Anyone tried Dapsone or Danazol recently?

I know there are probably threads regarding these already but nice to have a current perspective

I'll take that as a 'no' then as no one has responded

I've tried them both, but not recently.

Danazol caused hives and Dapsone gave me fevers. I wasn't on either long enough to get any possible response.

Hi,
I was on 400mg of Danazol last fall. PLts went high but so did LFTs. My new hemo, says he would not give it to females. It did work well at the beginning to get me out of a crash. I'd say its worth a try. BTW I was also taking 75mg of Promacta daily plus prednisone.

M

I was given 100mg of Dapsone for 3 weeks whilst I was also having my 4 dose course of Rituximab but it made no difference to my count. I didn't feel any side effects but I remember that they were concerned about my oxygen levels which would drop to 92%.
My hemo did say at the time (2.5 years ago now) that it was one treatment that she wouldn't give again.

mrsb04,

I have gone back through old postings, and personal reports of dapsone use are rarely mentioned; dapsone is mostly mentioned as part of a long list of unsuccessful treatments that someone has tried, either with poor success or with negative side effects. Anecdotally, from PDSA members, it seems to have a low success rate. I much prefer scientific data.

From the studies I have read, dapsone has about a 50% response rate.
(Note that "response" includes people whose platelets are not normalized, only increased to a safe level). With that response rate, it does not qualify as a first line treatment for ITP, but when first line treatments fail, it can be an effective steroid-sparing drug.

Over one million new cases of leprosy are reported every five years, and most of them are treated with dapsone, so unlike some of the newer treatments, the risk profile is well known. New users should be tested for G6PD deficiency and monitored for hemolytic anemia and hypersensitivity reactions.

Here are links to threads where dapsone research was discussed:

pdsa.org/forum-sp-534/7-treatment-general/28423-dapsone.html#49299

pdsa.org/forum-sp-534/5-newly-diagnosed-a-frequently-asked-questions/27939-hopeless-depressed-suicidal.html?start=30#49406

I don't know, Rob. I like to take scientific evidence and weigh it along with anecdotal evidence. These aren't testimonials here, they are actual, real life experiences. I started to doubt studies when the Dex studies always said that Dex is well-tolerated. I don't believe that for a second. Very few can tolerate Dex. I also can't understand why, if Dapsone has such a high success rate, it has not picked up more speed as a first line or even second line treatment.

Sandi,

You wrote: "I also can't understand why, if Dapsone has such a high success rate, it has not picked up more speed as a first line or even second line treatment." I don't think dapsone is effective enough to be used first line, or even second line, but it is surprising to me that it is not used more often when other second line treatments have failed, or when costs of other 2nd line treatments are a major concern.


You wrote: "I started to doubt studies when the Dex studies always said that Dex is well-tolerated. I don't believe that for a second. Very few can tolerate Dex."

I think the researchers would define tolerate to mean being able to complete a course of treatment without having to discontinue treatment due to adverse effects. I don't remember reading here (on PDSA) of anyone discontinuing a course of HDD treatment for any reason. Though many have chosen not to repeat this treatment, many others have opted to use repeated courses of HDD. Admittedly, many of those who "tolerated" the drug would say that they found it "intolerable". It's a matter of semantics.

Many would also say that they found the effects of high dose prednisone to be "intolerable". And how many have discontinued treatment due to side effects?

To see how researchers apply the word "tolerate", I looked at the use of the word in the following 2015 Blood Journal study, which compared 95 patients receiving high-dose dexamethasone vs. 97 patients receiving 1 mg/kg prednisone.

www.bloodjournal.org/content/bloodjournal/early/2015/10/16/blood-2015-07-659656.full.pdf
High-dose dexamethasone versus prednisone for treatment of adult immune thrombocytopenia: a prospective multicenter randomized trial

Safety:

"Both treatments were well tolerated in general. Most of the adverse effects were mild to moderate (graded 1 or 2) and usually resolved spontaneously after medication was completed."
...
"Of the two patients who discontinued treatment due to adverse effects in the PDN arm, one was a 74-year old woman who suffered from pneumonia and required intravenous antibiotics to control the infection; the other was a 59-year old woman with grade 3 hyperglycemia and no history of diabetes mellitus or impaired glucose tolerance.
Neither patient showed an elevation in platelet count by the time of exit. No patients exited the study due to adverse effects in the HD-DXM arm."

Discussion:

"Most adverse effects were tolerable. Occurrence of adverse events was more frequent and long-lasting in the PDN arm, with two cases discontinuing therapy due to adverse effects. The better tolerance of high-dose dexamethasone might be attributed to its limited duration, as adverse events in this arm were usually transient and spontaneously resolved after the completion of medication. The treatments were also well tolerated in patients ≥ 60 years. High-dose dexamethasone allowed avoidance of the safety risks associated with the long-lasting administration of prednisone."

