Ioxaglic acid

1268.86

1268.88

261-560-1

Z40X7EI2AF

DTXSID5023166

C61793

V - Various

2924296000

194

2.51 (est)

2.545g/cm3

>254°C

887.9ºC at 760 mmHg

490.8ºC

1.786

H2O: soluble

Store in tight container as defined in the USP-NF. This material should be handled and stored per label instructions to ensure product integrity.

1.83X10-39 mm Hg at 25 deg C (est)

pKa = 0.99 (carboxylic acid) (est)

NONH for all modes of transport

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.

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

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.

Ioxaglate was detected at a concentration range of approximately 500 to 4.0X10+6 ng/L in an industrial waste water of the Netherlands in 2002(1).

Adverse reactions after administration of iodinated contrast agents may be worsened in patients displaying agitation, anxiety, and pain. Appropriate management, such as sedation, may be required before the procedure. Adequate hydration and normal electrolyte balance must be ensured, especially in elderly patients, infants, small children, patients with renal damage (oliguria, polyuria) or hyperuricemia, multiple myeloma, patients diagnosed with plasmacytoma or diabetes mellitus, particularly if it is longstanding. As this drug is a contrast agent, it may cause minor or major reactions that may be serious or lethal. They may be rapid (within 60 minutes) or delayed (up to 1 week). Emergency measures must be immediately available in high risk individuals, especially in patients taking B-blockers in whom adrenaline and vascular perfusion would not be effective. There are several conditions in which caution must be observed while administering this contrast drug: **Renal Disease/Hepatic Disease** Particular attention is required if the patient has both hepatic and renal failure, which increases the risk of contrast agent retention. **Cardiovascular Disease** In patients with manifest or incipient heart failure, coronary disease, pulmonary hypertension, or valvular heart disease, the risks of pulmonary edema, myocardial ischemia and arrhythmia and severe hemodynamic disturbances is heightened after the administration of an iodinated contrast agent. Cases of Torsade de Pointes have been identified in patients using sodium and meglumine ioxaglate, therefore loxaglic acid should be administered very carefully to patients who have/may develop prolongation of QTc, including patients taking other medicines that contribute to cardiovascular QT prolongation. **Pheochromocytoma Patients** Patients with phaeochromocytoma may suddenly develop hypertension after intravascular administration of a contrast agent, which may require appropriate management before the examination **Thyroid Disease** Following injection of iodinated contrast agent, specifically in patients with goiter or a history of hypothyroidism, there is a risk of either an episode of hyperthyroidism or induction of a new episode of hypothyroidism. There is also a risk of hypothyroidism in newborns who have received, or whose mother has received, an iodinated contrast agent. Screening for hypothyroidism should be performed routinely after administration of the product to newborns and judiciously to premature babies by assaying TSH and possibly free T4, 7-10 days and 1 month after iodine overload. **Asthma** Asthma should be controlled before injecting the iodinated contrast agent. Particular attention is required if the asthmatic attack has occurred within eight days prior to administration of loxagic acid, because of the increased risk for bronchospasm. **Myasthenia gravis** Administration of a contrast agent may exacerbate the symptoms of myasthenia gravis. **Use in pregnancy** In the patient screening and with appropriate tests, it is advisable to identify possible pregnancy in women of childbearing age. Exposure of the female genital tract to x-rays warrants careful evaluation of the benefit-to-risk ratio.

Intravenous injection of ioxaglate (4 g iodine kg(-1)), an iodinated radiographic contrast medium, caused a marked protein extravasation, pulmonary edema and a decrease in the arterial partial oxygen pressure in rats. All of these reactions to ioxaglate were reversed by the pretreatment with gabexate mesilate (10 and 50 mg kg(-1), 5 min prior to injection) or nafamostat mesilate (3 and 10 mg kg(-1)), in which the inhibition was complete after injection of nafamostat mesilate (10 mg kg(-1)). Both gabexate mesilate and nafamostat mesilate inhibited the activity of purified human lung tryptase, although the latter compound was far more potent than the former. Ioxaglate enhanced the nafamostat-sensitive protease activity in the extracellular fluid of rat peritoneal mast cell suspensions. Tryptase enhanced the permeability of protein through the monolayer of cultured human pulmonary arterial endothelial cells. Ioxaglate, when applied in combination with rat peritoneal mast cells, also produced the endothelial barrier dysfunction. These effects of tryptase and ioxaglate were reversed by nafamostat mesilate. Consistent with these findings, immunofluorescence morphological analysis revealed that tryptase or ioxaglate in combination with mast cells increased actin stress fiber formation while decreasing VE-cadherin immunoreactivity. Both of these actions of tryptase and ioxaglate were reversed by nafamostat mesilate. These findings suggest that tryptase liberated from mast cells plays a crucial role in the ioxaglate-induced pulmonary dysfunction. In this respect, nafamostat mesilate may become a useful agent for the cure or prevention of severe adverse reactions to radiographic contrast media.|Renal failure has been reported in patients with liver dysfunction who were given an oral cholecystographic agent followed by an intravascular iodinated radiopaque agent and also in patients with occult renal disease, notably diabetics and hypertensives. In these classes of patients there should be no fluid restriction and every attempt made to maintain normal hydration, prior to contrast medium administration, since dehydration is the single most important factor influencing further renal impairment.

