Danazol, low dose Promacta with a twist of slow remission

Had a discussion with my Hema last week about starting low dose Danazol (50 mg per day) and tapering out of Promacta (12.5 mg). Note that this is the lowest dose available for both drugs. If all goes well I'll take Danazol all of 2018. Studies show that one has to take the drug for a year to achieve a durable multi-year remission. First dose should be Monday and will take both Danazol and Promacta for 4 weeks and then check counts. Doc expects a noticeable increase at around 6 weeks. For reference, the range of response times is 0 to 6 months. But that statistic is for all responding ITP'ers and a much higher starting dose level.

As I've mentioned before, my insurance co has declined to pay for Danazol when one has ITP. They prefer to pay $4,000 per month for Promacta over the $35 per month for Danazol. I have leveraged this fact for 2017.

The reason I am trying Danazol is that my own steroid and IVIG response follows row '3' in my ITP treatments table. Recall that this table was derived by me reading a large number of reported responses (a retrospective study) from members of this forum and summarizing the results of successes stories. For row 3, PDSA members have reported achieving remission with Danazol treatments in the past. Also worth noting, no row 3 (only) member has ever reported remission with Rituxan, Promacta, Nplate, or even IVIG - which they respond strongly too.

Although the normal starting dose of Danazol is much higher, this study suggests a strong Danazol responder can start on 50 mg and still achieve remission. Apparently strong responders can titrate down to 50 mg so a strong responder can start out on 50 mg without issue.

A little bit about Danazol. I had read that one of the things Danazol does is increase one's Thrombopoietin (TPO) production. My Hema confirmed this. Recall that TPO causes the body to produce platelets. With that it makes more sense why Danazol works well with a row 3 response. Row 3 folks are very sensitive to Promacta. Thus they are very sensitive Danazol because of the TPO dynamic.
Danazol also affects the immune system in several ways. Here is a study that does a good job of enumerating them. See paragraph 3.2.
Some things in the study worth commenting on. Quoting:
"It induces a decrease in Fcγ receptor expression on monocytes that could lead to a decrease in platelet phagocytosis"
This sounds like it works a bit like IVIG.
"Moreover, danazol promotes lymphocyte differentiation into regulatory T lymphocytes"
This sound like it helps to put regulatory balance into the self / non-self identification of TPO and/or platelets. Perhaps this aspects is how long lasting remissions are possible with Danazol.

One last tidbit. AFAIK, this low of a dose is safe for women as well.

Good luck with your personal experiments Hal. Maybe things will go how your group modeling theory predicts, and maybe they won't, but you are sure to learn something in the process.

Regarding your current status, I recall that you were quite responsive to promacta. What have your counts been lately? Have you tried spacing out your promacta doses with a gap of several days between to see if your counts hold? I vaguely recall that you would run a little too high (over 100) when you were on that lowest dose. But I could be remembering wrong too!

Did the side effects make you decide to quit? Or is it that you tried decreasing and your counts didn't hold? Or is it that you really think Danazol is going to do it for you and you are eager to try that. Just curious. We all have to go with our gut about what treatment might be best for us. You can always change your mind and go back to promacta I would think.

Good luck.

Good luck, Hal. Keep us posted. Most people ended up quitting because of the side effects. Hopefully they won't be too bad for you.

m23b, not quite that good of a response.
During the Promacta titration process, I tried a 50/skip/skip. That put me at 56. More recently, a 25/25/skip gave me a 91 count. 25/12.5 was ok too. One time was 99 and another was 135. Last week, after being on 12.5 straight for over a month, gave a 52 count. Headaches are a non trivial problem for me at any dose higher than 12.5. LOL, besides D.Mann's radically improving progress, it's CindyAnn that is setting records for sensitivity.
Looking back in comparison, Rituxan was a serious risk. Though the probability of being affected by the risk is really low. Danazol risk profile is different. At the higher doses non serious risks are common, causing many to discontinue early on. But at 50 mg I'm not expecting a problem. Some have written to suggest low dose Danazol should be considered a 'first line' treatment for ITP. Yes, right up there with steroids and IVIG. Not many folks go into remission with just steroids, and not many are sensitive enough to Danazol to try an extended treatment, but the low risk involved suggests to try both.
For me I'm looking for not needing any treatments. Promacta would never get me there. Danazol has a chance. Statistically, a strong chance. LOL, statistics outweighs gut feelings.

