UPDATE – BLACK BOX WARNING
On May 23, 2007, the FDA requested that a black box warning be added to all gadolinium-based contrast agents, used during MRI and MRA, to inform health care providers of the risk of a serious, debilitating, and potentially fatal adverse reaction known as Nephrogenic Systemic Fibrosis. Patients with certain kidney and liver related health conditions are those at risk for this serious drug side effect.
The Gadolinium-Based MRI Contrast Agents
- Omniscan (gadodiamide) manufactured by GE Healthcare based in Chalfont St. Giles in the United Kingdom
- Magnevist (gadopentetate dimeglumine) manufactured by Bayer Schering Pharma in Berlin, Germany
- OptiMARK (gadoversetamide) made by Mallinkrodt Inc. based out of Missouri in the United States
- ProHance (gadoteridol) manufactured by Bracco Diagnostics in Princeton, New Jersey
- MultiHance (gadobenate dimeglumine) also made by Bracco Diagnostics
The FDA has requested that this strong black box warning be added to all five contrast agents, though it is not clear to date if all these agents present an equal risk of Nephrogenic Systemic Fibrosis.
These contrast agents are used during Magnetic Resonance Imaging (MRI) and Magnetic Resonance Angiography (MRA) diagnostic testing. Use of these agents helps to make these scans easier to read by healthcare professionals.
It is estimated that over 200 million people have received gadolinium-based contrast agents since the early 1980s. An estimated 30 million people have received gadodiamide (Omniscan) alone, which is the agent most frequently associated with the serious gadolinium side effect Nephrogenic Systemic Fibrosis.
What is Nephrogenic Systemic Fibrosis?
Nephrogenic Systemic Fibrosis (NSF) is a rare but serious, potentially debilitating, and possibly fatal condition that primarily affects the skin and connective tissue but can also affect numerous other organs. NSF was first recognized in numerous patients in California in 1997 and first described in medical literature in 2000.
Originally, this disease was called Nephrogenic Fibrosing Dermopathy, because it was considered a fibrosing skin condition occurring exclusively in patients with renal failure. However, later autopsy findings indicated that this disease can affect several other bodily organs and systems including:
- the skeletal tissue;
- pleura (the lining of the lungs);
- pericardium (lining of the heart);
- myocardium (the muscle wall of the heart);
- and dura (a membranous covering of the brain and spinal cord).
As of 2006, 200 cases of Nephrogenic Systemic Fibrosis had been reported in various countries including the United States, the United Kingdom, the Netherlands, France, Denmark, Austria, and Belgium. Patients affected by this serious gadolinium side effect have included Caucasians and Afro-Americans.
Who is at Risk for Nephrogenic Systemic Fibrosis?
Not every patient who receives gadolinium MRI contrast agents is at risk for NSF. The FDA has informed the public that there have been no reports of nephrogenic systemic fibrosis among patients with normal kidney and liver functioning.
Patients with the following conditions do appear to be at a significant risk of nephrogenic systemic fibrosis after receiving gadolinium MRI contrast agent:
- Patients with kidney insufficiency
- Patients with acute renal failure
- Patients with dialysis-dependant chronic renal failure
- Patients with chronic liver disease
- Patients who have recently had or will soon have liver transplantation
Most, but not all, of the patients with renal insufficiency required dialysis at the time they received gadolinium and subsequently developed nephrogenic systemic fibrosis.
According to medical data, gadolinium is almost entirely processed through the kidneys. Thus, in patients with renal insufficiency, the body takes longer to break down and excrete this contrast agent, which may contribute to the increased risk among this patient population. However, the exact cause of nephrogenic systemic fibrosis is not entirely understood.
In most reported cases of nephrogenic systemic fibrosis, patients have received gadolinium before MRI of the abdomen or pelvic regions and MRA. Most patients who have developed NSF have been between the ages of 24 to 64.
The FDA is now recommending that all patients be screened for kidney problems before receiving a gadolinium MRI contrast agent. Patients who are found to have specific liver and kidney problems should not be given these contrast agents under any circumstances, according to the FDA.
Of the various published medical studies that have investigated the link between gadolinium and nephrogenic systemic fibrosis, most indicate that nephrogenic systemic fibrosis develops 2 to 11 weeks after a patient receives an intravenous dose of gadolinium.
What are the Signs and Symptoms of Nephrogenic Systemic Fibrosis?
Symptoms of nephrogenic systemic fibrosis begin the in peripheral extremities and spread toward the center of the body. Some patients experience symptoms in the abdominal area, but none experience symptoms in the face and neck.
