ml/kg.
Paediatric

1 to 1,5 ml/kg (usual single 250 ml

angiocardiography

injection dose - 1,25 ml/kg
body mass). When multiple
injections are given, total
administered dose should
not exceed 5 ml/kg.

Safety and effectiveness of Optiray 300 and Optiray 320 in children of four weeks or less, in any
other indication than those listed above have not yet been established. Safety and effectivenessof Optiray 350 in children have not yet been established and should therefore not be used inchildren until further data becomes available.

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Guerbet South Africa (Pty) Ltd
Optiray 350 (50, 75, 100, 125, 200 & 500 ml) Solution for Injection
Optiray 320 (50, 100 ml) Solution for Injection
Optiray 300 (30, 50, 100, 125 ml) Solution for Injection

Method of administration
Optiray formulations are sterile, non-pyrogenic, aqueous solutions intended for intravascularadministration as diagnostic radio-opaque media.

The dosage depends on the type of investigation and the technique used. It is recommended
that intravascularly administered iodinated contrast agents are warmed to body temperature
prior to injection. The lowest dose necessary to obtain adequate visualisation should be used.
If, during administration, a reaction occurs, the injection should be stopped until the reaction
has subsided.

Patients should be well-hydrated prior to and following Optiray administration. No othermedicines should be mixed with the solution due to the risk of chemical incompatibility. Sterile
technique must be used in all vascular injections involving contrast media. All solutions should
be inspected visually for particulate matter and discolouration prior to administration andshould not be used if particles are observed or discolouration has occurred.

4.3 Contraindications
Hypersensitivity to ioversol or to any of the ingredients, including excipients.
Proven hypersensitivity to iodine-containing contrast media.
Manifest hyperthyroidism.
Pregnancy and lactation (see section 4.6 Fertility, Pregnancy and Lactation).

4.4 Special warnings and precautions for use
Diagnostic procedures which involve the use of iodinated intravascular contrast agents suchas Optiray 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 healthcare
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Guerbet South Africa (Pty) Ltd
Optiray 350 (50, 75, 100, 125, 200 & 500 ml) Solution for Injection
Optiray 320 (50, 100 ml) Solution for Injection
Optiray 300 (30, 50, 100, 125 ml) Solution for Injection

professional competent in recognising and treating adverse reactions of all types, should
always be available.

Fatal reactions have been associated with the administration of water-soluble
contrast media including Optiray. It is, therefore of the utmost importance that acourse of action is carefully planned, in advance, for the treatment of serious
reactions, and that appropriate and adequate facilities and personnel be readily
available in case of a severe reaction. Patients should be observed for a possible
severe reaction, during, and for at least 30 to 60 minutes after administration of
Optiray. Patients with known or suspected hypersensitivity to iodinated contrast
media should be closely observed.
The presence of renal damage in diabetic patients is one of the factors predisposing
to renal impairment following Optiray administration. This may precipitate lactic
acidosis in patients who are taking biguanides, such as metformin. As a precaution,
biguanides should be stopped prior to the time of the Optiray examination for 48
hours and reinstated only after control of renal function has been regained.

Hypersensitivity
Patients should be informed that allergic reactions may develop up to several days post
administration; in which case a medical practitioner should be consulted immediately.
Pre-testing cannot be relied on to confidently predict severe allergic reactions. The thoroughassessment of the medical history of the specific patient may be more accurate in predicting
potential adverse reactions. A positive history of allergies is not a contraindication but does
require caution (see section 4.3 Contraindications). Pre-medication with antihistamines andcorticosteroids to avoid or minimise allergic reactions should be considered. However, this premedication does not always prevent the occurrence, but may reduce both the incidence andseverity of severe adverse events.

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Guerbet South Africa (Pty) Ltd
Optiray 350 (50, 75, 100, 125, 200 & 500 ml) Solution for Injection
Optiray 320 (50, 100 ml) Solution for Injection
Optiray 300 (30, 50, 100, 125 ml) Solution for Injection

Intolerance to ioversol
Optiray may cause anaphylaxis or other manifestations of allergy, including nausea, vomiting,dyspnoea, erythema, urticaria and hypotension.

