Mirvaso has been approved by the FDA.

[Brady Barrows]

Ps, the fact that most people report the same time window of paleness and then increased and severe redness and flushing (typically worse than what they normally experience), namely between 7-12 hours (most often 8 or 9 hours) makes it more realistic to me, to blame this reaction on the brimonidine itself, the way it acts and the normal rebound flushing it gives to people with weak and reactive enough blood vessels. See below info on typical allergic reactions. The timeframe mentioned there for allergic reactions is much broader and it seems that a repeated exposure to an allergen will not normally result in an allergic reaction after exactly 8-10 hours. Almost everyone here with a negative experience mentioned this however. Also, there are a lot of allergic skin reactions possible when someone experience (cosmetical) allergic reactions, including not only flushing but also blisters, rashes, skin eruptions and so on. So far the only and predominant reaction people mention is exactly the same thing: very heavy flushing, burning and redness: no rashes, blisters or skin damage. Again, that seems just the typical side effect of the brimonidine once it wears off, not an allergic reaction. And on top, 18 out of 20 would get an allergic reaction to Mirvaso here? really?

http://www.medicinenet.com/cosmetic_allergies/article.htm

"The time it takes for symptoms of irritant contact dermatitis to appear varies. For stronger irritants, such as perfumes, a reaction may occur within minutes or hours of exposure. However, it may take days or weeks of continued exposure to a weaker irritant, such as soap, before symptoms appear. In some cases, a person can develop an allergic sensitivity to a product after years of use."

http://www.nlm.nih.gov/medlineplus/ency/article/000005.htm

"Although first-time exposure may only produce a mild reaction, repeated exposures may lead to more serious reactions. Once a person has had an exposure or an allergic reaction (is sensitized), even a very limited exposure to a very small amount of allergen can trigger a severe reaction.
Most severe allergic reactions occur within seconds or minutes after exposure to the allergen. However, some reactions can occur after several hours, particularly if the allergen causes a reaction after it has been eaten. In very rare cases, reactions develop after 24 hours."

Nat,

These are helpful links and explanations for an allergic reaction to a medicine. My limited understanding is that an allergic reaction to an allergen can illicit an immune response. However, there appears to me to be a slim gray line between and allergic reaction to a drug and the rebound effect. I am hoping to understand this eventually so I can clearly explain it to others.

[Brady Barrows]

Brady Barrows are you for real ? How much are you being paid by galderma . You are a disgrace

The RRDi doesn't get one dime from Galderma. I certainly don't get any money from Galderma. I am not making any rude remarks.

[hozer2k]

Brady,

It is your list and that is fine. But you are giving stats for the list quite often and continue to link to it. At that point, it can (and should) be evaluated by other members to make sure it adds up. Otherwise, it is just a list that you can adjust to whatever your goals are.

But if you want to claim it as a semi-official record and link to it, then I would think you should state some sort of criteria and make the error potential known (not currently discussed). My personal opinion is that you are too loose with the "positive" criteria seeing as the drug clearly yields a positive experience followed by a negative experience at a later time. Any initial reports should basically be thrown out with that understanding, but again that is my opinion. I think any rational and logical person would agree.

And thanks for making the effort Brady. We do appreciate that. I remember the time you started making the list. I had already logged *many* hours reading every single post (some multiple times) by then. I am sure many of us have spent a lot of time reading about it...you are not the only one. Many of us have suffered direct consequences of this drug that has affected our lives and then have come back here to report their experiences to help others from making the same mistake. I especially tip my hat to those people

[Brady Barrows]

Brady,

It is your list and that is fine. But you are giving stats for the list quite often and continue to link to it. At that point, it can (and should) be evaluated by other members to make sure it adds up. Otherwise, it is just a list that you can adjust to whatever your goals are.

But if you want to claim it as a semi-official record and link to it, then I would think you should state some sort of criteria and make the error potential known (not currently discussed). My personal opinion is that you are too loose with the "positive" criteria seeing as the drug clearly yields a positive experience followed by a negative experience at a later time. Any initial reports should basically be thrown out with that understanding, but again that is my opinion. I think any rational and logical person would agree.

