Gadolinium does not have FDA approval for breast MRI

feh

I received a return telephone call just now from a Drug Information Officer with the FDA.  She confirmed that none of the gadolinium products have FDA approval for breast MRI

 The FDA considers this off-label use, "the practice of medicine."  She said, further, that the decision to use the gadolinium, or any other off-label product usage, resets with the Medical Boards.

The FDA will only take action about this off-label practice when it received sufficient complaints; in this case, from women who may have side effects from receiving the gadolinium product as part of a contrast breast MRI.  To me, that would include all the fouled, unreadable contrast breast MRIs.

There are no long-term studies concerning the use of gadolinium in women. 

feh

I clicked the "New Topic" button -- don't know what happened.  I think this should be a Topic line in Tests, Treatments and Side Effects, but I don't see how to insert it?

migallen

Hmmm, I just had my mri on Dec. 27, 2010 where the techs inserted the IV.  Well, the IV came out and made quite a mess on the table, and they had to re-insert the iv with more contrast.  I wonder that what might have done to me.  Any one have any side affects from the gadolinium?

jacee

I had localized redness in the area where the IV was inserted...maybe 4-5 inches above and below and sort of splotchy red areas adjacent. Didn't itch or anything, but certainly caught my eye. There is much to be read about lawsuits concerning gadlinium. I hate that we are a slave to these products. We so fear the alternative, that we subject ourselves to almost anything recommended!!

feh

I am sorry.  I did not post this to frighten.  I think this is a matter that must be properly evaluated.  It never occurred to me that there would not be FDA approval, but I think I overestimate the FDA's reach.

The best we can do is file reports with the FDA for any gadolinium contrast MRI reactions.

otter

Twiddle, I don't understand why you are emphasizing this issue at this time. 

Doctors have had the authority to use licensed, FDA-approved products for off-label applications for many decades.  Lots of the drugs women are given for breast cancer are being used off-label.  For example, Aromasin and Femara are being used off-label any time they are prescribed as first-line hormonal therapy in women with early-stage breast cancer.  (Arimidex is the only AI that is actually approved for that use.)  And, Taxotere (docetaxel) is being used off-label when it's given to women with Stage I breast cancer, since its FDA-approved indications are for "treatment of patients with locally advanced or metastatic breast cancer after failure of prior chemotherapy," and for "the adjuvant treatment of patients with operable node-positive breast cancer." Also, the "T/C" (Taxotere/Cytoxan) regimen so many early-stage women are getting these days has not specifically been approved by the FDA.  So, the use of that chemo regimen is off-label.

Any reactions to any drugs should be reported, first to our doctors and then, if necessary, to the FDA.  It doesn't matter whether those drugs are being used according to label or off-label.  Gadolinium is no different -- anyone having an adverse reaction to gadolinium ought to report it.  I've had two contrast breast MRI's so far, and each time, I was interviewed by a nurse several days prior to the procedure to find out whether I'd had any adverse reactions or complications previously.  I then had to verify the information I'd given the nurse when I arrived for the procedures.

You said this:  "The FDA will only take action about this off-label practice when it received sufficient complaints..."  What is it you are trying to accomplish, exactly?  Are you trying to convince the FDA that it should prohibit the use of Gadolinium for breast MRI's?  IMHO that would be a terrible disservice to women who benefit from the improved sensitivity of MRI over either mammography or ultrasonography.  (I am one of those women, so I do have an interest in the subject you've raised.)

You also said this:  "... side effects from receiving the gadolinium product as part of a contrast breast MRI.  To me, that would include all the fouled, unreadable contrast breast MRIs."  How is it that you think an "unreadable" contrast breast MRI should be included among the "side effects" from receiving gadolinium?  What do you mean by "fouled"?  IMHO, calling a technically unreadable MRI image a "side effect" of gadolinium is like saying improper positioning for a mammogram is a "side effect" of radiation.

I can't figure out what your stake is in this, but it does seem to me that you are posting this to frighten women into believing that they are at particular risk because the gadolinium is being used off-label. Why do you think the use of gadolinium in breast MRI's would pose a greater risk than it does in any other (approved) contrast procedure?

