VISIPAQUE

Iodixanol injection, USP is a dimeric, iso-osmolar, nonionic, water-soluble, radiographic contrast medium for intravascular (intravenous and intra-arterial) use.

It is provided as a ready-to-use sterile, pyrogen-free, and preservative free, colorless to pale yellow solution.

The chemical formula is 5,5´-[(2-hydroxy-1,3-propanediyl) bis(acetylimino)] bis[N,N´-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-­1,3-benzenedicarboxamide] with a molecular weight of 1,550.18 (iodine content 49.1%).

Iodixanol (C 35 H 44 I 6 N 6 O 15 ) has the following structural formula: Iodixanol injection, USP is available in two strengths: Iodixanol Injection, USP, 270 mg Iodine/mL (550 mg Iodixanol/mL), 0.074 mg calcium chloride dihydrate, 1.87 mg sodium chloride, 1.2 mg tromethamine, and 0.1 mg edetate calcium disodium.

Injection, USP, 320 mg Iodine/mL (652 mg Iodixanol/mL), 0.044 mg calcium chloride dihydrate, 1.11 mg sodium chloride, 1.2 mg tromethamine and 0.1 mg edetate calcium disodium.

Sodium chloride and calcium chloride have been added, resulting in an isotonic solution for injection providing for both concentrations a sodium/calcium ratio equivalent to blood.

The pH is adjusted to 7.4 with hydrochloric acid and/or sodium hydroxide to achieve a range between pH 6.8 and 7.7 at 22°C. Structure 11.2 Physical Characteristics The two concentrations of iodixanol injection, USP (270 mg Iodine/mL and 320 mg Iodine/mL) have the following physical properties: TABLE 4 Physical Properties of Iodixanol Injection, USP Parameter Concentration (mg Iodine/mL) 320 270 Osmolality (mOsmol/kg water) 290 290 Viscosity (cP) @ 20°C 26.6 12.7 @ 37°C 11.8 6.3 Density (g/mL) @ 20°C 1.369 1.314 @ 37°C 1.356 1.303.

Iodexanol, Trumetamol and Iodixanol radiography are a substance used during radiation imaging techniques for various veins and arteries, such as digital vascular imaging, cardiograms, brain blood vessels, ocean arteries, entrails, platonic spectroscopy of the head and body, ocean vein imaging, coronary coronary examination.

Carefully used under the supervision of a doctor in the following cases: pregnancy and breastfeeding; cardiovascular diseases; diabetes; liver failure; hemocistin urea; hyperthyroidism or hypothyroidism; multiple pure tumor; adrenal gland tumor; sickle anaemia; lung disease; kidney failure.

Intravascular injection of iodixanol opacifies vessels in the path of flow of the contrast agent, permitting visualization of internal structures.

In imaging of the body, iodinated contrast agents diffuse from the vascular into the extravascular space.

In a 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. 12.2 Pharmacodynamics Following administration of iodixanol, 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 is present, it suggests that radiographic contrast enhancement is at least in part dependent on the accumulation of iodine-containing medium within the lesion and outside 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 to 60 seconds following rapid intravenous injection.

Opacification of the calyces and pelves in patients with normal renal function becomes apparent within to 3 minutes, with optimum contrast occurring within to 15 minutes. 12.3 Pharmacokinetics Distribution In an in vitro human plasma study, iodixanol did not bind to protein.

The volume of distribution in adults was 0.26 L/kg body weight, consistent with distribution to extracellular space.

In 40 healthy, young male volunteers receiving a single intravenous administration of iodixanol in doses of 0.3 gram Iodine/kg to 1.2 gram Iodine/kg body weight, the elimination half-life was 2.1 hr. (± 0.1).

Renal clearance was 110 ± 14 mL/min, equivalent to glomerular filtration (108 mL/min).

These values were independent of the dose administered.

Iodixanol does not undergo metabolism.

In adults, approximately 97% of the injected dose of iodixanol is excreted unchanged in urine within 24 hours, with less than 2% excreted in feces within five days post-injection.

Forty pediatric patients ≤12 years old, with renal function that is normal for their age, received multiple intra-arterial administrations of iodixanol in doses of 0.32 gram Iodine/kg to 3.2 gram Iodine/kg body weight.

The elimination half-lives for these patients are shown in Table 5.