An increased risk of such reactions is

associated with patients who have a history of increased sensitivity to iodine, or known
allergies, asthma or hypersensitivity. In such patients, the benefit should clearly outweigh therisk (see section 4.3 Contraindications).

Severe cutaneous adverse reactions (SCAR)
SCAR 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 generalized 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 ioversol.

Coagulation disorders
The anticoagulant effect of non-ionic X-ray contrast media, such as Optiray has been shown,in vitro, to be less than that of conventional ionic agents at comparable concentrations. Similar
results were found in some in vivo studies. Serious, rarely fatal, thromboembolic events
causing myocardial infarction and stroke have been reported during angiographic procedureswith both ionic and nonionic contrast media. Therefore, meticulous intravascular administration
technique is necessary, particularly during angiographic procedures, to minimise
thromboembolic events. For this reason, standard angiographic catheters should be flushed
frequently and prolonged contact of blood with contrast agent in syringes and catheters should
be avoided.

Thyroid disorders
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Guerbet South Africa (Pty) Ltd
Optiray 350 (50, 75, 100, 125, 200 & 500 ml) Solution for Injection
Optiray 320 (50, 100 ml) Solution for Injection
Optiray 300 (30, 50, 100, 125 ml) Solution for Injection

Reports of thyroid storm following the intravascular use of iodinated radiopaque agents inpatients with hyperthyroidism or with an autonomously functioning thyroid nodule, suggest thatthe additional risk be evaluated in such patients before use of Optiray (see section 4.3
Contraindications).

Cardiovascular diseases
In angiographic procedures, the possibility of dislodging plaques or damaging or perforating
the vessel wall should be considered during catheter manipulations and Optiray injection. Test
injections to ensure proper catheter placement are recommended.
Angiography should be avoided whenever possible in patients with homocystinuria becauseof the risk of inducing thrombosis and embolism.
Patients with congestive heart failure should be observed for several hours following theprocedure to detect delayed haemodynamic disturbances, which may be associated with atransitory increase in the circulating osmotic load.

Thromboembolic disorders
In patients with advanced atherosclerosis, serious uncontrolled/severe hypertension, cardiac
decompensation, senility, preceding cerebral thrombosis or embolism, special caution should
be exercised. Cardiovascular reactions as bradycardia, rising or falling of blood pressure may
occur more often.

Central nervous system disorders
Serious neurological events, including permanent paralysis, have been observed following
direct injection into cerebral arteries or vessels supplying the spinal cord, or inangiocardiography. A cause-effect relationship to the contrast medium has not been
established since the patients’ pre-existing condition and procedural technique are causative
factors in themselves.

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Guerbet South Africa (Pty) Ltd
Optiray 350 (50, 75, 100, 125, 200 & 500 ml) Solution for Injection
Optiray 320 (50, 100 ml) Solution for Injection
Optiray 300 (30, 50, 100, 125 ml) Solution for Injection

Encephalopathy has been reported with the use of Optiray (see section 4.8). 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 usuallyoccur within minutes to hours after administration of ioversol and generally resolve 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.

Renal insufficiency
Combinations with nephrotoxic medicines should be avoided. 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, or anuria, diabetes mellitus, homozygous sickle cell disease, multiple
myeloma or other paraproteinaemia, particularly when large doses are administered. Serious
renal effects, including acute renal failure, may occur in these patients. Effective hydration
prior to the administration of Optiray is essential and may decrease the risk of renal injury.
Preparatory dehydration is dangerous and may contribute to acute renal failure especially in
myelomatous patients since this may predispose the patient to precipitation of the myeloma
protein.

Phaeochromocytoma
Administration of Optiray to patients known or suspected of having phaeochromocytoma
should be performed with extreme caution. If, in the opinion of the, medical practitioner the
possible benefits of such procedures outweigh the considered risks, the procedure may be
performed; however, the amount of Optiray injected should be kept to an absolute minimum.
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Guerbet South Africa (Pty) Ltd
Optiray 350 (50, 75, 100, 125, 200 & 500 ml) Solution for Injection
Optiray 320 (50, 100 ml) Solution for Injection
Optiray 300 (30, 50, 100, 125 ml) Solution for Injection

The blood pressure should be assessed throughout the procedure, and measures fortreatment of a hypertensive crisis should be available. Due to risk of a hypertensive crisis, apremedication with α- and ß-blockers is advisable when Optiray is administeredintravascularly.

