Gadodiamide

573.66

574.102234

84F6U3J2R6

DTXSID9048647

C65795

V - Various

2846909000

188

MW 1071.15. Osmolality (37 °C, 0.5 molarity): 789 mOsM/kg water. Viscosity (cP): 2.0 (20 °C), 1.4 (37 °C); density at 20 °C: 1.13; logP (butanol/water): -2.1 /Gadodiamide injection/

419ºC

Freely soluble in water

Protect Omniscan from strong daylight and direct exposure to sunlight. Do not freeze. Freezing can cause small cracks in the vials, which would compromise the sterility of the product. Do not use if the product is inadvertently frozen. Store Omniscan at controlled room temperature 20 deg -25 °C (68 deg -77 °F); excursions permitted to 15 deg -30 °C (59 deg -86 °F).

LD50 i.v. in mice: 14 mmol/kg (Chang)

Osmolality (37 °C, 1.0 molarity): 111 umol/kg water

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.

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

IDENTIFICATION AND USE: Gadodiamide is a contrast agent for intravenous use in MRI to visualize lesions with abnormal vascularity (or those thought to cause abnormalities in the blood-brain barrier) in the brain (intracranial lesions), spine, and associated tissues. HUMAN EXPOSURE AND TOXICITY: The possibility of a reaction, including serious, life threatening, fatal, anaphylactoid or cardiovascular reactions or other idiosyncratic reactions should always be considered especially in those patients with a known clinical hypersensitivity, a history of asthma, or other allergic respiratory disorders. Gadolinium-based contrast agents increase the risk for nephrogenic systemic fibrosis (NSF) in patients with acute or chronic severe renal insufficiency and in patients with acute renal insufficiency of any severity due to the hepato-renal syndrome or in the perioperative liver transplantation period. In these patients, avoid use of gadolinium-based contrast agents unless the diagnostic information is essential and not available with non-contrast enhanced MRI. Among the factors that may increase the risk for NSF are repeated or higher than recommended doses of a gadolinium-based contrast agent and the degree of renal function impairment at the time of exposure. Inadvertent intrathecal use of Omniscan has occurred and caused convulsions, coma, sensory and motor neurologic deficits. Following 1157 gadodiamide-enhanced examinations, measured serum calcium spuriously dropped from 8.65 to 8.33 mg/dL and 34 patients had spurious critical hypocalcemia (<6 mg/dL). Of 60 patients with high-dose gadodiamide injection and renal insufficiency, 36.7% had spurious critical hypocalcemia immediately post MRI. In 216 patients with renal insufficiency, the mean serum magnesium level increased slightly from 1.69 to 1.77 mEq/L following gadodiamide injection. ANIMAL STUDIES: Gadodiamide injection has been shown to have a remarkably low acute lethal toxicity, superior to that of gadopentetate dimeglumine injection or gadoterate meglumine. In comparison with gadopentetate dimeglumine injection, gadodiamide injection had fewer effects on cardiovascular and hemodynamic function after rapid iv injection in anesthetized dogs. Similar to all known iv administered diagnostic imaging agents, gadodiamide injection produces vacuolization of the proximal tubular cells in the kidney, without any change in renal function. The vacuolization was only moderate in degree and was shown to have regressed partially during the 7 days after administration. Gadodiamide injection produced no significant irritation when administered by a variety of intravascular and extravascular routes. In monkeys, administration of gadodiamide daily for 28 days had no effect on the kidney . The compound was well tolerated in monkeys for 28 consecutive days. In rats, significant toxicity occurred only at high doses, particularly in male animals, and the pattern of toxicity (involving the stomach, testes, and skin) suggested a disturbance of zinc metabolism. Studies in rabbits showed that gadodiamide at doses 5 times the maximum recommended human dose increased the incidence of skeletal and visceral abnormalities in the offspring. Gadodiamide has been shown to have an adverse effect on embryo-fetal development in rabbits that is observed as an increased incidence of flexed appendages and skeletal malformations administered for 13 days during gestation (approximately 2 times the maximum human cumulative dose) . Skeletal malformations may be due to maternal toxicity since the body weight of the dams was significantly reduced in response to gadodiamide administration during pregnancy. The results of the following genotoxicity assays were negative: bacterial reverse mutation assay, CHO/HGPRT forward mutation assay, CHO chromosome aberration assay, and the in vivo mouse micronucleus assay.

