DAFLON 500 mg is the only phlebotrope which has been demonstrated to have an active ingredient that is micronized. This technique reduces the size of its particles to less than 2 microns in diameter, allowing better absorption after oral administration,(1-2) and leading to better clinical efficacy.(3)

References:

1. Johnston AM. Effects of micronization on digestive absorption of diosmin. Phlebology. 1994;9(suppl 1):4-6.
2. Garner RC, Leong D, Gregory S, Whattam M, Calam A, Garner JV. Comparison of the absorption of micronized (Daflon 500® mg) and nonmicronized diosmin tablets after oral administration to healthy volunteers analyzed by accelerator mass spectometry. J Pharm Sci. 2002;91:32-40.
3. Cospite M, Dominici A. Double-blind study of the pharmacodynamic and clinical activities of 5682 SE in venous insufficiency. Advantages of the new micronized form. Int Angiol. 1989;8(suppl 4):61-65.
   

The clinical benefits of DAFLON 500 mg compared with nonmicronized diosmin are due to its micronized form, which guarantees greater absorption and indeed, significantly greater clinical efficacy in treating chronic venous insufficiency. This superior clinical efficacy has been demonstrated in a clinical trial comparing DAFLON 500 mg, 2 tablets daily, to diosmin 900 mg/day.(1) The results showed that DAFLON 500 mg was on average 30% more effective in improving signs and symptoms of chronic venous insufficiency (P<0.05) than nonmicronized diosmin. Leg edema assessed by ankle circumference also decreased in a significantly greater proportion of the DAFLON 500 mg group than of the nonmicronized diosmin group (P<0.01).

Similar results have been observed in patients suffering from haemorrhoidal disease. In a significant manner, DAFLON 500 mg improves more symptoms and signs than nonmicronized diosmin, and significantly reduces the number of recurrent episodes. (2) (P<0.02),

References:

1. Cospite M, Dominici A. Double-blind study of the pharmacodynamic and clinical activities of 5682 SE in venous insufficiency. Advantages of the new micronized form. Int Angiol. 1989;8(suppl 4):61-65.
2. Cospite M, Cospite V. Treatment of haemorrhoids with Daflon 500 mg. Phlebology.1992;7 (suppl 2):53-56.
   

The mode of action of DAFLON 500 mg has been clearly demonstrated through several trials. DAFLON 500 mg acts on all the components of venous disease: veins, lymphatics, and capillaries.

-DAFLON 500 mg increases venous tone by prolonging the vasoconstrictor effect of noradrenaline on the vessel wall, and reduces blood venous stasis.(1)
-DAFLON 500 mg increases lymphatic contractions and improves lymphatic drainage.(2)
-DAFLON 500 mg reduces the inflammatory process at the microcirculatory level, inhibiting the adhesion, migration, and activation of leukocytes. This reduces capillary hyperpermeability and increases capillary resistance.(3-8)

References:

1. Duhault J, Pillon G. Mécanisme d'action de Daflon 500 mg sur le tonus veineux noradrénergique. Artères Veines. 1992;11:217-218.
   
   
2. McHale NG, Hollywood MA. Control of lymphatic pumping: Interest of Daflon 500 mg. Phlebology. 1994;(suppl 1):23-25.
   
   
3. Behar A, Lagrue G, Cohen-Boulakia F, Baillet J. Study of capillary filtration by double labelling I131-albumin and Tc993 red cells. Application to the pharmacodynamic activity of Daflon 500 mg. Int Angiol. 1989;8(suppl 4):27-29.
   
   
4. Galley P. Activité de Daflon 500 mg sur la résistance capillaire. Etude contrôlée à double insu contre placebo. J Int Med. 1987;99(suppl):26-27.
   
   
5. Damon M, Flandre O, Michel F, Perdrix L, Labrid C, Crastes-de-Paulet A. Effect of chronic treatment with a purified flavonoid fraction on inflammatory granuloma in rat. Arznimittelforschung/Drug Res. 1987;37:1149-1153.
   
   
6. Korthuis RJ, Gute DC. Postischemic leukocyte/endothelial cell interactions and microvascular barrier disruption in skeletal muscle: Cellular mechanisms and effect of Daflon 500 mg. Int J Microcirc. 1997;17(suppl 1):11-17.
   
