Nausea with NPlate

Three days from now will be the one year anniversary of the day I was first diagnosed with ITP. (It feels much longer!)
I've been on NPlate for about 6 months now and within the past several weeks or so noticed increased occurrence of nausea. About every other week I have at least one very intense wave of nausea that once made me vomit and the other times I desperately wanted to. I have a very strong stomach, and prior to a few weeks ago I honestly can't remember the last time I vomited. I know it was well before I met my spouse and we've been together 7 years now. It was rather startling.

It didn't occur to me until recently that there may be a correlation with the NPlate. I didn't have these intense waves of nausea initially-- just headaches with dose increases and fatigue. I'm getting weekly headaches now, though I've been on the same dose for 7 weeks at this point, & having worse insomnia and stomach issues.

Has anyone else noticed a worsening of side-effects over time? Generally, I hear of side-effect symptoms subsiding over time.

Oliver-- hi, I've been on Nplate for 4 years and find my side effects of headache and insomnia are very dose dependent. Can you lower your dose? Target counts are supposed to be 50K. My platelets are lower usually, around 30K to 50K. That suits me, I don't want high counts on these drugs. Do you notice your symptoms recur on a particular day of the week? I get mine usually on day 5 after injection.
I'm on 408mcg total dose (5mcg per kg). When my dose was increased to 454mcg I had a worsening of headaches, insomnia- I think dizziness, maybe nausea? don't recall. So just dropping the dose a bit helped so much. My side effects come and go. Some weeks nothing, some weeks a mild morning headache that goes away when I stand up and drink coffee.
With Nplate I have had the experience of the side effects going away with time. But when I was on Promacta it seemed like the side effects got worse and weirder over time. I went off of Promacta to see if it was the drug, and I always felt better within 24-48 hours after quitting. I tried with the drug several times so am clear that Promacta gives me unusual side effects- memory lapses, brain fog. Most people have no side effects so its very individual.

Hi Poseymint,
When I switched docs 2 months ago we adjusted my dose for a target range of 30-50; which suits me much better than the 50-200 range my previous doc set. I highly agree with you about high counts! When I switched offices I was on 5mcg/kg, and new doc gave me the option of trying 4mcg/kg since I was above 50. I dropped to 13, which he said was too low, & increased it again.

At my old office they gave me 260mcg or 270mcg depending on a weight fluctuation of 2lbs; which sent my count all over the place. Currently, my new doc is keeping me at 250mcg for 6 weeks and seeing what my body does over that period of time.

I had been fluctuating around that range (30-50) for 4 weeks, then this past week dropped to 20. They kept me on the same dose to see what happens next week, but at this point I doubt they would be willing to decrease it any.

I frequently get headaches on Thursdays or Fridays, and my injections are on Thursdays. Then, they often last on-and-off for 3-5 days. I have not yet noticed a pattern with the nausea. I had been thinking it was diet-related, but now I'm wondering about the NPlate.

Thank you for your reply and input!

Oliver- Your new doc sounds much smarter about Nplate. I strongly believe in keeping the dose constant. Your story of counts all over the place is exactly what I've been thinking happens when dose is always being adjusted. I told my hemo that my counts crashed to 3K and 5K because the dose was adjusted from 495 to 453 and back and forth. He said thats impossible that such a little dose adjustment would cause counts to crash. BUT I agree with you, it happens! He lets me do what I want even when he doesn't agree, so I have been on the same dose of 408mcg for over a year. Counts have dropped to 13 and 15 when I missed a week or was traveling and had 9days in between injections. My counts seem to always come back up if I stay on the same dose and just ride it out.

Its really wasteful for your old doc to prescribe 260mcg because it comes in vials of 250. They cost around $2500. So if you get 260 they are only using a tiny drop of a second vial and dumping the rest. Thats what they do at my clinic anyway. They told me they have to dump the leftovers, can't give it to someone else. Crazy. Well, its too bad if you are having intolerable side effects. My headaches last for about 5 min, I doubt I could tolerate feeling bad for several days. If you haven't tried Promacta, many people like it and have achieved remission on it. best of luck!

Oliver, that is strange.
I've got a really strong stomach as well and rarely get any nausea. But from about 1 week to 3 weeks ago I was getting a mild nausea feeling in the late morning. It lasted a couple of weeks and seems to have gone now. I have to wonder if there is some sort of summer flu going around. That you might get better soon, and, counts may go back up higher than your last count of 20 when you recover.

poseymint wrote: Oliver- Your new doc sounds much smarter about Nplate. I strongly believe in keeping the dose constant. Your story of counts all over the place is exactly what I've been thinking happens when dose is always being adjusted... My counts seem to always come back up if I stay on the same dose and just ride it out.