... Urine and serum profiles were monitored for 24 days after iv injections of saline, diatrizoate, iohexol, gadopentetate dimeglumine, and gadodiamide in high doses (4.59 mmol/kg body weight) in rats that received a weekly intraperitoneal (ip) injection of cisplatin (1 mg/kg) for 10 weeks. There were 10 rats in each group. ... Light and electron microscopy showed severe morphologic changes, including tubular dilatation, atrophy, and necrosis induced by cisplatin; however, the contrast media did not induce any additional morphologic changes. Gadopentetate dimeglumine, diatrizoate, and iohexol significantly increased (3-20 times) albuminuria compared with iv saline in cisplatin nephropathy, whereas gadodiamide did not. Albuminuria was highest after diatrizoate injection. All four contrast media caused an immediate and transient significant increase in the excretion of the brush border enzymes alkaline phosphatase and gamma-glutamyltransferase (125-500 times) and the cytoplasmatic enzymes alanine aminopeptidase and lactate dehydrogenase (16-100 times). Compared with saline, the ionic agents significantly increased the excretion of both glucose (two times) and sodium (three to five times), whereas the nonionic agents did not. /The authors concluded that/ high doses of radiologic and magnetic resonance contrast agents cause temporary dysfunction in rats with cisplatin nephropathy. Gadodiamide caused the least dysfunction and diatrizoate the most.|... /The case of/ a 54-year-old woman in whom a /spuriously/ "critically low" serum calcium level was measured with standard colorimetric assay after gadodiamide-enhanced magnetic resonance imaging /is reported/. The same phenomenon was noted in 2 other patients ... Repeat serum calcium measurements performed several hours later were within normal limits. Commercially available gadolinium-based contrast agents might precipitate critically low serum calcium values when measured by standard colorimetric assay. Physician awareness of gadodiamide-induced spurious hypocalcemia might prevent unnecessary therapeutic interventions.|... A case in which a 78-year-old man had a /spuriously/ "critically low" serum calcium level measured with use of standard colorimetric assay after gadodiamide administration during magnetic resonance angiography /is reported/. Reanalysis of the same serum specimen using absorption spectroscopy revealed normal calcium values, confirming the diagnosis of spurious hypocalcemia.

LD50 Mouse iv 14 mmol/kg|LD50 Mouse iv 34 mmol/kg /Gadodiamide injection/

Anaphylactoid and anaphylactic reactions, with cardiovascular, respiratory and/or cutaneous manifestations, resulting in death have occurred. ... If a hypersensitivity reaction occurs, stop Omniscan Injection and immediately begin appropriate therapy. Observe patients closely, particularly those with a history of drug reactions, asthma, allergy or other hypersensitivity disorders, during and up to several hours after Omniscan Injection.|Gadolinium-based contrast agents (GBCAs) increase the risk for nephrogenic systemic fibrosis (NSF) among patients with impaired elimination of the drugs. Avoid use of GBCAs in these patients unless the diagnostic information is essential and not available with non-contrasted MRI or other modalities. NSF may result in fatal or debilitating fibrosis affecting the skin, muscle and internal organs. Do not administer Omniscan to patients with: chronic, severe kidney disease (GFR < 30 mL/min/1.73 sq m), or acute kidney injury. Screen patients for acute kidney injury and other conditions that may reduce renal function. For patients at risk for chronically reduced renal function (e.g., age > 60 years, hypertension or diabetes), estimate the glomerular filtration rate (GFR) through laboratory testing. Do not exceed the recommended Omniscan dose and allow a sufficient period of time for elimination of the drug from the body prior to any readministration|In patients with renal insufficiency, acute renal failure requiring dialysis or worsening renal function have occurred, mostly within 48 hours of Omniscan Injection. The risk of renal failure may increase with increasing dose of gadolinium contrast. Use the lowest necessary dose of contrast and evaluate renal function in patients with renal insufficiency. Acute renal failure was observed in < 1% of patients in Omniscan clinical studies.|Nephrogenic systemic fibrosis may be caused by gadolinium (Gd)-containing magnetic resonance imaging contrast agents. Most reported cases were associated with one particular agent, gadodiamide. Yet, unidentified cofactors might explain why only a minority of renal failure patients exposed to gadodiamide develop nephrogenic systemic fibrosis. We conducted a case-control study of 19 histologically verified cases and 19 sex- and age-matched controls. All subjects had chronic renal failure when exposed to gadodiamide. Clinical, biochemical and pharmacological data were retrieved from medical records. Cases had been exposed to a mean gadodiamide dose of 0.29 mmol/kg (range 0.18-0.50) shortly before first signs of nephrogenic systemic fibrosis. Controls had been exposed to 0.28 mmol/kg (0.13-0.49). Cumulative gadodiamide exposure while in chronic kidney disease stage 5 was significantly higher among cases compared with controls (0.41 vs 0.31 mmol/kg, P = 0.05) and among severe cases (n = 9) compared with non-severe cases (0.49 vs 0.33 mmol/kg, P = 0.02). Severe cases developed primarily among patients in regular hemodialysis therapy at exposure. Cases had higher serum concentrations of ionized calcium and phosphate than controls and tended to receive higher doses of epoietin-beta than controls at time of exposure. Severe cases were treated with higher doses of epoietin-beta than non-severe cases at exposure (10.8 vs 4.4 10(3) IU/week, P = 0.02). Increasing cumulative gadodiamide exposure, high-dose epoietin-beta treatment, and higher serum concentrations of ionized calcium and phosphate increase the risk of gadodiamide-related nephrogenic systemic fibrosis in renal failure patients. Severe cases seem to develop primarily among patients in regular hemodialysis therapy at exposure.

