HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use OPTIRAY safely
and effectively. See full prescribing information for OPTIRAYOPTIRAY® (ioversol) injection, for intra-arterial or intra-venous use
Initial U.S. Approval: 1988
WARNING: RISKS WITH INADVERTENT INTRATHECALADMINISTRATIONFOR INTRA-ARTERIAL AND INTRAVENOUS USE ONLY

Inadvertent intrathecal administration may cause death, convulsions, cerebral
hemorrhage, coma, paralysis, arachnoiditis, acute renal failure, cardiac arrest,
seizures, rhabdomyolysis, hyperthermia, and brain edema. (5.1)
RECENT MAJOR CHANGES
Warnings and Precautions, Thyroid Dysfunction in Pediatric Patients 0 to 3 Years ofAge (5.8)
2/2023

13US0223

INDICATIONS AND USAGE
OPTIRAY is a radiographic contrast agent indicated for the following:
Intra-arterial Procedures (1.1)
Adults:• Cerebral Arteriography (300, 320 mg iodine/mL)• Peripheral Arteriography (300, 320, 350 mg iodine/mL )• Visceral and Renal Arteriography, Aortography (320 mg iodine/mL)• Coronary Arteriography and Left Ventriculography (320, 350 mg iodine/mL)
Pediatric Patients: Angiocardiography (320, 350 mg iodine/mL)

OPTIRAY® 350[Ioversol Injection 74%]

OPTIRAY® 320[Ioversol Injection 68%]

OPTIRAY® 300[Ioversol Injection 64%]

Intravenous Procedures (1.2)
Adults:• Computed tomography (CT) Imaging of Head and Body (300, 320, 350 mg iodine/mL)• Venography (300, 320, 350 mg iodine/mL)• Intravenous Excretory Urography (300, 320, 350 mg iodine/mL)• Intravenous Digital Subtraction Angiography (350 mg iodine/mL)

FULL PRESCRIBING INFORMATION: CONTENTS*
WARNING: RISKS WITH INADVERTENT INTRATHECAL ADMINISTRATION
1

INDICATIONS AND USAGE
1.1 Intra-arterial
1.2 Intravenous

2

DOSAGE AND ADMINISTRATION
2.1 Important Administration Instructions
2.2 Radio Frequency Identification (RFID)-Tagged Syringe		 Directions for Use
2.3 Intra-arterial Procedures in Adults
2.4 Intravenous Procedures in Adults
2.5 Pediatric Dosing

3
4
5

6

DOSAGE AND ADMINISTRATION
Adjust the volume and concentration of OPTIRAY. Modify the dose accounting forfactors such as age, body weight, vessel size, blood flow rate within the vessel. Pleasesee details in full Prescribing Information. (2)DOSAGE FORMS AND STRENGTHSOPTIRAY (ioversol) Injection comes in three strengths: 300 mg iodine/mL (ioversol64%), 320 mg iodine/mL (ioversol 68%), 350 mg iodine/mL (ioversol 74%) in single-dosevials, bottles, or syringes. (3)CONTRAINDICATIONS
Symptomatic Hyperthyroidism (4)WARNINGS AND PRECAUTIONS• Hypersensitivity Reactions: life-threatening or fatal reactions can occur. Always haveemergency equipment and trained personnel available. (5.2)• Contrast Induced Acute Kidney Injury: Acute injury, including renal failure, can occur.
Minimize dose aand maintain adequate hydration to minimize risk. (5.3)• Cardiovascular Adverse Reactions: hemodynamic disturbances including shock andcardiac arrest may occur during or after administration. (5.4)• Thyroid Dysfunction in Pediatric Patients 0 to 3 Years of Age: Individualize thyroid
function monitoring based on risk factors such as prematurity. (5.8)
ADVERSE REACTIONS
The most common reaction is nausea, occurring at a rate of 1 percent. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact LIEBEL-FLARSHEIM COMPANY
LLC at 855-266-5037 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
USE IN SPECIFIC POPULATIONS• Lactation: A lactating woman may pump and discard breast milk for 8 hours after
OPTIRAY administration. (8.2)
See 17 for PATIENT COUNSELING INFORMATION.

DOSAGE FORMS AND STRENGTHSCONTRAINDICATIONSWARNINGS AND PRECAUTIONS
5.1 Risks Associated with Inadvertent Intrathecal
		 Administration
5.2 Hypersensitivity Reactions
5.3 Contrast Induced Acute Kidney Injury
5.4 Cardiovascular Adverse Reactions
5.5 Thromboembolic Events
5.6 Extravasation and Injection Site Reactions
5.7 Thyroid Storm in Patients with Hyperthyroidism
5.8 Thyroid Dysfunction in Pediatric Patients 0 to 3 Years of Age
5.9 Hypertensive Crisis in Patients with Pheochromocytoma
5.10 Sickle Cell Crisis in Patients with Sickle Cell Disease
5.11 Severe Cutaneous Adverse Reactions
ADVERSE REACTIONS
6.1 Clinical Trials Experience

WARNING: RISKS WITH INADVERTENT INTRATHECAL ADMINISTRATIONFOR INTRA-ARTERIAL AND INTRAVENOUS USE ONLY

Inadvertent intrathecal administration may cause death, convulsions, cerebral
hemorrhage, coma, paralysis, arachnoiditis, acute renal failure, cardiac arrest,
seizures, rhabdomyolysis, hyperthermia, and brain edema. [see Warnings andPrecautions (5.1)]
INDICATIONS AND USAGE

OPTIRAY is indicated for:1.1 Intra-arterial

In adults• OPTIRAY 300: cerebral arteriography and peripheral arteriography.
• OPTIRAY 320: cerebral arteriography, peripheral arteriography, visceraland renal arteriography, aortography, coronary arteriography, and left
ventriculography.

