Rosacea Support Group » doxycycline

The BEST Treatment for Rosacea

David Pascoe — Tue, 19 Apr 2011 10:45:26 +0000

Once you have been diagnosed with rosacea, everyone naturally wants to know What is the best treatment for rosacea?

Wouldn’t it be great if there was a simple answer to this question that satisfied everyone who has rosacea!

Hopefully it doesn’t come as a surprise to find out that there is no known panacea for rosacea.

This high level paper from The Journal of Family Practice seeks to summarise the available published research into rosacea treatments. Thus the treatments being labelled `best’ by this study are only ever going to be the ones that have been proven by years of research and development and real life testing.

What I’m trying to warm you up to is the idea that you should only ever expect to see the well known prescription topical and systemic treatments emerge from these sorts of studies.

Clinical Inquiries: What is the most effective treatment for acne rosacea?

J Fam Pract. 2011 Feb;60(2):108a-c., May D, Kelsberg G, Safranek S.

Topical metronidazole and azelaic acid are equally effective for the papulopustular lesions of acne rosacea, although metronidazole is better tolerated. Oral doxycycline, tetracycline, and metronidazole are also effective, but not enough evidence exists to determine whether one is more effective than another or more effective than topical therapy (strength of recommendation [SOR]: A, systematic review and individual randomized controlled trials [RCTs]).

Some evidence supports a benefit for topical sodium sulfacetamide with sulfur, and benzoyl peroxide (SOR: B, small single RCTs).

Pulsed-light and laser therapy may improve the erythema and telangiectasias associated with acne rosacea (SOR: C, case series).

All patients with acne rosacea should use sunscreen and emollients, and avoid skin irritants (SOR: C, expert opinion)

Recommendations

The American Acne and Rosacea Society guidelines state that good evidence supports topical treatments—metronidazole,
azelaic acid, and sulfacetamide/sulfur—as well as anti-inflammatory doses of oral doxycycline.

The guidelines also list other topical and oral antibiotic treatments, but cite low-quality evidence for their efficacy and concerns about the emergence of antibiotic resistance. They advise appropriate skin care, including gentle cleansers, moisturizers, and sun protection.

Full Article PDF: What is the most effective treatment for acne rosacea?

Best Topical Therapy

Topical Metronidazole (Metrogel) and Azelaic Acid (Finacea) are indicated as being better than placebo, but “the studies
were generally weak because of poor methodology and reporting, small sample sizes, and lack of quality-of-life measures.”

Overall Metrogel is better tolerated than Finacea.

Best Systemic Therapy

Oral Metronidazole (Flagyl) and Oral Tetracycline as well as anti-inflammatory dose oral doxycycline (Periostat/Oracea) have been found to be effective.

Best Therapy for Redness

The best therapy for redness and broken blood vessels was found to be pulsed light therapy, laser therapy and photodynamic therapy with red light. No great surprises there.

Other Tips

“They advise appropriate skin care, including gentle cleansers, moisturizers and sun protection”. That is good advice we should all heed.

Can YOU Answer This Question?

Perhaps this paper won’t happily satisfy everyone’s quest for rosacea relief, but maybe you can.

You meet a newly diagnosed rosacea sufferer who is distressed. You have memories of being there yourself. What advice will you give them – what do you think is the best treatment for rosacea?

Cutis posts Oracea Phase 4 (ORCA) papers for free online

David Pascoe — Tue, 18 Jan 2011 10:45:03 +0000

Late last year Galderma generated quite a lot of publicity in the lead up to the release of the Phase 4 trials of Oracea.

Phase IV trials typically try to replicate the efficacy and safety of drugs seen in Phase III trials, but on a much larger scale. Phase IV trials are conducted after a drug is already generally available. Physicians typically use the Phase IV results to build confidence in prescribing a particular medicine.

The ORCA study was able to confirm that the majority of sufferers of the papules and pustules of rosacea were clear or near-clear after 12 weeks of being on Oracea. The redness associated with the rosacea lesions was also similarly reduced after 12 weeks.

