Micronised purified flavonoid fraction: A review of its use in chronic venous insufficiency, venous ulcers and haemorrhoids

Drugs

Volumn 63, Issue 1, 2003, Pages 71-100

  Lyseng Williamson, Katherine A ^a   Perry, Caroline M ^a  

^a ADIS INTERNATIONAL LIMITED   (New Zealand)

Author keywords

[No Author keywords available]

Indexed keywords

DAFLON; DIOSMETIN; FLAVONE DERIVATIVE; FLAVONOID; HESPERIDIN;

ABDOMINAL PAIN; CHRONIC VEIN INSUFFICIENCY; COST EFFECTIVENESS ANALYSIS; DIARRHEA; DROWSINESS; DRUG ABSORPTION; DRUG DISTRIBUTION; DRUG EFFICACY; DRUG ELIMINATION; DRUG METABOLISM; DRUG TOLERABILITY; DYSPEPSIA; FATIGUE; HEADACHE; HEMORRHOID; HUMAN; INSOMNIA; LEG ULCER; LEUKOCYTE ACTIVATION; LEUKOCYTE ADHERENCE; MICROCIRCULATION; NAUSEA; PHARMACODYNAMICS; QUALITY OF LIFE; REVIEW; STOMACH DISEASE; TABLET; ULCER; VEIN TONE; VERTIGO; VOMITING;

ADMINISTRATION, ORAL; ANTI-INFLAMMATORY AGENTS; CHRONIC DISEASE; CLINICAL TRIALS; DIOSMIN; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG ADMINISTRATION SCHEDULE; HEMORRHOIDS; HUMANS; PARTICLE SIZE; VARICOSE ULCER; VENOUS INSUFFICIENCY;

EID: 0037248572     PISSN: 00126667     EISSN: None     Source Type: Journal    
DOI: 10.2165/00003495-200363010-00005     Document Type: Review

References (111)

