NEW CELLCEPT WARNING!!!!

[lruffner]

I know this probably doesn't belong in this thread, but I am not sure where to start it....sorry Sluff! lol.

I was just put on Cellcept and when researching it further, I was completely shocked to see the new FDA warnings put out there in the last month, especially since I wasn't even told about it by a "professional." I am going to have to discuss this in detail with the docs before I take anymore. I will paste and provide the link for the story. I then looked up this disease they are talking about and it's pretty scary.

http://www.newsinferno.com/archives/2889

CellCept Linked to Fatal Neurological Disease
Date Published: Thursday, April 10th, 2008
   


Last November, Swiss drug maker Roche alerted the US Food and Drug Administration (FDA) about reports of a neurological disease—progressive multi-focal leukoencephalopathy—that is often fatal, occurring in patients taking its drug CellCept. CellCept is used to help the body avoid rejection following organ transplantation. Now, regulators trying to determine whether organ transplant drugs made by Roche and Novartis increase the risk of the often-fatal disease. The FDA also said today that it is reviewing similar risks with Myfortic, a drug made by another Swiss drug maker—Novartis—that is used to prevent kidney transplant rejection.

CellCept—generically known as mycophenolate mofetil—is part of a class of drugs called immunosuppressants and was approved in 1995 to prevent rejection of solid organ transplants, including kidney, heart, and liver. When CellCept is used in with cyclosporine and corticosteroids, it greatly reduces the patient’s immune system from attacking the transplanted organ. As with all immunosuppressants, CellCept carries certain risks, including development of lymphoma and other malignancies and is also linked to an increased risk of developing opportunistic infections and sepsis.

The FDA announced the process to review the reports and consider revised labeling for the medications takes approximately two months. Until then, regulators advise doctors and patients to watch for neurological symptoms. Progressive multi-focal leukoencephalopathy attacks the brain and central nervous system and is usually fatal. Symptoms include vision problems, loss of coordination, and memory loss. According to the FDA, patients who the disease are often permanently disabled.

Christopher Vancheri, a Roche company spokesman, confirmed 10 cases of progressive multi-focal leukoencephalopathy in CellCept patients, adding that over 500,000 patients have used CellCept since 1995, when it was approved in the US.

Last October, CellCept was linked to miscarriage and birth defects, prompting the FDA to add a new boxed warning to its label last November. That labeling remains under FDA review. The potential for side effects was considered so great that the FDA advised women of childbearing age to use two methods of birth control before, during, and after CellCept treatment. Meanwhile, European regulators added language about the neurological disease to CellCept packaging and, this February, Roche sent a letter to European doctors, highlighting the labeling changes. The letter stated problems were reported in kidney, heart, and lung transplant patients and the neurological disorder was seen in patients taking the drug for a form of lupus, a CellCept use not approved by regulators.

Roche said it is difficult to sort out the role of its drug in the reports since many patients had other diseases and were taking other drugs. According to the Roche letter—which the FDA posted to its Website today, determining the role of the drug in the reports poses some challenges because many patients taking the drug were suffering with other illnesses and also on other drugs, “However, the contributory role of CellCept cannot be excluded.”

A spokeswoman for Novartis said the company is not aware of any instances of the neurological disease in patients taking its drug and plans to cooperate with any labeling changes recommended by regulators.

Progressive multi-focal leukoencephalopathy is associated with at least one other drug, Tysabri, which is used to treat multiple sclerosis. Tysabri was actually removed from the market in 2005 because several patients taking it had died of the disorder.  In 2005, the law firm of Parker Waichman Alonso filed suit against Elan Inc. and Biogen Idec, the makers of Tysabri, on behalf of a woman who died from progressive multi-focal leukoencephalopathy while taking that drug.  When contacted, Jerry Parker, the managing partner of Parker Waichman said that Tysabri case had been resolved, but that the resolution remained confidential.


EDITED: Moved to proper section - okarol/admin

[vandie]

I was aware of the malformations and miscarriage.  But it came out post transplant, so I found it doing my own research.  When I questioned my surgeon and pharmacist, it was recommended I use three forms of birth control.  The company has been sued for facial malformations in newborns to mothers taking Cellcept.
Thanks for this story.  We all need to keep each other updated.

[Treasure]

I do recommend that you contact your doctor and your pharmacist on this...but I don't think I would recommend going off the CellCept without directions from my doctor.

I took both CellCept and Myfortic for many months, until I lost my transplant. I'll have to do further research to see if there are any indications that these drugs may have harmed me.