Dose adjustments to account for differences in elimination half-life in pediatric patients less than 6 months of age have not been studied.

TABLE 5 MEAN ELIMINATION HALF-LIFE* IN PEDIATRIC PATIENTS Age Range Number of Patients Elimination half-life (hr. ± SD) Newborn to < 2 months 8 4.1 ± 1.4 2 to 6 months 8 2.8 ± 0.6 6 to 12 months 9 2.4 ± 0.4 1 to 2 years 5 2.3 ± 0.6 2 to 12 years 10 2.3 ± 0.5 Adults 40 2.1 ± 0.1 Renal Impairment: In patients with significantly impaired renal function, the total clearance of iodixanol is reduced and the half-life is increased.

In a study of 16 adult patients who were scheduled for renal transplant, the mean creatinine clearance was 13.6 ± 4.7 mL/min).

In these patients, plasma half-life was 23 hours (t 1/2 for typical patients = 2.1 hours).

Contrast enhancement time in kidneys increased from 6 hours to at least 24 hours.

Dose adjustments in patients with renal impairment have not been studied.

In patients with normal blood brain barriers and severe renal impairment, iodinated contrast agents have been associated with blood-brain barrier disruption and accumulation of contrast in the brain.

Iodixanol has been shown to be dialyzable.

In an in vitro hemodialysis study, after 4 hours of dialysis with a cellulose membrane, approximately 36% of iodixanol was removed from the plasma.

After 4 hours of dialysis with polysulfone membranes, approximately 49% of iodixanol was removed.

Non-ionic material, containing iodine, is one of the colorful substances used during radiography, where it removes and conceals blood vessels, when the coloured substance flows, allowing for the radiation imaging of the internal body structures.

The drug also contains trometamol as the equivalent factor for the pH control.

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The following clinically significant adverse reactions are described elsewhere in the labeling: Risks Associated with Inadvertent Intrathecal Administration Hypersensitivity Reactions Contrast-Induced Kidney Injury Cardiovascular Adverse Reactions Thromboembolic Events Thyroid Dysfunction in Pediatric Patients to 3 Years of Age Severe Cutaneous Adverse Reactions Most common adverse reactions (incidence greater than 0.5%) in adult patients after iodixanol injection: Discomfort, warmth, pain; Cardiovascular: angina.

Gastrointestinal: diarrhea, nausea, vomiting.

System: agitation, anxiety, insomnia, nervousness, dizziness, headache, migraine, unusual skin sensations, sensory disturbance, fainting, sensation of spinning.

Skin: itchy rash, severe itching, hives.

Smell, taste, and vision alteration.

Pediatric patients experienced similar adverse reactions.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Iodixanol is often associated with sensations of discomfort, warmth or pain.

In a subgroup of 1,259 patients; 30% who received iodixanol or a comparator had application site discomfort, pain, warmth or cold.

Iodixanol had a trend toward fewer patient reports of moderate or severe pain or warmth.

Pain was reported in 2% of patients receiving iodixanol and 10% of patients receiving a comparator.

Heat was reported in 29% of patients receiving iodixanol and 51% of patients receiving a comparator.

Table 3 shows the incidence of events reported in blinded, controlled clinical studies of iodixanol in a total of 1,244 adult patients.

Adverse events (AEs) are listed by body system and in decreasing order of occurrence greater than 0.5% of patients.

One or more adverse events were reported in 20% of patients during the study period (24 to 72 hours).

In a 757 patient subgroup, the number of women reporting adverse events was 83/299 (28%) and the number of men was 77/458 (16%).

A total of 3% of women and 0.8% of men reported chest pain.

TABLE 3 ADVERSE EVENTS REPORTED IN CONTROLLED CLINICAL TRIALS IN GREATER THAN 0.5% OF 1,244 ADULT PATIENTS RECEIVING IODIXANOL OR OTHER IODINATED CONTRAST AGENTS NUMBER OF PATIENTS EXPOSED Iodixanol N (%)= 1,244 Pooled Comparators N (%) = 861 Number of Patients with Any Adverse Event 248 194 Body As a Whole Patients With Any Event 41 22 Edema (any location) 7 0 Cardiovascular Patients With Any Event 37 39 Angina Pectoris/Chest Pain 28 22 Gastrointestinal Patients With Any Event 51 46 Diarrhea 7 6 Nausea 35 32 Vomiting 10 11 Nervous System Patients With Any Event 101 60 Agitation, Anxiety, Insomnia, Nervousness 10 0 Dizziness 8 8 Headache/Migraine 31 15 Paresthesia 12 1 Sensory Disturbance 10 9 Syncope 8 1 Vertigo 30 20 Skin (not including application site) Patients With Any Event 42 18 Nonurticarial Rash or Erythema 26 4 Pruritus 20 3 Urticaria 6 10 Special Senses Patients With Any Event 57 38 Parosmia 6 4 Taste Perversion 43 32 Scotoma 14 2 The following selected adverse events were reported in ≤0.5% of the 1,244 patients.