1

Revised: 2/2023

6.2 Postmarketing Experience
7

8

FULL PRESCRIBING INFORMATION

1

Pediatric Patients: CT Imaging of the Head and Body, and Intravenous Excretory
Urography (320 mg iodine/mL)

10
11

12

13

16

17

DRUG INTERACTIONS
7.1 Drug-Drug Interactions
7.2 Drug/Laboratory Test Interactions
USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
8.2 Lactation
8.4 Pediatric Use
8.5 Geriatric Use
8.6 Renal Impairment
OVERDOSAGEDESCRIPTION
11.1 Chemical Characteristics
11.2 Physical Characteristics

2
DOSAGE AND ADMINISTRATION
2.1 Important Administration Instructions• Scan immediately after completion of the intravenous administration.

• OPTIRAY is for intravascular use only [see Boxed Warning, Contraindications (4),and Warnings and Precautions (5.1)].
• Use sterile technique for all handling and administration of OPTIRAY.
• Inspect glass and plastic containers prior to use for breakage or other damage
and do not use damaged containers.
• Warm OPTIRAY and administer at body or room temperature.
• Inspect OPTIRAY for particulate matter or discoloration before administration.
Do not administer if OPTIRAY contains particulate matter or is discolored.
• Do not mix OPTIRAY with other drugs, solutions or total parenteral nutrition
mixtures.
• Use the lowest dose necessary to obtain adequate visualization.
• Adjust the volume and concentration of OPTIRAY. Modify the dose
accounting for factors such as age, body weight, vessel size, blood flow rate
within the vessel, anticipated pathology, degree and extent of opacification
required, structure(s) or area to be examined, disease processes affecting thepatient, and equipment and technique to be employed.
• Avoid extravasation when injecting OPTIRAY; especially in patients withsevere arterial or venous disease [see Warnings and Precautions (5.6)].
• Hydrate patients before and after OPTIRAY administration [see Warnings andPrecautions (5.3)].
• Discard unused portion of OPTIRAY from single-dose container after use.

2.2 Radio Frequency Identification (RFID)-Tagged Syringe Directions for Use• The RFID-tagged syringe must be used with an Optivantage Injector with
RFID technology [see How Supplied/Storage and Handling (16.2)]. The RFID
tag allows for the exchange of product information such as lot number,
expiration, concentration, and identification of the syringe as being “unused”
prior to use and “used” after product administration.
• Do not operate any part of the Optivantage Injector System and RFID-tagged
syringes within 6 inches (15 cm) of a pacemaker and/or defibrillator.
• If the RFID tag is damaged or otherwise non-functional, the OPTIRAY syringewith the non-functional RFID tag may still be used; however, no data will betransferred to the injector.

2.3 Intra-arterial Procedures in Adults• Cerebral Arteriography
Use OPTIRAY 300 or OPTIRAY 320. The recommended dose for visualization of cerebral
arteries is shown below (may repeat as necessary):
Diagnostic area

Dose

Maximum Cumulative
Dose

carotid or ver tebral
arteries

2 mL to 12 mL

aortic arch injection(four vessel study)

20 mL to 50 mL

200 mLNONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
13.2 Animal Toxicology and/or Pharmacology
HOW SUPPLIED/STORAGE AND HANDLING
16.1 How Supplied
16.2 Storage
16.3 Handling
PATIENT COUNSELING INFORMATION*Sections or subsections omitted from the full prescribing information are notlisted.
• OPTIRAY 350: peripheral arteriography coronary arteriography, and left
ventriculography.
In pediatric patients• OPTIRAY 320 and OPTIRAY 350: angiocardiography.

1.2 Intra-venous

In adults• OPTIRAY 300: CT imaging of the head and body, venography, and intravenous
excretory urography.
• OPTIRAY 320: CT imaging of the head and body, venography, and intravenous
excretory urography.
• OPTIRAY 350: CT imaging of the head and body, venography, intravenous
excretory urography, and intravenous digital subtraction angiography (IV-DSA).
• In pediatric patients OPTIRAY 320: CT imaging of the head and body, andintravenous excretory urography.

2

OPTIRAY 320

50 mL to 150 mL

OPTIRAY 350

50 mL to 150 mL

OPTIRAY is indicated for intravascular use only [see Dosage and Administration(2.1)]. Inadvertent intrathecal administration can cause death, convulsions, cerebral
hemorrhage, coma, paralysis, arachnoiditis, acute renal failure, cardiac arrest, seizures,
rhabdomyolysis, hyperthermia, and brain edema.