Now, The journal Cutis has posted the papers that describe the details of the Oracea Phase 4 trial online. You can read the full text of these papers online for free.

The supplement contains the 3 papers listed below and an introduction. Download the PDF for the full details.

The ORCA (Oracea for Rosacea: A Community-Based Assessment) Trial: A Large-Scale, Phase 4 Trial in Papulopustular Rosacea

VOL. 86 NO. 5S[i] NOVEMBER 2010

An Open-Label, Community-Based, 12-Week Assessment of the Effectiveness and Safety of Monotherapy With Doxycycline 40 mg
(30-mg Immediate-Release and 10-mg Delayed-Release Beads), Guy F. Webster, MD, PhD

Rosacea is a common inflammatory disorder of the skin of middle-aged and older adults. A unique 40-mg formulation of doxycycline (30-mg immediate-release and 10-mg delayed-release beads) developed for its anti-inflammatory properties is the only US Food and Drug Administration–approved oral medication for the disorder.
This report describes the results of the Oracea for Rosacea: A Community-Based Assessment (ORCA) trial, a phase 4 trial of the 40-mg formulation as monotherapy in adults with mild to severe papulopustular rosacea. A total of 1197 participants were enrolled in the monotherapy arm of the 12-week open-label study at 271 community-based investigational sites.

The primary outcome measure was a change in the 5-point investigator global assessment (IGA) score from baseline to end point (week 12). Secondary outcome measures included change in the 5-point clinician erythema assessment (CEA) score from baseline to end point, IGA success, and adverse events (AEs).

The monotherapy per-protocol (PP) population was selected a priori as the primary analysis population and safety assessments were performed on all participants who received at least 1 dose of the study drug. In the PP population of 826 monotherapy participants who completed the trial, approximately 75% of participants with mild to severe rosacea at baseline were clear or near clear by week 12 according to IGA scores.

Furthermore, approximately 75% of participants had CEA scores reflecting none or mild erythema after 12 weeks. In the safety population of 1196 participants, treatment-related AEs were reported in 6.7% of participants that were mainly mild or moderate in severity.

Adverse events that occurred in more than 1% of the safety population included diarrhoea (1.2%), nausea (1.3%), and headache (1.0%). The incidence of fungal and yeast infections was 0.4%. The results of the ORCA trial support the effectiveness and safety of the 40-mg formulation of doxycycline in patients with papulopustular rosacea.

Effectiveness and Safety of Doxycycline 40 mg (30-mg Immediate-Release and 10-mg Delayed-Release Beads) Once Daily as Add-on Therapy to Existing Topical Regimens for the Treatment of Papulopustular Rosacea: Results From a Community-Based Trial, James Q. Del Rosso, DO

Rosacea is a prevalent inflammatory skin disorder that affects approximately 16 million individuals in the United States. Although its exact etiology is unknown, basic science, histologic evidence, and clinical evidence suggest that it is inflammatory in nature.

In this 12-week, open-label, multicenter, community-based, phase 4 trial, we evaluated the anti-inflammatory effects of once daily subantimicrobial-dose doxycycline 40 mg (30-mg immediate-release and 10-mg delayed release beads) in participants with papulopustular rosacea (PPR) who were receiving topical therapy (metronidazole, azelaic acid, and/or sodium sulfacetamide–sulfur) at the time of the study entry but whose rosacea symptoms were still present.

The primary outcome measure was the change in the investigator global assessment (IGA) score from baseline to end of study (week 12). Secondary outcome measures were changes from baseline to end of study in the clinician erythema assessment (CEA) score, treatment responders (IGA score of clear, near clear), and safety.
After week 12, 75.7% of participants in the per-protocol (PP) population had IGA scores of clear or near clear. In addition, there were significant differences in the distribution of baseline and week 12 IGA scores in the PP group (P=.0012). At week 12, most participants (63.6%) had mild CEA scores; the distribution was significantly different from baseline (P=.0407). Only 7% of participants had treatment-related adverse events (AEs), mostly mild or moderate in severity.

