Indication

DAFLON 500 mg is an oral phlebotropic drug indicated in the treatment of venous disease, i.e, chronic venous insufficiency (CVI) and haemorrhoidal disease (HD).

Origin and composition of DAFLON 500 mg

DAFLON 500 mg, micronized, purified flavonoid fraction (MPFF), is a semisynthetic phlebotropic drug whose active ingredients are micronized diosmin (90%) and hesperidin (10%). Hesperidin is extracted from a species of Rutaceae aurantieae of the citrus genus, a type of immature small orange harvested and dried in Spain, North Africa, and China. Diosmin, a member of the flavonoid family, is synthesized starting from this raw material.(1,2)

Why is the micronized form of DAFLON 500 mg important?

Micronization means that the active ingredient of DAFLON 500 mg undergoes a high-tech grinding process with a jet of air at supersonic velocities, reducing the size of standard particles from more than 20 µm to less than 2 µm. Thanks to its micronized form, DAFLON 500 mg has better and faster absorption, and thus an increased bioavailability, which leads to faster and more powerful clinical efficacy in venous disease.(3-7)

DAFLON 500 mg has a comprehensive and rigorously demonstrated mode of action, which enables it to fight simultaneously all the pathophysiological aspects of venous disease, affecting the veins, lymphatics, and microcirculation.

• Veins
  DAFLON 500 mg prolongs the vasoconstrictor effect of noradrenaline on the vein wall,(8) even under warm and acidotic conditions, increasing venous tone, and therefore reducing venous capacitance, distensibility, and stasis. This increases the venous return and reduces venous hyperpressure present in patients suffering from CVI.
  
  
• Lymphatics
  DAFLON 500 mg improves lymphatic drainage by increasing the frequency and intensity of lymphatic contractions, and by increasing the total number of functional lymphatic capillaries. Furthermore, DAFLON 500 mg decreases the diameter of lymphatic capillaries and the intralymphatic pressure (9,10)
  
  
• Microcirculation
  At the microcirculation level, DAFLON 500 mg reduces capillary hyperpermeability and increases capillary resistance by protecting the microcirculation from damaging processes. DAFLON 500 mg reduces the expression of endothelial adhesion molecules (ICAM1, VCAM1),(11) and inhibits the adhesion, migration, and activation of leukocytes at the capillary level. This leads to a reduction in the release of inflammatory mediators, principally oxygen free radicals and prostaglandins (PGE2, PGF2).(12-18)
  This protective and reinforcing action on the venous and lymphatic system, associated with the vasculoprotective effect on the microcirculation, explains the restorative and protective efficacy of DAFLON 500 mg in chronic venous insufficiency and haemorrhoidal disease, both of which are associated with perivascular inflammation and edema.

In patients suffering from CVI, DAFLON 500 mg provides significant relief by improving disabling symptoms, (18-20) such as pain, heavy legs, cramps, and sensation of swelling. Moreover, DAFLON 500 mg also significantly improves clinical signs, such as leg edema,(20,21) skin disorders,(22) and venous leg ulcer.(23,24)
This improvement of signs and symptoms contributes to a significant increase in patients' quality of life, as assessed with a validated international scale specific to CVI: the CIVIQ questionnaire.(19)

• Venous leg ulcer
  In venous leg ulcer, the combination of DAFLON 500 mg and conventional compression therapy has been proven not only to accelerate the healing rate, but also to increase the total number of completely healed leg ulcers.(23,24) A recent study confirmed the same and also showed that addition of Daflon 500 reduces healing time by 1 month (25) and improves cost – effectiveness ratio by 45%.
  
  
• Postsurgical and postradiotherapy lymphedema
  Administration of DAFLON 500 mg, 2 tablets daily, for 6 months in patients who had lymphedema after breast cancer surgery leads to a 1.5% to 13.4% decrease in circumference of the affected arm, an improvement in tissue elasticity, and an improvement in lymphatic drainage functional parameters, evaluated by isotope scan.(26) Another double-blind, placebo controlled study, with an equal treatment period and dosage, demonstrated that DAFLON 500 mg induces and increases the velocity of lymphatic drainage on isotope scan, improves functional disturbances, and constantly decreases the volume of the affected arm.(27)

In acute haemorrhoidal attacks, DAFLON 500 mg is highly effective, right from the second day of treatment, in improving all signs and symptoms, such as bleeding, pain, discharge, tenesmus, and proctitis, thereby reducing the consumption of oral analgesics.(28,29)

The efficacy of DAFLON 500 mg associated with fiber supplement has been superior to fiber supplement alone and equivalent to rubber-band ligation plus fiber supplement in stopping anal bleeding due to haemorrhoids.(31)