Homozygous sickle cell diseaseIn patients with homozygous sickle cell disease, hyperosmolar agents such as X-ray contrast
media, including Opitray, may affect sickling of the erythrocytes. Hence, there is a need for
careful consideration before the intra-arterial administration of such agents to patients withhomozygous sickle cell disease.

Extravasation
Optiray should be injected with caution to avoid perivascular application. This is especially
important in patients with severe arterial or venous disease. However, significant extravasationof Optiray may occur, especially during the use of power injectors. Generally, it is tolerated
without substantial tissue injury applying conservative treatment. However, serious tissue
damage (e.g. ulceration) has been reported in isolated cases requiring surgical treatment.

Anaesthetised patient
General anaesthesia may be indicated in selected patients.

However, a slightly higher

incidence of adverse reactions has been reported in these patients, probably due to the
hypotensive effect of the anaesthetic.

Venography
In patients with suspected phlebitis, serious ischaemia, local infections or complete occlusionof the venous system special caution should be exercised.

Peripheral angiography
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Guerbet South Africa (Pty) Ltd
Optiray 350 (50, 75, 100, 125, 200 & 500 ml) Solution for Injection
Optiray 320 (50, 100 ml) Solution for Injection
Optiray 300 (30, 50, 100, 125 ml) Solution for Injection

There should be pulsation in the artery, into which the Optiray will be injected. In patients withthromboangiitis obliterans or ascending infections in combination with serious ischaemia theangiography should only be performed with special caution, if at all.

Coronary arteriography and left ventriculography
In these procedures cardiac decompensation, serious dysrhythmias, ischaemia andmyocardial infarction may occur.

Paediatric angiocardiography
Paediatric patients at higher risk of experiencing adverse events during Optiray administration
may include those having asthma, a sensitivity to medication and/or allergies, congestive heart
failure, a serum creatinine greater than 132,6 µmol/L or those less than 12 months of age.

Paediatric population
Hypothyroidism or transient thyroid suppression may be observed after exposure to iodinatedcontrast media.
This adverse reaction should also be observed in newborns whose mothers have received aniodinated contrast medium during pregnancy (see section 4.6).
The incidence of hypothyroidism in patients younger than 3 years of age exposed to iodinatedcontrast media ranges between 1 % and 15 % depending on the age of the subjects and thedose of the iodinated contrast agent.
Younger age, very low birth weight, prematurity, and the presence of other conditions, suchas, admission to neonatal or paediatric intensive care units, and cardiac conditions areassociated 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 catheterization, andcomputed tomography (CT).
Special attention should be paid to paediatric patients below 3 years of age because an
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Guerbet South Africa (Pty) Ltd
Optiray 350 (50, 75, 100, 125, 200 & 500 ml) Solution for Injection
Optiray 320 (50, 100 ml) Solution for Injection
Optiray 300 (30, 50, 100, 125 ml) Solution for Injection

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
within 3 weeks following exposure to iodinated contrast media.
In neonates and particularly in premature neonates, it is recommended to control TSH level
and T4, 7-10 days and 1 month after the administration of iodinated contrast media.
If hypothyroidism is detected, thyroid function should be monitored as appropriate even whenreplacement treatment is given.

Laboratory test interactions
Optiray may reduce the capacity of the uptake of iodine by the thyroid gland. The results of
PBI (protein-bound iodine) and radioactive iodine uptake studies, which depend on iodine
estimation, will not accurately reflect thyroid function for up to 16 days following administrationof Optiray. However, thyroid function tests not dependent on iodine estimation, e.g. T3 resin
uptake and total or free thyroxine (T4) assays are not affected.

