Three studies recently published in “Radiology” have shown that certain gadolinium-containing medications, including Magnevist and Omniscan, used in MRI scans may leave potentially toxic residue in the brains of patients who have had the agents administered to them.
Some patients who have received gadolinium-type contrast agents have reported decline in cognitive and thought processes but the manufacturers have claimed that the same studies confirming brain residue did not demonstrate “brain injury”. The manufacturers of the gadolinium-based contrast agents have denied liability but some patients may be filing lawsuits regarding medical injuries.
About Gadolinium-based Contrast Agents (GBCAs)
Gadolinium has long been known to be toxic in nature, though its use around the world has been widespread as a radio-contrast agent in MRI procedures as it has dramatically improved the quality of diagnostic information that can be gained from an imaging procedure.
Unfortunately, even though it is helpful to many patients, gadolinium has caused a number of serious health concerns including nephrogenic systemic fibrosis (NSF), kidney damage, liver damage, cardiac damage, and is most recently suspect due to its deposition in brain tissue.
There are three basic types of gadolinium-based contrast agents (GCBAs) including:
- Linear standard relaxivity agents (Magnevist, Omniscan, OptiMARK)
- Macrocyclic agents (Dotarem, Gadavist, ProHance)
- High-relaxivity agents (Ablavare, Eovist, MultiHance)
Damage caused by GCBAs appears to be related to how much of the central molecule “gadolinium” is allowed to “escape” from the medication. Older “linear” agents such as Magnevist and Omniscan, are more likely to emit gadolinium than newer “macrocyclic” agents which hold the molecule in a chemical “cage”.
In addition, evidence has shown that though the agents do leave deposits of gadolinium in tissues such as bone, skin and connective tissue, it was previously thought that the gadolinium would not be of significant concern in “normal” patients with functioning kidneys and that the medications would likely not cross the blood-brain barrier. The medications were expected to clear body tissues within a reasonable amount of time and to never have entered brain tissue.
The recent journal report is concerning to medical professionals as it indicates that previous beliefs may be untrue and need reconsideration.
About Magnevist and Omniscan
Magnevist is a radiocontrast agent manufactured by Bayer Healthcare, a Germany-based pharmaceutical and medical products giant, with estimated annual revenue of $44 billion. It contains the gadolinium substance, gadopentetate dimeglumine.
Omniscan is manufactured by GE Healthcare, a division of General Electric which has estimated annual revenue of $148 billion. Omniscan contains the gadolinium substance, gadodiamide.
Magnevist was first approved in 1987 and was the first MRI contrast agent to be used, Omniscan was approved in 1993, followed by OptiMARK in 1999. Since then, newer agents have been introduced but these agents have continued to see widespread use, particularly in the U.S.
Magnevist, Omniscan and OptiMARK are of the older gadolinium type of MRI contrast agents with a different type of chemical structure than newer agents. The older agents are “linear” in chemical structure and may be more likely to release the gadolinium molecule itself, making them more toxic than newer agents which hold the gadolinium molecule in a macrocyclic complex, similar to a chemical cage.
Reportedly, the gadolinium agents in Magnevist and Omniscan were unable to cross the “blood-brain” barrier, meaning they could not enter actual brain tissue in a healthy patient and were limited to circulation in the bloodstream, however some MRI patients have “leaky” vessels which are a primary reason for MRI procedures but which may also allow the drug to enter the brain.
The studies discussed in the recent Radiology journal article indicate that not only does gadolinium enter brain tissue but that it may remain there after the MRI procedure has been completed and the drug is expected to have cleared the body. The studies examined neurologic and brain tissue of deceased patients who had previously had Magnevist or Omniscan. Patients who had multiple MRIs showed higher rates of drug residue.
Critics of older medications such as Magnevist and Omniscan have noted that newer agents, such as the macrocyclic Gadavist, are available and may be safer than the “linear” agents. However even though these drugs were approved in Europe and other places around the world as early as 1998, Bayer did not even apply for U.S. FDA approval for Gadavist until 2010 – after reports of another potentially fatal side effect had come to light.