Gadodiamine's use as a contrast agent in magnetic resonance imaging (MRI) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: The elements of the lanthanide series typically occur as the +3 ion either in solution or in compounds(1). Based on the Gd3+/Gd reduction potential of -2.28 V(1), gadolinium(III) ions do not undergo oxidation-reduction reactions under normal environmental conditions(SRC). Gadolinium ions are likely to adsorb to soils(SRC). In general, metal cations in solution are attracted to the negatively charged surfaces of soil particles(2). The extent of adsorption of metal ions to soils depends on the pH, the mineral content, and organic content of the soil(2). Gadolinium compounds do not volatilize from dry or moist soil surfaces due to their ionic character(SRC).

Bioconcentration is not expected to be an important fate process due to the ionic nature of gadolinium compounds. (SRC)

Ionic gadolinium compounds will not volatilize from dry or moist soils or from water surfaces. (SRC)

While data specific to gadodiamide were not located(SRC, 2014), the literature suggests that some contrast agents 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).

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Omniscan is administered to a nursing woman. /Omniscan/|EXPERIMENTAL: The disposition of gadodiamide injection ... was characterized in the pregnant and lactating rat. After a single iv dose of 0.3 mmol/kg 14C-labeled gadodiamide to rats on day 18 of gestation, the maximum levels of radioactivity in the fetus were attained at 5 min, and were approximately 170 times lower than those in the maternal plasma. The AUC ratio of fetal to maternal blood was less than 0.1. Moreover, the distribution percentage of radioactivity in the fetus were on the average 0.01% of the administered dose up to 4 hr, and trace amounts of radioactivity were present in fetal tissues at 24 hr after dosing. Whole body autoradiography showed that the smallest amounts of radioactivity were present in the fetus, whereas the highest concentrations of radioactivity were noted in the fetal membrane and the kidney at 24 hr after dosing. These results indicate that exposure of the developing rat fetus to gadodiamide after maternal drug administration is quantitatively small. The radioactivity levels in the milk increased with time, reaching a maximum 1 hr after dosing, and gradually decreased to levels below detection limits over 8 hr. A comparison of the AUCs of milk and plasma showed the comparatively small amounts of the drug excreted into milk.

