Brady Barrows

Mirvaso

29 posts in this topic

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Official Mirvaso Web Site

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Mirvaso has set up the following RED IS WRONG web site (redirects to mivaso.com).

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Mirvaso is a treatment released by Galderma in August/September 2013. Posts from users should be in this thread. It was announced in late February 2014 that Mirvaso is approved to be released in the EU. NICE has announced release in the UK is set for July 2014. MarketWatch reports on April 16, 2014 it is available in the UK. For more information on Mirvaso click here. If you have something you know about Mirvaso please post in this thread. It was announced in May 2014 that Galderma released this prescription in Canada as Onreltea (for a product description click here).

Here is the link to the prescription handout in pdf. Here is the link to the package insert.

"Once‐daily brimonidine gel 0.33% allowed patients to rapidly control their facial redness and significantly improved patient‐reported outcomes in the treatment of persistent facial erythema of rosacea."

David Pascoe has an excellent breakdown explanation of the clinical trial results of the 330 trial users for the 29 days and the 276 trial users for the 365 days which shows excellent results.

As of November 2013, The price ranges from $266 to $274 for one tube (30 grams) at the different drugs stores in the USA. Source. David Pascoe has pointed out that in the UK Mirvaso may only cost £34 ($57) a tube which is quite a price difference! For more info click here.

Galderma is offering ways to save on Mirvaso if you click here.

savings-cards.pngMirvaso Mirror AppGet the Mirvaso Mirror App

"Approximately 80% of patients treated with brimonidine experience a significant improvement without erythema worsening as an adverse event. Attention to optimizing skin barrier function, setting patient expectations, and strategies to minimize potential problems may possibly reduce further the number of patients who experience side effects." [6]

You should be aware that Mirvaso's active ingredient is bromonidine and that initial reports of using bromonidine for rosacea may produce rebound effects that you should be aware of. [1] [2] It has been known from at least 2002 that brimonidine results in allergic reactions. [3] However, one report concluded the following:

"Once-daily topical BT gel 0.5% is not only efficacious at reducing facial erythema but also exhibits response within 30 minutes of application in a significant number of patients throughout both Phase III studies." [4]

For example, Mistica reports:

"I am a brimonidine victim. I ended up in the ER twice with the most horrific rebound flushing. I had nose bleeds, split lips and terrible flushing as the blood surged through my face looking for the weakest route. It would dart about, first engorging the side of my nose, then upper lip area, then the cheek, etc." 4th September 2013 12:04 AM Post #70Read a full report

"We report a unique case of facial erythema of rosacea that responded to brimonidine gel with effective blanching for two years until the patient developed a paradoxical erythema reaction. This is an adverse reaction physicians should be aware of with continued prescription of brimonidine gel for their rosacea patients." [7]

Rebound vs Allergic Reaction - What's the Difference?

Scroll down to Post #6 and Post #9 in this thread to understand the difference between rebound and an allergic reaction. You are currently reading post #1 (see top right corner for post number).

According to Galderma, Mirvaso has had excellent results in clinical trials and you can read the results of those clinical trials in the prescription handout in pdf. You may read a conversation with the then current president of Galderma, Francois Fournier, about Mirvaso by clicking here. A few days later, the same magazine announced Fournier's ousting as president of Galderma. On December 9, 2013, the DHealthcare Daily reported in an article by Bradford Pearson, Layoffs Hit Fort Worth-based Pharma Company Galderma.

According to WebMD the top side effects of using Mirvaso are Redness of Skin and Temporary Redness of Face and Neck and classify this as 'less severe' and then list other sides effects as 'infrequent' or 'less severe.' Epocrates Online reports the following common reactions:

  • erythema
  • flushing
  • burning sensation
  • allergic contact dermatitis

A similar warning is also reported by Clinical Advisor. JAAD has published the first article on the rebound effect of Mirvaso by Routt and Levitt [1]

Galderma now has acknowledged that rebound is a concern with this post:

hcp-about-barker.png

source:
http://mirvaso.com/hcp/about-mirvaso/

Anecdotal Reports

From initial reports from rosacea online groups and forums, there are few reports that Mirvaso is successful with rosacea sufferers. For example, hozer2K reports after reading posts at RF and other forums that he has found little successful posts using Mirvaso and a few have reported rebound effects. You should be aware that in a study done to know the incidence of allergy to brimonidine in patients treated for glaucoma that 25% of the patients were allergic to brimonidine. [1] However, Anna Holmes, Ph.D., explains, "Allergic sensitization was measured by patch testing patients across the Mirvaso clinical development program with suspected allergic contact dermatitis. The overall incidence of confirmed sensitization was less than 1%. Sensitization can occur, but the incidence is low." (See Post #7 below)

To report SUSPECTED ADVERSE REACTIONS, contact Galderma Laboratories, L.P. at 1-866-735-4137 or

FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

News Blurbs

The following news blurbs from TV stations appear as legitimite news items but should be taken with the knowledge that they follow a pattern from a 'news feed' source that may be hired to promote Mirvaso. The pattern is for the news station to find a local doctor willing to appear on camera showing a willing patient who is being treated for Mirvaso. The report names the patient and the doctor and in each case the patient gives a positive report for Mirvaso. Since there is no follow through by the TV station on the patient, so we have no idea if after some time, say weeks or months later, if there are reports of rebound or if any of these patients later sing the Mirvaso Blues. For more information on how media news blurbs could be PR announcements masked as a news item, read this article by prwatch.org.

Here is the list:

(1) Ginger Royer's report shown on KPLC 7 News, Lake Charles, Louisiana, December 4, 2013: http://www.kplctv.com/story/24130820/new-fda-approved-gel-for-rosacea?autoStart=true&topVideoCatNo=default&clipId=9597783

(2) Rosemary Stockinger's report shown on KDKA News, Pittsburg, PA, December 6, 2013: http://pittsburgh.cbslocal.com/2013/12/06/fda-approves-new-treatment-for-rosacea/

Rosemary Stockinger is mentioned in a similar report shown on WCBS, New York on December 9, 2013: http://newyork.cbslocal.com/2013/12/09/newly-approved-gel-may-help-rosacea-patients/

 

TV

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There is a report that a television series, My Naked Secrets, Season 3, Episode 7, Ana, details how Ana became one of the first patients to use Mirvaso in Europe. See Post #1332 by rosaceaclearwannabe • You can view the episode in iTunes, Episode 2, Ana in the UK (not available in USA).

