Coauthors of The Lighthouse Project provide facts about Gadolinium Toxicity to FDA Advisory Committee
As coauthors of The Lighthouse Project, we have provided written comments about the toxic effects of gadolinium and gadolinium retention in patients with normal renal function to the FDA’s Medical Imaging Drugs Advisory Committee in advance of its September 8, 2017 meeting. We will be making a brief oral presentation during the Open Public Hearing portion of the meeting which will be held at the FDA’s White Oak Campus in Silver Spring, Maryland.
Our comments are built around the following 6 major points that we cover in making the case that the FDA needs to take action regarding the use of Gadolinium-based Contrast Agents (GBCAs) administered for contrast-enhanced MRIs.
1. Medical literature documents toxicity of gadolinium and systemic implications.
2. The Risk Factors for adverse results are many.
3. NSF-Like Symptoms in patients with normal renal function.
4. Gadolinium from GBCAs does not clear the body in a few days, or even in a few months, allowing plenty of time for the Gd ion to dissociate from the chelate.
5. Underreported Symptoms from Contrast MRIs is a serious problem.
6. There is evidence of clinical implications of gadolinium deposition.
Our detailed comments can be found here: Comments-from-Lighthouse-Project-FDA-2017-N-1957 . We also included the following supporting materials:
- Sharon’s 2012 Letter to the FDA (SWilliams-2012FDALetter-FDA-2017-N-1957)
- Our Symptom Survey of the Chronic Effects of Retained Gadolinium from Contrast MRIs (Lighthouse Symptom Survey copy for Docket FDA-2017-N-1957), and
- Our most recent report, Gadolinium Retention from Contrast MRIs in 70 Cases with Normal Renal Function – 24-hour Urine Test Results (Lighthouse 70 Case Retention Study copy for Docket FDA-2017-N-1957)
We will report back later about our experience at the FDA Advisory Committee Meeting.
Sharon Williams and Hubbs Grimm
Sharyl Attkisson, five-time Emmy Award winner, and recipient of the Edward R. Murrow investigative reporting award, featured Gadolinium Toxicity in her June 11 edition of Full Measure. Chuck Norris and his wife Gena Norris both talked about her struggle with her related symptoms that resulted in them spending over $1,000,000 on special care.
Our own Sharon Williams was also featured in the segment, both for her own symptoms and for her advocacy including letters to the FDA in starting in 2012 and the maintenance of this website..
Y0u can see a video of the program and read the dialogue here:
On July 21, 2017, the European Medicines Agency (EMA) confirmed previous recommendations to suspend the use of three linear gadolinium-based contrast agents (GBCAs) used for MRIs, citing potential risks from brain deposition of gadolinium. The use of one other linear GBCA will be restricted to liver scans.
The 3 suspended agents are Magnevist (gadopentetic acid), Omniscan (gadodiamide), and OptiMark (gadoversetamide). The agent restricted to liver scans is MultiHance (gadobenic acid).
Read the article on Aunt Minne about this action here:
The official announcement from the EMA can be found here:
Additional information on the EMA website can be found here:
We are encouraged by the EMA’s action and believe that the FDA should take a similar stance.
Patients and their doctors should report all adverse events and clinical symptoms to the FDA or the appropriate governing authority in their country. Chronic symptoms that develop soon after MRIs with contrast could be manifestations of the harm done by gadolinium deposition in the brain, bones, and elsewhere in the body.
On Monday, May 22, 2017, the FDA issued its second Safety Announcement about gadolinium retention in the brain. The following text is the FDA’s complete announcement.
FDA Drug Safety Communication: FDA identifies no harmful effects to date with brain retention of gadolinium-based contrast agents for MRIs; review to continue
This is an update to the FDA Drug Safety Communication: FDA evaluating the risk of brain deposits with repeated use of gadolinium-based contrast agents for magnetic resonance imaging (MRI)issued on July 27, 2015.