Just askin.

otter

LtotheK

I can say this:  my oncologist yesterday says there is now question about MRIs,and she cites the gadolinium as an issue.  We didn't have time to pursue it further, but her general take was there is question about the safety of annual MRI for BC patients.  Rather akin to the newest studies on the safety of CT/PET scans...

thenewme

Hi Otter,

Thanks for articulating what I've been thinking!

Twiddle, I had a contrast pelvic MRI last week, so your post also makes me wonder whether whatever concerns you have about gadolinium in breast MRI also apply to non-breast gadolinium contrast MRIs? 

ETA- I know there have been recent changes to gadolinium labeling per the FDA, but that has to do with labeling the known (although still rare and mostly limited to a very specific subset of compromised patients) nephrologic risks of gadolinium.  I don't think that's what Twiddle is referring to in this post, however.  See the FDA statement here:  Gadolinium

LRM216

Thank you, Otter, you saved me a lot of typing!  I agree totally with your post.  We can get extremist about much in the medical world, but sometimes there are just no alternatives.  In addition, if everyone really knew how many things are used off-label (and have been for years), they would be shocked.  It's a fact of life that there is not a medicine known to man (meds, contrast fluids, etc. - even tylenol!) that has not caused great harm to some, and absolutely no harm to others.  When dealing with science, that is the risk one must take.

beccad

MRI doe not have the radiation concerns that a CT/Pet scan, or for that matter a Nuclear Medicine Bone Scan or a Nuclear Medicine MUGA scan would have.  This is because MRI does not use any radioactive source, either with an X-Ray Tube or by injecting a radioactive isotope.  The concern with SE's from Gadolinium has been stated above (Nephrologic Risks).

I work in a Radiology  Department, and know that if a patient is above 50, has diabetes,  or any renal issues, the MRI technologist must get lab work on that patient before they can administer Gadolinium.  The patients creat. must be below a specific level, and they also have to do a GFR calculation.  If these results are too high Gad.  will not be used and the patients referring Dr. will be notified. 

I don't know what was meant by fouled exams.  However, I do know that some patients by no fault of their own cannot hold perfectly still for an MRI, and unfortunatly MRIs do take a longer period of time than most radiology studies, and in a radiology department "motion is not our friend"

I do realize that I have gotten on my radiology soapbox, but it needed to be said.

Beesie

otter, thanks for your great post.  And LRM, I agree with you completely.  With every test we take and with every pill or treatment we have, there is some level of risk.  Most times the risk is very small but the simple fact is that out there somewhere, someone will have a negative effect.  So with every test we take and with every pill or treatment we have, there's a risk/benefit assessment.  Whether we do it ourselves (our individual decisions on whether or not to take Tamoxifen, for example) or whether our doctors do it for us (in deciding to order a test or prescribe a pill) or whether the FDA does it (in approving certain tests and certain treatments for particular people and particular situations) or whether an independent body does it (the ACS and the Radiologist association, in recommending breast MRIs for women in particular situations), a risk/benefit assessment is done.

In my case when it comes to breast MRIs, as someone with dense breast tissue who's already had BC, the benefit for me in terms of early detection is huge. Might the gadolinium put me at a very slight risk?  Yup, but I don't care and I'm not going to worry about it because that risk is miniscule when compared to the benefit I get from having the MRI (improving my odds of early detection and peace of mind knowing that nothing was seen on the MRI).

By the way, I do find it interesting that all of sudden there are concerns being raised about MRIs. About 2 years ago on this board, there was a lot of discussion about the radiation risks from mammos and there were a number of women who were saying that all women should only get MRIs because there is no risk to MRIs.  I responded that I didn't believe for a minute that there was no risk to MRIs.  Perhaps because MRIs were a relatively new technology the risks hadn't been discovered/documented yet but I simply couldn't believe that there could be no risk at all. That didn't mean however that I ever thought that MRIs were bad or should be avoided.  It's simply reality.  We cannot live life without risk.  And for someone to expose themselves to a significantly greater risk simply because of an irrational fear of a much smaller risk makes no sense at all. To encourage others to do that is irresponsible.  Discussing is good. Assessing pros and cons is good. Fear mongering is not. 

Letlet

After chemo, gadoliniun is like gatorade to me. I got the worst of it already.

feh

Otter -- What's my "stake" in this?  That, and your loathsome, convoluted interpretation of my post, and stating that I posted this to frighten women, is unconscionable.

