Eltrombopag Rollercoaster

Hi,
I've had ITP for 10 years now. When my counts are low, I always find myself looking through this discussion forum for words of wisdom and inspiration. You've helped me so much over the years! This is however my first posting so this feels like a bit of a milestone. I go through times of remission and then, for no apparent reason, crash to low counts which then get medication attention. Most have been dealt with steroids, one with Rituximab (which gave me over a year of complete remission) and my most recent was just over 3 weeks ago (with a count of 2) which led me to giving Eltrombopag (Promacta, Revolade) a try. I started on 50mg daily and my count rose to 352 in under 2 weeks. I was then taken off the meds to allow my count to go down with an aim of catching me as I went below 100. In under a week, I was back to a count of 20 which is when I started the meds again, this time at a 25mg dose. After 3 days though, I've now had the unwelcome news that my count is back to 2 again so I'm back on the 50mg tablets albeit only until Monday (next blood test). I'm so disappointed that I ended up right back where I started. I'm having regular tests so feel closely monitored and hopefully this is an 'early days' issue which will resolve itself but I'm finding that window of 50 to 150 pretty hard to hit, let alone stay in, right now. I'd appreciate hearing from you if you have had this experience or have any thoughts to share with me. Many thanks in advance.

I started on Eltrombopag 25mg 3 weeks ago with a count of 11. Weekly bloods were 36, 63, and then 14 this Monday but I was full of cold at the time, which always drops my count. Off to GPs for another FBC later today then back to see haematologist on Monday. If count below 50 I expect my dose will be increased. Anne

Hi Anne,
Hope you get some good news on Monday and that your count will have recovered enough for you to stay on the same dose. I'm off to eat some curly kale for lunch - can't say I'm a fan of the stuff but I do find myself drawn to it on low platelet count days!

It can take a while to get the dose adjusted. Stopping the drug can cause huge drops, and when the dose is constantly adjusted to reflect counts, you just end up chasing counts and never get any where. Hang in there with the 25 mg's and give it a few weeks. If need be, adjust it higher. some people have used 37.5 mg's or alternate day doses because 25 was too low and 50 was too high for them. There will be ups and downs along the way, but that doesn't mean that the drug isn't working.

It takes on average 12 days to see some kind of response to Promacta (Presumably, it would take the same amount of time to see a response to a dosage change):

onlinelibrary.wiley.com/doi/10.1111/ejh.12725/full European Journal of Haematology September 2016
Eltrombopag safety and efficacy for primary chronic immune thrombocytopenia in clinical practice

It takes about 10 weeks to reach a steady-state response, and about 4 weeks to reach 80% of the steady-state response:

www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/DevelopmentResources/UCM455677.pdf
Figure 10. Predicted median platelet counts following 50 mg, 25 mg, and 15 mg for all subjects for 14 weeks

You already know that 50 mg is too high a dose for you. Sandy is right: stick with the 25 mg dose and give it enough time to work. Remember, Promacta tells your body to make more platelets, but it takes time for those platelets to grow.

Thank you so much for this advice. Your reasoning makes great sense to me. I would really like to try a stretch on 25mg to see if that works for me. Thanks for sharing those references - I had not seen those dose responses before. I'll keep you posted on my progress!

Count 13th March - 68,000
I have always been described as 'drug responsive' (a status I am very grateful for) ... and I do seem rather sensitive to this one!

I got my count done this morning and already have the result back. It's 68 which is way higher than I expected (... especially with finding new bruising this morning?!). So in summary, I have been on 25mg Eltrombopag since last Monday after having been taken off the meds as I'd gone too high ... had a count of 2 on Thursday ... I persisted with the 25mg tablets (apart from one 50mg on Thursday before writing my post) and get a count of 68 today. Next FBC planned for this Thursday. I am very grateful to be at this safer count but am surprised that it has happened so soon after my count of 2 on Thursday. I'm conscious that after only one week, I'm nowhere near 'steady state' yet and my count is still probably in that upward early part of the response curve. Seems as though I'll be trying a dose lower than 25mg soon. Any titration tips on how/when to go lower than 25mg? Keen to get the timing right this time so I don't have to come off the drug all together again ... I have found the last few weeks a bit scary - I'd never experienced the too low/too high thing in that short period of time before ...

