Prospective Multicenter Study of the Safety of Gadoteridol in 6163 Patients

Abstract

Background: The safety of gadolinium-based contrast agents is of fundamental importance. Purpose: To determine the frequency and severity of immediate-type adverse reactions to approved doses of gadoteridol in patients referred for routine gadoteridol-enhanced MRI in actual clinical practice settings. Study Type: Prospective, observational. Population: In all, 6163 subjects were enrolled (mean age: 56.7 AE 15.4 years; range: 6-93 years). Field Strength/Sequence: 1.5T and 3.0T. Assessment: Assessment was of immediate adverse reactions by the investigating radiologist using the MedDRA System Organ Class and preferred term. Statistical Tests: Summary statistics for continuous variables, descriptive statistics for demographic characteristics. Results: Overall, 19 adverse events occurred in 13 (0.21%) patients, of which 15 in 10 (0.16%) patients were considered related to gadoteridol administration. These events were evenly distributed between male and female subjects and all occurred in adults. Twelve of the 15 related events in eight (0.13%) patients were considered mild in intensity (rapidly selfresolving), while the remaining three events in two patients (0.03%) were considered moderate in intensity. None were of severe intensity and no serious adverse events occurred. Data Conclusion: The rate of immediate-type adverse events following exposure to approved doses of gadoteridol is extremely low, and mostly limited to transient and self-resolving symptoms. Level of Evidence: 2 Technical Efficacy Stage: 5This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Safety and diagnostic efficacy of gadoteridol for magnetic resonance imaging of the brain and spine in children 2 years of age and younger

“…There was no impact on serum creatinine levels and no effects on vital signs or ECG recordings in those infants in whom determinations were made. In terms of safety, our findings confirm the low incidence of acute/subacute adverse events reported by Cho et al [11] in adult and pediatric subjects undergoing routine contrast-enhanced MRI with gadoteridol. Moreover, they bear excellent comparison with findings for other macrocyclic GBCAs in children under 2 years of age [17,[25][26][27][28].…”

“…A second limitation is that our study was insufficiently powered to assess safety in terms of allergic-like reactions. Although a study by Cho et al [ 11 ] in 6,163 patients, including 52 pediatric patients between 2 and 18 years of age, suggests that the incidence of allergic-like reactions to gadoteridol is comparable to incidences observed after exposure to other macrocyclic GBCAs, to our knowledge no adequately powered prospective studies have been performed to investigate the incidence of allergic-like reactions to any GBCA in children younger than 2 years of age. Third, we did not include diffusion tensor imaging (DTI) or diffusion-weighted imaging (DWI) in the evaluation.…”

“…Gadoteridol (ProHance; Bracco, Milan, Italy) is a macrocyclic GBCA, recently approved by the United States Food and Drug Administration (FDA) for use in children younger than 2 years of age, including term neonates [8], with r1 relaxivity similar to the r1 relaxivity values of other macrocyclic GBCAs [9]. Gadoteridol has been shown to have similar safety and efficacy profiles to those of other macrocyclic GBCAs in adults [10,11]. Notably, however, the rate of clearance of gadoteridol from rat brain and body tissues is more rapid than that of the macrocyclic GBCAs gadobutrol and gadoterate meglumine, resulting in significantly lower levels of retained gadolinium in the first weeks and months after administration [12][13][14][15].…”

The TRUTH confirmed: validation of an intraindividual comparison of gadobutrol and gadoteridol for imaging of glioblastoma using quantitative enhancement analysis

“…Given the similar imaging performances of gadoteridol and gadobutrol and assuming similar commercial practicality, the choice of which GBCA to choose comes down to an evaluation of potential safety issues. Whereas prospective multicentre studies of gadobutrol and gadoteridol reveal no differences in terms of immediate contrast reactions [31][32][33][34], animal studies of gadolinium (Gd) retention suggest that gadoteridol is cleared much more from brain and other body tissues than gadobutrol [35][36][37][38][39] resulting in lower levels retained Gd for longer periods of time. However, no signs or symptoms associated with brain Gd retention have yet emerged despite concerted research effort [25][26][27][28], and while the possibility of long-term effects on human health is an area of concern [40], no data are yet available that point to differences between the macrocyclic GBCAs in terms of impact on long-term human health.…”

Clinical Safety of Gadoteridol, Representative of the Macrocyclic Class of Gadolinium‐Based Contrast Agents

“…The large prospective, multicenter study published in this issue of the journal establishes once again, through objective assessment, the very low rate of immediate adverse events (0.16%) related to gadoteridol administration (ProHance). It confirms the excellent safety profile for gadoteridol, in concordance with the other prospective, multicenter studies for this agent as well as for the two alternative macrocyclic gadolinium‐based contrast agents (GBCAs).…”