Rosacea and Doxium (Calcium Dobesilate)

Written by on January 1, 2006 in doxium, research with 21 Comments

Calcium dobesilate is a vasoactive drug with presumed effects on endothelial integrity, capillary permeability and blood viscosity. It is often recommended for venous disorders, and also prescribed for diabetic retinopathy and other microvascular disorders. (from dobest-II.pdf)

Therapeutic response of rosacea to dobesilate, European Journal Medical Research. 2005 Oct 18;10(10):454-6., Cuevas P, Arrazola JM., Department of Research, Hospital Ramon y Cajal, Madrid, Spain.

Despite an incomplete understanding of the pathogenesis of rosacea, therapeutic modalities continue to expand. The principal subtype of rosacea includes erythematotelangiestatic rosacea, which is characterized by uncontrolled angiogenesis. Angiogenic growth factors such as fibroblast growth factors (FGF) and vascular endothelial growth factor (VEGF) are currently targets of intense effort to inhibit deregulated blood vessel formation in diseases such as cancer. Here we report a 33-years-old woman with erythematotelangestatic rosacea who responds to a daily treatment of topically applied dobesilate, an inhibitor of FGF, with an improvement in erythema and telangectasia after two weeks. Thus, dobesilate might be useful in the treatment of rosacea and other diseases that depend on pathologic angiogenesis.

I am attempting to get a copy of the full paper from the author. The author has also published these related articles ;

Dobesilate is an angiogenesis inhibitor Eur J Med Res. 2005 Sep 12;10(9):369-72. Aberrant angiogenesis is essential for the progression of solid tumors and hematological malignancies. Antiangiogenic therapy is one of the most promising approaches to treat such diseases. Dobesilate is an oral agent for treatment of vascular complications of diabetic retinopathy. We have examined the possibility that this compound could interfere with the process of angiogenesis in a mouse gelatine sponge assay using acidic fibroblast growth factor (aFGF) as an inducer of neovascularization. According to the results reported here, dobesilate remarkably reduced vessel ingrowth in aFGF-containing subcutaneous sponges in mice. These findings suggest that dobesilate could be an effective agent in the treatment of angiogenesis-dependent diseases involving FGFs.

Dobesilate in the treatment of plaque psoriasis. Eur J Med Res. 2005 Sep 12;10(9):373-6. Fibroblast growth factor (FGF)-mediated pathways participate in many of the cellular events implicated in the pathogenesis of psoriasis. Thus, targeting FGF signals may be potentially therapeutic in the treatment of psoriasis. We report for the first time on a 43-year-old man with chronic-type plaque psoriasis with a daily topical treatment of dobesilate, a new FGF inhibitor. As early as at day 14, the patient had cleared or achieved excellent improvement of psoriatic skin lesions. Topical dobesilate offers the potential for treatment of plaque psoriasis without atrophy or other local side effects associated with the use of topical corticosteroids.

Treatment of basal cell carcinoma with dobesilate (PDF). J Am Acad Dermatol. 2005 Sep;53(3):526-7 Calcium dobesilate (calcium dihydroxy-2,5 benzenesulfonate; Doxium; OM Laboratories Ltd, Meyrin- Geneva, Switzerland) has been used widely for treating vascular disease, especially diabetic retinopathy and chronic venous insufficiency. Based on our previous demonstration that dobesilate inhibits cell proliferation and promotes apoptosis in glioma cell cultures by acting as an FGF (fibroblast growth factors) inhibitor, we assessed the effect of topical dobesilate treatment on one case of BCC.

Update: the full article appears to be available here: Therapeutic response of rosacea to dobesilate.

Read more about: doxium, research

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About the Author: David Pascoe started the Rosacea Support Group in October 1998. .

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21 Reader Comments

  1. jigar soni says:

    is it work on diabetic retinopathy

  2. Sophie says:

    This paper is available from http://www.infotrieve.com. The results are very impressive after 2 weeks of treatment with a cream containing 2.5% calcium dobesilate applied twice daily with improvement in telangectasia and erythema. Symptoms of flushing, buring and stinging sensations were all reduced after treatment with no recurrence 4 months after stopping the therapy.

    Calcium dosileate is presently available in pill form only for treatment of diabetic retinopathy and chronic venuous insuffiency. Found P. Cuevas has a patent for a theraputic cream but the product does not seem to be available at present.