1. Nicolaides AN. Investigation of chronic venous insufficiency; a consensus statement. Circulation 2000 Nov 14; 102: e126-63
2. Italian College of Phlebology. Guidelines for the diagnosis and treatment of chronic venous insufficiency. Int Angiol 2001 Jun; 20 (2 Suppl. 2): 1-37
3. Struckmann JR, Nicolaides AN. Flavonoids: a review of the pharmacology and therapeutic efficacy of Daflon 500 mg in patients with chronic venous insufficiency and related disorders. Angiology 1994 Jun; 45 (6): 419-28
4. International Task Force. The management of chronic venous disorders of the leg: an evidence-based report. Phlebology 1999; 14 Suppl. 1: 1-126
5. Nicolaides AN, Geroulakos G. Objective evaluation of the pharmacoclinical properties of Daflon 500 mg. Drugs Today 1995; 31 Suppl. E: 37-40
6. Takase S, Schmid-Schönbein GW, Bergan JJ. Leukocyte activation in patients with venous insufficiency. J Vasc Surg 1999 Jul; 30 (1): 148-56
7. Ono T, Bergan JJ, Schmid-Schönbein GW, et al. Monocyte infiltration into venous valves. J Vasc Surg 1998 Jan; 27 (1): 158-66
8. Takase S, Bergan JJ. Schmid-Schönbein G. Expression of adhesion molecules and cytokines on saphenous veins in chronic venous insufficiency. Ann Vasc Surg 2000 Sep: 14 (5): 427-35
9. Fowkes FGR, Evans CJ, Lee AJ. Prevalence and risk factors of chronic venous insufficiency. Angiology 2001; 52 Suppl. 1: S5-15
10. Evans CJ, Fowkes FGR, Ruckley CV, et al. Prevalance of varicose veins and chronic venous insufficiency in mean and women in the general population: Edinburgh Vein Study. J Epidemiol Community Health 1999; 53 (3): 149-53
11. Nicolaides AN, Hussien MK, Szendro G, et al. The relation of venous ulceration with ambulatory venous pressure measurements. J Vasc Surg 1993; 17: 414-9
12. Valencia IC, Falabella A, Kirsner RS, et al. Chronic venous insufficiency and venous leg ulceration. J Am Acad Dermatol 2001; 44 (3): 401-24
13. Wille-Jørgensen P, Jørgensen T, Andersen M, et al. Postphlebitic syndrome and general surgery: an epidemiologic investigation. Angiology 1991; 42 (5): 397-403
14. Porter J.M., Moneta GL. Reporting standards in venous disease: an update. International Consensus Committee on Chronic Venous Disease. J Vasc Surg 1995; 21 (4): 635-45
15. Van den Oever R, Hepp B, Debbaut B, et al. Socio-economic impact of chronic venous insufficiency: an underestimated public health problem. Int Angiol 1998; 17 (3): 161-7
16. Ruckley CV. Socioeconomic impact of chronic venous insufficiency and leg ulcers. Angiology 1997 Jan; 48 (1): 67-9
17. De Castro Silva M. Chronic venous insufficiency of the lower limbs and its socio-economic significance. Int Angiol 1991; 10 (3): 152-7
18. Brand FN, Dannenberg AL, Abbott RD, et al. The epidemiology of varicose veins: the Framingham Study. Am J Prev Med 1988; 4 (2): 96-101
19. Nelzén O, Bergqvist D, Lindhagen A, et al. Chronic leg ulcers: an underestimated problem in primary health care among elderly patients. J Epidemiol Community Health 1991; 45: 184-7
20. Thomson WHF. The nature of haemorrhoids. Br J Surg 1975; 62: 542-52
21. Loder PB, Kamm MA, Nicholls RJ, et al. Haemorrhoids: pathology, pathophysiology and aetiology. Br J Surg 1994; 81: 946-54
22. Pfenninger JL, Surrell J. Nonsurgical treatment options for internal hemorrhoids. Am Fam Physician 1995 Sep 1; 52 (3): 821-34
23. Godeberge P. Daflon 500 mg in the treatment of hemorrhoidal disease: a demonstrated efficacy in comparison with placebo. Angiology 1994 Jun; 45 (6 Pt 2): 574-8
24. Abramowitz L, Godeberge P, Staumont G. et al. Clinical practice guidelines for the treatment of hemorrhoidal disease [in French]. Gastroenterol Clin Biol 2001; 25 (6-7): 674-702