I'm in very close contact with a very supportive Haematology department but I'm also keen to tap into the depth of experience you guys have with this relatively new medication. Many thanks!

Count back up to 36 after the cold abated. Saw Consultant at clinic this morning. Staying on Eltrombopag 25mg/ day and dropping Prednisolone to 7.5mg/day, then 7mg next week. Repeat bloods every Friday & back to clinic 4 weeks today. May have to alternate 25mg/50mg Eltrombopag if platelets drop too much during steroid taper.

CThom, have you tried Kale crisps? By far my favourite way of consuming the stuff.

Hi! So pleased to hear from you - I was wondering how you got on today. All the best to you as you reduce your steroids.
Any food with the word 'crisps' in it get my vote !

CThom:

Great count today! Perfect! Stick with what you are doing for now and see how things go over the next few weeks. Don't change anything yet!

CThom wrote: Count 13th March - 68,000
I have always been described as 'drug responsive' (a status I am very grateful for) ... and I do seem rather sensitive to this one!

I got my count done this morning and already have the result back. It's 68 which is way higher than I expected (... especially with finding new bruising this morning?!). So in summary, I have been on 25mg Eltrombopag since last Monday after having been taken off the meds as I'd gone too high ... had a count of 2 on Thursday ... I persisted with the 25mg tablets (apart from one 50mg on Thursday before writing my post) and get a count of 68 today. Next FBC planned for this Thursday. I am very grateful to be at this safer count but am surprised that it has happened so soon after my count of 2 on Thursday. I'm conscious that after only one week, I'm nowhere near 'steady state' yet and my count is still probably in that upward early part of the response curve. Seems as though I'll be trying a dose lower than 25mg soon. Any titration tips on how/when to go lower than 25mg? Keen to get the timing right this time so I don't have to come off the drug all together again ... I have found the last few weeks a bit scary - I'd never experienced the too low/too high thing in that short period of time before ...

I'm in very close contact with a very supportive Haematology department but I'm also keen to tap into the depth of experience you guys have with this relatively new medication. Many thanks!

Great count CThom! That is perfectly in the target zone for eltrombopag. I hope you manage to stabilize around counts like that.

Regarding kale, I've been trying to increase my consumption as well. I like juicing it or throwing it in a smoothie, though I don't know if liquifying it like that negates the "sticky platelet" benefits of the veggie.

It's also yummy sauteed and cooked with white beans. There are lots of recipes to try. Good luck with your next blood work and I hope your numbers stay good!

Today's count 94K
I was really hoping for the count to still be in double digits at this stage (it's still such early days on this dose) so rather relieved that it was ... just
Next count planned on Monday and staying on the 25mgs for now ...
Many thanks for your best wishes momto3boys. Our favourite vegetable sautéed with beans does indeed sound rather nice! I was pleased to see on your thread that you were feeling positive after your recent count. Great news!

A funny thought ... a few years back when struggling with the side effects of immune suppression medication, a good friend of mine suggested I did some positive visualisation exercises to help me relax. So I got in the habit of taking a moment once in a while picturing myself making some lovely new platelets and my immune system only picking stuff out of my blood which should not be there leaving my platelets alone ... The funny thing is that this visualisation process has now become rather complicated on TPOs as it now involves picturing some but not too many platelets being made and my immune system being allowed to eat some up but not too many ....

No, you don't want counts in double digits! You have a very good count right now and if it bounced between 30k and 100k you are right in target range.

CThom wrote: Today's count 94K
I was really hoping for the count to still be in double digits at this stage (it's still such early days on this dose) so rather relieved that it was ... just
Next count planned on Monday and staying on the 25mgs for now ...
Many thanks for your best wishes momto3boys. Our favourite vegetable sautéed with beans does indeed sound rather nice! I was pleased to see on your thread that you were feeling positive after your recent count. Great news!

