Iodixanol

Soluble in water

1.85e-01 g/L

Breast Feeding; Lactation; Milk, Human; Contrast Media; Diagnostic Agents

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

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.

/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.

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.

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.

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.

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.

/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.

/LABORATORY ANIMALS: Acute Exposure/ The neural tolerability of iodixanol has been assessed in studies in mice and dogs. The animals received up to 4 injections in the cisterna cerebellomedullaris while under light anesthesia. Iotrolan was included as a reference study in 1 study. The observations comprised assessment of clinical behavior, cerebrospinal fluid analysis, hematology, clinical chemistry and/or macroscopic and microscopic examination at necropsy. In addition, the repeated-dose dog study, urinalysis and opthalmoscopy were performed, electrocardiograms obtained, and respiratory rate, blood pressure and rectal temperature measured. Clinical signs and minor pathological changes caused by the injection procedures were seen in all studies in some animals treated with iodixanol as well as in control animals. Single (2.0 g I/kg) and repeated (0.960 g I/kg) intracisternal administration of iodixanol to mice caused no significant toxicological effects. Two dogs treated with a high dose of iodixanol (0.256 g I/kg; 0.8 mL/kg) had pathological changes (meningeal inflammation and/or necrosis) that were more severe than those observed in control dogs. Single and repeated intracisternal administration of 0.128 g I/kg (0.4 mL/kg) of iodixanol to dogs, however, caused no significant toxicological effects. Apart from the findings in the 2 dogs, the neurological and neuropathological changes elicited by iodixanol were similar to those induced by control or reference substances. The results from these intracisternal toxcity studies in mice and dogs indicate a significant margin of safety regarding the use of iodixanol in clinical intra-thecal indications.

/LABORATORY ANIMALS: Acute Exposure/ The effects of the ... contrast media (CM) iodixanol on renal function and morphology were investigated in 7 independent studies in rats, rabbits and monkeys and compared with other iodinated CM. No significant effect on serum creatinine levels was seen at doses up to and including 5 g I/kg in rats and 10.5 g I/kg in rabbits. An immediate and transient increase in proteinuria was found in rabbits when 10.5 g I/kg was administered as a bolus, and when 12.5 g I/kg was administered as a slow infusion in a comparative study with several CM. Increased serum elimination half-life was shown by measuring serum iodine concentrations after the infusion of 12.5 g I/kg. The effect of a high dose of iodixanol on proteinuria and elimination half-life were in this study in the same range as those of the monomeric nonionic CM, but less pronounced than those of the monomeric ionic CM. Reduced renal capacity was induced in male rats by performing unilateral nephrectomy 4 weeks before i.v. injection of iodixanol or iopamidol (2g I/kg). The administration of CM did not affect renal function monitored as serum concentrations of creatinine and urea. The vacuolation of renal proximal tubular cells and kidney iodine retention were investigated in rats 48 hours after administration of different doses of iodixanol or iotrolan. The no-effect level for vacuolation was 0.5 g I/kg for both CM. Iodine retention was higher in male than females rats, and was higher for iodixanol than iotrolan at the 2 highest dose levels (3 and 5 g I/kg). No difference in iodine retention was found at the other dose levels (0.25-1g I/kg). The reversibility of renal proximal tubular vacuolation after administration of iodixanol was studied in male rats (1.2 g I/kg) and monkeys (1.2 and 3.6 g I/kg). The vacuolation was more pronounced in rats than in monkeys. Vacuolation was completely reversed in all rats 3 weeks after dosing, and 2 of 3 monkeys 3 days after a dose of 1.2 g I/kg. The degree of vacuolation evident in renal percutaneous biopsy specimens from monkeys 14 days after i.v. administration of iodixanol at a dose of 3.5 g I/kg was not significantly different to that in control animals. In conclusion, iodixanol affected renal function to the same degree as did the nonionic monomeric and dimeric comparative media, but to a lesser degree than the ionic monomers. The degree of renal proximal tubular cell vacuolation induced by iodixanol seems to be species-dependent, being less pronounced and more quickly reversed in monkeys than rats.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Long-term animal studies have not been performed with iodixanol to evaluate carcinogenic potential.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ 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.

For more Non-Human Toxicity Excerpts (Complete) data for Iodixanol (9 total), please visit the HSDB record page.

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.

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)

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).

/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/

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.

V08AB09

V - Various

QV - Various

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).

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.

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). ...

Excreted unchanged

Iodixanol metabolites have not been demonstrated.

HW8W27HTXX

IODIXANOL

Established Pharmacologic Class [EPC] - Radiographic Contrast Agent

Mechanisms of Action [MoA] - X-Ray Contrast Activity

Iodixanol is a Radiographic Contrast Agent. The mechanism of action of iodixanol is as a X-Ray Contrast Activity.

IODIXANOL

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.

MEDICATION

Use (kg; approx.) in Germany (2009): >5000