Occupational exposure to gadolinium compounds may occur through dermal contact with these compounds at workplaces where gadolinium is produced or used. Monitoring data indicate that the general population may be exposed to gadolinium compounds via ingestion of contaminated drinking water. Limited monitoring data indicate that exposure may occur via ingestion of contaminated food and inhalation. Direct exposure to gadolinium compounds among the general population will also be to those administered contrast agents containing gadolinium prior to MRI procedures. (SRC)

Contrast Media|Omniscan is a gadolinium-based contrast agent indicated for intravenous use in MRI to visualize lesions with abnormal vascularity (or those thought to cause abnormalities in the blood-brain barrier) in the brain (intracranial lesions), spine, and associated tissues. /Included in US product label/|Omniscan is a gadolinium-based contrast agent indicated for intravenous use in MRI to facilitate the visualization of lesions with abnormal vascularity within the thoracic (noncardiac), abdominal, pelvic cavities, and the retroperitoneal space. /Included in US product label/|... To evaluate the safety and effectiveness of gadodiamide-enhanced magnetic resonance (MR) angiography with single and triple doses in the assessment of abdominal arterial stenoses ... One hundred five patients were included in the randomized, double-blind, phase III multicenter trial. Results of MR angiography with 0.1 mmol/kg and 0.3 mmol/kg doses of gadodiamide were compared with those of digital subtraction angiography (DSA) and according to dose ... No serious adverse events were observed. The mean contrast index at the region proximal to the primary stenosis was significantly higher in the triple-dose group (P = 0.03). Mean 95% CI values for the difference in depicted degree of stenosis between DSA and postcontrast MR angiography improved from -3.4% +/- 4.7 (SD) in the single-dose group to -1.2% +/- 4.7 in the triple-dose group. Mean values for overall image quality on the visual analogue scale improved with the triple dose (P = 0.02). Confidence in diagnosis was high at postcontrast MR angiography in 88% and 96% of cases in the single- and triple-dose groups, respectively ... Gadodiamide-enhanced MR angiography performed with single and triple doses is safe and effective for assessing major abdominal arterial stenoses. Although high agreement between MR angiography and DSA was achieved with both doses, triple-dose MR angiography was superior in the evaluations of image quality, degree of arterial stenoses, and confidence in diagnosis.|... The safety and diagnostic efficacy of MultiHance (gadobenate dimeglumine) in the central nervous system (CNS) were evaluated in a double-blind, multicenter, phase III clinical trial ... Two hundred five patients highly suspected of having a CNS lesion (by previous imaging exam) were enrolled at 16 sites in the United States. Patients were randomized to one of three incremental dosing regimens. Magnetic resonance imaging with Omniscan (gadodiamide) at doses of 0.1 and 0.3 mmol/kg was compared with MultiHance (gadobenate dimeglumine) at doses of 0.05 and 0.15 mmol/kg and at 0.1 and 0.2 mmol/kg ... Compared with predose images alone, efficacy was demonstrated in each of the gadobenate dimeglumine and gadodiamide groups (single and cumulative doses) as indicated by the level of diagnostic information, number of lesions detected, and contrast-to-noise ratio measurements. The level of diagnostic information from gadobenate dimeglumine at 0.1 mmol/kg was equivalent to that with gadodiamide at the same dose. One of the two blinded reviewers found equivalence between the gadobenate dimeglumine 0.05 mmol/kg dose and gadodiamide at 0.1 mmol/kg. Both reviewers found the level of diagnostic information to be equivalent after the second dose of contrast for all three dosing regimens. The cumulative doses of gadobenate dimeglumine were well tolerated and as safe as gadodiamide ... Gadobenate dimeglumine is comparable to gadodiamide in terms of safety and efficacy for imaging of CNS lesions, with a possible advantage in imaging applications owing to enhanced T1 relaxivity.