  3. Thanks for the information Sophie. I found a PDF of the full article here: Therapeutic response of rosacea to dobesilate.

  4. Sophie says:

    Thanks, Digital Davo,

    My downloaded version was black & white. Seeing the photographs in colour is very encouraging. Am hoping that this therapy comes on the market soon as it appears to have few side-effects and offers treatments for rosacea, psoriasis and basal cell carcenoma.

    Calcium dobesilate is presently used orally to treat diabetic retinopathy and chronic venous insufficiency.

  5. Sophie says:

    Calcium dobesilate is not available in the U.S. or Canada at present. The drug in pill form is sold under the name, Doxium, in Europe, South Africa, Central & South America, and China for treatment of diabetic retinopathy and chronic venuous insufficiency.

    From what I have been able to find out, Sanchez & Arrozola applied for a patent for a theraputic cream containing calcium dobesilate. This treatment would likely appear on the European market before (or if ever) it comes on the market in the U.S./Canada.

  6. Pavla says:

    Sophie,
    Please let me know where did you find the information that Sanchez and Arrozola applied for the patent for the therapeutic cream with calcium dobesilate. I read the article from message No. 3 but I understood it was only a succesfull test on one woman. I live in Europe so I would like to purchase this cream as soon as possible because no medication helped me with teleagiectasic-erythematous rosacea on whole face. Thank you very much in advance.

  7. I had a quick search and found the following patent that looks like it could be it. Unfortunately patents are quite hard to read also hard to fit into the context of other products and inventions.

    (WO/2008/020028) 2,5 DIHYDROXYBENZENE COMPOUNDS FOR THE TREATMENT OF ROSACEA

    The invention relates to the use of a 2,5-dihydroxybenzene derivative of formula (I) or a pharmaceutically acceptable salt or solvate, isomer or prodrug thereof in preparing a medicinal product for the treatment and/or prophylaxis of rosacea.

    davidp.

  8. pavla says:

    Thank you very much, David.
    I read all pages carefully and now understand the patent itself doesn´t guarantee the topical cream shall be produced in near future. We can only hope. But I will check with my doctor and drug store the possibility to make a cream with Ca dobesilate ingredient based on doctor´s prescription. To be honest I do not hope at all because I do not believe Ca dobesilate is available for such use and, what is much worst, I do not expect my dermatologist would be informed about possible use of Ca dobesilate for rosacea treatment. I have experience doctors are informed about available drugs in world, but this is not same case.
    Unfortunately, this is the first time I feel it can work for redness and capillaries.

  9. I can see dobelisate being available as a suppository, but of course there is no indication that this would work for the skin. As you say it is a very long way from a patent to a proven and generally available product. For one there has to be a party willing to invest in bringing it all the way to the market.

    davidp.

  10. Sophie says:

    Pavla, Digital Davo,

    Calcium dobesilate is also used in combination with cortisone to treat hemeroids. Cortisone is the absolute worst thing for rosacea because it promotes angiogenesis. Would suggest avoidance of any suppository compound.

    I was able to buy Doxium 500 in Nicaragua (500 mg of calcium dobesilate in a dissolvable caplet) from a drugstore without a prescription. Doxium is available in Europe, China, New Zealand, Central America and South America but not U.S. or Canada. It is used to treat diabetic retinopathy which is characterized by angiogenesis (growth of blood vessels) and chronic veinous insufficiency (failure of the valves in blood vessels in the legs resulting in swollen legs, cramping oedema and discomfort). Doxium is also available at online pharmacies.

    I have prepared my own 2.5% solution by weight using a commercial moisturizer as the base (0.5 g Cal. dobesilate to 19.5 g cream). Just started my own 2 week experiment in combination rigorous avoidance of rosacea triggers ie. sun, alcohol, spicy food, heavy exercise, etc. Since rosacea skin is generally highly reactive, the moisturizer that I use is very non-reactive ie. no perfumes or harsh chemicals. The compound inside the caplets is a powder which readily dissolves.

    Obviously, this isn’t perfect science and your doctor would be committing an ethical violation to help you to do this. Given that calcium dobesilate in the form of Dobest (manufactured by Wallace Pharmaceuticals) or Doxium (manufactured by Johnson & Johnson) is not even on the market in Canada, I believe it will be many years before a theraputic cream is available in Canada. Calcium dobesilate has no known drug interactions or side effects and has been widely used in Europe for decades.

