Iodixanol

Iodixanol
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Gloria Picoy [2]

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Overview

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Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Intra-arterial

• Iodixanol 270 mgI/mL is indicated for intra-arterial digital subtraction angiography.
• Iodixanol 320 mgI/mL is indicated for angiocardiography (left ventriculography and selective coronary arteriography), peripheral arteriography, visceral arteriography, and cerebral arteriography.

Intravenous

• Iodixanol (270 mgI/mL) is indicated for CECT imaging of the head and body, excretory urography, and peripheral venography.
• Iodixanol (320 mgI/mL) is indicated for CECT imaging of the head and body, and excretory urography.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Iodixanol in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Iodixanol in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

The recommended dose in children over 1 year of age for the evaluation of:

Intra-arterial Administration for Cerebral, Cardiac chambers and related major arteries, and Visceral Studies

VISIPAQUE 320 mgI/mL as 1 to 2 mL/kg. The recommended total dose of VISIPAQUE should not exceed 4 mL/kg.

Intravenous Administration for Contrast Enhanced Computerized Tomography or Excretory Urography

VISIPAQUE 270 mgI/mL as 1 to 2 mL/kg. The recommended total dose of VISIPAQUE should not exceed 2 mL/kg.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Iodixanol in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Iodixanol in pediatric patients.

Contraindications

• Iodixanol is not indicated for intrathecal use.
• In the pediatric population prolonged fasting and the administration of a laxative before VISIPAQUE injection are contraindicated.

Warnings

Serious adverse events-Inadvertent intrathecal administration

Serious adverse reactions have been reported due to the inadvertent intrathecal administration of iodinated contrast media that are not indicated for intrathecal use. These serious adverse reactions include: death, convulsions, cerebral hemorrhage, coma, paralysis, arachnoiditis, acute renal failure, cardiac arrest, seizures, rhabdomyolysis, hyperthermia, and brain edema. Special attention must be given to insure that this drug product is not administered intrathecally.

Nonionic, iodinated contrast media inhibit blood coagulation in vitro less than ionic contrast media. Clotting has been reported when blood remains in contact with syringes containing nonionic contrast media. The use of plastic syringes in place of glass syringes has been reported to decrease but not eliminate the likelihood of in vitro clotting.

Serious, rarely fatal, thromboembolic events causing myocardial infarction and stroke have been reported during angiocardiographic procedures with both ionic and nonionic contrast media. Therefore, meticulous intravascular administration technique is necessary, particularly during angiographic procedures, to minimize thromboembolic events. Numerous factors, including length of procedure, catheter and syringe material, underlying disease state, and concomitant medications, may contribute to the development of thromboembolic events. For these reasons, meticulous angiographic techniques are recommended, including close attention to guidewire and catheter manipulation, use of manifold systems and/or three-way stopcocks, frequent catheter flushing with heparinized saline solutions, and minimizing the length of the procedure.

Serious or rare fatal reactions have been associated with the administration of iodine-containing radiopaque media. It is of utmost importance to be completely prepared to treat any reaction associated with the use of any contrast agent.

Caution must be exercised in patients with severely impaired renal function, combined renal and hepatic disease, combined renal and cardiac disease, severe thyrotoxicosis, myelomatosis, or anuria, particularly when large doses are administered.

Intravascularly administered iodine-containing radiopaque media are potentially hazardous in patients with multiple myeloma or other paraproteinaceous diseases, who are prone to disease induced renal insufficiency and/or renal failure. Although neither the contrast agent nor dehydration has been proven to be the cause of renal insufficiency (or worsening renal insufficiency) in myelomatous patients, it has been speculated that the combination of both may be causative. Special precautions, including maintenance of normal hydration and close monitoring, are required. Partial dehydration in the preparation of these patients is not recommended since it may predispose the patient to precipitation of the myeloma protein.