/BOXED WARNING/ WARNING: NOT FOR INTRATHECAL USE AND NEPHROGENIC SYSTEMIC FIBROSIS (NSF). NOT FOR INTRATHECAL USE: Inadvertent intrathecal use of OMNISCAN has caused convulsions, coma, sensory and motor neurologic deficits. NEPHROGENIC SYSTEMIC FIBROSIS (NSF): Gadolinium-based contrast agents (GBCAs) increase the risk for NSF among patients with impaired elimination of the drugs. Avoid use of GBCAs in these patients unless the diagnostic information is essential and not available with non-contrasted MRI or other modalities. NSF may result in fatal or debilitating fibrosis affecting the skin, muscle and internal organs. Do not administer Omniscan to patients with: chronic, severe kidney disease (GFR < 30 mL/min/1.73 sq m), or acute kidney injury. Screen patients for acute kidney injury and other conditions that may reduce renal function. For patients at risk for chronically reduced renal function (e.g., age > 60 years, hypertension or diabetes), estimate the glomerular filtration rate (GFR) through laboratory testing. Do not exceed the recommended Omniscan dose and allow a sufficient period of time for elimination of the drug from the body prior to any readministration|Gadolinium-based contrast agents (GBCAs) increase the risk for nephrogenic systemic fibrosis (NSF) among patients with impaired elimination of the drugs. Avoid use of GBCAs among these patients unless the diagnostic information is essential and not available with non-contrast enhanced MRI or other modalities. The GBCA-associated NSF risk appears highest for patients with chronic, severe kidney disease (GFR < 30 mL/min/1.73 sq m) as well as patients with acute kidney injury. Do not administer Omniscan to these patients. The risk appears lower for patients with chronic, moderate kidney disease (GFR 30-59 mL/min/1.73 sq m) and little, if any, for patients with chronic, mild kidney disease (GFR 60-89 mL/min/1.73 sq m). NSF may result in fatal or debilitating fibrosis affecting the skin, muscle and internal organs. ... Screen patients for acute kidney injury and other conditions that may reduce renal function. Features of acute kidney injury consist of rapid (over hours to days) and usually reversible decrease in kidney function, commonly in the setting of surgery, severe infection, injury or drug-induced kidney toxicity. Serum creatinine levels and estimated GFR may not reliably assess renal function in the setting of acute kidney injury. For patients at risk for chronically reduced renal function (e.g., age > 60 years, diabetes mellitus or chronic hypertension), estimate the GFR through laboratory testing. Among the factors that may increase the risk for NSF are repeated or higher than recommended doses of a GBCA and the degree of renal impairment at the time of exposure. Record the specific GBCA and the dose administered to a patient. When administering Omniscan, do not exceed the recommended dose and allow a sufficient period of time for elimination of the drug prior to any readministration|Anaphylactoid and anaphylactic reactions, with cardiovascular, respiratory and/or cutaneous manifestations, resulting in death have occurred. Personnel trained in resuscitation techniques and resuscitation equipment should be present prior to Omniscan administration. If a hypersensitivity reaction occurs, stop Omniscan Injection and immediately begin appropriate therapy. Observe patients closely, particularly those with a history of drug reactions, asthma, allergy or other hypersensitivity disorders, during and up to several hours after Omniscan Injection.|FDA Pregnancy Risk Category: C /RISK CANNOT BE RULED OUT. Adequate, well controlled human studies are lacking, and animal studies have shown risk to the fetus or are lacking as well. There is a chance of fetal harm if the drug is given during pregnancy; but the potential benefits may outweigh the potential risk./|For more Drug Warnings (Complete) data for GADODIAMIDE (24 total), please visit the HSDB record page.

