On December 19, 2017, the FDA issued an update to its Drug Safety Communication regarding brain retention of gadolinium-based contrast agents (GBCAs) used for MRIs. Despite mounting evidence that GBCAs leave gadolinium in the brain, bones, and other tissues of all patients who undergo MRIs with contrast, the FDA has decided not to suspend the use of any GBCAs. This is in stark contrast to the actions taken by the European Medicine’s Agency and the U.K.’s Medicines and Healthcare Products Regulatory Agency. Those agencies suspended the use of the linear agents Magnevist, Omniscan, and OptiMark, while requiring changes to all GBCA product labeling. The Japanese Ministry of Health, Labour and Welfare restricted the use of non-specific linear GBCAs only to cases where there is no alternative and it also required changes to product labeling.
In its Safety Alert, the FDA acknowledged that “linear GBCAs result in more retention and retention for a longer time than macrocyclic GBCAs”. However, the FDA concluded that “the benefit of all approved GBCAs continues to outweigh any potential risks”. This action was taken despite “reports of adverse events involving multiple organ systems in patients with normal kidney function”.
In response to the issue of gadolinium retention, the FDA is requiring several actions to alert health care professionals and patients about gadolinium retention after an MRI using a GBCA. These include requiring a new patient Medication Guide for each agent, providing educational information that every patient will be asked to read before receiving a GBCA, and taking actions that can help minimize problems. The FDA is also requiring manufacturers of GBCAs to conduct human and animal studies to further assess the safety of gadolinium-based contrast agents. Product labeling for all GBCAs must be changed to include new warnings and precautions.
Each GBCA will have a patient Medication Guide with agent specific information, and content that is required for all gadolinium-based contrast agents; the Medication Guide for MultiHance and ProHance have recently been released. The Radiology Department of each institution will create educational handouts that every patient will be asked to read before signing the consent form for his or her MRI or MRA with a GBCA.
Patients must be fully-informed about potential risks.
While the new patient Medication Guide and informational handouts are a step in the right direction, they do not tell the entire story about gadolinium toxicity, and therefore do not fully-inform patients about potential risks. Telling a patient who has never heard of gadolinium before that only “trace amounts of gadolinium may stay in the body long-term” downplays the problem and does not reflect the long-term clinical symptoms reported by patients with normal kidney function.
Gadolinium is a toxic metal and any amount that remains in the brain and other parts of the body should be cause for serious concern. While the linear GBCAs are the least stable, macrocyclic agents have been found to leave residual gadolinium in patients’ bodies as well. Based on the published scientific facts about the toxic effects of gadolinium and the mounting evidence of gadolinium deposition in people with normal kidney function, the FDA must do more to protect patients. People must be fully-informed about potential risks and the long-term effects of gadolinium retention before being asked to sign a consent form that may do more to protect others than to protect them.
12/19/2017 – FDA Safety Announcement
Gadolinium-based Contrast Agents (GBCAs): Drug Safety Communication – Retained in Body; New Class Warnings https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm589580.htm
12/14/2017 – Gov.UK- Drug Safety Update; Medicines and Healthcare Products Regulatory Agency
Gadolinium-containing contrast agents: removal of Omniscan and iv Magnevist, restrictions to the use of other linear agents
11/28/2017 – Japanese Ministry of Health, Labour and Welfare
7/20/2017 – European Medicines Agency (EMA)
EMA’s final opinion confirms restrictions on use of linear gadolinium agents in body scans
1/2018 – MultiHance Medication Guide
1/2018 – ProHance Medication Guide