5.2 Hypersensitivity Reactions

Body Imaging
OPTIRAY may be administered by bolus injection, by rapid infusion, or by a combinationof both. The recommended dosing is shown below:• Scanning interval will vary with indication and target organ.
Bolus Injection

Infusion

OPTIRAY 300

25 mL to 75 mL

50 mL to 150 mL

OPTIRAY 320

25 mL to 75 mL

50 mL to 150 mL

OPTIRAY 350

25 mL to 75 mL

50 mL to 150 mL

Dose

Maximum Cumulative
Dose

aorta-iliac runoff

60 mL (range 20 mL to 90 mL)

250 mL

common iliac, femoral

40 mL (range 10 mL to 50 mL)

250 mLsubclavian, brachial

20 mL (range 15 mL to 30 mL)

250 mL• Intravenous Urography
Use OPTIRAY 350, OPTIRAY 320, or OPTIRAY 300. The recommended dose is shown
below:
Usual DoseHigh Dose
Urography

Maximum DoseOPTIRAY 300

50 mL to 75 mL

1.6 mL/kg

150 mLOPTIRAY 320

50 mL to 75 mL

1.5 mL/kg to 2 mL/kg

150 mLOPTIRAY 350

50 mL to 75 mL

1.4 mL/kg

140 mL• Intravenous Digital Subtraction Angiography (IV-DSA)
Use OPTIRAY 350. The recommended dose range per injection is 30 mL to 50 mL;
may repeat as necessary with a maximum cumulative dose of 250mL.
Injection rates will vary depending on the site of catheter placement and vessel size.
• Central catheter injections are usually made at a rate of between 10 mL/secondand 30 mL/second.
• Peripheral injections are usually made at a rate of between 12 mL/second and
20 mL/second.

Diagnostic area

Dose

Maximum Cumulative
Dose

Aorta

45 mL (range 10 mL to 80 mL)

250 mL• Angiocardiography
Use OPTIRAY 350 or OPTIRAY 320. The recommended single ventricular dose is1.25 mL/kg (range 1 mL/kg to 1.5 mL/kg). The maximum cumulative dose is 5 mL/kg up
to a maximum total volume of 250 mL.
Intravenous Procedures• Computed Tomography
Use OPTIRAY 320.
Head and Body Imaging
The recommended dose in pediatric patients is 1.5 mL/kg to 2 mL/kg (range 1 mL/kg to
3 mL/kg).

Celiac45 mL (range 12 mL to 60 mL)

250 mLsuperior mesenteric

45 mL (range 15 mL to 60 mL)

250 mLrenal or inferior mesenteric

9 mL (range 6 mL to 15 mL)

250 mL• Intravenous Urography
Use OPTIRAY 320. The recommended dose for pediatric patients is 1 mL/kg to 1.5 mL/kg(range 0.5 mL/kg to 3 mL/kg); with a maximum cumulative dose not exceeding 3 mL/kg.

3• Coronary Arteriography and Left Ventriculography
Use OPTIRAY 320 or OPTIRAY 350. The recommended dose for visualization of thecoronary arteries and left ventricle is shown below (may repeat as necessary):
Diagnostic area

Dose

Maximum Cumulative
Doseleft coronary

8 mL (range 2 mL to 10 mL)

250 mLright coronary

6 mL (range 1 mL to 10 mL)

250 mLleft ventricle

40 mL (range 30 mL to 50 mL)

250 mL

2.4 Intravenous Procedures in Adults• Computed Tomography
Use OPTIRAY 300, OPTIRAY 320 or OPTIRAY 350 for head and body imaging.

4

DOSAGE FORMS AND STRENGTHS

Injection: clear, colorless to pale yellow solutions containing no undissolved
solids, available in the following strengths and single-dose containers:
mg ofioversol
per mLmg oforganicallyboundiodine
per mL

Presentations
Vials

Bottles

Hand-held
syringesPowerinjectorsyringes

OPTIRAY
300(Ioversol
64%)

636

300

No

Yes

Yes

Yes

OPTIRAY
320(Ioversol
68%)

678

320

Yes

Yes

Yes

Yes

OPTIRAY
350(Ioversol
68%)

741

350

No

Yes

Yes

Yes

3

5.4 Cardiovascular Adverse Reactions

OPTIRAY increases the circulatory osmotic load and may induce acute or delayed
hemodynamic disturbances in patients with congestive heart failure, severely impaired
renal function, combined renal and hepatic disease, combined renal and cardiac
disease, particularly when repetitive or large doses are administered.
Life-threatening or fatal cardiovascular reactions have occurred with the use of
OPTIRAY, including cardiac arrest, hypotensive collapse, and shock. Most deaths occur
within 10 minutes of injection; with cardiovascular disease as the main underlying
factor. Cardiac decompensation, serious arrhythmias, and myocardial ischemia or
infarction can occur during coronary arteriography and ventriculography.
Based upon literature reports, deaths from the administration of iodinated contrast
agents range from 6.6 per 1 million (0.00066 percent) to 1 in 10,000 patients(0.01 percent). Use the lowest necessary dose of OPTIRAY in patients with congestive
heart failure and always have emergency resuscitation equipment and trained
personnel available. Monitor all patients for severe cardiovascular reactions.
Angiocardiography
Serious, fatal, thromboembolic events causing myocardial infarction and stroke
can occur during angiographic procedures with OPTIRAY. During these procedures,increased thrombosis and activation of the complement system occurs. Risk factors forthromboembolic events include: length of procedure, catheter and syringe material,
underlying disease state, and concomitant medications.
To minimize thromboembolic events use meticulous angiographic technique.
Avoid blood remaining in contact with syringes containing OPTIRAY, which increases
the risk of clotting. Avoid angiocardiography in patients with homocystinuria becauseof the risk of inducing thrombosis and embolism [see Clinical Pharmacology (12.2)].