Thus the 40-mg formulation of doxycycline proved to be effective and well-tolerated in a real-world setting in participants with rosacea who were receiving topical therapy but still experiencing symptoms.

A Community-Based Study of the Effectiveness of Doxycycline 40 mg (30-mg Immediate-Release and 10-mg Delayed-Release Beads) on Quality of Life and Satisfaction With Treatment in Participants With Rosacea, Hilary E. Baldwin, MD

Changes to the skin of the face in patients with rosacea have the potential to substantially impair multiple domains of quality of life (QOL); however, the number of publications providing evidence for this topic is limited.

This 12-week, open-label, community-based, phase 4 trial of 1421 participants is the largest study of the disease to date. It explores the effects of mild to severe rosacea and its treatment on QOL.

Participants were treated with doxycycline 40 mg (30-mg immediate-release and 10-mg delayed-release beads) as monotherapy or add-on treatment to existing topical therapy. This article examines QOL issues in the primary analysis population consisting of 966 participants who completed the trial without a major protocol violation. Quality of life was assessed at baseline and study end (week 12) with the RosaQoL , a validated 21 -question instrument.

Participant and investigator satisfaction with treatment also were evaluated. In the monotherapy group, the mean RosaQoL score was 3.3 at baseline and 2.8 at end of study. In the add-on therapy group, the mean RosaQoL score was 3.2 at baseline and 2.8 at end of study. The improvement in QOL was both clinically and statistically significant (P=.0001) and was similar in both monotherapy and add-on therapy groups.

Most participants expressed satisfaction with treatment and approximately 90% of the community-based investigators reported that they were likely or very likely to continue prescribing this formulation. The study demonstrates that the impaired QOL in patients with rosacea can be substantially improved during a 3-month period by once-daily treatment with the anti-inflammatory activity of subantimicrobial-dose doxycycline

Supported by an educational grant from Galderma Laboratories, L.P. It seems reasonable to me that because this research is funded externally to the journal, the full text of the papers can be made available for free.

The Elephant in the room

Whilst this data confirms that Oracea can continue as a mainstream rosacea treatment, the spectre of the impending availability of generic Oracea also hangs over this product’s long term profit making ability.

Doxycycline is as good as Low Dose Accutane (0.3mg/kg/day)

David Pascoe — Wed, 15 Dec 2010 10:45:07 +0000

This study as described in a AAD Poster Session, compared 3 different doses of isotretinoin/accutane with a somewhat standard low dose regime of doxycyline.

The study was able to show that 0.3mg/kg/day of accutane was as effective as 100mg of Doxycycline for 14 days; followed by 50mg a day thereafter.

A dose of accutane of 0.3mg/kg/day is 18mg per day for a 60kg person (132 pounds).

There are other studies for low dose accutane that used doses more like the the very low 0.1mg/kg/day also examined in this trial.

The standard therapy with oral antibiotics for rosacea is described here as 100mg a day of doxycycline for 14 days and then the sub-antimicrobial dose of 50mg a day thereafter. Oracea is a similar low dose doxycycline, comprising a daily treatment of 30mg plus 10mg delayed release.

My Take

Whilst this study was able to show that around 20mg a day of accutane compared favorably to 100/50mg of doxycyline, because of the higher safety concerns with accutane, I would think doxycycline would win in most clinical situations. If you are getting a benefit from a low dose of doxycycline, seek thorough advice before considering switching to accutane.