    The Sanchez’s study mentions that rosacea is characterized by angiogenesis in the early stages which stops as the condition advances. I believe that the patient would likely have been beyond the initial phase of the disease which is why this study is so promising.

    You might also look for Doxivenil gel or cream which is a topical treatment to ease symptoms of chronic venous insufficiency and varicose veins. The ingredients are calcium dobesilate and heparinoid and I was not able to find out about heparinoid. I was not able to find out the strength of this compound. The website also mentions that the product has no known drug interactions.

    Note: The patent also lists a company which has presumably been formed by Sanchez et al to develop this product: Action Medicines, S.L., Costa Brava 14-B, Portal2, 7-A, E-28034 Madrid.

    Hope this helps.

  11. Sophie says:

    Pavla,

    You have to realize that this is a sample size of 1. Normally, drugs are approved on the basis of clinical trials involving thousands of patients.

    Few physicians prescribe drugs for off-label applications let alone on the basis of such a limited study. It would be unethical to do so.

    My father suffered with severe rosacea on his nose and my siblings have more advanced cases than me with thickening of the tissue in the cheeks and extensive taglia. Rosacea is a progressive vascular disorder. I have been treated with intense light pulse therapy with minor improvement which is not lasting. I have the spontaneous pustules, taglia, thickening tissue, flushing.

    In my travels, I did discover a great pharmaceutical grade makeup manufactured by Glo Minerals which provides very good coverage and can match any skin tone. Found it better to match your own natural tone than use yellow which tends to look awful.

  12. Pavla says:

    Sophie,
    I am very excited your are already doing your test. That is what I am thinking about from the first moment. The only problem is to convince a doctor to issue a prescription because this drug is not available freely. As it looks now Doxium is available in our country but in hard form, so I have to travel abroad to purchase it.
    I hope you inform your treating results soon.
    Best Regards,
    Pavla

  13. Sophie says:

    Pavla,

    The base that I used has reacted with the calcium dobesilate turning the cream pink after several days. I decided to discontinue use after 1 week. Have seen reduction in redness in cheek area. Am currently experimenting with 4 other alternative bases (small amount mixed with calcium dobesilate; next to a sample of the base material for colour reference).

    Did come across a pharmacy in Valetta that carries doxivenil cream and get. Believe this is Valetta, capital of Malta.

    http://www.malpharma.com/Om.html

    Doxivenil is manufactured by OM Pharma of Switzerland who also manufacture Doxium (this is the product that I purchased in Nicaragua without a prescription) although I did not find Doxivenil on their website. Their products are distributed throughout Europe, Central & South America and Asia but not in North America. Have come across several websites in Romania that reference Doxivenil.

    http://www.ompharma.com/

    Many seniors suffer from chronic veinous insufficiency, leg cramps, restless legs at night and varicose veins. It may be easier to convince a doctor to prescribe doxivenil to such a patient and ask the patient to give you a small sample. Chances are pretty good that you may have an elderly relative or a friend who knows someone suffering these symptoms. Clinical trials show relief of oedema (swelling of legs), pain due to swelling, cramping etc., and good tolerance by patients.

    Given that the original experiment was conducted over a 2 week period with the patient using the product twice daily, and the symptoms had not returned 6 months later, it would seem likely that one could use the cream for 2 weeks and discontinue use until a flareup. One has to assume that the way the product was used indicates that it would not be desirable to use the product habitually but as a periodic control.

  14. Sophie says:

    Pavla,

    Have you tried Noritate cream 1% (also known as Metronidazole 1%)? This cream helps to reduce redness, tissue swelling and breakouts from rosacea. Have used it and it definitely is very effective at controlling the symptoms of rosacea. 2 yrs of hot flashes have made my skin much worse and it now has spontaneous breakouts.

    Intense Light Pulse and laser treatments can help reduce spider veins and excessive flushing. Laser treatments are a bit rough I have been told. ILP helped reduce spider veins in my face and has reduced flushing. There is a risk of hyperpigmentation particularly with dark skin with both treatments.

    The other possibility to consider is lifestyle. Rosacea has triggers like alcohol, spicy food, heavy exercise, and stress. Stress is one of the more subtle triggers that we don’t tend to notice. A diary noting when you have flare-ups might be useful in identifying what triggers you are susceptible to.