This makes perfect sense to me. I've noticed big swings when my dose was adjusted, and they seem to level out over the next week or two. It makes me very nervous about dose adjustments.

poseymint wrote: Its really wasteful for your old doc to prescribe 260mcg because it comes in vials of 250.

I learned this at the Conference and from my new doc. My old doc said they mixed it up every week from a powder(?) When he was tweaking my dose for a target range of 30-50 that's why he said it was ok to just do 250-- one whole vial-- rather than 265. I REALLY appreciate this!

poseymint wrote: If you haven't tried Promacta, many people like it and have achieved remission on it. best of luck!

I tried Promacta first, and at 75mg dropped into the low 20s, so she switched me to NPlate because she said it "wasn't working". I wasn't particularly upset about this, as I HATED Promacta. The empty stomach thing was extremely difficult for me, and I appreciate that NPlate isn't metabolized through the liver. While I'm not wild about having to go in every week for blood work and an injection, I've been consistently working with the same infusion nurse since I've been at the new place and I LOVE her! I also feel much more confident that this new doc knows what he's doing.

Thank you for sharing your experiences and for your support! *squishes!*

Hal9000 wrote: Oliver, that is strange.
I've got a really strong stomach as well and rarely get any nausea. But from about 1 week to 3 weeks ago I was getting a mild nausea feeling in the late morning. It lasted a couple of weeks and seems to have gone now. I have to wonder if there is some sort of summer flu going around. That you might get better soon, and, counts may go back up higher than your last count of 20 when you recover.

Thanks, Hal! This is encouraging. I'll be interested to see how my symptoms do over the next few weeks.

By the by, my new doc decided he didn't want to try Fostamatinib with me. He is not encouraged by the "low batting average", and said the toxicity profile was much higher than NPlate. Since the NPlate is working for me, he doesn't want to mess with it. He's not willing to try it with any of his patients at this time, but now that he knows more about it and that it's out there would consider it if a patient is refractory to everything else.

Oliver091117 wrote: ...
By the by, my new doc decided he didn't want to try Fostamatinib with me. He is not encouraged by the "low batting average", and said the toxicity profile was much higher than NPlate. Since the NPlate is working for me, he doesn't want to mess with it. He's not willing to try it with any of his patients at this time, but now that he knows more about it and that it's out there would consider it if a patient is refractory to everything else.

Not willing? I don't know about you, but that is hugely disappointing to me. What a let down. Though rare, I'd ask him if he'd treat someone with it who lost Nplate response. That neutralizes the toxicity rebuttal.

Thanks Hal,
Actually, I was more disappointed that he's not willing to work with me to get off meds than I was about his unwillingness to try Fostamatinib with me. I appreciated his concern about toxicity, and it makes sense to me that an oral drug would be harder on the liver, etc.

I got the feeling he would be willing to try it with a patient who lost NPlate response or who was refractory to everything else and posed a significant bleeding risk. You said it's rare to loose NPlate response-- do you know how frequently this does occur?

My biggest frustration is lack of body autonomy. I strongly feel it is important for doctors to educate patients to the risks/ benefits of different treatments (or lack, thereof), and to work WITH us to make decisions that we feel the most comfortable with for ourselves. If I did feel very strongly about trying Fostamatinib I would be livid by this particular refusal.

I agree with your doctor, Oliver regarding Fostamanitib. I wouldn't risk trying a brand new drug when you are responding to Nplate. My doctor hasn't mentioned Fostamanitib probably because its really expensive, just as costly as Nplate. Nplate has been around for 10 years so there is much more known about it. Plus the low response rate of 18% compared to 80% with Nplate- and some folks (11%?) had liver enzymes in the trials- high ALT AST.
That said, its still great that the drug companies recognize ITP and are working on drugs- more options the better!
My experience with doctors "educating and working with patients".. well, they WILL work with me IF I educate myself and present what I want to them. My docs (hemo and rheumatologist) will usually go along with what I want. But it does take time to build a rapport with a doctor.

poseymint wrote: That said, its still great that the drug companies recognize ITP and are working on drugs- more options the better!

