Reuters is reporting that the panel supported new warnings for General Electric's Omniscan and Covidien Inc.'s OptiMark that say they should not be used in patients with severe kidney disease. The panel felt that Omniscan and OptiMark. along with Bayer's Magnevist appeared to carry a higher NSF risk than similar products. The recommendations represented a "preponderance of opinion" on the panel, and not a formal vote, Reuters said.
Meanwhile, Dow Jones News Service is reporting that the same FDA panel also recommended restricting the use of Magnevist to patients without kidney severe kidney disease. However, according to Reuters, there was less consensus on the panel in regards to Magnevist.
The FDA is not required to follow the recommendations of its advisory panels, but it usually does so.
NSF is a debilitating disease that leads to excessive formation of connective tissue in the skin and internal organs. It is characterized by high blood pressure, burning, itching, swelling and hardening of the skin. Other symptoms include red or dark patches on the skin; pain deep in the hip bones or ribs and muscle weakness. NSF can progress to the point of causing severe stiffness in joints, and it can lead to death.
Gadolinium Contrast Dyes are approved for use in Mri procedures, and are sometimes used off-label in MRA studies. It appears that NSF only develops in people with pre-existing kidney disease. In 2007, the FDA asked the manufacturers of all gadolinium Contrast Dyes to add a black box warning to the product labels about their association with NSF. Since the warning, the FDA and the makers of gadolinium Contrast Dyes have continued to collect data about their association with NSF.
According to documents released last month by the FDA in advance of today's meeting, the highest risk of NSF was associated with Omniscan, Magnevist and OptiMark. The lowest risk was associated with Prohance and Multihance, both marketed by Bracco Diagnotics. However, the FDA was unable to rule out a risk for any of the agents.
FDA staff said it was too early to reach conclusions about Bayer's Eovist and Lantheus Medical Imaging's Ablavar, two recently approved gadolinium agents.
According to Dow Jones, at today's FDA advisory panel meeting, radiologists said that clinicians have essentially stopped using gadolinium agents in patients with severe kidney disease. The panel was also told that reports of NSF have dropped significantly since the black box warning was mandated.
Last month, Europe's health regulatory agency said Omniscan, Magnevist and OptiMark shouldn't be used in patients with severe kidney problems.
As we previously reported, Covidien has already decided to modify the label of OptiMark to contraindicate its use in patients with severe kidney impairment because of its association with NSF.
Gadolinium Contrast Dyes are approved for use in Mri procedures, and are sometimes used off-label in MRA studies. These agents were first introduced in the 1980s, and there are currently five such Dyes on the market. They are: OptiMARK, by Covidien Inc., Prohance and Multihance, both by Bracco Diagnostics, Bayer Healthcare’s Magnevist and GE Healthcare’s Omniscan.
NSF is a debilitating disease that leads to excessive formation of connective tissue in the skin and internal organs. It is characterized by high blood pressure, burning, itching, swelling and hardening of the skin. Other symptoms include red or dark patches on the skin; pain deep in the hip bones or ribs and muscle weakness. NSF can progress to the point of causing severe stiffness in joints, and it can lead to death.
It appears that NSF only develops in people with pre-existing kidney disease. In September 2007, the FDA asked the manufacturers of all gadolinium Contrast Dyes to add a black box warning to the product labels about its association with NSF. The FDA also warned that patients with kidney disease should avoid gadolinium Contrast agents, and that the lowest possible dosage should be administered to such patients if use of the Dyes cannot be avoided.
Since the 2007 black box warning, the FDA has continued to collect data on gadolinium Contrast Dyes and NSF. According to documents released last month by the FDA, the highest risk of NSF was associated with Omniscan, Magnevist and OptiMARK. The lowest risk was associated with Prohance and Multihance. However, the agency said “the data do not appear to rule out an NSF risk for each of the agents.” FDA reviewers said the extent of risk from any of the agents was unknown. One study of Omniscan estimated the chances of developing NSF was 4 percent among patients with severe kidney impairment.