[Chris]

Wrong place to ask, but have you heard the news about Prograf? I was told that in April of this year that Astellas lost...can't think of the term and now that can lead to a generic version of Prograf. There is suppose to be some sort of assistance program, but I haven't looked it up yet.

[okarol]

Date created: April 10, 2008, updated April 16, 2008

Communication About an Ongoing Safety Review of
CellCept (mycophenolate mofetil) and Myfortic (mycophenolic acid)

This information reflects FDA’s current analysis of available data concerning these drugs.  Posting this information does not mean that FDA has concluded there is a causal relationship between the drug product and the emerging safety issue.  Nor does it mean that FDA is advising health care professionals to discontinue prescribing this product. FDA is considering, but has not reached a conclusion about whether this information warrants any regulatory action.  FDA intends to update this document when additional information or analyses become available.

FDA is investigating a potential association between the use of CellCept (mycophenolate mofetil) and Myfortic (mycophenolic acid), medicines used to prevent organ rejection, and the development of progressive multifocal leukoencephalopathy (PML), a life-threatening disease.

PML is a rare disorder that affects the central nervous system.  When it occurs, it is usually in patients with immune systems suppressed by disease or medicines.  It happens when the polyomavirus, also known as the JC virus, is activated.  The JC virus is found in most adults but does not usually cause symptoms.  Scientists do not know exactly how the JC virus is activated.  Once activated, the JC virus attacks the cells that make myelin, the protective coating around nerve cells.  Signs and symptoms of PML can include localized neurologic signs and symptoms including vision changes, loss of coordination, clumsiness, memory loss, difficulty speaking or understanding what others say, and weakness in the legs.  Many patients who develop PML die.  Patients who survive may have permanent disability due to irreversible nerve damage. More information on PML can be found at the National Institutes of Health website.

CellCept is approved to prevent heart, liver, and kidney transplant rejection and Myfortic is approved to prevent kidney transplant rejection.  Mycophenolate mofetil, the drug ingredient in CellCept, is metabolized by the body to mycophenolic acid, the drug ingredient in Myfortic.  Both CellCept and Myfortic are used with other drugs to suppress the immune system.

On November 8, 2007, Roche, the maker of CellCept, submitted an evaluation of its PML cases in patients who have received CellCept in addition to other immunosuppressive medicines. Roche also submitted recommendations to the FDA for including information about PML in the CellCept prescribing information.  On March 14, 2008, Roche informed the FDA of the Dear Health Care Professional letter PDF document it issued in Europe on February 18, 2008.

Roche is aware of cases of PML in transplant recipients and patients with systemic lupus erythematosus (SLE), an autoimmune disorder that is sometimes treated with CellCept; however, CellCept and Myfortic are not approved for treating SLE or similar autoimmune disorders.

Roche is aware of cases of PML in transplant recipients and patients with systemic lupus erythematosus (SLE), an autoimmune disorder that is sometimes treated with CellCept; however, CellCept and Myfortic are not approved for treating SLE or similar autoimmune disorders.

FDA is reviewing data, including postmarketing reports it has received of PML in patients who took CellCept, and the proposed revisions to the CellCept prescribing information.  FDA has asked Novartis, the maker of Myfortic to revise the Myfortic prescribing information to include the same information about PML included in the CellCept prescribing information.

FDA anticipates it may take about 2 months to complete its review of the postmarketing reports and the proposed revised prescribing information for CellCept and Myfortic about PML.  As soon as FDA completes the review, FDA will communicate the conclusions and recommendations to the public.  Until further information is available, patients and healthcare professionals should be aware of the possibility of PML, such as localized neurologic signs and symptoms in the setting of a suppressed immune system, including during therapy with CellCept and Myfortic.  Decreasing total immunosuppression may improve the outcome of patients who develop PML.

This communication is in keeping with FDA’s commitment to inform the public about its ongoing safety reviews of drugs.

FDA urges both healthcare professionals and patients to report side effects from the use of CellCept and Myfortic to the FDA's MedWatch Adverse Event Reporting program

    * online at [www.fda.gov/medwatch/report.htm];
    * by returning the postage-paid FDA form 3500 [available in PDF format at [www.fda.gov/medwatch/getforms.htm] to 5600 Fishers Lane, Rockville, MD 20852-9787;
    * faxing the form to 1-800-FDA-0178; or
    * by phone at 1-800-332-1088


Date created: April 10, 2008, updated April 16, 2008

http://www.fda.gov/cder/drug/early_comm/mycophenolate.htm

[spacezombie]

Yeah, I saw this warning a couple of weeks ago. It totally freaked me out since I used to be on tons of cellcept... and probably will be again after my transplant.

