Advised to start chelation

[Mseth]

My mother has been advised to start chelation therapy. From dx, she has received 20 units, and is doing fine as of now, being able to care for herself, has decent appetite and so on..Her recent ferritin levels are 2600 at one lab and 3600 at another, within the same week.
The chelation drug prescibed is Assunra(made by Novartis), same as Exjade.It is used extensively by Thalassemia patients(mostly children), who are transfusion dependent from birth due to a genetic disorder.

I am extremely worried about if and how she will tolerate this medicine. She is 77 years. I understand the iron overload and associated toxicity, but would be gratfeul if i could get some advice on the following:
1. How long(months/years) does the iron overload take to cause damage?
2. The iron overload may create damage at a later stage, but the chelation drug will start its renal & hepatic damage almost immediately, is it better to not take the chelation drug?
3. If the kidney & liver get affected, will the affects reverse on stopping the drug?
4. Will normal anti-nausea/anti-diarhea medicines help control these symptoms?
5.What are the factors that one should consider before starting on this? Is it advisable to get heart & liver MRI done to see if there is already an overload happening?
Thanks in advance for any suggestions and experience.

[Birgitta-A]

Hi Mseth,
It takes years for iron overload to cause serious damage in the liver (we manage well with 33% of the liver) and the heart.

If the creatinin or liver tests will increase too much the drug will be stopped. We manage well with one kidney which means that we have much reserve capacity.

I don't think we will get new liver cells or that the kidneys are repaired but that will not be a problem if these organs are OK initially.

It is important to start slowly with the drug and look out for adverse effects. I could only tolerate 500mg Exjade/day but according to my weight I should have had 1250mg. My WBC decreased when I took 1000mg. I had no other adverse effects.

I think it will be OK to control lever and kidney blood tests and follow them closely.

I had MRI of heart and liver done after about 50 units of blood. There was not a trace of iron overload. I had started with Desferal after 40 units of blood. Now I have received 186 units of blood with Desferal during 4 Days with trsfusions. My ferritin is about 1900. My liver tests are OK.
Kind regards
Birgitta-A

[Mseth]

Originally Posted by Birgitta-A

Hi Mseth,
It takes years for iron overload to cause serious damage in the liver (we manage well with 33% of the liver) and the heart.

Hi Birgitta-A,

Thanks for the reply. My next question is if there is an answer as to how many years can one manage without chelation, if getting regular transfusions. How does one decide whether or not to take the drug and risk the adverse effects. The mixed reports on whether or not chelation is an advantage for older MDS patients confuses the issue further.

[Birgitta-A]

Hi Mseth,
Yes, this question is complicated. I don't think anybody knows how long we can manage with txs without chelation. Some doctors mention that patients who are supposed to live more than two years should start chelation when the ferritin level is more than 1000.

If your mother's liver and kidney tests are OK she could start to take 250 mg Exjade per day. The tests could be controlled every week. If they are OK the Exjade dose could be increased slowly.

You know all iron chelators can decrease the frequency of txs. Eventually the chelators decrease the oxidative stress in the bone marrow.
Kind regards
Birgitta-A

[Mseth]

Hi Birgitta-A, thanks for the suggestion, i agree that a low dose may be the best way to start. Always very anxious with any new drug. I hope and pray that she is able to tolerate it and has good response in bringing down the ferritin.

[Birgitta-A]

Hi Mseth,
Here is an abstract from the Hematology Conference about MRI examinarion of MDS patients. In short they show that they often don't find iron in heart (cor) though many patients had iron in the liver.

This finding is not new - I have read it several times before.

http://www.mdsbeacon.com/resources/m...2013/abs/2819/
Kind regards
Birgitta-A

[Mseth]

Hi Birgitta-A,

Thanks for the link, is it that the tests are not accurate for seeing iron in the heart, or that iron overload does not happen in the heart and mainly affects liver.
The drug insert(it is made in switzerland, and marketed in India under name Asunra), mentions increased creatinine levels as a very common affect. As you have suggested, weekly monitoring will be important, my mother will start with 100 mg(1 tab), and increase gradually over next few weeks.
Thanks for sharing your experience and information.

[Birgitta-A]

Hi Mseth,
In this abstract they write that the method perhaps isn't OK for measuring iron in the heart. Otherwise they write that MDS patients are different from Thalassemia patients who start with txs when they are children and that in MDS the liver often manage to protect the heart and other organs during several years.
Kind regards
Birgitta-A

[Mseth]

Originally Posted by Birgitta-A

in MDS the liver often manage to protect the heart and other organs during several years.

Hi Birgitta-A,
While this finding is encouraging it also confuses the issue on whether using chelating drugs is an advantage or not in elderly MDS patients, the drug may lead to a deterioration in quality of life and other adverse effects quicker than what they may experience without chelating agents.

[Birgitta-A]

You know many patients can take Exjade - perhaps not the full dose - for years without adverse effects.

In Sweden Desferal that is given intavenously in a port during four days in connection with txs is the first drug. I have received 75 doses of Desferal in a small home pump without any complications or adverse effects.