J Am Acad Dermatol 2009;60:AB41. Abstract P1162

http://www.aad.org/meetings/annual/_doc/JaadPosterAbstractSupplement.pdf

Double-blind, double-dummy, randomized, placebo-controlled, ﬁve armed, multicenter phase II/III study to evaluate the efﬁcacy and safety of different concentrations of isotretinoin versus doxycycline in the treatment of rosacea, subtype II and III

Harald Gollnick, University Magdeburg, Magdeburg, Sachsen-Anhalt, Germany, Carmen Matthies, Almirall Hermal GmbH, Reinbek, Schleswig-Holstein, Germany, Renate von der Weth, Almirall Hermal GmbH, Reinbek, SchleswigHolstein, Germany

A double-blind, randomized, placebo-controlled, ﬁve-armed, multicenter study including 573 patients with rosacea subtypes II and III in 35 centers in Germany was performed to evaluate the efﬁcacy and safety of different concentrations of isotretinoin in the treatment of rosacea. Patients were treated in a randomized assignment either with one of three different doses of isotretinoin (0.1, 0.3, or 0.5 mg/kg body weight), with standard therapy with oral antibiotics (100 mg doxycycline daily for 14 days, then reduction to 50 mg daily), or with placebo.

As the primary objective, the reduction in the total sum of facial papules and pustules/noduli after a 12-week treatment was compared between the treatment groups.

In an interim analysis after about 45 patients per group had been treated, all three isotretinoin doses showed a clearly higher reduction of lesions compared to placebo, whereas treatment with 0.3 mg/kg showed the clearest reduction of lesions with a statistically signiﬁcant superiority versus placebo (P < .005).

In the second part of the study, the efficacy of the most efficient isotretinoin dose (0.3 mg/kg) was compared to standard therapy with doxycycline, and the other arms of the study were closed. Treatment with isotretinoin 0.3 mg/kg showed statistically significant non inferiority versus treatment with doxycycline (P < .001).

With isotretinoin 0.3 mg/kg, lesions were reduced for 90% compared to 83% with doxycycline treatment. Physicians diagnosed complete remission in 24% and marked improvement in further 57% of the patients with isotretinoin treatment, versus remission in 14% and marked improvement in 55% of the patients treated with doxycycline. Seventy-eight per cent of the patients treated with isotretinoin rated therapy success as ‘‘excellent’’ or ‘‘good,’’ compared to 64% of the patients treated with doxycycline.

Data on drug safety reveal a similar safety profile for the treatment of rosacea with isotretinoin 0.3 mg/kg as with treatment of acne with isotretinoin. No new, severe safety concerns were found; only an increase of cholesterol occurred slightly more often (in 19% of patients) than in acne treatment. Clinically relevant changes in blood count did not occur in any patient. Because of the low dose, isotretinoin has a positive risk/benefit profile for the treatment of rosacea.

Isotretinoin 0.3 mg/kg is an efficient and well tolerated treatment for rosacea subtypes II and III and can be used as an alternative to standard therapy with oral antibiotics.

Commercial support: The study was sponsored by Laboratories Almirall, S.A.

Accutane Dose 22mg a day compares well to low doses of Doxycycline

David Pascoe — Tue, 20 Apr 2010 10:45:39 +0000

A paper that Rosacea News previewed in November last year: Accutane dose of 22mg a day works best: EADV has now been published in the JDDG: Journal of German Society of Dermatology.

As we learned from the EADV paper, the Spanish pharmaceutical company Almirall is hoping to promote their “branded version of isotretinoin in the treatment of rosacea.” It seems like a bold move; to attempt to market oral isotretinoin as an alternative to oral antibiotics.

For those enrolled in this blind study, 0.3 mg/kg per day was found to be as effective as 50mg a day of doxycycline at treating the papules, pustules and phymatous growth of rosacea.

Getting the dose right is important if you want to try Isotretinoin as a treatment for your troublesome rosacea. How do you know if you are taking too much ? A high dose of accutane can lead to unpleasant side effects and even worsen the flushing associated with rosacea.

If you consider an average weight of 166 pounds (around 75kg) this paper would lead to a recommended dosage of around 22mg a day. Even this amount may be viewed as moderate to high when compared to advice from Dr. Plewig that “doses of isotretinoin typically used in the United States and Europe are far too high. For many patients, as little as 2.5 mg twice a week, which he describes as `a drop of rain on a dusty road’ is adequate.”