    Just some possibilities to consider. There are lots of different treatment options for patients. I know it’s frustrating when a medication doesn’t work but sometimes, you find a treatment that works best for you if you perservere.

    I once read about a lady who went through 19 different medications before she found one that worked for her depression. The result of her persistence was greater quality of life. So often as women, we look after others rather than giving ourselves the care we need.

  15. Pavla says:

    Sophie,
    I am very pleased to her your home-made cream helped.
    I would like to inform you I also start treatment with Doxium today. I just received parcel from Madrid hospital. I sent e-mail to Mr. Cueavas describing my condition, enclosed detail photos and offered myself for tests. He replied quickly and informed me they are performing observative study, so if I agree to sign free participation in the study he will send the cream to my address. I also had to promise to send good photographs before and each week of treatment which shall last 4-6 weeks. Cream shall be applied in the morning and evening. I do not know if they need more patiens for tests.
    My daughter is 4 years and has very invasive erythematous rosacea with lots of pimples, visible teleangiectasis and permanent red spots on cheeks. It started to attack her nose, chin and eyes. Her disease is much worst in compare with me, first signs appeared at the age of 1 year. I never had visible teleangiectasis in childhood, first pink spots appeared when I was 14. I even do not have too many pimples or pustules. And when they appear, Metronidazol 1%cream helps me. But not to my daughter. I think I did not sleep well in last 2 years because I can see new disturbed area each month on her face. There is no other approved medication for Rosacea in our country (I live in Czech Rep.). My friend helped me to arrange Sulfacet-R Lotio in USA. I think it calmed her redness a little but was not able to stop creating of new inflammed spots, pimples never dissappeared. I tried 15% azelaic acid on myself but the stinging and itching was not acceptable without use of moisture cream before. Result was bad – more redness. But I think it can work on pustules when applied locally.
    I know the research of Ca.Dobesilate for Rosacea is still in the innitial phase but the case of my daughter is very tristful for our family. I can not wait next 10-20 years for new approved product for erythematous subtype. The fact that Mr. Cueavas offered Ca.Dobesilate cream for my daughter as well makes me think it probably is not toxic or too dangerous, also due to fact it can be taken orally by adults. To be honest I hoped he will do so, because in the patent is mentioned thy claim to use Ca. Dobes. on children too.
    Metronidazol used to be a subject of my first hope, but failed. This is my second hope and if it fails again I will have to start beleive our doctor who says : “There is no God for this disease”.

  16. Pavla says:

    Sophie,
    I´m pleased to hear your home-made medication worked already after one week of use. Hope you noticed next improvment after the second week again.
    I am going to start treatment with Doxium today. I sent e-mail to Mr. Cuevas/Madrid where I described my condition, enclosed detail photographs and offered myself for tests. He replied quickly and offered he sends the cream if I agree to send photographs before and each week of treatment, which shall last 4-6 weeks. I also had to sign free participation in this study.
    The cream is in tube, has white colour and is rather greasy. It shall be applied in the morning and evening.
    I have 4year old daughter. She has very invasive rosacea. She has lots of pimples, teleangiectasis on cheeks and nose, pink spots on chin and it already attacked her eyes – itching. We both tried Metronidazol cream 1%, but it helped only to me. But I do not have noticable teleangiectasis or pimples and did not have signs in childhood. Later my friend helped me to arrange Sulfacet-R Lotio from USA. It calmed some of her redness but did not stop creating of new pimples and new inflammed spots. I tried 15% azelaic acid on myself only with bad result – more redness – although I suppose it can work well for pustules if applied just locally. But it is recommended for pustules only, I understand.
    I mentioned my daughter´s case in e-mail to Mr. Cuevas as well and he offered same cream for her too. To be honest I hoped he will do so because there is mentioned in the patent that the claim for use includes children.
    The lack of approved drugs worldwide made me think about experimental medicine for my child too because her situation is very tristfull and there is no time to wait additional 10-20 years for something new.
    If this cream does not help, I shall start to believe our doctor who says : There is no God for erythematous rosacea.

  17. Sophie says:

    Pavla,

    This is wonderful news. Your daughter’s condition must be heart-breaking. So glad to hear that Dr. Cuevas has sent you the cream. Good luck with your efforts.

