The brimonidine trial: it was not what I had hoped ...(2010)

Please look here for updates on Mirvaso's launch and patients product review
For a long time rosacea patients waited for a product with the working title Sansrosa. A working title for the product that would later become known as Mirvaso, made by Galderma. Promises were made that it would topically shut down blood vessel dilation, and turn our rosacea faces pale. There was a real rush and excitement going through the online rosacea communities. In the meantime, around 2010, some bad flushers had already started to try an optical eye gel with brimonidine tartrate in it, as that would be more or less the type of active ingredient of Sansrosa. Here is a summary of the trial I did myself at the time. It was not what I had hoped it to be. This is a summary I wrote some time later, below is the exact stuff we discussed and wrote on the forum at the time, which is more precise. I mixed the brimonidine tartrate powder with some water (scroll down for more details on this) and applied it to my cheeks. No burning luckily from it and after about 10 minutes my skin started to feel tight. After 30 minutes it turned ghostly pale. I was elevated and excited. Whenever the effect seemed to wear off, I applied a little bit more. After some time, when I was at a party that evening, I felt the effect wearing off completely and worse, I had such bad rebound flushing and redness. There seemed no stopping, no cold pack or fan or cold air helped. Had to sit it out and it lasted about 12 hours. Way too long for me to use this substance regularly. What a shame, because initially it really seems to shut down the blood vessel dilation. But the rebound flushing seems not a good thing, especially in the long run.

2011 has overall been up and down, but a good part of the time my skin wasn't too bad, within the still severe ranges generally
I can't post the worst of the worst flushes, I wasn't in the mood to picture them, but these are some impressions of the good days and the less good days. Besides, I am still on the same medication (clonidine, propranolol, remeron, Xyzal). Left cheek (my right one) still pale from the brimonidine which was freshly applied, the other having pretty bad rebound flushing, which lasted at least 12 hours and I couldn't calm it down, whatever I tried.

Patchiness after applying the brimonidine

solution, paler spots become visible. 

 

My left cheek is evened out 

and pretty pale now. 

Left cheek (my right) is fully pale now, but the right cheek, 

where I applied the brimonidine first (waited an hour or so in between) is starting to burn and get red after 5 hrs

 On the other cheek the brimonidine also starts to wear off
after some hours. Some redness keeps breaking through and
soon there is all over redness and more flushing than before
applying the brimonidine

Next day

Update (10th december 2013)                               
I received some questions on the forum by a user named Makron about the exact sort of Brimonidine trial I did, so had to look for the exact posts I made at the time, and while I was at it, I might just as well put them here. I added some info here last night about attempting to match the 3,3 mg/ml brimonidine (free base, equaling 5 mg brimonidine tartrate) in Mirvaso back then with my own mixture, to get an similar sort of problem. Mirvaso wasn't launched yet by then however and I couldn't know the composition of Mirvaso yet. I used 2 mg/ml of brimonidine tartrate (and later some more, between 2 and 3 mg) to match the brimonidine eye gel that was tested by some rosacea patients at the time. Below are links and blog posts from 2010 to further explain this. With the remainings of my 5 gr batch of bought brimonidine tartrate, I thought at the time that I could come near the Sansrosa (working titel of current drug Mirvaso) dose during the next trial/mix, as there was still talk then that Sansrosa would consist of around 3 mg/ml of brimonidine tartrate. Instead of the 5 mg/ml brimonidine tartrate it contains now. Hence why Mirvaso now seems way too strong perhaps for some patients, and needs to be diluted according to some derms and reps. My aim back then was to match the brimonidine eye gel with 2 mg/ml of brimonidine tartrate however, as is in the forum posts from 2010, added below. (Mirvaso wasn't a point of reference back then. This poster tried to make it sound like it was for me, and that I lied about the dose and tried to match the brimonidine experience in hindsight with the current Mirvaso drug, but that is based on an already corrected inaccuracy of me in the few red summarizing sentences I added 2 nights ago here; I meant to say that our reference point while making the mix was the eye gel and erroneously summarized that we aimed for Mirvaso instead, which wasn't even out yet, and which turned out to be stronger than we then anticipated the drug to become. I did think at the time however that the second batch of home made brimonidine mix -which I didn't report on in detail like the first try as it turned out exactly the same and with even more and quicker 'rebound' (or at least very bad) flushing and redness and throbbing of the face- equalled the brimondine tartrate/base carrier ratio and in hindsight this was incorrect as Mirvaso turned out to be stronger). To be clear, I haven't used Mirvaso, as it isn't available yet here. Back in 2010 some rosacea patients mentioned they got pale skin from using a brimonidine eye gel on their face. As we said at the beginning of the mirvaso threads, these brimonidine tests are not directly comparable, as I used 2 mg/ml brimonidine tartrate and then 3 mg/ml in a water solution (not equalling the 5 mg tartrate per gram Mirvaso) and splashed a lot more than a pea size on my face. At the time, there was no Mirvaso and people were waiting for Sansrosa as it was called then for a good 5+ years already. 