LD50 Dog intravenous >10.2 g Iodine/kg|LD50 Rabbit intravenous >6.4 g Iodine/kg|LD50 Rat intravenous >8.0 g Iodine/kg|LD50 Rat intravenous 13,300 mg/kg|LD50 Mouse intravenous 11.2 g Iodine/kg

In patients with advanced renal disease, iodinated contrast media should be used with caution and only when the need for the examination dictates, since excretion of the medium may be impaired. Patients with combined renal and hepatic disease, those with severe hypertension or congestive heart failure and recent renal transplant recipients present an additional risk. Renal failure has been reported in patients with liver dysfunction who were given an oral cholecystographic agent followed by an intravascular iodinated radiopaque agent and also in patients with occult renal disease, notably diabetics and hypertensives. In these classes of patients there should be no fluid restriction and every attempt made to maintain normal hydration, prior to contrast medium administration, since dehydration is the single most important factor influencing further renal impairment.|Since intravascular administration of contrast media may promote sickling in individuals who are homozygous for sickle cell disease, fluid restriction is not advised.|Administration of radiopaque materials to patients known or suspected to have 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 treatment of a hypertensive crisis should be available.|Angiography should be avoided whenever possible in patients with homocystinuria because of the risk of inducing thrombosis and embolism.|For more Populations at Special Risk (Complete) data for Ioxaglate (9 total), please visit the HSDB record page.

Ioxaglic acid binds very weakly to plasma proteins and is quickly eliminated unchanged by the kidneys (glomerular filtration with no re-absorption or tubular secretion).

Ioxaglate's production and use as a diagnostic contrast agent(1) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 10(SRC), determined from a structure estimation method(2), indicates that ioxaglate is expected to have very high mobility in soil(SRC). The estimated pKa of ioxaglate is 0.99(3), indicating that this compound will exist almost entirely in the anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization from moist soil is not expected because the compound exists as an anion and anions do not volatilize. Ioxaglate is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.8X10-39 mm Hg at 25 °C(SRC), determined from a fragment constant method(5). Iodinated X-ray contrast agents are considered non-biodegradable by microorganisms(6).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 10(SRC), determined from a structure estimation method(2), indicates that ioxaglate is not expected to adsorb to suspended solids and sediment(SRC). An estimated pKa of 0.99(3) indicates ioxaglate will exist almost entirely in the anion form at pH values of 5 to 9 and, therefore, volatilization from water surfaces is not expected to be an important fate process(SRC). According to a classification scheme(4), an estimated BCF of 3(SRC), from an estimated log Kow of 2.51(5) and a regression-derived equation(6), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Iodinated X-ray contrast agents are considered non-biodegradable by microorganisms(7).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), ioxaglate, which has an estimated vapor pressure of 1.8X10-39 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase ioxaglate may be removed from the air by wet or dry deposition(SRC). Ioxaglate contains chromophores that absorb at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

Iodated diagnostic contrast agents such as diatrizoate are very persistent in aquatic environments(1). Ioxaglate is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(2). Ioxaglate contains chromophores that absorb at wavelengths >290 nm(2) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 3 was calculated in fish for ioxaglate(SRC), using an estimated log Kow of 2.51(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of ioxaglate can be estimated to be 10(SRC). According to a classification scheme(2), this estimated Koc value suggests that ioxaglate is expected to have very high mobility in soil. The estimated pKa of ioxaglate is 0.99(3), indicating that this compound will exist almost entirely in the anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).