Sandi, it's been a long time ago. But I have trouble thinking you would try Danazol. Yet you did. Before TPO-RAs and before Rituxan the ITP world must have been very, very different then. Do you recall, was your starting dose 200mg three times a day? For a woman, that would sound really scary to me.
About the 'What the Health' video. I think you mentioned that you need to cut out milk, yes? I cut it out months ago but wonder about its significance for some. Maybe give that one a good long abstinence?

Hal:

It was my Hemo's idea to try Danazol. This was back in 1998. He actually started me out with Win-Rho (five weekly treatments that didn't raise counts one bit). It was a waste of time and money and I should have never agreed to any more after the first one didn't work. I didn't know any better. So my counts were basically below 10k the entire time. Then he suggested Danazol. Odd choice, I know, but he was trying to avoid steroids. There was no Rituxan or TPO's back then. I started Danazol and was only on it for about two weeks. I don't remember the dose, but I don't think I took it three times a day. Within a week I had a huge boil on my chin. I wasn't even one to get acne, ever, so that was obviously a side effect (acne is listed, but this was definitely boil-like and hideous). After another week, I broke out in hives so that was the end of that. I stopped the drug and the hives went away and never came back.

Danazol was used more often back then, but still not a common choice. I can only remember it working for one guy named Gary. He took it for years. No way to know if his counts would have stayed up without the drug but he kept taking it. I remember another woman named Kara who was determined to stick with it no matter what. She thought it was the lesser of the evils. It didn't work very well for her and she stuck it out for many months. Her main side effect was horrible mood swings and she ended up stopping because of that. Everyone else that tried it ended up stopping because it either didn't work or they couldn't tolerate it. It's not been a very popular ITP treatment. I used to be able to keep up with every single person on this Forum. For years, I remembered who they were and what treatments they tried. That got much harder as the years went by.....so many people come and go and my memory went with them.

I haven't had milk in years so that's not a problem. I rarely eat any milk products mainly because I don't like them. I have ice cream once in a while. I've read a lot of things about milk not being good for the human body and can't really remember why. I think the thing is that humans are consuming cow antibodies meant for baby cows. Same thing that occurs with babies and mother's breast milk, but of course that is meant to happen. There is a lot of research coming out now too that states that the milk/calcium thing doesn't exist. I'll let you do your own research on that if you want to. Milk products also make me produce a lot of mucas so I stay away from it mainly for that reason.

My hema refused danazol for me yesterday, but she willing to give me 20mg of prednisone along with nplate but only for a month.

What is your count?

Jay, I think I know where EmilyK is going. That sounds like a lot of Prednisone when one is taking Nplate (or Promacta). Perhaps you are considering Prednisone with nothing else?

I wondered too why you'd want to add Prednisone when N-Plate is working so well.

Because I want to get into remission by producing more platlets.

Combination therapy produces more platlets than just nplate.

One week after nplate+pred gave me 250k+ now I think I get only half that number.

Producing more platelets doesn't cause remission. We have plenty of people here who get into the 500,00's and just drop back down when treatment wears off.

Volunteering to take 20mg of Pred a day for more than 3 days is beyond my comprehension.

Jay, you like me would prefer the state of remission. LOL, it should be the fifty-first state. Especially prefer remission if it can be achieved safely and with minimal risk.

You know EmilyK seems to have a reliable partial remission going on. A little refresh of Promacta seems to be the only maintenance. I wonder of the possibility that you might be in a similar situation but having a harder time getting the partial remission stable. I say this because your counts are really stable for weeks at a time.

Here is an idea. Maybe good, maybe not so good. When you go for a weekly count check, how about this:
If you need Nplate, fine, get it
If your count is high enough to skip Nplate, take one dose of Pred, 10mg or something, I dunno

With this strategy maybe you can extend the Nplate shots out even longer then you are now. Or, perhaps you can leverage this idea and think up something better. Something that achieves your goal.