And thanks for making the effort Brady. We do appreciate that. I remember the time you started making the list. I had already logged *many* hours reading every single post (some multiple times) by then. I am sure many of us have spent a lot of time reading about it...you are not the only one. Many of us have suffered direct consequences of this drug that has affected our lives and then have come back here to report their experiences to help others from making the same mistake. I especially tip my hat to those people

Indeed, it was your list that inspired me to make my own list which saved me some time since you listed the names of the posters. Anecdotal reports are just that, and are not 'official' in any way, shape or form. Your list is as valid as my list since it is simply my post of what I have found. At least I give the url to the original post so anyone can verify it. My goal is to simply make it easier to find the actual user reports rather than going through (as it stands right now) 85 pages of comments that contains 95% other information not relating to user experience. Most would simply give up trying to find user reports since the discussion is more about Galderma than user reports. This forum is probably the most active one that I am aware of.

[Brady Barrows]

Rebound Flushing is a symptom especially for people who flush when they tend to over due things . its not allergic reaction

I got the following reply from Dr. Raymond Peat with regard to my question regarding the difference between an allergic reaction and a rebound:

"I don't think either allergy or rebound would be the best description for the direct promotion of the secretion of inflammatory cytokines by a vasoconstrictor drug or its excipients. Since nitric oxide, prostaglandins, and inflammatory cytokines probably contribute to the problem, non-toxic inhibitors of those, such as vitamins A, E, and K, aspirin, and caffeine might be helpful for the basic problem."

Dr. Peat then includes three clinical papers to consider. See Post #6.

[nat007]

Yeah I agree actually with Hozer2.. Its great that you put all the effort into make inventories Brady, and I do the same on my blog and know it takes a lot of reading and time, but in the end that is something we chose to do, voluntarily, because we find it interesting and like to help people somehow with it. We don't necesarily earn respect or authority with it and if we come to the wrong conclusions, then I think its fair for people to correct us. In the end none of us are doctors and we just read and come to some conclusions based on the information that is available. I also think that to count an initial positive comment as a positive review is not good enough and leaves a lot of space and uncertainty, as the proof of the pudding is actually in the 2nd wave of effects of Mirvaso; everyone gets pale first. There is no real misunderstanding about that and what is truly of interest of most people here is what happened after those 8-12 hours in terms of flushing and redness. Or even after several days of use. Maybe the people who only reported positive effects in an anecdotal one time report can be contacted to be sure they stick to their initial review after some continuous days of use? The thing is that if you don't take that false error factor into consideration, the evaluation can seem flawed to people here, which seems a shame considering the amount of time it demanded?

I see how you want to keep an open mind about the rebound and whether it could be allergic or not; it would be interesting if it was due to an allergy but to me it seems unlikely given the arguments in post 833 i think it was. The difference is that when the bad flares which people report are due to an allergy, that would mean it is not the blame of Mirvaso; its simply a case of the patient not tolerating the drug due to an auto immune response. But if this is a common side effect of the actual active ingredient, which I believe, that makes it a whole different ball game and people can be disappointed with Galderma for not tackling this issue (and they were aware of this characteristic of brimonidine as a doctor on the board mentioned it to them).

No no vendetta, im sorry if I sounded like I wanted to start one, absolutely not, your input is highly validated

[nat007]

I got the following reply from Dr. Raymond Peat with regard to my question regarding the difference between an allergic reaction and a rebound:

"I don't think either allergy or rebound would be the best description for the direct promotion of the secretion of inflammatory cytokines by a vasoconstrictor drug or its excipients. Since nitric oxide, prostaglandins, and inflammatory cytokines probably contribute to the problem, non-toxic inhibitors of those, such as vitamins A, E, and K, aspirin, and caffeine might be helpful for the basic problem."

Dr. Peat then includes three clinical papers to consider. See Post #6.

Wow, so if I read this correctly he says that a vasoconstricting drug like Mirvaso, actually triggers the secretion of inflamatory and blood vessel widening substances in our skin? Resulting in the widening of the blood vessels, the extra redness, flushing and inflammation? That would be even WORSE imo than it just causing a temporary 'rebound' widening of the blood vessels after first constricting them.. Seems like another reason to be very cautious with this stuff in the short and long run. And if I read it correctly, it would also mean that this doctor thinks these effects and rosacea worsening which people experience after using Mirvaso are directly related to the Mirvaso

[Brady Barrows]

Yeah I agree actually with Hozer2.. Its great that you put all the effort into make inventories Brady, and I do the same on my blog and know it takes a lot of reading and time, but in the end that is something we chose to do, voluntarily, because we find it interesting and like to help people somehow with it. We don't necesarily earn respect or authority with it and if we come to the wrong conclusions, then I think its fair for people to correct us. In the end none of us are doctors and we just read and come to some conclusions based on the information that is available. I also think that to count an initial positive comment as a positive review is not good enough and leaves a lot of space and uncertainty, as the proof of the pudding is actually in the 2nd wave of effects of Mirvaso; everyone gets pale first. There is no real misunderstanding about that and what is truly of interest of most people here is what happened after those 8-12 hours in terms of flushing and redness. Or even after several days of use. Maybe the people who only reported positive effects in an anecdotal one time report can be contacted to be sure they stick to their initial review after some continuous days of use? The thing is that if you don't take that false error factor into consideration, the evaluation can seem flawed to people here, which seems a shame considering the amount of time it demanded?