A funny thought ... a few years back when struggling with the side effects of immune suppression medication, a good friend of mine suggested I did some positive visualisation exercises to help me relax. So I got in the habit of taking a moment once in a while picturing myself making some lovely new platelets and my immune system only picking stuff out of my blood which should not be there leaving my platelets alone ... The funny thing is that this visualisation process has now become rather complicated on TPOs as it now involves picturing some but not too many platelets being made and my immune system being allowed to eat some up but not too many ....

:lol: I am laughing at your difficulty in visualization with the complexities of the processes. That's cute.

Sounds like you continue to have a fabulous response on 25mg, congratulations! Maybe you will be able to titrate your dose down even further if you continue to climb upwards.

Hi there,

It's been a while since my last post and my rollercoaster is ongoing. After 2 weeks on 25mgs, my count continued to climb and was even threatening to go higher than 150 so my dose was altered to 25mgs for 6 days out of 7 (meaning I'd drop a dose a week). This all sounded great in theory apart from that, following my first dose dropped, my count crash down to 10 4 days later. I then persisted on the 25mgs tablets (promising myself never to drop a dose ever again). My count recovered to 30 by the following week but then, 3 weeks later, whilst keeping on a steady dose of 25mg daily, I crashed down to a count of 4 (last Thursday). I was so disappointed! I was really hoping that I would not be visiting these low count numbers this frequently.

I am now on a dose of 25mg one day and 50mg the next. Let's see what happens now ...

Thanks for sharing CThom. This is exactly what I've experienced with the TPOs- the crash after adjusting the dose. I've taken both Promacta and Nplate, and I've found that even the slightest change in dose can have totally unpredictable results! I believe there is a 12.5mg dose pill of Eltrombopag- people have mentioned it. So that might be helpful if its available. Is there any reason why your counts went to 4 last week? Are you having any side effects?

I'm on Nplate and for a while I kept getting dose adjustments from 453mcg to 495mcg and back again. I really believe that is a bad idea but its not always under my control. Counts were between 33-82, which is fine but I crashed to 3K and 5K for no apparent reason. (except the dose changing)
In January the counts spiked up to 325K after an illness, I skipped a week then requested a lower dose, 412.5mg. I'm actually having better and more stable counts on the lower dose. (?) They trended down for a couple weeks but I kept with the same dose and they came back up.
Nplate 412.5mcg--- 53 58 78 50 47 31 27 33 52 54 57

Good luck. Hope you get back up to 50K soon and find stability!

Posey, have you noticed? Are there some folks that don't seem to have a stability problem with the TPO agonists? Do you suppose there is some types of ITP that do have stability problems and other types that don't?

Yes, Hal- good question. Some people have more problems with stability than others, for sure! Ask "Midwest" Janet- she has such a hard time getting stable. My counts are fairly stable on Nplate and Eltrombopag. I mean even to the point of being freaky like- 40 41 42 42 39 41 (Nplate back in 2015) I have never had wild swings though they have crashed as I mentioned.

I think? the reason I have stable counts on Nplate is that it seems to be effective in my system for only 9 days. So the doses don't piggy back on top of each other. I think the dose peaks on days 5-7. For many people, an Nplate dose might be effective for 2 weeks or longer, so the weekly doses accumulate. Then the counts go way up, the doctor drops the dose or gives no Nplate that week. So several doses quit working at once and the counts crash. maybe? I don't really know if thats true but its kind of what I've gathered from what everyone has said. There are other factors too, like how fast platelets are being destroyed at any given time.

The reason I believe Nplate stays effective in my system for only about 9 days is that I have missed a dose- doctor's office closed for holiday. And I will get bruises, symptoms on about day 9, so I know my counts have dropped.

In CThom's story it appears that his 25mg Eltrombopag (Promacta) was only effective for one day, so when he skipped a day his counts quickly fell. Why did his counts creep up to over 150 if the drug wasn't accumulating? I have no idea. Four times I quit Promacta (cold turkey from 50mg) and each time my counts SLOWLY drifted down over a period of a couple weeks. Why did I not crash? I haven't a clue. haha All said, they are pretty good drugs for ITP, though a bit unpredictable.