Here is more of what I have written on the Rosacea Forum at the time:

18th August 2010 10:40 AM: "I tried brimonidine also several days, after dear Wrinkledclue helped me get some, and my chin was clearly paler after use. Next day some on the cheek, and I did see a lighter skin tone, but... also a rash after some time. Rough skin, so to speak and burning a bit. So my theory is, that the brimonidine is working but the preservative and alcohols that are added to the ophthalmic solution are too much for my paper thin skin. So, tried to order some pure brimonidine powder from the pharmacist, but available (sic; unavailable).... Probably because the pharmaceuticals (Falcon in this case) won't give away the active ingredients. So I googled and found some suppliers in China (..). Emailed some of them and the problem now is that they send it in a big dose, minimum of 100 g. mostly (which costs about 800 US dollars!!) and I could get 5 g. from one supplier, for 200 US dollars. Now, I am a big dumbo with those measuring quantities. What do you guys think? It seemed very little to me, 5 g, but then I saw the solution and it only has 0,2% brimonidine in it. So perhaps 5 g is quite a lot actually then? I discussed it with the pharmacist and he said that he can either put the powder in a cream or gel for me, or I can mix it myself daily with water, so we don't need a preservative. I will have to find out how much powder exactly I can use in a drop of water, don't want it to be too much... What do you guys think? These Chinese factories supply the product to the big pharmaceuticals, so I hope it is safe. What about the price? Seems very high to me, but I don't know how much we would need for daily use? And perhaps there are more people interested in this and want to join in?"

Then on 2nd September 2010 05:05 PM: "Ok, the brimonidine powder arrived! Just a small sealed see through bag with whit´ish powder in it. Did email the Chinese woman again to stress again how important it is to have proper brimonidine so I can truly give it a try and perhaps pass the company details on if it works, so I guess it´s a matter of trust now, and perhaps even white skin! A friend has a very precise measuring thing, to my surprise (for honey actually) and I have been able to measure 0,2 g. I have put it in 100 ml of bottled water, all things first sterilized in boiling water. And I have patted the solution on my chin and part of my right cheek AND make pictures of the skin, so perhaps I can detect pale skin in some time. The skin is feeling a bit tingling and numb´ish now, not really numb but it feels a little bit different then the other skin. No burning though, nothing uncomfortable. I am a little bit afraid it will do nothing and I just threw away 200 dollars... To be continued...

2nd September 2010 09:12 PM: So far so good. I put the brimonidine solution on my lower left cheek and chin and within time white patches showed. I have put more of the solution on the spaces in between and it´s still patchy, but def. very pale patches. Chin is completely pale now and left lower cheek has very clear patches. My skin seems to handle it, although it feels ´tight´ and a bit numb at the same time and can tingle. It´s weird, not painful. I am aware of the feeling of the skin, unlike other normal skin. But nothing too bad. Have to see now if the dreaded rebound flare comes. Does anyone have an idea how I can avoid the patches and just have even pale skin? Will mail Tony Chu as well about it, I know he´s interested in this and perhaps he also (like my pharmacist on the phone) has an idea about the percentage and solution. I don´t understand why it shows in patches.....To be continued..