The estimated pKa of ioxaglate is 0.99(1), indicating that this compound will primarily exist as an anion in the aqueous environment and anions do not volatilize from water or moist soil surfaces. Ioxaglate is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.8X10-39 mm Hg(SRC), determined from a fragment constant method(2).

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).|SURFACE WATER: Ioxaglate concentrations in surface water of the Netherlands between 1996 and 2005 ranged from approximately 12 to 50 ng/L with an outlier at 300 ng/L(1).

Ioxaglate salts cross the placental barrier in humans and are excreted unchanged in human milk.

Occupational exposure to ioxaglate may occur through dermal contact with this compound at workplaces where ioxaglate is produced or used. Limited monitoring data indicate that the general population may be exposed to ioxaglate via dermal contact with water containing this compound. Exposure to ioxaglate among the general population may be limited to those administered the drug. (SRC)

This medicinal product is for diagnostic use only in adults and children as a low-osmolality medium,.

Intravascular injection of a radiopaque diagnostic agent opacifies those vessels in the path of the flow of the contrast medium, permitting radiographic visualization of the internal structures of the human body until significant hemodilution occurs.|Contrast Media|THERAPEUTIC CATEGORY: Diagnostic aid (radiopaque medium)|HEXABRIX is indicated for use in pediatric angiocardiography, selective coronary arteriography with or without left ventriculography, peripheral arteriography, aortography, selective visceral arteriography, cerebral angiography, intra-arterial digital subtraction angiography, intravenous digital subtraction angiography, peripheral venography (phlebography), excretory urography, contrast enhancement of computed tomographic head imaging and body imaging, arthrography and hysterosalpingography. /Included in US product label/|For more Therapeutic Uses (Complete) data for Ioxaglate (7 total), please visit the HSDB record page.

/BOXED WARNING/ SEVERE 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.|Ionic iodinated contrast media inhibit blood coagulation, in vitro, more than nonionic contrast media. Nonetheless, it is prudent to avoid prolonged contact of blood with syringes containing ionic contrast media. Serious, rarely fatal, thromboembolic events causing myocardial infarction and stroke have been reported during angiographic 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. 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 or 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 contrast medium reaction.|As with any contrast medium, serious neurologic sequelae, including permanent paralysis, can occur following cerebral arteriography, selective spinal arteriography and arteriography of vessels supplying the spinal cord. The injection of a contrast medium should never be made following the administration of vasopressors since they strongly potentiate neurologic effects. In patients with subarachnoid hemorrhage, a rare association between contrast administration and clinical deterioration, including convulsions and death, has been reported. Therefore, administration of intravascular iodinated contrast media in these patients should be undertaken with caution.|A definite risk exists in the use of intravascular contrast agents in patients who are known to have multiple myeloma. In such instances anuria has developed resulting in progressive uremia, renal failure and eventually death. Although neither the contrast agent nor dehydration has separately proved to be the cause of anuria in myeloma, it has been speculated that the combination of both may be causative factors. The risk in myelomatous patients is not a contraindication to the procedure; however, partial dehydration in the preparation of these patients for the examination is not recommended since this may predispose to precipitation of myeloma protein in the renal tubules. No form of therapy, including dialysis, has been successful in reversing the effect. Myeloma, which occurs most commonly in persons over 40, should be considered before instituting intravascular administration of contrast agents.|For more Drug Warnings (Complete) data for Ioxaglate (29 total), please visit the HSDB record page.

This drug allows for the visualization of important organs and structures in the body. It binds to tissues, allowing the blockage of X-rays and diagnostic visualization in various soft tissues and body cavities. The joint spaces in addition to the uterus and fallopian tubes may be visualized by the direct injection of the contrast medium into the region to be studied.