If gadolinium is not meant to be used in breast MRI, it might well be that it effects the clarity of MRI images.  That is what I meant by a fouled contrast MRI.  No one is offering 100% proof that finding the most miniscule breast anomaly, results in a better outcome.

At the very least, I do believe that there needs to be greater monitoring of drugs given to women by the FDA.  This is not to say that if disease is directly threatening a life, non-FDA approved drugs should not be attempted with proper and careful medical supervision.

You say that reports should be made.  Well, the FDA rep told me that was not happening with breast MRI contrast - that would be with the exception of the nephritis issue.  Avastin was just removed from use - was it not?

Here's my stake in this:  my daughter's life.  My life.  The lives of other women.

Fearless_One

Well, since it's not actually a drug, that might be why they don't oversee it.   It is the 64th element in the periodic table, a rare earth mineral.   But someone with a stronger chemistry backround could tell you more.   But I do know that it is not supposed to be used in patients with kidney disease, they use something else - not sure what.  

Now if someone tells me Arimidex isn't regulated by the FDA, then I'll worry.  But I'm not too worried about this.   Maybe I should be?   But I'm not.   I have dense breasts, so I had to get used to it.   Mammos are useless on me so had to get breast MRI's.

otter

Fearless, you are correct in pointing out that gadolinium contrast agents should not be used in people with severe kidney disease. 

Unfortunately, doing MRI without a contrast agent means the radiologist will not be able to see changes in blood flow (vascularity) that help distinguish malignant from benign masses. Apparently, there are 2 non-gadolinium contrast agents that have been used for MRI.  One of those contains iron ("Feridex"); the other contains manganese ("Teslascan").  But, those 2 agents have only been approved for MRI scans of liver lesions.  One imaging alternative is iodine-containing compounds, but those are thought to be even worse than gadolinium as far as severe reactions; and they involve exposure to X-rays which MRI does not.

The warnings about the risk of nephrogenic systemic fibrosis (NSF) with gadolinium-based contrast agents are all over the internet and easy to find (as are the solicitations from law firms about the subject).  Here's an example of a precautionary post, from a Mayo Clinic Q & A site:  http://www.mayoclinic.com/health/gadolinium/AN01637; and here's a very recent (Fall 2010) warning from the FDA:  http://www.fda.gov/Drugs/DrugSafety/ucm223966.htm  The FDA first recommended a boxed warning about NSF risk with gadolinium-based agents in 2007; this past Fall they announced a requirement for stronger warnings on the package labels.

Until recently, there were 5 gadolinium-based contrast agents approved by the FDA for use in MRI.  According to the 2010 FDA link I cited above, there are now 7 gadolinium-based agents. The original 5 are "MultiHance" (gadobenate dimeglumine), "Omniscan" (gadodiamide), "Magnevist" (gadopentetate dimeglumine), "ProHance" (gadoteridol), and "OptiMARK" (gadoversetamide).  Note that these contrast agents are not gadolinium in its elemental form. To create the contrast agents, pharmaceutical companies chelate the gadolinium with huge organic molecules. So, the gadolinium-based contrast agents are drugs; and their manufacture, safety, and effectiveness, most certainly are regulated ("overseen") by the FDA.

As it was explained to me at my last MRI (October 2010), those 5 contrast agents are not exactly the same -- each behaves slightly differently in the body.  Medical imaging facilities often have preferences for one over the others.  Sometimes that preference is based on perceived risk of NSF; sometimes not.  Until the FDA came out with its 2010 warning, the medical evidence of risk of NSF was pretty much the same with all 5 agents. The most recent FDA information said the risk appears to be greater with Magnevist, Omniscan, and OptiMARK.  Even so, an imaging facility might choose to use one of the higher-risk agents for certain patients.  (I developed severe nausea during my first MRI, so they switched to one of the other gadolinium-based agents for my 2nd one to keep that from happening again.) 

The FDA still says there have been no reports of NSF occuring in people with normal kidney function.  The most significant risk is among people with acute kidney damage or chronic, severe kidney disease. Higher-than-recommended doses of contrast agent or repeat doses are also associated with greater risk of NSF.

Here's a page on the FDA site that explains how and why gadolinium-based agents are used for MRI:  http://www.fda.gov/Drugs/DrugSafety/DrugSafetyNewsletter/ucm142889.htm  The information on that page concerning NSF risk is out of date, but the rest is useful.