A rare, potentially fatal condition, known as nephrogenic systemic fibrosis (NSF) was identified in 1997, five years after the contrast agents were introduced but physicians were initially mystified as to the cause. In 2001, Omniscan had been implicated in a three cases of renal toxicity and pancreatitis and Magnevist has also been implicated in at least on episode of cardiac failure after its use but gadolinium-containing contrast agents did not become a known suspect as a factor in the development of NSF until early in 2006.
After study of the condition, a Danish radiologist reported case studies of MRI patients who had developed the disorder. The reports initially included 30 patients, which was later expanded to over 150 patients. The Danish Medicines agency sounded the alarm, identifying 25 specific cases linked to Omniscan. In June of 2007, the Commission on Human Medicines in the UK issued an advisory warning against the use of Omniscan in renal patients.
The same Danish radiologist was subsequently sued for libel by General Electric in the UK High Court with GE claiming that there was a “reporting bias” and that “no causal link” had been proven.
In December of 2006, the FDA began to investigate reports of gadolinium-related NSF occurrences and in 2007, the agency required that a “black box” warning be placed on labeling regarding the risk of NSF in gadolinium-based contrast agents. Internal documents show that GE’s own experts urged the company to limit the use of Omniscan in certain patients, but the advice was ignored.
Two FDA reviewers had advised banning Omniscan, Magnevist and a similar drug, Optimark for use patients with severe kidney disease but the agency did not act on that advice until 2010 when it recommended that the drugs not be used at all in patients with impaired kidneys.
These new studies are especially concerning to medical experts as they show the first evidence that the chemical crosses the blood-brain barrier and may also be deposited in other areas of patient’s bodies in those who do not have decreased kidney function.
Side Effects of Magnevist and Omniscan
All medications, including contrast agents like Magnevist and Omniscan may have side effects. Most of these are mild to moderate but some may be more severe or life-threatening.
Less serious side effects may include:
- Hot flash or flushing
- Unpleasant taste in mouth
- Burning or pain at injection site
- Cold feeling or clamminess
More serious effects may include:
- Allergic reaction
- Facial or tongue swelling
- Difficulty breathing
- Neurological symptoms
- Mood changes
- Speech disorder
- Renal symptoms
- Urinary incontinence
- Increased thirst
- Urinary urgency
- Nephrogenic Systemic Fibrosis
- Raised skin plaques
- Skin papules
- Colored skin areas
Any serious adverse event symptoms should be reported to a medical professional immediately and treated as an emergency.
MRI Drugs Lawsuits
Many patients and families of those who were diagnosed with or died from NSF after receiving Magnevist, Omniscan, or OptiMARK have filed lawsuits against the manufacturers. Some of these lawsuits have been settled, while others are still pending.
Recently, attention has begun to focus on other damage that may be caused by GCBA drugs like Magnevist and Omniscan and some patients have reported significant cognitive decline with resulting job loss and personal difficulties. Many of these patients have formed support groups, including one on Facebook regarding the damage that may be caused by GCBAs
Even though the recent studies indicate that gadolinium toxic residue may be left behind in brains of patients who have had MRI procedures, manufacturers have stated that the studies showed that “no clinical effect” such as “brain injury” has been confirmed and have denied liability, though it is notable that the reports only addressed autopsy results.
Investigators have indicated that additional research is needed to further examine the effects, and many patients who have suffered cognitive or other neurological effects may be filing lawsuits against Bayer, GE and other manufacturers.
If you or a loved one has suffered medical injury after receiving gadolinium-containing MRI drugs such as Magnevist or Omniscan, you may be eligible for compensation for medical costs, lost wages and pain and suffering.
Notwithstanding claims relating to this product, the drug/medical device remains approved by the U.S. FDA.