While I don't personally want to be on drugs I highly agree with you!

poseymint wrote: My experience with doctors "educating and working with patients".. well, they WILL work with me IF I educate myself and present what I want to them. My docs (hemo and rheumatologist) will usually go along with what I want. But it does take time to build a rapport with a doctor.

I'm biding my time and hoping to build a rapport with this new doc so I can do just that. I'm feeling so horribly impatient at the moment. It ebbs and flows. Sometimes I feel more patient.

Thank you for your input and support!

Oliver, I recall seeing a study (back around 2016) which indicated about a 10% loss of response (antibody developed toward Nplate) of Nplate in the general ITP population. Also that the response was lost most often around 10 to maybe 14 months of taking it. The PDSA search function is half broken and I couldn't get a hold of the history to find it.

I did find this on "Interventional Study in Adults With Immune Thrombocytopenia Purpura (ITP) Receiving Romiplostim". It indicates a (2+1)/69 = 4% probability. See 'Measured Values' in section 5.
clinicaltrials.gov/ct2/show/results/NCT01143038?sect=Xba80156#outcome5

My own problem here is that I think the probability number is higher in folks who are row 4 - maybe 20%. I dunno. If Nplate response was lost a few options come to mind outside of leveraging Fostamatinib. No particular order:
One would be to try low dose Cyclosporine and a relative low dose Promacta. There are a few instances of those doing just that here on PDSA. Rob16 describes the plight of 'drbean7218' well here:
pdsa.org/discussion-group/6-general-itp-discussion/27398-4-aug-2018-my-platelet-count-was-122.html?start=210#56024
A second option would be to go back to 75mg Promacta and occasional IVIG, as has worked previously.
A third option would be to try just MMF and shoot for remission. There are studies which suggest either MMF or Cyclosporine can work for row 4. I don't think I've seen anyone with row 4 try MMF here on PDSA.
A fourth option would be to try low dose Cyclosporin with either MMF or lower dose Danazol and shoot for remission.
A fifth option would be to try 75mg Promacta with low dose Danazol.
That's all that immediately come to mind.

I do NOT know the risk profile of Fostamatinib. It is a new drug. It is hard for me to think that the risk profile of Cyclosporine, or MMF, is better than Fostamatinib.

In defense of your doctor. He probably deals with push back to offering drugs like Cyclosporine or MMF often once the risks are made aware to the patient. If you appear knowledgeable and step up to the plate with something, he'll likely do whatever you want.

Hopefully this discussion will help you have a better conversation with your doctor.

Thanks, Hal!
I also wanted to ask you-- a while back you mentioned that you think I may be a combo of rows 3 & 4 based on my drug responses. (I realized that I never did, in fact, have IVIg by itself-- the last time I received IVIg I still had Promacta in my system, then started NPlate a couple weeks later-- so I don't know if that changes things...) You also predicted that a 4.5 dose of NPlate would be probable based on the average of typical doses for rows 3 & 4 (1 & .
My question is whether those numbers indicate the typical dose needed to sustain a count over 50. So, if I'm shooting for a target range of 30-50, how does that factor in? Perhaps it's comparing apples to oranges... I don't know.

Also, how would having a row 3 & 4 combo affect probability of loss of response to NPlate? Would that average out at 15%?

Oliver091117 wrote: Thanks, Hal!
I also wanted to ask you-- a while back you mentioned that you think I may be a combo of rows 3 & 4 based on my drug responses. (I realized that I never did, in fact, have IVIg by itself-- the last time I received IVIg I still had Promacta in my system, then started NPlate a couple weeks later-- so I don't know if that changes things...)

That's ok. It's when a good dose of steroids are added with IVIG makes it difficult. It is difficult to determine which is contributing to a count increase.
The biggest hint that you are 3 and 4 is the 5 week partial (not a full) response to IVIG. With only a 3 one would expect a full response that tails off after 4+ weeks. The partial response is a telling sign that another antibody is in play. Then, with the high dose of Promacta required, it made sense that the other antibody is 4.

You also predicted that a 4.5 dose of NPlate would be probable based on the average of typical doses for rows 3 & 4 (1 & .

The 4.5 Nplate dose was a very rough guess. You get 4.5 when you say: row 3 is contributing to half the platelet loses and row 4 is contributing the other half. It could easily have been a different ratio other than half. The dominate contribution is row 4 in the math. It is the 'elephant in the room'.