I see how you want to keep an open mind about the rebound and whether it could be allergic or not; it would be interesting if it was due to an allergy but to me it seems unlikely given the arguments in post 833 i think it was. The difference is that when the bad flares which people report are due to an allergy, that would mean it is not the blame of Mirvaso; its simply a case of the patient not tolerating the drug due to an auto immune response. But if this is a common side effect of the actual active ingredient, which I believe, that makes it a whole different ball game and people can be disappointed with Galderma for not tackling this issue (and they were aware of this characteristic of brimonidine as a doctor on the board mentioned it to them).

No no vendetta, im sorry if I sounded like I wanted to start one, absolutely not, your input is highly validated

I appreciate your gracious comment above. I have added the following note just before my list of anecdotal reports:

Please note about the following anecdotal reports:
Initially many users report positive results from using Mirvaso, then later report negative 'rebound' results. So be aware that the few Positive Reports may later be moved to the Negative Reports upon evidence of a change.

[nat007]

I appreciate your gracious comment above. I have added the following note just before my list of anecdotal reports:

Please note about the following anecdotal reports:
Initially many users report positive results from using Mirvaso, then later report negative 'rebound' results. So be aware that the few Positive Reports may later be moved to the Negative Reports upon evidence of a change.

That's great. I think its a highly interesting and currently hotly debated topic so any insight in the figures is great, thanks for that.

[Mistica]

Hello Brady,

Just to remind you, in case you missed it in my post, I was examined by an immunologist at the time of my severe rebound and no allergy was found. I had tryptase, histamine and all the IgA, IgG, IgE, etc tested and they were all normal. The doctor was looking for mastocytosis as well, and seemed to be rather disappointed that my levels were not suggestive of this.

Now, to be fair I do have other health issues, but they are not related to allergy.

Rebound flushing.
I was already a bad flusher, but it had become significantly better in some ways over the preceding year or so.

How rebound worked in me.

I had a very pink baseline redness all over my face with much redder cheeks, nose. I had to be very vigilante with my diet and environment and still relied heavily on ice packs to control flushing, but with this preventive regime, my flushing was definitely downgraded to what it had been.

When I first applied brimonidine, it paled me unnaturally, but at the same time, the visible vessels appeared to be more prominent against their ghostly background.

From memory, I spent the first day test driving it around the house.
Then I decided to go out. First to the dentist and then the mall.
I was pretty stunned to experience a fairly small, but intense area of flushing on my upper right cheek.
The area became very hot and deepened in colour.
It looked unnatural, as if I had painted it on with marked borders.

We left the dentist and walked around the mall. After some time the area completely vanished.
I rinsed my face when I came home and went to bed. By morning, my face was fully reddish again, but no worse, as far as I recall.

The pattern thereafter was the same type of 'break through' intense vasodilation. It would appear in one area, disappear and then appear elsewhere, such as in the middle of my upper lip area. It would again, be really intense. (That pattern is not indicative of any type of allergy).
Then I would be worse by morning.
At the time, I had to attend several dental appointments and because the air conditioning was not working properly in the clinic, I foolishly relied on brimonidine to get me through the appointments, thinking, just one more day, etc. Big mistake.
I was much worse every morning and my severe flushing was returning.
I tried quitting cold turkey, but that made me much worse and then I began another foolish experiment of gradually diluting the drug, more and more. But it did not work and I got stuck in a vicious cycle of calming and intense flushing.

After application my face did pale, but the 'break through' flushing was occurring more and more and in the end you could see it happening. It was as if a mole were burrowing under my skin, travelling through the plumbing at high speed. Coming out here and there randomly. I noted another poster comment on this weird pattern of flushing. When the inside of my right ear started to flush, it became very painful.
My upper cheeks especially the right suffered the most. To this day, it is a vascular mess.
In the end, the brimonidine didn't work at all. It was as if the receptors it was influencing, completely dysfunctioned. The final application had the opposite effect. It caused extreme flushing. Of course a scientist could give you a run down of likely biochemical reactions. My layperson's report is brimonidine caused a raging, flushing inferno, and it was one hellacious ride I wished I had never embarked upon.