Though the agency’s drug safety unit said the risk associated with the gadolinium Contrast Dyes “does not compel removal of specific (imaging agents) from the U.S. market”, it has recommended that the drug labels note the varying levels of risks with each product.
That issue will be addressed at the December 8 advisory panel meeting. However, as we previously reported, Covidien has already decided to modify the label of OptiMark to contraindicate its use in patients with severe kidney impairment because of its association with NSF. At the time, a spokesperson for the company told Reuters that “it was prudent to act now, rather than wait for a causal link… to be established” between the imaging drugs and NSF.
NSF is a debilitating disease that leads to excessive formation of connective tissue in the skin and internal organs. It is characterized by high blood pressure, burning, itching, swelling and hardening of the skin. Other symptoms include red or dark patches on the skin; pain deep in the hip bones or ribs and muscle weakness. NSF can progress to the point of causing severe stiffness in joints, and it can lead to death.
Gadolinium Contrast Dyes are approved for use in Mri procedures, and are sometimes used off-label in MRA studies. These agents were first introduced in the 1980s, and there are currently five such Dyes on the market. They are: Covidien's OptiMARK; Prohance and Multihance, both by Bracco Diagnostics; Bayer Healthcare’s Magnevist; and GE Healthcare’s Omniscan.
It appears that NSF only develops in people with pre-existing kidney disease who are exposed to the gadolinium agents. In September 2007, the U.S. Food & Drug Administration (FDA) asked the manufacturers of all gadolinium Contrast Dyes to add a black box warning to the product labels about its association with NSF. The FDA also warned that patients with kidney disease should avoid gadolinium Contrast agents, and that the lowest possible dosage should be administered to such patients if use of the Dyes cannot be avoided.
The Mayo Clinic study involved 94,917 patients exposed to gadolinium agents at the Mayo Clinic between January 1, 1999 and December 31, 2006. Of that group, 3,779 patients were on hemodialysis, 1,694 patients had undergone a kidney transplant, and 717 patients had liver transplants. A total of 61 patients had a clinical diagnosis of NSF.
The study found that 1% of patients undergoing hemodialysis, and 0.8% of patients who have undergone kidney transplant were at risk of developing NSF. The risk for liver transplant patients was 0%.
The study authors advocated for the development of new guidelines for the administration of gadolinium agents.
We reported previously this week that the FDA is still looking into the association between gadolinium agents and NSF. On Wednesday, we reported that an FDA review had found that OptiMARK, Magnevist and Omniscan carried a higher risk of NSF than other gadolinium agents on the market. Though the agency’s drug safety unit said the risk associated with the gadolinium Contrast Dyes “does not compel removal of specific (imaging agents) from the U.S. market”, it has recommended that the drug labels note the varying levels of risks with each product. An outside panel of experts will take up the issue in December.
Following the news from the FDA, Covidien announced it would be modifying the label on OptiMARK to contraindicate its use in patients with severe kidney impairment. Mallinckrodt Inc., a Covidien company, has submitted this label change to the FDA and says it is implementing the new label in the U.S. effective immediately. Covidien also will update its educational materials to help physicians make informed decisions regarding the appropriate use of OptiMARK.
Gadolinium Contrast Dyes are approved for use in Mri procedures, and are sometimes used off-label in MRA studies. These agents were first introduced in the 1980s, and there are currently five such Dyes on the market. These Dyes include: Omniscan by GE Healthcare; OptiMARK by Mallinckrodt/Tyco Healthcare; Magnevist by Bayer/Schering AG/Berlex; ProHance by Bracco Diagnostics and MultiHance by Bracco Diagnostics.
In September 2007, the Food & Drug Administration Gabriel movie full (FDA) asked the manufacturers of gadolinium Contrast Dyes to add a black box warning to the products' labels regarding their association with NSF. The FDA also warned that patients with kidney disease should avoid gadolinium Contrast agents.
NSF is a debilitating disease that leads to excessive formation of connective tissue in the skin and internal organs. It is characterized by high blood pressure, burning, itching, swelling and hardening of the skin. Other symptoms include red or dark patches on the skin; pain deep in the hip bones or ribs and muscle weakness. NSF can progress to the point of causing severe stiffness in joints, and it can lead to death.