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

Administration of radiopaque materials to patients known to have, or suspected of having, pheochromocytoma should be performed with extreme caution. If, in the opinion of the physician, the possible benefits of such procedures outweigh the considered risks, the procedures may be performed; however, the amount of radiopaque medium injected should be kept to an absolute minimum. The blood pressure should be assessed throughout the procedure, and measures for the treatment of hypertensive crisis should be readily available. These patients should be monitored very closely during contrast-enhanced procedures.

Contrast agents may promote sickling in individuals who are homozygous for sickle cell disease when the agents are administered intravascularly.

Dehydration, Renal Insufficiency, Congestive Heart Failure

Preparatory dehydration is dangerous and may contribute to acute renal failure in patients with advanced vascular disease, congestive heart disease, diabetic patients, and other patients such as those on medications which alter renal function and the elderly with age-related renal impairment. Patients should be adequately hydrated prior to and following intravascular administration of iodinated contrast agent. Dose adjustments in renal impairment have not been studied.

Iodinated contrast agents may cross the blood-brain barrier. In patients where the blood-brain barrier is known or suspected to be disrupted, or in patients with normal blood-brain barrier and associated renal impairment, CAUTION MUST BE EXERCISED IN THE USE OF AN IODINATED CONTRAST AGENT.

Patients with congestive heart failure receiving concurrent diuretic therapy may have relative intravascular volume depletion, which may affect the renal response to the contrast agent osmotic load. These patients should be observed following the procedure to detect delayed hemodynamic renal function disturbances.

Immunologic Reactions

The possibility of a reaction, including serious, life-threatening, fatal, anaphylactoid or cardiovascular reactions, should always be considered. Increased risk is associated with a history of a previous reaction to contrast agent, a known sensitivity to iodine and known allergies (i.e., bronchial asthma, drug, or food allergies), other hypersensitivities, and underlying immune disorders, autoimmunity or immunodeficiencies that predispose to specific or nonspecific mediator release. If during administration there is evidence of an allergy-like reaction, the injection should be discontinued and appropriate treatment initiated.

Skin testing cannot be relied upon to predict severe reactions and may itself be hazardous to the patient. A thorough medical history with emphasis on allergy and hypersensitivity, immune, autoimmune and immunodeficiency disorders, and prior receipt of and response to the injection of any contrast agent may be more accurate than pretesting in predicting potential adverse reactions.

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. Extreme caution should be exercised in considering the use of iodinated contrast agents in patients with these histories or disorders. Patients with a history of allergy or drug reaction should be observed for several hours after drug administration.

Anesthesia

General anesthesia may be indicated in the performance of some procedures in selected patients; however, a higher incidence of adverse reactions have been reported in these patients. It is not clear if this is due to the inability of the patient to identify untoward symptoms or to the hypotensive effect of anesthesia, which can prolong the circulation time and increase the duration of exposure to a contrast agent.

Angiocardiography

In angiographic procedures, the possibility of dislodging plaques, or damaging or perforating the vessel wall with resultant pseudoaneurysms, hemorrhage at puncture site, dissection of coronary artery, etc., should be considered during catheter manipulations and contrast agent injection. Angiography may be associated with local and distal organ damage, ischemia, thrombosis and organ failure (e.g., brachial plexus palsy, chest pain, myocardial infarction, sinus arrest, hepatorenal function abnormalities, etc.). Test injections to ensure proper catheter placement are suggested. During these procedures, increased thrombosis and activation of the complement system has also occurred.

Angiocardiography should be avoided whenever possible in patients with homocystinuria because of the risk of inducing thrombosis and embolism.

In an uncontrolled study of 204 patients who received VISIPAQUE Injection and who had cardiovascular disease associated with either Class II-IV congestive failure, angina, recent myocardial infarction, left ventricular ejection fraction of < 35% or valvular disease, the patients were evaluated for the types of interventions needed for treatment of adverse events. The reported type and frequency of adverse events were comparable to those in all clinical intra-arteriographic studies. Of 204 patients, 63 (31%) of patients had 99 adverse events. Of the 99 events, 68 (68%) required medical intervention of some type. Patients with 17 (17%) of these adverse events required treatment with cardioversion, multiple medications, prolonged hospitalization or intensive care. These interventions were not compared to a control group of similar patients who did not have coronary arteriography.