I ended up in the ER twice, as I have previously mentioned as the break through flushing was so intense, my nose bled and my lips split. I did not receive any useful help, and of course in retrospect I wished I had not gone there either, as the awful lights and stress just amplified the reaction and flushing.
I was given one dose of prednisone during my second visit and they only served to make me much worse!

Of course, the stress all this caused just made the flushing much worse still! I couldn't sleep as each time I lay back on my pile of pillows and started to drift off to sleep, it was as if the final brace holding back the build up of flushing, broke down and the blood raged through the veins in a torrent!. I was so painful! I cried in pain. Ice packs did not help at that point and of course, you have to be careful with icing. It is an art.
I started to stay awake most of the night due to the pain and flushing. Lack of sleep worsens flushing, so this was just another nail in the coffin, so to speak. This continued for weeks.
In the end, I fell asleep out of exhaustion and the flushing raged all night, for several nights.
Then it stopped. Well, the intensity stopped, but I was left with damage. I was, again, a severe flusher. It took some weeks for the earache to subside. My doctor told me the canal was inflamed and then peeled.

The original area of breakthrough flushing on my upper right cheek, extended it's borders to encompass a much larger area and it remains today. I have even had IPL, which did not help much. The upper cheek suffered some kind of nerve damage. I expect that is not the right word, 'damage' as it is not numb, but it can hurt, a type of feeling that drives me crazy. A dull, sickening feeling much like hitting your elbow.

I am happy to say, that these days, the nerve pain/sensation has reduced a lot and I can go months without it being present.
The area is still highly vascularised however.

I am an extreme case, and it was made much worse by my foolish decision to try and wean myself off the drug over time with gradual dilutions.
I suppose the only good thing to come of my horrendous adventure is an insight to what might happen to others should they decide to continue use of brimonidine.

I can not emphasize enough what a big mistake it is to try and reduce vascular symptoms with this drug.

I hope this long post helps clarify what I mean by rebound flushing. I can only equate it to holding a garden hose, the pressure builds up, and when you release the end, a torrent pumps out.
Of course the hose flow quickly returns to it's previous state, where as the face does not.

[Starlite]

The RRDi doesn't get one dime from Galderma. I certainly don't get any money from Galderma. I am not making any rude remarks.

Well, there seems to be some sort of conflict of interest. The RRDi is pleased to announce the appointment of Michael C. Chen, Ph.D., Medical Science Liaison for Galderma Lab, to the RRDi MAC.

[nat007]

Well, there seems to be some sort of conflict of interest. The RRDi is pleased to announce the appointment of Michael C. Chen, Ph.D., Medical Science Liaison for Galderma Lab, to the RRDi MAC.

Aha.. and as recent as 3 weeks ago. Surely hope that Brady stays objective here, despite having a medical 'Liaison' for Galderma on board.. Sharp Starlite

And hugs for Mistica, thanks for always sharing your personal experiences here, you have been through so much xx

[Starlite]

Aha.. and as recent as 3 weeks ago. Surely hope that Brady stays objective here, despite having a Galderma 'Liaison' for Galderma on board.. Sharp Starlite

Interesting timing for sure. You have held you ground well Nat, under what I would define as some extreme pressure to back off on your clear and valid report. Much respect. Mistica too.

[Starlite]

Nat,


According to Anna Holmes, Ph.D, who is an RRDi MAC member and works for Galderma, she posted the following in my post on Mirvaso:

And another one too..

[nat007]

Interesting timing for sure. You have held you ground well Nat, under what I would define as some extreme pressure to back off on your clear and valid report. Much respect. Mistica too.
and
"Nat, According to Anna Holmes, Ph.D, who is an RRDi MAC member and works for Galderma, she posted the following in my post on Mirvaso:

You'd think this forum would be a safe haven for rosacea sufferers, where they can share stuff in all sincerity, but I guess people like Nase and Dr Darm (was that his name?) and Galderma reps (not saying Brady is one but there have been some other first time posters with surprisingly strong pro Galderma messages) will always try to manipulate, as there is money to be made. Not saying per sé that Brady was trying to intentionally influence the discussion pro Galderma, he still came up with 18 bad Mirvaso responses versus maybe 3 undecided ones, but this does reek slightly of a mingling of interests, not great this.

Wow and another Ph.D on his RRDI, how in heavens name did I not pick up on that at the time (Starlite making her name proud again, ur a star).