Gadoteridol (SQ-32692)

Risk of Nephrogenic Systemic Fibrosis in Patients With Stage 4 or 5 Chronic Kidney Disease Receiving a Group II Gadolinium-Based Contrast Agent: A Systematic Review and Meta-analysis

JAMA Intern Med 2020 Feb 1;180(2):223-230.31816007 PMC6902198

Importance: Risk of nephrogenic systemic fibrosis (NSF) to individual patients with stage 4 or 5 chronic kidney disease (CKD; defined as estimated glomerular filtration rate of <30 mL/min/1.73 m2) who receive a group II gadolinium-based contrast agent (GBCA) is not well understood or summarized in the literature. Objective: To assess the pooled risk of NSF in patients with stage 4 or 5 CKD receiving a group II GBCA. Data sources: A health sciences informationist searched the Ovid (MEDLINE and MEDLINE Epub Ahead of Print, In-Process & Other Non-Indexed Citation, and Daily and Versions), Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Open Grey databases from inception to January 29, 2019, yielding 2700 citations. Study selection: Citations were screened for inclusion in a multistep process. Agreement for final cohort inclusion was determined by 2 blinded screeners using Cohen κ. Inclusion criteria consisted of stage 4 or 5 CKD with or without dialysis, administration of an unconfounded American College of Radiology classification group II GBCA (gadobenate dimeglumine, gadobutrol, gadoterate meglumine, or Gadoteridol), and incident NSF as an outcome. Conference abstracts, retracted manuscripts, narrative reviews, editorials, case reports, and manuscripts not reporting total group II GBCA administrations were excluded. Data extraction and synthesis: Data extraction was performed for all studies by a single investigator, including publication details, study design and time frame, patient characteristics, group II GBCA(s) administered, total exposures for patients with stage 4 or stage 5 CKD, total cases of unconfounded NSF, reason for GBCA administration, follow-up duration, loss to follow-up, basis for NSF screening, and diagnosis. Main outcomes and measures: Pooled incidence of NSF and the associated upper bound of a 2-sided 95% CI (risk estimate) for the pooled data and each of the 4 group II GBCAs. Results: Sixteen unique studies with 4931 patients were included (κ = 0.68) in this systematic review and meta-analysis. The pooled incidence of NSF was 0 of 4931 (0%; upper bound of 95% CI, 0.07%). The upper bound varied owing to different sample sizes for gadobenate dimeglumine (0 of 3167; upper bound of 95% CI, 0.12%), gadoterate meglumine (0 of 1204; upper bound of 95% CI, 0.31%), gadobutrol (0 of 330; upper bound of 95% CI, 1.11%), and Gadoteridol (0 of 230; upper bound of 95% CI, 1.59%). Conclusions and relevance: This study's findings suggest that the risk of NSF from group II GBCA administration in stage 4 or 5 CKD is likely less than 0.07%. The potential diagnostic harms of withholding group II GBCA for indicated examinations may outweigh the risk of NSF in this population. Trial registration: PROSPERO identifier: CRD42019123284.

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

J Magn Reson Imaging 2020 Mar;51(3):869-870.31614049 10.1002/jmri.26957

Dosage of Gadoteridol and adverse reactions relative to gadopentetate

Am J Health Syst Pharm 1995 Nov 15;52(22):2556-9.8590239 10.1093/ajhp/52.22.2556

Compliance with an institution's dosage guidelines for Gadoteridol was determined, and adverse reactions to Gadoteridol and gadopentetate were compared. Departmental policy in March 1993 set the standard dose of Gadoteridol at 0.1 mmol/kg. A dose of 0.05 mmol/kg was set for patients with suspected acoustic neurinomas or pituitary microadenomas. Guidelines allowing a high dose of 0.2 or 0.3 mmol/kg were also established for specific indications involving suspected metastatic disease or inadequate contrast enhancement at the standard dose. Data on Gadoteridol use were collected concurrently from May 1993 to January 1994 and included the dose, the indication for the dose, and any adverse reactions. Safety data for patients who had received gadopentetate between June 1988 and March 1990 were also collected and reviewed. The subjects in this retrospective analysis represented the same broad population as those involved in the concurrent evaluation of Gadoteridol use. The frequency and types of adverse events in the two groups were compared. During the gadoteridol-review period, 8377 patients underwent magnetic resonance imaging studies; 3558 (42.5%) of them received Gadoteridol. Of the 3558 doses given, 3375 (94.9%) were 0.1 mmol/kg (the standard dose). Compliance with the guidelines for nonstandard doses was 90% for the 0.3-mmol/kg dose, 74% for the 0.2-mmol/kg dose, and 39% for the 0.05-mmol/kg dose. There were 101 adverse reactions to Gadoteridol in 75 (2.1%) of the 3558 recipients. The reactions were mild to moderate and self-limiting. Records for 4892 gadopentetate recipients were analyzed. There were adverse reactions in 62 patients (1.3%). Again, most reactions were mild to moderate. The use of Gadoteridol at a medical center generally complied with institutional guidelines. Gadoteridol was well tolerated whether given in standard or high doses. The frequencies and types of adverse reactions to Gadoteridol and gadopentetate were similar.

Physicochemical properties of Gadoteridol and other magnetic resonance contrast agents

Invest Radiol 1992 Aug;27 Suppl 1:S2-6.1506149

Investigation of the ototoxicity of Gadoteridol (ProHance) and gadodiamide (Omniscan) in mice

Acta Otolaryngol 2016 Nov;136(11):1091-1096.27315460 10.1080/00016489.2016.1193892

Conclusion: In the mouse, when a tympanic perforation is present, Gadoteridol does not seem to cause ototoxicity. Gadodiamide may cause mild ototoxicity other than toxicity to the outer hair cells of the cochlea. Objectives: Endolymphatic hydrops have been visualized through intra-tympanic injection of gadolinium-based contrast agents (GBCAs) and three-dimensional fluid-attenuated inversion recovery (3-D FLAIR) magnetic resonance imaging. However, reports on the safety of GBCAs are limited. This study aimed to assess ototoxicity of Gadoteridol and gadodiamide. Method: In a prospective, randomized, controlled trial, myringotomies in the left ear were performed in 20 male C57 BL/6 mice. After testing the baseline auditory brainstem response (ABR) (range = 8-32 kHz), the test solution (Gadoteridol, gadodiamide, saline, or cisplatin) was injected into the left ear. ABR testing was repeated 14 days after test solution application. In morphological experiments, images of post-mortem surface preparations were assessed for cochlear hair cell status. Results: At 14 days following Gadoteridol application, there was no significant change in ABR thresholds at 8, 16, or 32 kHz. Gadodiamide application caused a significant change in the ABR threshold at 8 kHz. Apparent cochlear hair cell loss was not observed in the surface preparation after Gadoteridol or gadodiamide application.