[lruffner]

I do recommend that you contact your doctor and your pharmacist on this...but I don't think I would recommend going off the CellCept without directions from my doctor.

I took both CellCept and Myfortic for many months, until I lost my transplant. I'll have to do further research to see if there are any indications that these drugs may have harmed me.

I had just started it yesterday. I had only taken one pill and did not take another one. I am one of thsoe freak wonders of the world with medication....if it can happen, it will happen to me...lol. I am going to hve heavy discussions with my doc and pharmacist before I continue, because I need what brain I have left! 

[stauffenberg]

Of course you should not discontinue any immunosuppressive drug until after discussing this intention with the nephrologist, since before any part of the immunosuppressive regimen can be omitted, it has to be replaced by some other drug to make up the resulting shortfall in protection of the graft from rejection.

The problem is that all of the immunosuppressive drugs have terrible side-effects, including neurological disease, brain deterioration, bone disease, lethal infections, arteriosclerosis, atherosclerosis, anemia, excess lipids in the blood, heart disease, liver disease, and destruction of the kidney.  Cyclosporine was developed from mold found growing on the outside of a sewer pipeline in Sicily, so you can imagine how healthy that is for you.  Compared to all the problems of all the other immunosuppressive drugs, the fact that Cellcept causes 10 cases of leukoencephalopathy out of half a million patients is nothing special.

[lruffner]

I have not had a transplant, they are just seeing if any treatment will make a difference for my FSGS. I think most people know that they have to take immunosuppression drugs if they have had a transplant, or they will die. I take special interest in serious side effects of medicine, as well as warnings like that, because I think everyone should be diligent about the drugs they are given and what they can do to them. Just my opinion and my choice.

I saw a lady who had thrown herself into complete autoimmune hepatitis, without one single living liver cell, just from drinking green tea and taking supplements. They didn't know if she would make it.......

I originally posted this under 'general discussion' strictly because I have not had a transplant, so sorry for the confusion.


 

Of course you should not discontinue any immunosuppressive drug until after discussing this intention with the nephrologist, since before any part of the immunosuppressive regimen can be omitted, it has to be replaced by some other drug to make up the resulting shortfall in protection of the graft from rejection.

The problem is that all of the immunosuppressive drugs have terrible side-effects, including neurological disease, brain deterioration, bone disease, lethal infections, arteriosclerosis, atherosclerosis, anemia, excess lipids in the blood, heart disease, liver disease, and destruction of the kidney. Cyclosporine was developed from mold found growing on the outside of a sewer pipeline in Sicily, so you can imagine how healthy that is for you. Compared to all the problems of all the other immunosuppressive drugs, the fact that Cellcept causes 10 cases of leukoencephalopathy out of half a million patients is nothing special.

[mariannas]

I didn't have a great experience with CellCept.  I had been on Imuran (Azathioprine) for about 20 years and my doctor switched me to CellCept in an effort to preserve my kidney function.  I was fine for the first 4 years or so with minimal issues, but for about a year I was having really bad diarrhea.  It got worse within the last 6 months to the point that I was losing weight rapidly and was hovering around 80 pounds (even at 5'0 that was too skinny).  They did an endoscopy and colonoscopy last month and discovered colitis that they believe to be from the CellCept.  My doctor switched me back to Imuran and I've been 150% better.  I'm actually retaining the nutrients I eat and have gained a little weight too. Now I'm about 88 pounds and feeling stronger and healthier. 

[lruffner]

I didn't have a great experience with CellCept. I had been on Imuran (Azathioprine) for about 20 years and my doctor switched me to CellCept in an effort to preserve my kidney function. I was fine for the first 4 years or so with minimal issues, but for about a year I was having really bad diarrhea. It got worse within the last 6 months to the point that I was losing weight rapidly and was hovering around 80 pounds (even at 5'0 that was too skinny). They did an endoscopy and colonoscopy last month and discovered colitis that they believe to be from the CellCept. My doctor switched me back to Imuran and I've been 150% better. I'm actually retaining the nutrients I eat and have gained a little weight too. Now I'm about 88 pounds and feeling stronger and healthier.

Do you think that they may have also checked for Celiac disease? It can have the same effects as well. Stress can bring it out....my uncle found out that he had it, after a stressful family situation, and lost 70 lbs. He wasn't overweight to begin with, so you can imagine what a 6'4" man looked like 70 lbs. underweight. I guess as long as you are retaining and absorbing nutrients, you probably don't have it, so all is well.