"In conclusion, results from this prospective, multicenter, randomized, controlled study
suggest that one or two courses of high-dose dexamethasone provides a more effective and more rapid response as initial treatment of ITP, with at least comparable long-term prognosis and better tolerance when compared with conventional prednisone. High-dose dexamethasone also enables patients to avoid the burden of long-term corticosteroids."

Rob16 wrote: I think the researchers would define tolerate to mean being able to complete a course of treatment without having to discontinue treatment due to adverse effects. I don't remember reading here (on PDSA) of anyone discontinuing a course of HDD treatment for any reason. Though many have chosen not to repeat this treatment, many others have opted to use repeated courses of HDD. Admittedly, many of those who "tolerated" the drug would say that they found it "intolerable". It's a matter of semantics.

Most people finish it because it's only 4 days. They suck it up and keep going, plus by the time it gets too bad, they are nearly done. It seems like a tricky way to phrase it if you ask me. It's not very tolerable. Misleading wording.

As far as Prednisone, I think people keep going with that because they are new to ITP and afraid of the alternative (low platelets). They also tend to do what the doctors tell them in the beginning. I don't know many people who are years into ITP and still doing high dose Prednisone, unless they have had long remissions in between.

"Most people finish it because it's only 4 days."
That's the whole point. Most people finish it because they can tolerate it for four days.

One could just as well claim it is "tricky" and "misleading" wording to say it is not tolerable, when nearly everyone is able to tolerate it for the short time it is prescribed.

Hi,
I'm recently out of the denial phase of being diagnosed with ITP. For a long while, I sat in a safe zone but in Oct 2016, my platelet counts kept diving for zero. I did 2 rescues of dex when I dropped into single figure counts (which was absolutely horrible - both being below 10, and the dex side effects) - it boosted my counts from 6 to 250 within 8 days, but a fortnight later I was back to 20 where I did a second dex treatment (4 days of 40mg). That was the same - a big spike then back diving for the floor.

I then tried IVIG which got me back up to 160 but then I started to drop again. My hemo decided to give Dapsone a try.

I've found no real side effects taking the drug (100mg daily). I started 23rd Dec - by mid Jan I was holding steady at 50, and this week I'm up to 113. I know its only early days, but fingers crossed this continues.
Cheers,
Dave

Hi Dave. That is an interesting history. Sounds like you haven't had ITP long (< 6 months, yes?) and Dapsone is doing you VERY well.

Wow, 250 off of a dex pulse sounds great too. A bit surprised doc didn't go for more of that. Must have been the side effects?

Question for you. Have you or your doc given thought to what the trigger for ITP was? A flu virus, or ?

Hi Dave,

Usually Dapsone is not tried until more modern drugs have proven unsuccessful. Other drugs have a higher rate of success, though Dapsone has a pretty decent response rate even among patients who don't respond to other treatments. Do you have any idea how you ended up on Dapsone so early in your treatment? Was cost an issue?

We have very few members who have tried Dapsone. Please stick around and keep us updated on your progress.

Hi Hal and Rob,
I was actually diagnosed 2 years ago in an accidental fashion. I went to the doctors with the flu (which may have been the trigger??) and they sent me for chest xrays. The chest xrays were fine but found compression fractures in my vertebrae (which ended up being an old rugby injury) - they were concerned I had osteop. and thus began a battery of tests over about 5 months including detailed bloodwork. Doctors were hinting at multiple myeloma or leukemia until I had a bone marrow biopsy and the Hemo confimed ITP. Given the dire lead up, I thought I had dodged a bullet! My levels over the next 18 months were around the 40-70 so we did nothing but monitor. It has only been the last 4 months that things took a turn for the worse.

Hal, the Dex was a fantastic spike, but the side effects were awful! I couldn't think clearly - couldn't sleep - my skin peeled - and I felt very anxious. Its not something I would like to do ongoing. I'm assuming it was the flu I had that triggered the ITP, but I really don't know. Maybe the fact that the Dapsone is working means it might have been more a bacterial infection??

We've only given the IVIG a go once and it was 3 days of slow IV. It did have an impact but was an imposition and I got severe headaches (apparently slowing down the dose rate might fix this). And the impact was only good for 3-4 weeks before it looked like I needed further intervention.

We tried Dapsone as a bit of a hail mary. The hemo was quite open about the fact that no-one is really sure why it works, but it works well for some. The drug is cheap in Australia, is not toxic and has very few (if any) side affects. It was really just giving something a go before trying other 2nd line drugs.