Selective coronary arteriography should be performed only in patients for whom the expected benefits outweigh the procedural risk. Also, the inherent risks of angiocardiography in patients with chronic pulmonary emphysema must be weighed against the necessity for performing this procedure.

Venography

In addition to the general precautions previously described, special care is required when venography is performed in patients with suspected thrombosis, phlebitis, severe ischemic disease, local infection, venous thrombosis or a totally obstructed venous system.

Extreme caution during injection of a contrast agent is necessary to avoid extravasation. This is especially important in patients with severe arterial or venous disease.

Adverse Reactions

Clinical Trials Experience

Iodixanol was administered to 1244 patients. The comparators administered to 861 patients included low osmolar nonionic, and high and low osmolar ionic contrast media.

Serious, life-threatening and fatal reactions have been associated with the administration of iodine-containing contrast media, including VISIPAQUE Injection. In clinical trials, 3/1244 patients given VISIPAQUE Injection and 1/861 patients given a comparator died within 5 days or later after drug administration. Also, 7/1244 patients given VISIPAQUE Injection and 8/861 given a comparator had serious adverse events. Rare reports of anaphylaxis have been documented during postmarket surveillance.

As with other contrast agents, VISIPAQUE is often associated with sensations of discomfort, warmth or pain. In a subgroup of 1259 patients, for whom data are available; similar percentages of patients (30%) who received VISIPAQUE or a comparator had application site discomfort, pain, warmth or cold. VISIPAQUE had a trend toward fewer patient reports of moderate or severe pain or warmth; however, whether or not this related to the dose, rate of administration, site of injection or concentration has not been determined.

The following table of incidence of events is based upon blinded, controlled clinical trials with VISIPAQUE Injection in controlled clinical studies in which VISIPAQUE (1244 patients) was compared with low osmolar nonionic (iohexol, iopromide), a low osmolar ionic (ioxaglate), and a high osmolar ionic (diatrizoate) contrast agents. This listing includes all reported adverse events regardless of attribution. Adverse events (AEs) are listed by body system and in decreasing order of occurrence greater than 0.5% in the VISIPAQUE group.

As the table shows, one or more adverse events were recorded in 248 of 1244 (20%) patients during the clinical trials, with the administration of VISIPAQUE Injection or within the defined duration of the study follow-up period (24 to 72 hours). In intravenous and intra-arterial procedures, the incidence and type adverse reaction was similar to those of the studied nonionic comparators (iohexol). In a 757 patient subgroup for which data are available, women reported more adverse events 83/299 (27.8%) than men 77/458 (16.2%). Women reported more chest pain (9/299 or 3%) than men (4/458 or 0.8%).

The following selected adverse events were reported in ≤0.5% of the 1244 patients in controlled clinical trials who received VISIPAQUE Injection.

• Body as a Whole—General Disorders: back pain, fatigue, malaise.
• Cardiovascular Disorders: arrhythmias, cardiac failure, conduction abnormalities, hypotension, myocardial infarction.
• Nervous System: cerebral vascular disorder, convulsions, hypoesthesia, stupor, confusion.
• Gastrointestinal System Disorders: dyspepsia.
• Hypersensitivity Disorders: pharyngeal edema.
• Respiratory System Disorders: asthma, bronchitis, dyspnea, pulmonary edema, rhinitis.
• Renal System Disorders: abnormal renal function, acute renal failure, hematuria.
• Peripheral Vascular Disorders: flushing, peripheral ischemia.
• Skin and Appendage Disorders: hematoma, increased sweating.
• Special Senses, Other Disorders: tinnitus.
• Vision Disorders: abnormal vision.