NSF is a relatively new disease. In fact, the first known diagnosis of NSF only occurred in 1997, but it wasn't until September 2000 that details of the disease were published in the medical journal Lancet. It appears that it only develops in people with pre-existing kidney disease.
Several studies have strongly suggested a link between NSF and gadolinium Contrast Dyes. This latest study, published in the journal Nephrology Dialysis Transplantation, consisted of a systemic review and meta-analysis of seven controlled studies that have examined the association between gadolinium Contrast Dyes and NSF.
The meta-analysis found very strong evidence of a causal relationship between NSF and gadolinium Contrast Dyes. According to a press release detailing the University of Pennsylvania study, that evidence included:
* consistently similar results and large magnitude of effect shown in all studies analyzed;
* a clear temporal relationship found in all but one study;
* a dose-response relationship shown in three studies. Two studies did not find this relationship and the other studies did not examine the relationship.
In addition, gadodiamide is excreted renally, so it is biologically plausible for it to cause NSF, the investigators observed. Furthermore, gadodiamide is both detectable and quantifiable in the tissues of patients with NSF. Finally, the researchers cited a case in which a patient who had clinical resolution of NSF developed the condition again when re-exposed to a gadolinium Contrast Dye.
The authors of the meta-analysis concluded that their findings suggest a "potent and significant" association between gadolinium Contrast Dyes and NSF among patients with advanced chronic kidney disease.
In February 2008, the U. S. Judicial Panel on Multidistrict Litigation designated the U.S. District Court for the Northern District of Ohio as the venue for NSF lawsuits pending in federal courts. The Judicial Panel on Multidistrict Litigation of the United States Courts was created in 1968. Since then, it has consolidated hundreds of thousands of lawsuits that involved high numbers of plaintiffs, including litigation over asbestos, breast implants and other matters.
Currently, there are just over 400 lawsuits pending in the Multidistrict Litigation. At a status conference held on March 6, Judge Dan Aaron Polster announced that the first trials will begin next January. The parties involved in the litigation have each selected 10 cases, known as Eligible Trial Pool Cases, which are currently undergoing early discovery in preparation for the first trials. Those 20 will be narrowed down to 10, with 5 chosen by the plaintiffs and 5 chosen by the defendants for the first trials. Defendants and plaintiffs will then select two from each sides' list for the first four trials.
NSF is a devastating condition that affects people with pre-existing kidney problems. There is currently no cure for NSF and no one understands its specific cause. The disorder is characterized by high blood pressure, burning, itching, swelling and hardening of the skin. Other symptoms include red or dark patches on the skin; pain deep in the hip bones or ribs and muscle weakness. NSF can progress to the point of causing severe stiffness in joints, and it can lead to death.
A growing mountain of evidence has linked NSF to gadolinium Contrast Dyes, and it is theorized that people with kidney problems may not be able to quickly eliminate gadolinium from their body. In September 2007, the Food & Drug Administration (FDA) asked the manufacturers of gadolinium Contrast Dyes to add a black box warning to the product labels about its association with NSF. The FDA also warned that patients with kidney disease should avoid gadolinium Contrast agents if they must undergo an Mri or MRA procedure.
NSF is debilitating, and sometimes fatal disease, that affects people with pre-existing kidney diseases who have undergone Mri studies that involve gadolinium Contrast Dyes. There is currently no cure for NSF and no one understands its specific cause. The disorder is characterized by high blood pressure, burning, itching, swelling and hardening of the skin. Other symptoms include red or dark patches on the skin; pain deep in the hip bones or ribs and muscle weakness. NSF can progress to the point of causing severe stiffness in joints, and it can lead to death.
The evidence that gadolinium Contrast agents play a role in the development of NSF is fast becoming irrefutable. Dutch scientists made the first connection between NSF and gadolinium in 2006. Since then, researchers at Yale University have reported that 95-percent of those with NSF had undergone a Magnetic Imaging Resonance (Mri) procedure that involved a gadolinium Contrast Dye two to three months before their symptoms appeared. Researchers at Massachusetts General Hospital also have found that kidney patients who had undergone Mris with gadolinium Contrast Dyes were 10 times more likely to develop NSF than patient who had not been exposed to such agents.