For more information see what accutane dose works for rosacea ?

Systemic isotretinoin in the treatment of rosacea – doxycycline- and placebo-controlled, randomized clinical study. J Dtsch Dermatol Ges. 2010 Mar 12.

Authors: Gollnick H, Blume-Peytavi U, Szabó EL, Meyer KG, Hauptmann P, Popp G, Sebastian M, Zwingers T, Willers C, von der Weth R

Summary Background: Systemic isotretinoin has been known for decades to be effective in the treatment of severe forms of rosacea, but it must be used off-label because of the lack of evidence-based data.

Patients and Methods: 573 patients with rosacea subtype II and III received one of three different dosages of isotretinoin (0.1 mg, 0.3 mg, or 0.5 mg per kg body weight), doxycycline (100 mg daily for 14 days, then 50 mg daily) or placebo in a double-blinded, randomized way for 12 weeks in 35 German centers.

Results: Isotretinoin 0.3 mg/kg proved to be the most effective dose with significant superiority versus placebo. Isotretinoin 0.3 mg/kg showed also significant non-inferiority versus doxycycline with reduction of lesions of 90 % compared to 83 % with doxycycline. Investigators diagnosed complete remission in 24 % and marked improvement in further 57 % of patients with isotretinoin treatment, in contrast to remission in 14 % and marked improvement in 55 % of patients treated with doxycycline. Isotretinoin 0.3 mg/kg revealed a similar safety profile as for the treatment of acne. Isotretinoin 0.5 mg/kg showed more dermatitis facialis as compared to 0.3 mg/kg.

Conclusions: Isotretinoin 0.3 mg/kg is an effective and well-tolerated therapy option for the treatment of rosacea subtype II and III and can therefore be used successfully as an alternative to therapy with oral antibiotics.

Accutane Dose of 22mg a Day Works Best: EADV

David Pascoe — Wed, 18 Nov 2009 13:02:54 +0000

A summary from a the recent 18th Congress of the European Academy of Dermatology and Venereology has presented some findings relating to the most effect dosage of accutane to treat rosacea.

Accutane (Isotretinoin) has been successfully prescribed in low doses to treat rosacea, and especially the `lumps and bumps’ of rosacea that have not responded to other treatments.

Despite some good published papers that deal with treating rosacea with low doses of accutane, officially isotretinoin needs to be prescribed `off label’ for treating rosacea.

For those enrolled in this blind study, 0.3 mg/kg per day was found to be as effective as 50mg a day of doxycycline at treating the papules, pustules and phymatous growth of rosacea.

Dr. Erdogan et.al. suggested that “In our small group, using a daily dose of 10 mg of isotretinoin, we did not observe such adverse effects. Although we selected patients resistant to treatment with a long history of complaints, our results confirmed the efficacy of isotretinoin use, but whether remissions will continue after the cessation of treatment is not addressed by our study.”

Further, advice from Dr. Hofer suggests doses of around 3mg to 8mg in what he calls his continuous microdose regime are suitable for treating rosacea. In 2000, Palmer et al. showed that continuous microdose isotretinoin (CMI) treatment (0.04-0.11 mg/kg daily) was sufficient to control adult relapsing acne, but they mentioned that this is an unlicensed method administration.

This paper will hopefully give some weight to the argument that under controlled circumstances, in the right doses, and for the indicated rosacea symptoms, low dose accutane can be a viable treatment.

If indeed this research helps lead to accutane being available as an on-label prescription for rosacea sufferers, then that is good news especially for those desperate for relief from the recalcitrant lumps and bumps of rosacea.

Optimal Isotretinoin Dosing for Rosacea Identified

BERLIN (EGMN)–Isotretinoin could be headed for a new indication as a licensed treatment for rosacea.

