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Questions and Answers on Gadolinium-Containing Contrast Agents
1. What is gadolinium and what is its use in clinical
medicine?
Gadolinium is a paramagnetic metal ion. Paramagnetic ions, such
as gadolinium, tend to move into magnetic fields. This trait makes
paramagnetic ions such as gadolinium useful for Magnetic Resonance
Imaging (MRI) and Magnetic Resonance Angiography (MRA). Gadolinium
is approved for use with MRI as a contrast agent to provide a
clearer picture of body organs and tissues. It is also used for MRA,
another imaging procedure.
Gadolinium-containing contrast agents are manufactured by a
chelating process, a procedure in which large organic molecules form
a stable complex around the gadolinium. The chelate reduces the
chances of toxicity that could result from exposure to free
gadolinium. This stable complex is eliminated via the kidneys in
patients with normal functioning kidneys.
2. What is the difference between MRA and MRI?
MRA is a special type of MRI used to study blood vessels. MRA is
utilized to detect, diagnose and aid in the treatment of heart
disorders, stroke, and vascular diseases.
3. Can an MRI and MRA be performed without
gadolinium-containing contrast?
MRI can be performed without contrast. However,
gadolinium-containing contrast agents provide better diagnostic
information in many instances as compared to MRI without contrast.
The use of a gadolinium-containing contrast agent to enhance MRA is
not FDA approved. MRA is able to provide detailed images of blood
vessels without gadolinium-containing contrast. The use of
gadolinium-containing contrast agents has been reported to enhance
MRA.
4. Are there other approved MRI contrast agents that do not
contain gadolinium?
There are no other approved MRI contrast agents. Imaging contrast
agents, such as iodinated contrast agents are used in Computed
Tomography, plain X-ray and X-ray angiography. However, these
iodinated contrast agents require X-ray imaging rather than MRI.
5. What is the concern regarding gadolinium-containing
contrast agents?
The information in the May 29, 2006, press release from the
Danish Medicines Agency (DMA) and the January 2006 report by Grobner
et al in Nephrology, Dialysis and Transplantation describe patients
with renal failure who developed a rare, potentially
life-threatening condition called Nephrogenic Systemic Fibrosis/Nephrogenic
Fibrosing Dermopathy (NSF/NFD). The DMA was concerned because all
patients received a gadolinium enhanced MRA procedure a few weeks to
a few months before developing NSF/NSD.
6. What is Nephrogenic Systemic Fibrosis/Nephrogenic Fibrosing
Dermopathy (NSF/NFD)?
NSF/NFD was first described in the medical literature in 2000.
The first case of NSF/NFD was seen in 1997. The disease is seen in
patients that have noticeably advanced renal failure. The disease
causes fibrosis of the skin and connective tissues throughout the
body. Patients develop skin thickening that may prevent bending and
extending joints, resulting in decreased mobility of joints. In
addition, patients may experience fibrosis that has spread to other
parts of the body such as the diaphragm, muscles in the thigh and
lower abdomen, and the interior areas of lung vessels. The clinical
course of NSF/NFD is progressive and may be fatal.
7. What is the treatment for NSF/NFD?
There is no consistently successful treatment for NSF/NFD.
Improving renal function seems to slow or arrest NSF/NFD and may
even result in a gradual reversal of NSF/NFD.
8. How many gadolinium-containing contrast agents has FDA
approved? Was NSF/NFD seen with all of the U.S.-approved
gadolinium-containing contrast agents?
There are five FDA approved gadolinium-containing contrast agents
(Omniscan, OptiMARK, Magnevist, ProHance, and MultiHance).
Omniscan is the only approved gadolinium contrast agent in the
countries where the Grobner report originated. FDA is actively
investigating all gadolinium-containing contrast agents for any
possible association with NSF/NFD.
9. Does the gadolinium-containing contrast agent (Omniscan)
cause NSF/NFD?
Whether the gadolinium agent causes NSF/NFD is unknown. However,
case reports from the DMA are of enough concern that FDA is further
investigating a possible link between the condition and
administration of gadolinium.
10. Why doesn’t the FDA feel that the evidence for causality
between gadolinium-containing contrast agents and the development of
NSF/NFD is conclusive?
The evidence associating the administration of a
gadolinium-containing contrast agent to NSF/NFD is from case reports
in patients with complicated medical histories. Concurrent medical
illness and/or use of other medications may be a factor in the
development of the condition. Further evaluation of these factors as
well as use of gadolinium-containing contrast agents in patients
with renal failure and in patients that develop NSF/NFD will be
required.
11. What actions will FDA take regarding the new information
about gadolinium-containing contrast agent administration and the
development of NSF/NFD in patients with advanced renal disease?
FDA is continuing to evaluate these reports, is undertaking
discussions with experts in the field, will review results of
previous and ongoing clinical trials with gadolinium-containing
contrast agents, and is working with the manufacturers to review all
safety reports and adverse event reports. FDA will assess all
available information to determine if product labeling changes or
other actions are necessary for gadolinium-containing contrast
agents.
12. What information was known about serious side effects
prior to the approval of gadolinium-containing contrast agents?
The 5 U.S. approved gadolinium-containing contrast agents were
approved between 1988 and 2004. In the combined pre-marketing
studies for these approved gadolinium-containing contrast agents,
over 3000 patients were studied.
The most common serious side effect from gadolinium-containing
contrast agents is an allergic reaction that is usually mild but can
occasionally be severe and even result in fatalities. Some patients
develop skin conditions, such as rash, sweating, itching, hives, and
facial swelling. Most of these conditions are considered allergic in
nature. Gadolinium-containing contrast agents can be very irritating
to the veins into which injected, with superficial inflammation or
irritation of blood vessels and blood clots.
Very few patients with severely compromised kidney function or those
on dialysis were studied in the pre-marketing studies. The labels
for gadolinium-containing contrast agents caution that the risk of
toxic reactions may be greater in patients with impaired kidney
function because gadolinium is mostly excreted by the kidney.
13. What should patients do with this new information?
If you have severely impaired kidney function and you received a
gadolinium contrast MRA, you should bring this to the attention of
your treating physician. If you have advanced kidney failure and a
physician has prescribed an MRI or MRA study with contrast, ask if
there are alternative diagnostic contrast agents or tests that could
be as effective.
14. What should healthcare providers do in response to this
new information?
Physicians should be cautious regarding the use of
gadolinium-containing contrast agents, especially at high doses, in
patients with advanced renal failure. If such a patient receives
gadolinium contrast MRA, prompt dialysis should be considered.
Physicians should also report all cases of NSF/NSD to the FDA
MedWatch at
http://www.fda.gov/medwatch/.
15. What additional actions are likely to follow?
FDA will complete its ongoing analysis of these preliminary
findings and then consider multiple options such as: modifying the
product label or requiring additional studies. FDA may also consider
risk management options.
16. Where can I find more information about
gadolinium-containing agents and about NSF/NFD?
The package inserts provide more information about all of the
approved gadolinium-containing agents. More information about NSF/NFD
can be found at the following website: http://www.pathmax.com/dermweb/.
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Gadolinium-Containing Contrast Agents
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Date created: June 8, 2006, updated December 22, 2006 |