Postmarketing Experience

Additional adverse events reported in other clinical studies and in foreign postmarketing surveillance and foreign clinical trials with the use of VISIPAQUE Injection are: anaphylactic reactions, anaphylactoid reactions, hypoglycemia, amnesia, cardiac arrest, hypertension, dyskinesia, hemorrhage not otherwise specified, polymyalgia rheumatica, pulmonary embolism, respiratory depression, and cortical blindness.

Adverse Reactions in Pediatric Patients

The overall character, quality, and severity of adverse reactions in pediatric patients is similar to that reported in adult populations from domestic and foreign postmarketing surveillance and other information. Selected commonly reported adverse events in pediatrics include: vomiting, nausea, fever, rash, and pruritus. Less frequently reported events are apnea, disseminated intravascular coagulation, atrioventricular block and bundle branch block, arrhythmia, cardiac failure, renal failure and taste perversion.

Drug Interactions

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

Other drugs should not be mixed with VISIPAQUE Injection.

Drug/Laboratory test interactions

The results of protein bound iodine and radioactive iodine uptake studies, which depend on iodine estimation, will not accurately reflect thyroid function for at least 16 days following administration of iodinated contrast agents. However, thyroid function tests which do not depend on iodine estimations (e.g., T3 resin uptake and total or free thyroxine T4 assays) are not affected.

As reported with other contrast agents, VISIPAQUE may produce a false-positive result for protein in the urine using Multistix®. However, the Coomassie blue method has been shown to give accurate results for the measurement of urine protein in the presence of VISIPAQUE. In addition, care should be used in interpreting the results of urine specific gravity measurements in the presence of high levels of VISIPAQUE and other contrast agents in the urine. Refractometry or urine osmolality may be substituted.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): B Reproduction studies performed in rats and rabbits at doses up to 2.0 gI/kg [1.3 times the maximum recommended dose for a 50 kg human, or approximately 0.2 (rat) and 0.4 (rabbit) times the maximum recommended dose for a 50 kg human following normalization of the data to body surface estimates] have not revealed evidence of impaired fertility or harm to the fetus due to iodixanol. Adequate and well-controlled studies in pregnant women have not been conducted. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Iodixanol in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Iodixanol during labor and delivery.

Nursing Mothers

It is not known whether VISIPAQUE Injection is excreted in human milk. However, many injectable contrast agents are excreted unchanged in human milk. Although it has not been established that serious adverse reactions occur in nursing infants, caution should be exercised when intravascular contrast agents are administered to nursing women because of the potential for adverse reactions, and consideration should be given to temporarily discontinue nursing.

Pediatric Use

The safety and efficacy of VISIPAQUE has been established in the pediatric population over 1 year of age for arterial studies and for intravenous procedures. Use of VISIPAQUE in these age groups is supported by evidence from adequate and well controlled studies of VISIPAQUE in adults and additional safety data obtained in pediatric studies. Although VISIPAQUE has been administered to pediatric patients less than 1 year of age, the relative safety of the volumes injected, the optimal concentrations, and the potential need for dose adjustment because of prolonged elimination half-lives have not been systematically studied.

Iodixanol was administered to 459 pediatric patients. There were 26 patients administered VISIPAQUE Injection in the birth to <29 day age range, 148 from 29 days to 2 years, 263 from 2 to <12 years, and 22 from 12 to 18 years. The mean age was 4.4 years (range <1 day to 17.4 years). Of the 459 patients, 252 (55%) were male and 207 (45%) were female. The racial distribution was: Caucasian-81%, Black-14%, Oriental-2%, and other or unknown-4%. The demographic information for the pool of patients who received a comparison contrast agent was similar.

In pediatric patients who received intravenous injection for computerized tomography or excretory urography, a concentration of 270 mgI/mL was used in 144 patients, and a concentration of 320 mgI/mL in 154 patients. All patients received one intravenous injection of 1-2 mL/kg.