How did the cellcept affect your kidney function? The Imuran? I would rather be on something else, but will have to discuss it with the docs. What type of kidney disease do you have? I am always looking for new ideas for treatment, since my docs seem so unconcerned.

[Deanne]

I took Cellcept for a while to treat FSGS, too. I'm still pre-ESRD. It didn't do any good for me. I don't *think* it did any brain damage, but how can I tell which brain cells died from Cellcept and which ones died from age? I know I've lost a few! I also had diarrhea from Cellcept.

[lruffner]

Did any medicine do any good for you? I am pre-ESRD too, but not for long I am afraid. The cellcept problem doesn't eat brain cells....it destroys the sheaths around them. I believe it is fatal, so I am sure you are ok 

[angela515]

I took CellCept with my first transplant.. which means I took it the whole time I was pregnant with both of my children. I was never told of any of those warnings back then, luckily for me my children are the cutest kids in the world and have none of those problems that can occur.

As for now, I am on Prograf and Rapamune... both have their side effects of course, and Rapamune can cause Lung Failure, Lung cancer, Lung Disease, Lung anything pretty much and that's why I was taken off of it this last week when I was having lung problems... but I am back on it now and on a very small dose of 1mg per day. They were thinking of switching me to CellCept... but I may just want to deal with Lung problems. Geesh. It also causes low white blood cell counts.

CRAZY.

[mariannas]

Do you think that they may have also checked for Celiac disease? It can have the same effects as well. Stress can bring it out....my uncle found out that he had it, after a stressful family situation, and lost 70 lbs. He wasn't overweight to begin with, so you can imagine what a 6'4" man looked like 70 lbs. underweight. I guess as long as you are retaining and absorbing nutrients, you probably don't have it, so all is well.

How did the cellcept affect your kidney function? The Imuran? I would rather be on something else, but will have to discuss it with the docs. What type of kidney disease do you have? I am always looking for new ideas for treatment, since my docs seem so unconcerned.

Oh yes...they checked for Celiac (my step grandfather has it and that was my first thought)...and IBS...and Crohn's. 

You know...I was on Imuran for 20+ years before my kidney function started declining and that's when I went on CellCept.  I had another 4 years or so before I had to start dialysis so it's hard to say whether or not the CellCept preserved the kidney function or not.  I mean...what if I had stayed on the Imuran?  Would I have had less time or more?  It's just too hard to say. 

As for the type of kidney disease I have...I was born with minimal function in my kidneys so I needed a transplant when I was 3.  I'm 26 now so things have gone pretty well I'd say.  Better than we'd ever thought, at least!

[angela515]

I never had problems with Imuran.

[mariannas]

I didn't have problems with Imuran either...just the CellCept.  I was switched because my doctor thought it might prolong my kidney function and with the CellCept there is a decreased chance to getting the immunosuppresant caused cancers like lymphoma.  I'm actually going to talk to my doctor today about what is better...living with GI issues or the chance of cancer.  I think I'd rather have the GI issues if it won't lead to something more serious down the line.

[Deanne]

Sorry for the delayed response lruffner! I assume that question was for me anyway.

Prednisone helped somewhat. It reduced my protein spill from 10 grams/day to 3 grams/day. Maybe it would have helped more, but my quality of life on it was poor and I had to come off from it. After that, I tried Cellcept and Cyclosporine. Neither did any good and I had side effects from each. Prednisone gave me diabetes and muscle-wasting, Cellcept gave me diarrhea, and Cyclorsporine gave me peripheral nepropathy. Thanksfully, the issues all resolved once I came off the meds, except that I never got back the full range of motion back in my knees that prednisone took away.

[paddbear0000]

Lately there's been a lot more 'hubbub' about miscarriage and birth defects while taking Cellcept. I've been doing a lot of research on it. My husband and I have decided to try and have a child before attempting a transplant because of this. I am willing to risk needing to go on dialysis due to the pregnancy. We are going to make an appointment with a high risk OB-GYN first though to discuss this.

_________________________________________________________________________________________

Medscape Alerts
CellCept Linked to Pregnancy Loss, Congenital Malformations
Yael Waknine

October 29, 2007 — Mycophenolate mofetil (CellCept, Roche) has been linked to an increased risk for first trimester pregnancy loss, the US Food and Drug Administration warned healthcare professionals today.

The warning was based on postmarketing data from the US National Transplantation Pregnancy Registry (NTPR) and Roche worldwide adverse reporting system, which also revealed an increased risk for congenital malformations. These have included ear and facial abnormalities (including cleft lip/palate) in particular, as well as anomalies of the distal limbs, heart, esophagus, and kidneys.

