Rosacea Support Group » metrogel

The Wheels on the Bus Go Round and Round

David Pascoe — Tue, 27 Jul 2010 20:05:17 +0000

Just published in the June 2010 edition of the Journal of Drugs in Dermatology is a study comparing “Finacea in combination with Oracea” with “Metrogel in combination with Oracea”.

Seeing this abstract published makes me want to let out a loud groan.

So much of what we see as recently published rosacea research is just recycled sameness. The actual result of most of these self-similar papers is pretty minimal.

It really doesn’t help rosacea sufferers much to know that the many permutations of the popular and already understood treatments all perform the same.

So the wheels on the bus go round and round, but on this route, the bus never seems to actually get anywhere.

Here is just a sample of the published research showing where this research bus is heading;

This sort of research does provide good pharmaceutical marketing stories I guess and I suppose it justifies researchers’ efforts, but I am left wondering where this effort could be better utilised.

J Drugs Dermatol. 2010 Jun;9(6):607-13.

Efficacy of topical azelaic acid (AzA) gel 15% plus oral doxycycline 40 mg versus metronidazole gel 1% plus oral doxycycline 40 mg in mild-to-moderate papulopustular rosacea.

Del Rosso JQ, Bruce S, Jarratt M, Menter A, Staedtler G.

Rosacea is a leading reason why people seek the care of a dermatologist, accounting for nearly 7 million office visits annually. Pharmacologic treatments include both topical and oral medications, which are increasingly being used in combination, especially at the outset of therapy. This exploratory study assesses the safety, effectiveness and speed of onset of two common topical agents for the treatment of rosacea azelaic acid gel (AzA) 15% and metronidazole gel 1% used in conjunction with anti-inflammatory dose doxycycline (40 mg once daily). Men and women (n = 207) with mild-to-moderate papulopustular rosacea were enrolled and randomized to receive either AzA gel 15% twice daily plus doxycycline 40 mg once daily (AzA group) or metronidazole gel 1% once daily plus doxycycline 40 mg once daily (Metro group) for 12 weeks. Both regimens were safe, efficacious and well tolerated. Efficacy parameters revealed a possible trend toward greater and earlier benefit with the AzA-based regimen than with the metronidazole-based regimen. These findings warrant further investigation in a sufficiently powered study.

I’ll end this note with a comment that why, seriously, would this study encourage the creation of a more detailed study ?

Oracea and Metrogel FREE for low income no insurance

David Pascoe — Fri, 09 Apr 2010 10:44:29 +0000

Being prescription items, Oracea and Metrogel 1% are too expensive for many rosacea sufferers, even those with basic medical insurance.

Thanks to a tip from chenoarae; Oracea and Metrogel 1% are both available for free for residents of the US who don’t have insurance of any sort and are on a low income.

Some pharmaceutical companies offer a Patient Assistance Program (PAP) where they provide their products for free or for a much reduced rate to individuals or families who are under-insured or uninsured.

Thankfully for rosacea sufferers, Galderma offers such a program and generously includes both Metrogel 1% 60gm and Oracea 40mg.

Do I qualify ?

If there is just 1 person in your household, and your incoming including social security and pension benefits is less than $21,660 then you may qualify for the Patient Assistance Program. The income limit is $29,140 for a couple and $36,620 for a household of 3, $44,100 for a household of 4.

Further, the following additional requirements are applied;

Medicare Part D enrollees are not eligible.
Patient must not qualify/or must not be eligible for any private insurance prescription coverage such as an HMO or PPO.
Patient must not be enrolled in Medicare Part D, and must not qualify to any state/federal assistance with prescription medications.

The drugs are supplied only for the use of the patient, who has a medical need and cannot afford them. We are also told that they are not to be sold or traded.

How do I apply ?

The application form needs to be signed by your doctor and faxed to the Galderma PAP for each prescription fill.

Print the following form: Patient Assistance Program Enrollment Application and take it to your doctor to sign and fax along with the supporting documentation to Galderma in Chicago.