5.6 Extravasation and Injection Site Reactions

Extravasation can occur with OPTIRAY administration, particularly in patients withsevere arterial or venous disease and can be associated with pain, hemorrhage
and necrosis. Ensure intravascular placement of catheters prior to injection.
Monitor patients for extravasation and advise patients to seek medical care forprogression of symptoms.

5.7 Thyroid Storm in Patients with Hyperthyroidism

OPTIRAY is contraindicated in patients with symptomatic hyperthyroidism[see Contraindications (4)]. Thyroid storm has occurred following the intravascular use ofiodinated radiopaque agents in patients with hyperthyroidism or with an autonomously
functioning thyroid nodule. Evaluate the risk in such patients before use of OPTIRAY.

5.8 Thyroid Dysfunction in Pediatric Patients 0 to 3 Years of Age

Thyroid dysfunction characterized by hypothyroidism or transient thyroid suppression
has been reported after both single exposure and multiple exposures to iodinatedcontrast media (ICM) in pediatric patients 0 to 3 years of age.
Younger age, very low birth weight, prematurity, underlying medical conditions
affecting thyroid function, admission to neonatal or pediatric intensive care units, andcongenital cardiac conditions are associated with an increased risk of hypothyroidism
after ICM exposure. Pediatric patients with congenital cardiac conditions may be at
the greatest risk given that they often require high doses of contrast during invasive
cardiac procedures.
An underactive thyroid during early life may be harmful for cognitive and neurologicaldevelopment and may require thyroid hormone replacement therapy. After exposure
to ICM, individualize thyroid function monitoring based on underlying risk factors,
especially in term and preterm neonates.

5.9 Hypertensive Crisis in Patients with Pheochromocytoma

Hypertensive crisis has occurred after the use of iodinated radiopaque contrast agentsin patient with pheochromocytoma. Closely monitor patients when administering
OPTIRAY if pheochromocytoma or catecholamine-secreting paraganglioma issuspected. Inject the minimum amount of OPTIRAY necessary and have measures fortreatment of hypertensive crisis readily available.

CONTRAINDICATIONS

Symptomatic hyperthyroidism.

Head Imaging
The recommended dosing is shown below:

Acute kidney injury, including renal failure, may occur after OPTIRAY administration.
Risk factors include: pre-existing renal impairment, dehydration, diabetes mellitus,
congestive heart failure, advanced vascular disease, elderly age, concomitant use ofnephrotoxic or diuretic medications, multiple myeloma / paraproteinaceous diseases,
repetitive and/or large doses of an iodinated contrast agent.
Use the lowest necessary dose of OPTIRAY in patients with renal impairment.
Adequately hydrate patients prior to and following OPTIRAY administration. Do not use
laxatives, diuretics, or preparatory dehydration prior to OPTIRAY administration.

5.5 Thromboembolic Events

2.5 Pediatric Dosing• Visceral and Renal Arteriography and Aortography
Use OPTIRAY 320. The recommended dose for visualization for the aorta and visceralarteries is shown below (may repeat as necessary):

OPTIRAY can cause life-threatening or fatal hypersensitivity reactions including
anaphylaxis and anaphylactic shock. Manifestations include respiratory arrest,
laryngospasm, bronchospasm, angioedema, and shock. Most severe reactions develop
shortly after the start of the injection (e.g. within 1 to 3 minutes), but delayed reactions
may occur. There is an increased risk in patients with a history of a previous reaction tocontrast agent, and known allergies (i.e., bronchial asthma, drug, or food allergies), andother hypersensitivities. Premedication with antihistamines or corticosteroids to avoid or
minimize possible allergic reactions does not prevent serious life-threatening reactions,but may reduce both their incidence and severity.
Obtain a history of allergy, hypersensitivity, or prior hypersensitivity reactions toiodinated contrast agents. Always have emergency resuscitation equipment andtrained personnel available and monitor all patients for hypersensitivity reactions.

5.3 Contrast Induced Acute Kidney Injury• Venography
Use OPTIRAY 300, OPTIRAY 320 or OPTIRAY 350. The recommended dose is 50 mL to
100 mL per extremity; with a maximum cumulative dose of 250 mL.

200 mL• Peripheral Arteriography

CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.2 Pharmacodynamics
12.3 Pharmacokinetics

50 mL to 150 mL

Intra-arterial Procedures

Use OPTIRAY 300, OPTIRAY 320 or OPTIRAY 350. The recommended dose forvisualization of peripheral arteries is shown below (may repeat as necessary):
Diagnostic area

Infusion
OPTIRAY 300

5WARNINGS AND PRECAUTIONS
5.1 Risks Associated with Inadvertent Intrathecal Administration

5.10 Sickle Cell Crisis in Patients with Sickle Cell Disease

4

Iodinated contrast agents may promote sickling in individuals who are homozygous
for sickle cell disease. Hydrate patients prior to and following OPTIRAY administration,5

use OPTIRAY only if the necessary imaging information cannot be obtained withalternative imaging modalities, and inject the minimum amount necessary.

5.11 Severe Cutaneous Adverse Reactions

Severe cutaneous adverse reactions (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), acutegeneralized exanthematous pustulosis (AGEP) and drug reaction with eosinophilia
and systemic symptoms (DRESS). Reaction severity may increase and time toonset 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.