Reviews

Julie Zuckerman, PA-C

Crutchfield Dermatology Report of 27 year old rosacea sufferer

Positive and Negative Anecdotal Reports

Please note about the following anecdotal reports in two spreadsheets (Positive and Negative):

Positive

66 reports

Negative

242 reports

Follow Up on the Above Anecdotal Reports

It is rarely possible to follow up on Positive Mirvaso anecdotal reports since most posters only post once and there is no way to follow up if the user has rebound issues later. See Post #24 below for more information by scrolling down (you are currently viewing post #1).

Ambiguous Reports

Scroll down down in this thread to Post #15 for a list of ambiguous anecdotal reports using Mirvaso.

Addendum on the above anecdotal reports

The above reports came from various online rosacea support groups, YouTube, WebMD, and other sites. The source of each report is shown in the last column of the spreadsheet.

Treato

http://treato.com/Brimonidine,Mirvaso/?a=s

This cute video explains Treato:

WebMD

http://www.webmd.com/drugs/drugreview-164982-Mirvaso+top.aspx?drugid=164982&drugname=Mirvaso+top&pageIndex=0&sortby=3&conditionFilter=-500

Another board to visit if you are interested is the Cafepharma Galderma thread on Mirvaso (posters apparently are professional reps of pharmaceutical companies):

http://www.cafepharma.com/boards/showthread.php?t=538135

Et Cetera

There is a lot of non user comments about Mirvaso in the above threads and you have to search carefully to actually find a post by someone who actually has a prescription for Mirvaso who reports what they are experiencing, but I have done a search at this point in time for a significant number of hours and have confirmed what hozer2K reports that there are few reports confirming what Galderma is touting in their advertisements for Mirvaso. This may be because those users who accept a prescription for Mirvaso and it works for them simply do not report their success in online rosacea support groups and go their merry way happy as larks.

It takes a lot of time and searching to find actual user reports, and I will continue to work on this as I have time. I could use some help with this, but since I am basically the only person posting in this entire forum with the exception of the two guests (see posts #2, #3, and #4) that found a loophole, I simply don't have the time to browse all these posts. If I get time, I will resume the search. If you have the time, and can log into this forum, I would appreciate some help and simply post in this thread what you have found is your experience with Mirvaso or post links to those users who have reported their experience with Mirvaso. I could use some volunteer help with this thread. We do need volunteer forum moderators. The RRDi does indeed provide perks if you volunteer.

RRDi Members may post their experience with Mirvaso below in this thread. Guest_Julie_S is the first guest to actually report her experience which is in this thread as Post #2 and #3. Another guest posted #4 who reports Mirvaso is wonderful. However, if you read Post #5 which I also posted, it explains that Posts #2 & 3 and Post #4 are created by guests who were able to post until I closed the gate. Only RRDi members can post now. And the problem with RRDi members is that they do not post in our forum. I don't know why? I sent an email to all the members asking them to post and what we can do to make it easier to post. No replies.

You may wonder why the RRDi doesn't usually allow guest posts of anonymous posters. The RRDi Member Forum requires your contact information and has over 1000 members. However these members simply do not post here, for whatever reason. I have sent out a newsletter asking specifically what can we do to make the RRDi forum easier to post and received no solutions on what we can do to stimulate RRDi Members to post here. The other problem is that of the 1000+ members, some opt out of the newsletter, and I get a huge number of bounce back messages since everyone changes their email addresses just as they do cell phone numbers, which makes it even more difficult to send the newsletter since I received a notice from our host that if we send another newsletter with as many bounce back messages as the last one, they will shut us down. It is a huge undertaking to weed out the members who do not have valid email addresses, and I did do this volunteer work. If anyone wants to volunteer to help me with moderating this forum, please contact me

One odd item is that those who post positive Mirvaso experiences usually post once and then we never hear from them again. So there is no way to follow up on these positive reports to see if these users experience rebound issues later since we usually never hear from them again.

End Notes

[1]

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JAAD ONLINE:

Abstract:

Rebound erythema and burning sensation from a new topical brimonidine tartrate gel 0.33%

Ethan T. Routt, BA Jacob O. Levitt, MD

Full Article:

http://www.jaad.org/article/S0190-9622(13)01177-8/fulltext

PDF:

Rebound erythema and burning sensation from a new topical brimonidine tartrate gel 0.33%

PubMed:
J Am Acad Dermatol. 2014 Feb;70(2):e37-8. doi: 10.1016/j.jaad.2013.10.054.
Rebound erythema and burning sensation from a new topical brimonidine tartrate gel 0.33%.
Routt ET, Levitt JO.

[2] J Am Acad Dermatol. 2014 May;70(5):e109-10. doi: 10.1016/j.jaad.2014.01.853.
Brimonidine effective but may lead to significant rebound erythema.
Ilkovitch D1, Pomerantz RG2.

[3] Can J Ophthalmol. 2002 Feb;37(1):21-6.
Allergic reactions to brimonidine in patients treated for glaucoma.
Blondeau P, Rousseau JA.
Department of Ophthalmology, Université de Sherbrooke, Que.

[4] J Drugs Dermatol. 2014 Jun 1;13(6):699-704.
Improvement in facial erythema within 30 minutes of initial application of brimonidine tartrate in patients with rosacea.
Jackson JM, Fowler J, Moore A, Jarratt M, Jones T, Meadows K, Steinhoff M, Rudisill D, Leoni M.