It took me 8 years to get a remission. I had three years treatment free in the middle of that time once due to Prednisone. I stopped going for counts after a year though and when I finally did (forced by my GP), my counts were in the 20's. I have no idea how long they were down there since I hadn't had a count for a long time. I might have gone two years with low counts and never knew it. Avoidance was a good thing! When I discovered counts in the 20's, I had four more years of struggling with counts. Choices were pretty limited back then. All I really had at that time was Prednisone since nothing else worked for me.

Hello,
New to this discussion. I'm very interested in the general approach to Promacta headaches. I started 50 mg Promacta two weeks ago. After one week, platelets 54,000, high normal HCT. After two weeks, 75,000, above normal range HCT, but now I'm getting daily, morning headaches. I get migraines, so I started taking my imitrex which constricts vessels and headaches resolve, but I can't take this daily! It seems from the posts I've read that the strategy is to maintain platelets around 50,000 to avoid headaches, is that about right? Question: what is causing the headaches? I'm thinking increased cell count (my hematocrit went significantly above normal) is causing my vessels to swell to accommodate and swelling vessels in the brain equals headache. I guess the additional megakaryocytes, platelets, immune-mediated platelets, immune-mediated megakaryocytes all equate to more cells and larger cell complexes. Anyway, I'd like to know if the 50,000 number is a good target. I talked to my hemo dr. about reducing the 50 mg dose, but she said, "no", it's not indicated unless I go much higher. I'm tempted to just cut the 50 mg tab in half and take 25, but I'm afraid to do that. If I get enough responses here to keep at 50,000, I'll just have to tell her sorry, it's my body and I want to maintain at 50,000. By the way, I did Winrho for probably 8 years, first sporadically then more frequently until I was getting treatment every 2 months. My hemo dr. never ran kidney function tests. I saw Dr. Liebman with USC Keck School of Medicine for a second opinion because a bone marrow biopsy I insisted on getting from my regular hemo dr. showed mild reticulin fibrinogen and my RBCs started going high normal. Dr. Liebman ran oodles of tests. My gfr is low normal for my age and he said he suspects I might have some kidney damage from repeated hemolysis events--when your RBCs lyse, the hemoglobin, but more particularly, the iron is toxic to the kidneys. I thought this only happened on the rare occasions you developed HUS (hemolytic uremic syndrome). Word to the wise who are taking Winrho: get your kidney function tested periodically. I'm seeing a nephrologist in January to see what's going on. He also thinks my high RBCs are from sleep apnea (JAX-2 was negative). Thanks, everyone, for your suggestions re: headaches and optimum platelet number to avoid them.

There is nothing wrong with taking the lowest possible dose that will maintain counts around 50. 25 might do it for you, or a 25/50 alternate day dose. That could lessen the side effects. See what the count is after 3 weeks and go from there.

Thank you, Sandi! I'm due for a CBC in two weeks. I put in a call to my hemo dr. on Friday to discuss (again) reducing to 25 then seeing if the 50 count maintains. It seems they want to keep you as high as possible, but what good is that if you're miserable? Another AM headache today. The headaches aren't slight. If I don't treat, they progress along my typical migraine pathway with diarrhea, nausea, and vomiting. Found that out the hard way when earlier in the week I decided to wait to see if it would go away on its own. Dr. Liebman at USC is recommending mycophenolate for goal of possible remission. The Immunosuppressants scare me, but I think I trust his judgment LOL. His informal research shows about 1/3 go into long-term remission, 1/3 go into short-term remission, and 1/3 don't have beneficial effects. After I'm finished with my university semester and after consulting with the nephro dr. in January, I may proceed. Sometimes I get so mad that I have ITP--like why can't I be normal?! Thanks again for your prompt reply. I really appreciate you!

No, keeping a patient on a dose that is higher than needed when the patient has bad side effects is ridiculous. Not all doctors are like that. Promacta is one of the best ITP treatments when dosed properly. It has a good success rate and few side effects. Many people find that headaches go away within a few weeks of taking the drug. If not, lowering the dose can help. You responded quickly and by the next count, your counts could be even higher. If so, I would insist on a lower dose. It's your body and you have to live with the side effects.