6ADVERSE REACTIONS

The following clinically significant adverse reactions are described elsewhere in
the labeling:• Risks Associated with Inadvertent Intrathecal Administration [see Warnings andPrecautions (5.1)]• Hypersensitivity Reactions [see Warnings and Precautions (5.2)]• Contrast Induced Acute Kidney Injury [see Warnings and Precautions (5.3)]• Cardiovascular Adverse Reactions [see Warnings and Precautions (5.4)]• Thromboembolic Events [see Warnings and Precautions (5.5)]• Thyroid Dysfunction in Pediatric Patients 0 to 3 Years of Age [see Warnings andPrecautions (5.8)]• Severe Cutaneous Adverse Reactions [see Warnings and Precautions (5.11)]

6.1 Clinical Trials Experience
Adult Patients
Because clinical trials are conducted under widely varying conditions, adverse
reaction rates observed in the clinical trials of a drug cannot be directly comparedto rates in the clinical trials of another drug and may not reflect the rates observed inpractice.
The following listing shows adverse reactions based upon clinical trials with OPTIRAY(ioversol) in 4,187 patients. Adverse reactions are listed by organ system according
to clinical importance. More severe reactions are listed before others in a system
regardless of incidence. The most common reaction is nausea, occurring at a rate of
1 percent.
Cardiac disorders
Cardiac arrest, myocardial infarction, arrhythmia, atrioventricular block complete,atrioventricular block, nodal rhythm, bradycardia, angina pectoris, palpitations
Ear and labyrinth disorders
Vertigo, tinnitus
Eye disorders
Vision blurred, periorbital edema, conjunctivitis
Gastrointestinal disorders
Nausea, vomiting, abdominal pain, dysphagia, dry mouth
General disorders and administration site conditions
Chest pain, pain, injection site pain, injection site hematoma, extravasation, pyrexia,
swelling, asthenia, malaise, fatigue, chills
Infections and infestations
Rhinitis
Injury, poisoning, and procedural complications
Heart injury, vascular pseudoaneurysm
Investigations
Electrocardiogram ST segment depression, blood pressure decreased
Metabolism and nutrition disorders
Acidosis
Musculoskeletal and connective tissue disorders
Muscular weakness, muscle spasms, back pain
Nervous system disorders
Cerebral infarction, aphasia, tremor, dizziness, presyncope, headache, paraesthesia,
dysgeusia
Psychiatric disorders
Hallucination, visual hallucination, disorientation, anxiety
Renal and urinary disorders
Urinary retention, renal pain, polyuria
Respiratory, thoracic, and mediastinal disorders
Laryngeal edema, hypoxia, pulmonary edema, dyspnea, hyperventilation, cough,sneezing, nasal congestion
Skin and subcutaneous tissue disorders
Urticaria, rash, pruritus, swelling face, hyperhidrosis, erythema
Vascular disorders
Hypertension, hypotension, arterial spasm, vasospasm, vasodilation, flushing
Pediatric Patients
In clinical studies involving 311 patients for pediatric angiocardiography, contrast
enhanced computed tomographic imaging of the head and body, and intravenous
excretory urography; 6% of patients reported an adverse reaction, with the mostcommon adverse reactions being nausea and fever. Adverse reactions reported weresimilar in quality and frequency to the adverse events reported by adults.

6

6.2 Postmarketing Experience

The following additional adverse drug reactions have been reported during postapproval use of OPTIRAY. Because these reactions are reported voluntarily from a
population of uncertain size, it is not always possible to reliably estimate frequency or
establish a causal relationship to drug exposure.
Cardiac disorders: coronary artery spasm, cyanosis, arrhythmia (ventricular fibrillation,tachycardia, extrasystole), ECG abnormal.
Endocrine disorders: Hyperthyroidism, hypothyroidism.
Eye disorders: temporary blindness, conjunctivitis (including eye irritation, ocular
hyperemia, watery eyes).
Gastrointestinal disorders: tongue edema, salivary hypersecretion.
General disorders and administration site conditions: injection site reactions including
pain, hemorrhage, and necrosis especially after extravasation [see Warnings andPrecautions (5.6)], face edema, feeling hot.
Immune system disorders: hypersensitivity reactions including fatal anaphylactic
shock.
Nervous system disorders: seizure, loss of consciousness, somnolence, hypoesthesia,
dyskinesia, amnesia.
Respiratory disorders: Respiratory arrest, asthma, bronchospasm, laryngeal spasm andobstruction, throat irritation, dysphonia.
Skin and subcutaneous tissue disorders: Reactions range from mild (e.g. rash,erythema, pruritus, urticaria, and skin discoloration) to severe: [e.g. StevensJohnson syndrome and toxic epidermal necrolysis (SJS/TEN)], acute generalized
exanthematous pustulosis (AGEP) and drug reaction with eosinophilia and systemic
symptoms (DRESS).
Vascular Disorders: phlebitis, thrombosis.

7
DRUG INTERACTIONS
7.1 Drug-Drug Interactions

Metformin
In patients with renal impairment, metformin can cause lactic acidosis. Iodinatedcontrast agents appear to increase the risk of metformin induced lactic acidosis,
possibly as a result of worsening renal function. Stop metformin at the time of,or prior to, OPTIRAY administration in patients with an eGFR between 30 and
60 mL/min/1.73 m2; in patients with a history of hepatic impairment, alcoholism orheart failure; or in patients who will be administered intra-arterial iodinated contrast
agents. Re-evaluate eGFR 48 hours after the imaging procedure, and reinstitute only
after renal function is stable.
Radioactive Iodine
Administration of iodinated contrast agents may interfere with thyroid uptakeof radioactive iodine (I-131) and decrease therapeutic efficacy in patients withcarcinoma of the thyroid. The decrease in efficacy lasts for 6-8 weeks.
Oral Cholecystographic Contrast Agents
Renal toxicity has been reported in patients with liver impairment who were
given oral cholecystographic agents followed by intravascular contrast agents.
Administration of OPTIRAY should be postponed in patients who have recently
received a cholecystographic contrast agent.

