Adipiodon

1139.76

1139.76

210-105-5

TKQ858A3VW

DTXSID6023153

C61791

Crystals|White, crystalline powder

V - Various

2924296000

133

5.16 (est)

Solid

2.8g/cm3

307 °C (decomp)

908.6ºC at 760 mmHg

503.3ºC

nD21.5 1.3294 (c = 0.445 in methanol)

0.46g/L(20 ºC)

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

1.07X10-24 mm Hg at 25 deg C (est)

LD50 in mice, rats (mg/kg): 2380 ±290, 4430 ±310 i.v. (Rosenberg)

Nearly odorless

pH of saturated solution is 3.5-5.9

pKa = 1.44 (est)

NONH for all modes of transport

3

DG0949500

In the event that crystallization occurs, the solution may be clarified by placing the vial in hot water and shaking gently for several minutes or until the solids redissolve. If cloudiness persists, discard the preparation. Allow the solution to cool to body temperature before administering.

P264, P280, P302+P352, P305+P351+P338, P321, P332+P313, P337+P313, P362

H315

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.

Diphenhydramine hydrochloride (Benadryl) and meglumine iodipamide (Cholografin) were mixed in varying proportions and found to consistently form a dense amorphous precipitate.

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

|Warning|H315 (100%): Causes skin irritation [Warning Skin corrosion/irritation]|P264, P280, P302+P352, P305+P351+P338, P321, P332+P313, P337+P313, and P362|The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.

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.

Ionic radiocontrast agents like iodipamide 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. Acute IV LD50 is 5000 mg/kg in rat, 3195 mg/kg in mouse, and 1200 mg/kg in dog.

FDA Pregnancy Risk Category: D /POSITIVE EVIDENCE OF RISK. Studies in humans, or investigational or post-marketing data, have demonstrated fetal risk. Nevertheless, potential benefits from the use of the drug may outweigh the potential risk. For example, the drug may be acceptable if needed in a life-threatening situation or serious disease for which safer drugs cannot be used or are ineffective./|Administration of radiopaque materials to patients known or suspected to have pheochromocytoma should be performed with extreme caution. ...|... It is also contraindicated in patients with concomitant severe impairment of renal and liver function.|Contrast media have been shown to promote the phenomenon of sickling in individuals who are homozygous for sickle cell disease when the material is injected intravenously or intra-arterially.

Iodipamide's production and use as a diagnostic contrast(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 1.4X10+4(SRC), determined from a structure estimation method(2), indicates that iodipamide is expected to be immobile in soil(SRC). However, the estimated pKa of iodipamide is 1.44(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. Iodipamide is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.1X10-24 mm Hg at 25 °C(SRC), determined from a fragment constant method(5). Iodinated X-ray contrast agents are considered nondegradable by microorganisms(6).|AQUATIC FATE: Iodipamide is not expected to adsorb to suspended solids and sediment based upon anionic nature of this compound. The estimated pKa of iodipamide is 1.44(1), indicating that this compound will exist primarily as an anion in the aqueous environment and anions do not volatilize from water. According to a classification scheme(2), an estimated BCF of 10(SRC), from an estimated log Kow of 5.16(3) and a regression-derived equation(4), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Iodinated X-ray contrast agents are considered nondegradable by microorganisms(5).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), iodipamide, which has an estimated vapor pressure of 1.1X10-24 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 iodipamide may be removed from the air by wet or dry deposition(SRC). Iodipamide does not contain chromophores that absorb at wavelengths >290 nm(4) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).

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

An estimated BCF of 10 was calculated in fish for iodipamide(SRC), using an estimated log Kow of 5.16(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 iodipamide can be estimated to be 1.4X10+4(SRC). According to a classification scheme(2), this estimated Koc value suggests that iodipamide is expected to be immobile in soil. The estimated pKa of iodipamide is 1.13(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 iodipamide is 1.44(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. Iodipamide is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.1X10-24 mm Hg(SRC), determined from a fragment constant method(2).

While data specific to iodipamide were not located(SRC, 2012), the literature suggests that some pharmaceutically active compounds originating from human and veterinary therapy are not eliminated completely in municipal sewage treatment plants and are therefore discharged into receiving waters(1). Wastewater treatment processes often were not designed to remove them from the effluent(2). Selected organic waste compounds may be degrading to new and more persistent compounds that may be released instead of or in addition to the parent compound(2).

Occupational exposure to iodipamide may occur through dermal contact with this compound at workplaces where iodipamide is produced or used. Use data indicate that limited general population exposure to iodipamide will be via administration of pharmaceutical products containing iodipamide. (SRC)

Iodipamide is used as a contrast agent for cholecystography and intravenous cholangiography.

Contrast Media|Cholografin Meglumine is indicated for intravenous cholangiography and cholecystography as follows: (a) visualization of the gallbladder and biliary ducts in the differential diagnosis of acute abdominal conditions, (b) visualization of the biliary ducts, especially in patients with symptoms after cholecystectomy, and (c) visualization of the gallbladder in patients unable to take oral contrast media or to absorb contrast media from the gastrointestinal tract. /Included in US product label/|THERAPEUTIC CATEGORY: Diagnostic aid (radiopaque medium-cholecystographic)|THERAPEUTIC CATEGORY (VETERINARY): Diagnostic aid (radiopaque medium)

Iodipamide meglumine is contraindicated for use in intrathecal procedures.|Iodipamide meglumine is contraindicated in patients with a hypersensitivity to salts of iodipamide or who exhibit sensitivity reactions to the test dose. It is also contraindicated in patients with concomitant severe impairment of renal and liver function.|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 inadvertently administered intrathecally.|The possibility exists for inadvertent administration into the intrathecal space during epidural administrations. Therefore, epidural administration procedures, such as pain management catheter placement, should not be performed with use of this product.|For more Drug Warnings (Complete) data for Iodipamide (15 total), please visit the HSDB record page.