25. Hulme-Moir M, Bartolo DC. Hemorrhoids. Gastroenterol Clin North Am 2001 Mar; 30 (1): 183-97
26. Johanson JF, Sonnenberg A. The prevalence of hemorrhoids and chronic constipation: an epidemiologic study. Gastroentrology 1990 Feb; 98: 380-6
27. Les Laboratoires Servier. Daflon: product description [online]. Available from URL: http://www.servier.com/pro/phlebologie/daflon.asp [Accessed 2002 Sep 12]
28. 14C-diosmin tablets after oral administration to healthy volunteers by accelerator mass spectrometry and liquid scintillation counting. J Pharm Sci 2002 Jan; 91 (1): 32-40
29. Ramelet AA. Clinical benefits of Daflon 500 mg in the most severe stages of chronic venous insufficiency. Aragiology 2001 Aug; 52 Suppl. 1: S49-56
30. Ramelet AA. Pharmacologic aspects of a phlebotropic drug in CVI-associated edema. Angiology 2000 Jan; 51 (1): 19-23
31. Coleridge Smith PD. Neutrophil activation and mediators of inflammation in chronic venous insufficiency. J Vasc Res 1999; 36 Suppl. 1: 24-36
32. Takase S, Lerond L, Bergan JJ, et al. The inflammatory reaction during venous hypertension in the rat. Microcirculafion 2000; 7: 41-52
33. Coleridge Smith PD. Update on chronic-venous-insufficiency-induced inflammatory processes. Angiology 2001; 52 (8 Suppl. 1): S35-42
34. Haas PA, Fox Jr TA, Haas GP. The pathogenesis of hemorrhoids. Dis Colon Rectum 1984; 27 (7): 442-50
35. 99mred cells. Application to the pharmacodynamic activity of Daflon 500 mg. Int Angiol 1988; 7 (2 Suppl.): 35-8
36. Shoab SS, Porter J, Scurr JH, et al. Endothelial activation response to oral micronised flavonoid therapy in patients with chronic venous disease- a prospective study. Eur J Vasc Endovasc Surg 1999 Apr; 17 (4): 313-8
37. Shoab SS, Scurr JH, Coleridge-Smith PD. Plasma VEGF as a marker of therapy in patients with chronic venous disease treated with oral micronised flavonoid fraction: a pilot study. Eur J Vasc Endovasc Surg 1999 Oct; 18 (4): 334-8
38. Shoab SS, Porter JB, Scurr JH, et al. Effect of oral micronized purified flavonoid fraction treatment on leukocyte adhesion molecule expression in patients with chronic venous disease-a pilot study. J Vasc Surg 2000 Mar; 31 (3): 456-61
39. Korthuis RJ, Gute DC. Adhesion molecule expression in postischemic microvascular dysfunction: activity of a micronized purified flavonoid fraction. J Vasc Res 1999; 36 Suppl. 1: 15-23
40. Friesenecker B, Tsai AG, Allegra C, et al. Oral administration of purified micronized fiavonoid fraction suppresses leukocyte adhesion in ischemia-reperfusion injury: in vivo observations in the hamster skin fold. Int J Microcirc Clin Exp 1994; 14 (1-2): 50-5
41. 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 May; 48 (5): 391-9
42. Pickelmann S, Nolte D, Leiderer R, et al. Effects of the phlebotropic drug Daflon 500 mg on postischemic reperfusion injury in striated skin muscle: a histomorphologic study in the hamster. J Lab Clin Med 1999 Nov; 134 (5): 536-45
43. Bouskela E, Cyrino FZGA, Lerond L. Leukocyte adhesion after oxidant challenge in the hamster cheek pouch microcirculation. J Vasc Res 1999; 36 Suppl. 1: 11-4
44. 2 release and histological changes. Arzneimittelforschung 1987 Oct; 37 (10): 1149-53
45. Lonchampt M, Guardiola B, Sicot N, et al. Protective effect of a purified flavonoid fraction against reactive oxygen radicals: in vivo and in vitro study. Arzneimittelforschung 1989 Aug; 39 (8): 882-5
46. Jean T, Bodinier MC. Mediators involved in inflammation: effects of Daflon 500 mg on their release. Angiology 1994 Jun; 45 (6 Pt 2): 554-9
47. Stucker O, Bonhomme E, Lenaers A, et al. Daflon 500 mg depresses bradykinin-ischemia-induced microvascular leakage of FITC Dextran in rat cremaster muscle. Int Angiol 1989; 8 (4 Suppl.): 39-43
