Assessment of utilization and pharmacovigilance based on spontaneous adverse event reporting of gadopentetate dimeglumine as a magnetic resonance contrast agent after 45 million administrations and 15 years of clinical use.

PURPOSE: Although contrast agents have become indispensable tools in magnetic resonance and their safe and effective use the foundation of many essential diagnostic procedures, only limited summary information on their utilization and pharmacovigilance is available to the community. After voluntary access to the manufacturer spontaneous adverse event database, we assessed the available data for gadopentetate dimeglumine. MATERIAL AND METHODS: Gadopentetate dimeglumine (Gd-DTPA, Magnevist; Berlex/Schering AG, Berlin, Germany) became commercially available in 1988 and is currently marketed in 101 countries. Using the manufacturer's continuous and cumulative database on product distribution and spontaneous adverse event (AE) reporting, we categorized AEs and assessed their cumulative occurrence after 10, 20, and 45 million applications that occurred in 1993, 1997, and 2002, respectively. Furthermore, we reviewed publications in Medline to assess prevalence of the 4 most common MR contrast agents in the indexed literature. RESULTS: Gd-DTPA has been used in more than 45 million magnetic resonance imaging procedures since 1988 and is currently used globally in more than 5 million applications annually. The broadest category of spontaneously reported AEs, subjective symptoms, occurs in less than 0.01% of procedures. Within the total AEs reported, the distribution of serious and nonserious reports was 9.3% and 90.7%, respectively. The rates of AE reporting have changed over time, with increased rates in the second reporting period (1993 to 1997), followed by substantially lower rates in subsequent years. AE reporting rates are the most comprehensive data available; however, there will always be some underestimation of the true event rates. Although no substantial differences were noted among major age groups, substantial differences in reporting frequency were found among regions, with the United States reporting nearly twice as many AEs as Europe in the postmarketing phase. CONCLUSION: The postmarketing utilization and pharmacovigilance analysis of Gd-DTPA has revealed temporal changes and regional differences, overall with an excellent safety profile. Its extensive utilization and safety information have firmly established it as highly used and safe magnetic resonance imaging agent.