Label Change for Exjade-Important!

Courtesy of CAF.

http://www.cooleysanemia.org/index.php?option=com_content&view=article&id=260%3Alabel-change-for-exjade&catid=1%3Alatest-news&Itemid=1

February 25, 2010 - The FDA and Novartis Oncology have announced new prescribing information for deferasirox (Exjade) because of recent findings that the drug may cause renal, hepatic and gastrointestinal damage.


New language was added to the contraindications, warnings and precautions, and drug interactions sections of the prescribing information, including a "black boxed warning."  The FDA and companies use these warnings when they want clinicians to pay particular attention to possible risks.  In this case, this warning indicates that deferasirox may cause renal and hepatic impairment and/or failure and gastrointestinal hemorrhage. Reactions were severe enough to be fatal in some patients.

Reactions were more often seen in older patients, as well as those with high-risk myelodysplastic syndromes, underlying renal or hepatic impairment or low platelet counts. The FDA said therapy with deferasirox requires close patient monitoring, including measurement of serum creatinine and/or creatinine clearance as specified in the prescribing information, and serum transaminases and bilirubin as specified in the prescribing information.

Ellis Neufeld, MD, Chair of CAF's Medical Advisory Board, comments, "Expert thalassemia centers and clinicians have known about these risks before the warning was added to the Exjade label.  Fortunately, most thalassemia patients are young compared to the older adults who had severe or fatal outcomes to Exjade use.  However, in the thalassemia population, stomach and duodenal ulcers, bleeding, liver and kidney problems have been noted, and therefore close monitoring is suggested.  Also fortunately, most thalassemia patients who take Exjade do so without these unwanted side effects."

As always, if you have specific questions about how this new information applies to you, please contact your clinicians.

The FDA has more information, including a letter to health care professionals (click here) and full prescribing information (click here) at its website (click here for FDA website).

Yet, Ferriprox is not approved in the US? And again, Novartis has known about this for years but has been very slow to add this information to the labels.

I am very concerned about the long term use of Exjade, especially in older patients. I do not see this as a lifelong chelator, but I really don't think patients should look at any one chelator as the answer. Most doctors will tell you that a variety of different chelators during a lifetime, is a better approach that will address iron deposits throughout the body.

I am very concerned about the long term use of Exjade, especially in older patients. 

Me too, Andy!


Lena.

We should really emphasize how important regular monitoring is when a patient uses Exjade or Ferriprox, and also don't forget the annual monitoring for desferal users. These are powerful drugs that can have serious side effects. No chelating drug should EVER be taken unless under a doctor's supervision.

With this information about Exjade, in addition to the regular monitoring of kidney and liver functions, parents and patients need to watch for signs that something is wrong. Ongoing drops in hemoglobin levels, which cannot be explained by other factors, such as recent illness or an antibody reaction or overactive spleen, should be investigated for an explanation for the blood loss. Any blood in the urine or feces should be immediately reported to the doctor. If the doctor is not aware of the connection between Exjade and hemorrhage, show the doctor the new labeling. Ongoing stomach or intestinal duress should also be reported to the doctor.

Chelators have allowed thals to live but we must always respect the fact that these are powerful drugs that can cause reactions in some patients. No one chelator can be said to be ideal for every patient, so sometimes trial is the only way to learn if a chelator is suitable.

And please, do not overreact to this information. Please note that these problems have been reported in a small minority of users and the most severe cases have been mostly found in older patients with pre-existing conditions. We need to stay vigilant but that does not mean go into a panic anytime you have a suspicion that something may be wrong.

And once again, we come back to the same conclusion. New and safer chelators are an absolute must and those chelators already in development should get priority status for funding so the drugs can be trialed to see if they can be brought to the market. Starch DFO needs funding and I think everyone can see why.

Thanks for the info Andy, I hope there will be new chelators available soon,and i hope Ferriprox would be approved soon for US patients.It is scary but we have to fight and chelate no matter what.

Zaini.

I agree that we need more chelators. Unforunately my daughter can't take Ferriprox even when it is approved in the US. Ferriprox can cause permanent neutropenia in patients with Diamond Blackfan anemia (which is my daughter's diagnosis). Her only choices right now are Exjade and Desferal.

Scott

hi to all an tanx for this topic
I was search for like that coz here in iran I hear pataint can register for exjade but when I ask my Dr he say I advise you dont use that coz of hep C and it have effect on that so I wanted to ask this matter so find this whats your idea?