In pediatric patients who received intra-arterial and intracardiac studies, a concentration of 320 mgI/mL was used in 161 patients. Of the 161 patients in the intra-arterial studies, the mean age was 2.6 years. Twenty-two patients were < 29 days of age; 78 were 29 days to 2 years of age; and 61 were over 2 years. Most of these pediatric patients received initial volumes of 1-2 mL/kg and most patients had a maximum of 3 injections.

Optimal volumes, concentrations or injection rates of VISIPAQUE have not been established because different injection volumes, concentrations, and injection rates were not studied. The relationship of the volume of injection with respect to the size of the target vascular bed has not been established. The potential need for dose adjustment to maximize efficacy of computerized tomography, or to minimize the toxicity to other immature body tissues, has not been studied in neonates or infants with immature renal function.

In the above patients, adverse events were associated with decreasing age and intra-arterial procedures. In general the type of adverse events reported are similar to those of adults. Although the frequency of events appears to be comparable, the percentages cannot be confirmed because of the different ability of pediatric and adult patients to report adverse events.

Geriatic Use

Of the total number of patients in clinical studies of VISIPAQUE in the U.S., 254/757 (34%) were 65 and over. No overall differences in safety or effectiveness were observed between these patients and younger patients, and 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. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Gender

There is no FDA guidance on the use of Iodixanol with respect to specific gender populations.

Race

There is no FDA guidance on the use of Iodixanol with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Iodixanol in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Iodixanol in patients with hepatic impairment.

Females of Reproductive Potential and Males

Iodixanol did not impair the fertility of male or female rats when administered at doses up to 2.0 gI/kg (1.3 times the maximum recommended dose for a 50 kg human, or approximately 0.2 times the maximum recommended dose for a 50 kg human following normalization of the data to body surface area estimates).

Immunocompromised Patients

There is no FDA guidance one the use of Iodixanol in patients who are immunocompromised.

Administration and Monitoring

Administration

Intravenous

Monitoring

There is limited information regarding Iodixanol Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Iodixanol and IV administrations.

Overdosage

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. VISIPAQUE Injection does not bind to plasma or serum protein and can be dialyzed.

Pharmacology

There is limited information regarding Iodixanol Pharmacology in the drug label.

Mechanism of Action

There is limited information regarding Iodixanol Mechanism of Action in the drug label.

Structure

Iodixanol has the following chemical structure:

Pharmacodynamics

As with other iodinated contrast agents, following administration of VISIPAQUE Injection, the degree of enhancement is directly related to the iodine content in an administered dose; peak iodine plasma levels occur immediately following rapid intravascular injection. Iodine plasma levels fall rapidly within 5 to 10 minutes. This can be accounted for by the dilution in the vascular and extravascular fluid compartments.

Intravascular Contrast

Contrast enhancement with iodinated contrast agents appears to be greatest immediately after bolus injections (15 seconds to 120 seconds). Thus, greatest enhancement may be detected by a series of consecutive two-to-three second scans performed within 30 to 90 seconds after injection (i.e., dynamic computed tomographic imaging).

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.

Contrast Enhanced Computerized Tomography (CECT)

AS WITH OTHER IODINATED CONTRAST AGENTS, THE USE OF VISIPAQUE INJECTION CONTRAST ENHANCEMENT MAY OBSCURE SOME LESIONS WHICH WERE SEEN ON PREVIOUSLY UNENHANCED CT SCANS.

In CECT some performance characteristics are different in the brain and body. In CECT of the body, iodinated contrast agents diffuse rapidly from the vascular into the extravascular space. Following the administration of iodinated contrast agents, the increase in tissue density to x-rays is related to blood flow, the concentration of the contrast agent, and the extraction of the contrast agent by various interstitial tissues. Contrast enhancement is thus due to relative differences in extravascular diffusion between adjacent tissues.

In normal brain with an intact blood-brain barrier, contrast enhancement is generally due to the presence of iodinated contrast agent within the intravascular space. The radiographic enhancement of vascular lesions, such as arteriovenous malformations and aneurysms, depends on the iodine content of the circulating blood pool.