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

Following the intravascular route of injection, Ioxaglic acid is rapidly transported through the circulatory system to the kidneys. The pharmacokinetics of radiopaque contrast media given by the IV route are described by a two-compartment model with a rapid alpha phase for drug distribution and a slow beta phase for the elimination of the drug. Following the intravenous administration of 50 mL of ioxaglic acid in 10 healthy volunteers, the mean peak plasma concentration occurred at two (1-3) minutes, reaching a concentration of 2.1 (1.8-2.8) mg/mL. Approximately 50 percent of the intravenously administered dose was recovered in the urine at two hours, and 90% percent was recovered at the 24 hour time point.|Excreted unchanged in the urine The liver and small intestine provide the major alternate route of excretion. In patients with severe renal impairment, the excretion of this contrast medium through the gallbladder and into the small intestine sharply increases.|Ioxaglate salts cross the placental barrier in humans and are excreted unchanged in human milk.|245 ml/kg|Following intravascular injection, HEXABRIX is rapidly transported through the circulatory system to the kidneys and is excreted unchanged in the urine. The pharmacokinetics of intravascularly administered radiopaque contrast media are usually best described by a two compartment model with a rapid alpha phase for drug distribution and a slower beta phase for drug elimination.|Following the intravenous administration of 50 mL of HEXABRIX in 10 normal volunteers, the mean peak plasma concentration occurred at two (1-3) minutes, reaching a concentration of 2.1 (1.8-2.8) mg/mL. Approximately 50 (42-67) percent of the intravenously administered dose was recovered in the urine at two hours, and 90 (68-105) percent was recovered at 24 hours.|Following intravenous injection, HEXABRIX is rapidly excreted by the kidneys. HEXABRIX may be visualized in the renal parenchyma one minute following bolus injection. Maximum radiographic density in the calyces and pelves occurs in most instances within 7 to 12 minutes after injection. In patients with severe renal impairment, contrast visualization may be substantially delayed.|In brain scanning, contrast media do not accumulate in normal brain tissue due to the blood brain barrier (BBB). The increase in x-ray attenuation usually seen in normal tissue following contrast medium injection is due to the presence of the contrast medium in the blood pool. Disruption in the BBB, such as occurs in malignant tumors of the brain, allows accumulation of contrast medium within the interstitial tumor tissue; adjacent normal brain tissue does not contain the contrast medium.|For more Absorption, Distribution and Excretion (Complete) data for Ioxaglate (8 total), please visit the HSDB record page.

Excreted unchanged.

Hexabrix 320 is rapidly eliminated by the kidneys with a half-life of about 90 minutes|In 10 patients with normal renal function, the alpha and beta half-lives of HEXABRIX were 12 (4-17) and 92 (61-140) minutes, respectively.

Ioxaglic acid is an iodine-containing, low osmolality contrast agent. Ioxaglate is a molecule that consists of six iodine atoms and achieves water solubility by ionization; thus, it is a 3.0 ratio ionic agent. By far the most successful and widely used contrast agents in use today are the iodinated contrast media, which were introduced into clinical practice in the 1950s. Approximately 75 million doses of iodinated contrast agents are administered worldwide each year. The iodinated contrast agents fall into 4 groups. Each group has unique chemical, physical, and biologic properties. These various contrast agents are required to meet the demands of a broad variety of imaging modalities. All agents share a similar function group—a tri-iodinated benzene ring. Iodine plays an imperative role in the attenuation of x-ray signal. The atomic radius of a covalently bonded iodine atom is about 133 picometers, falling within the same range of the wavelengths of x-rays: 10 to 10,000 picometers. Therefore, x-rays are easily attenuated by the iodine atoms. In addition, iodine atoms covalently bonded to a benzene ring have 2 main advantages: (1) 3 large atoms located in such close proximity increase the effective molecular size, attenuating longer-wavelength x-rays, and (2) covalent bonding to a stable organic functional group (for example, benzene) decrease the risk of toxic adverse effects from free iodide molecules. Ionization is an important characteristic to note in contrast media preparations. Compounds are classified as either ionic or nonionic. The ionic compounds dissociate in aqueous solution and therefore have a higher osmolality. The anion is the radiopaque portion of the molecule, however, both the anion and cation are osmotically active. Compared with nonionic media such as ioxaglic acid, ionic contrast media have more adverse hemodynamic effects, especially in patients with heart disease. The nonionic media are water soluble but do not dissociate in solution. Nonionic agents possess lower osmolality because there are fewer particles in solution. The nonionic contrast agents are more hydrophilic than ionic agents, resulting in lower osmolality, reduced binding to plasma proteins, decreased tissue binding, and a decreased tendency to cross cell membranes. The low-osmolality of ioxaglic acid reduces the risk of adverse events. The occurrence of adverse reactions is more common after the use of high-osmolarity agents: about 15% with a high-osmolarity agent versus 3% with a low-osmolarity agent. The use of high-osmolarity agents has decreased significantly in recent years. Most adverse effects and adverse reactions to this group of drugs are multifactorial and are likely due to a combination of direct cellular toxicity, the ionic state (for example, ionic vs nonionic), or the osmolarity of the injected contrast drug.