   
7. Friesenecker B, Tsai AG, Allegra C, Intaglietta M. Oral administration of purified micronized flavonoid fraction suppresses leukocyte adhesion in ischemia-reperfusion injury: In vivo observations in the hamster skin fold. Int J Microcirc. 1994;14:50-55.
   
   
8. Bouskela E, Donyo KA. Effects of oral administration of purified micronized flavonoid fraction on increased microvascular permeability induced by various agents and on ischemia/reperfusion in the hamster cheek pouch. Angiology. 1997;48:391-399.

DAFLON 500 mg accelerates lymph flow by increasing the contraction of lymphatics in term of their frequency and their amplitude, and it increases the number of functional lymphatic capillaries. This facilitates the drainage of interstitial fluid into the lymphatic system, and therefore reduces edemas.(1,2)

References:

1. McHale NG, Hollywood MA. Control of lymphatic pumping: interest of Daflon 500 mg. Phlebology. 1994;(suppl 1):23-25.
   
   
2. Allegra C, Bartolo M Jr, Cassiani D, Carioti B. Microlymphography assessment of Daflon 500 mg activity in patients with chronic venous insufficiency. Lymphology.1998;31(suppl):12-16

Studies have shown that the answer of this question is yes. Thanks to its capacity in improving lymphatic drainage, DAFLON 500 mg has been used in patients with lymphedema of the upper limb post mastectomy. Two important studies conducted in patients with postmastectomy lymphedema of the arm have demonstrated its usefulness in those cases. The results showed a significant reduction in lymphedema after a 6-month treatment at the dose of 2 tablets daily.(1,2)

References:

1. Pecking AP, Rambert P. Evaluation by lymphoscintigraphy of a micronized flavonoid fraction (Daflon 500 mg) in the treatment of upper limb lymphedema. Int Angiol. 1995;14(3 suppl 1):39-43.
   
   
2. Pecking AP, Février B, Wargon C, Pillion G. Effect of Daflon 500 mg on lymphedema secondary to breast cancer treatment. Lymphology. 1998;31(suppl):21-24.

DAFLON 500 mg reduces the expression of endothelial adhesion molecules (ICAM1, VCAM1), and inhibits leukocyte adhesion, migration and activation, reducing the release of inflammatory mediator.(1,2) Moreover, DAFLON 500 mg reduces capillary hyperpermeability and increases capillary resistance.(3,4)

References:

1. Shoab SS, Porter J, Scurr JH, Coleridge-Smith PD. Endothelial activation response to oral micronised flavonoid therapy in patients with chronic venous disease. A prospective study. Eur J Vasc Endovasc Surg. 1999;17:313-318.
   
   
2. Korthuis RJ, Gute DC. Postischemic leukocyte/endothelial cell interactions and microvascular barrier disruption in skeletal muscle: cellular mechanisms and effect of Daflon 500 mg. Int J Microcirc. 1997;17(suppl 1):11-17.
   
   
3. Bouskela E, Donyo KA. Effects of oral administration of purified micronized flavonoid fraction on increased microvascular permeability induced by various agents and on ischemia/reperfusion in the hamster cheek pouch. Angiology. 1997;48:391-399.
   
   
4. Galley P. Activité de Daflon 500 mg sur la résistance capillaire. Etude contrôlée à double insu contre placebo. J Int Med. 1987;99(suppl):26-27.

It has been clearly demonstrated in several studies conducted according to the recommendations of the Alexander House Group as double-blind, placebo-controlled trials, that DAFLON 500 mg at a dosage of 2 tablets daily, in combination with compression therapy, significantly accelerates healing of venous ulcers and increases the number of healed ulcers.(1,2)It also reduces time to ulcer healing by 1 month and improves cost-effectiveness ratio by 45% (3)

References:

1. Guilhou JJ, Dereure O, Marzin L, et al. Efficacy of Daflon 500 mg in venous leg ulcer healing. A double-blind, randomized, controlled versus placebo trial in 107 patients. Angiology. 1997;48:77-85.
   