The workhorse oral retinoid has been used off label to treat challenging cases of rosacea for more than 2 decades. However, Barcelona-based Almirall recently sponsored a successful multicenter randomized trial aimed at earning an indication from regulatory authorities for its branded version of isotretinoin in the treatment of rosacea, Dr. Harald Gollnick said at the annual congress of the European Academy of Dermatology and Venereology.

The double-blind, 12-week study involved 224 patients with the papulopustular or phymatous forms of rosacea. Participants in the five-armed trial were randomized to isotretinoin at 0.1, 0.3, or 0.5 mg/kg per day; doxycycline at 100 mg per day followed by 50 mg per day; or placebo, explained Dr. Gollnick, professor of dermatology at Otto-von-Guericke University, Magdeburg, Germany, and president of the European Board of Dermato-Venereology.

The optimal isotretinoin dose proved to be 0.3 mg/kg per day. Its efficacy was superior to placebo and similar to that of doxycycline, with both regimens achieving a 90% reduction in papules and pustules at 12 weeks, according to Dr. Gollnick, who is also chairman of the Global Alliance to Improve Outcomes in Acne, an international group of acne experts.

“That means in the near future we’ll most probably have an on-label indication for isotretinoin in rosacea,” he said.

Over the years isotretinoin has been used off label to treat rosacea, but the best dose was a matter of guesswork. The Almirall-sponsored trial is particularly welcome because it is the first formal study aimed at defining the optimal dose, added Dr. Gollnick.

The 0.3 mg/kg dose was associated with a low rate of side effects, consisting mainly of mild lipid changes and liver enzyme elevations. The 0.5 mg/kg dose wasn’t any more effective, and it produced more irritation and facial dermatitis. The 0.1 mg/kg dose, while significantly better than placebo, was less effective than 0.3 mg/kg.

Topical therapies for rosacea include 0.5%-2% metronidazole, azelaic acid, 0.025% tretinoin, and 2.5%-5% permethrin. Systemic treatments include metronidazole at 500 mg/day, minocycline at 50 mg/day, tetracyclines at 0.5-1.5 g/day, and a subantimicrobial formulation of doxycycline.

Over to You

What dose of accutane have you found to work best for you ?

Doryx + Applesauce, for Those Who Can’t Swallow Tablets

David Pascoe — Mon, 29 Jun 2009 15:28:47 +0000

If you have trouble swallowing tablets, here is an official FDA sanctioned tip. Open the tablet and sprinkle the delayed release pellets on to a spoonful of applesauce. This is a good option for anyone who finds swallowing the capsule difficult.

This advice is only given for the 100mg and 75mg delayed release formulations of doryx which contain specially coated pellets of doxycycline hyclate. A clinical trial confirmed that the absorption of doxycycline is comparable when the table is taken whole or sprinkled on applesauce, both with and without water.

From Daily Med, Current Medical Information, Doryx (doxycycline hyclate) Tablet, Delayed Release

DORYX Tablets contain specially coated pellets of doxycycline hyclate, a broad-spectrum antibiotic synthetically derived from oxytetracycline, in a delayed-release formulation for oral administration.

Sprinkling the Tablet on Applesauce

Doryx Tablets may also be administered by carefully breaking up the tablet and sprinkling the tablet contents (delayed release pellets) on a spoonful of applesauce. The delayed release pellets must not be crushed or damaged when breaking up the tablet. Any loss of pellets in the transfer would prevent using the dose. The applesauce/Doryx mixture should be swallowed immediately without chewing and may be followed by a glass of water if desired. The applesauce should not be hot, and it should be soft enough to be swallowed without chewing. In the event that a prepared dose of applesauce/Doryx tablet cannot be taken immediately, the mixture should be discarded and not stored for later use.

The FDA has also issued instructions on how to prepare 100mg tablets of doxycycline (in an emergency), for children and adults who cannot swallow pills. See Mixing Doxycycline Hyclate 100mg Tables with Food. This method crushes a tablet into 4 teaspoons of water and then combines this with 3 teaspoons of milk, or chocolate milk or chocolate pudding or apple juice + sugar.