Body as a

Disorders: back pain, fatigue, malaise Cardiovascular.

Disorders: arrhythmias, cardiac failure, conduction abnormalities, hypotension, myocardial infarction Gastrointestinal System.

Disorders: dyspepsia Hypersensitivity.

Disorders: pharyngeal edema Nervous System: cerebral vascular disorder, convulsions, hypoesthesia, stupor, confusion Peripheral Vascular.

Disorders: flushing, peripheral ischemia Renal System.

Disorders: abnormal renal function, acute renal failure, hematuria Respiratory System.

Disorders: asthma, bronchitis, dyspnea, pulmonary edema, rhinitis Skin and Appendage.

Disorders: hematoma, increased sweating Special Senses, Other.

Disorders: tinnitus Vision.

Disorders: abnormal vision 6.2 Post-marketing Experience The following additional adverse reactions have been identified during post approval use of iodixanol.

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to exposure.

Disorders: Cardiac arrest, palpitations, spasms of coronary arteries, hypertension, and flushing Endocrine.

Disorders: Hyperthyroidism, hypothyroidism Eye.

Disorders: Transient visual impairment including cortical blindness, diplopia, and blurred vision Gastrointestinal.

Disorders: Abdominal pain, pancreatitis, salivary gland enlargement General.

Disorders and Administration Site Conditions: Chills, pyrexia, pain and discomfort, administration site reactions including extravasation Immune System.

Disorders: Hypersensitivity reactions, anaphylactic shock including, life-threatening or fatal anaphylaxis Nervous System.

Disorders: Tremor (transient), coma, disturbance in consciousness, transient contrast-induced encephalopathy caused by extravasation of contrast media (including amnesia, hallucination, paralysis, paresis, transient speech disorder, aphasia, dysarthria) Psychiatric.

Disorders: Anxiety, agitation Respiratory, Thoracic, and Mediastinal.

Disorders: Cough, sneezing, throat irritation or tightness, laryngeal edema, pharyngeal edema, bronchospasm Skin and subcutaneous tissue disorders: Reactions range from mild (e.g. rash, erythema, pruritus, urticaria, and skin discoloration) to severe: [e.g. Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), acute generalized exanthematous pustulosis (AGEP) and drug reaction with eosinophilia and systemic symptoms (DRESS)] 6.3 Pediatric Adverse Reactions The overall character, quality, and severity of adverse reactions in pediatric patients is similar to that reported in adult patients from post marketing surveillance and other information.

Additional safety data was obtained in studies of iodixanol in 459 pediatric patients.

A total of 26 patients ranged in age from birth to <29 days, 148 ranged from 29 days to 2 years, 263 from to <12 years, and from 12 to 18 years.

A total of 252 (55%) of the patients were male.

The racial distribution was

Caucasian-81%, Black-14%, Oriental-2%, and other or unknown-4%.

The proportion of patients undergoing an intra-arterial procedure by age was: 92 % (<29 days), 55% (29 days to 6 months), and 29 % (>6 months).

In these studies, adverse events were numerically higher in pediatric patients less than one year of age compared to older pediatric patients.

In pediatric patients who received intravenous injections of iodixanol for computerized tomography or excretory urography, a concentration of 270 mg Iodine/mL was used in 144 patients, and a concentration of 320 mg Iodine/mL in 154 patients.

All patients received one intravenous injection of 1 mL/kg to 2 mL/kg. In pediatric patients who received intra-arterial and intracardiac studies, a concentration of 320 mg Iodine/mL was used in 161 patients.

Twenty-two patients were <29 days of age; 78 were 29 days to 2 years of age; and were over 2 years.