   
2. Glinski W, Chodynicka B, Roszkiewicz J, et al. The beneficial augmentative effect of micronized purified flavonoid fraction (MPFF) on the healing of leg ulcers: a multicenter controlled study. Phlebology. 1999;14:151-157.
   
   
3. Roztocil K, stvrtinova, strejcek j Efficacy of a 6-month treatment with Daflon 500mg in patients with venous leg ulcers associated with chronic venous insufficiency. Int Angiol 2003; 22:24-31

For patients affected by chronic venous insufficiency, 2 tablets daily which can be administered as a single dose in the morning, in the evening or 1 tablet twice daily.(1,2)

For patients suffering from acute haemorrhoidal attacks(2) the dosage of DAFLON 500 mg is:

• 6 tablets daily for 4 days (2 tablets three times per day), then
• 4 tablets daily for 3 days (2 tablets two times per day).

Then, you can consolidate the venous improvement with 2 tablets daily, in order to reduce recurrences.(3,4)

References:

1. Laurent R, Gilly R, Frilleux C. Clinical evaluation of a venotropic drug in man. Int Angiol. 1988;(suppl 2):39-43
   
   
2. Meney G. Chronobiology and clinical activity of Daflon 500 mg in chronic venous insufficiency. Phlebology.1994;9(suppl 1):15-18.
   
   
3. Cospite M. Double-blind, placebo-controlled evaluation of clinical activity and safety of Daflon 500 mg in the treatment of acute haemorrhoids. Angiology. 1994;45:566-573.
   
   
4. Godeberge P. Daflon 500 mg is significantly more effective than placebo in the treatment of haemorrhoids. Phlebology. 1992;7(suppl 2):61-63

Yes, in chronic venous insufficiency, several studies have demonstrated that the longer the treatment duration, the greater the improvement of signs and symptoms as well as patients' quality of life.(1-3) The efficacy of DAFLON 500 mg is reinforced by a long-term treatment. In haemorrhoidal disease, studies have shown that maintenance therapy with 2 tablets daily of Daflon 500 mg during 2 months, significantly reduces the frequency and severity of attacks.(4,5)

References:

1. Guillot B, Guilhou JJ, Pointel JP, et al. A long term treatment with a venotropic drug. Results on efficacy and safety of Daflon 500 mg in chronic venous insufficiency. Int Angiol.1989;8(suppl 4):67-71.
   
   
2. Jantet G. Relief study: first consolidated European data. Angiology. 2000;51:31-37.
   
   
3. Jantet G. Chronic venous insufficiency- worldwide results of the RELIEF Study. Angiology. In press.
   
   
4. Godeberge P. Daflon 500 mg is significantly more effective than placebo in the treatment of haemorrhoids. Phlebology. 1992;7(suppl 2):61-63.
   
   
5. Misra MC, Parshad R. Randomized clinical trial of micronized flavonoids in the early control of bleeding due to acute internal haemorrhoids. Br J Surg. 2000;87:868-872.

DAFLON 500 mg can be combined with any therapeutic agent; in fact no drug interactions have been reported. This point is very important, considering that patients can suffer concomitant diseases and may require other therapies. Even more, on long-term treatment compared with placebo, no evidence was found of any statistically significant variation in laboratory parameters, such as red cell count, hemoglobin, hematocrit, liver function (SGPT, SGOT), or other blood parameters (glucose, total lipids, cholesterol, triglycerides, uric acid).

References:

1. Meyer O. Safety of use of Daflon 500 mg confirmed by acquired experience and new research. Angiology. 1994;45:579-584.

References:

1. Misra MC, Parshad R. Randomized clinical trial of micronized flavanoids in the early control of bleeding due to acute internal hemorrhoids Br J Surg. 2000. 87:868-872.
2. Buckshee K, Takkar D, Aggarwal N. Micronized flavanoids therapy in internal hemorrhoids of pregnancy. Int J Gynecol Obstet 1997; 57:145-151.
3. Pinjala RK, Abraham TK et al. Long-term treatment of chronic venous insufficiency of the leg with micronized purified flavonoid fraction in the primary case setting of India. Phlebology 2004; 19:179-184.