Safety of Gadoterate Meglumine (Gd-DOTA) as a Contrast Agent for Magnetic Resonance Imaging: Results of a Post-Marketing Surveillance Study in Japan

Background: Safety is a primary concern with contrast agents used for MRI. If precautions could be taken before the repeated administration of gadolinium-based contrast media, then the awareness and management of adverse reactions would be more efficient. Objectives: To assess the safety and efficacy of gadoterate meglumine (Gd-DOTA) [Magnescope® in Japan, Dotarem® in other countries], a gadolinium-based contrast agent, in patients undergoing imaging of the brain/spinal cord and/or trunk/limbs, and to identify factors associated with the onset of adverse reactions. Methods: The study ran for 4 years and included 3444 cases. The study was conducted before it became known that gadolinium-based contrast agents could trigger the development of nephrogenic systemic fibrosis. Patients for whom the contrast agent was indicated and who underwent imaging of the brain/spinal cord and/or trunk/limbs by MRI were enrolled. There were 1300 inpatients who were followed up during hospitalization (for several days), and 2144 outpatients who were followed up for at least 2 hours on-site. After Gd-DOTA administration, 13 patient baseline characteristics were used to explore factors that might predict a greater likelihood of acute non-renal adverse reactions. The physician’s appraisal of the efficacy of Gd-DOTA was also assessed. Results: A total of 40 adverse reactions were recorded in 32 patients, giving an overall incidence of adverse reactions of 0.93%. Gastrointestinal disorders were the most commonly reported adverse reactions (0.49%). Most adverse reactions reported were of mild intensity and no serious adverse reactions were reported. This study found that statistically significant risk factors for adverse reactions were general patient condition, liver disorder, kidney disorder, health complications, concomitant treatments, and Gd-DOTA dose (although the incidence of adverse reactions was not dose dependent). In the majority of cases (99.53%), the efficacy of Gd-DOTA was rated as ‘effective’ or ‘very effective’; only the presence of kidney disorder was associated with a significantly greater likelihood of Gd-DOTA inefficacy. Conclusion: Overall, this postmarketing surveillance study did not reveal any untoward or unexpected findings concerning the safety or efficacy of Gd-DOTA. The low incidence of adverse reactions (<1%) and the absence of serious adverse reactions reported during the survey period showed that Gd-DOTA was very well tolerated. The use of Gd-DOTA as an MRI-enhancing contrast medium in the clinical practice setting appears to be safe and effective.