Iodixanol

1550.18

1550.18

1533716-785-6

HW8W27HTXX

760069

DTXSID2045523

C65931

V08AB09|V - Various

2924299090

339

0.5

Solid

1.32 g/cm³

262-267°C (dec.)

1250.9±65.0 °C at 760 mmHg

710.3±34.3 °C

n 1.4128 ±0.0003

Freely soluble in water, sparingly soluble in methanol, practically insoluble in methylene chloride.

Refrigerator

0 mm Hg at 25 deg C (est)

LD50 i.v. in mice: 21 gI/kg (Palmers)

7.2-7.6 (c = 320 mg I/L)

Osmolality 290 mOsm/kg H2O|Hydroxyl radical reaction rate constant = 1.19X10-10 cu cm/molec-sec at 25 °C (est)

NONH for all modes of transport

Stable and nont reactive.

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.|SRP: Wastewater from contaminant suppression, cleaning of protective clothing/equipment, or contaminated sites should be contained and evaluated for subject chemical or decomposition product concentrations. Concentrations shall be lower than applicable environmental discharge or disposal criteria. Alternatively, pretreatment and/or discharge to a permitted wastewater treatment facility is acceptable only after review by the governing authority and assurance that "pass through" violations will not occur. Due consideration shall be given to remediation worker exposure (inhalation, dermal and ingestion) as well as fate during treatment, transfer and disposal. If it is not practicable to manage the chemical in this fashion, it must be evaluated in accordance with EPA 40 CFR Part 261, specifically Subpart B, in order to determine the appropriate local, state and federal requirements for disposal.

/Investigators sought/ to test the compatibility of trisodium citrate, a catheter lock solution, with iodinated contrast medium. ...Ioxaglate... was tested. In all tests, 2 mL of contrast medium were mixed with 2 mL of trisodium citrate solution. ...Ioxaglate provoked a highly viscous gluelike precipitation when mixed with trisodium citrate. /It was concluded that/one must be aware of the potential for precipitation when contrast medium is mixed with trisodium citrate solution. Before trisodium citrate solution is injected, the catheter should be thoroughly flushed with saline if a contrast medium has previously been injected through it.

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including iodixanol, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

Respiratory Protection: Where respirators are deemed necessary to reduce or control occupational exposures, use NIOSH-approved respiratory protection and have an effective respirator program in place. Gloves: Chemically compatible. For handling solutions, ensure that the glove material is protective against the solvent being used. Use handling practices that minimize direct hand contact. Employees who are sensitive to natural rubber (latex) should use nitrile or other synthetic nonlatex gloves. Use of powdered latex gloves should be avoided due to the risk of latex allergy. Eye Protection: Safety glasses with sideshields are recommended. Face shields or goggles may be required if splash potential exists or if corrosive materials are present. Approved eye protection (e.g., bearing the ANSI Z87 or CSA stamp) is preferred. Maintain eyewash facilities in the work area. Protective clothing: For handling of laboratory scale quantities, a cloth lab coat is recommended. Where significant quantities are handled, work clothing may be necessary to prevent take-home contamination.|Airborne exposure should be controlled primarily by engineering controls such as general dilution ventilation, local exhaust ventilation, or process enclosure. Local exhaust ventilation is generally preferred to general exhaust because it can control the contaminant at its source, preventing dispersion into the work area. An industrial hygiene survey involving air monitoring may be used to determine the effectiveness of engineering controls. Effectiveness of engineering controls intended for use with highly potent materials should be assessed by use of nontoxic surrogate materials. Local exhaust ventilation such as a laboratory fume hood or other vented enclosure is recommended, particularly for grinding, crushing, weighing, or other dust-generating procedures.

As with all fires, evacuate personnel to a safe area. Firefighters should use self-contained breathing equipment and protective clothing.|Water spray, dry chemical, carbon dioxide, or foam as appropriate for surrounding fire and materials.

Wear approved respiratory protection, chemically compatible gloves, and protective clothing. Wipe up spillage or collect spillage using a high-efficiency vacuum cleaner. Avoid breathing dust. Place spillage in appropriately labeled container for disposal. Wash spill site.

As a general rule, when handling USP Reference Standards, avoid all contact and inhalation of dust, mists, and/or vapors associated with the material. Clean equipment and work surfaces with suitable detergent or solvent after use. After removing gloves, wash hands and other exposed skin thoroughly.|As with all dry powders, it is advisable to ground mechanical equipment in contact with dry material to dissipate the potential buildup of static electricity.|SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.|SRP: Contaminated protective clothing should be segregated in such a manner so that there is no direct personal contact by personnel who handle, dispose, or clean the clothing. The completeness of the cleaning procedures should be considered before the decontaminated protective clothing is returned for reuse by the workers. Contaminated clothing should not be taken home at the end of shift, but should remain at employee's place of work for cleaning.