4.5 Interaction with other medicines and other forms of interaction
The following interactions have been reported after the administration of other iodinatedcontrast media. They are generally accepted as being attributable to this class of contrast
media.
No interaction studies have been performed.

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 before the examination. The use of metformin should not be
resumed for 48 hours, and should only be restarted if renal function/serum creatinine remains
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Guerbet South Africa (Pty) Ltd
Optiray 350 (50, 75, 100, 125, 200 & 500 ml) Solution for Injection
Optiray 320 (50, 100 ml) Solution for Injection
Optiray 300 (30, 50, 100, 125 ml) Solution for Injection

within the normal range or has returned to baseline.

Interleukin
Patients treated with interleukin may develop a higher rate of adverse reactions. The reason
has not yet been clarified. An increased or delayed occurrence of these reactions within aperiod of 2 weeks was observed after administration of interleukin.

Diuretics
In case of diuretic-induced dehydration, patients are at increased risk of acute renal failure
when using iodinated contrast media. Close monitoring is required to ensure adequate
hydration before administration of Optiray. The lowest necessary dose of Optiray consistent
with a diagnostic result should be used.

Vasopressor
The arterial injection of Optiray should never be made following the administration ofvasopressors, since they strongly potentiate neurological effects.

Oral cholecystographic agents
Renal toxicity has been reported in patients with liver dysfunction who were given oralcholecystographic medicines followed by intravascular contrast agents. Administration of
Optiray should therefore be postponed in patients who have recently received acholecystographic contrast agent.

4.6 Fertility, Pregnancy and Lactation
Not to be used during pregnancy or lactation (see section 4.3 Contraindications).
Safety in pregnancy and lactation has not been established.

Pregnancy
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Optiray 350 (50, 75, 100, 125, 200 & 500 ml) Solution for Injection
Optiray 320 (50, 100 ml) Solution for Injection
Optiray 300 (30, 50, 100, 125 ml) Solution for Injection

There has been limited human use of Optiray in pregnancy. However, since any X-ray
investigation during pregnancy may involve a potential foetal risk, the risk/benefit ratio should be
carefully weighed. If a better known and safer alternative is available, an X-ray investigation
involving Optiray should be avoided.

Optiray contains iodine which may induce foetal dysthyroidism if the examination takes place
after more than 14 weeks of amenorrhoea. Thyroid function of neonates should be closely
monitored during the first week of life if iodinated contrast was administered to the motherduring pregnancy. It is recommended that thyroid function be monitored again at 2 weeks ofage.

Breastfeeding
It is not known whether Optiray is excreted in human breast milk. However, Optiray may be
excreted unchanged in breast milk. Caution should be exercised when Optiray is administered to
women breastfeeding their infants, because of potential adverse events, and mothers given
Optiray should discontinue breastfeeding for one day.

4.7 Effects on ability to drive and use medicines
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 injection.

4.8 Undesirable effects
Frequencies for adverse drug reactions are defined as follows:
Very common (≥1/10)
Common (≥1/100 to <1/10)
Uncommon (≥1/1000 to <1/100)
Rare (≥1/10,000 to <1/1000)
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Guerbet South Africa (Pty) Ltd
Optiray 350 (50, 75, 100, 125, 200 & 500 ml) Solution for Injection
Optiray 320 (50, 100 ml) Solution for Injection
Optiray 300 (30, 50, 100, 125 ml) Solution for Injection

Very rare (<1/10,000)
Not known (cannot be estimated from the available data)a. Summary of the safety profile
Adverse reactions following the use of Optiray formulations are generally independent of thedose administered. Usually, they are mild to moderate, of short duration and resolve
spontaneously (without treatment). However, even mild adverse reactions may be the firstindication of a serious, generalized reaction that can occur rarely after iodinated contrast
media.

Such serious reactions may be life-threatening and fatal, and usually affect the

cardiovascular system. Most adverse drug reactions to Optiray formulations occur withinminutes after administration, however contrast related hypersensitivity reactions may occur
with a delay of some hours up to several days.

b. Tabulated summary of adverse reactions
From clinical studies, mild discomfort, including sensation of heat or cold, pain during the injection,
and/or transient taste perversion, was noted in 10 % to 50 % of patients. In a large post-marketing
study, other side effects occurred in a total of 1,1 % of the patients; the most frequent were nausea(0,4 %), skin reactions such as urticaria or erythema (0,3 %), and vomiting (0,1 %). All other eventsoccurred in less than 0,1 % of the patients.