48. Bouskela E, Svensjö E, Cyrino FZGA, et al. Oxidant-induced increase in vascular permeability is inhibited by oral administration of S-5682 (Daflon 500 mg) and alpha-tocopherol. Int J Microcirc Clin Exp 1997; 17 Suppl. 1: 18-20
49. Cesarone MR, Laurora G, De Sanctis MT, et al. Capillary filtration and ankle edema in patients with venous hypertension: effects of Daflon. Angiology 1993; 44 (1): 57-61
50. Juteau J, Bakri F, Pomies P, et al. The human saphenous vein in pharmacology: effect of a new micronized flavonoidic fraction (Daflon 500 mg) on norepinephrine induced contraction. Int Angiol 1995; 14: 8-13
51. Gargouil YM, Perdrix L, Chapelain B, et al. Effects of Daflon 500 mg on bovine vessels contractility. Int Angiol 1989; 8 (4 Suppl.): 19-22
52. 2+ of the smooth muscle contractile apparatus in the rat isolated femoral vein. Br J Pharmacol 1994 Apr; 111 (4): 978-80
53. Delbarre B, Delbarre G, Pillion G, et al. Effects of Daflon 500 mg on haemoconcentration and alterations of white blood cell count elicited by the upright position in anaesthetized dogs. Int Angiol 1995 Sep; 14 (3 Suppl. 1): 23-5
54. Bouskela E, Cyrino FZGA, Lerond L. Effects of oral administration of different doses of purified micronized flavonoid fraction on microvascular reactivity after ischaemia/reperfusion in the hamster cheek pouch. Br J Pharmacol 1997 Dec; 122 (8): 1611-6
55. McGregor L, Bellangeon M, Chignier E, et al. Effect of a micronized purified flavonoid fraction on in vivo platelet functions in the rat. Thromb Res 1999; 94: 235-40
56. McHale NG, Hollywood MA. Control of lymphatic pumping: interest of Daflon 500 mg. Phlebology 1994; 9 Suppl. 1: 23-5
57. Labrid C. Pharmacologic properties of Daflon 500 mg. Angiology 1994 Jun; 45 (6 Pt 2): 524-30
58. Barbe R, Amiel M. Pharmacodynamic properties and therapeutic efficacy of Daflon 500 mg. Phlebology 1992; 7 Suppl. 2: 41-4
59. Ibegbuna V, Nicolaides AN, Sowade O, et al. Venous elasticity after treatment with Daflon 500 mg. Angiology 1997 Jan; 48 (1): 45-9
60. Bergan JJ, Schmid-Schönbein GW, Takase S. Therapeutic approach to chronic venous insufficiency and its complications: place of Daflon 500 mg. Angiology 2001 Aug; 52 Suppl. 1: S43-7
61. Galley P, Thiollet M. A double-blind, placebo-controlled trial of a new veno-active flavonoid fraction (S 5682) in the treatment of symptomatic capillary fragility. Int Angiol 1993 Mar; 12 (1): 69-72
62. Belcaro G, Cesarone MR, De Sanctis MT, et al. Laser Doppler and transcutaneous oximetry: modern investigations to assess drug efficacy in chronic venous insufficiency. Int J Microcirc Clin Exp 1995; 15 Suppl. 1: 45-9
63. Ener BK. Dorsal pedal venous oximetry for assessing treatment of chronic venous insufficiency: effects of Daflon 500 mg. Vasc Surg 2000; 34 (1): 43-9
64. Allegra C, Bartolo Jr M, Carioti B, et al. An original microhaemorheological approach to the pharmacological effects of Daflon 500 mg in severe chronic venous insufficiency. Int J Microcirc Clin Exp 1995; 15 Suppl. 1: 50-4
65. Struckmann JR. Clinical efficacy of micronized purified flavonoid fraction: an overview. J Vasc Res 1999; 36 Suppl. 1: 37-41
66. Cova D, De Angelis L, Giavarini F, et al. Pharmacokinetics and metabolism of oral diosmin in healthy volunteers. Int J Clin Pharmacol Ther Toxicol 1992 Jan; 30 (1): 29-33
67. Messmer K. Daflon 500 mg: expert report on the preclinical documentation. Courbevoie Cedex, France: Institut de Recherches Internationales Servier, 1997 Oct