100mg a day of Doxycycline is no better than Oracea

David Pascoe — Fri, 18 Jan 2008 02:05:33 +0000

Collagenex is reporting today that Oracea is equally effective as 100mg of doxycycline. This latest press release is a culmination of a trial that we have reported previously – oracea plus metrogel, better than 100mg doxycycline plus metrogel ? and also a 2007 SkinMed paper; maximum effective dose of doxycycline is 40mg a day.

The main point of the trial was to show that a dosage higher than Oracea’s 40mg a day, won’t result in a better decrease in papules and pustules, but may show side effects commonly associated with higher doses of antibiotics.

If Oracea is too costly to be a part of your rosacea regime, you should consider 50mg a day of generic doxycycline. This is likely to be a much cheaper alternative but also offer the same benefits as oracea.

A paper related to this press release was titled Anti-Inflammatory Dose Doxycycline (40 mg Controlled-Release) Confers Maximum Anti-Inflammatory Efficacy in Rosacea and had the following conclusion ;

Higher mg/kg doses led to higher plasma concentrations but did not lead to increased clinical efficacy. Anti-inflammatory dose doxycycline (40-mg controlled-release formulation) conferred peak anti-inflammatory efficacy in the treatment of rosacea.

From today’s Press Release:

Oracea is a patented, delayed release formulation of doxycycline, 40 mg, that is the only FDA-approved treatment for the papules and pustules associated with rosacea. Doxycycline at much higher doses is often prescribed off-label by dermatologists for the treatment of rosacea. The study demonstrated that the higher, antimicrobial dose does not provide a greater clinical benefit than the anti-inflammatory dose of 40 mg, controlled release. However, the higher dose was associated with a significantly higher incidence of adverse events.
…
In contrast, a clear difference was observed between the two treatment groups (Oracea vs. 100mg doxycycline) in the incidence of adverse events, primarily gastrointestinal reactions. Gastrointestinal adverse events, including nausea, vomiting, diarrhea and stomach discomfort, were observed in 26% of patients administered 100 mg of doxycycline versus only 5% in the Oracea group.
…
This study has demonstrated that, in patients with rosacea, increasing the daily dose of doxycycline to 100 mg does not lead to greater efficacy than Oracea, but has a much greater incidence of gastrointestinal side effects. In addition, Oracea’s onset of action was not different from the 100 mg doxycycline dose.”

Get Ready for Oracea for Treating Ocular Rosacea

David Pascoe — Wed, 12 Dec 2007 06:27:10 +0000

Thanks for the tip from Ben. A clinical trial listed for treating both facial and ocular rosacea with Oracea suggests that Oracea might soon be marketed directly as an ocular rosacea treatment.

This phase 2 trial’s purpose is to determine the safety and efficacy of sub-antimicrobial dose doxycycline in the treatment of patients who have both blepharitis and facial rosacea.

The trial is due to complete in July 2008. The conditions treated include Blepharitis, Meibomianitis & Dry Eye. Interestingly the trial participants will take either oracea or a placebo for a period of 84 days. This suggests that 3 months is a reasonable treatment period for Oracea.

We know that Collagenex holds up to 6 patents relating to Oracea. One of these patents, which was highlighted by Rosacea News in May 2006, covers treating ocular and facial rosacea at the same time with one treatment.

A survey from the NRS suggested that eye symptoms are often undiagnosed in rosacea sufferers. Additionally some sufferers of facial rosacea are only diagnosed when their opthamologist finds one of the related conditions such as blepharitis or meibomianitis.

Extending the marketing reach of Oracea to be a FDA approved treatment for ocular rosacea is another sign that Collagenex are serious about growing the market for their products. Even though doxycycline is not new science, it is still a good thing if the revenues generated by Oracea can be re-invested in developing promising new-styled treatments like Sansrosa/COL-118.