DAFLON 500 mg combined with haemorrhoidectomy significantly reduces the risk of postoperative bleeding.(31) In a recent study , Daflon 500 when used in combination with short- term antibiotic and anti-inflammatory treatment reduced both the duration and extent of post operative symptoms ( pain, tenesmus, pruritus ) and wound bleeding following haemorrhoidectomy.(32)

In long-term treatment for chronic haemorrhoidal disease, DAFLON 500 mg has been proven to significantly reduce recurrence, duration, number, and severity of haemorrhoidal attacks.(30,33)

1. Labrid C. Pharmacologic properties of Daflon 500 mg. Angiology. 1994;45:524-530.
   
   
2. Struckman J. Pharmacological and pharmacoclinical properties of DAFLON 500 mg. Drugs Today. 1995;31(suppl E):26-36.
   
   
3. Chaumeil JC. Micronization: a method of improving the bioavailability of poorly soluble drugs. Methods Find Exp Clin Pharmacol. 1998;20:211-215.
   
   
4. Johnston AM. Effects of micronization on digestive absorption of diosmin. Phlebology. 1994;9(suppl 1):4-6.
   
   
5. 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.
   
   
6. 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.
   
   
7. Cospite M, Cospite V. Treatment of haemorrhoids with DAFLON 500 mg. Phlebology.1992;7(suppl 2):53-56.
   
   
8. Duhault J, Pillon G. Mécanisme d'action de DAFLON 500 mg sur le tonus veineux noradrénergique. Artères Veines. 1992;11:217-218.
   
   
9. McHale NG, Hollywood MA. Control of lymphatic pumping: interest of DAFLON 500 mg. Phlebology. 1994;(suppl 1):23-25.
   
   
10. Allegra C, Bartolo M Jr, Cassiani D, Cartioti B. Microlymphography assessment of DAFLON 500 mg activity in patients with chronic venous insufficiency. Lymphology. 1998;31(suppl):12-16.
    
    
11. 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.
    
    
12. 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 to No 4):27-29.
    
    
13. 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.
    
    
14. Longchampt M. Protective effect of purified flavonoid fraction against reactive oxygen radicals: In vivo and in vitro study. Arzneimittelforschung/Drug Res. 1989;39:882-885.
    
    
15. 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.
    
    
16. 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.
    
    
17. 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.
    
    
18. 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.
    
    
19. Laurent R, Gilly R, Frilleux C. Clinical evaluation of a venotropic drug in man. Int Angiol. 1988;(suppl 2):39-43.
    
    
20. Jantet G. Relief study: first consolidated European data. Angiology. 2000;51:31-37.
    
    
21. Blume J, Langehbahn H, de Champvallins M. Quantification of edema using the volometer technique: therapeutic application of DAFLON 500 mg in chronic venous insufficiency. Phlebology.1992;7(suppl 2):37-40.
    
    
22. Boineau-Géniaux D. Activité thérapeutique du DAFLON 500 mg sur les troubles trophiques de l'insuffisance veineuse. Act Med Int Angiologie. 1988;(suppl 73):20-22.
    
    
23. 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.
    
    
24. 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.
    
    
25. Roztocil K, Stvrtinova V, Strejcek J. Efficacy of a 6 month treatment with Daflon 500 mg in patients with Venous leg ulcers associated with chronic venous insufficiency. Int Angiol 2003, 22: 24-31
    
    
26. Pecking AP, Rambert P. Evaluation by lymphoscintigraphy of a micronized flavonoid fraction (DAFLON 500 mg) in the treatment of upper limb lymphedema. Int Angiology. 1995;14(3 suppl 1):39-43.
    
    
27. 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.
    
    
28. 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.
    
    
29. 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.
    
    
30. Ho YH, Tan M, Seow-Choen F. Micronized purified flavonoid fraction compared favorably with rubber band ligation and fiber alone in the management of bleeding haemorroids. Dis Col Rectum.2000;43:66-69.
    
    
31. Ho YH, Tan M, Seow-Choen F, Goh HS. Prospective randomized controlled trial of a micronized flavonidic fraction to reduce bleeding after haemorroidectomy. Br J Surg.1995;82:1034-1035.
    
    
32. La Torre F., Nicolai AP clinical use of micronized purified Flavonoid Fraction for treatment of symptoms after haemorrhoidectomy : results of a randomized, controlled clinical trial. Dis colon Rectum 2004;47: 704-710
    
    
33. Godeberge P. DAFLON 500 mg is significantly more effective than placebo in the treatment of haemorrhoids. Phlebology. 1992;7(suppl 2):61-63.