68. Les Laboratoires Servier. Daflon 500: summary of product characteristics [online]. Available from URL: http://www.servier.com/pro/phlebologie/daflon_spc.asp [Accessed 2002 Sep 12]
69. Chassignolle J-F, Amiel M, Lanfranchi G, et al. Activité thérapeutique de Daflon 500 mg dans l'insuffisance veineuse fonctionnelle [in French]. J Int Med 1987; 99 (Suppl.): 32-7
70. Gilly R, Pillion G, Frileux C. Evaluation of a new venoactive micronized flavonoid fraction (S 5682) in symptomatic disturbances of the venolymphatic circulation of the lower limb: a double-blind, placebo-controlled study. Phlebology 1994; 9 (2): 67-70
71. Cospite M, Dominici A. Double blind study of the pharmaco-dynamic and clinical activities of 5682 SE in venous insufficiency. Advantages of the new micronized form. Int Angiol 1989; 8 (4 Suppl.): 61-5
72. Tsouderos Y. Are the phlebotonic properties shown in clinical pharmacology predictive of a therapeutic benefit in chronic venous insufficiency?: our experience with Daflon 500 mg. Int Angiol 1989 Oct-1989 31; 8 (4 Suppl.): 53-9
73. Menyhei G, Acsady G, Hetenyi A, et al. Chronobiology and clinical activity of Daflon 500 mg in chronic venous insufficiency. Phlebology 1994; 9 Suppl. 1: 15-8
74. Jantet G. Chronic venous insufficiency: worldwide results of the RELIEF study. Reflux assEssment and quaLity of life improvEment with micronized Flavonoids. Angiology 2002; 53 (3): 245-56
75. Guillot B, Guilhou JJ, de Champvallins M, 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 (4 Suppl.): 67-71
76. Launois R, Reboul-Marty J, Henry B. Construction and validation of a quality of life questionnaire in chronic lower limb venous insufficiency (CIVIQ). Qual Life Res 1996; 5: 539-54
77. Les Laboratoires Servier. Data on file. 2002
78. Guilhou J-J, Février F, Debure C, et al. Benefit of a 2-month treatment with a micronized, purified flavonoidic fraction on venous ulcer healing: a randomized, double-blind, controlled versus placebo trial. Int J Microcirc Clin Exp 1997; 17 Suppl. 1: 21-6
79. Gliñski W, Chodynicka B, Roszkiewicz J, et al. The beneficial augmentative effect of micronised purified flavonoid fraction (MPFF) on the healing of leg ulcers: an open, multicentre, controlled, randomised study. Phlebology 1999; 14 (4): 151-7
80. Cospite M. Double-blind, placebo-controlled evaluation of clinical activity and safety of Daflon 500 mg in the treatment of acute hemorrhoids. Drugs Today 1995; 31 Suppl. E: 49-55
81. Misra MC, Parshad R. Randomized clinical trial of micronized flavonoids in the early control of bleeding from acute internal haemorrhoids. Br J Surg 2000; 87 (7): 868-72
82. Ho Y-H, Tan M, Seow-Choen F. Micronized purified flavonidic fraction compared favorably with rubber band ligation and fiber alone in the management of bleeding hemorrhoids: randomized controlled trial. Dis Colon Rectum 2000 Jan; 43 (1): 66-9
83. Buckshee K, Takkar D, Aggarwal N. Micronized flavonoid therapy in internal hemorrhoids of pregnancy. Int J Gynaecol Obstet 1997 May; 57 (2): 145-51
84. Ho Y-H, Foo CL, Seow-Choen F, et al. Prospective randomized controlled trial of a micronized flavonidic fraction to reduce bleeding after haemorrhoidectomy. Br J Surg 1995 Aug: 82 (8): 1034-5
85. Meyer O. Safety of use of Daflon 500 mg confirmed by acquired experience and new research. Phlebology 1992; 7 Suppl. 2: 64-8
86. Tsouderos Y, Lecomte M. Dalfon 500 mg: review of clinical data. Neuilly-sur Seine, France: Les Laboratoires Servier, 2001 Dec
87. Les Laboratoires Servier. Daflon: questions and answers [online]. Available from URL: http:///www.servier.com/pro/phlebologie/daflon_faq.asp [Accessed 2001 Sep 12]
88. Ramelet A-A, Monti M. Drug Therapy. Phlebology: the guide. 4th ed. Paris, France: Elsevier, 1999: 303-18