2nd September 2010 10:39 PM: Ai ai ai, this is looking promising! I´m not easily positive when it comes to rosacea, but my cheek (I wrote left cheek, but just realized that´s on my pictures, its actually my right, detail) is PALE. Stays like that when facing a trigger (and the other one does flare up).The patchiness is still there but seems to fill up a bit and the difference is quite dramatic I think. Skin feels still a little bit tight but that´s about it. Note that my upper skin is paper thin and always irritated and dry, so I expected more troubles from it. I just can´t believe this, and am sort of waiting for the disappointment to throw me back in reality. Will see how the cheek is tomorrow morning and if still good, will put the solution on both cheeks then. Just thin from what I understood this brimonidine is the active ingredient also in the upcoming Sansrosa cream. But wouldn't it be much better for rosaceans to mix the active ingredient themselves into either water or their own cream? I am almost certain there will be some kind of alcohol or preservative in that cream. This way we have the pure active ingredient and almost no irritants to the skin. Thanks Wrincledclue for suggesting the brimonidine eye drops!!!!

3rd September 2010 10:13 AM: this morning still pale on the treated area´s, the rest moderately flushed. So far no other side effects. I called the pharmacist to ask how I can store the solution. I first disinfected the weighting scale and measuring cup in boiling water and used bottled water from a sealed bottle by the way, just to be on the safe side. He said that it can be stored in the fridge, to preserve it longer. The molecules of brimonidine are small he said and it´s very soluble to water, so he doesn´t expect crystals to be formed in the fridge. I put the solution straight on my face. I put some of the liquid in a little cup and put it on my skin with my finger, as much as needed and I also ´paint´ more on the patches that are blotchy. Not sure if this is too much though, as it´s the strength of the normal eye drop solution, but it´s been working.. I have ordered the 5 g sample here:

sales6@sinochem-nanjing.com

Miss Fairy Yang

The corporation is Sinochem Nanjing, website: http://www.sinochem-nanjing.com/

3rd September 2010 08:32 PM: Very bad rebound in right cheek. Left one is fine for some reason. The right cheek has already a red patch this morning but now it´s full blown all over the cheek, haven´t had it this bad in a long time. Not sure if it is brimonidine related, I did have some irritation from indirect sunlight earlier this week, but this is really full force flushing. Will give my skin some days to calm down again and see again.   
                                                                                            
4th September 2010 10:58 AM: Big flare on the left cheek as well this morning. Am having two red flushed cheeks again. Am sure now that it has to do with the after effect of the brimonidine, as the left cheek was not too bad before I put brim. on it. Have to sit it out now and see how long it takes for the skin to settle again. Big bummer, as I was over the moon with my pale complexion. But if this is the standard, then the flare ups might not be worth the positive effects perhaps. Although it might also be an option to keep using the brimonidine solution every other 8-10 hours and be a step ahead of rebound flushing. The thing is though, that I am not yet certain if this stuff can cause long term damage or alterations to the facial blood vessels and I don't want to risk anything here. But the test is completed for now, it works and it has after effects. I am sad that I have to go through the busy weekend looking like this and feeling burned up, and more sad that I can't put  the brimonidine on my face at the moment, but well. Is there anyone with suggestions perhaps? It works, but why do I (others) get rebound flushing? It can't be the inactive ingredients, as there are none in my case. I would love to use this daily but am not convinced I am not making matters worse in the long run with it. Then note the responses from other forum users, including our highly valued moderator Melissa W at #113, who echoed this same experience.

