Glivec 800mg single dose?

Hi Rebecca,

You should be able to split the Gleevec dose without any problem. This is because Gleevec has a long half-life(18 hours). Once you have taken a full dose of Gleevec it doesn't matter how you split taking the next days' dose. Your body will have the full level of Gleevec it needs.

I am surprised that your doctor didn't know this.

Here is an article by Dr. D'Amato (a GIST specialist) who explains it much better than I can.

Zavie

Dr. D'Amato speaks about splitting GLEEVEC dosage
Below message from Dr D'Amato regarding her opinion on Gleevec dosing. It can be posted.

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The ideal dose of Gleevec is 400 mg a day for the majority of GIST patients. Known exon 9 patients should try for a higher dose of 800 mg a day. How many times a day someone needs to take a medicine is determine by the half-life of the drug. The half-life is the time taken for the amount of drug in the body to fall by half. The shorter the half-life of the drug, the more frequently someone needs to take it. The longer the half-life the less frequently some needs to take it. The half-life for Gleevec is about 18 hours. There is also another metabolite with a half-life of 40 hours, and that is why you must stop Gleevec for a few days to a week prior to starting a new drug. Since Gleevec has a long half-life, taking the pill once a day is sufficient to have an adequate amount of drug in the body. If the half-life were say, 6 hours, then you would have to take it more frequently like 2-3 times a day.

Now, if a patient is not tolerating the 400 mg (or 800 mg) well and would like to try for example, 200 mg in the morning and 200 mg in the evening, that is perfectly acceptable because there will be enough in the blood stream because of the long half time. In short: long half life: ok to take once a day OR more frequently since the level in the blood will stay the same; short-half life: only ok to take more frequently since if take once a day will not have enough in blood stream. Gleevec has a long half-life

Retrieved from "http://gistsupport.medshelf.org/Dr._D%27Amato_speaks_about_splitting_GLE..."

Zavie Miller
Ottawa, Canada

e-mail: zmiller@sympatico.ca

Hello Rebecca

Where are you being treated? Perhaps if its not a specialist centre you could ask for a second opinion at one? 800mg would be the norm for someone Dx in blast crisis I think, taken in two doses one am one pm. Plus there are many other factors to look at that need specialist testing of the blood - to check for the factors that have got you to blast crisis.

Not sure where you live, but some of the specialist centres in UK are Newcastle - Dr S O'Brien, Liverpool, Hammersmith, Kings College hospital London, Cardiff. Addenbrookes. Birmingham.

I urge you to get to one of these specialists as soon as possible. If you post where you are in the UK I am sure one of us will be able to let you know the nearest specialist centre to you.

Please insist on an answer from the Dr who increased the doseage. As Michael has said don't be put off. It's very very important that you get excellent advice and care, particularly at this early stage of your diagnosis. CML is a rare cancer and in many hospitals the consultants have never seen another case. (We know we are special !!!) If you don't feel well enough to argue your point perhaps you could take a strident family member or friend to make the case for you. This is your health and hard as it seems even in UK, where we are so lucky to have our brilliant NHS we still have to stand up and fight sometimes.

I do hope you are able to get some clear answers on Monday, remember we are all here to help, and many of us have had to battle for the right treatment in a specialist centre, so can help you find your way through the system.

Good luck,
Pennie.

Dear Rebecca,
I am sorry you have been diagnosed with CML and that you are in blastic phase.
I would advise that you must ask you doctor exactly what this means in your case. The fact that you are being treated with imatinib (Glivec) at 400mg to combat this more agressive phase of the disease seems a little low.....

Blast crisis is an aggressive phase of this disease and needs urgent expert intervention. This might be a higher dose (800mg) of imatinib and careful monitoring of your blast cell counts.

It might help you (and us) to better understand your exact situation if you asked your doctor to tell the % of blast cells are in your marrow/peripheral blood.
Usually blast crisis is determined by more that 30% of blast cells evident in you marrow and/or blood tests.
over 5% and up to 30% usually signifies the disease is entering accelerated phase.
Less that 5% is normal for chronic phase.

It might be that your disease has suddenly jumped from chronic straight to blast phase- as this can happen with a small number of patients- the accelerated phase is missed out.

No matter what your blast count must be intensively monitored so that if imatinib is seen not to be controlling the disease, it might be that you would need high dose chemotherapy to rescue your marrow and get you back into chronic phase... at which point a TKI (either imatinib/Glivec or one of the newer 2nd generation drugs- dasatinib/Sprycel or nilotinib/Tasigna) would be given.

I cannot stress too strongly that you need to be at a centre that has extensive experience in treating CML. Leeds is the nearest highly expert centre to Sheffield as I understand the geography ;o)
Dr Graham Smith is very experienced with treating patients with imatinib and other TKI's.... you might consider a second opinion at least?

As Pennie and Michael have said... you need to be your own stong advocate in this a situation and if you can't manage that on your own (it is quite difficult to think of all the right questions and then also remember the answers if you are under the stress of a new diagnosis) then please take somebody that will help you find out the docotrs plans for getting your disease back into chronic phase as soon as possible. This should be the prime goal of your therapy right now and as CML in blast crisis is notoriously difficult to treat with TKI's alone then, it might be that you need to ask your doctors if and why they are confident that they can do this with 800mg imatinib/Glivec.

Regarding side effect of the higher dose... Zavie has advised you well that you can split the dose in two... just make sure you take the tablets with plenty of water and after a large meal. If you split the dose between after a large breakfast and then again after a large meal in the afternoon then you have the best chance of overcoming sickness and keeping the drug in your body so it can do its work. You need to get your drug levels up as fast as possible... imatinib with high carb meals seems to be the best way to combat sickness and vomiting for most people.

Please keep us updated and do consider a second opinion.

best wishes,
Sandy