gadoxetic-acid-disodium and Kidney-Diseases

Background Safety data on routine clinical use of gadoxetate disodium for liver magnetic resonance imaging (MRI) is not reported yet. Purpose To assess the safety profile of gadoxetate disodium for liver MRI in the routine clinical setting. Material and Methods Six multicenter studies were performed in Europe, USA, Australia, and Asia to evaluate the safety and efficacy of gadoxetate disodium (Primovist®/Eovist®) enhanced liver MRI. Patients received a single intravenous bolus injection of the standard approved dose of 0.025 mmol/kg body weight (0.1 mL/kg). The number of patients, the characteristics of adverse events, related adverse events, and serious adverse events were analyzed. Results A total of 8194 patients were included in the database. A total of 141 patients (1.7%) reported 230 AEs of which 129 were considered being related to the use of gadoxetate disodium by the investigators. None of the AEs in the pediatric population ( n = 52) were related. The most frequent AEs independent of relationship to the drug included dyspnea (25/0.31%), nausea (22/0.27%), liver disorders (13/0.16%), and renal disorders (9/0.11%). Nine related SAEs were recorded. No patient died during the studies. Conclusion Gadoxetate disodium for liver MRI is safe and well tolerated in the routine clinical setting.

Topics: Adolescent; Adult; Age Distribution; Aged; Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Contrast Media; Drug-Related Side Effects and Adverse Reactions; Dyspnea; Female; Gadolinium DTPA; Humans; Infant; Infant, Newborn; Internationality; Kidney Diseases; Liver Diseases; Magnetic Resonance Imaging; Male; Middle Aged; Nausea; Prevalence; Risk Factors; Sex Distribution; Treatment Outcome; Young Adult

The objective of this study was to assess the risk of gadoxetate disodium in liver imaging for the development of nephrogenic systemic fibrosis (NSF) in patients with moderate to severe renal impairment.. We performed a prospective, multicenter, nonrandomized, open-label phase 4 study in 35 centers from May 2009 to July 2013. The study population consisted of patients with moderate to severe renal impairment scheduled for liver imaging with gadoxetate disodium. All patients received a single intravenous bolus injection of 0.025-mmol/kg body weight of liver-specific gadoxetate disodium. The primary target variable was the number of patients who develop NSF within a 2-year follow-up period.. A total of 357 patients were included, with 85 patients with severe and 193 patients with moderate renal impairment, which were the clinically most relevant groups. The mean time period from diagnosis of renal disease to liver magnetic resonance imaging (MRI) was 1.53 and 5.46 years in the moderate and severe renal impairment cohort, respectively. Overall, 101 patients (28%) underwent additional contrast-enhanced MRI with other gadolinium-based MRI contrast agents within 12 months before the start of the study or in the follow-up. No patient developed symptoms conclusive of NSF within the 2-year follow-up.. Gadoxetate disodium in patients with moderate to severe renal impairment did not raise any clinically significant safety concern. No NSF cases were observed.

Topics: Adult; Aged; Aged, 80 and over; Contrast Media; Female; Follow-Up Studies; Gadolinium DTPA; Humans; Kidney Diseases; Liver; Magnetic Resonance Imaging; Male; Middle Aged; Nephrogenic Fibrosing Dermopathy; Prospective Studies; Risk; Severity of Illness Index; Young Adult

Topics: Gadolinium DTPA; Humans; Kidney Diseases; Nephrogenic Fibrosing Dermopathy; Patients

This study was undertaken to quantify tissue gadolinium (Gd) deposition in hepatorenally impaired rats exposed to gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) by means of inductively coupled plasma mass spectrometry (ICP-MS) and to compare differences in Gd distribution among major organs as possible triggers for nephrogenic systemic fibrosis.. Five hepatorenally impaired rats (5/6-nephrectomized, with carbon-tetrachloride-induced liver fibrosis) were injected with Gd-EOB-DTPA. Histological assessment was conducted and Gd content of the skin, liver, kidneys, lungs, heart, spleen, diaphragm, and femoral muscle was measured by inductively coupled plasma mass spectrometry (ICP-MS) at 7 days after last injection. In addition, five renally impaired rats were injected with Gd-EOB-DTPA and the degree of tissue Gd deposition was compared with that in the hepatorenally impaired rats.. ICP-MS analysis revealed significantly higher Gd deposition in the kidneys, spleen, and liver (p = 0.009-0.047) in the hepatorenally impaired group (42.6 ± 20.1, 17.2 ± 6.1, 8.4 ± 3.2 μg/g, respectively) than in the renally impaired group (17.2 ± 7.7, 5.4 ± 2.1, 2.8 ± 0.7 μg/g, respectively); no significant difference was found for other organs. In the hepatorenally impaired group, Gd was predominantly deposited in the kidneys, followed by the spleen, liver, lungs, skin, heart, diaphragm, and femoral muscle. Histopathological investigation revealed hepatic fibrosis in the hepatorenally impaired group.. Compared with renally impaired rats, tissue Gd deposition in hepatorenally impaired rats exposed to Gd-EOB-DTPA was significantly increased in the kidneys, spleen, and liver, probably due to the impairment of the dual excretion pathways of the urinary and biliary systems.