In tissues with a break in the blood-brain barrier, contrast agent accumulates within interstitial spaces of the brain. The time to maximum contrast enhancement can vary from the time that peak blood iodine levels are reached to one hour after intravenous bolus administration. This delay 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. The mechanism by which this occurs is not clear.

IN PATIENTS WITH NORMAL BLOOD-BRAIN BARRIERS and RENAL FAILURE, iodinated contrast agents have been associated with blood-brain barrier DISRUPTION and ACCUMULATION OF CONTRAST IN THE BRAIN.

The usefulness of contrast enhancement for the investigation of the retrobulbar space and of low grade or infiltrative glioma has not been demonstrated. Calcified lesions are less likely to enhance. The enhancement of tumors after therapy may decrease. The opacification of the inferior vermis following contrast agent administration has resulted in false-positive diagnosis. Cerebral infarctions of recent onset may be better visualized with contrast enhancement. Older infarctions may be obscured by the contrast agent.

Pharmacokinetics

Distribution

In an in vitro human plasma study, iodixanol did not bind to protein. The volume of distribution was 0.26 L/kg body weight, consistent with distribution to extracellular space.

Metabolism

Iodixanol metabolites have not been demonstrated.

Excretion

Plasma and urine levels suggest that body clearance of iodixanol is primarily due to renal clearance. 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. In 40 healthy, young male volunteers receiving a single intravenous administration of VISIPAQUE Injection in doses of 0.3 to 1.2 gI/kg body weight, the elimination half-life was 2.1 hr (± 0.1); and renal clearance was 110 mL/min (±14), equivalent to glomerular filtration (108 mL/min). These values were independent of the dose administered.

Nonclinical Toxicology

Carcinogenesis and mutagenesis

Long-term animal studies have not been performed with iodixanol to evaluate carcinogenic potential. Iodixanol was not genotoxic in a series of studies including the Ames test, the CHO/HGPRT assay, a chromosome aberration assay in CHO cells, and a mouse micronucleus assay.

Clinical Studies

Iodixanol was administered to 1244 adult patients. The comparators administered to 861 adult patients included low osmolar nonionic, and high and low osmolar ionic contrast media. Approximately one-half (590) of the VISIPAQUE patients were 60 years of age or older; the mean age was 56 years (range 18-90). Of the 1244 patients, 806 (65%) were male and 438 (35%) were female. The racial distribution was: Caucasian-85%, Black-12%, Oriental <1%, and other or unknown-3%. The demographic information for the pool of patients who received a comparison contrast agent was similar.

There were 1235 patients given VISIPAQUE and 855 patients given other contrast agents were evaluated for efficacy. Efficacy assessment was based on quality of the radiographic diagnostic visualization (i.e., either excellent, good, poor, or none) and on the ability to make a diagnosis (i.e., either confirmed a previous diagnosis, found normal, or diagnosed new findings). Results were compared to those of active controls (ioxaglate, iohexol, iopromide, and meglumine-sodium diatrizoate) at concentrations which were similar to those of VISIPAQUE Injection.

Intra-arterial administration

Angiocardiography, cerebral arteriography, peripheral arteriography, and visceral arteriography were studied with either one or both concentrations of VISIPAQUE Injection (270 mgI/mL or 320 mgI/mL). In these intra-arterial studies, diagnostic visualization ratings were good or excellent in 100% of the patients and a radiologic diagnosis was made in all (100%) of the patients given VISIPAQUE Injection. In additional intra-arterial studies, overall quality of diagnostic visualization was rated optimal in the majority of patients and a radiologic diagnosis was made in all (100%) of the patients administered VISIPAQUE Injection. Results were compared to those of active controls (ioxaglate, iohexol, iopromide). The number of patients studied in each indication is provided below.