    I use a line of non-irritating skin products by Shikai (available at http://www.shikai.com). Highly recommend the soap free Shikai shampoo, the colloidal oatmeal shower gel, borage facial cleanser & borage moisturizer. These products are designed for skin that is very sensitive, hyper-reactive, chronically dry. The borage cream has been show to improve conditions like exema and skullcap (red rash that babies get on their head and underarms).

    Best wishes with your efforts. Have a wonderful holiday.

  18. Sophie says:

    I realize this thread is pretty old. Just wanted to let others know that Dr. Cuevas accepted me as a participant in his clinical trial of the 2.5% Calcium dobesiliate cream. I had to arrange and pay for international shipping and managed to get the product into Canada (the product was described as a skin cream for customs purposes).

    I have been using the skin cream for 2 weeks in the morning and evening. Redness has visibly decreased. My skin feels smooth and soft where there were small bumps previously. Spontaneous breakouts have also stopped. The study above was conducted over 4 weeks.

    Anyone interested in participating in the clinical trial can submit photographs to Dr. Pedro Cuevas at:

    pedro.cuevas@hrc.es

    Dr. Pedro Cuevas
    Servicio de Histología
    Departamento de Investigación
    Hospital Ramón y Cajal
    Ctra. de Colmenar, km. 9.100
    28034-Madrid-Spain

    Tel. (0034) 913368290

    If you are planning a trip to Spain, Madrid has the best tapas in Spain. Another great reason to visit this country.

  19. Thanks for the info Sophie. It would be great to hear from any others that decide to try this new cream.

  20. Pavla says:

    I took part in this clinical trial together with my 4-year-old daughter starting Dec.16, 2008 and finished after 8 weeks of use.
    We sent photos to Dr. Cuevas weekly.
    I was informed in advance this trial shall last at least 4-6 weeks so I was not surprised when I did not find any change after 2 weeks. But already in the beginning I evaluated the cream as very greasy and informed Dr. Cuevas. I never received any standpoint to this discovery.
    My daughter had no positive result after 6 weeks so we stopped use. I even can see more redness on her face and new visible teleangiectasis. This active ingredient is not going to be a medicine for her.
    I did not notice any positive change in my case after 6 weeks but also no worsening. Dr. Cuevas replied to my sceptic e-mail that it is safe to use Doxium cream longer and suggested to use it 2 more weeks. After 8 weeks of use I did not see anything good again but have following experience.
    In the end of my treatment I used mineral make-up which I removed by Cetaphil cleanser. I felt burning immediately after Cetaphil contact with my face. I did not pay enough attention to this and cleaned my face with Cetaphil completely. It burned so much that immediate cleaning with running water did not help from burning. My face became red and today , almost 4 months later I am not OK. I am more red in compare with December 2008. I started to use 1% metronidazol cream again in order to calm down my redness and dryness. Within 2-3 days many bumps appeared on my overdried face together with a red rash around my lips looking like some dermatitis. 1%metronidazol did not solve my problem so I went to doctor who evaluated my new bumps as ACNE. I received prescription for Fucidin gel which heals existing bumps with leaving red scars ; and does not help to stop creating new. The dryness was finally solved by Rozex Cream 0,75%.
    I understand that CA.Dobesilate is a sort of salt and suppose the prolonged length of use has caused my skin dry and sensitive on touch. I do not recomment to use it longer than 6 weeks to those who do not see positive results within this period; and, perhaps the use of other face cleanser during the treatment might be better.

  21. Sophie says:

    Pavla,

    I am really sorry to hear that you have had a bad reaction. Thank you for letting us know about the dangers of prolonged use and using Cetaphil in combination with this cream. It sounds like an allergic reaction.

    Digital Davo,

    My skin improved for 4 weeks and then seemed to regress in week 5. I discontinued use after reading Pavla’s post. I believe that the cream was starting to react with my makeup.

    This week, I started using the cream again sparingly at night after washing my face with a colloidal oatmeal soap (Aveeno moisturizing bar) rather than putting my makeup over the product and this approach seems to be working very well. The red areas of my face have lightened considerably but there are a couple of areas that I am trying to improve. My sister has also gone on the trial and noticed an improvement within the first 2 weeks; her skin is significantly improved at week 4. Her condition was very extreme with thickening of the tissue and spider veins.

    From Pavla’s experience, it appears that the cream does not work on all patients and that it needs to be treated as a medication to be used with caution.

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