You may also like to include the PAP Physician Instructions for your doctor’s information.

Within 8 days of the application you will receive a prescription card that will enable you to pick up your prescription at any local pharmacy.

Are there other options ?

If you don’t qualify for this program you may find that generic metrogel or 50mg a day of generic doxycycline offer you similar benefits to the branded treatments at a much reduced cost.

Galderma also offers an Oracea and Metrogel 1% Coupon program it calls the Oracea Savings Card and Metrogel 1% Co-pay Card.

The Oracea Savings Card will allow you to co-pay as little as $15 a month or even a $0 co-payment. You will need comprehensive medical insurance for this option of course.

What is this mysterious Nycomed 0444 Gel ?

David Pascoe — Fri, 20 Nov 2009 12:31:10 +0000

The Clinical Trials register has listed a just completed trial for something cryptically called 0444 Gel. The Gel is targeted for the papules and pustules of rosacea. Apparently the study started in January 2008 and has just been completed.

Study of 0444 Gel in the Treatment of Inflammatory Lesions of Rosacea

Sponsor: Nycomed US Inc

The aim of this trial is to assess the efficacy of 0444 Gel in the Treatment of Inflammatory Lesions of Rosacea.

Treatment medication will be administered as follows: A thin film of gel will be applied and rubbed into the entire face once daily for a period of 70 days.

So what could this gel be ? As far as I can see, likely candidates include Solaraze as well as a new generic form of metrogel. These two classes of products are manufactured by companies related to or owned by Nycomed.

Solaraze

We learnt from a 2006 AAD Poster Session that Solaraze was being studied as a treatment for rosacea. SOLARAZE (diclofenac sodium-3%) Gel is indicated for the topical treatment of actinic keratoses (AKs).

SOLARAZE Gel is a registered trademarks of PharmaDerm, a Division of Nycomed US, Inc.

Solaraze is currently marketed in the US, Europe and Australia.

Generic Metrogel

Nycomed has a sister division Fougera Generics. A press release in 2005 alterted us to the fact that Fougera was poised to make generic metrogel 0.75%. Indeed you can find details on Fougera’s web site for Metronidazole Topical Lotion 0.75% (compares to MetroLotion) and Metronidazole Topical Cream 0.75% (compares to MetroCream).

Other Guesses

Any other guesses ? If you have more information about 0444 Gel please post in the comments below.

Top 5 Cheap Rosacea Treatments

David Pascoe — Thu, 29 Jan 2009 12:09:07 +0000

Distressed with the expense of exotic rosacea treatments ? The stress of rosacea is enough without also having to worry about how to afford treatments. Finding affordable rosacea treatments is a real challenge.

So here we go; my top 5 suggestions to help you find cheap rosacea treatments.

1. Make your own cleanser

Colloidal Oatmeal has promise as natural product because of it’s cleansing, moisturizing, buffering, soothing, protecting and anti-inflammatory properties.

While products like Linda Sy’s Mild Oatmeal Facial Cleanser and Aveeno Oatmeal Anti-Itch are not cheap recommendations, you should be able to source colloidal oatmeal easily from a health food store. Colloidal Oatmeal is defined as a product made from grinding and processing whole oat grain with strict requirements on the particle size and fat content. The small particle size and the way that it disperses in water means that when it deposits on the skin it forms an occlusive barrier.

Try mixing a small amount of Colloidal Oatmeal with warm water and lathering it on your face. Gently remove it with cool water.

See also the Homemade Mixes Forum and the Custom Topical Formulations resources page for more suggestions on making your own super cheap topicals.

2. Use generic prescriptions

Newer releases of antibiotics like Oracea and Solodyn can be extremely expensive, especially without medical insurance. One alternative is to discuss with your doctor the possibility of trying generic doxycycline instead.

Doses of 50mg a day of doxycycline will closely match the amount of active antibiotic in Oracea and Solodyn. Higher doses many also be of benefit until the inflammation of rosacea subsides. Generic doxycycline is far more affordable that these 2 newly released re-packaged antibiotics.