Angiocardiography was evaluated in two randomized, double-blind clinical trials in 101 adult patients given VISIPAQUE Injection 320 mgI/mL and 97 given iohexol 350 mgI/mL. Seven additional angiocardiography studies were performed in 217 adult patients given VISIPAQUE Injection 320 mgI/mL, 37 given iohexol 350 mgI/mL, 40 given meglumine-sodium diatrizoate 370 mgI/mL, and 96 given ioxaglate 320 mgI/mL. Visualization ratings were good or excellent in 100% of the patients given VISIPAQUE; a radiologic diagnosis was made in the majority of the patients. The results were similar to those of the active controls. Confirmation of the radiologic findings by other diagnostic methods was not obtained.

Cerebral arteriography was evaluated in two randomized, double-blind clinical trials in 51 adult patients given VISIPAQUE Injection 320 mgI/mL and 48 given iohexol 300 mgI/mL. Two additional cerebral arteriography studies were performed in 15 adult patients given VISIPAQUE Injection 270 mgI/mL, 40 patients given VISIPAQUE Injection 320 mgI/mL, and 40 patients given ioxaglate 320 mgI/mL. Visualization ratings were good or excellent in 100% of the patients given VISIPAQUE a radiologic diagnosis was made in the majority of the patients. The results were similar to those of the active controls. Confirmation of the radiologic findings by other diagnostic methods was not obtained.

Peripheral arteriography was evaluated in two randomized, double-blind clinical trials in 49 adult patients given VISIPAQUE Injection 320 mgI/mL, 25 given iohexol 350 mgI/mL, and 25 given ioxaglate 320 mgI/mL. Four additional peripheral arteriography studies were performed in 41 adult patients given VISIPAQUE Injection 270 mgI/mL, 85 patients given VISIPAQUE Injection 320 mgI/mL, 37 given iohexol 300 mgI/mL, and 47 given iopromide 300 mgI/mL. Visualization ratings were good or excellent in 100% of the patients given VISIPAQUE; a radiologic diagnosis was made in the majority of the patients. The results were similar to those of the active controls. Confirmation of the radiologic findings by other diagnostic methods was not obtained.

Visceral arteriography was evaluated in two randomized, double-blind clinical trials in 55 adult patients given VISIPAQUE Injection 320 mgI/mL, 26 given iohexol 350 mgI/mL, and 25 given ioxaglate 320 mgI/mL. Visualization ratings were good or excellent in 100% of the patients given VISIPAQUE; a radiologic diagnosis was made in the majority of the patients. The results were similar to iohexol. Confirmation of the radiologic findings by other diagnostic methods was not obtained. The risk added to renal arteriography by giving VISIPAQUE could not be analyzed.

Similar studies with digital subtraction angiography (DSA) were completed with comparable findings noted in cerebral arteriography, peripheral arteriography, and visceral arteriography. Studies have not been conducted to determine the lowest effective concentration.

Intravenous administration

Excretory urography, contrast-enhanced computed tomography (CECT) of the head, CECT of the body, and peripheral venography were studied with either one or both VISIPAQUE Injection concentrations (270 mgI/mL or 320 mgI/mL). In these intravenous studies, diagnostic visualization ratings were good or excellent in 96-100% of the patients and a radiologic diagnosis was made in all (100%) of the patients given VISIPAQUE Injection. Results were compared to those of the active control. The number of patients studied in each indication is provided below.

Excretory urography was evaluated in one uncontrolled, unblinded clinical trial in 40 patients, 20 given VISIPAQUE Injection 270 mgI/mL and 20 given VISIPAQUE Injection 320 mgI/mL, and in two randomized, double-blind clinical trials in 50 adult patients given VISIPAQUE Injection 270 mgI/mL, 50 patients given VISIPAQUE Injection 320 mgI/mL, and 50 patients given iohexol 300 mgI/mL. Visualization ratings were good or excellent in 100% of the patients given VISIPAQUE; a radiologic diagnosis was made in the majority of the patients. The results were similar to those of the active control. Confirmation of the radiologic findings by other diagnostic methods was not obtained.