7.2 Drug/Laboratory Test Interactions• Protein-Bound Iodine, Radioactive Iodine Determinations
The results of 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 administration of iodinated contrast agent. However, thyroid
function tests that do not depend on iodine estimations, e.g., T3 resin uptake andtotal or free thyroxine (T4) assays are not affected.

8
USE IN SPECIFIC POPULATIONS
8.1 Pregnancy

Risk Summary
Postmarketing data with OPTIRAY use in pregnant women are insufficient todetermine if there is a risk of drug-associated adverse developmental outcomes.
Ioversol crosses the placenta and reaches fetal tissues in small amounts [see Data].
In animal reproduction studies, no adverse developmental effects were observed
following daily intravenous administrations of ioversol to pregnant rats (fromGestation Day 7 to 17) and rabbits (Gestation Day 6 to 18) at doses 0.35 and0.71 times, respectively, the maximum recommended human dose.
The estimated background risk of major birth defects and miscarriage for the indicatedpopulation is unknown. All pregnancies have a background risk of major birthdefects, loss, or other adverse outcomes. In the U.S. general population, the estimatedbackground risk of major birth defects and miscarriages in clinically recognizedpregnancies is 2-4% and 15-20%, respectively.
Data
Human Data
Literature reports show that ioversol crosses the placenta and is visualized in
the digestive tract of exposed infants after birth.
Animal Data
Developmental toxicity studies were conducted with ioversol given intravenously atdoses of 0, 0.2, 0.8, and 3.2 g iodine/kg/day from Gestation Day 7 to 17 and 6 to 18,
in rats and rabbits, respectively. No adverse effects on embryo-fetal development
were observed in either species at the maximum dose tested (3.2 g iodine/kg/day).
Maternal toxicity was observed in rabbits at 0.8 and 3.2 g iodine/kg/day.

adverse effects on the breastfed infant from OPTIRAY or from the underlying maternal
condition.

7

OPTIRAY320

OPTIRAY
350

Clinical Considerations
Interruption of breastfeeding after exposure to iodinated contrast agents is notnecessary because the potential exposure of the breastfed infant to iodine is small.
However, a lactating woman may consider interrupting breastfeeding and pumping
and discarding breast milk for 8 hours (approximately 5 elimination half-lives) after
OPTIRAY administration in order to minimize drug exposure to a breastfed infant.

Ioversol content(mg/mL)

636

678

741

Iodine content(mg I/mL)

300

320

350

Osmolality(mOsm/kg water)

651

702

792

8.4 Pediatric Use

Viscosity (cps)at 25°Cat 37°C

8.2
5.5

9.9
5.8

14.3
9.0

Specific Gravity
at 37°C

1.352

1.371

1.405

Safety and effectiveness in pediatric patients have been established for the useof OPTIRAY 350 and OPTIRAY 320 in angiocardiography; and for OPTIRAY 320 incomputed tomographic imaging of the head and body, and intravenous excretoryurography. Use of OPTIRAY 350 and OPTIRAY 320 in these age groups is based oncontrolled clinical trials involving 159 patients for pediatric angiocardiography;
computed tomographic imaging of the head and body, and intravenous excretoryurography. In general, the types of adverse reactions reported are similar to those of
adults [see Adverse Reactions (6.1)].
Safety and effectiveness of OPTIRAY 300 has not been established in pediatricpatients.
Pediatric patients at higher risk of experiencing adverse reactions to OPTIRAY include
patients with: asthma, sensitivity to medication and/or allergens, congestive heart
failure, serum creatinine greater than 1.5 mg/dL, or age less than 12 months.
Thyroid function tests indicative of thyroid dysfunction, characterized byhypothyroidism or transient thyroid suppression have been uncommonly reported
following iodinated contrast media administration in pediatric patients, including termand preterm neonates; some patients were treated for hypothyroidism. After exposure
to iodinated contrast media, individualize thyroid function monitoring in pediatricpatients 0 to 3 years of age based on underlying risk factors, especially in term andpreterm neonates [see Warnings and Precautions (5.8) and Adverse Reactions (6.2)].

8.5 Geriatric Use

Ioversol is nearly completely excreted as parent drug by the kidney, and the risk ofadverse reactions to OPTIRAY may be greater in patients with impaired renal function.
Because elderly patients are more likely to have decreased renal function, dose
selection should be cautious usually starting at the low end of the dosing range,
reflecting the greater frequency of decreased hepatic, renal or cardiac function, andof concomitant disease or other drug therapy.

8.6 Renal Impairment

Ioversol is nearly completely excreted as parent drug by the kidney and renal
impairment is expected to reduce the rate of elimination. Ioversol can be removed
by dialysis.

10

OVERDOSAGE

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 symptomatictherapy.
Ioversol does not bind to plasma or serum protein and is, therefore, dialyzable.