In 2007, the Food & Drug Administration (FDA) asked the manufacturers of gadolinium Contrast Dyes to add a black box warning to the product labels about its association with NSF. The FDA also warned that patients with kidney disease should avoid gadolinium Contrast agents.
For the study detailed in Radiology, researcher analyzed cases of biopsy-confirmed NSF among all patients who received a gadolinium-based Contrast agent between January 1, 1997, and June 30, 2007. In total, there were 31 biopsy-confirmed cases of NSF in 10 men and 21 women. The patients ranged in age from 13 to 82 years.
The researchers found that hemodialysis helped prevent NSF in patients with an estimated glomerular filtration rate (eGFR)- a measure of kidney function - of less than 15 mL/min. Increased risk of NSF was associated with patients with an eGFR of less than 30 mL/min who received a higher dose of gadolinium Contrast Dye, and who also experienced acute renal failure, delayed hemodialysis after Contrast agent injection, proinflammatory events, and hyperphosphatemia, a condition where there is abnormally elevated level of phosphate in the blood.
The study also found that the dosage level of the gadolinium agent played a role in the development of NSF. The occurrence NSF after gadolinium-based Contrast agent administration without screening for renal function were 0 of 74,124 patients with a standard gadolinium dose and 15 (0.17%) of 8,997 patients with the high dose. The incidence associated with the high dose increased to 0.4% in the patients who received hemodialysis and increased to 8.8% in patients who had an eGFR less than 15 mL/min but had not received hemodialysis treatment.
Eleven of 69 patients with acute renal failure who received a high dose when their creatinine level was increasing developed NSF when hemodialysis was delayed for more than two days.
The authors of the study concluded that the chances of a patient developing NSF could be lessened by first identifying those with eGFR in the range of 30 mL/min or less. Those patients should receive a lower dose (no more than 0.1 mmol/kg). Finally, the authors wrote that patients "who have acute renal failure with increasing serum creatinine levels or who are in a dialysis regimen at the time of gadolinium-based Contrast agent administration should undergo hemodialysis shortly after the gadolinium-enhanced MR examination."
NSF is a devastating condition that affects people with pre-existing kidney problems. There is currently no cure for NSF and no one understands its specific cause. The disorder is characterized by high blood pressure, burning, itching, swelling and hardening of the skin. Other symptoms include red or dark patches on the skin; pain deep in the hip bones or ribs and muscle weakness. NSF can progress to the point of causing severe stiffness in joints, and it can lead to death.
The evidence that gadolinium Contrast agents play a role in the development of NSF is fast becoming irrefutable. Dutch scientists made the first connection between NSF and gadolinium in 2006. Since then, researchers at Yale University have reported that 95-percent of those with NSF had undergone a Magnetic Imaging Resonance (Mri) procedure that involved a gadolinium Contrast Dye two to three months before their symptoms appeared. Researchers at Massachusetts General Hospital also have found that kidney patients who had undergone Mris with gadolinium Contrast Dyes were 10 times more likely to develop NSF than patient who had not been exposed to such agents.
In September 2007, the Food & Drug Administration (FDA) asked the manufacturers of gadolinium Contrast Dyes to add a black box warning to the product labels about its association with NSF. The FDA also warned that patients with kidney disease should avoid gadolinium Contrast agents.
According to the lawsuit, the plaintiff received an injection of Magnevist gadolinium Contrast Dye on March 23, 2001. The Brooklyn Center, Minn. woman was diagnosed with NSF in February 2007. The lawsuit, which names Bayer-Schering and its subsidiary Berlex Laboratories as defendants, says that the plaintiff continues to suffer from the severe, debilitating and progressive fibrotic changes associated with NSF. This has permanently disabled, disfigured and severely impaired the plaintiff.