Hi zs,

I don't know why your doctor suggests to stay away from exjade ---I suppose he told you that, because of the side effects exjade might have on liver but I know many thals here who chelate with exjade regardless their having Hep C - in fact one of them is on Hep C therapy with interferon and ribavirin at the same time.


Lena.

in that case u think it is wise to start that or not?

Zs,

unfortunately I cannot answer that question - I am not a doctor and I am not aware of your personal condition. Only your doctor can say. I have just passed on the information of what I have experienced and seen happening here.Why don't you discuss it with your doctor informing him of what you know from this site?

Lena.

hi dear lena

 I know that so tanx for share your experience I hear that news that register for exjade this week and my Dr was

 in conferance these day so I cant see him I speak about exjade some time ago and he answer me

so I wanted  to collect good  info and ask him next week so tanx for sharing experince that may make good info

You are welcome, zs

I wish I could be of more help...
but the only thing we are able to do is to share our experience and this may help. Doctors must take it from there.

Lena.

I agree with Lena. Your doctor has to evaluate the status of your liver to see whether Exjade will be suitable for you. If your liver function tests already show high levels, the doctor may not want to allow Exjade use because it can make those levels go even higher.

I want to thank Lena for bringing this to my attention. There is a further recommendation about monitoring when using Exjade (deferasirox, Asunra, desirox) concerning kidney function.

http://www.ncbi.nlm.nih.gov/pubmed/19493602

Fanconi syndrome due to deferasirox.

Rafat C, Fakhouri F, Ribeil JA, Delarue R, Le Quintrec M.

Université Paris Descartes, Hôpital Necker, APHP, Paris, France.

Deferasirox is an innovative iron-chelating treatment. However, preliminary data have suggested that kidney toxicity may be a major issue in the management of patients receiving this drug. We report a case of Fanconi syndrome associated with acute renal insufficiency in a patient receiving deferasirox. The latter has to be added to the expanding list of drugs that may induce Fanconi syndrome. Careful monitoring of kidney function and markers of proximal tubular injury are mandatory in patients undergoing treatment with deferasirox.

We already knew about the kidney function tests but checking for "markers of proximal tubular injury " is a new recommendation and is very important.

For more information about Fanconi syndrome see
http://www.nlm.nih.gov/medlineplus/ency/article/000333.htm

Fanconi syndrome is a disorder of the kidney tubes in which certain substances normally absorbed into the bloodstream by the kidneys are released into the urine instead.
Causes

Fanconi syndrome can be caused by faulty genes, or it may result later in life due to kidney damage. Sometimes the cause of Fanconi syndrome is unknown.

Common causes of Fanconi syndrome in children are genetic defects that affect the body's ability to break down certain compounds such as:

    * Cystine (cystinosis)
    * Fructose (fructose intolerance)
    * Galactose (galactosemia)
    * Glycogen (glycogen storage disease)

Cystinosis is the most common cause of Fanconi syndrome in children.

Other causes in children include:

    * Exposure to heavy metals such as lead, mercury, and cadmium
    * Lowe's disease, a rare genetic disorder of the eyes, brain, and kidneys
    * Wilson's disease

In adults, Fanconi syndrome can be caused by various things that damage the kidneys, including:

    * Certain medications, including azathioprine, cidofovir, gentamicin, and tetracycline
    * Kidney transplant
    * Light chain deposition disease
    * Multiple myeloma
    * Primary amyloidosis

Symptoms

    * Passing large amounts of urine, which can lead to dehydration
    * Bone pain
    * Weakness

Exams and Tests

Laboratory tests may show that excess amounts of the following substances may be lost in the urine:

    * Amino acids
    * Bicarbonate
    * Glucose
    * Magnesium
    * Phosphate
    * Potassium
    * Sodium
    * Uric acid

Loss of these substances can lead to a variety of problems. Further tests and a physical exam may show signs of:

    * Dehydration due to excess urination
    * Growth failure
    * Osteomalacia
    * Rickets
    * Type 2 renal tubular acidosis

I need to also point out that Fanconi syndrome has been observed in thalassemia independent of Exjade. This is believed to be primarily the result of iron damage and oxidation in the kidneys. So, lack of chelation is another factor in Fanconi's and thalassemia.

In the more developed countries, proper testing should not be a problem, as long as the doctors are aware of this. I would suggest that all patients using Exjade take this brief quote above and show it to their doctors so the doctors are aware of this recommendation.

can someone tell me why thals get hep c>?

Hep C is contracted from infected blood that is used for transfusions. In most places the blood is now safe, but testing didn't start until the early 90's or later, so anyone transfused before then may have been exposed to Hep C.