Following intravenous administration of Cholografin Meglumine, iodipamide is carried to the liver where it is rapidly secreted. The contrast medium appears in the bile within 10 to 15 minutes after injection, thus permitting visualization of the hepatic and common bile ducts, even in cholecystectomized patients. The biliary ducts are readily visualized within about 25 minutes after administration, except in patients with impaired liver function. The gallbladder begins to fill within an hour after injection; maximum filling is reached after two to two and one-half hours. The contrast medium is finally eliminated in the feces without passing through the enterohepatic circulation, except for approximately 10 percent of the intravenously administered dose which is excreted through the kidneys.

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

To characterize the saturation kinetics of iodipamide, timed samples of blood, urine, and bile were taken from two unanesthetized dogs infused with iodipamide at increasing rates to achieve various steady state blood concentrations. Biliary excretion rate of iodipamide reached an asymptote with increasing blood concentration, indicating a biliary transport maximum (Tm) of 15.2 to 16.2 mgI/min. Urinary excretion was not a pure, first order process and urinary excretion rate was higher than the glomerular filtration rate corrected for plasma protein binding, suggesting that active tubular secretion may play a part. Extrarenal elimination followed Michaelis-Menten kinetics. Estimates of maximum rate (Vm) and Michaelis-Menten constant (Km) were obtained graphically. The estimated values of Vm were 4 to 6 times that of biliary Tm. In acute infusion experiments the iodipamide excreted in the bile and urine and that remaining in the organs analyzed accounted for only a fraction of the dose administered; no significant accumulation of iodipamide was found in the liver.|The contrast agent for biliary tract visualization, iodipamide, is strongly bound to serum albumin. The relationship between the affinity of the contrast agent for albumin and its preferential uptake and excretion by the liver has been unclear. The role of serum albumin on hepatic uptake and excretion of iodipamide therefore was investigated on the isolated perfused rabbit liver. With the perfusate containing fully reconstituted rabbit plasma protein or 3.5 g/100 mL rabbit albumin alone, the iodipamide excretion is initially extremely slow. It then increases gradually to about 6 mug/gm liver per min by 60 minutes and thereafter remains constant. The half-time of transfer to the bile is about 130 min. Without albumin in the perfusate the initial clearance rate of iodipamide is rapid, with half-time transfer to the bile of about 40 min. Rabbit serum globulins have no effect on iodipamide excretion. Thus, binding of iodipamide to albumin retards the transfer of iodipamide from plasma to the bile, probably due to competition between albumin and the anion binding protein of the liver.|The contrast medium is eliminated in the feces without passing through the enterohepatic circulation, except for approximately 10 percent of the intravenously administered dose which is excreted through the kidneys.

Hepatic.

Organic iodine compounds block x-rays as they pass through the body, thereby allowing body structures containing iodine to be delineated in contrast to those structures that do not contain iodine. The degree of opacity produced by these iodinated organic compounds is directly proportional to the total amount (concentration and volume) of the iodinated contrast agent in the path of the x-rays. Iodipamide's primary excretion through the hepato-biliary system and concentration in bile allows visualization of the gallbladder and biliary ducts.|... The iodine in the contrast medium is responsible for the absorption of x-rays and the resulting opacification of the organ system or other area under investigation. ...

/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/ 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 inadvertently administered intrathecally.|/CASE REPORTS/ A 73 year old patient with a chronic cholangitis developed protracted anaphylactic shock after intravenous injection of methylglucamine iodipamide. The post-mortem examinations showed no evidence for septicemia. Although endotoxin-shock cannot be completely excluded, the most likely cause of death was an allergic reaction.|/CASE REPORTS/ There have been only two reports of severe hepatotoxic reaction caused by meglumine iodipamide. Lately we experienced such a reaction in an 66-year old female with chronic intrahepatic cholestasis. After drip infusion cholangiography was performed by infusing 40 ml. of 50% meglumine iodipamide (Biligrafin) intravenously, the patient developed nausea and abdominal pain. Her serum transaminase rose to more than 2,000 K-A units on the third day and gradually returned to normal by the 18th day. The macrophage migration inhibition test of her blood was positive for meglumine iodipamide. Accordingly some delayed type of hypersensitivity in the above reaction could be considered. When a larger amount than a recommended dose of meglumine iodipamide is infused in cholangiography, a severe hepatotoxic reaction might be induced, especially in icteric cases.|/CASE REPORTS/ Linear densities which were thought to represent meglumine iodipamide were seen in the renal papillary tubules of three patients for respectively four, six and nine days following intravenous cholangiography (IVC). All three patients were children with hepato-biliary disease. Two patients had biliary roundworm infestation, and one patient had hepatic dysfunction and intestinal ascariasis with possible biliary involvement. Haematuria and renal enlargement were seen in one patient, but the cholangiogram was not conclusively implicated as a cause. This renal tubular "sludging" of biliary contrast medium is recorded because of its potential nephrotoxic significance. The possible causes are discussed.|/CASE REPORTS/ Two cases of meglumine iodipamide (Cholografin) hepatotoxicity were confirmed by liver biopsy. The hepatic lesion was centrilobular in location and resolved within a short period of time. Nausea and vomiting commonly reported after intravenous cholangiography may be clinical manifestations of this entity.

Adipiodon

Cholografin Meglumine (lodipamide Meglumine Injection USP 52%) is available in single dose vials of 20 mL

Iodipamide disodium salt used as 20% solution. Iodipamide bis(N-methylglucamine) salt is more soluble in water than the disodium salt. Used as 40% solution

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