Another reason was cost - I've read that Rituximab seems to be the one drug working well from skimming the forums here. Unfortunately, in Australia the drug is not covered for ITP, and so a single treatments costs around AUD$16,000+. So, for many here, this is more a last resort option rather than something you try first.

Thanks for your interest and comments!

Just to confirm with the Rituximab - a single treatment meaning the 4 sessions once per week will cost around the $16,000 in total.

darcher,

Unfortunately, there is no treatment for ITP that does not have potentially serious side effects, and that includes Dapsone.
You commented that Dapsone "is not toxic and has very few (if any) side effects." Actually, it can be toxic, and can have side effects.

www.nejm.org/doi/full/10.1056/NEJMoa1213096#t=abstract
About 0.5 to 3.6% of persons treated with dapsone have a drug hypersensitivity syndrome, which was first described by Lowe and Smith in 1949 and termed “dapsone hypersensitivity syndrome” in 1951. The syndrome is a severe idiosyncratic drug reaction characterized by the clinical triad of fever, rash, and systemic involvement (most commonly of the liver and the hematologic system), which can cause severe organ dysfunction. The dapsone hypersensitivity syndrome is usually manifested 4 to 6 weeks after the initiation of therapy.

According to that article, dapsone sensitivity syndrome, when it occurs, has a 9.9% fatality rate.

Hemolysis may also occur, especially in patients with glucose-6-phosphate dehydrogenase deficiency.

Please familiarize yourself with the potential risks so you can be watchful for them.
www.rxlist.com , www.drugs.com and en.wikipedia.org/wiki/Dapsone all have useful information.

Oh my, skin peeled with Dex? Ouch. Didn't know it could get that bad, that quickly.

There are some other folks on here that have spectacular responses to steroids too - which makes me inquire. How about allergies? Allergies to foods, or, environmental substances? Allergic to some medications? Work with chemicals?

On a side note, I responded poorly to Dex. This makes me think Dapsone is unlikely to work for me. Or perhaps, give a partial response.

In reference to toxicity. Do you know if 100 mg is a low, normal, or high dose?

Thanks for the web references Rob. And yes, I was being overly flippant regarding the drug. My Hemo went through the issues with dapsone hypersensitivity syndrome and we did screening for G6PD deficiency before commencing treatment. IF you don't develop any negative symptoms, then compared to taking prednisone or dexamethasone, it's a lot more pleasant.
Of course, I would rather not be taking any drugs at all if it could be helped. Fingers crossed, that might be a reality one day when they find a cure for ITP!
Cheers,
Dave

Hi Hal,
Yes, the Dex definitely worked but was quite short term. As to allergies, I have the regular style hay fever but nothing too unusual. I don't have any food allergies, drug allergies or work with chemicals.
You say you don't respond well to Dex - what sort of therapy do you use to keep platelet counts up?
As to dose, I think 100mg / day of Dapsone is about the norm for ITP but don't quote me on that. So far I'm still responding well but I'm not out of the danger period yet. Complications usually present between 4-8 weeks if they present at all - I'm at the 5 week mark.

Cheers,
Dave

Interesting Dave. Others here with great Dex responses have similarly reported Hay Fever allergies. The question of whether the flu, in combination with Hay Fever, caused the drop down below the 40-70 range is interesting. Seems likely.

Do you suppose your doc wanted to try a Hail Mary with Dapsone because of your nice steroid response?

As for my counts, after the Dex failure, one IVIG treatment has worked well. Seems to have raised counts from 10-something range to 30-something range - though I have quit gluten also. Just finished Rituxan and am watching for a response. Flat line so far.

113 after a few weeks on Dapsone sounds nice. Did your doc give you an indication (percentage) that remission was possible with it? When you say complications can occur in the 4 to 8 week range, is that because of a potential bad liver reaction from Dapsone, or ?

Hi Hal,
Well, I spoke too soon. The Dapsone ended up causing a complication with my liver. My platelet counts dropped 2 weeks ago from 113 to 40 and my liver function tests were off the charts. I stopped the Dapsone immediately and 10 days later my liver function tests are almost back into normal range and my platelet counts are steady at 44. At least it wasn't Dapsone Hypersensitivity Syndrome

So, its back to the drawing board. Monitor and react.

That's great about IVIG working, and from all I have read, Rituxan can take months to kick in. I have my fingers crossed for you!!

Cheers,
Dave

Oh my darcher Dave. That link to Dapsone Hypersensitivity Syndrome was alarming. Thankfully the odds are very low (%?) for that.

Dapsone was showing so much potential. It is very unfortunate the liver did not cooperate. So, have you developed a reaction plan if counts crash again?

Also, have you given any thought to Auto Immune Paleo diet or Vegetarian diet in the mean time? Others put a lot of credence into those. Especially with allergies.