4th September 2010 10:07 PM: "Thanks guys. I think the worst is already over, Will try different amounts in the near future. flushing wise. Still redness on mostly one cheek, but clear patches of skin are showing already in between and the full force flushing seems over. So I think the flushing reaction is about 8 hours or something. Perhaps about as long as the paleness reaction is, so that´s not a good thing. Don´t know either Melissa why some, like WC, are not having the rebound flushing. I do have to admit that I used the solution (similar to 0,2%) very generously on my face, and didn´t use the 2 drops, but more. So that might have added to the reaction afterwards. But only afterwards, not during the 8/10 hours of action, then I was very pale. Questions indeed. Will wait till skin is back to its old self and try again in time, as I am very impressed with how it works. Just don´t know why this rebound flushing is happening. These different amounts, 3 mg/ml brimonidine tartrate in water, was used at another evening (trying it a second time), not the same first evening, I mixed that one up in my former post, its been a good few years since already.

End verdict for me: brimonidine works and quite dramatically pales the skin. But the rebound is too severe and too long lasting to make this a workable treatment for me. There is also a lot of worry about weakening the blood vessels in the long run and potentially worsening the rosacea. I won't use brimonidine again. HERE you can read about the trials with brimonidine's big brother, Mirvaso.

New York trip, May 2006

New York, 2006

In May 2006, my mother and her new husband took me, my sister and his 3 adult children on a 4 day trip to New York!! Instead of a honeymoon for themselves, awwww. It was fab. I had had an IPL treatment with Dr. Peter Crouch only a few months prior, which gave me 3 weeks of post treatment (severe) flaring and inflammation, enough to call the whole IPL thing off forever, but luckily my skin hadn't endured any long term damage and was still able to make the 8 hour flight from Amsterdam and those days in the Big Apple. I wouldn't have wanted to miss it. I was still taking diclofenac 100 mg, three times a day at this point, as part of the post treatment anti inflammatory protocol (as I had such a bad inflammatory skin reaction to the IPL). I had been a little bit worried about the long plane trip, but luckily the airplane had small fresh air vents above the chairs. and I was also surprised how chilly they keep the temperature high up in the air. I mean, I've taken short haul flights before within Europe and they can crank the temperature right up then, especially in winter. But my sister, a travel agent, had already told me that she always needs extra blankets on long haul flights, so not to worry. I had to use all my self restraint and determination not to eat the food they offered in the air.. I just reminded myself to stick to this one mission; avoid full blown flushing attacks. I am really sensitive to.. well basically everything, but ALSO to food with preservatives and spices like pepper. I couldn't risk it, but it was hard saying no to the nice meals that everyone around me was eating. When we arrived at Newark airport, we had to stand in a long line for several hours to get past custom security. I was a bit shocked to see so many militant looking security army personal there, with kalashnikovs, but we had the 9/11 attacks still freshly in our minds, so no complaining from us of course. Unfortunately I did get red and a bit flushed during this long waiting in a warm airport. When we finally got out, we took a cab to Manhattan and of course the whole trip to this iconic city was already very exciting. We all know New York from the countless movies that have been shot there and I know about American architecture, including the works of Frank Lloyd Wright and the whole New York grid street system, as well as high rising buildings like the Empire State Building. I was cooing with joy when we saw the Manhattan skyline from our cab window. My sister was also jumping in her seat from anticipation. It turned out she found New York too crowded, too busy, too "big town'ish" and prefers Washington. Not me! 

My mother had arranged a hotel at Broadway, a nice retro looking hotel where the workers were sharp witted and a bit brass, which we loved. It was called Milford Plaza, and nowadays doesn't seem to exist anymore in its old form. We all had our own rooms and when we walked out we were right into the hustle and bustle of Manhattan. I had to go out right away to look for a ventilator, as I didn't think a European style fan with different socket and possibly different voltage system would be of any use. It was after 6 PM by then and my farmers mind was stressing out already, worried that all the shops would be closed by now. Haha, not in New York, baby. Everything seemed open forever, and I only had to walk one block to find a convenience type of store with fans available. Sorted! We went out for dinner and had really been looking forward to a gigantic American style meal, so there was no discussion about it being a hamburger joint. Meals weren't thát gigantic, but more than enough and we just loved seeing American faces and hearing American (well, New York) accents. 