The following adverse reactions have been collected after Optiray administration from clinical
trials and post-market experience, including post-market surveys.
Infections and infestations
Rare:rhinitis

Immune system disorders
Very rare:

anaphylactoid (hypersensitivity) reaction

Not known:

anaphylactic shock

Endocrine disorders
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Not known:

hypothyroidism*

Psychiatric disorders
Very rare:

confusional state; agitation; anxiety

Nervous system disorders
Uncommon:dizziness; dysgeusia; headache; paraesthesia

Rare:syncope; tremor

Very rare:loss of consciousness; paralysis; speech disorders; somnolence; stupor;aphasia; dysphasia; hypoaesthesia

Not known:

seizure; contrast-induced encephalopathy; amnesia; dyskinesia

Eye disorders
Rare:vision blurred; eye swelling; periorbital oedema

Very rare:

conjunctivitis allergic (including eye irritation, ocular hyperaemia, lacrimation
increased, conjunctival oedema)Not known:

blindness transient

Ear and labyrinth disorders
Rare:vertigoVery rare:tinnitus

Cardiac disorders
Rare:tachycardia

Very rare:heart block; arrhythmia; angina pectoris; bradycardia; atrial fibrillation;
electrocardiogram abnormal

Not known:

cardiac arrest; ventricular fibrillation; arteriospasm; coronary extrasystoles;
palpitations

Vascular disorders
Uncommon:blood pressure increased

Rare:hypotension; flushing

Very rare:

cerebrovascular disorder; phlebitis; hypertension; vasodilation

Not known:

shock; thrombosis; vasospasm; cyanosis; pallor

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Optiray 320 (50, 100 ml) Solution for Injection
Optiray 300 (30, 50, 100, 125 ml) Solution for Injection

Respiratory, thoracic and mediastinal disorders
Uncommon:sneezingRare:laryngeal oedema; laryngo spasm; dyspnoea; laryngeal obstruction (incl.
throat tightness, stridor); nasal congestion; cough; throat irritation

Very rare:pulmonary oedema; pharyngitis; hypoxia

Not known:

respiratory arrest; asthma; bronchospasm; dysphonia

Gastrointestinal disorders
Common:nauseaUncommon:vomitingRare:

dry mouth

Very rare:

sialoadenitis; abdominal pain; tongue oedema; dysphagia; salivary
hypersecretion

Not known:

diarrhoea

Skin and subcutaneous tissue disorders
Uncommon:urticaria; erythema; pruritus

Rare:

rash

Very rare:

angioedema; hyperhidrosis (incl. cold sweat)

Not known:

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS
syndrome); Acute Generalized Exanthematous Pustulosis (AGEP);
Erythema Multiforme (EM), Stevens Johnson Syndrome (SJS) / Toxic
Epidermal Necrolysis (TEN)

Musculoskeletal, connective tissue and bone disorders
Very rare:muscle spasms

Renal and urinary disorders
Rare:

micturition urgency

Very rare:acute kidney injury; abnormal renal function; incontinence; haematuria;
creatinine renal clearance decreased; blood urea increased

Not known:

anuria; dysuria

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Optiray 320 (50, 100 ml) Solution for Injection
Optiray 300 (30, 50, 100, 125 ml) Solution for Injection

Congenital, familial and genetic disorders
Not known:

congenital hypothyroidism

General disorders and administration site conditions
Very common:

feeling hot

Common:

pain

Rare:

face oedema; pharyngeal oedema; feeling cold; tremor; chills

Very rare:

chest pain; injection site reactions (incl. pain, erythema, and haemorrhage
up to necrosis especially after extravasation); malaise; asthenia; fatigue;
feeling abnormal, oedema, sluggishness