Hi Hal,

Yes, Dapsone Hyersensitivity looks scary! Very thankful it wasn't down that path.
At the moment we're playing the waiting game and I believe we will be loking at Rituxan. Based on blood tests this morning, my platelets have dropped from 44 - 24 in a week, but my liver is basically back in normally functioning range. I think I'm going to be up for a Predisone 'save', while we line up a Rituxan programme. It takes a bit of wrangling here as its not covered by health insurance for ITP (hence, its expensive), and I believe there is some screening involved?
How are you going since you had the Rituxan? Any improvement in the counts?

As to diet, I'm currently working my way towards a Semi-Vegan diet. I've weaned myself of dairy and alcohol (not that I drink much anyway) for the last month, and up-ing the Veggies so that I only have an animal protein meal once every second day, whilst avoiding all processed foods. Taking it slow so that its sustainable and making it a lifestyle change.

Have you also gone down the diet change path?
Cheers,
Dave

Dave, Thank you for reporting back to us on your experience with dapsone. There is plenty of data on dapsone, but we have few people on this forum who can put a face on this data.

People tend to shrug off potential side effects of any treatment when the frequency is low. All treatments for ITP have serious potential side effects. All ITP patients should be knowledgeable of and watchful for those side effects. Make sure that your doctor is performing all recommended screening before starting treatment, and all recommended follow up testing once treatment begins. You cannot always count on your doctor taking all precautions.

Dave is alive because his doctor was conscientious with follow up. Make sure that your doctor is conscientious, too, whatever the treatment.

Rituxan as an example of poor prescreening:

ascopubs.org/doi/full/10.1200/jco.2012.43.7509 Journal of Clinical Oncology
Hepatitis B, Rituximab, Screening, and Prophylaxis: Effectiveness and Cost Effectiveness
... and in a North American teaching hospital only 36.6% of patients treated with rituximab ... had HBV testing although rates increased to 67.4% after introduction of guidelines.

www.rxlist.com/rituxan-drug.htm#BW

www.iwmf.com/sites/default/files/docs/Rituximab-Associated_Infections-Seminars_in_Hematology.pdf
Rituximab-Associated Infections

Well said Rob.
Yesterday I asked what my HbA1c result was. My consultant asked why I'd had it done.
I was stunned. NICE guidelines categorically state monitor 1 month after initiation of oral corticosteroids, and every 3 months thereafter.
What worries me is people who do not have access to internet/libraries and cannot find the information they need.

Dave, at this point it seems IVIG did more for me than Rituxan. However as we both know, it can take awhile.

About diets. I initially tried a bunch of things in that area. In hind sight, I don't think I gave each thing I tried enough time. It was my second and longer attempt at going gluten free did I realize it was a problem. I suspect food allergies is an ITP culprit all its own. Each of those diets, auto immune and vegan, cuts out different things. But I wonder if it is the individual's possible allergy to the removed item(s) is the underlining effect in ITP. I think this leads to some believing one diet is better for ITP than another. Personally, I would look for sneezing or a runny nose when consuming a certain food. That response is immediate. IMHO, a platelet response could take a month to see.

Hi All,
Just thought I would report back on this one. After being taken off Dapsone due to adverse liver function tests, we tried starting it again at a lower dose. The liver function had returned to normal within a month, so re-commenced at 50mg. My platelets bounced back to about 30, and after a month we upped the dose back to the recommended 100mg per day.

My platelets sat between 30-60 for the next month or 2, then started to slowly decline and my liver function started to get worse. My liver then went off the charts and we quit the Dapsone experiment. After a couple of weeks on no drugs while my liver levels returned to normal and my platelets edged back down, I'm now back on Prednisone.

So, after meeting with my Hemo this week, they are recommending a splenectomy. We talked about Rituximab, and an NPlate style approach, however they seemed to think I would be a good candidate for splenectomy and then we could avoid all drugs (apart from vaccinations and regular penicillin). If it works. And I don't get a serious bacterial infections. Etc.

Still not sure how I feel about a splenectomy given the very one-way nature of going down this path.

I know what you mean. I have already tried Rituxin and it did nothing but help me get the flu which landed me in the ER with a 3 count. Promcata is working but minor side effects and long term cost scare the hell out of me. I have opted for surgery in an attempt to avoid the daily drugs, both costs and long term effects on my body. I am having the old spleen removed tomorrow morning.

Dave, sorry Dapsone has not worked out for you.
Since you have both a good steroid and IVIG response one would expect to respond to Rituxan. Also for that response group, it is pretty rare to get remission from NPlate/Promacta. Here is one you haven't mentioned. User ' julia ' achieved remission on Imuran after 3 years.