Another possibility is to ask your doctor about generic metronidazole. The patent for metrogel (the 0.75% version specifically) has expired so generic equivalents are now available in several countries around the world. For more information see generic metrogel.

3. Hunt for Bargain Suggestions

Many of the `regular’ treatments for rosacea such as systemic and topical antibiotics are quite expensive. Be on the hunt for things you can try that are more reasonably priced. Here are some suggestions

Prosacea: this can be sourced over the counter at places like Walgreens and Rite Aid for around $10. It seems to be an ok treatment for rosacea. Prosacea is based on a sulphur preparation.
Cetaphil Gentle Skin Cleanser and Cetaphil Moisturizing Cream or Lotion are two under-rated skincare products. They are cheap, mild and easily available. If you can incorporate these in to your daily skincare regime then you are off to a good start to cheaply caring for your rosacea skin.
Try to source a cheap zinc oxide based sunscreen. Some countries have cancer foundations that are good at providing affordable, simple sunscreens. You might be fortunate enough to find a low irritant formulation free of chemical sunscreens.

4. Manufacturer Rebates

Drug manufacturers recognise that their products can still be quite expensive by the time they get to the consumer. To try to mitigate this impost, rebates or coupons are sometimes offered.

A quick search revealed the following ; $10 Mail-In Rebate for Metrogel, and Save $10 on Finacea Instantly.

The very expensive Oracea also offers a Savings Card where you could save $25 per prescription for those without prescription insurance and help some insured patients pay no more than $25 per month. The similarly expensive Solodyn is also offering a $35 rebate.

One program that you may not be aware of is offered by Galderma. Galderma will provide Oracea and Metrogel FREE for low income and no insurance sufferers of rosacea.

While these manufacturer rebates come and go, keep an eye out for promotions offered by the manufacturers. Be aware of all the small print also as refunds can take many weeks to arrive, and promotions can be revoked at any time.

5. Ask for Physician Samples

When new drugs are being promoted, the sales team are desperate to find as many outlets as possible. This might mean that your doctor or specialist has drug samples just waiting to be handed out. Check with your local doctor’s surgery, and maybe even ring a few dermatologist to see if they ever get samples from the drug companys’ sales teams.

You might be lucky enough to find a good source for free samples. This is one asset that is worth trying to chase down and link up with.

Please Help

`Cheap’ and `Rosacea Treatment’ don’t often appear together in the same sentence. Treatments, especially prescription treatments that have been developed and marketed for rosacea sufferers are notoriously expensive – to the point of being unobtainable for many.

Do you have any recommendations for your fellow rosacea sufferers that are on a budget ?

NEW: Oracea and Metrogel FREE for low income no insurance
cetaphil gentle skin cleanser well tolerated
cetaphil moisturizing cream helps rosacea dry skin
Prosacea User Reviews
generic metrogel soon – Fougera
Rosacea Support Community: Homemade Mixes
RSRP: Custom Topical Formulations

metrogel also works for seborrheic dermatitis

David Pascoe — Tue, 13 May 2008 02:30:14 +0000

This paper found that 0.75% metrogel worked just as well as ketoconazole 2% cream in treating SD. The study found that both were able to offer significant improvement with similar side effects. The authors suggest that because there is so little evidence of anti fungal activity of metronidazole, it is difficult to speculate that this is the reason for its efficacy in treating SD. Patients with rosacea were excluded from this study, so there is a good finding here that even if you only suspect that you have seborrheic dermatitis, metrogel is a good opening treatment option.

Metronidazole 0.75% gel vs. ketoconazole 2% cream in the treatment of facial seborrheic dermatitis: a randomized, double-blind study, D Seckin, O Gurbuz, O Akin, JEADV, Volume 21 Issue 3 Page 345-350, March 2007.

Background: Recently, two placebo-controlled studies have shown that topical metronidazole was effective in the treatment of seborrheic dermatitis.