11 DESCRIPTION
11.1 Chemical Characteristics
OPTIRAY (ioversol injection) is a non-ionic radiographic contrast agent. OPTIRAY
formulations are sterile, nonpyrogenic, aqueous solutions intended for intravascularuse. Ioversol is designated chemically as N,N’-Bis (2,3-dihydroxypropyl)-5[N-(2-hydroxyethyl) -glycolamido] -2,4,6-triiodoisophthalamide. The molecular weightof ioversol is 807.11 and the organically bound iodine content is 47.2%.
The structural formula of ioversol is as follows:
OPTIRAY is available in three strengths:• OPTIRAY 300 (ioversol injection 64%): Each mL contains 300 mg organicallybound iodine, 636 mg ioversol, 3.6 mg, tromethamine, 0.2 mg edetate calcium
disodium.

The OPTIRAY formulations are clear, colorless to pale yellow solutions containing
no undissolved solids. Crystallization does not occur at room temperature. OPTIRAY
solutions have osmolalities 1.8 to 2.8 times that of plasma (285 mOsm/kg water) as
shown in the above table and are hypertonic under conditions of use.

12.2 Pharmacodynamics

Following administration of OPTIRAY, the degree of enhancement is directly related
to the iodine content in an administered dose. Peak iodine plasma levels occur
immediately following rapid injection. The time to maximum contrast enhancement
can vary, depending on the organ, from the time that peak blood iodine
concentrations are reached to one hour after intravenous bolus administration.
When a delay between peak blood iodine concentrations and peak contrast ispresent, it suggests that radiographic contrast enhancement is at least in part
dependent on the accumulation of iodine-containing medium within the lesion andoutside the blood pool.
For angiography, contrast enhancement is greatest immediately (15 seconds to
120 seconds) after rapid injection. Iodinated contrast agents may be visualized in
the renal parenchyma within 30-60 seconds following rapid intravenous injection.
Opacification of the calyces and pelves in patients with normal renal function
becomes apparent within 1-3 minutes, with optimum contrast occurring within
5-15 minutes.

12.3 Pharmacokinetics

In 12 healthy volunteers (6 receiving 50 mL and 6 receiving 150 mL of OPTIRAY 320),
elimination half-life was 1.5 hours for both doses.
Distribution
In an in vitro human plasma study, ioversol did not bind to protein. The volume of
distribution in adults was 0.26 L/kg body weight, consistent with distribution to theextracellular space.

OPTIRAY 300
Glass

25x50 mL bottles
12x100 mL bottles
12x150 mL bottles
12x200 mL fill/250 mL bottles

Excretion
Greater than 95% of the administered dose was excreted in urine within the first
24 hours, with the peak urine concentration occurring in the first two hours afteradministration.

20x100 mL fill/125 mL power injector syringes

Plastic

20x50 mL hand held syringes
20x75 mL fill/125 mL power injector syringes
20x100 mL fill/125 mL power injector syringes
20x125 mL power injector syringes
20x100 mL fill/125 mL power injector syringes
20x125 mL power injector syringes

OPTIRAY 320
Glass

25x20 mL vials
25x50 mL bottles

0019-1332-90
0019-1332-00

RFID-Tagged Syringe Description
This information is for UltrajectTM syringes containing OPTIRAY that have beenlabeled with a Radio Frequency Identification (RFID) tag. When used with an
RFID-enabled OptivantageTM injector, this tag allows for the exchange of productinformation such as lot number, expiration, concentration, and identification of
the syringe as being “unused” prior to use and “used” after product administrations.
Patient information is not used in any form with this RFID technology.
OPTIRAY product quality is not influenced by the use of this RFID tag.
RFID-Tagged Syringe Directions for Use
For the RFID Technology to function, the syringe must be used with an Optivantage
Injector with RFID technology [see Dosage and Administration (2.2)]. Function of
the RFID technology is not dependent on syringe orientation as it is placed in theinjector. Instructions for use of injector are provided on the injector interface screen
and operator’s manual.
If the RFID tag is damaged or otherwise non-functional, the injector will notify theuser. Should this occur the OPTIRAY syringe with the non-functional RFID tag may still
be used but no data will be transferred to the injector.
Regarding interference with medical devices, the RFID tag and injector system meet
the IEC 60601-1-2 requirements for emission and immunity standards for medical
devices. Follow all manufacturers’ guidelines and do not operate any part of the
Optivantage Injector System and RFID-tagged syringes within 6 inches (15 cm) ofa pacemaker and/or defibrillator.

16.2 Storage• Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F).
• Protect from strong daylight or direct exposure to the sun.
• Store up to 40°C (104°F) for up to one month in a contrast media warmer
utilizing circulating warm air.
• May store OPTIRAY for periods longer than one month.
• Store OPTIRAY RFID-tagged syringes at the same conditions listed for the drug
product.
• Discard OPTIRAY syringes, glass bottles, and their contents if they are frozen orif crystallization occurs.

16.3 Handling• Do not re-autoclave plastic container because of possible damage to syringe.
• RFID-tagged syringes require no special handling.

OPTIRAY is a clear, colorless to pale yellow, sterile, pyrogen-free, aqueous solution
available in three strengths. The products are supplied in containers from which
the air has been displaced by nitrogen. OPTIRAY is supplied in the following singledose configurations:25x50 mL bottles
12x100 mL bottles
12x150 mL bottles
12x200 mL fill/250 mL bottles

0019-1323-85
0019-1323-00
0019-1323-27*Radio Frequency Identification (RFID) Technology

13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

OPTIRAY 350
Glass

0019-1323-78
0019-1323-52
0019-1323-95
0019-1323-90
0019-1323-87

0019-1332-06
0019-1332-11
0019-1332-16
0019-1332-21

RFID-Tagged Syringes*

Elimination
Metabolism
Ioversol does not undergo significant metabolism, deiodination or biotransformation.