A U.S. Food and Drug Administration (FDA) review to date has not identified adverse health effects from gadolinium retained in the brain after the use of gadolinium-based contrast agents (GBCAs) for magnetic resonance imaging (MRI). All GBCAs may be associated with some gadolinium retention in the brain and other body tissues. However, because we identified no evidence to date that gadolinium retention in the brain from any of the GBCAs, including GBCAs associated with higher retention of gadolinium, is harmful, restricting GBCA use is not warranted at this time. We will continue to assess the safety of GBCAs and plan to have a public meeting to discuss this issue in the future.
Our recommendations for health care professionals and patients remain unchanged from July 2015 when we informed the public that we were investigating this potential risk with GBCAs. As is appropriate when considering the use of any medical imaging agent, health care professionals should limit GBCA use to circumstances in which additional information provided by the contrast agent is necessary, and assess the necessity of repetitive MRIs with GBCAs. Patients, parents, and caregivers should talk to their health care professionals if they have any questions or concerns about the use of GBCAs with MRIs. Retention of gadolinium affects only GBCAs, and does not apply to other types of scanning agents used for other imaging procedures, such as those that are iodine-based or radioisotopes.
GBCAs contain gadolinium, a type of heavy metal, that is linked to a carrier molecule. MRIs are a way to scan the body for problems such as cancer, infections, or bleeding. GBCAs are injected into a vein to enhance the quality of the MRI images of internal organs, blood vessels, and tissues, which helps health care professionals diagnose medical conditions. There are two types of GBCAs based on their chemical structures, linear GBCAs and macrocyclic GBCAs.
We evaluated scientific publications1-17 and adverse event reports submitted to FDA. Some human and animal studies looked at GBCA use over periods longer than a year. These publications and reports show that gadolinium is retained in organs such as the brain, bones, and skin. The publications show that linear GBCAs retain more gadolinium in the brain than macrocyclic GBCAs. However, our review did not identify adverse health effects related to this brain retention.
To date, the only known adverse health effect related to gadolinium retention is a rare condition called nephrogenic systemic fibrosis (NSF) that occurs in a small subgroup of patients with pre-existing kidney failure. NSF is a painful skin disease characterized by thickening of the skin, which can involve the joints and cause significant limitation of motion within weeks to months. Recent publications report cases of reactions involving thickening and hardening of the skin and other tissues in patients with normal kidney function who received GBCAs and did not have NSF; some of these patients also had evidence of gadolinium retention.3, 12, 16 We are continuing to evaluate such reports to determine if these fibrotic reactions are an adverse health effect of retained gadolinium.
The manufacturer of OptiMARK (gadoversetamide), a linear GBCA, updated its label with information about gadolinium retention in various body organs such as the brain, skin, and other organs. We are reviewing the labels of other GBCAs to determine if changes are needed.
A recent review by the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) also identified no adverse health effects with gadolinium retention in the brain, but that Committee recommended suspending the marketing authorization of certain linear GBCAs because they cause a greater retention of gadolinium in the brain compared to macrocyclic GBCAs. The Committee’s recommendation is currently undergoing an appeal, which will be further reviewed by the PRAC and subsequently by the EMA’s Committee for Medicinal Products for Human Use.18
We are continuing to assess the safety of GBCAs. FDA’s National Center for Toxicological Research (NCTR) is conducting a study on brain retention of GBCAs in rats. Other research is also being conducted about how gadolinium is retained in the body. We will update the public when new information becomes available and we plan to have a public meeting to discuss this issue in the future.
We urge patients and health care professionals to report side effects involving GBCAs or other medicines to the FDA MedWatch program, using the information in the “Contact FDA” box at the bottom of the page.
The list of approved GBCAs and References included with this FDA Communication can be found here: https://www.fda.gov/Drugs/DrugSafety/ucm559007.htm
The link to MedWatch can be found on the Contact FDA page.