Thank you so much for your comments. It's so great hear from people who understand the frustrations associated with being on these meds.

I really don't know why my count dropped to 4 last week. By then I'd been on a steady 25mg dose for 4 weeks (since that one dose I had missed and now of course deeply regret doing so). I have not been ill - all I did different was have a busy and fun Easter week-end! When my count gets to single figures, I have no energy and I get lots of bruising and petechiae especially on my legs. I'm better above a count of 20ish. I am very concerned about what I'm potentially doing to myself taking 50mg one day and 25mg the next. I've been doing this for 5 days now and I'm still getting new symptoms which are telling me that not all is well in platelet world. I'm concerned that I'm probably playing havoc with the platelet production and destruction processes. Promoting one and then triggering the other to do it's worst on the 25mg days (with the whole process delayed by 4-5 days as seems to be the case)! I have asked about a 12.5mg tablet but it does not seem to be available. I'm based in the UK - I don't know if it's different in the US.
I spent 15 years as a research scientist so am probably over thinking the experimental design aspects on this. I suppose it's just about trying something and seeing what happens but there seem to be so many variables at play! As said on these threads, it's about trying a dose and sticking with it which is what I'm so keen to do but I'm finding this tricky when confronted with decision making when at low (so far 2k and 4k) or too high counts.

I apologise for the 'low positivity' tone of this message - My usual humour and bounciness seem to have escaped me for the mo!

CThom
Don't beat yourself up, I can't see how missing a single dose of Eltrombopag caused your drop, it has a plasma elimination half-life of approximately 26 to 35 hours in patients with ITP.
www.accessdata.fda.gov/drugsatfda_docs/label/2015/207027s000lbl.pdf
Anne

CThom wrote: Thank you so much for your comments. It's so great hear from people who understand the frustrations associated with being on these meds.

I really don't know why my count dropped to 4 last week. By then I'd been on a steady 25mg dose for 4 weeks (since that one dose I had missed and now of course deeply regret doing so). I have not been ill - all I did different was have a busy and fun Easter week-end! When my count gets to single figures, I have no energy and I get lots of bruising and petechiae especially on my legs. I'm better above a count of 20ish. I am very concerned about what I'm potentially doing to myself taking 50mg one day and 25mg the next. I've been doing this for 5 days now and I'm still getting new symptoms which are telling me that not all is well in platelet world. I'm concerned that I'm probably playing havoc with the platelet production and destruction processes. Promoting one and then triggering the other to do it's worst on the 25mg days (with the whole process delayed by 4-5 days as seems to be the case)! I have asked about a 12.5mg tablet but it does not seem to be available. I'm based in the UK - I don't know if it's different in the US.
I spent 15 years as a research scientist so am probably over thinking the experimental design aspects on this. I suppose it's just about trying something and seeing what happens but there seem to be so many variables at play! As said on these threads, it's about trying a dose and sticking with it which is what I'm so keen to do but I'm finding this tricky when confronted with decision making when at low (so far 2k and 4k) or too high counts.

I apologise for the 'low positivity' tone of this message - My usual humour and bounciness seem to have escaped me for the mo!

Hang in there CThom! I have had unexplained dips along the way with eltrombopag and always find myself wondering how they happen. One week up in the 100s, then suddenly 18. Keeps us frustrated and trying to manage the doses in different ways. Even when I dropped really low for me, I found that being on the medication allowed me to be asymptomatic at those counts, so I guess that's something.

It sounds like you are unfortunately having symptoms at your drops; I hope things go back up for you. We do have a 12.5 mg tablet here in the US that, if you can get access, may help titrate your dosage more slowly the next time around. I guess you'll have to work with your doctor to decide if you want to give the 25mg daily dosage more time to get you up a little higher again. My responses to the medicine seem to take a while when I increase the dose. When I first started, I took around a full four weeks to see any improvement. It's easy to wait when you don't have symptoms and extremely low counts! Adding a day or two at 50mg may be enough to help you through your current crash, and really isn't such a dramatic dosage change from what you've been on. Good luck!