Ioxaglate salts are dialyzable.|Prophylactic therapy including corticosteroids and antihistamines should be considered for patients who present with a strong allergic history, a previous reaction to a contrast medium, or a positive pre-test since in these patients the incidence of reaction is two to three times that of the general population. Adequate doses of corticosteroids should be started early enough prior to contrast medium injection to be effective and should continue through the time of injection and for 24 hours after injection. Antihistamines should be administered within 30 minutes of the contrast medium injection. Recent reports indicate that such pre-treatment does not prevent serious life-threatening reactions, but may reduce both their incidence and severity. A separate syringe should be used for these injections.|/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/

/HUMAN EXPOSURE STUDIES/ ...Ioxaglate was administered intra-arterially to 20 consecutive patients ... ...The intra-arterially administered contrast medium elicited a marked increase of /fibrinopeptide A (FpA) and thrombin-antithrombin III complexes (TAT)/, together with an anticoagulant effect. /The authors conclude that ioxaglate is/ able to interfere with the clotting/fibrinolytic system in the general circulation when /it is/ administered to patients at the usual dosages. ... The procedure (ie, arterial catheter versus intravenous infusion) seems to be more important than the category of contrast medium in conditioning the magnitude of these effects.|/HUMAN EXPOSURE STUDIES/ ... In a multicenter study, 20 patients with mild to severe reactions to iodinated contrast material and 20 control subjects without reactions were evaluated. Ionic contrast material was associated with 18 (90%) of 20 reactions. Concentrations of plasma histamine, tryptase, urinary methylhistamine, specific immunoglobulin E (IgE) against ioxitalamate or ioxaglate, and the anaphylatoxins C3a and C4a were measured with radioimmunoassays; complement C3 and C4 levels were measured with nephelometry. Histamine levels were increased in 14 patients; tryptase levels, in 16; and methylhistamine levels, in six. Histamine and tryptase values correlated with the severity of the reaction (P < 0.02 and P < 0.004, respectively). Significantly higher levels of specific IgE against ioxaglate (P < 0.005) and ioxitalamate (P = 0.045) were found in patients. No differences were found for complement fractions. Skin test results in two patients with life-threatening reactions were positive for the administered contrast material. /Investigators concluded that/ histamine release and mast cell triggering are related to severe reactions. An IgE-related mechanism is strongly suspected. ...|/HUMAN EXPOSURE STUDIES/ ... Twenty-one patients undergoing either intravenous pyelography or arteriography with Ioxaglate were studied. Renal clearance studies were carried out 1 day before and 1 day after administration of Ioxaglate (173 +/- 37 mL) injected into each patient. None experienced any adverse reaction. Mean serum creatinine, glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and urinary NAG excretion were unaltered by ioxaglate. No patient suffered a nephrotoxic reaction or acute oliguria that required dialysis as a result of the administration of contrast material. In the subset of seven patients receiving cyclosporine the same results were observed. In the subset of 10 patients with a GFR lower than 60 mL/min before injection of Ioxaglate were also observed no significant change in mean GFR, ERPF and urinary NAG excretion. Only two patients had a transient decrease of GFR of between 10 and 20%. The results of this study show that the ionic, low osmolar contrast medium ioxaglate may be used safely in patients with a renal transplant thus extending previous data obtained in patients with chronic renal failure.|/HUMAN EXPOSURE STUDIES/ The effect of thyroid function was investigated in 22 patients undergoing arteriography with a new low osmolality contrast medium--sodium and meglumine ioxaglate (Hexabrix). Plasma thyroxine (T4), thyroxine resin uptake (TRU) and free thyroxine index (FTI) were measured before and at varying intervals up to 56 days after the arteriogram. Despite the large doses of Hexabrix used (up to 89.6 g of iodine), these tests of thyroid function did not reveal any significant change from pre-angiographic levels. It is concluded that Hexabrix as used for arteriography does not affect thyroid function. /sodium meglumine ioxaglate/|For more Human Toxicity Excerpts (Complete) data for Ioxaglate (29 total), please visit the HSDB record page.

Hexabrix

Each milliliter /of HEXABRIX/ contains 393 mg of ioxaglate meglumine, 196 mg of ioxaglate sodium and 0.10 mg edetate calcium disodium as a stabilizer. The solution contains 3.48 mg (0.15 mEq) sodium in each milliliter and provides 32% (320 mg/mL) organically bound iodine.|/Available as:/ HEXABRIX Glass Vials/Bottles 25x50 mL vials; 12x100 mL fill/150 mL bottles; 12x200 mL fill/250 mL bottles.