As far as Mycophenolate, I've taken it for Lupus. I had to quit because the side effects were horrible. The brain fog was so bad that I couldn't function at work, plus I caught every illness out there and it would take forever to go away. I was even on a low dose. Promacta can cause remission too at about the same percentage as Mycophenolate.

You will find that in time, life can be normal with ITP. It just takes a while to fine-tune the meds and then it just becomes part of life.

sseiler, with some folks Promacta itself seems to cause headaches. In others, unusually reactive (wacky) platelets cause headaches. See this thread. In either case, lessening of the dose should lessen the severity. But if one switched to Nplate, one would expect the headaches to go away in the former case, and remain in the later.

As for 25 mg Promacta, normally one would try a 50/25 split before going to 25 everyday unless your counts were really high. Going to half the dose will roughly half the count. So you'd need a 100 count to reasonably expect 25 mg to give you a 50 count.

You mention that you do well with WinRho. Let me guess. You respond well to steroids and your IVIG response last about two weeks. Yes? I ask because I'm collecting statistics on various treatments.

Hal, I agree that going 25/50 alternating would be a good idea. But I respectfully disagree that lowering dose from 50 to 25 will half the counts- its possible but not guaranteed. I have not always seen logic in numbers when changing doses with the TPOs. What I've noticed is that changing doses up or down can cause counts to crash or skyrocket (or behave logically). Thats been my experience with both Promacta and Nplate. With Nplate my counts have crashed when dose was increased as well as decreased- so go figger.

Sseiler- I had been on Promacta off and on since 2012-2015, now I'm on Nplate for past 2+ years. I believe its safer to keep counts right around 50 and not a lot higher. Drew Provan is an ITP expert in the UK and he likes his patients to be between 35-50K. Depends on your symptoms too, I don't have a problem with bleeding so I am comfortable with counts lower. My hematologist likes my counts around 50 but is comfortable with my counts going down to 10, so doctors are different. I lowered my Nplate dose when I was having headaches (from 495 to 412) and my counts stayed to same. The two drugs are somewhat similar but different. I was having side effects on Promacta- brain fog, memory issues, sense of detachment. So I switched to Nplate and have none of those side effects. I occasionally have a morning headache that goes away quickly with a drink of coffee. I feel very good on Nplate esp at that lower dose. good luck!

Posey, obviously count's are never guaranteed. That's a bit of an over statement. But still, let me see if I get what you are saying. Since dose changes don't necessarily follow logic, she should try 12.5 mg dose then? Especially so, given the headaches? Have I got it?

My two cents....she should wait until the next CBC and see what the count is. If it's above 75k, try the 25/50 alternate day dose and see how that goes, then take it from there. She had a pretty good initial response and it might keep getting better and if so, keep lowering the dose enough to maintain counts around 50k. If the headaches don't get better, try N-Plate.

Danazol update. Four weeks ago, at start, count was 52 with Promacta only. Count now is 60 with both Promacta and Danazol. Not a significant increase. Asked doc today if she wanted to increase dose or give it another 4 weeks. Going to give it another 4 weeks.

As for side effects of 50 mg Danazol per day, well, not much. The first day I took it I got a headache. One low dose Aspirin took care of it. Recall that I often have the sensation of a headache coming on at higher doses of Promacta. But at only 12.5 mg of Promacta, the sensation is rare. So here is the odd thing with Danazol. The headache sensation location has moved. It moved from the back of the head and is now more central/nasal. Odd. Also, the sensation is getting even weaker. Almost imperceptible now.

Another thing. Recall that one of the side effects of Promacta is memory impairment or brain fog. Sort of like an impaired ability to think. So the first day I took Danazol it was like a brain fog veil had been lifted. Apparently Promacta was giving me brain fog and I hadn't realized it.

No rashes, no boils, and liver remains ok. LOL, the worst Danazol symptom: I got a pimple last week. The best part about Danazol: it seems to have diminished what little side effects I get from Promacta. Didn't expect this at all.

Good luck, Hal. For some reason I'm thinking that I took 200 mg's a day. It was a long time ago though.