[5] J Eur Acad Dermatol Venereol. 2015 Dec; 29(12): 2405–2410. Published online 2015 Sep 28. doi:  10.1111/jdv.13305, PMCID: PMC5054962
Brimonidine gel 0.33% rapidly improves patient‐reported outcomes by controlling facial erythema of rosacea: a randomized, double‐blind, vehicle‐controlled study
A.M. Layton, M. Schaller,  B. Homey,  M.A. Hofmann,  A.P. Bewley,  P. Lehmann,  C. Nohlgård,  D.B. Sarwer,  N. Kerrouche,  and Y.M. Ma 

[6] Adv Ther. 2016; 33(11): 1885–1895.
Published online 2016 Aug 25. doi:  10.1007/s12325-016-0404-8
PMCID: PMC5083782
Multidisciplinary Consideration of Potential Pathophysiologic Mechanisms of Paradoxical Erythema with Topical Brimonidine Therapy
James R. Docherty, Martin Steinhoff, Dianne Lorton, Michael Detmar, Gregor Schäfer, Anna Holmes, and Anna Di Nardo

[7] Paradoxical Erythema Reaction of Long-term Topical Brimonidine Gel for the Treatment of Facial Erythema of Rosacea
J Drugs Dermatol. 2016;15(6):763-765
June 2016 | Volume 15 | Issue 6 | Case Report | 763 | Copyright © 2016
Erin Lowe MSIV and Scott Lim DO

 

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Hi I am a Mirvaso user. This drug is horrible and I predict there will be a class action lawsuit against it.

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I am writing this because I had a horrible night last night due to Mirvaso. I went to a dermatologist on Wednesday to address my skin concerns, which were redness and bumpiness. He started me on antibiotics, topical acne medication at night, and Mirvaso in the morning.

Before I started taking the drug I went online and looked at people's opinions. I noticed that there were several people who had reported problems with rebound flushing. I also noticed that in the clinical trial, the actual success rate compared to placebo was shockingly low. I am not a medical expert so I decided to shrug it off and take use the cream anyway.

The first day that I used the product, I noticed a significant redness reduction after about an hour. My skin would stay pretty pale. I actually thought I looked almost too pale. My skin looked somewhat unnatural, kind of yellow, since there was no red in it. I am white by the way.

I continued to use the product though, because it did take away my redness.

On the fifth day of use the sh*t hit the fan. I am not someone who flushes, just someone with persistent redness. It's hard to judge your own appearance, but I would say that I was on the less red side of the spectrum. I had redness on my cheeks, nose and sometimes chin, enough that I felt self-conscious without foundation or concealer on. On day five of using Mirvaso, I applied the cream to my face at 7:00AM and waited for it to work while I got dressed. It took enough redness out of my face that I decided I could skip wearing foundation that day, even though I was going to be working in an environment where hundreds of people would be looking at me. Well, that was a mistake. That day I had to spend some time out in the cold and also a lot of time running around inside. At 7:30PM my face became extremely hot. I it felt like I had an extreme sunburn, which I new I didn't as I'd loaded up on sunscreen and it was November in New York. My face was so painful. I had to continue working in front of hundreds of people. It was really embarrassing. My whole face was beet red, redder than I had ever seen it in my life. From edge to edge it just looked completely scorched and was really uncomfortable. The redness far exceeded the normal surface area of my face that in normally red. I was distraught and really wanted to burst into tears because I wasn't sure if I was going to have any other reaction to it or if the damage would be permanent.

I just got off the phone with my doctor and he said it is like a cosmetic camouflage, which doesn't actually treat the redness. He said that the flushing at the 12 hour mark is normal. I have decided to spend the money I would have spent on more Mirvaso on a good foundation and concealer.

The redness episode was last night. Today my face seems to have returned to it's normal level of partial redness.

I am posting this long story to help people who are trying to decide whether or not to use Mirvaso. I feel like the numbers on the drug company's website don't present a very compelling argument in favor of using it. The study they cite in their prescribing information states that they began with 1210 subjects, but that some had to drop out because of redness or flushing. They conducted the full study on a total of 833 subjects, meaning that 387 subjects dropped out of the study. It doesn't say why all of these dropouts occurred, so I wonder what percentage of those was from adverse reactions to the drug. You'll notice that they report that in the trial, 4% suffered from erythema or redness and 3% suffered from flushing. This makes it seem like a rare side effect. The dropout rate is just under 32 percent. While there may have been other factors which caused people to drop out, if we assume that all dropouts were caused by redness or flushing, this would make the total percentage of people with either redness or flushing 33.7 percent. I would love to see numbers from Galderma about how many people left the study because it was exacerbating instead of treating their problem.

Another bit of information that I would like to pass on before ending this diatribe is that Mirvaso is only a temporary treatment, which lasts for several hours. It will not cure roseacea or lessen it at all. I basically see it as a glorified form of makeup, except when the "makeup" wears off you run the risk of looking ten times worse. I am female, so it is easier for me to wear makeup that it is for males, for whom it is often not socially acceptable, so I do understand that some people may feel this is a better alternative to makeup. My advice is that if you do decide to use it, make sure that it is for a day when you won't be out for more that 12 hours.

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I've been using this med for over a month and I am doing great. It has given me confidence and has improved my life on a daily basis

admin Note:

Jimmi may be the same one who wrote the following on December 19, 2013:

"It sounds like more people are having better results with Mirvaso. I know that it has totally improved my life overall. Good luck everyone and Happy Holidays!" source

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Admin Note

When creating this forum on Mirvaso there was a loop hole that allowed guests to post. Hopefully this loophole has been closed. We will do further testing on this. The above two guests are not members of the RRDi. Our policy does not allow non members to post. However, in this case, I have allowed both posts to remain for now and you have been notified that the RRDi has clearly explained that the guest members above, Julie_S and Jimmi_* found the loophole and are not verified members of the RRDi.

Addendum

I closed the gate and now guests cannot post. Only RRDi Members can post in this thread.

By the way, if you want to post anonymously like our two 'guests' did in this forum the RRDi allows you to post anonymously. Read this post

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Rebound

rebound (verb) [ no obj. ] (rebound on/upon) (of an event or situation) have an unexpected adverse consequence for (someone, esp. the person responsible for it): Nicholas's tricks are rebounding on him.
rebound (noun) • [ usu. as modifier ] the recurrence of a medical condition, esp. after withdrawal of medication: rebound hypertension.

(obviously there are more definitions for rebound but I picked the pertinent ones)

Found this medical dictionary that said:

rebound : a spontaneous reaction; especially: a return to a previous state or condition following removal of a stimulus or cessation of treatment --withdrawal of antihypertensive medication may lead to a rebound hypertensive crisis—<Emergency Medicine>

Allergic Reaction to Medicine

Any prescription or nonprescription medicine can cause an allergic reaction. Allergic reactions are common and unpredictable. The seriousness of the allergic reaction caused by a certain medicine will vary.

Allergic Reaction to a Medicine - WebMD

So one of my questions is how does one differentiate an allergic reaction from rebound? Isn't it possible that what everyone is calling a rebound could be an allergic reaction to a medicine? It seems logical to me it that what everyone is calling a rebound could be an allergic reaction to brimonidine since the reaction happens rather quickly. Most of the reports of brimonidine treatment for rosacea indicate this happens within the first few days of initial treatment.

All the examples of rebound I found listed for rebound above involve using a drug for a long period and then stopping the drug and a rebound happens, for example, rebound headaches.

Take for example those who have an allergy to penicillin. If given penicillin they react quickly with rashes, hives, itchy eyes, swollen tongue, and in severe cases anaphylactic reaction. Usually one finds out rather quickly if one has an allergy to penicillin. It seems logical to me that since most of the 20 or so reports that I have collected from the various anecdotal reports show that what everyone is calling 'rebound' may be an allergic reaction. I am no doctor, but when using medical terms we should try to use the correct ones.

Could the RRDi MAC Members comment on this?

Note: I sent emails to all the MAC members about this question and some responded by email to me the following (while others replied directly in this thread - note Post #7 by Dr. Anna Holmes):

Reply from Raymond Peat, Ph.D.,:

"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 gave the following references:

J Neurosci Res. 2002 Jan 15;67(2):264-74.
Tumor necrosis factor expressed by primary hippocampal neurons and SH-SY5Y cells
is regulated by alpha(2)-adrenergic receptor activation.
Renauld AE, Spengler RN.
Department of Pathology, School of Medicine and Biomedical Sciences, Buffalo, New
York, USA.
Neuron expression of the cytokine tumor necrosis factor-alpha (TNF), and the regulation of the levels of TNF by alpha(2)-adrenergic receptor activation were investigated. Adult rat hippocampal neurons and phorbol ester (PMA) differentiated SH-SY5Y cells were examined. Intracellular levels of TNFmRNA accumulation, as well as TNF protein and that released into the supernatant were quantified by in situ hybridization, immunocytochemistry and bioanalysis, respectively. Both neuron cultures demonstrated constitutive production of TNF. Activation of the alpha(2)-adrenergic receptor increased intracellular levels of TNF mRNA and protein in SH-SY5Y cells after addition of graded concentrations of the selective agonist, Brimonidine (UK-14304) to parallel cultures. Intracellular levels of mRNA were increased in a concentration-dependent fashion within 15 min of UK-14304 addition and were sustained during 24 hr of receptor activation. In addition, the levels of TNF in the supernatant were increased in both types of neuron cultures within 15 min of alpha(2)-adrenergic receptor activation. Furthermore, levels of TNF significantly increased in the supernatants of both neuron cultures after potassium-induced depolarization. A reduction in this depolarization-induced release occurred in hippocampal neuron cultures after exposure to the sympathomimetic tyramine with media replacement to deplete endogenous catecholamines. This finding reveals a role for endogenous catecholamines in the regulation of TNF production. Potassium-induced depolarization resulted in the release of TNF in hippocampal neuron cultures within 15 min but not until 24 hr in SH-SY5Y cultures demonstrating a temporally mediated event dependent upon cell type. Neuron expression of TNF, regulated by alpha(2)-adrenergic receptor activation demonstrates not only how a neuron controls its own production of this pleiotropic cytokine, but also displays a normal role for neurons in directing the many functions of TNF.
Copyright 2002 Wiley-Liss, Inc.

Br J Ophthalmol. 2007 Jan;91(1):29-32.
Measurement of inflammatory cytokines by multicytokine assay in tears of patients
with glaucoma topically treated with chronic drugs.
Malvitte L, Montange T, Vejux A, Baudouin C, Bron AM, Creuzot-Garcher C, Lizard G.
CHU Dijon, Service d'Ophtalmologie, 3 rue du Faubourg Raines, 21000 Dijon,
France. laure.malvitte@wanadoo.fr
AIM: To investigate the ocular surface inflammatory response to chronic topical treatments in patients with glaucoma by measuring the cytokine level in tears using multiplex bead analysis.
METHODS: Tear samples were collected from 21 patients with glaucoma and 12 healthy volunteers. Tears were analysed for the presence of 17 cytokines: interleukin (IL)1beta, IL2, IL4, IL5, IL6, IL7, IL8, IL10, IL12, IL13, IL17, granulocyte colony stimulating factor, granulocyte-macrophage stimulating factor, interferon (INF)gamma, monocyte chemotactic protein (MCP)1, macrophage inflammatory protein 1beta and tumour necrosis factor (TNF)alpha. The cytokines in each sample of tears were measured using multiplex bead analysis with microspheres as solid support for immunoassays.
RESULTS: In the tears of treated patients, proinflammatory cytokines (IL1beta, IL6, IL12, TNFalpha) were significantly increased compared with controls. T helper (Th)1 (INFgamma, IL2) and Th2 (IL5, IL10, IL4) type cytokines were also significantly higher (p<0.05); however, the most marked increase was observed with Th1 cytokines. The expression of chemokine IL8 and MCP1 was also increased in the treated group.
CONCLUSION: This study shows that pro-inflammatory cytokine secretion by conjunctival cells is increased in response to topical treatments for glaucoma. The characterisation of cytokines in tears was previously limited by the small volume attainable, a limitation that has been overcome by multiplex analysis.

Am J Physiol Heart Circ Physiol. 2006 Jul;291(1):H231-8.
Brimonidine evokes heterogeneous vasomotor response of retinal arterioles:
diminished nitric oxide-mediated vasodilation when size goes small.
Rosa RH Jr, Hein TW, Yuan Z, Xu W, Pechal MI, Geraets RL, Newman JM, Kuo L.
Department of Opthamology and Surgery, Scott and White Eye Institute, Texas A & M
University System Health Science Center, Temple, TX 76508, USA.
rrosa@swmail.sw.org

Brimonidine, an alpha2-adrenergic receptor (AR) agonist, has been employed in the treatment of glaucoma due to its beneficial effects on intraocular pressure reduction and neuroprotection. In addition, some studies have implicated that brimonidine might influence ocular blood flow; however, its effect on the retinal microcirculation has not been documented. Herein, we examined the vasomotor action of brimonidine on different branching orders of retinal arterioles in vitro and determined the contribution of the alpha2-AR subtype and the role of endothelium-derived nitric oxide (NO) in this vasomotor response. First- and second-order retinal arterioles of pigs were isolated, cannulated, and pressurized for functional studies. Videomicroscopic techniques were employed to record diameter changes in response to brimonidine. RT-PCR was performed for detection of alpha-AR and endothelial NO synthase (eNOS) mRNA in retinal arterioles. All first-order arterioles (82 +/- 2 microm ID) dilated dose dependently to brimonidine (0.1 nM to 10 microM) with 10% dilation at the highest concentration. Second-order arterioles (50 +/- 1 microm ID) responded heterogeneously with either dilation or constriction. The incidence and magnitude of vasoconstriction were increased with increasing brimonidine concentration. Administration of the NO synthase inhibitor NG-nitro-L-arginine methyl ester abolished the brimonidine-induced vasodilation in first- and second-order arterioles. Regardless of vessel size, vasomotor responses (i.e., vasodilation and vasoconstriction) of retinal arterioles were sensitive to the alpha2-AR antagonist rauwolscine. Consistent with the functional data, alpha2A-AR and eNOS mRNAs were detected in retinal arterioles. Collectively, our data demonstrate that brimonidine at clinical doses evokes a consistent NO-dependent vasodilation in first-order retinal arterioles but a heterogeneous response in second-order arterioles. These vasomotor responses are mediated by the activation of alpha2-AR. It appears that brimonidine, depending on the concentration and vessel size, may alter local retinal blood flow.

Reply from Robert Latkany, M.D.:

"Mirvaso is 0.33% brimonidine gel. Brimonidine has been used to lower intraocular pressure on the eyes for glaucoma for years. It typically is not a first line agent and has had several modifications over the years. The most recent formulation is Alphagan P 0.1% by Allergan. This concentration appears to cause less redness and irritation than the higher concentration bottles. In fact, I often use this drop to decrease the redness in some patients with fairly prominent vessels that are disfiguring. I am pretty sure there is an ophthalmologist seeking a patent on the use of brimonidine to address "red eyes". So all that said, there is probably a role here for facial erythema. But further studies will need to be done on what concentration is most appropriate and what frequency is needed. My guess is it should be given in 4 week cycles in a diluted concentration but a study should easily determine the most successful approach."

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Allergic sensitization was measured by patch testing patients across the Mirvaso clinical development program with suspected allergic contact dermatitis. The overall incidence of confirmed sensitization was less than 1%. Sensitization can occur, but the incidence is low.

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Allergic sensitization was measured by patch testing patients across the Mirvaso clinical development program with suspected allergic contact dermatitis. The overall incidence of confirmed sensitization was less than 1%. Sensitization can occur, but the incidence is low.

Thanks Dr. Holmes,

Can you explain the difference between an allergic reaction and rebound which is what many are calling the experience they are having with Mirvaso? (See Post #1 above > Subheading - Positive and Negative Anecdotal Reports)

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Allergic reaction is a immune-mediated process which requires a previous contact of antigen presenting cells to the drug. This first contact shows no symptoms in the person, and it is known as sensibilization. Once one person is sensibilized, the second contact to the drug leads to a rapid reaction including rash, itchy eyes, swollen tongue, and even, anaphylactic reaction.

Rebound is a NON-immune-mediated process in which the symptoms are caused for the effect or the lack of effect (discontinuation) of a drug. This reaction is rather quickly, but no immune cells are implicated, in overall terms.

Hope my comments help you

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Allergic reaction is a immune-mediated process which requires a previous contact of antigen presenting cells to the drug. This first contact shows no symptoms in the person, and it is known as sensibilization. Once one person is sensibilized, the second contact to the drug leads to a rapid reaction including rash, itchy eyes, swollen tongue, and even, anaphylactic reaction.

Rebound is a NON-immune-mediated process in which the symptoms are caused for the effect or the lack of effect (discontinuation) of a drug. This reaction is rather quickly, but no immune cells are implicated, in overall terms.

Hope my comments help you

Thanks so much for clearing this up. Can I ask you to comment about the number of negative anecdotal reports that are initially being reported in other rosacea online groups that are listed in post #1 above and how there are relatively few positive reports. One thought is that those who have positive reports rarely post in online rosacea groups but negative posters will post their results. Just curious what your thoughts are on this topic.

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Dr. Andrea Towers of Miami has the following video showing how Mirvaso works. On the actual YouTube site are anecdotal reports (comments). Some of these reports I have used in Post #1 either negative or positive.

The Daily Buzz News Blurb on Mirvaso with Michelle Yarn:

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The following news blurbs follow the same pattern from a common news feed that may be a Public Relation's way to promote Mirvaso to the TV Stations. Notice the same woman being treated with Mirvaso is in both news blurbs.

KTVI TV news blurb, September 24, 2013, by Randi Naughton, interviews Madhavi Kandula, MD:

http://fox2now.com/2013/09/24/dr-kandula-new-rosacea-drug-approved-by-the-fda/

WWL TV New Orleans news blurb, October 18, 2013, by reporter Meg Farris who interviews Mary Lupo, MD on the subject of rosacea and the release of Mirvaso:

http://www.wwltv.com/news/health/Doctors-recommend-new-adult-acne-treatment-228237401.html

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Ambiguous Posts

(1) jaygee
"Wow is all I can say. I have that diffuse redness that is so hard to get rid of. I have been using makeup to cover up the redness and as a guy this is obviously tough. Yesterday I tried it but witnessed mild results. I had to go to work so I used make up to cover up. But today I used more than I did yesterday. I think when they say pea sized amount they really mean as big as a pea. Even when using thepea sized amount, I saw little difference at the 30 minute mark. However, for me at the 1 hour mark, I looked in the mirror and wow. I have not looked this way since I was 19 (I'm 24 now).
So yes, this works icon_smile.gif The key is to use enough. Hoping for no rebound. Feeling so happy" jaygee 26th September 2013 09:13 PM Post #325

"I'm a 24 year old male with persistent redness on cheeks and temples. I flush too. I use makeup to cover up the redness and that does an okay job. Anyways, I Got the drug a couple of weeks ago. I used pea sized amounts as directed on the first day and saw little change to my face if at all. Nothing like the "ghost" complexions that many people say they have experienced. The next day I tried putting more on and for whatever reason, this time the stuff worked well enough to notice a difference. Again, not "ghost-like" but a definite improvement. However, in about 5-6 hours the stuff wore off and the redness came back under my makeup which has never happened before. So I stopped using it for awhile. Now for the last week or so I have been using the very smallest amount, like hardly any but just a little on my face. I don't get any rebound, but to be honest I'm not sure if the results are there either. That's just the psychology of rosacea I think; it is sometimes difficult to know if something is actually working or not. jaygee 14th October 2013 Post #696

(2) Girl-in-DC
"I have used Mirvaso as prescribed for one week.
I find that it significantly reduces redness that I experience primarily on my cheeks, nose and forehead. Success!
But after 6 or 7 hours the flushing/burning/full face sunburn is a new sensation and unwelcome side effect. The BRIGHT red, hot to the touch face is uncomfortable and of course, extremely embarrassing. It lasts for several hours or until I reapply Mirvaso.

Is this a lasting effect? Will my body adjust to Mirvaso? Do all users experience this 7-hour sunburn or does it diminish over time?
I am trying to decide whether to give my body time to adjust to this drug, or whether I am making my rosacea worse." December 16, 2013 Post #136

(3) J. Rode

"I guess Im in that small percentage of people whose skin reacts negatively to this product. At first my face looks good but then within 3 hours I experience deep red flushing on my forehead, cheeks and chin (a butterfly) that is so intense it lasts all day and looks drastically worse than my mild rosacea. Ive applied it in the a.m. but will try applying it in the p.m. I don’t want to discontinue use until ive given the product a fair try. BTW, a small tube cost me $50 and the cap is not user friendly." March 15, 2014

(4) red11

"It works ok not as good as I thought! My cheeks still stay red not as bad as normal they are usually extreamly red anyway, defo get a bit of rebound flushing but flushing is the worst part for me anyway so it's hard to judge if its much worse or not. I would not pay full wack for mirvaso but being on prescription isn't quite as bad on the wallet." May 3, 2014

(5) Rosy Girl

"So far I’m very disappointed. Mirvaso is much more of a cosmetic than a treatment. It does take away surface redness, but as someone else pointed out this makes broken capillaries and acne scars appear more prominent. For me, the other problem is that in the morning my skin is worse than ever: more red, even in places I wasn’t red before, and broken out. My skin looks so bad I can’t go out in public … without using Mirvaso. It’s a vicious cycle. Would it work better if I stuck with it for a month? I’m not sure I’m wiling to wait that long. I’d rather work hard at soothing my skin so it looks “OK but not great” all the time." April 28, 2014

(6) Linda Linda, 55-64 Female on Treatment for less than 1 month (Patient)

"My Derm Dr gave me 2 tiny thimble tube samples. Told me to use it withOUT my make up so I could see the difference. I have really sensative skin and many of the products she has prescribed has been a waste of money. Using Mirvaso without my makeup was a mistake; my face was flaming RED :( I could feel it and was embarrassed! So I tried it one morning underneath my foundation having given it a chance to dry. By golly I think my face looked better and less red for a longer period of time. I'll never wear it without my makeup again unless I don't have to go to work or out in public. Had to see my Derm Dr a week later on another issue and asked for more Mirvaso samples. I want to be sure I like it before I spend the money to buy it. It is so new that my insurance company may not cover it. She told me the rep was really stingy with it. I gotta wonder how they expect someone to like their product and know it works with just 2 tiny thimble tubes of it. She gave me one more. So, so far it works underneath my foundation but I hope as with other reviews that it doesn't let me down. I'd hate to spend big bucks and still walk around with a flaming red face which would show half way through the day without Mirvaso which now I can go longer without the redness coming through so soon in the day. She gave me a $50 off coupon so I'm afraid this stuff may be more expensive than I can afford, but I may have to try one full prescription tube of it to be sure - it may be worth working a part-time job to use it! I'll keep y'all posted!" June 20, 2014

(7) MagnificenT

"Hello there.

I have been struggling with rosacea for several years now, if you would like to familiarize with my full story, it is here: http://www.rosaceagroup.org/The_Rosa...he-rosacean-me

In short, I ran out of possible treatment solutions, since even IPL and V-beam did not seem to have any effect. I learnt a couple of months ago about Mirvaso and I decided I would try it out as soon as it hits Europe, no matter what. I went through all opinions I could find and 90% of them were negative, so I prepared myself for another dramatic disappointment, but... This time it was different.

I suffer from diffused, permament and very noticeable redness on my cheeks, my forehead and chin are rather clean, so it stands out greatly. It gets worse when I do not cling to my diet. Plus, I react to all possible triggers (weather, heat, alcohol, spicy stuff, exercise, selected food, stress, I also get red when I am tired and when I don't sleep well, which is awkward).

Till now, I have been using Mirvaso for 10 days. I apply it in the very morning, the effect lasts about 8 hours. And it is incredible. The pictures below do not reflect the reality too well - in the *after* picture I still look pinkish, but in fact I am vampire pale, more like a sickly look from serious food poisioning. I did my best to take them in the same light and face position, with one hour difference.

One may think it is an ultimate solution (even though temporary), but Mirvaso has some drawbacks as well:

1. If I get exposed to sun with Mirvaso on, some weird things happen: I get random bumps and red patches which disappear when I walk out from the sun. So in summer Mirvaso is a big no-no, unless you stay inside all the time.

2. I cannot smoke with Mirvaso. I know it may seem hard to believe, but as soon as I smoke having it on my face, I get red. It might be a motivation to give up smoking, which is not so bad after all. Please note that without Mirvaso smoking has no effect on my skin colour.

3. My triggers still get me red, but only to a limited extent. I still cannot drink alcohol, exercise heavily etc.

4. Mirvaso does not make the pimples and imperfections pale. If you suffer from this type of rosacea, I believe it will not be a good solution for you. I had only one pimple when I tried it first, and it stood out greatly compared to my pale face.

5. Mirvaso does not give you any sense of confidence. In my case, it sometimes stops working after 5 hours, I get red for an hour, and it starts working again till late afternoon. I still have not figured out why it works like this.

I do not mix Mirvaso with any moisturizer, I use it only once per day. I wash my face gently only in the evening with mineral water and I apply Avene Antirougeurs for the night. In the morning, before applying Mirvaso, I only spray my face with thermal water and dry it with paper tissues after 5 seconds. That's my whole routine.

Overall, I would recommend Mirvaso to people who are fed up with looking for any ray of hope and who do not react to any treatment. I was lucky enough not to get major side effects like other people. I still use it with caution and reservation, it is only my second week. It does not make your face look normal, you will appear sick, with dark circles around your eyes, and all broken capillaries are visible, as they do not get constricted.

However, I would think twice before using it if you have a very photosensitive and delicate skin. It is actually a miracle it works for me, since I react badly to anything on my face, sometimes even water irritates me. I gave it a try since my redness couldn't be any worse (I assume) as you see in the pictures, so I didn't have much to risk." Post #1 on August 10, 2014

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An authority on this subject sent me this:

Rebound is a multifactorial effect. The two top reasons for a Mirvaso-induced rebound affect are:
1. The stimulation of Hypoxia-Inducible Factors from adjacent skin cells and from within the vascular smooth cell layer of the blood vessels - these are potent dilators that measure oxygen saturation in and around cells to ensure adequate oxygen delivery. Over constriction or hours of constriction can greatly deplete oxygen saturation and inadvertently stimulate very potent dilators.
2. Over time, alpha-1 and alpha-2 adrenoceptor stimulation increases the production of inducible nitric oxide, which is the primary inflammatory form of nitric oxide -- we see this a lot in Vascular Micro-Physiology and Pharmacology.
The other problem that patients will note over time is a decreased constrictor response (different from rebound dilation):
1. This is because overstimulation of alpha adrenoceptors results in downregulation of receptors (ie. they decrease in number on the vessel surface and internalize)
2. G-Proteins uncouple from active alpha adrenoceptors which blocks the signal cascade transduction -- which in turn -- blocks the ability of vessels to constrict
This is an oversimplification of a complex physiological process, but that is why it is always better to block a potent dilator than add an active constrictor.

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I asked Dr. Joseph Fowler who was one of the authors of a recent paper on this treatment the following and you can note his response which he gave me permission to copy and paste here:

Date: Fri, 13 Jun 2014 08:16:35 -1000
Subject: Question about Mirvaso Rebound Reports

Dr. Fowler,
 
Saw your name on the following abstract:

http://www.ncbi.nlm.nih.gov/pubmed/24918560?dopt=Abstract

 
Are you aware of the list of 213 anecdotal reports we have been collecting with rebound issues with using Mirvaso? Here is the list:
 
 
So far we have only collected 57 positive reports:
 
We have a post on Mirvaso here which you might want to comment on the rebound issue:
 
 
If you have any issues with logging into the above post, let me know so I can personally assist you. If you could just take 15 minutes and give a comment on the rebound issue we have reported hearing about that would benefit rosacea sufferers. Thanks.
 
Brady Barrows
RRDi Director
 
Dr. Fowler replied on June 16:
 

Dear Brady,

In the clinical trials that I am aware of, there were few if any reports of this "rebound" phenomenon occurring. Also, in the many patients that I have prescribed the drug for, I have had a few who felt Mirvaso did not work as well as they wished. But I have had only 1 patient have worsening of redness as the drug effect wears off. So while I'm sure there are some patients who don't like Mirvaso, the majority in my experience have had beneficial effects.

As I am sure you are aware, it is much more likely for someone to send in negative comments than to report in when they are satisfied with a product. Perhaps those who are experiencing unwanted effects haven't been initially counseled by the prescribing doc about appropriate usage and application techniques? perhaps other diagnoses instead of or in addition to rosacea are in the mix? Perhaps there are other reasons for less than optimal success being reported. At any rate, since the effect of topical brimo is very transient, I can't imagine any serious adverse effects and any "reaction" lasting more than a few days probably suggests something else is going on in the patient's skin. It is unfortunate that not all patients respond perfectly to this or any other drug, but from what I have seen it is a very valuable agent to combat erythema of rosacea.

Regards,
Joseph Fowler MD

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J Drugs Dermatol. 2014 Jul 1;13(7):821-6.

Optical coherence tomography imaging of erythematotelangiectatic rosacea during treatment with brimonidine topical gel 0.33%: a potential method for treatment outcome assessment.

Abstract
Background: Patients with moderate to severe rosacea often seek treatment to reduce erythema and vascular markings. Few studies have looked at the effectiveness of the novel treatment, brimonidine topical gel 0.33%, trademark name Mirvaso®, in the treatment of rosacea. We report the use of optical coherence tomography (OCT) scanning to monitor the effectiveness of Mirvaso® on in vivo skin. OCT is a non-invasive optical imaging technique that can provide high-resolution imaging of vessel and cellular morphology. OCT may be useful as a pre-treatment assessment tool for identifying possible morphologic features in the skin that may serve as outcome predictors. OCT may also serve as a monitoring tool in the treatment of rosacea.<br /> Objective: To examine and describe how OCT skin morphology changes when exposed to brimonidine topical gel 0.33% in the treatment of erythematotelangiectatic rosacea.<BR /> Methods: Normal in vivo telangiectasias and erythematous patches and papules were examined prior to treatment clinically, dermatoscopically, and through OCT scans. Brimonidine topical gel 0.33% was applied to the face and OCT images were acquired at defined time intervals: baseline; immediately (<5 minutes) after application; 4 hours after application; and after 2 weeks' once daily application. OCT morphology was then described.<BR /> Results: OCT imaging showed an increase in the mean gray value (MGV), a measure of dermal reflectivity, corresponding to a decrease in dermal edema. MGV measurements for the nasal telangiectasia were: baseline, MGV 10,471 (standard deviation [sD] 6,847); immediate, MGV 15,634 (SD 8,983); after 4 hours, MGV 16,357 (SD 7,647); and after 2 weeks, MGV 15,505 (SD 6,870). MGV measurements for the chin erythema were: baseline, MGV 8,850 (SD 4,969); immediate, MGV 10,799 (SD 5,266); after 4 hours, MGV 12,419 (SD 6,714); and after 2 weeks, MGV 13,395 (SD 6,170). No significant change in vessel lumen diameter was appreciated. Vessel lumen diameter for the facial papule ranged from 0.13 mm at baseline, 0.09 mm immediately after treatment, 0.09 mm after 4 hours, and 0.11 mm after 2 weeks.<BR /> Conclusions: OCT scanning showed a decrease in the dermal hyporeflectivity of the dermis consistent with a decrease in dermal edema. The OCT scans obtained did not show any significant change in vessel lumen diameter. These results may reflect an increase in vascular tone, which can be attributable to the clinical improvement and decreased erythema noted in the patient. This technology could potentially be used for the non-invasive in vivo monitoring of other topical treatments.J Drugs Dermatol. 2014;13(7):821-826.

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Could we get the last post in laymen's terms? I just spot-tested Mirvaso yesterday and was throughly impressed (no noticable rebound!)

However, I'm nervous about going all in for a couple days as I've heard that is when it becomes the worst.

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Mister Twiggy,

I had the same reaction to this report, what are they saying anyway? Wish one of the MAC members would explain, but they are very busy and I don't want to waste their time on such a question. My overall feeling is that this report says Mirvaso is positive, especially the sentence that includes the following:

"the clinical improvement and decreased erythema noted in the patient"

Keep us informed of your experience. Appreciate you posting in this thread especially.

BB

Could we get the last post in laymen's terms? I just spot-tested Mirvaso yesterday and was throughly impressed (no noticable rebound!)

However, I'm nervous about going all in for a couple days as I've heard that is when it becomes the worst.

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A study was released today published by the JEADV in its July issue that reports brimonidine tartrate (BT) 0.5% gel "subjects achieved a clinically meaningful improvement in both CEA and PSA scales were more likely to report satisfaction with the overall appearance of their skin (P < 0.001)." No mention of rebound in the abstract.

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Anecdotal Reports Collected into Two Spreadsheets

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. You should be aware that it is rarely possible to validate anecdotal reports. Most users hide behind a display name so there is no way to know who is actually posting which means that the same user could be posting as different or multiple posters. The other issue with anecdotal reports is that any report could be totally false and is a ruse to sway user opinion. However, the reason rosacea sufferers use display names is for privacy and some of these reports may be authentic, useful or helpful. The anecdotal posts contained in this thread on Mirvaso (Posts #2, #3 and #4 in this thread above cannot be verified) if any are posted by RRDi Members can be confirmed if necessary by the RRDi administration by contacting the member if the member chooses to confirm the report. However, the anecdotal reports collected from different sources from various internet sites not associated with the RRDi are now in two spreadsheets for positive and negative. Just click on the link in the last column of the spreadsheet to view the sources of the report. After Post #5, in this thread, there may be some members of the RRDi who may actually post a Mirvaso experience. So far members of the RRDi have not posted one Mirvaso experience. The RRDi can validate all posts from Post #5 on, since these reports can be confirmed because we have names and addresses of the poster and their IP address. Due to our privacy policy we are not allowed to reveal the identities of any RRDi member who posts, but we can validate the person exists and can follow up on the individual who reports a Mirvaso experience by email, postal address or telephone (if they choose to reply back). Each anecdotal report mentioned in the the spreadsheets below has a link with the number of reports under Postive or Negative which shows the source of the report at the end column in the spreadsheet. So you have been duly informed about the following anecdotal reports which we have collected and are now listed in detail in spreadsheets as either positive or negative:

Positive

Negative

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The following was received from one of the RRDi MAC Members:

Dear Colleages,

Since Mirvaso was lanched in my country (Spain), I have observed poor impact on my clinical practice: This drug is targeted to reduce erythema on rosácea (Flushing) with many researches supporting its efectivity. However, most of my patients suffering from rosacea do not complain on flushing, but permanent redness for which brimonidine gel is not indicated. This reduces dramatically the prescription of this drug on my daily clinical practice.
I have discussed this matter with my local colleages and they have found the same limitation in this way.
What's your opinion about?

Regards,
Husein Husein-ElAhmed MD

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