Objective: To compare the efficacy and safety of metronidazole 0.75% gel with that of ketoconazole 2% cream in the treatment of facial seborrheic dermatitis.

Methods: A total of 60 consecutive patients with facial seborrheic dermatitis were included. Patients were randomized into two groups. One group used ketoconazole 2% cream with metronidazole gel as vehicle; the other group used metronidazole 0.75% gel with ketoconazole cream as vehicle for a 4-week treatment period. Main outcome measures were change in clinical severity scores, patients’ and investigator’s global evaluation of improvement and frequency of side-effects.

Results: All the assessments were made by an investigator who was unaware of which group the patients were allocated to. Mean percentage decrease in clinical severity scores from baseline to last available visit was 63.4% (95% CI 57.7–69) and 54.4% (95% CI 47.9–61) in the ketoconazole- and metronidazoletreated patients, respectively (P = 0.31). Eighty-two per cent of patients in the ketoconazole group vs. 79% of patients in the metronidazole group rated their global improvement as significant or moderate (P > 0.05). No statistically significant difference in the frequency of side-effects was detected between the two groups. The results of this study need to be confirmed in further studies involving large numbers of patients.

Conclusion: Our data demonstrated that metronidazole 0.75% gel had a comparable efficacy and safety profile with that of ketoconazole 2% cream in the treatment of facial seborrheic dermatitis.

Galderma buys CollaGenex for $420m

David Pascoe — Tue, 26 Feb 2008 15:12:55 +0000

Collagenex is set to become a subsidiary of the much bigger Galderma, after CollaGenex agreed to a merger. So 2 of the biggest pharmaceutical companies involved with make rosacea treatments are to become the same company.

Galderma has long been associated with rosacea treatment, and is best known for the metronidazole based topicals metrogel, metrocream and metrolotion. CollaGenex has become known in recent years for their promotion of the oral rosacea treatment Oracea. Further, Collagenex is developing the Sansrosa technology as topical treatment for the redness and flushing of rosacea.

Galderma was formed in 1981 as a joint venture between Nestle and L’Oreal.

It seems like an excellent fit to me with both offering complimentary products. Additionally it is also good news for the creation of new rosacea treatments as the combined resources of the 2 companies can be targeted toward new products.

Read some further news coverage:

how metrogel works II – free oxygen radicals

David Pascoe — Tue, 04 Sep 2007 01:48:14 +0000

Another recently published paper that seeks to understand the role of Reactive Oxygen Species in the development of rosacea. The inflammatory pathway that leads to rosacea symptoms is slowly gaining more and more attention.

All rosacea sufferers should do themselves a favor and do some reading on the role of inflammation in rosacea. This is the most exciting direction for rosacea research, in my opinion. Though it can feel like you are reading a foreign language, I’d encourage everyone to stick at it.

More links at the bottom, but 2 places to start: Examining Inflammation as a Common Factor in Theories of Rosacea Pathophysiology (via Collagenex’s RosaceaToday info site) and Role of Inflammation (put together by Dan in the RSRP).

Even though there is a bit of a love hate relationship with the metronidazole based rosacea treatments, examining how it works is leading to some new and useful research.

Properties of metronidazole on free oxygen radicals in a skin lipid model system.

J Pharm Pharmacol. 2007 Aug; 59(8):1125-30, Authors: Narayanan S, Hunerbein A, Getie M, Jackel A, Neubert RH

Reactive oxygen species (ROS) play a vital role in the pathophysiology of the skin disease rosacea, a chronic, genetically-determined and UV-triggered disease, leading to facial redness and blemishes and exhibiting a deep impact on a patient’s self-esteem and quality of life. ROS can cause oxidative damage to nucleic acids, sugars, proteins and lipids, thereby contributing to adverse effects on the skin.

Metronidazole has been the first-line topical agent therapy for many years; nevertheless the mechanism of action is still not well understood. The therapeutic efficacy of metronidazole has been attributed to its antioxidant effects, which can involve two pathways: decreased generation of ROS within tissues or scavenging and inactivation of existing ROS. Previous investigations have shown that metronidazole reduces ROS by decreasing ROS production in cellular in-vitro systems. The aim of the following study was to demonstrate that metronidazole additionally exhibits antioxidative properties in a cell-free system, by acting as an antioxidant scavenger.