Published prospective NTPR data from 24 female transplant patients with 33 pregnancies showed that 45% of pregnancies ended in spontaneous abortion. Of 18 live-born infants, 4 (22%) had structural malformations.

Postmarketing data collected by the company from 1995 to 2007 supported these findings; 25 of 77 women exposed to systemic mycophenolate during pregnancy had spontaneous abortions, and 14 had a malformed infant or fetus; 6 of the malformed offspring had ear abnormalities.

As a result, the pregnancy category for mycophenolate has been changed from C to D, according to an alert sent from MedWatch, the FDA's safety information and adverse event reporting program.

Women of childbearing potential are required to use 2 methods of contraception beginning 4 weeks before initiation of therapy and should have a negative serum or urine pregnancy test during the week before the first dose. Contraceptive use should continue during treatment and for 6 weeks after its discontinuation.

Patients should also be made aware that mycophenolate reduces estrogen/progestin blood levels and could theoretically reduce the efficacy of oral contraceptive pills.

Healthcare professionals are encouraged to enroll mycophenolate-exposed pregnant women in the national registry by calling 1-877-955-6877.

Mycophenolate mofetil is indicated for use with cyclosporine and corticosteroids for the prophylaxis of organ rejection in patients receiving allogenic renal, cardiac, or hepatic transplants.

Adverse events related to mycophenolate should also be reported to the FDA's MedWatch reporting program by phone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, online at http://www.fda.gov/medwatch, or by mail to 5600 Fishers Lane, Rockville, MD 20852-9787.

[okarol]

Jenna's transplant team said if she decides to get pregnant then they would have her change her meds at least for 6 weeks prior to conception and during the pregnancy to avoid the problems related to CellCept and birth defects. Then she would resume the CellCept after delivery.

[pelagia]

I finally remembered to check back on this.  Here's an update from this link:

http://www.fda.gov/cder/drug/early_comm/mycophenolate.htm

In a banner at top it says:

"FDA has completed its review of postmarketing reports of PML in patients who took CellCept and Myfortic. The prescribing information for CellCept and Myfortic now includes information on PML in the Warnings and Adverse Events sections. Roche and Novartis issued Dear Health Care Professional Letters on May 29, 2008 outlining the changes to the prescribing information."

[angelface2008]

has anyone had severe vision problems after being on cellcept? i am 30 year old female living with lupus for 22years. in 2004 my doctor put me on cellcept. right after 3 months i started noticing vision changes.i kept telling my nephrologists about my worsening eye problems but he thought it was not related to cellcept. to make the long story short, i am now blind in the left eye and my right eyes vision reads 20/70. i just came off of cellcept this past july, but unfortunately it is to late for me. anyone have any advice or suggestions? please help? thanks

[Chris]

Just thought about this, even though I did not find anything about CellCept and vision yet when you PM'd the question to me. When I had eye surgery post transplant, my eye didn't heal like it should as the doctor told me because of my immunosuppressants. The cornea had trouble  healing and many things were tried. Not sure if that was due to Prograf or CellCept, hard to tell. Also have a cataract growing now after surgery that will require another surgery. However, with me there are many possibilities to that cause. As far as CellCept for the treatment of Lupus, what I found was that it was not approved as a treatment, but was being studied. The best I can do immediately is suggestions on low vision aides and technology.

[okarol]

Date created: April 10, 2008, updated April 16, 2008

Communication About an Ongoing Safety Review of
CellCept (mycophenolate mofetil) and Myfortic (mycophenolic acid)


PML is a rare disorder that affects the central nervous system.  When it occurs, it is usually in patients with immune systems suppressed by disease or medicines.  It happens when the polyomavirus, also known as the JC virus, is activated.  The JC virus is found in most adults but does not usually cause symptoms.  Scientists do not know exactly how the JC virus is activated.  Once activated, the JC virus attacks the cells that make myelin, the protective coating around nerve cells.  Signs and symptoms of PML can include localized neurologic signs and symptoms including vision changes, loss of coordination, clumsiness, memory loss, difficulty speaking or understanding what others say, and weakness in the legs.  Many patients who develop PML die.  Patients who survive may have permanent disability due to irreversible nerve damage. More information on PML can be found at the National Institutes of Health website.

Roche is aware of cases of PML in transplant recipients and patients with systemic lupus erythematosus (SLE), an autoimmune disorder that is sometimes treated with CellCept; however, CellCept and Myfortic are not approved for treating SLE or similar autoimmune disorders.

[Chris]

Guess I should have reread the topic. I did not find that on Lupus.org,which sems to me would be important after reading the website.