Safety of gadobutrol in more than 1,000 pediatric patients: subanalysis of the GARDIAN study, a global multicenter prospective non-interventional study.

Katja Glutig,Ravi Bhargava,Hans-Joachim Mentzel,Petra Palkowitsch,Gabriele Hahn,Winfried Willinek,Christian Kunze,Wolfgang Hirsch,Jürgen F Schaefer

doi:10.1007/s00247-016-3599-6

Abstract

BackgroundGadobutrol is a gadolinium-based contrast agent, uniquely formulated at 1.0 mmol/ml. Although there is extensive safety evidence on the use of gadobutrol in adults, few studies have addressed the safety and tolerability of gadobutrol in pediatric patients.ObjectiveThis subanalysis of data from the GARDIAN study evaluated the safety and use of gadobutrol in pediatric patients (age <18 years).Materials and methodsThe GARDIAN study was a large phase IV non-interventional prospective multicenter post-authorization safety study performed in Europe, Asia, North America and Africa. A total of 23,708 patients were included who were scheduled to undergo cranial or spinal MRI, liver or kidney MRI, or MR angiography with gadobutrol enhancement. The primary study endpoint was the overall incidence of adverse drug reactions (ADRs) and serious adverse events (SAEs) following gadobutrol administration.ResultsThe GARDIAN study included 1,142 children (age <18 years) who received gadobutrol at a mean dose of 0.13 (range 0.04–0.50) mmol/kg body weight. Gadobutrol was well tolerated in these children, with low rates of ADRs (0.5%) and no SAEs, consistent with results in adults enrolled in the GARDIAN study. Rates of adverse events and ADRs were unrelated to pediatric age or gadobutrol weight-adjusted dose. There were no symptoms suggestive of nephrogenic systemic fibrosis. Investigators rated the contrast quality of gadobutrol-enhanced images as good or excellent in 97.8% of pediatric patients, similar to the main study population.ConclusionGadobutrol is very well tolerated and provides excellent contrast quality at the recommended weight-adjusted dose in children (age <18 years), similar to the profile in adults.

Highlights

Gadobutrol (Gd-DO3A-butrol, Gadovist®, Gadavist®; Bayer Pharma, Leverkusen, Germany) is a second-generation gadolinium-based contrast agent (GBCA) used to enhance tissue contrast in MRI for a range of approved indications in adults and children of all ages [1]
Gadobutrol was well tolerated in these children, with low rates of adverse drug reactions (ADRs) (0.5%) and no serious adverse events (SAEs), consistent with results in adults enrolled in the GARDIAN study
As observed in adults enrolled in GARDIAN [17], gadobutrol was very well tolerated in children, with low rates of adverse events (AEs) (0.7%) and ADRs (0.5%), and no SAEs

Summary

Introduction

Gadobutrol (Gd-DO3A-butrol, Gadovist®, Gadavist®; Bayer Pharma, Leverkusen, Germany) is a second-generation gadolinium-based contrast agent (GBCA) used to enhance tissue contrast in MRI for a range of approved indications in adults and children of all ages [1]. Release of gadolinium ions has been associated with the development of nephrogenic systemic fibrosis (NSF) in people with impaired renal function [8, 9]. In view of these characteristics, gadobutrol has been placed by the American College of Radiology, European Medicines Agency (EMA), and the European Society of Urogenital Radiology in the lowest risk category for development of NSF [10,11,12]. There is extensive safety evidence on the use of gadobutrol in adults, few studies have addressed the safety and tolerability of gadobutrol in pediatric patients

Results

Discussion

Conclusion