Guerbet

Stability & Experience

The first and most used Macrocyclic GBCA in MRI ^1–2
More than 170 million doses of Dotarem^® have been administered worldwide ³

GBCA, gadolinium-based contrast agent; MRI, magnetic resonance imaging

Dotarem^® is now used in an
MRI procedure
every 3 seconds worldwide ³

Dotarem^® is approved for use in Adults, Pediatric patients, and Term Neonates (0–2 years) for CNS and Whole-body MRI, and Angiography ^*4

No dose adjustment needed for patients with:

• Renal function impairment (mild to severe)
• Hepatic function impairment ⁴

Dotarem^® is indicated in angiography in patients above 18 years old. CNS: Central Nervous system

Dotarem^®'s safety profile has been established in clinical trials and supported by over 35 years of real-world usage ^3-6

Most adverse events were mild in intensity and transient in nature ⁶

Dotarem^® demonstrated a low incidence of immediate adverse events compared with other GBCAs in the real world ^7,8

McDonald JS, Hunt CH, Kolbe AB, et al. Radiology. 2019; 292:620–627.

Retrospective study in 158,100 patients (median age 55 years [IQR 40–67], 51% women); Injections: 140,645 Omniscan^®, 94,109 Gadovist^®, 39,138 MultiHance®, and 8,053 Dotarem^® AAE, Actual Adverse Events; GBCA, gadolinium-based contrast agent.
Single-center experience from reference studies; individual outcomes may vary.

* Reactions per 10,000 injections: MultiHance^® 33; Gadovist^® 20; Omniscan^® 9; Dotarem^® 5
** Reactions per 10,000 injections: MultiHance^® 18; Gadovist^® 16; Omniscan^® 10, Dotarem^® 7.
*** Physiologic-type reactions, including nausea, vomiting, warmth/chills, anxiety, vasovagal reaction, arrhythmia, and convulsions were classified according to American College of Radiology criteria.

Fukushima Y, Ozaki D, Taketomi-Takahashi A, et al. Eur J Radiol. 2024; 176:111504.

*Chemotoxic-type reactions, including nausea, vomiting, chills, anxiety and vasovagal reactions, were classified according to the European Society of Urogenital Radiology (ESUR) Guidelines.
Retrospective study in 18,431 patients with no previous history of AAR (median age 63 years [IQR: 48, 72]; Injections: ProHance^® 16,638, Dotarem^® 14,738, Primovist ® 4,270, Magnevist ^® 4,002, Gadovist ^® 2,179) and 100 patients with a previous history of AAR (median age 56 years [IQR: 40,66]; Injections: ProHance ^® 120, Dotarem ^® 167, Primovist ^® 63, Magnevist ^® 21, Gadovist ^® 47) Single-centered experience from reference studies; individual outcomes may vary.
AAR, Actual Adverse Reaction; GBCA, gadolinium-based contrast agent.

Dotarem^® demonstrated a low incidence of immediate adverse events compared with other GBCAs in the real world ^7,8

McDonald JS, Hunt CH, Kolbe AB, et al. Radiology. 2019; 292:620–627.

Fukushima Y, Ozaki D, Taketomi-Takahashi A, et al. Eur J Radiol. 2024; 176:111504.

Dotarem^® showed both high kinetic and thermodynamic stability compared to other GBCAs ⁹

Adapted from Porta M, et al. Biometals. 2008; 21:469–90.
GBCA, gadolinium-based contrast agent

High thermodynamic and kinetic stability minimize the risk of gadolinium dissociated from the chelated complex ⁹

+Thermodynamic stability

Real-life safety data from international pharmacovigilance databases:

Dotarem^® showed a low percentage of symptoms associated with gadolinium exposure (SAGE) ¹⁰

EV: EudraVigilance (European Medicines Agency database)
FAERS: Food and Drug Administration Adverse Event Reporting System

In the REMIND study, Dotarem^® was found non-inferior to Gadovist^® in the overall visualization and characterization of primary brain tumors ¹¹

REMIND study: A multicenter, double-blind, randomized, controlled intraindividual, crossover, non-inferiority study ¹⁰

Primary Criterion: Non-inferiority of Dotarem^® (gadoteric acid) versus Gadovist^® (gadobutrol) for the overall visualization and characterization of primary brain tumors was demonstrated. The estimated differences from readers were between the lower limits of the 95% confidence intervals (CI) and the non-inferiority margin: 2.3% (95% CI, −1.3 to 5.9), −2.5% (95% CI, −6.5 to 1.4), and 0.6% (95% CI, −1.8 to 3.1). +Study info

The two contrast agents demonstrated identical appearance in lesion visualization and characterization ¹¹

Case Study A ¹¹

A 46-year-old woman with glioblastoma.

T1 spin-echo images (1.5T) show an approximate 65-mm lesion. Time interval between the two MRI examinations was 7 days.

Images are examples from reference studies; individual outcomes may vary.

Dotarem^®

0.1 mmol/kg body weight

Gadovist^®

0.1 mmol/kg body weight

Dotarem^®

0.1 mmol/kg body weight

Gadovist^®

0.1 mmol/kg body weight

Case Study B ¹¹

A 46-year-old woman with glioblastoma.

T1 spin-echo images (1.5T) show an approximate 30-mm mass. Time interval between the two MRI examinations was 8 days.

Images are examples from reference studies; individual outcomes may vary.