Touring bus

The next day we decided to act like forthright tourists and to get on an open rood touring bus. Hans, my mothers husband, has knee issues and walking through the whole of Manhattan, just to get some first impressions, seemed silly. I also really liked the cool air on my skin in the bus. I had been lucky with the weather, as it was dry and not too sunny, yet comfortable around 18-21 degrees or so all week. My skin had been OK during the night; I had windows open and used my fan. I was relieved that my skin was only mildly pink. We took the usual touristic route, but managed to also see parts of The Village, Soho and even Harlem. We went full out as tourists, making photos of pretty much every crossroad, even though at some point the buildings weren't that spectacular. I even have stacks of photos (all analogue still) of American flags waving left, right and center. Anything American, and we wanted to record it. We had lunch close by the hotel and decided to split up, allowing each of us to do different things. My sister and I wanted to pass the MoMa museum, eat as many types of cheese cake as we could find, and we also wanted to get on top of the Empire State building and see the 9/11 site, which was at that time still a black construction site-hole in the ground. When we arrived at the Empire State building, there was actually a line of people waiting. Knowing what sort of lines are daily business as usual in Amsterdam (think the Anne Frank house for instance), it beats me now why we had casually expected that we could just hop in the elevator and get to the top without delay :) Soooo we had to wait a good half hour. The lift was already exciting, golden, decadent with lots of mirrors. When we made it to the top it was pleasantly windy and I was mesmerized by the view. My sister however took a few looks left and right and declared, in typical tour operator style: "So, we've seen it (check), lets go down again". I said No way, I want another 15 minutes at least to just absorb the views thank you. It was something I had never seen before, as Manhattan in general was something entirely new. Europe is all quaint and old and all that, but I had never been in a city where the eye is drawn vertically, upwards, instead of horizontally. It felt like being hugged and tugged tight by all these buildings. And on a practical not: shade everywhere! Wind too. The buzz I felt there was exciting. So many people, everybody so busy, shops open all hours of the day and night, the sounds, the ever sounding sirens of police or ambulances, it all gave an urgent sort of thrill that you won't get in European cities in my experience. So viewing the city from above was pretty breathtaking. 

I tried to pinpoint the different neighborhoods. Central park was easy and again, this whole grid business was so new, European cities aren't built that way (although Paris / Haussmann got renovated in a neat, non-organic way and ok ok, Barcelona has a grid system in some parts of the center).  From above, I could see the true beauty of this impeccably designed city. Then we took the subway to the former World Trade center site. The sheer size of the spots where the two towers had once stood was very profound to see. We took our time thinking about the events and what had happened there 5 years prior. Then we wanted to go to Coney island, but found out we needed to take a train to get there and that it was actually a bit of a ride.... And we had a dinner 'date' set, so unfortunately had to skip the beach. Shame. 

That evening we went to a broadway show; The Phantom of the Opera. We had all had a say in the choice of show and I was happy that the phantom had won it, I really like some of the music from it. This one in particular:

By then I had been pigging out, simply put, on all sorts of foods, because New York tempts you with it around every corner. Cheesecake was a complete hit with my sister and me, although she had a lot more restraint with it haha, I ate 3 different ones a day and honestly gained a few kilo's during my stay. When we got back from the Phantom, I was a bit flushed, and had my colitis play up. I don't tolerate gluten well, get a very swollen cramped digestive tract from it, so that evening was more or less spent on my hotel room while the rest went out for drinks later on. Still, nothing bad enough to keep me away from cheese cake the days after :D Third day my sister, mother and new stepdad went to Soho and Chinatown. We took our time to walk around these neighborhoods and also visited Little Italy, which turned out to be a few streets only (or as far as we could tell). It was a lovely day, not too warm, and we had lunch in Soho and just strolled around. We also went to the Wall Street area and to some sort of harbour. That evening my mother had arranged for all of us to go on a boat cruise sort of thing, with entertainment and a buffet. I loved having fresh air there and being able to pick my own menu. The entertainment was good and at some point many guests made it to the dance floor. I especially remember some song being played, which was en vogue at the time, and everyone doing this choreographed dance routine! I only know of the Macarena over here where everyone joined in to do the same dance moves, (and more recently the gangnam style) but this dance routine involved everyone dancing in a line and wiggling, using hands and also jumping in different positions. 'Very American', we concluded. I'm not a dancing queen so my efforts to join in were pretty dorky. With regards to the gangnam style song I have such fond memories; I helped out running a B&B at the time, hosting long term holidays for handicapped adults (I think I have to say physically and mentally challenged people nowadays), and they had the mental capacities of 12 year olds mostly, sometimes younger, but when this song was put on, the whole group came to life, jumped up, and ferociously did their version of the gangnam style dance, sometimes even recognizable. Hilarious, we had a lot of fun organizing disco evenings and karaoke competitions with them). So that boat trip was a hit as well with everybody and I loved seeing the Brooklyn Bridge and the Manhattan skyline again but now from the water perspective. 