Hal- Interesting that Danazol cleared your side effects from Promacta. You just never know. haha good luck, hope it works!
I had memory impairment with Promacta, and like you I didn't realize I had it. I had been having the experience of going into a room and not knowing why I had come there (not totally unusual for me). But then I was driving on a very familiar road and all of a sudden didn't know where I was. And I couldn't remember where I had been. I just kept driving until I came to a familiar intersection, then my memory came back. So I quit Promacta cold (my counts don't crash when I quit). And in about 24 hours my mental clarity came back- it was really amazing the difference. I have only read one post where the person said they had brain fog from Promacta. It also gave me headaches.

Hi Hal,
Sorry for lapse and thank you so much for your input and help. Full-time job, part-time MPH student, two sons (college and high school), and life envelop me. Here's some info for your stats. I did ok on prednisone. It was the first treatment my hemo dr. tried when I came in as a new patient. I can't remember exact number for improvement, but I'm sure not above 100,000. I was on for 6 weeks or so and it thrashed me with moon face, etc, so never again. I have taken Winrho since then. I have never taken anything else since I tolerate Winrho well and it does the job. I used to need Winrho twice a year, then at some point, treatments became more and more frequent. This year I needed Winrho every 2-3 months. I take it when my platelets go down to 15,000 to 25,000. Sometimes my platelets just crash suddenly. Winrho never took me above 55,000. Now with the concerns with my kidneys, I'll see how 50 mg Promacta does. Currently, I'm at 100,000 with headaches and maybe a little anorexia/nausea--not exactly sure on that. I'm set to try mycophenolate mid-December. Nervous about it, but I really like Dr. Liebman at USC and hope this does the trick. Based on what he knows of my ITP (and he spent a lot of time with me), he believes it's due to a T-reg dysfunction, and he thinks an attempt at re-setting my T-reg cells has a good chance of remission. Anyway, thanks again.

Hi Poseymint,
I just read your posts and found it interesting about the sense of detachment. I don't feel like I have brain fog or memory issues, but there may be some subtle psychological thing going on and the sense of detachment seems the closest to describing it. I'm not completely sure. I suppose it's like others have said. You don't always know the effects of a drug until you get off it and then feel appreciably different. In any event, I appreciate your input and I thank you!
Sue

Thank you Sandi. But it's time for me to confess. The feelings build up over time. I need to stop with the platelet stuff. I feel real-bad with threats like 'give me all your platelets and nobody gets hurt'. It is mean and I shouldn't say things where it's all about me and to hell with everyone else. Those that have platelets worked hard for theirs and I, I just want a free ride. I can kick this habit. I know that if I don't, I could end up on some episode of 'Cops'. A video of me caught in the act would be hard to live that reputation down.

Posey, I likely would never have been able to quantify it as a fog without its immediate lift with Danazol. All this headache stuff with Promacta is odd. Don't know what to make of it. Thank goodness Nplate is an alternative, heh?

sseiler, good luck with the MPH program. Thanks for the additional info. All those in my data which have responded to WinRho have been either row 1 or row 3, with the majority being row 1. Hence my guess to you.
It sounds like your count response to WinRho was partial (never above 55). Also that the response duration changed significantly at one point. The steroid response sounds better than poor and worse than good. These characteristics make me ponder if more than a single row is at work. Sorry to say, since you've not had IVIG before figuring which row or rows are at play is more like guessing.
I suppose you've looked at row 3 of my table which has Mycophenolate (aka MMF, aka Cellcept) listed. With the limited data I have, those that achieve remission with it have a typical Promacta dose response of 12 to 25 mg. AFAIK a partial response to MMF could lead to a partial remission - no data there.

Hi Hal,
Printed your table. Thanks for the information and the journal articles. I look forward to reading them. I've never heard of autoantibodies to thrombopoetin or the receptor. I knew sometimes platelets are attacked and sometimes the megakaryocytes, If you have type 3 or 4, would your thrombopoietin level be normal? I think when hemo dr. checked, my levels were in a normal range. Anyway, the only thing the hemo dr. ever tested was a basic immune panel of various types including lupus, antiphospholipid, etc. Platelet antibodies were positive, but nothing else was. Can they check for the antibodies you listed in your table to definitively figure out target? I really need to get a copy of my entire medical record from hemo dr. It has been nine years and I can't really remember timeline and responses. Thanks again.

Hal:

I think we're all fairly used to your snarky self by now.