Safety of gadoxetate disodium: Results from the clinical phase II–III development program and postmarketing surveillance

Abstract

Purpose: To summarize the safety data of gadoxetate disodium, reported in 12 Phase II and III clinical development studies and in the postmarketing surveillance database. Materials and Methods: Patients with liver lesions received gadoxetate disodium-enhanced liver magnetic resonance imaging (MRI). Adverse events (AEs) were recorded and evaluated with regard to a potential drug relationship. Subgroup analyses were run on patients with special medical history. Worldwide spontaneous AEs and adverse drug reactions (ADRs) from postmarketing safety surveillance were analyzed. Results: A total of 1989 patients were included in the clinical development program. A total of 1581/1989 (79.5%) patients received the finally approved dose of 0.025 mmol/kg body weight. 10.1% of patients reported AEs, 4.1% were classified as related AEs. Nausea and headache were the most frequently reported related AEs, with 1.1% each. Age, history of contrast media allergy, liver cirrhosis, or impaired liver or renal function did not significantly impact the frequency and type of AEs. The postmarketing safety surveillance database encompassed more than 2.2 million patients. Nausea was the most frequent ADR, with a reporting rate of 0.00652%; all other symptoms were below 0.004%. Conclusion: Gadoxetate disodium for liver MRI has an excellent safety profile. G adoxetate disodium is a magnetic resonance imaging (MRI) contrast agent developed for detection, localization, and characterization of liver lesions.Gadoxetate disodium belongs to the class of linear ionic gadolinium-based contrast agents (GBCAs). The contrastenhancing effect is mediated by the gadolinium complex gadolinium-ethoxybenzyl-diethylene-triamine penta-aceticacid (Gd-EOB-DTPA). It features a high T 1 relaxivity of 6.9 L mmol 21 s 21 at 1.5T (in plasma). 1,2 After intravenous application, gadoxetate disodium is distributed in the extracellular space and selectively taken up by the hepatocytes, thus providing both dynamic and hepatocyte-specific imaging. In healthy patients about 50% is excreted via the kidneys and 50% via the biliary system. 3,4 Signal enhancement of the liver parenchyma and liver-to-lesion contrast starts within 10 minutes and is highest at about 20 minutes after administration with a plateau lasting for at least to 45 minutes postinjection. 5,6The safety profile of gadoxetate disodium has been demonstrated in several (controlled) clinical studies 7-9 and in postmarketing studies. So far, since approval in March 2004 through March 2014, more than 2.2 million patients have been exposed to gadoxetate disodium worldwide. The purpose of this evaluation was to systematically summarize the safety data of gadoxetate disodium collected in Phase II and III clinical development studies and additionally to analyze 10-year results from the global postmarketing surveillance database.View this article online at wileyonlinelibrary.com.

The Incidence, Classification, and Management of Acute Adverse Reactions to the Low-Osmolar Iodinated Contrast Media Isovue and Ultravist in Contrast-Enhanced Computed Tomography Scanning

“…However, no previous studies had been conducted to investigate and compare the AARs induced by these 2 contrast agents in a large population to support the presume, though there is no lack of surveillance studies performed to prove the safety and tolerability of iodinated contrast media. 3–7 …”

Diagnostic Efficacy and Safety of Gadoxetate Disodium vs Gadobenate Dimeglumine in Patients With Known or Suspected Focal Liver Lesions: Results of a Clinical Phase III Study

“…This is in line with large safety reviews of both agents. Endrikat et al 20 reported 10.1% of AEs of which 4.1% were classified as related to gadoxetate disodium administration in an analysis of 12 clinical development studies, including 1989 patients. Likewise, Shellock et al 21 found 18% of AEs with 14% AEs considered related to gadobenate dimeglumine administration in a review of 79 clinical studies, including 2982 patients.…”

Safety profile of gadoxetate disodium in elderly patients (≥65 years)

“…No further imaging was needed in the gadoxetate disodium group, and comparison of efficacy parameters demonstrated diagnostic superiority in the gadoxetate disodium enhanced MRI group (6). The excellent safety profile of gadoxetate disodium has been demonstrated in several clinical studies and in post-marketing experience (1,7–9). As of 30 April 2016, more than 3.6 million patients have been exposed to gadoxetate disodium worldwide since approval in March 2004.…”