A simple skin lipid model (oxidative) system and a complex skin adapted lipid system in conjunction with thiobarbituric acid (TBA) test, a quantitative assay for the detection of malondialdehyde (MDA) and therefore lipid peroxidation, were used to determine the antioxidative properties of metronidazole after UV irradiation. Results clearly show that metronidazole has antioxidative properties in a cell-free environment, acting as a free radical scavenger. Simple skin lipid model: in the presence of 10, 100 and 500 mug mL(-1)metronidazole the MDA concentration was reduced by 25, 36 and 49%, respectively. Complex skin lipid system: in the presence of 100 and 500 mug mL(-1)metronidazole the MDA concentration was reduced by 19 and 34%, respectively.

The results obtained in this study and from previous publications strongly suggest that metronidazole exhibits antioxidative effects via two mechanisms: decrease in ROS production through modulation of neutrophil activity and decrease in ROS concentration by exhibiting ROS scavenging properties. The remarkable clinical efficacy of metronidazole in the treatment of rosacea is probably due to its ability to decrease ROS via different mechanisms, thereby protecting skin components from induced damage.

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%.

metrogel: how it gets into your skin

David Pascoe — Mon, 18 Jun 2007 05:22:00 +0000

Two recently published papers look at the processes involved when you apply metrogel topically. The first abstract just tells us that they undertook some new ways of measuring metronidazole absorption, but doesn’t reveal their results.

The second abstract suggests that a cream based metronidazole formulation (presumably metrocream, but could also include Noritate) had the greatest absorption when tested with human skin. They suggest that future research is needed to determine if indeed this makes any difference to rosacea symptoms.

Previously Rosacea News reported ;

metrogel, metrolotion, metrocream, noritate, once and twice per day – all the same same

“Despite quite a lot of activity in the marketing and development of the metronidazole treatments (lotion, cream, gel, generic equivalents, metrogel 1%, once per day, twice per day) this research suggests that the formulation and treatment frequency make little difference to the treatment outcome. So if you can tolerate one of the available formulations, there is likely marginal benefit from changing to another.”

Metronidazole based treatments do seem to attract a lot of research, maybe even too much research given the marginal improvement that many rosacea sufferers experience from the metro triplets. Imagine if the research poured in metronidazole was directed to new, leading edge treatments.

As background, from `measuring niacinamide (vitamin B3) moisturizer and skin barrier‘:

“Confocal Raman microspectroscopy (CRS), in contrast, is a new technique that combines the well attested method of Raman spectroscopy (the study of inelastic scattering of light, rather than its absorption) with confocal microscopy, allowing noninvasive, realtime, in vivo measures of molecular concentration profiles.”

Follow-up of drug permeation through excised human skin with confocal Raman microspectroscopy. Eur Biophys J., 2007 Jun 13, Tfayli A, Piot O, Pitre F, Manfait M.

Skin is a multilayered organ which covers and protects the surface of human body by providing a barrier function against exogenous agents. Meanwhile, the efficacy of several topically applicated drugs is directly related to their penetration through the skin barrier. Several techniques are commonly used to evaluate the rate, the speed and the depth of penetration of these drugs, but few of them can provide real-time results. Therefore, the use of nondestructive and structurally informative techniques permits a real breakthrough in the investigations on skin penetration at a microscopic scale.

Confocal Raman microspectroscopy is a nondestructive and rapid technique which allows information to be obtained from deep layers under the skin surface, giving the possibility of a real-time tracking of the drug in the skin layers. The specific Raman signature of the drug enables its identification in the skin. In this study, we try to follow the penetration of Metronidazole, a drug produced by Galderma as a therapeutic agent for Rosacea treatment, through the skin. The first step was the spectral characterization of Metronidazole in the skin. Then micro-axial profiles were conducted to follow the penetration of the drug in the superficial layers, on excised human skin specimens. For more accurate information, transverse sections were cut from the skin and spectral images were conducted, giving information down to several millimeters deep. Moreover, the collected spectra permit us to follow the structural modifications, induced by the Metronidazole on the skin, by studying the changes in the spectral signature of the skin constituents.