Maximum Effective Dose of Doxycycline is 40mg a Day

David Pascoe — Mon, 10 Sep 2007 01:02:21 +0000

There has been a lot of copy written about so-called low dose or anti-inflammatory dose doxycycline. This form of antibiotic therapy is one of the more promising recent therapeutic developments ; it will likely become a widely known and available treatment.

This recently published paper shows that a daily dose of 40mg of doxycycline is as effective in reducing the lesions of rosacea as a higher dose of 100mg or 200mg a day.

Note that this is a statistical study using existing clinical trial data, and that the authors work for Collagenex, who were bought by Galderma. Galderma are the makers of Oracea.

Great Publicity Opportunity

This result is a great result for the marketability of Oracea – you don’t need to take a higher dose of doxycycline, just take Oracea – or so the story goes.

Anti-Inflammatory Dose Doxycycline (40 mg Controlled-Release) Confers Maximum Anti-Inflammatory Efficacy in Rosacea.

Skinmed. 2007 Sep-Oct;6(5):221-6., Theobald K, Bradshaw M, Leyden J., CollaGenex Pharmaceuticals Inc, Newtown, PA.

Background. Two large clinical trials have recently demonstrated the efficacy of a 40-mg controlled-release formulation of doxycycline in the treatment of rosacea, a dose well below the conventional level of 100 to 200 mg/d. Since no formal dose-response studies have been conducted, the authors analyzed phase 3 data to determine whether a dose-efficacy relationship exists.

Methods. Standard parametric regression analyses were used to estimate the correlations between dose (mg/kg body weight) and overall drug exposure (area under the curve [AUC]) in a phase 1 pharmacokinetic study and between dose and efficacy (mean change from baseline in total inflammatory lesion count at week 16) in 2 pooled phase 3 clinical efficacy studies. Additional regressions were run at each visit for the clinical efficacy studies to determine whether results differed across visits. A regression analysis was also performed in a subset of patients who showed a greater efficacy response.

Results. We found overall drug exposure (AUC) to have a highly significant correlation with dose (mg/kg) (r=0.49; P=.006). In contrast, clinical efficacy did not correlate with dose at any of the visits at week 3 (r=0.01; P=.85), week 6 (r=0.04; P=.53), week 12 (r<0.01; P=.98), and week 16 (r=0.03; P=.64) or among the subset of patients who showed greater clinical benefit.

Conclusions. Higher mg/kg doses led to higher plasma concentrations but did not lead to increased clinical efficacy. Anti-inflammatory dose doxycycline (40-mg controlled-release formulation) conferred peak anti-inflammatory efficacy in the treatment of rosacea.

Related Articles:

Oracea plus Metrogel, Better than 100mg Doxycycline plus Metrogel ?

David Pascoe — Wed, 04 Jul 2007 09:24:32 +0000

A clinical trial, sponsored by CollaGenex, is recruiting patients to see how Oracea compares to doxycycline (100mg once a day) when combined with metrogel 1%.

We can see from a Collagenex annual report that COL-101 was the name for Periostat MR, which then became Oracea.

Safety and Efficacy Study to Compare Two Rosacea Treatment Regimens

Purpose: To compare the safety and efficacy of two treatment regimens: 1) COL-101 and metronidazole gel 1%; 2) Doxycycline hyclate 100 mg and metronidazole gel 1%

Official Title: A Clinical Trial to Determine the Effects of COL-101 Administered Once Daily With Metronidazole Topical Gel, 1% Versus Doxycycline Hyclate 100 mg Administered Once Daily With Metronidazole Topical Gel, 1% in Patients With Moderate to Severe Rosacea

This trial follows on from a 2005 paper that studied the combination of periostat and metrogel. That study concluded that combining sub antibiotic dose doxycycline with metrogel 0.75% was better than metrogel on its own.

Combining a systemic antibiotic with metronidazole has been the mainstay of rosacea treatment for several years. What we are seeing here is updates to studies since the introduction of oracea and metrogel 1%.