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

The objective of this study was to determine the gadolinium (Gd) concentration remaining in human bone tissue after administration of standard clinical doses of 2 Gd-based contrast agents: ProHance and Omniscan. After administration of 0.1 mmol/kg of Gd chelate to patients undergoing hip replacement surgery, bone specimens were collected and analyzed, and compared with an age-matched control population without a history of Gd chelate administration. Bone specimens were collected fresh, refrigerated, and subsequently frozen. After grinding and freeze-drying, tissue digestion was performed using Teflon bombs and concentrated nitric acid. A method for analysis of Gd in bone specimens was developed and validated using inductively coupled plasma mass spectroscopy (ICP-MS). Results were compared with a previous study using a different technique for analysis of the same tissue specimens. Tissue retention was 1.77+/-0.704 microg Gd/g bone (n=9) for Omniscan and 0.477+/-0.271 microg Gd/g bone (n=10) for ProHance measured by ICP-MS. These findings confirmed results from the previous ICP-AES study. Omniscan (Gd[DTPA-BMA]) left approximately 4 times (previous study 2.5 times) more Gd behind in bone than did ProHance (Gd[HP-DO3A]).|Twenty-seven patients--nine with severely reduced renal function (glomerular filtration rate, 2-10 mL/min), nine undergoing hemodialysis, and nine undergoing continuous ambulatory peritoneal dialysis--were followed up for 5, 8, and 22 days, respectively, after receiving gadodiamide injection (0.1 mmol per kilogram body weight). Gadodiamide injection caused no changes in renal function. In patients with severely reduced renal function, the elimination half-life of gadodiamide injection was prolonged (34.3 hours +/- 22.9) compared with data in healthy volunteers (1.3 hours +/- 0.25). An average of 65% of the gadodiamide injected was eliminated during a hemodialysis session. After 22 days of continuous ambulatory peritoneal dialysis, 69% of the total amount of gadodiamide was excreted; this reflects the low peritoneal clearance. In all patients, no metabolism or transmetallation of gadodiamide was found. ...|The pharmacokinetic behavior of gadodiamide was consistent with its extracellular distribution. ... Gadodiamide was shown to be excreted rapidly, primarily through the kidneys. In rats, 94% of the administered dose was excreted in the urine within the first 24 hours after administration. Approximately 1% to 4% appeared in the feces during the same period.|... /In rats/ following iv dosing of gadodiamide (NaCa DTPA-BMA) (0.015 mmol/kg) in a (14)C-labeled form, plasma concentrations of the drug declined rapidly with an elimination half-live of 0.31 hr, a distribution volume of 244 mL/kg and a plasma clearance of 9.2 mL/min/kg. These results demonstrate that NaCa DTPA-BMA distributes into the extracellular fluid compartment and is renally excreted via glomerular filtration. Of the dose of radioactivity given, 86.6% was excreted in urine by 4 hr after injection, and 95.3% in urine and 3.3% in feces by 120 hr. ...|For more Absorption, Distribution and Excretion (Complete) data for GADODIAMIDE (10 total), please visit the HSDB record page.

In addition, experiments were done /in rats/ to clarify the in vivo metabolism of gadodiamide (NaCa DTPA-BMA). Results show small quantities of transchelated forms of NaCa DTPA-BMA in urine. HPLC analysis demonstrated these metabolites were the Zn and Cu forms of the drug, resulting from displacement of the Ca ion in the NaCa DTPA-BMA molecule by endogeneous Zn or Cu. Further analyses by HPLC and ICP-AES demonstrate that the unchanged parent drug, the Zn and the Cu forms occur in relative quantities of approximately 92%, 7%, and 1%, respectively. This demonstrates that the Ca ion in caldiamide sodium can be replaced by Zn or Cu ions in vivo, but only to a small extent.

... /In rats/ following iv dosing of gadodiamide (NaCa DTPA-BMA) (0.015 mmol/kg) in a (14)C-labeled form, plasma concentrations of the drug declined rapidly with an elimination half-live of 0.31 hr ...|The pharmacokinetic behavior of gadodiamide was consistent with its extracellular distribution. Its half-life in rats, rabbits, and monkeys was short, 18, 38, and 75 minutes, respectively.|The pharmacokinetics of intravenously administered gadodiamide in normal subjects conforms to an open, two-compartment model with mean distribution and elimination half-lives (reported as mean + or - SD) of 3.7 + or - 2.7 minutes and 77.8 + or - 16 minutes, respectively.|... The average half-time of gadodiamide was 1.93 hr (SD 0.55) /in thirteen hemodialysis patients with abdominal disease receiving iv gadodiamide (0.1 mmol/kg body weight)/.|Twenty-seven patients--nine with severely reduced renal function (glomerular filtration rate, 2-10 mL/min), nine undergoing hemodialysis, and nine undergoing continuous ambulatory peritoneal dialysis--were followed up for 5, 8, and 22 days, respectively, after receiving gadodiamide injection (0.1 mmol per kilogram body weight). Gadodiamide injection caused no changes in renal function. In patients with severely reduced renal function, the elimination half-life of gadodiamide injection was prolonged (34.3 hours +/- 22.9) compared with data in healthy volunteers (1.3 hours +/- 0.25). ...