Okay. Those are the facts.  NSF is rare, and has never been reported in someone with normal kidney function; but it's important to inform our medical providers of any evidence that our kidneys might not be functioning normally.  (We can't assume they know that.)

Despite all that gloom-and-doom, I still have seen no evidence that women having contrast breast MRIs might be at greater risk of NSF or other complications than people having contrast MRIs of other body parts. The injection is i.v.; the drug goes to the same place(s).  In fact, I found one website that claimed the dose of gadolinium for a breast MRI is lower than that used for other MRI procedures:  http://breastcancer.about.com/od/breastcancerglossary/p/gadolinium.htm

otter

[Edited to add: I'm sorry this post is so long, but I thought it was important to get some facts out there.]

Fearless_One

Otter, I think you know more than my onc, lol!  Thank you for all that info...

Eh, I can't speak for others, but for me, I am more afraid of a tumor lurking in my dense breasts than of MRI contrast material.

feh

Otter:  None of the gadolinium-based contrast agents have been approved by the FDA for breast imaging.  The FDA information office I spoke with stated that none are approved.  That is a fact.  It is erroneous to state, "So, the gadolinium-based contrast agents are drugs; and their manufacture, safety, and effectiveness, most certainly are regulated ("overseen") by the FDA."

And I have additional concerns about the MRI being used unless disease is proven.  The effect of the bombardment of radio frequencies and being subjected to the very strong magnetic field, continues to be listed as inconsequential.  However, direct experience -- pain in joints, earache, within two weeks following MRI; 3-day earlier menses, 3 weeks following MRI.  Could any of this be due to a host of other causes?  Absolutely.  But why not track this sort of thing.

 So, I checked to see where one can report possible side MRI effects.  (Note that I am speaking solely about MRI now, forget the contrast medium).  Go ahead and read this, and tell me that I am wrong in my understanding that the FDA does not offer direct reporting of possible side effects from medical devices, like the MRI, and that the rules were changed so that only the manufacturers are required to keep records of reported incidents.

http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/PostmarketRequirements/ReportingAdverseEvents/default.htm

It is one thing to utilize available technology when one believes it to be the best chance.  But isn't it in our best interest to demand direct regulation, as well as incident reporting mechanisms for a practice that may have undocumented side effects, from a pragmatic standpoint alone.

purple32

work in a Radiology Department, and know that if a patient is above 50, has diabetes, or any renal issues, the MRI technologist must get lab work on that patient before they can administer Gadolinium.

Maybe where you are ,...not so where I live. NO bloodwork required unless hx of renal disease.

CautionInMedicalSettings

In that gadolinium has been found to leave deposits in bone and neural tissue of the brain, and that it enters the placenta, the question must be asked: Do MRI's with gadolinium leave deposits in breast tissue, and, does the gadolinium of a contrast MRI, as does low-dose radiation of mammography, cause double- strand breaks in tumor-suppressor DNA and in metastasis-suppressor DNA? And where online are there disinterested studies which answer these questions? And why is it that written informed consent requirement for both mammography and MRI which requires up-to-date disclosure of all known medical dangers of MRI's and mammography? And why are women not given this information?

Online there are reports of gadolinium causing life-threatening conditions, such as the creation of blood clots, severe allergic reactions, &c., in patients whose labs reported normal kidney function before contrast MRI's.

BarredOwl

Perhaps I am missing something, but I was not under the impression that the contrast agents used are radioactive or that the MRI device uses ionizing radiation. If that is the basis for the hypothesized induction of double-stranded breaks in DNA, it would appear inconsistent with the information and documentation provided by other posters earlier in this thread.

I thought the principle behind MRI was "magnetic resonance" (magnetism, which is why they ask you about any metal components in your body). The link provided by Otter states:

http://www.fda.gov/Drugs/DrugSafety/DrugSafetyNews...

"Gadolinium is a paramagnetic metal ion. Paramagnetic ions, such as gadolinium, move differently within a magnetic field. This trait makes gadolinium useful for magnetic resonance imaging (MRI)."

May I ask if you have a reference which supports a molecular mechanism whereby a paramagnetic metal ion might be able to induce double-stranded breaks in DNA?

BarredOwl

Hank2

Why has the URL you and Otter posted been removed? Doesn't boost my confidence.