Rosacea Support Group » doxycycline

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 doxycycline 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 ocular oracea

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 make Oracea.

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%.

ocular rosacea, MMP8 and doryx

David Pascoe — Mon, 23 Jan 2006 02:37:00 +0000

Another paper confirming the importance of MMP and the inflammation found in ocular and facial rosacea. This follows up on another recent article suggesting that a diagnostic test for ocular rosacea could be based on the “high abundance of oligosaccharides in the tear fluid of patients with ocular rosacea”. MMPs have also been shown as important in the inflammatory pathway in other studies, see below.

Tear fluid levels of MMP-8 are elevated in ocular rosacea-treatment effect of oral doxycycline, Graefe’s Archive for Clinical and Experimental Ophthalmology, 2006 Jan 13;:1-6, Authors: Maatta M, Kari O, Tervahartiala T, Peltonen S, Kari M, Saari M, Sorsa T

BACKGROUND: Ocular rosacea (OcR) is a chronic inflammatory disease especially affecting lid margins. Previous studies have shown that it is accompanied by increased levels and activation of tear fluid gelatinases. Matrix metalloproteinase 8 (MMP-8; collagenase 2) levels and activation are commonly elevated in many inflammatory conditions. Therefore we studied here whether MMP-8 concentration and activation in tear fluid are increased also in OcR, and if an oral doxycycline regimen could rectify the situation.

METHODS: Tear fluid samples were collected from 22 OcR patients and 22 healthy controls. The OcR patients were then treated with an oral doxycycline regimen for 8 weeks and tear fluid samples collected again after 4 and 8 weeks. Conjunctival brush cytology and patients’ subjective symptoms were scored. MMP-8 concentrations in the tear fluid were assessed by immunofluorometric assay and the molecular forms and isoenzyme expression of MMP-8 were studied by Western immunoblotting.

RESULTS: The mean MMP-8 concentration was statistically significantly higher in OcR (156.8+/-207.4 mug/ml) than in the normal subjects (53.5+/-66.7 mug/ml) (P=0.036), but decreased to 79.2+/-141.6 mug/l and 53.6+/-75.2 mug/l after 4 and 8 weeks doxycycline treatment, respectively. There was a statistically significant difference between the untreated OcR and the MMP-8 results after 4 or 8 weeks of oral doxycycline (P=0.041 and 0.069, respectively) and the OcR patients experienced statistically significant relief of their subjective symptoms (P=0.0001) after the doxycycline regimen. Both the normal and OcR tear fluid contained the larger, 60-80 kDa highly- glycosylated polymorphonuclear leukocyte-type MMP-8 isoform in Western immunoblotting, but not the 45-55 kDa less glycosylated mesenchymal-type isoform. MMP-8 activation was in practice present only in the OcR samples, and was inhibited by oral doxycycline.

CONCLUSIONS: MMP-8 concentration and activation degree in tear fluid are increased in OcR, probably reflecting increased inflammatory activity. Doxycycline effectively reduces these pathologically excessive levels and activation of MMP-8, and relieves patients’ subjective symptoms

biaxin (clarithromycin) vs. vibramycin (doxycycline)

David Pascoe — Tue, 20 Dec 2005 02:50:00 +0000

Clarithromycin versus doxycycline in the treatment of rosacea.

International Journal of Dermatology, 1997 Dec;36(12):942-6. Torresani C, Pavesi A, Manara GC, Department of Dermatology, Parma University, Italy.

Forty patients with rosacea were entered into a study comparing clarithromycin with doxycycline in the systemic treatment of mild and severe rosacea.

Results: At the end of the treatment, the overall results provided evidence for a hight clarithromycin efficacy profile in comparison with doxycycline.

Discussion: The etiology and pathogenesis of rosacea are still unknown. The systemic drugs first used in the treatment of rosacea were tetracyclines. This was followed by the introduction of metronidazole. Both therapies achieve significant improvements of dermatosis in 80% to 90% of cases, and no statistically significant differences were observed between them.