My question is whether those numbers indicate the typical dose needed to sustain a count over 50. So, if I'm shooting for a target range of 30-50, how does that factor in? Perhaps it's comparing apples to oranges... I don't know.

One can't really predict with accuracy. To start, there is too much variability from one person to the next. But here, the elephant has control. If he gets bigger or smaller all the numbers change.

Also, how would having a row 3 & 4 combo affect probability of loss of response to NPlate? Would that average out at 15%?
IMHO, it is the mere existence of row 4 that is the problem.

Imagine for just a moment that antibodies are attacking megakarocytes on the bone (row 4). Also that Nplate molecules are plugging into the megakarocytes to stimulate platelet production. Ask yourself, what could go wrong here. Well, one's immune system can start consuming megakarocytes that have Nplate on them. What does the immune system do. IMHO if it decides that it should destroy Nplate along with the megakarocytes, game over. One has antibodies which target Nplate. Does that make sense?

Ah! Thanks for explaining all of that to me, Hal-- very helpful! Fascinating stuff!

Feeling better these days Oliver? Nausea go away, or, still around?

Thanks for asking, Hal-- I haven't had any severe waves of nausea in a while, but still dealing with nausea and digestive issues. May be stress/anxiety related. Who knows?

I'm trying out doc #3 next week. I met with my doc on Monday (I missed my grandmother's funeral to keep the appointment; which felt absolutely awful to begin with). When I asked him if he could refrain from bringing up splenectomy again, as I'd heard his spiel and had already told him "no", he proceeded to lecture me for several minutes. The basic gist of it was: I can say anything I want to say; I consider it unethical to ask me to censor myself; I won't placate your delusions/ allow you to live in a fantasy world, this is the REAL world.

I'm not sure what he thinks my "delusions" are, but I know for certain we're not on the same page. When he was in the middle of his monologue I raised my hand and asked "can I stop you right there?" to try to clarify and have an actual dialogue, but he shot back with "no you may not!" and kept right on going. I was so livid I was ready to call the office and cancel all my appointments, but a friend suggested that I ask my infusion nurse for a recommendation for another doc in the practice. They were unable to get me in this week, but I'll be seeing him next Thursday. She kept saying that she thinks I'll really like him, but I'm pretty wary. All the same, I'm feeling hopeful in spite of myself

By the by, what came of your gluten experiment a couple months back? Yay or nay?

I guess I've been lucky Oliver. My doc goes along with my requests. She has told me in the past, something like: the patient is the customer and they make the final decisions. Maybe you can leverage that kind of thinking in some way.

Asking the infusion nurse was an excellent idea. The nurses are surely in-tune to what goes on. I think there is only one hematologist where I go - giving only one choice that is super close. They have a local PDSA meeting that I have started to go to. Discussion of doctors occurs often. Maybe they have meetings in your area. Hope the third doc will be the charm.

The gluten experiment showed that it had no affect on my counts. I think I even ate so much wheat and gluten that week that it was a heavy load on my liver - raising my ALT liver enzyme a tiny bit.

On the subject of 'stress'. If there is anyway to minimize it, I'd sure try to do that. I can't remember you commenting. Is there a possibility that stress triggered the ITP?

I am absolutely flabbergasted by his demeanor. God Complex.

Hal9000 wrote: I guess I've been lucky Oliver. My doc goes along with my requests. She has told me in the past, something like: the patient is the customer and they make the final decisions. Maybe you can leverage that kind of thinking in some way.

That's the kind of relationship I'm looking for with my doc, and I won't stop until I find it!

Hal9000 wrote: They have a local PDSA meeting that I have started to go to. Discussion of doctors occurs often. Maybe they have meetings in your area.

I actually just started up a group myself, as there was nothing in my area. I'm determined to meet other ITPers in my area and pool our resources/ support one another. Our first meeting is at the end of October, but I've met one other person so far with whom I've been able to talk.

Hal9000 wrote: The gluten experiment showed that it had no affect on my counts. I think I even ate so much wheat and gluten that week that it was a heavy load on my liver - raising my ALT liver enzyme a tiny bit.

OY! So, apparently gluten's not so great for you anyway, platelets aside? Are you able to enjoy some from time-to-time if it's not in such high quantities?

Hal9000 wrote: On the subject of 'stress'. If there is anyway to minimize it, I'd sure try to do that. I can't remember you commenting. Is there a possibility that stress triggered the ITP?