Early signs of nephrogenic systemic fibrosis, those developing within two weeks of gadolinium administration, include:
- Swelling (edema) of the legs, feet, hands and/or arms
- Joint pain
- Muscle pain
- Weakness in the extremities (arms, hands, feet and/or legs)
- Stiffness in the joints
- Bone pain (in the hips, ribs, or other area)
Later signs and symptoms of nephrogenic systemic fibrosis, those developing 2 to 11 weeks after gadolinium administration, can include:
- Persistent skin fibrosis (the formation of fibrous scar-like tissue), which can lead to
- skin tightness,
- skin thickness and/or
- woody induration and a skin condition making the skin look like orange peels
- red or dark patches on the skin
- itching, sharp pains and/or burning in the affected areas
- trouble moving (reduced range of motion) in the extremities
- stiffness in the upper and/or lower extremities
- Weakness and/or muscle pain
- Anatomical extension involving the lower abdomen, thighs, and antebrachium (area between elbow and wrist)
What Treatment is Available for Nephrogenic Systemic Fibrosis?
Unfortunately, nephrogenic systemic fibrosis lacks consistently effective treatment and prevention options. Based on medical research, it also seems that initiating dialysis shortly after the administration of gadolinium does NOT work to prevent the onset of nephrogenic systemic fibrosis. Researchers suspect that gadolinium rapidly triggers NSF in affected patients with renal insufficiency and that this condition cannot be reversed with hemodialysis.
The following treatments have been used with some success in patients with nephrogenic systemic fibrosis:
- Physical therapy
- Oral corticosteroids
- Oral pentoxifylline
- UV therapy
- Extracorporeal photopheresis (ECP)
- Liver/Kidney transplant
It seems that improving renal function, by a number of methods, can work to slow the progression of nephrogenic systemic fibrosis.
Because this disease is relatively new, nephrogenic systemic fibrosis treatments are still being explored and hopefully additional therapies will be developed in the future. Patients wishing to learn more about treatment of this condition should contact a medical expert.
What is the Outcome of Nephrogenic Systemic Fibrosis?
Nephrogenic Systemic Fibrosis can be a severely debilitating disease because the skin tightening and muscle and tendon involvement often lead to joint contractures, which can severely diminish range of motion in the extremities. Many patients lose the ability to walk because of joint contractures, muscle pain, and joint pain. These patients may have to use a cane or a wheelchair or may be bed ridden as a result of nephrogenic systemic fibrosis.
Some patients develop severe skin ulcerations. Others have suffered liver failure and died after developing nephrogenic systemic fibrosis.
This condition can also spread to numerous other organ systems such as the liver, lungs, heart and muscles. Multiple organ involvement is thought to increase the risk of death in patients with nephrogenic systemic fibrosis.
Previous Gadolinium Warnings
In June 2006, the FDA issued a public health advisory to warn medical professionals about the increased risk of nephrogenic systemic fibrosis with use of gadolinium MRI contrast agents. Despite this warning, several radiologists remained unaware of these serious dangers.
At this same time, one of the makers of a gadolinium-based contrast agent issued a health warning, but this warning was not issued in several countries where the product was used. No other makers of gadolinium contrast agents came forward at this time to warn patients of the serious risk of NSF.
In December 2006, medical experts concluded that all radiologists and other medical specialists need to be informed about this serious late adverse reaction that can occur after the administration of gadolinium contrast agents.
A Gadolinium Lawsuit
In May 2007, the mother of an Ohio man filed a lawsuit against Bayer, the makers of Magnevist, which is one of five gadolinium contrast agents. The 24-year-old man, Trevor Drake, was given this contrast agent before his MRI scan for end-stage renal disease and died in 2004 as a result of complications from nephrogenic systemic fibrosis.
The grieving mother of Drake is seeking compensatory and punitive damages on behalf of her late son’s estate.
This gadolinium lawsuit was filed in a U.S. Court with the help of gadolinium attorneys.
Contact our Gadolinium Attorneys
If you or a loved one has developed Nephrogenic Systemic Fibrosis after receiving a gadolinium-based contrast agent during an MRI or MRA, you may have the legal right to seek compensation for your losses and suffering, including medical expenses, disability, death, pain and suffering, and more. To receive a free no-obligation consultation, please contact our qualified and experienced Gadolinium Lawyers, who are dedicated to helping you and your family receive the compensation you deserve.