Non-ionic radiocontrast agents like iodixanol are cytotoxic to renal cells. The toxic effects include apoptosis, cellular energy failure, disruption of calcium homeostasis, and disturbance of tubular cell polarity, and are thought to be linked to oxidative stress.

The reported incidence of adverse reactions to contrast agents in patients with a history of allergy is twice that of the general population. Patients with a history of a previous reaction to a contrast agent are three times more susceptible than other patients. However, sensitivity to contrast media does not appear to increase with repeated examinations.|Administration of radiopaque materials to patients known to have, or suspected of having, pheochromocytoma should be performed with extreme caution. ... These patients should be monitored very closely during contrast-enhanced procedures.|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.|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.. ...|For more Populations at Special Risk (Complete) data for Iodixanol (9 total), please visit the HSDB record page.

Negligible

DRINKING WATER: It has been suggested that in all countries with an advanced medical care system, x-ray contrast media can be expected to be present in sewage effluent which, therefore, leads to potential contamination of receiving waters(1).

Occupational exposure to iodixanol may occur through inhalation and dermal contact with this compound at workplaces where iodixanol is produced or used. Exposure to iodixanol among the general population may include those administered this contrast agent. (SRC)

Iodixanol is a contrast agent during coronary angiography.|FDA Label

Iodixanol is indicated for contrast enhanced computerized tomography imaging of the head and body, excretory urography, and peripheral venography. /Included in US product label/|Iodixanol is indicated for angiocardiography (left ventriculography and selective coronary arteriography), peripheral arteriography, visceral arteriography, and cerebral arteriography. /Included in US product label/|Iodixanol is indicated for intra-arterial digital subtraction angiography. /Included in US product label/|Iodixanol is indicated for contrast enhanced computerized tomography imaging of the head and body, and excretory urography. /Included in US product label/|For more Therapeutic Uses (Complete) data for Iodixanol (6 total), please visit the HSDB record page.

The following selected adverse events were reported in ?0.5% of the 1244 patients in controlled clinical trials who received iodixanol injection: 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.|Additional adverse events reported in other clinical studies and in foreign postmarketing surveillance and foreign clinical trials with the use of iodixanol 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.|... 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.|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.|For more Drug Warnings (Complete) data for Iodixanol (28 total), please visit the HSDB record page.

Iodixanol is a contrast agent commonly used 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 imaging contrast agent with the same osmolality as blood (290mOsm/kg H20).

Substances used to allow enhanced visualization of tissues. (See all compounds classified as Contrast Media.)

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.|0.26 L/kg|Absorption and excretion of iodixanol 320 mg I/ml were investigated in rats after intragastric administration of 2.5 g I/kg b.w. Animals were observed for up to 96 hours after treatment, and blood, urine and feces taken at several time-points throughout the experiment. Concentrations of iodixanol in serum and urine were measured by means of reversed-phase high-performance liquid chromatography. Fecal concentrations of iodixanol, based on iodine measurements, were determined by X-ray fluorescence spectrometry. Serial radiographs were obtained and histopathological examination was performed on selected tissues. The results indicate that less than 1% of the intragastric dose of iodixanol is absorbed from the intestine into the blood stream. No adverse clinical signs were observed, and there were no treatment-related histomorphological findings.|In 40 healthy, young male volunteers receiving a single intravenous administration of iodixanol injection in doses of 0.3 to 1.2 gI/kg body weight, ... renal clearance was 110 mL/min (+/-14), equivalent to glomerular filtration (108 mL/min). These values were independent of the dose administered.|... In a study of 16 adult patients who were scheduled for renal transplant, the elimination of iodixanol 320 mgI/mL was studied. The patients' baseline mean creatinine levels were 6.3 mg/dL (+/-1.5) and mean creatinine clearances were 13.61 mL/min (+/- 4.67). ... In these patients, levels of iodixanol were detected 5 days after dosing. Contrast enhancement time in kidneys increased from 6 hours to at least 24 hours. ...|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.|For more Absorption, Distribution and Excretion (Complete) data for Iodixanol (14 total), please visit the HSDB record page.

Excreted unchanged|Iodixanol metabolites have not been demonstrated.