I don't really think txs and Deferal make my quality of life lower but I have been tx dependent since dx 2006 except for almost 3 years 2010-2013 when I had Thalidomide.
Kind regards
Birgitta-A

[Mseth]

Hi Birgitta-A,

It is the positive experience that some like you have, which encourages us to even think about giving it a try.
I will post the response once she starts.

Many thanks.

[Birgitta-A]

Good luck!
Kind regards
Birgitta-A

[Mseth]

Hi Birgitta-A,

Thanks for your good wishes. First week of 100 mg/day of Asunra(exjade equivalent) has gone off fine, now increased to 2X100 mg/day. Hematology doc will be unhappy with this low dose as he wanted to start with 800 mg/day. But gradual increase seems safer to do.

Thankyou.

[Birgitta-A]

Hi Mseyh,
Very good that you managed to make the doctor increase Asunra slowly. There is no hurry when your mother probably will take the drug during a very long time.

Do you follow your mother's counts and creatinine (a kidney test)?
Kind regards
Birgitta-A

[Mseth]

Hi Birgitta-A,

Yes, i follow the counts which are done every 2 weeks. Following the creatinine levels as well now, after 1 week of 100 mg asunra, creatinine is still same at 0.7 (ref range 0.5 - 1.5).
Thanks for taking the time to read my posts.
Regards.

[Birgitta-A]

Hi Mseth,
Good that your mother is OK this far and that you can support her!
Kind regards
Birgitta-A

[Mseth]

Hi Birgitta-A,

Is there a way to calculate how much the Ferritin should reduce with chelation and over what period of time? And the additional burden that comes with each transfusion?

Thanks.

[Marlene]

John was on lower doses of Exjade and it really took a long for the FE to come down. And at the time, he was not transfusion dependent. FE fluctuates too much to be a used as a reliable indicator of iron excretion.

If I am remembering correctly, each unit of packed red cells has 200 - 250 mg of iron.

This is from the RXlist.com http://www.rxlist.com/exjade-drug/cl...armacology.htm

"Pharmacodynamic effects tested in an iron balance metabolic study showed that deferasirox (10, 20, and 40 mg per kg per day) was able to induce a mean net iron excretion (0.119, 0.329, and 0.445 mg Fe/kg body weight per day, respectively) within the clinically relevant range (0.1-0.5 mg per kg per day). Iron excretion was predominantly fecal."

It's very difficult to reduce iron while still transfusion dependent. Sometime all you can do is stop or slow down further accumulation. A lot depend on the dosage you are taking. We knew of one person who did IV desferal 24/7 in order to get his FE lowered. That was a very aggressive approach.

[Mseth]

Marlene, thanks for responding. I now know not to expect a great reduction in ferritin, my mother is currently on 10 g per/kg dose, gradually increasing and keeping a watch on kidney & liver function.
Each unit adds in about 250 mg of iron, but not sure how much it directly adds to ferritin. I read sometime back that its 100 ferritin points per unit, but have not found that article again.

[Marlene]

Sorry....thought you meant iron when asking about the FE.

I don't think you can actually depend on FE to be an accurate indicator. Once it's elevated over 1000, pretty much anything can cause it to rise. John's would bounce around all the time. We'd see jumps of 1500 points and then drop the next week. So many things can effect it. It seems it would stabilize for months within a specific range and then all of a sudden drop only to hold at that level for a while. The closer we got to 1500 the less erratic it behaved.

Once it gets below 1000, it seems to behave better. But our doc said that even then, you need to look at the entire iron profile.

John had to stop it eventually because his kidneys were being effected. He never got to full dose so it was very slow going for him.

[Mseth]

Hi Marlene,

Thanks for sharing the experience.Did you find any specific foods or remedies that helped the side effects & tolerbality even a little bit? I have read some posts emphasising on keeping well hydrated which helps to some extent.

[Marlene]

There was nothing that seemed to help him with the exjade side effects. And we tried many things. Homeopathy helps a tiny bit but Exjade always won out in the end. Nausea was the most troubling. He would just have to take a break from it for about a week or two and then start up again. He had the same problem with desferal.

John was on a low dose for about two years. He started at 500 and worked up to 750 mg. 1000mg was too much for him. It wasn't until the last couple of months that his kidney panel was off. Even 250 mg would cause the creatinine to rise.

[Lbrown]

I'm taking exjade, but I really don't understand why the dose is based on your weight, when the blood transfusions aren't. I'm supposed to take 2000 mg a day but I usually take 1500 mg.

Deb

[Mseth]

Hi Deb,

Its good you are able to tolerate 1500 mg/day, how long have you been on chelation and are you able to have lesser side effects than when you started?
Do you monitor your kidney & liver functions regularly?
The heme doc says that with Asunra(the exjade equivalent in India), most tolerate well and if there is an issue, it normally happens within 1st week or so, after which the body begins to adapt to it.

Thanks for sharing your experience.

[Lbrown]

I guess I've been taking exjade for 3 years or more. I wish it was as cheap here (Canada) as it is in India though. I really hate taking it and sometimes I am able to get away without taking it for awhile. I get my counts done every 2 weeks, creatinine and ferritin too.

Deb