Percutaneous absorption kinetics of topical metronidazole formulations in vitro in the human cadaver skin model, Adv Ther. 2007 Mar-Apr;24(2):239-46, Elewski BE
Topical formulations containing identical active agents are available in various vehicles and concentrations, which may affect percutaneous absorption. This study was undertaken to evaluate the in vitro percutaneous absorption pharmacokinetics of metronidazole in different vehicles and concentrations as the active agent in 6 topical formulations. Formulations were applied to sections from 3 cadaver skin donors, and percutaneous absorption of metronidazole was measured over a 48-h test period through the finite dose technique and the use of Franz diffusion cells. Metronidazole penetrates into and through human cadaver skin.

Data show the general ranking of delivery of similar concentrations of metronidazole according to vehicle as cream > lotion > gel. The 48-h penetration of metronidazole in the human cadaver skin model was greatest with cream formulations and lowest with gel formulations. These results reveal the importance of the vehicle selected for penetration of metronidazole into the skin. The relevant target zone in rosacea is the dermis because this is the area where inflammation takes place. Additional studies are warranted to examine absorption of metronidazole into the relevant target zone and the correlation of absorption with efficacy.

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Further Reading:

so just how does metrogel work ?

David Pascoe — Tue, 20 Mar 2007 07:58:00 +0000

I have mentioned a few times in the past that the way that metrogel helps rosacea is unknown. This statement deserves some clarification. Actually the way that metronidazole works is well known. How the effect of metrogel leads to a benefit in rosacea, well, that is something worth exploring some more later on.

You may wonder why there is so much emphasis on the metronidazole based products ? As much as metrogel and its friends metrocream, metrolotion, rozex, noritate (and indeed generic metrogel, also from fougera) are not a panacea for rosacea, they do represent the single most proven treatment specifically for rosacea. Thus newly diagnosed rosacea sufferers are quite likely to leave their doctor’s surgery with a script for metro-something. All the studies show that in many cases metrogel does indeed work. Further, other studies clearly show that combining metrogel with antibiotics results in better clearance.

So back to `how does it work ?’ Well my one sentence summary is “metronidazole breaks down into a substance that kills the DNA of the cells of some particular bacteria and protozoa”.

Thanks to Dan for sending me the following links ;

From DrugBank: Metronidazole

Pharmacology: Metronidazole, a synthetic antibacterial and antiprotozoal agent of the nitroimidazole class, is used against protozoa such as Trichomonas vaginalis, amebiasis, and giardiasis. Metronidazole is extremely effective against anaerobic bacterial infections and is also used to treat Crohn’s disease, antibiotic-associated diarrhea, and rosacea.

Mechanism of Action: Unionized metronidazole is selective for anaerobic bacteria due to their ability to intracellularly reduce metronidazole to its active form. This reduced metronidazole then disrupts DNA’s helical structure, inhibiting bacterial nucleic acid synthesis and resulting in bacterial cell death.

From Antibiotics that Inhibit Nucleic Acid Synthesis

Figure 11-8. Structure of metronidazole and its mechanism of action. Metronidazole enters an aerobic bacterium where, via the electron transport protein ferrodoxin, it is reduced. The drug then binds to DNA, and DNA breakage occurs.

(An anaerobic organism is any organism that does not require oxygen for growth. Protozoa are a particular type of single cell organisms.)

This naturally leads to the followup question – if eliminating the substances that metronidazole (and for the purposes of this argument, lets include systemic antibiotics as well) is active against leads to relief from some rosacea symptoms, what does that say about the possible cause of rosacea ? Now, that is a question that there isn’t much agreement about and something worth talking about some more, later.

Further Reading ;