The lawsuit alleges that Magnevist is defective, and that the defendants failed to adequately test Magnevist and failed to warn patients about its potential to cause NSF. The lawsuit further alleges that the chemical make-up of Magnevist makes it more likely that gadolinium will become free within the bodies of recipients, thereby making it more likely that kidney patients will develop NSF.
NSF is a debilitating disease that was first seen in patients in 1997, and it wasn’t mentioned in medical literature until 2000. NSF leads to excessive formation of connective tissue in the skin and internal organs. It is characterized by high blood pressure, burning, itching, swelling and hardening of the skin. Other symptoms include red or dark patches on the skin; pain deep in the hip bones or ribs and muscle weakness. NSF can progress to the point of causing severe stiffness in joints, and it can lead to death.
There is currently no cure for NSF and no one understands its specific cause. However, the evidence that gadolinium Contrast agents play a role in its development is fast becoming irrefutable. Dutch scientists made the first connection between NSF and gadolinium in 2006. Since then, researchers at Yale University have reported that 95-percent of those with NSF had an Mri that involved a gadolinium Mri Contrast Dye two to three months before their symptoms appeared. Researchers at Massachusetts General Hospital also have found that kidney patients who had undergone Mris with gadolinium Mri Contrast Dyes were 10 times more likely to develop NSF than patient who had not been exposed to such agents.
The Food & Drug Administration (FDA) asked the manufactures of gadolinium Contrast Dyes to add a black box warning to the product labels about NSF risks in 2007. The FDA also warned that people with kidney disease should avoid gadolinium Contrast agents. However, this is not always possible. If an Mri with a gadolinium Contrast Dye is required, the FDA has warned that the dose of the gadolinium Contrast agent should not exceed that recommended in the product's label and that a repeat administration of the gadolinium Contrast agent should not be performed until enough time has passed to allow for the gadolinium Contrast agent from the first Mri to be eliminated from the body. The FDA recommends that patients already undergoing dialysis receive a dialysis treatment shortly following administration of a gadolinium Contrast Dye. Dialysis may help eliminate the gadolinium from the body, however it is not known if this will actually prevent NSF.
The FDA has also warned that the use of gadolinium Contrast Dyes in a procedure call Magnetic Resonance Angiography (MRA) could put kidney patients at an even greater risk of developing NSF because these procedures often use far more gadolinium than a typical Mri. The FDA has not approved the use of gadolinium Contrast Dyes for use in MRA.
NSF
was first seen in patients in 1997, and it wasn’t mentioned in medical literature until 2000. NSF leads to excessive formation of connective tissue in the skin and internal organs. It is characterized by high blood pressure, burning, itching, swelling and hardening of the skin. Other symptoms include red or dark patches on the skin; pain deep in the hip bones or ribs and muscle weakness. NSF can progress to the point of causing severe stiffness in joints, and it can lead to death.
There is currently no cure for NSF and no one understands its specific cause. However, the evidence that Gadolinium Mri Contrast agents play a role in its development is fast becoming irrefutable. Researchers at Yale University have reported that 95-percent of those with NSF had an Mri that involved a Gadolinium Mri Contrast Dye two to three months before their symptoms appeared. Researchers at Massachusetts General Hospital also have found that kidney patients who had undergone Mris with Gadolinium Mri Contrast Dyes were 10 times more likely to develop NSF than patient who had not been exposed to such agents.
For patients with NSF, life can become a living hell. Their skin can become so hardened that it resembles marble, while joints stiffen to the point that movement becomes impossible. The disease can also affect the heart, lungs and liver, and NSF can lead to death. Unfortunately, there are no effective treatments for NSF, although some patients have improved following a kidney transplant.
Gadolinium Mri Contrast Dyes are used in Mris because they make it far easier for a diagnostician to differentiate between normal and abnormal tissue. While the tests can be done without the gadolinium based Contrast agent, they are nowhere near as effective. The FDA has warned that patients with kidney problems not be given Gadolinium based Mri Contrast Dyes unless it is absolutely necessary. Unfortunately, there are not yet any alternatives to gadolinium based Mri Contrast agents.