The pharmacologic mechanisms of action of both metronidazole and tetracyclines have been widely investigated. The therapeutic activity of tetracyclines seems to be related to their anti-inflammatory efficacy.

Clarithromycin, a recently synthesized macrolide, has been proven to be able to penetrate in phagocytes in vitro. The present study reveals that clarithromycin is a powerful tool in the treatment of rosacea. It yields improvements which are significantly more consistent when compared with those obtained with doxycycline. In contrast with tetracyclines and metronidazole, clarithromycin is a very safe therapy inducing only occasional and slight side effects. This significantly increases patient compliance and is of particular interest when considering the long-term therapy required. The mechanism of action of the drug in dermatosis has not yet been established. It is conceivable that clarithromycin also has anti-inflammatory capabilities.

PubMed Extract (Full Article available from the Author.)

doxycycline and eye surface repair

David Pascoe — Mon, 17 Oct 2005 03:05:00 +0000

Doxycycline is a broad spectrum antibiotic that chelates metal ions and is frequently used as part of treatment of ocular surface diseases. Its therapeutic value has been attributed to an ability to inhibit matrix metalloproteinase activity and both matrix metalloproteinase and interleukin-1 synthesis. Smith and Cook studied corneal epithelial cell and keratocyte cultures and in this study they demonstrated that the minimum concentration of doxycycline required to inhibit the activities of corneal matrix metalloproteinase is similar to that required to inhibit these enzymes in other tissues. If this concentration is achievable in the tears of patients treated systemically for ocular surface disorders in addition to inhibiting matrix metalloproteinases that have been pathologically activated doxycycline may kill migratory keratocytes or fibroblasts responsible for the formation of scar tissue as well as promote complete coverage of the ocular surface with epithelial basal cells.

From BJO At A GlanceDOXYCYCLINE, DOES IT REPAIR OCULAR SURFACE?

Doxycycline—a role in ocular surface repairBritish Journal of Ophthalmology, 2004;88:619-625Keywords: interleukin-1; corneal epithelial cells; corneal keratocytes; doxycycline; matrix metalloproteinases

Background/aims: Doxycycline is a broad spectrum antibiotic that chelates metal ions and is frequently used as part of the treatment of ocular surface diseases. Its therapeutic value has been ascribed to an ability to inhibit matrix metalloproteinase (MMP) activity and both MMP and IL-1 synthesis. The aim of this study was to evaluate the role of doxycycline as an inhibitor of corneal MMPs and assess its contribution to ocular surface repair mechanisms.

Methods: Corneal epithelial cell and keratocyte cultures were grown to confluence and incubated with IL-1, LPS, doxycycline, or doxycycline and LPS in serum free medium for 4 days. The cells were either harvested and assayed for caspase-3 activity or stained with either AE5 or antivimentin antibodies. Media samples were concentrated and assayed for MMP activity by zymography or using a fluorigenic substrate. ELISA was used to quantify IL-1, MMPs -1,-2,-3,-9, and TIMPs -1 and -2.

Results: IL-1 and LPS had no effect on MMP/TIMP production by cultured corneal epithelial cells and keratocytes. Corneal MMP-2 inhibition by doxycycline was partially [Ca2+] dependent but irreversible. At the minimum inhibitory concentration, 100 µm, doxycycline had no apparent effect on MMP and TIMP production, but ultimately caused the death of keratocytes and some of the epithelial cells that detached from their basement membrane. Caspase-3 activity was not detected in dead or dying keratocytes. The mechanism of cell death in cultured corneal epithelial cells was not caspase-3 related apoptosis as the activity of this enzyme, normally detectable, was lost. The epithelial cells that survived doxycycline treatment did not bind antivimentin antibody and compared with controls, reacted less with the AE5 antibody. They were probably transient amplifying cells.

Conclusions: Doxycycline irreversibly inhibits corneal MMP-2 activity by chelating the metal ions that are catalytically and structurally essential. Corneal MMP/TIMP production in vitro is not modulated by IL-1, LPS, or doxycycline. The therapeutic value of doxycycline may depend upon its effective concentration at the ocular surface and probably relates to its chelating properties.