RFID-Tagged Syringes*

8

20x75 mL fill/125 mL power injector syringes
20x100 mL fill/125 mL power injector syringes
20x125 mL power injector syringes

20x100 mL fill/125 mL power injector syringes

Intravascular injection of ioversol opacifies vessels in the path of the flowof the contrast medium, permitting visualization of the internal structures until
significant hemodilution occurs.
In imaging of the body, iodinated contrast agents diffuse from the vascular into theextravascular space. In normal brain with an intact blood-brain barrier, contrast does
not diffuse into the extravascular space. In patients with a disrupted blood-brain
barrier, contrast agent accumulates in the interstitial space in the region of disruption.

16 HOW SUPPLIED/STORAGE AND HANDLING
16.1 How SuppliedSome physical and chemical properties of these formulations are listed below:

20x50 mL hand held syringes
20x50 mL fill/125 mL power injector syringes
20x75 mL fill/125 mL power injector syringes
20x100 mL fill/125 mL power injector syringes
20x125 mL power injector syringes

Plastic

Animal studies indicate that ioversol does not cross the blood-brain barrier.

11.2 Physical Characteristics

0019-1323-11
0019-1323-16
0019-1323-21

Plastic

12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action

13.2 Animal Toxicology and/or Pharmacology• OPTIRAY 320 (ioversol injection 68%): Each mL contains 320 mg organicallybound iodine, 678 mg of ioversol, 3.6 mg tromethamine, 0.2 mg edetate
calcium disodium.
• OPTIRAY 350 (ioversol injection 74%): Each mL contains 350 mg organicallybound iodine, 741 mg ioversol, 3.6 mg tromethamine, 0.2 mg edetate calcium
disodium.
The pH of the OPTIRAY formulations is adjusted to 6.0 to 7.4 with hydrochloric acidor sodium hydroxide. All solutions are sterilized by autoclaving and contain nopreservatives. Ioversol does not dissociate in solution.

12x100 mL bottles
12x150 mL bottles
12x200 mL fill/250 mL bottles

RFID-Tagged Syringes*

No long term animal studies have been performed to evaluate carcinogenic potential.
Nonclinical studies show that ioversol is not mutagenic and does not affect fertility.

8.2 Lactation
Risk Summary
There is no information about the presence of ioversol in human or animal milk,
the effects of the drug on the breastfed infant, or the effects of the drug on milk
production. However, iodinated contrast agents are excreted unchanged in humanmilk in very low amounts with poor absorption from the gastrointestinal tract of thebreastfed infant. The developmental and health benefits of breastfeeding should
be considered along with the mother’s clinical need for OPTIRAY and any potential

OPTIRAY
300

17

PATIENT COUNSELING INFORMATION

Hypersensitivity Reactions
Advise the patient concerning the risk of hypersensitivity reactions that can occur
both during and after OPTIRAY administration. Advise the patient to report any signs
or symptoms of hypersensitivity reactions during the procedure and to seek medical
attention for signs or symptoms experienced after discharge [see Warnings andPrecautions (5.2)].
Advise patients to inform their physician if they develop a rash after receiving
OPTIRAY [see Warnings and Precautions (5.10)].

NDC Number

Contrast Induced Acute Kidney Injury
Advise the patient concerning appropriate hydration to decrease the risk of contrast
induced kidney injury [see Warnings and Precautions (5.3)].

0019-1333-06
0019-1333-11
0019-1333-16
0019-1333-21

Extravasation
If extravasation occurs during injection, advise patients to seek medical care forprogression of symptoms [see Warnings and Precautions (5.6)].

0019-1333-78
0019-1333-95
0019-1333-90
0019-1333-87
0019-1333-00
0019-1333-27

Thyroid Dysfunction
Advise parents/caregivers about the risk of developing thyroid dysfunction after
OPTIRAY administration. Advise parents/caregivers about when to seek medical carefor their child to monitor for thyroid function [see Warnings and Precautions (5.8)].
Manufactured by:
Liebel-Flarsheim Company LLC
Raleigh, NC 27616
Made in USA

90019-1323-02
0019-1323-06

GBT 13US0223

10

11

NUMBER OF COLORSGlobal Labeling Department
JOB INFORMATION

Product Brand andDescriptor:

OPTIRAY

GTIN:

None

GBU:

Pharmaceuticals

REV:

02/2023

Liebel-Flarsheim Company LLC
A subsidiary of Guerbet

Black
Regulatory Affairs
1034 South Brentwood
Richmond Heights, MO 63117 USA

GBU-SPECIFIC INFORMATION
Manufacturing Site: Raleigh

ADDITIONAL JOB INFORMATION
Job #:

230039Dimensions:22.75” W x 12.75” H

Artwork/Part #:GBT 13US0223

MetricDimensions:577.85 mm W x 323.85 mm H (approx)

Print Process:

Offset Lithography

Package Type: Insert

Barcode Format:

Code 128

File Name:TECHNICAL INFORMATION

InDesign
Linked Images: Structure outline.eps
Insert Grayscale logo.eps

Application:

Print Vendor:
Country:
Graphic Designer
Date:

CCL - Chicago
United States (US)jg5
August 30, 2023

OTHER INFORMATION

1323ra-in0000-us0223.indd

Additional Notes:

Notes:
Fonts Used:

Myriad Pro Family