/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 TKO /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) 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/ Gadolinium-based contrast agents (GBCAs) increase the risk for nephrogenic systemic fibrosis (NSF) among patients with impaired elimination of the drugs. Avoid use of GBCAs in these patients unless the diagnostic information is essential and not available with non-contrasted MRI or other modalities. NSF may result in fatal or debilitating fibrosis affecting the skin, muscle and internal organs. Do not administer Omniscan to patients with: chronic, severe kidney disease (GFR < 30 mL/min/1.73 sq m), or acute kidney injury. Screen patients for acute kidney injury and other conditions that may reduce renal function. For patients at risk for chronically reduced renal function (e.g., age > 60 years, hypertension or diabetes), estimate the glomerular filtration rate (GFR) through laboratory testing. Do not exceed the recommended Omniscan dose and allow a sufficient period of time for elimination of the drug from the body prior to any readministration. /GBCA/|/SIGNS AND SYMPTOMS/ Anaphylactoid and anaphylactic reactions, with cardiovascular, respiratory and/or cutaneous manifestations, resulting in death have occurred. ... If a hypersensitivity reaction occurs, stop Omniscan Injection and immediately begin appropriate therapy. Observe patients closely, particularly those with a history of drug reactions, asthma, allergy or other hypersensitivity disorders, during and up to several hours after Omniscan Injection.|/CASE REPORTS/ ... A case in which a 78-year-old man had a /spuriously/ "critically low" serum calcium level measured with use of standard colorimetric assay after gadodiamide administration during magnetic resonance angiography /is reported/. Reanalysis of the same serum specimen using absorption spectroscopy revealed normal calcium values, confirming the diagnosis of spurious hypocalcemia.|/CASE REPORTS/ Nephrogenic systemic fibrosis (NSF) is a recently recognized clinicopathologic entity. It is believed to be related to exposure to gadolinium-containing magnetic resonance imaging agents with gadolinium deposition in the tissues, including skin and other organs. It mainly affects patients on dialysis therapy. Pregnancy in dialysis patients is a rare occurrence. We present a case of a dialysis patient who developed NSF after exposure to gadodiamide and went on to have a successful pregnancy while on hemodialysis therapy. The patient had marked clinical and histological improvement in NSF during and after her pregnancy. This also correlated with decreasing gadolinium levels in skin biopsy tissue specimens. We discuss the interplay of factors involved in the successful pregnancy and improvement in NSF lesions in this patient.|For more Human Toxicity Excerpts (Complete) data for GADODIAMIDE (12 total), please visit the HSDB record page.

gadodiamide

Omniscan (gadodiamide) Injection is the formulation of the gadolinium complex of diethylenetriamine pentaacetic acid bismethylamide, and is an injectable, nonionic extracellular enhancing agent for magnetic resonance imaging. Omniscan is administered by intravenous injection. Omniscan is provided as a sterile, clear, colorless to slightly yellow, aqueous solution. Each 1 mL contains 287 mg gadodiamide and 12 mg caldiamide sodium in Water for Injection.

Analyte: gadodiamide; matrix: chemical identification; procedure: infrared absorption spectrophotometry with comparison to standards|Analyte: gadodiamide; matrix: chemical identification; procedure: atomic absorption spectrophotometry with detection at 342 nm and comparison to standards|Analyte: gadodiamide; matrix: chemical purity; procedure: liquid chromatography with detection at 658 nm and comparison to standards|Analyte: gadodiamide; matrix: pharmaceutical preparation (injection selection); procedure: infrared absorption spectrophotometry with comparison to standards (chemical identification)|Analyte: gadodiamide; matrix: pharmaceutical preparation (injection solution); procedure: retention time of the major peak of the liquid chromatogram with comparison to standards (chemical identification)

Analyte: gadodiamide; matrix: tissue (bone); procedure: inductively coupled plasma-mass spectrometry; limit of quantitation: 0.1-20 ug Gd/g bone|Analyte: gadodiamide; matrix: tissue (bone); procedure: inductively coupled plasma-atomic emission spectroscopy; limit of detection: 0.1-0.2 ug/g bone|Analyte: gadodiamide; matrix: blood (serum), peritoneal dialysate, feces; procedure: high-performance liquid chromatography; limit of quantitation: 0.9 uM Gd|Analyte: gadodiamide; matrix: blood (serum), peritoneal dialysate, feces; procedure: inductively coupled plasma atomic emission spectroscopy; limit of quantitation: 6.5 uM Gd (serum), 1.6 uM Gd (peritoneal dialysate), 11 nmol Gd/g dry weight (feces)|Analyte: gadodiamide; matrix: blood (serum), urine; procedure: high-performance liquid chromatography with detection at 658 nm; limit of detection: 0.3 uM (serum); 1.1 uM (urine)

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