Most of these pediatric patients received initial volumes of 1 mL/kg to 2 mL/kg and most patients received a maximum of 3 injections.

The adverse effects of overdosage of any contrast agent may be life-threatening and affect mainly the pulmonary and cardiovascular systems.

Treatment of an overdosage is directed toward the support of all vital functions and prompt institution of symptomatic therapy.

Iodixanol injection does not bind to plasma or serum protein and can be dialyzed.

Iodixanol is contraindicated for intrathecal use

Not indicated for intrathecal use.

Individualize the combination of volume and concentration of iodixanol injection considering age, body weight, size of the vessel, rate of blood flow within the vessel, and other applicable factors.

CT of the head and body, iodixanol injection may be used with an automated contrast injection system or contrast media management system cleared for use with iodixanol injection.

For the adult patients, the maximum recommended total dose of iodine is 80 grams.

Patients should be adequately hydrated prior to and following the intravascular administration of iodinated contrast agents.

See full prescribing information for complete dosing and administration information. 2.1 Important Dosage and Administration Instructions Iodixanol injection is for intravascular use only Use sterile technique for all handling and administration of iodixanol injection.

Do not use if tamper-evident ring is broken or missing.

Warm iodixanol injection and administer at body or room temperature.

Inspect iodixanol injection for particulate matter or discoloration before administration, whenever solution and container permit.

Do not administer if iodixanol injection contains particulate matter or is discolored.

Do not mix iodixanol injection with, or inject in intravenous lines containing, other drugs or total nutritional admixtures.

Use the lowest dose necessary to obtain adequate visualization.

Individualize the volume, strength, and rate of administration of iodixanol injection.

Consider factors such as age, bodyweight, vessel size, blood flow rate within the vessel, anticipated pathology, degree and extent of opacification required, structures or area to be examined, disease processes affecting the patient, and equipment and technique to be employed.

The maximum recommended total dose of iodine for adults is 80 grams.

Avoid extravasation when injecting iodixanol injection; especially in patients with severe arterial or venous disease.

Hydrate patients before and after iodixanol injection administration. 2.2 Intra-arterial Dosage and Administration Intra-arterial digital subtraction angiography (IA-DSA) (270 mg Iodine/mL and 320 mg Iodine/mL) Angiocardiography (left ventriculography and selective coronary arteriography), peripheral arteriography, visceral arteriography, and cerebral arteriography (320 mg Iodine/mL) Use injection rates approximately equal to the flow rate in the vessel being injected.

The usual single injection volumes or total dose per patient (mL/kg) for adults and adolescents over 12 years of age are listed in Table 1: TABLE 1 ADULTS and PEDIATRIC PATIENTS 12 YEARS OF AGE AND OLDER IODIXANOL INJECTION SINGLE DOSE RECOMMENDATIONS FOR INJECTION INTO SELECTED ARTERIES ARTERIOGRAPHY IA-DSA 1 Maximum Total Dose Intra-arterial Injection Sites 320 mg Iodine/mL 270 mg Iodine/mL 320 mg Iodine/mL Carotid Arteries 10 mL to 14 mL 5 mL to 8 mL Usually Not to Exceed 175 mL Vertebral Arteries 10 mL to 12 mL 5 mL to 8 mL Right Coronary Artery 3 mL to 8 mL Usually Not to Exceed 200 mL Left Coronary Artery 3 mL to 10 mL Left Ventricle 20 mL to 45 mL Renal Arteries 8 mL to 18 mL 10 mL to 25 mL -

• Usually Not to Exceed 250 mL Aortography 30 mL to 70 mL 20 mL to 50 mL 10 mL to 50 mL Major Branches of Aorta 10 mL to 70 mL 5 mL to 30 mL 2 mL to 10 mL Aortofemoral Runoffs 20 mL to 90 mL -

• 6 mL to 15 mL Peripheral Arteries 15 mL to 30 mL -

• 3 mL to 15 mL 1 IA-DSA = Intra-arterial Digital Subtraction Angiography 2.3 Intravenous Dosage and Administration Computed Tomography of the Head or Body (270 mg Iodine/mL and 320 mg Iodine/mL) Excretory Urography (270 mg Iodine/mL and 320 mg Iodine/mL) Peripheral Venography (270 mg Iodine/mL) Coronary Computed Tomography Angiography (CCTA) (320 mg Iodine/mL) Recommended dosage of iodixanol injection is dependent on: the administration procedure, patient weight, and CT device factors, as detailed in Table 2.