Not known:

pyrexiac. Description of selected adverse reactions
Adverse reactions may be classified as follows:a. Hypersensitivity reactions:
Serious anaphylactic reactions generally affect the cardiovascular and respiratory
system. These may be life-threatening and include anaphylactic shock, cardiac andrespiratory arrest, or pulmonary oedema. Patients with a history of allergic reactions
are at increased risk of developing hypersensitivity reactions. Other type 1 (immediate)
reactions such as nausea and vomiting, skin rashes, dyspnoea, rhinitis, paraesthesia
or hypotension.
b. Vasovagal reactions:e.g. Dizziness or syncope which may be caused either by the contrast medium, or by
the procedure.
c. Cardiologic side effects:
During cardiac catheterisation e.g. angina pectoris, ECG changes, cardiac
dysrhythmias, conductivity disorders and coronary spasm, which may be caused by
the contrast medium or by the procedure.
d. Nephrotoxic reactions:
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In patients with pre-existing renal damage or renal vasopathy e.g. decrease in renal
function with creatinine elevation. These adverse effects may be transient in the
majority of cases. In single cases, acute renal failure has been observed.
e. Neurotoxic reactions:
After intra-arterial injection of the contrast medium e.g. visual disorders, disorientation,paralysis, convulsions, or fits. These symptoms are generally transient and abate
spontaneously within several hours or days. Patients with pre-existing damage of theblood-brain barrier are at increased risk of developing neurotoxic reactions.
f.

Local reactions:
At the injection site e.g. rashes, swelling, vasospasm and inflammation.

g. Extravasation:
Can cause serious tissue reactions, the extent of which is dependent on the amountand strength of the contrast solution in the tissues.

d. Paediatric population
Frequency, type and severity of adverse reactions in children are expected to be the same asin adults.
*Thyroid dysfunction was observed in paediatric patients 0 to 3 years of age following theadministration of iodinated radiopaque agents.

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicine is important. It
allows continued monitoring of the benefit/risk balance of the medicine. Healthcare providers
are asked to report any suspected adverse reactions to SAHPRA via the “6.04 Adverse Drug
Reactions Reporting Form” found online under SAHPRA publications:
SAHPRA: https://www.sahpra.org.za/Publications/Index/8.
Guerbet South Africa (Pty) Ltd: pharmacovigilance.za@guerbet.com

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Optiray 320 (50, 100 ml) Solution for Injection
Optiray 300 (30, 50, 100, 125 ml) Solution for Injection

4.9 Overdose
In overdose, side effects will be exacerbated and exaggerated. Overdose of Optiray is potentiallyfatal and may affect the respiratory and cardiovascular system.
Treatment should be symptomatic & supportive. Dialysis can be used to remove Optiray from theblood.

5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
A 28 Contrast media
Pharmacotherapeutic group: Water soluble, nephrotropic, low osmolar X-ray contrast media
ATC code: V08AB07
Ioversol is a non-ionic X-ray contrast medium. 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.

5.2 Pharmacokinetic properties
The pharmacokinetic profile of ioversol, together with its hydrophilic properties and a very low
level of binding to serum and plasma proteins, indicate that ioversol, is distributed within theextracellular fluid space and eliminated through the kidneys by glomerular filtration. The mean( se*) half-lives after doses of 50 ml and 150 ml of ioversol, 320 were 113  8,4 and 104  15
minutes respectively. Elimination via the faeces is negligible. No significant metabolism,
deiodination, or biotransformation of ioversol, has been observed.
More than 95 % of the administered dose is excreted within the first 24 hours, with the peakurine concentration occurring in the first 2 hours after administration.
*Standard error

5.3 Preclinical safety data
There were no findings in the preclinical testing of Optiray which could be of relevance for the
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prescriber in recognising the safety of this product used for the authorised indications, andwhich are not already included in other sections of the leaflet.

6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Trometamol, trometamol hydrochloride, sodium hydroxide and/or hydrochloric acid (for pH: 6,0 to7,4), sodium calcium edetate, water for injections.

6.2 Incompatibilities
No other medicine should be mixed with Optiray.

6.3 Shelf-life
3 years
The solution is supplied in single dose or multi-dose containers.
Any unused portion of single dose containers should be discarded.
Any unused portion of multi-dose containers (500 ml) should be discarded within 10 hours after
first opening.