2.1 hours. In patients with significantly impaired renal function (mean creatinine clearance rate, 9.91 [± 3.58] mL per minute), the plasma half-life is increased to 23 hours.|Forty pediatric patients < or = 12 years old, with renal function that is normal for their age, received multiple intra-arterial administrations of iodixanol injection in doses of 0.32 to 3.2 gI/kg body weight. The elimination half-lives for these patients are ...: 0.185 hr -1 (newborn to 2 months old), 0.256 hr -1 (2 to <6 months old), 0.299 hr -1 (6 months to<1 year), 0.322 hr -1 (1 to<2 years), and 0.307 hr -1 (2 to < or = 12 years old). The adult mean terminal elimination rate constant is 0.336 hr-1. ...|In 40 healthy, young male volunteers receiving a single intravenous administration of iodixanol injection in doses of 0.3 to 1.2 gI/kg body weight, the elimination half-life was 2.1 hr (+/- 0.1) ...|... Iodixanol was rapidly excreted, mainly via the kidneys, with a plasma half-life in rats and monkeys of 25 and 76 mins, respectively. ...|... In a study of 16 adult patients who were scheduled for renal transplant, the elimination of iodixanol 320 mgI/mL was studied. ... In these patients, the plasma half-life was increased to 23 hours (normal t1/2 = 2 hours). ...

Organic iodine compounds attenuate x-rays as they pass through the body, thereby allowing the body structures containing iodine to be delineated in contrast to those structures that do not contain iodine. The degree of opacity produced by these compounds is directly proportional to the total amount (concentration and volume) of the iodinated contrast agent in the path of the x-rays. After intravascular administration, iodixanol makes opaque those internal structures in its path of flow, allowing their visualization until significant hemodilution and elimination occur.|Intravascular injection of iodixanol opacifies those vessels in the path of flow of the contrast agent, permitting radiographic visualization of the internal structures until significant dilution and elimination occurs.

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/SIGNS AND SYMPTOMS/ 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.|/SIGNS AND SYMPTOMS/ ... 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.|/SIGNS AND SYMPTOMS/ Additional adverse events reported in other clinical studies and in foreign postmarketing surveillance and foreign clinical trials with the use of iodixanol 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.|/CASE REPORTS/ ... A 76-year-old woman with a history of coronary artery disease was admitted to the emergency department for recurrent transient ischemic attacks. Before combined percutaneous transluminal coronary angioplasty and carotid artery stenting (CAS) using iodixanol, the patient suffered from concomitant unstable angina and recurrent transient ischemic attacks. The total amount of iodixanol used during the CAS procedure was 300 mL. Contrast-induced encephalopathy, which manifested as aphasia, stupor, and full hemiparesis immediately after the combined procedure, was diagnosed by urgent computed tomography. Treatment was based on anti-edema drugs, and the patient made a complete recovery within 48 hours, without any neurological sequelae. ...|For more Human Toxicity Excerpts (Complete) data for Iodixanol (14 total), please visit the HSDB record page.

contrast media 2-5410-3

Visipaque

Iodixanol is a widely used iso-osmolar contrast medium agent. Similar to iohexol, it can also be a good exogenous marker for the measurement of glomerular filtration rate (GFR). /Investigators present/ the development and validation of an HPLC-UV method for quantification of iodixanol in human plasma. Internal standard, iohexol (20 uL, 1 mg/mL), and perchloric acid (30 uL, 20%, v/v) were added to plasma samples (300 uL), followed by neutralization with 10 uL potassium carbonate (5M). Samples were centrifuged and 10 uL of the supernatant was injected onto a C(18) EPS analytical column (3 um particle size, 150 mm x 4.6 mm). The extraction method yielded >95% recovery for both iodixanol and iohexol. The mobile phase consisted of 0.1% (w/v) sodium formate buffer and acetonitrile. Iohexol and iodixanol peaks were eluted at approximately 5 and 9 min, respectively using a fast gradient method. The assay lower limit of detection was 2.0 ug/mL and lower limit of quantification was 10 ug/mL. The calibration curves, assessed in six replicates, were linear over an iodixanol concentration range of 10-750 ug/mL. Intra- and inter-day accuracy was >95% and precision expressed as % coefficient of variation was <10%. This method is simple, accurate, precise and robust and can potentially be used for iodixanol quantification in large-scale clinical studies.|A simple isocratic high-performance liquid chromatographic method was developed for the determination of iodixanol in human plasma. Samples containing an internal standard were prepared for analysis using a simple clean-up procedure based on Sep-Pak C18 solid-phase extraction and chromatographed using a size-exclusion column with purified water as a mobile phase. The iodixanol peak was completely separated from the peaks of an internal standard and endogenous substances on this column. Three geometric isomers (exo-exo, endo-exo and endo-endo forms) of iodixanol could be eluted as a single peak. The method was found to be applicable to pharmacokinetic studies of iodixanol in human plasma.

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients