Jump to content
Acne.org
Search In
Find results that contain...
Find results in...

Recommended Posts

I have been using atralin to get rid of sunspots and hyperpigmentation caused from dermititis and the fungi picked up while living in the UK for 2 years that caused the worst outbreak in my life since puberty. I have been using the drug every night and am still totally clear with the exception of two small brown marks(clogged pores?) that have appeared around my beards hair follicules. Atralins website was shut down because of false marketing claims and manipulated data...I'm not expecting an IB at this point and I've had everyone from my dentist to coworkers ask how I keep everything so "perfect" and a few are also now on this drug too. I am wondering what this Coria/DOW Chemicals drug is actually doing in the long term even when the active ingredient is removed, especially after being forced to remove their entire marketing claims and is being "re-evaluated" by the FDA. Can other Atralin users that are over the age of 25+ tell me if its actually doing anything when ive had no IB and only shedding of skin that looks almost like lint, small flakes the size of a dot all over the face that is not noticible by anyone except when my glasses rub up against the ridge of my nose. I will admit this is the first topical drug for cosmetic purposes I have used that doesnt burn my face off at all and have had no side-effects except a slight itch/general discomfort towards the end of the day. I have never used a topical that actually smoothes the skin like this, brings back an even skin tone even when its triggered by an allergy or sulfates, and just generally makes it look like porcelin and not even a single spot...I dare say on the level of friends that have taken accutane and now want to hop onto this drug. The only thing that caused a huge flare up initially(just a red mess on both sides of my face "under" my skin that had small spots pop up and never really come to a head) was doxy that subsided after 3-4 months about 1 1/2 years ago to treat the infection and nystatin to get rid of the fungi. Anyway, here is the release from the feds.

DEPARTMENT OF HEALTH & HUMAN SERVICES - Public Health Service

Food and Drug Administration Silver Spring, MD 20993

Charity Abelardo

Acting Director, Regulatory Affairs

Dow Pharmaceutical Sciences, Inc.

1330 Redwood Way

Petaluma, CA 94954-1169

RE: NDA # 022070

AtralinTM (tretinoin) Gel, 0.05%

MA #70/89

The Office of Prescription Drug Promotion (OPDP) of the U.S. Food and Drug Administration

(FDA) has reviewed Dow Pharmaceutical Sciences, Inc.’s (Dow) direct-to-consumer website

and a professional detail aid (COR-137719-0610) submitted by Dow under cover of Form

FDA 2253 for its drug product, AtralinTM (tretinoin) Gel, 0.05% (Atralin Gel).1 The website

and detail aid are false or misleading because they make unsubstantiated claims, including

unsubstantiated superiority claims, overstate the efficacy of Atralin Gel, and omit material

facts and important risk information associated with the use of the product. Therefore, these

pieces misbrand Atralin Gel in violation of the Federal Food, Drug, and Cosmetic Act (FD&C

Act), 21 U.S.C. 352(a) & (n); 321(n). See 21 CFR 202.1(e)(5)(i),(iii); (e)(6)(i), (ii), (vii), (x);

(e)(7)(i).

Background

Below is the indication and summary of the most serious and most common risks associated

with the use of Atralin Gel.2

According to its FDA-approved product labeling (PI), Atralin Gel is indicated for topical

treatment of acne vulgaris.

Atralin Gel is associated with the following warnings and precautions: skin irritation, ultraviolet

light and environmental exposure, and use in patients with fish allergies. The most common

adverse reactions associated with Atralin Gel include dry skin, peeling/scaling/flaking skin,

skin burning sensation, and erythema.

1 Atralin Gel website at http://www.atralingel.com/ (last accessed October 18, 2011).

2 This information is for background purposes only and does not necessarily represent the risk information that should be included in the

promotional pieces cited in this letter.

Reference ID: 3097677

Charity Abelardo Page 2

Dow Pharmaceutical Sciences, Inc.

NDA # 022070/MA #70/89 Unsubstantiated Superiority/Unsubstantiated Claims

Promotional materials are misleading if they contain a drug comparison that represents or

suggests that a drug is safer or more effective than another drug, when this has not been

demonstrated by substantial evidence or substantial clinical experience.

The detail aid includes the following claims and presentations:

• “Advance to the head of the class”

• “Optimized tretinoin . . . .”

• “At” in the tradename circled and appearing to look like “A+”

• “Uniquely formulated for targeted delivery” along with claims of the purported benefits

of Atralin Gel’s micronized formulation

• “A smart combination for improved tolerability” along with claims of the purported

benefits of ingredients in Atralin Gel’s vehicle and an “A+” graphic

• “Superior delivery” along with a graph of in vitro data showing Atralin Gel with the

greatest mean cumulative level of tretinoin to the dermis at 24 hours compared to

Retin-A Micro® 0.1% gel and Retin-A Micro® 0.04% gel.”[3] A footnote to the graph

states, “In vitro data; clinical significance is unknown. Differences between products

were not statistically significant.”

These claims and presentations misleadingly suggest that Atralin’s formulation and its

purported greater delivery to the dermis result in superior safety and efficacy compared to

other tretinoin products. However, FDA is not aware of any substantial evidence from clinical

trials demonstrating that Atralin Gel 0.05% is more effective than another tretinoin product,

such as Retin-A Micro 0.1% or 0.04% gel. FDA is also not aware of substantial evidence

from adequate and well-controlled clinical trials of Atralin Gel versus another tretinoin product

of similar strength demonstrating that Atralin Gel is more tolerable. Although Atralin Gel

0.05% was associated with fewer adverse events in one clinical trial than Retin-A Micro 0.1%

gel, the strength of the Retin-A Micro was twice the strength of Atralin Gel in this trial.

Additionally, the trial failed to show that Atralin Gel’s efficacy was superior or non-inferior to

Retin-A Micro 0.1%, thus limiting the clinical relevance of the difference in adverse events.

Furthermore, we are unaware of evidence demonstrating that Atralin Gel has

pharmacological activity in the dermis, and there are no data to support that in vitro

percutaneous absorption data, as presented in the graph of comparative dermis levels at 24

hours, predict or correlate with comparative clinical efficacy. Moreover, in vitro percutaneous

absorption testing is conducted using healthy cadaver skin, animal skin, or a suitable

membrane. For topically administered drugs, disease state might affect drug penetration and

bioavailability. Due to the physiological difference between healthy and diseased skin, the in

vitro percutaneous absorption method is not adequate for assessing comparative in vivo

levels clinically at the dermis for different formulations. We note that the small footnote to the

presentation indicates that the clinical significance of the in vitro data is unknown and

differences between products were not statistically significant. However, this does not correct

the misleading impression.

3 Data on file, CORIA Laboratories.

Reference ID: 3097677

Charity Abelardo Page 3

Dow Pharmaceutical Sciences, Inc.

NDA # 022070/MA #70/89 The website makes the following claims (emphasis in original):

• “ATRALIN™ (tretinoin) Gel 0.05% is a prescription acne medication that is formulated

with a combination of moisturizing ingredients that you won’t find in any other

prescription acne treatment.” [ATRALINTM Gel homepage]

• “But unlike other acne medications, ATRALIN™ Gel is the only tretinoin formulation

that features a unique combination of ingredients that are known to moisturize and

hydrate skin.*” [Why ATRALINTM Gel is Right for You webpage]

• “ATRALIN™ Gel is formulated with a smart combination of ingredients that are known

to hydrate and moisturize skin.*” [ATRALINTM Gel for Teens webpage]

• “As we age, our skin loses moisture [4] and may be drier and more sensitive. You may

benefit from an acne treatment like ATRALIN™ (tretinoin) Gel 0.05% because it’s the

only tretinoin that offers a unique combination of ingredients that are known to

moisturize and hydrate skin.*” [ATRALINTM Gel for Adults webpage]

• “ATRALIN™ Gel contains a combination of ingredients that are known to moisturize

and hydrate skin* -making it more ideal for adult skin.” [ATRALINTM Gel for Adults

webpage]

*The contribution to efficacy of individual components has not been evaluated.

Similarly, the detail aid claims:

• “A smart combination for improved tolerability

• Sodium hyaluronate†

− Plays a role in moisturizing the stratum corneum due to its unique waterbinding

properties[5]

• Soluble collagen†‡

− Increases moisture content of the skin[6]

• Glycerin†

− Enhances the water-binding capacity of the stratum corneum[7]

†The contribution of individual components to efficacy has not been evaluated.

‡Soluble collagen comprises methylparaben, propylparaben, ethylparaben, butylparaben,

isobutylparaben, phenoxyethanol, fish collagen, and water.”

These claims misleadingly suggest that Atralin Gel is clinically superior to other tretinoin

formulations because the individual ingredients of Atralin Gel’s vehicle are purported to

provide specific clinical benefits, such as moisturizing and hydrating skin, when this has not

been demonstrated by substantial evidence or substantial clinical experience. Generally,

superiority claims must be supported by adequate and well-controlled head-to-head clinical

trials comparing appropriate doses and dose regimens of your drug and the comparator drug.

None of the references cited in the detail aid discuss adequate and well-controlled clinical

4 National Institute on Aging. Skin care and aging. www.niapublications.org. Accessed October 1, 2007.

5 Weindl G, Schaller M, Schafer-Korting M, Korting HC. Hyaluronic acid in the treatment and prevention of skin diseases; molecular, biological, pharmaceutical and clinical aspects. Skin Pharmacol Physiol. 2004;17(5):207-213.

6 Morganti P. Skin hydration. In: Magdassi S, Touitou E, eds. New Cosmetic Delivery Systems. New York, NY. Marcel Dekker, Inc;

1999:71-98.

7 Kraft JN, Lynde CW. Moisturizers: what they are and a practical approach to product selection. Skin Therapy Lett. 2005;10(5):1-8.

Reference ID: 3097677

Charity Abelardo Page 4

Dow Pharmaceutical Sciences, Inc.

NDA # 022070/MA #70/89 trials with Atralin Gel versus other tretinoin products in which clinical benefits of the individual

vehicle ingredients, including improved tolerability or efficacy, were demonstrated. In fact,

the references do not discuss Atralin Gel at all. In addition, the Description section of the PI

states, “the contribution to efficacy of individual components of the vehicle has not been

evaluated.” We note that this information is presented in the website and detail aid in

association with the claims; however, this does not mitigate the misleading impression.

Furthermore, according to the Adverse Reactions section of the PI, 16% of patients

experienced dry skin with Atralin Gel treatment and the Warnings and Precautions section of

the PI states, “Mild to moderate skin dryness may also be experienced; if so, use of an

appropriate moisturizer during the day may be helpful.”

Overstatement of Efficacy

Promotional materials are misleading if they represent or suggest that a drug is better or

more effective than has been demonstrated by substantial evidence or substantial clinical

experience.

The Why ATRALINTM Gel is Right for You webpage claims, “In fact, many dermatologists

prescribe a tretinoin because it works so well—even on tough acne. . . ” (underlined

emphasis added). This claim misleadingly suggests that the drug has been specifically

studied for the treatment of “tough” or severe acne in clinical trials, when this is not the case.

According to the Clinical Studies section of the PI, the safety and efficacy of Atralin Gel was

only studied in patients with mild to moderate acne vulgaris. Therefore, claims that suggest

that Atralin Gel has specifically demonstrated efficacy in treating severe acne are not

supported by substantial evidence.

The detail aid misleadingly overstates the efficacy of Atralin Gel by selectively presenting

more favorable lesion reduction data from the registration trials, while failing to include less

favorable Global Severity Score Success data, which measures overall acne severity and

was also a primary endpoint in the trials. Specifically, the detail aid claims that Atralin Gel

provides “Efficacy that makes a powerful impact.” This claim is followed by graphs showing a

36% versus 20% reduction in inflammatory lesions and a 41% versus 21% reduction in noninflammatory

lesions from baseline at week 12 for Atralin Gel and vehicle, respectively, in a

combined analysis of the registration trials. However, the presentation fails to report that

success based on the Global Severity Score was achieved by 21% and 23% of patients using

Atralin Gel versus 12% and 14% using vehicle in study 1 and study 2, respectively. 8 In the

absence of providing the Global Severity Score success data with this presentation, the detail

aid overstates the efficacy of the product.

Omission and Minimization of Risk Information

Promotional materials are misleading if they fail to reveal material facts with respect to

consequences that may result from the use of the drug as recommended or suggested by the

materials.

8 Success is defined as a score of 0 (clear) or 1 (very mild) for study 1 and a score of 0 or 1 with at least 2 grades reduction from baseline for

study 2.

Reference ID: 3097677

Charity Abelardo Page 5

Dow Pharmaceutical Sciences, Inc.

NDA # 022070/MA #70/89 The website makes the following claims:

• “ATRALIN™ Gel offers a low potential for irritation. Chances are you’ll stick with your

treatment if there’s less risk of irritation, which will help you get the best results.” [Why

ATRALINTM Gel is Right for You webpage]

• “ATRALIN™ Gel has a low potential for irritation.[9] This may help make your treatment

more tolerable as your acne is getting better.” [ATRALINTM Gel for Teens webpage]

• “ATRALIN™ Gel has low potential for irritation.[10] This may help you look better as

your acne is getting better.” [ATRALINTM Gel for Adults webpage]

• “The most common adverse reactions were mild to moderate irritation of the skin and

occurred during the first few weeks of treatment with ATRALIN™ Gel.” [ATRALINTM

Gel homepage, Why ATRALINTM Gel is Right for You, ATRALINTM Gel for Teens,

ATRALINTM Gel for Adults webpages, and detail aid ]

These specific pages within the website misleadingly minimize the risks of Atralin Gel by

implying that patients are likely to “stick” with their treatment because there is a “low

potential of skin irritation” associated with use of the drug, when this is not the case.

Furthermore, these webpages with the claims noted above, as well as the detail aid, also

omit material facts about the possible duration and/or severity of skin-related adverse

reactions and the potential need for discontinuation of the drug and therefore,

misleadingly suggest that Atralin Gel is safer than has been demonstrated by substantial

evidence or substantial clinical experience. These claims are particularly concerning

since the Warnings and Precautions section of the PI states that, "The skin of certain

individuals may become dry, red, or exfoliated while using Atralin Gel. If the degree of

irritation warrants, patients should be directed to temporarily reduce the amount or

frequency of application of the medication, discontinue use temporarily, or discontinue use

all together. . . .Tretinoin has been reported to cause severe irritation on eczematous or

sunburned skin. . . ." In addition, according to the Adverse Reactions section of the PI,

the most common adverse reactions (incidence > 5%) were dry skin (16% vs. 2%),

peeling/scaling/flaking skin (12% vs. 1%), skin burning sensation (8% vs. 2%), and

erythema (7% vs. <1%) in the Atralin Gel and vehicle groups, respectively. The Adverse

Reactions section of the PI also indicates that in some subjects the skin-related adverse

reactions persisted throughout the treatment period. Moreover, characterizing these

events as “mild to moderate irritation of the skin” fails to adequately communicate the

specific types of skin irritation associated with Atralin Gel, as described above.

Finally, the website and detail aid also completely omit the following important Warning and

Precaution regarding fish allergies: Atralin Gel contains soluble fish proteins and should be used with caution in

patients with known sensitivity or allergy to fish. Patients who develop pruritus or

urticaria should contact their health care provider.

9 Data on file, CORIA Laboratories, Ltd.

10 Data on file, CORIA Laboratories, Ltd.

Reference ID: 3097677

Charity Abelardo Page 6

Dow Pharmaceutical Sciences, Inc.

NDA # 022070/MA #70/89 Unsubstantiated Claims

The detail aid includes the following claims for Atralin Gel:

• “Uniquely formulated for targeted delivery”

• “Micronized tretinoin facilitates efficient delivery to the follicle*”

• “85% of tretinoin particles in Atralin Gel are <10 microns

− Follicular openings on the forehead can be as small as 11 microns[11]

• “Lipophilic tretinoin dissolves in sebum within the follicle

− Micronized tretinoin particles in Atralin Gel are small enough to easily enter

the follicular opening

− Fewer tretinoin particles may remain on the skin surface”

“*The clinical significance of micronization is unknown.”

These claims are accompanied by a schematic of Atralin Gel entering a follicle. The claims

and schematic misleadingly suggest that Atralin Gel’s micronized formulation confers a

beneficial effect on product safety and/or efficacy by enabling the majority of tretinoin

particles to enter follicles, when this has not been demonstrated by substantial evidence or

substantial clinical experience. Furthermore, the cited reference does not provide any

evidence that tretinoin, whether micronized or non-micronized, enters hair follicles. In fact,

according to the PI, the exact mode of action of tretinoin is unknown. The cited reference

discusses hair follicle density and size in different regions of the body, but contains no data

with tretinoin addressing penetration into follicles or the effect of particle size on follicular drug

absorption. Additionally, the reference provides information on hair follicle orifice size in

healthy skin. There is no information on hair follicle orifice size in diseased skin, specifically

skin with acne vulgaris. The disclaimer that, “The clinical significance of micronization is unknown” is not sufficient to correct the misleading impression created by the claims and

schematic.

The website makes the following claim (emphasis in original):

• “In a clinical study, the number of people who said they were dissatisfied by their self-appearance due to their facial acne was reduced by half after using

ATRALIN™ Gel for 12 weeks.” [12]

Share this post


Link to post
Share on other sites

this is so interesting! i used atralin for about a year with some improvement, but definitely not total improvement...so i've recently switched to retin-a .04. i used atralin in conjunction with aczone and duac and never noticed any negative side effects in terms of peeling/burning/etc...in fact, it may have actually made me more oily but i just assumed it wasn't strong enough for my stubborn clogged pores...will def ask my derm about this!

Share this post


Link to post
Share on other sites

Interesting. I started switching from diacneal to atralin almost a year ago, I think, and I am over 25 (31). I haven't had the great results that you have, although I have had essentially no irritation. I had an IB from the diacneal and was very slow to switch over the atralin, so I think that may have prevented an additional IB. I know my acne is hormonal b/c of location, etc, and it would have been nice to have results like you. I didn't read all that, I skimmed it, but what I did skim seems like there are issues with semantics as opposed to real risk ( I guess the fish allergy could qualify)? Unless I missed that part, LOL. I remember a substantial packet when I pick up my rx for this stuff. I figure any tretinoin is potentially risky and can cause irritation.

Share this post


Link to post
Share on other sites

The problem with Atralin is that the FDA reviewed the claims made by Coria/DOW Chems and claim that their entire marketing and study data was maniupulated and false, with the atralin gel actually showing no higher of a success rate than when used with the vessel alone. It drops to the same clearance level as when the tretinoin is removed and just the vessel(vehicle) was used in the patients that were pretty much given the placebo. The response from the company? Remove all marketing material from derms offices and shut down the website leaving only the prescribing information available.

Share this post


Link to post
Share on other sites

I used Atralin for about three months and saw no results. In fact, I think it made my skin as bad as it's ever been. I didn't have any irritation when I applied the product, but beyond that I don't think it did anything to help my complexion or fight acne.

Share this post


Link to post
Share on other sites

I used Atralin for about three months and saw no results. In fact, I think it made my skin as bad as it's ever been. I didn't have any irritation when I applied the product, but beyond that I don't think it did anything to help my complexion or fight acne.

Kinda second your opinion. The only consistent improvement was my forehead. My chin/mouth acne has gotten progressively worse and painful and i have begin to develop cyst on my jaw. What will the next step be for you?

Share this post


Link to post
Share on other sites
Kinda second your opinion. The only consistent improvement was my forehead. My chin/mouth acne has gotten progressively worse and painful and i have begin to develop cyst on my jaw. What will the next step be for you?

I used Atralin from late August '11 to early January '12. I stopped using it in early January '12 and I've been on Doxycycline since then. I'm pretty pleased with the results, but I know I can't stay it on forever.

Share this post


Link to post
Share on other sites

Hmmmm, wondering if I should switch to retin-a. I guess the original might be the best bet in this situation.

Share this post


Link to post
Share on other sites

Join the conversation

You can post now and register later. If you have an account, sign in now to post with your account.

Guest
Reply to this topic...

×   Pasted as rich text.   Paste as plain text instead

  Only 75 emoji are allowed.

×   Your link has been automatically embedded.   Display as a link instead

×   Your previous content has been restored.   Clear editor

×   You cannot paste images directly. Upload or insert images from URL.


  • Personalized Advice Quiz - All of Acne.org in just a few minutes

×