CECT of the head was evaluated in two randomized, double-blind clinical trials in 49 adult patients given VISIPAQUE Injection 270 mgI/mL, in 50 patients given VISIPAQUE Injection 320 mgI/mL, and in 49 patients given iohexol 300 mgI/mL. CECT of the body was evaluated in three randomized, double-blind clinical trials in 104 adult patients given VISIPAQUE Injection 270 mgI/mL, in 109 patients given VISIPAQUE Injection 320 mgI/mL, and in 101 patients given iohexol 300 mgI/mL. In both CECT of the head and body, visualization ratings were good or excellent in 100% of the patients given VISIPAQUE; a radiologic diagnosis was made in the majority of the patients. The results were similar to those of active controls. Confirmation of the radiologic findings by other diagnostic methods was not obtained.

Peripheral venography was evaluated in two randomized, double-blind clinical trials in 46 adult patients given VISIPAQUE Injection 270 mgI/mL and in 50 patients given iohexol 300 mgI/mL. Visualization ratings were good or excellent in 100% of the patients given VISIPAQUE; a radiologic diagnosis was made in the majority of the patients. The results were similar to those of the active control. Confirmation of the radiologic findings by other diagnostic methods was not obtained.

How Supplied

• Iodixanol Injection 270 mgI/mL
• Iodixanol Injection 320 mgI/mL

Storage

Stored between 20°C-25°C (68°F-77°F)

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

Patients receiving an iodinated intravascular contrast agent should be instructed to:

• Inform your physician if you are pregnant.
• Inform your physician if you are diabetic or if you have multiple myeloma, pheochromocytoma, homozygous sickle cell disease, or known thyroid disorder.
• Inform your physician if you are allergic to any drugs or food, or if you have immune, autoimmune or immune deficiency disorders. Also inform your physician if you had any reactions to previous injections of dyes used for x-ray procedures.
• Inform your physician about all medications you are currently taking, including nonprescription (over-the-counter) drugs, before you have this procedure.

Precautions with Alcohol

Alcohol-Iodixanol interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Iodixanol Brand Names in the drug label.

Look-Alike Drug Names

There is limited information regarding Iodixanol Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

Iodixanol

File:Iodixanol-2D-skeletal.svg
Pharmacokinetic data
Protein binding	Negligible
Metabolism	Excreted unchanged
Elimination half-life	2.1 hours
Excretion	Renal
Identifiers
IUPAC name 5 - [acetyl - [3 - [acetyl - [3,5-bis(2,3 - dihydroxypropylcarbamoyl) - 2,4,6 - triiodo - phenyl]amino] - 2 - hydroxy - propyl]amino] - N,N' - bis(2,3 - dihydroxypropyl) - 2,4,6 - triiodo - benzene - 1,3 - dicarboxamide
CAS Number	92339-11-2
PubChem CID	3724
E number	{{#property:P628}}
ECHA InfoCard	{{#property:P2566}}
Chemical and physical data
Formula	C35H44I6N6O15
Molar mass	1550.191

Iodixanol, is a contrast agent, sold under the trade name Visipaque®. Visipaque is commonly used as a contrast agent during coronary angiography, particularly in individuals with renal dysfunction, as it is believed to be less toxic to the kidneys than most other intravascular contrast agents. It is an iso-osmolar contrast agent, with an osmolality of 290 mOsm/kg H₂O, the same as blood. It is sold in 2 main concentrations 270 mgI/ml and 320 mgI/ml - hence the name Visipaque 270 or 320. It is sold in single dose units and a large 500ml plastic bottle for multi-dose dispensing

It was originally made by Nycomed, which then merged with Amersham which finally was bought by Jeff Immelt to become GE Healthcare. The majority of Visipaque is made in Cork, Ireland, with additional plants in China and Oslo. All Iodixanol bulk powder is made in Norway and shipped to the various plants for final manufacture.

For gradient density centrifugation, the product is known as OptiPrep.

A very similar product also manufactured by GE Healthcare is Omnipaque (Iohexol as the main drug substance).

External links

• [3]
• Template:DailyMed