6.4 Special precautions for storage
Store at or below 25 oC.
Keep the container in the outer carton in order to protect from light. Protect from X-rays.
Do not refrigerate.
Optiray may be stored for one month at 37 °C in a contrast media warmer with circulating air.
Discard the solution in case of discoloration or particulate matter.

6.5 Nature and contents of container
Optiray is packaged in type 1, colourless glass vials, fitted with 20 mm or 32 mm bromobutyl
rubber closures and aluminium cap seals.
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Optiray 350 (50, 75, 100, 125, 200 & 500 ml) Solution for Injection
Optiray 320 (50, 100 ml) Solution for Injection
Optiray 300 (30, 50, 100, 125 ml) Solution for Injection

Optiray 300:

30 ml (box of 10)
50 ml (box of 10 and 25)
100 ml (box of 10 and 12)

Optiray 320:

50 ml (box of 10 and 25)
100 ml (box of 10 and 12)

Optiray 350:

50 ml (box of 10 and 25)
100 ml and 200 ml (box of 10 and 12)
500 ml (box of 5, 6 and 10)

Optiray is also supplied in prefilled hand-held syringes and power-injector syringes made ofpolypropylene. Blue syringe tip cap and piston are made of natural rubber.
Optiray 300, 320 and 350: 50 ml (box of 10) Prefilled hand-held syringes
75 ml, 100 ml (box of 10) Prefilled power-injector syringes
Optiray 300 and 350:

125 ml (box of 10) Prefilled power-injector syringes

Not all pack sizes and box sizes may be marketed.

6.6 Special precautions for disposal and other handling
The following precautions should be followed when using Optiray 350 500 ml vials: Optiray
350 500 ml vials must only be used with administration devices, e.g. infusion pumps or dual
head injectors which are provided with reliable connecting tubes. Optiray 350 500 ml vials havea rubber stopper which can only be pierced once. The manufacturer’s instructions for thedevice must be followed. Any Optiray 350 in 500 ml vials which is unused at the end of the day
must be discarded.

7. HOLDER OF CERTIFICATE OF REGISTRATION
Guerbet South Africa (Pty) Ltd
Hertford Office Park, Building I
90 Bekker Road, Vorna Valley
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Guerbet South Africa (Pty) Ltd
Optiray 350 (50, 75, 100, 125, 200 & 500 ml) Solution for Injection
Optiray 320 (50, 100 ml) Solution for Injection
Optiray 300 (30, 50, 100, 125 ml) Solution for Injection

Midrand, Gauteng, 1682

8. REGISTRATION NUMBERS
Optiray 350 – 50 ml:

Z/28/420

Optiray 350 – 75 ml:

A40/28/0246

Optiray 350 – 100 ml: Z/28/422
Optiray 350 – 125 ml: 30/28/0282
Optiray 350:

34/28/0101

Optiray 320 – 50 ml:

Z/28/412

Optiray 320 – 100 ml: Z/28/421
Optiray 300 – 30 ml:

Z/28/414

Optiray 300 – 50 ml:

Z/28/418

Optiray 300 - 100 ml:

Z/28/417

Optiray 300 – 125 ml: 30/28/0281

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
18 September 1992

10. DATE OF REVISION OF THE TEXT
31 October 2023

Botswana: Schedule 2
Optiray 300: BOT 0700947; Optiray 350: BOT 0700948

Namibia: Schedule 2
Optiray 300-30 ml 19/28/0001; Optiray 300-50 ml 19/28/0002; Optiray 300-100 ml
19/28/0004; Optiray 300-125 ml 19/28/0005; Optiray 350-50 ml 19/25/0007; Optiray 350-75

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Optiray 320 (50, 100 ml) Solution for Injection
Optiray 300 (30, 50, 100, 125 ml) Solution for Injection

ml 19/28/0008; Optiray 350-100 ml 19/28/0009; Optiray 350-125 ml 19/28/0010; Optiray 350
19/28/0011

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