It's absolutely a possible trigger-- I have suspected long-term stress from the get-go. I have a LOT of tools in my toolbox to reduce stress/anxiety, and I do what I can. For me, I know finding a doctor who will respect my feelings and decisions about how I choose to treat my body will be half the "medicine" in and of itself, as it will greatly lower my stress level!

Sandi wrote: I am absolutely flabbergasted by his demeanor. God Complex.

Haha yeah... I'm sure he has plenty of patients who really like him, but that doesn't fly with me I don't think he's used to being challenged.

Oliver, that is an infuriating experience you are going through with your doctor. I can empathize. It's so difficult being in that place, feeling so powerless and unheard. I'm glad you continue to fight for yourself. You sound really clear and strong. I'm hoping the next doctor is exactly what you need and will work with you as a team.

I also have been starting to feel like I may be having some (increased) side effects from Nplate. I hope you can figure out why you are experiencing nausea. That's really great about starting an ITP group.

I'm glad I have a Haemo who believes in seeing patients as an important part of the treatment. 2 way discussions and give suggestions rather than orders regarding treatment. Fully accepts I am not having a splenectomy and is happy to treat me medically.

b2h wrote: Oliver, that is an infuriating experience you are going through with your doctor. I can empathize. It's so difficult being in that place, feeling so powerless and unheard. I'm glad you continue to fight for yourself. You sound really clear and strong. I'm hoping the next doctor is exactly what you need and will work with you as a team.

I also have been starting to feel like I may be having some (increased) side effects from Nplate. I hope you can figure out why you are experiencing nausea. That's really great about starting an ITP group.

Thanks, b2h! I am curious-- how long have you been on NPlate and what sorts of symptoms are you noticing now?

mrsb04 wrote: I'm glad I have a Haemo who believes in seeing patients as an important part of the treatment. 2 way discussions and give suggestions rather than orders regarding treatment. Fully accepts I am not having a splenectomy and is happy to treat me medically.

Delighted to hear that!

I met with my new hem yesterday and was very pleasantly surprised and relieved!

His personal philosophy of the doctor-patient relationship jives with mine-- he described it as "you're the Captain, and I'm the co-pilot". He very thoroughly and honestly answered all my questions and provided additional info I had not thought to ask/ had never been told by previous docs. (All my previous docs answered my questions like politicians-- refusing to actually answer the question I asked, and giving me rote answers designed to limit my options.)

He's also a big goof-ball and has a wonderful sense of humor! After I had told him that I am NOT having a splenectomy and do not want to discuss it, he joked that if I'm ever unconscious around him he's going to take a marker and draw a splenectomy scar on me! Everybody in the office absolutely adores working with him. He's so light-hearted and down-to-earth with everyone he interacts with.

He is willing to work with me to taper off the NPlate and put protocols in the system in case of an emergency; which is exactly what I've been wanting. I'm staying on my current dose of NPlate for the next 4 weeks, as I have a dance performance coming up and I don't want to mess around with that. We'll reconvene at that time to work out the details of how to proceed. We're going to go very slow and I have the option of changing my mind at any time. He also volunteered that we could try Fostamatinib if I would like to give it a go.

This week my count was 5; which I assumed was related to having a mild head-cold. Today it popped into my head, though, that diet may also be a contributing factor... My stomach has continued to be wonky and the only thing that seems to settle it is kombucha. I'm now wondering if having it every day for the past week could have affected my count. The past 9 weeks I've mostly been in the 30-50 range; which has been my target range. Has anyone else had this experience with kombucha? Or, is it most likely due to the head-cold? This is the first time I've caught a bug since well before diagnosis, so I have no frame-of-reference.

What a great visit! I like your doctor too!
Fostamatinib does not seem to have a great track record. I'd check that out before wasting time on it.
I have never heard of kombucha!

Oliver
Glad the new haemo is an improvement on previous ones.Sounds like my kind of doctor. Never tried Kombucha but I eat a high probiotic diet. Its never helped my platelet count but has reduced the amount of indigestion I used to get.
I tried Fostamatinib it was a complete waste of time.

I don't have any interest at this time in trying Fostamatinib-- I'd prefer get off all meds-- but I found the contrast between my two most recent docs rather striking! I appreciate the input, though!

I felt that the probiotics in Kombucha would be good for me, and it definitely is helping my stomach feel better. I remember reading something about green tea in the Warnings section, but can't seem to find it again. The kind that I've been drinking uses a combination of green and black tea. Who knows?