Topics: Animals; Carbon Tetrachloride Poisoning; Contrast Media; Gadolinium; Gadolinium DTPA; Kidney Diseases; Liver Cirrhosis; Liver Diseases; Male; Mass Spectrometry; Nephrectomy; Rats; Rats, Wistar

: The purpose of this study was to determine the pharmacokinetics (PKs), imaging properties, and safety of the liver-specific magnetic resonance (MR) imaging contrast agent gadoxetic acid disodium (Gd-EOB-DTPA) in subjects with various levels of hepatic impairment, renal impairment, or coexisting hepatic and renal impairment.. : In this single-center, open-label, parallel-group study, patients with varying degrees of renal and/or hepatic impairment were compared with healthy subjects matched for age, gender, and weight (control group). All subjects received a single intravenous bolus of Gd-EOB-DTPA (Primovist, Eovist, EOB-Primovist) 25 μmol/kg body weight. Samples of serum, urine, and feces were collected for PK analysis. MR imaging was performed before dosing and at preset times after dose administration to determine enhancement relative to predose signal intensity values. Safety was assessed by monitoring adverse events, laboratory values, vital signs, cardiac rhythm, oxygen saturation, and by physical examination findings.. : Gd-EOB-DTPA was well tolerated by all subjects. Total clearance of Gd-EOB-DTPA did not significantly change in patients with mild and moderate hepatic impairment (Child-Pugh A and B), compared with the control group. Mean urinary excretion was increased and mean fecal excretion was decreased in patients with hepatic impairment. Renal excretion was increased to between 72% and 96% of the dose administered in patients with very high bilirubin levels (>3 mg/dL), compared with 48% in the control group. Total clearance of Gd-EOB-DTPA was significantly reduced to 140 ± 45 mL/min and terminal elimination half-life (t1/2) was slightly, but not significantly, increased to 2.6 ± 0.9 hours in patients with severe hepatic impairment (Child-Pugh C), compared with the control group (209 ± 37 mL/min and 1.8 ± 0.2 hours, respectively). Liver MR signal enhancement (area under the curve of relative enhancement [%] over time) was similar in patients with mild and moderate hepatic impairment and in those in the control group, but was decreased by 38% in patients with severe hepatic impairment, compared with control. Peak liver enhancement, however, was still at a high level (118% ± 57%). PK and imaging parameters were not significantly affected in patients with moderate renal impairment (creatinine clearance, 30-50 mL/min). In patients with end-stage renal failure (ESRF), however, the PK profile of Gd-EOB-DTPA was significantly different, with an increased t1/2 (20.0 ± 7.0 hours vs. 1.8 ± 0.2 hours in the control group). During a 3-hour dialysis session that started 1 hour after administration of the intravenous dose, the serum levels in patients with ESRF declined by between 71% and 88% as a result of elimination by hemodialysis and parallel hepatobiliary excretion. This is comparable with the decline observed in healthy subjects (85%) during the 1- to 4-hour interval after injection.. : The results of the present study show that in humans with moderate renal impairment and mild-to-moderate hepatic impairment, no relevant changes in PK parameters, such as total clearance and t1/2, develop as a result of increased renal excretion to compensate in the case of hepatic impairment (or increased hepatic elimination in the case of renal impairment). The t1/2 of Gd-EOB-DTPA was markedly altered only in patients with ESRF. The high MR signal enhancement profile, observed even in patients with severe hepatic impairment, indicates that there is no need to adjust the dose of Gd-EOB-DTPA.

Topics: Adolescent; Adult; Area Under Curve; Contrast Media; Female; Gadolinium DTPA; Health Status Indicators; Humans; Kidney Diseases; Liver Diseases; Magnetic Resonance Imaging; Male; Metabolic Clearance Rate; Middle Aged; Prospective Studies; Regression Analysis; Risk Assessment; Statistics, Nonparametric; Young Adult

The authors investigated whether gadolinium-ethoxybenzyl-DTPA (Gd-EOB-DTPA) can be eliminated in the absence of the two usual excretory pathways (urinary or biliary) and whether a remaining excretory pathway is able to compensate for impaired liver or kidney function.. The study was performed using two groups of animals: group A animals underwent ligation of the common bile duct, and group B animals underwent ligation of the renal blood vessels. A dose of 0.1 mmol/kg Gd-EOB-DTPA or Gd-DTPA (control) was injected via a tail vein. Bile or urine were collected in fractions of 0 to 1, 1 to 2, 2 to 4, and 4 to 8 hours after administration of either contrast agent. At the end of the experiments, detainment of the contrast agents was determined by measurement of Gd concentrations.. Most of the Gd-EOB-DTPA was rapidly cleared from the body: 89.4% +/- 7.5% of the injected dose within 4 hours after bile duct ligation (group A) and 87.0% +/- 6.0% within 1 hour after ligation of renal vessels (group B). Eight hours after injection of Gd-EOB-DTPA, 3.0% +/- 2.4% of the administered dose of this contrast agent was found in the carcasses of group A animals, and 1.3% +/- 0.6% in carcasses of group B animals. By comparison, at 8 hours after injection, 1.9% +/- 3.2% of the injected Gd-DTPA was found in the carcasses of group A animals (no statistical significant difference as compared with Gd-EOB-DTPA), and 96.3% +/- 3.3% in carcasses of group B animals.. In the rat model, the magnetic resonance imaging contrast agent Gd-EOB-DPTA is rapidly and effectively eliminated by virtue of its dual-elimination pathway. The dysfunction of liver or kidney may be fully compensated by the remaining elimination pathway.

Topics: Animals; Bile; Contrast Media; Female; Gadolinium DTPA; Kidney Diseases; Liver Diseases; Organometallic Compounds; Pentetic Acid; Rats; Rats, Wistar