Ah - thank you for this very useful reference mrsb04 and for your words of encouragement momto3boys. I am seeing my usual consultant next week so it will be interesting to review all this data with him then. He has been away in recent months so it will be nice to catch up with him again.

There is an ITP conference in a couple of weeks arranged by the ITP Support Association (In London). I usually attend these events as they are always so informative but I will unfortunately be missing this one as my son will be sitting important exams around that time. I will thus be home baking muffins or anything else which might help a teenage boy with revision on Jane Eyre instead of listening to Dr Provan!

CThom wrote: There is an ITP conference in a couple of weeks arranged by the ITP Support Association (In London). I usually attend these events as they are always so informative but I will unfortunately be missing this one as my son will be sitting important exams around that time. I will thus be home baking muffins or anything else which might help a teenage boy with revision on Jane Eyre instead of listening to Dr Provan!

Haha, sorry that you are missing the conference this time around, but I can definitely sympathize with prodding a teenage boy through Jane Eyre! My oldest son (just turned 15) literally finished up with this novel earlier this week (fun coincidence). I wasn't so kind as to bake him muffins though, you are a nice parent! Maybe I'll bake for him as he works his way through A Tale of Two Cities next,

Good luck getting through the exams!

Posey, thanks for the detailed reply. Unfortunately there seem to be lots of examples of those that have a hard time with stability. Do any names come to mind besides yourself that have an easy time with stability?

Your thoughts on accumulated NPlate doses and crashing makes a lot of sense. Had not thought of it that way before.

As you state, when one stops Promacta counts should drift lower - just as they drifted up when starting the drug. But there does seem to be crashes with some folks when missing a dose or as they taper off. When you tapered off Promacta I suspect you did not crash for the same reason you don't have stability problems. That is, I suspect it depends on what type of ITP one has.

It's been a while since my last update so I thought I'd join in with the sharing of news today

I tried alternate doses of 25/50mg for 4 weeks but my count never really went anywhere. My last count was 10. The fatigue had really set in and I was finding work challenging. I was also having quite a few bleeding symptoms.

As 50mg seemed too much and 25mg not enough - I am now trying 50mg for 5 days followed by 25mg for 2. Has anyone tried this dosage before? My hematologist is being fab and really supportive which is great. Let's see what happens next ...

Curious. What did it get up to on 50 mg?

My count rose from 2 to 352 in under 2 weeks on 50mg daily.

Wow.
When you took steroids, did you get this same sort of ITP on / off response?
If so, just off hand, seems like count swings should be even larger with Promacta than with steroids.

I had a positive response to steroids (initial 60mg doses which were then tapered down). A course would return my count to normal albeit for different lengths of time (6months to a few years once). I did not tolerate steroids well though - each course feeling worse than the last ... it was then decided anyway that I'd had my fill of steroids and needed to find another solution.

CThom wrote: It's been a while since my last update so I thought I'd join in with the sharing of news today

I tried alternate doses of 25/50mg for 4 weeks but my count never really went anywhere. My last count was 10. The fatigue had really set in and I was finding work challenging. I was also having quite a few bleeding symptoms.

As 50mg seemed too much and 25mg not enough - I am now trying 50mg for 5 days followed by 25mg for 2. Has anyone tried this dosage before? My hematologist is being fab and really supportive which is great. Let's see what happens next ...

Sorry to hear that your counts aren't the best and it's bringing on fatigue and symptoms, phooey! I have done miscellaneous alternating doses when I was trying to get some stability coming down from 75mg (Things like 75, 75, 50, 75, 75, 50). I would recommend that you not do all of your 50 days followed by two 25 days back to back. Do something like 50, 50, 25, 50, 50, 25, 50 over the course of a week. This is more gradual than spiking two 25mg days at one time. It's all experimenting though and seeing what works for you. Good luck and I hope you can get the counts up with a little jiggling here and there!