Calibrate the intravenous injection rate so that image acquisition coincides with peak arterial concentration.

The time between iodixanol injection and peak arterial concentration varies between patients.

Selected dosing for different indications in adults and pediatric patients over 12 years of age are shown in Table 2.

TABLE 2 ADULTS and PEDIATRIC PATIENTS 12 YEARS OF AGE AND OLDER IODIXANOL INJECTION DOSING RECOMMENDATIONS FOR INTRAVENOUS CONTRAST ADMINISTRATION Study Type Comment 270 mg Iodine/mL 320 mg Iodine/mL Maximum Total Volume CT of Head or Body 1 Bolus 75 mL to 150 mL 75 mL to 150 mL 150 mL Infusion 100 mL to 150 mL 100 mL to 150 mL Excretory Urography Normal Renal Function 1 mL/kg 1 mL/kg 100 mL Venography Per lower extremity 50 mL to 150 mL 250 mL CCTA 1,2 Bolus injection with test bolus 3 or bolus tracking 50 mL to 150 mL 4 (4 mL to 7 mL per second) 150 mL For CT of the head and body, iodixanol injection may be used with an automated contrast injection system or contrast media management system cleared for use with iodixanol injection.

For pediatric patients aged to 17, recommended dose is 1 mL/kg to 2 mL/kg.

The main iodixanol injection volume may be preceded by a test bolus consisting of 20 mL iodixanol injection, immediately followed by a 20 mL saline flush, both injected at rate of 4 mL/sec to 7 mL/sec.

Injection of iodixanol injection with saline can be either biphasic (without dilution phase) or triphasic (with dilution phase).

Alternatively, a dose of 1 mL/kg may be used to calculate total iodixanol injection dose (excluding any test bolus).

CCTA acquired at < 120 kVp, the dose of iodixanol injection may be reduced by up to 15% in patients < 85 kg and BMI < 30 kg/m 2.

CCTA acquired on a scanner with more than 64 detector rows, the dose of iodixanol injection may be reduced in proportion to the scan duration. 2.4 Dosage in Pediatric Patients Less Than 12 Years of Age Intra-arterial Dosage and Administration Angiocardiography, cerebral arteriography, or visceral arteriography (320 mg Iodine/mL): The recommended dosage is 1 mL/kg to 2 mL/kg. The maximum dose should not exceed 4 mL/kg. Intravenous Dosage and Administration Computerized Tomography or Excretory Urography (270 mg Iodine/mL): The recommended dosage is 1 mL/kg to 2 mL/kg. The maximum dose should not exceed 2 mL/kg. 2.5 Instructions for Use with an Automated Contrast Injection System or Contrast Management System for CT of the Head and Body Iodixanol injection may be used with an automated contrast injection system cleared for use with contrast media. ◦ See above Important Dosage and Administration Instructions for iodixanol injection. ◦ See device labeling for information on device indications, instructions for use, and techniques to help assure safe use.

Iodixanol injection 320 mg Iodine/mL in 100 mL and 150 mL bottles may be used with a contrast media management system cleared for use with iodixanol injection 320 mg Iodine/mL in 100 mL and 150 mL bottles. ◦ See device labeling for information on device indications, instructions for use, and techniques to help assure safe use. ◦ Use sterile technique for penetrating the container closure of iodixanol injection 320 mg Iodine/mL and transferring iodixanol injection solution.

Clean the stopper with a pad soaked in sporicidal solution followed by a pad soaked in alcohol, then puncture the stopper.

The container closure may be penetrated only one time with a suitable sterile component of the contrast media management system cleared for use with iodixanol injection 320 mg Iodine/mL in 100 mL and 150 mL bottles. ◦ Once the iodixanol injection 320 mg Iodine/mL is punctured do not remove the bottle from the work area during the entire period of use. ◦ Maximum use time is 4 hours after initial puncture. ◦ Each bottle is for one procedure only.

Discard unused portion.

Iodixanol injection, USP is a ready-to-use sterile, pyrogen-free, preservative free, colorless to pale yellow solution available in two strengths.