Our last day was spent in Central Park and walking around the fancy shops in that part of town. We had lunch at Katz delicatessen (very good). But my sister is also a proud Mc Donalds client, priding herself on always eating at least once in whatever town or country she visits (and she went all over the planet for her work), and New York has the biggest Mc Donalds store she knew to tell me, so off we went after that. I ordered absolutely nothing there as I had lunched nciely at Katz and was otherwise still stuck on my cheesecake diet and had seen one in a fancy pastry shop around the corner. But I sat down with her in a monstrously big building with several floors, hearing her judge if the Big Mac was or wasn't exactly the same as it is at home. (I think it was). These days flew by and we all wished we could stay a week at least longer. We still wanted to see Brooklyn, Coney island, the statue of Liberty, many museums we missed, tours we wanted to see, jazz clubs we never saw and I bet there is enough to do there for every hour of every day of the whole year. But we had to go back again. At Newark we saw a Jewish convention arrive to meet some high rabbi who had just landed, and hundreds of chassidic looking jews were waiting and praying and reading their little books, which I found fascinating to see. The trip back was fine and I only was a little bit flushed from it. I was sorry I couldn't take New York with me in my suitcase. I took some of her along though; photos, some memories, some artifacts.. Tribal men in Papua New Guinea think that when you take a photo of them, you steal their soul. I hope I stole New Yorks soul with my photos and took her with me. I doubt it however, considering the abominable quality of most photos haha, New York unworthy! Luckily I wasn't the only one carrying a camera and was there a better one to use. But I loved the atmosphere of the city, the beauty of red bricks, metal and concrete. 

The distinct own 'look' of everything, the aloof attitude of the people. I like being left alone, walking around unwatched and New York did just that. She gave me a "Welcome" greeting when I arrived, just, and left me alone further. It is a city of big contrasts though, as all big cities are, and we only saw the sparkle and bustle of Manhattan mainly. Not the outer neighborhoods, not the graffiti filled school yards outside of the Upper East Side. Just a tourist, just a snapshot. But it made me understand why some people want to put up with the smog, the dirt, the hectic lifestyle, the tired eyes, ears and other senses, just to be able to daily walk through this city. Get charged by its energy, distracted by its liveliness. I particularly liked walking through areas of town where locals did their usual business. Walking in and out of Laundromats and Dry Cleaners, deli shops, the restaurants from all directions of the wind, people (still at the time) smoking in the street, always seemingly in a hurry. The iconic yellow cabs everywhere, making every photo by default more iconic instantly. Smart shops next to garbage bins that pile over. Priceless high rising apartments and then taking the cold dirty noisy subway. And of course; NEW YORK CHEESECAKE :)  Henry Miller had another take on this city however: 

“New York is cold, glittering, malign. The buildings dominate. There is a sort of atomic frenzy to the activity going on; the more furious the pace, the more diminished the spirit. A constant ferment, but it might just as well be going on in a test tube. Nobody knows what it’s all about. Nobody directs the energy. Stupendous. Bizarre. Baffling. A tremendous reactive urge, but absolutely uncoordinated.”