No preference between the two contrast agents was shown by off-site readers in the three quantitative secondary criteria

(Internal Morphology, Degree of Contrast Enhancement and Border Delineation). ¹¹

Data showed that GBCA solutions contained trace amounts of Non-Gadolinium rare earth elements (REEs), with levels varying by brand¹²

Dotarem^® – high-quality GBCA with least non-Gd rare earth elements in the solution compared to other conventional macrocyclic GCBAs ¹²

+Study info

Non-Gd Trace metals, including Non-Gd REE, Yttrium, Lead, and Barium
Adapted from Ben Salem D, Barrat JA. Talanta. 2021 1;221:121589
Non Gd REE, non-gadolinium rare earth element; GBCA, gadolinium-based contrast agent

Dotarem^® options for multiple clinical needs ⁴

Vials
5, 10, 15, 20 mL Pre-filled syringe
10, 15, 20 mL Multi-use packaging
60 and 100 mL

Click here to see Dotarem® Summary of Product Characteristics (SmPC).

This content is intended for healthcare professionals only. Dotarem^® (Gadoteric acid) is not registered in all countries. In countries where Dotarem^® (Gadoteric acid) is registered, indications and dosage may vary from country to country. For full information, please refer to the country’s local summary of product characteristics (SmPC). Trademarks are the property of their respective owner.

Reporting of adverse reactions is important. Guerbet encourages you to report any adverse reactions to your health authorities or local Guerbet representatives or through Pharmacovigilance.Headquarters@Guerbet.com

REFERENCES

1. Runge VM, et al. The developmental history of the gadolinium chelates as intravenous contrast media for magnetic resonance. Invest Radiol. 2011; 46:807–16.
2. Data on file: Guerbet internal data (2024 Q1 Global). Data exclude generic brands, except GE HealthCare (Clariscan ), Bayer (Dotagraf®), and local generics in Japan.
3. Data on file: Guerbet internal data (2024 Q1). Data based on sales estimation and annual results (1989–2021).
4. Dotarem^® Company Core Data Sheet V4 (May 2024).
5. Soyer P et al. Observational Study on the Safety Profile of Gadoterate Meglumine in 35,499 Patients: The SECURE Study. J Magn Reson Imaging. 2017; 45: 988-997
6. de Kerviler E, et al. Adverse Reactions to Gadoterate Meglumine: Review of Over 25 Years of Clinical Use and More Than 50 Million Doses. Invest Radiol. 2016; 51:544– 51.
7. McDonald et al., Acute Adverse Events Following Gadolinium-based Contrast Agent Administration: A Single-Center Retrospective Study of 281 945 Injections. Radiology. 2019; 292:620–627.
8. Fukushima Y, et al., Assessment of first-time and repeated acute adverse reactions to gadolinium-based contrast agents in MRI: A retrospective study. Eur J Radiol. 2024; 176:111504.
9. Port M, et al. Efficiency, thermodynamic and kinetic stability of marketed gadolinium chelates and their possible clinical consequences: a critical review. Biometals. 2008; 21:469–490.
10. Shahid I, et al. Use of Real-Life Safety Data From International Pharmacovigilance Databases to Assess the Importance of Symptoms Associated With Gadolinium Exposure. Invest Radiol. 2022; 57:664–673.
11. Maravilla KR, et al. Comparison of Gadoterate Meglumine and Gadobutrol in the MRI Diagnosis of Primary Brain Tumors: A Double-Blind Randomized Controlled Intraindividual Crossover Study (the REMIND Study). AJNR Am J Neuroradiol. 2017; 38:1681–1688.
12. Ben Salem D and Barrat JA. Determination of rare earth elements in gadolinium-based contrast agents by ICP-MS. Talanta. 2021; 221:121589.

P24003187 - November 2024

The REMIND Study

STUDY DESIGN:

A multicenter, double-blind, randomized, controlled intraindividual, crossover, noninferiority study enrolled 279 patients of which 249 (89%) completed. Patients with known or highly suspected primary brain tumors scheduled for contrast-enhanced magnetic resonance imaging (MRI) were included. Exclusion criteria included rapidly evolving brain tumors, recent treatment affecting lesion appearance, pregnancy or breastfeeding, contraindications to MRI, severe renal impairment, congestive heart failure, adverse reactions to gadolinium-based contrast agents, recent contrast agent use, or participation in another clinical trial within 30 days. Each patient underwent two identical MRI sessions within 2–14 days on 1.5T or 3T MRI systems with Dotarem^® (gadoteric acid 0.1 mmol/kg body weight) and Gadovist^® (gadobutrol 0.1 mmol/kg body weight). Images were evaluated by three independent neuroradiologists (one on-site, two off-site) for overall lesion visualization and characterization (primary endpoint, non-inferiority margin is set at −10%); secondary endpoints included lesion border delineation, internal morphology, contrast enhancement, and diagnostic confidence. Qualitative assessments, signal intensity measurements, and safety (adverse events, AEs), were also evaluated.

PATIENT DEMOGRAPHICS:

Patients ranged in age from 18–98 years, with a mean age of 53.6 ± 15.1 years; 64% were female. The most frequent diagnoses after MRI were tumors of the meninges (49.3%), glioma (14.9%), and tumors not otherwise specified (13.1%).

ALL POSTINJECTION ADVERSE EVENTS WERE MILD OR MODERATE:

The incidence of postinjection AEs was similar between the two contrast agents. Two serious AEs during the study were related to the primary brain tumor, not the contrast agent.

Reference: Maravilla KR et al. Comparison of Gadoterate Meglumine and Gadobutrol in the MRI Diagnosis of Primary Brain Tumors: A Double-Blind Randomized Controlled Intraindividual Crossover Study (the REMIND Study). AJNR Am J Neuroradiol. 2017; 38:1681-1688.