It is supplied in the following configurations: Iodixanol Injection, USP, 270 mg Iodine/mL: Product Code Unit of Sale Each 381100 NDC 65219-381-10 Unit of 10 NDC 65219-381-03 100 mL single-dose polypropylene bottle 381150 NDC 65219-381-50 Unit of 10 NDC 65219-381-05 150 mL single-dose polypropylene bottle Iodixanol Injection, USP, 320 mg Iodine/mL: Product Code Unit of Sale Each 383105 NDC 65219-383-05 Unit of 10 NDC 65219-383-02 50 mL single-dose polypropylene bottle 383110 NDC 65219-383-10 Unit of 10 NDC 65219-383-04 100 mL single-dose polypropylene bottle 383150 NDC 65219-383-50 Unit of 10 NDC 65219-383-06 150 mL single-dose polypropylene bottle 383200 NDC 65219-383-70 Unit of 10 NDC 65219-383-08 200 mL single-dose polypropylene bottle 16.2 Storage and Handling Protect iodixanol injection, USP from direct exposure to sunlight.

Store iodixanol injection, USP at controlled room temperature, 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) .

Iodixanol injection, USP may be stored in a contrast media warmer for up to one month at 37°C (98.6°F).

Do not freeze.

Discard any product that is inadvertently frozen, as freezing may compromise the closure integrity of the immediate container.

DO NOT USE IF TAMPER-EVIDENT RING IS BROKEN OR MISSING.

Protect iodixanol injection, USP from direct exposure to sunlight.

Store iodixanol injection, USP at controlled room temperature, 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) .

Iodixanol injection, USP may be stored in a contrast media warmer for up to one month at 37°C (98.6°F).

Do not freeze.

Discard any product that is inadvertently frozen, as freezing may compromise the closure integrity of the immediate container.

DO NOT USE IF TAMPER-EVIDENT RING IS BROKEN OR MISSING.

There are no data with iodixanol use in pregnant women to inform any drug-associated risks.

In animal reproduction studies, no developmental toxicity occurred with intravenous iodixanol administration to rats and rabbits at doses up to 0.24 (rat) or 0.48 (rabbit) times the maximum recommended human intravenous dose.

All pregnancies have a background risk of birth defect, loss or other adverse outcomes.

In the

U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Reproduction studies were performed in rats and rabbits with intravenous administration of iodixanol at doses up to 2 g Iodine/kg, daily, from implantation of the embryo (gestation day in rat; 6 in rabbit) through closure of the hard palate (gestation day in rats; 18 in rabbits).

No maternal toxicity occurred, and no adverse effects occurred on fetal survival, embryo-fetal development, or the ability of dams to rear a litter.

The safety and efficacy of iodixanol have been established in pediatric patients down to birth for angiocardiography, cerebral arteriography, visceral arteriography, CT imaging of the head and body, and excretory urography.

The safety and efficacy of iodixanol have also been established in pediatric patients 12 years and older for intra-arterial digital subtraction angiography, peripheral arteriography, peripheral venography and CCTA.

Use of iodixanol is supported by evidence from adequate and well controlled studies of iodixanol in adults and additional safety data obtained in 459 pediatric patients.

In general, the types of adverse reactions reported are similar to those of adults.

A higher number of adverse events in patients less than 1 year of age compared to older patients were observed in a study of iodixanol.

The elimination of iodixanol is slower in this.

Thyroid function tests indicative of thyroid dysfunction, characterized by hypothyroidism or transient thyroid suppression have been reported following iodinated contrast media administration in pediatric patients, including term and preterm neonates.

Some patients were treated for hypothyroidism.

After exposure to iodinated contrast media, individualize thyroid function monitoring in pediatric patients to 3 years of age based on underlying risk factors, especially in term and preterm neonates.

Pediatric patients at higher risk of experiencing an adverse reaction during and after administration of any contrast agent may include those with asthma, hypersensitivity to other medication and/or allergens, cyanotic and acyanotic heart disease, congestive heart failure, or a serum creatinine greater than 1.5 mg/dL.

Pediatric patients with immature renal function or dehydration may be at increased risk for adverse events due to slower elimination of iodinated contrast agents.

In clinical studies of iodixanol, 254/757 (34%) of patients were and over.

No overall differences in safety or effectiveness were observed between these patients and younger patients.

Other reported clinical experience has not identified differences in response between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

In general, dose selection for an elderly patient should be cautious usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.