89. Frick RW. Three treatments for chronic venous insufficiency: escin, hydroxyethylrutoside, and Daflon. Angiology 2000 Mar; 51 (3): 197-205
90. Coleridge Smith PD. The drug treatment of chronic venous insufficiency and venous ulceration. In: Gloviczki P, Yao JST, editors. Handbook of venous disorders: guidelines of the American Venous Forum. 2nd ed. London: Arnold, 2001: 309-21
91. Vanscheidt W, Jost V, Wolna P, et al. Efficacy and safety of a Butcher's broom preparation (Ruscus aculeatus L. extract) compared to placebo in patients suffering from chronic venous insufficiency. Arzneimittelforschung 2002; 52 (4): 243-50
92. Widmer L, Biland L, Barras JP. Doxium 500 in chronic venous insufficiency: a double-blind placebo. Controlled multicentre study. Int Angiol 1990; 9 (2): 105-10
93. Pittler MH, Ernst E. Horse-chestnut seed extract for chronic venous insufficiency: a criteria-based systematic review. Arch Dermatol 1998; 134: 1356-60
94. Wadworth AV, Faulds D. Hydroxyethylrutosides: a review of its pharmacology, and therapeutic efficacy in venous insufficiency and related disorders. Drugs 1992 Dec; 44: 1013-32
95. Travers JP, Makin GS. Reduction of varicose vein recurrence by use of postoperative compression stockings. Phlebology 1994; 9: 104-7
96. Clement DL. Venous ulcer reappraisal: insights from an international task force. J Vasc Res 1999; 36 Suppl. 1: 42-7
97. Nelzén O, Bergqvist D, Lindhagen A. Long-term prognosis for patients with chronic leg ulcers: a prospective cohort study. Eur J Vasc Endovasc Surg 1997; 13: 500-8
98. Dormandy JA. Pharmacologic treatment of venous leg ulcers. J Cardiovasc Pharmacol 1995; 25 Suppl. 2: S61-5
99. Anonymous. Consensus paper on venous leg ulcer. Alexander House Group. J Dermatol Surg Oncol 1992 Jul; 18 (7): 592-602
100. Falanga V, Fujitani RM, Diaz C, et al. Systemic treatment of venous leg ulcers with high doses of pentoxifylline: efficacy in a randomized, placebo-controlled trial. Wound Rep Reg 1999; 7 (4): 208-13
101. Colgan M-P, Dormandy JA, Jones PW, et al. Oxpentifylline treatment of venous ulcers of the leg. BMJ 1990; 300: 972-5
102. 1 in the treatment of venous ulcers- a double-blind, placebo-controlled trial. VASA 1989; 28 Suppl.: 39-43
103. Fletcher A, Cullum N, Sheldon TA. A systematic review of compression treatment for venous leg ulcers. Br Med J 1997 Sep 6; 315: 576-80
104. Mayberry JC, Moneta GL, Taylor LM, et al. Fifteen-year results of ambulatory compression therapy for chronic venous ulcers. Surgery 1991; 109 (5): 575-81
105. Moneta GL, Nicoloff AD, Porter JM. Compression treatment of chronic venous ulceration: a review. Phlebology 2000; 15: 162-8
106. Allegra C, Sarcinella R, Bartolo Jr M. Morphologic and functional changes of the microlymphatic network in patients with advancing stages of primary lymphedema. Lymphology 2002 Sep; 35 (3): 114-20
107. Franks PJ, Oldroyd MI, Dickson D, et al. Risk factors for leg ulcer recurrence: a randomized trial of two types of compression stocking. Age Ageing 1995; 24: 490-4
108. American Society of Colon and Rectal Surgeons. Practice parameters for the treatment of hemorrhoids [online]. Available from URL: http://www.fascrs.org/ascrspp-toh.html [Accessed 2002 Sep 26]
109. Moesgaard F, Nielsen ML, Hansen JB. et al. High-fiber diet reduces bleeding and pain in patients with hemorrhoids: a double-blind trial of Vi-Siblin. Dis Colon Rectum 1982; 25 (5): 454-6
110. Perez-Miranda M, Gomez-Cedenilla A, León-Colombo T, et al. Effect of fiber supplements on internal bleeding hemorrhoids. Hepatogastroenterology 1996; 43 (12): 1504-7
111. Shafik A. Role of warm-water bath in anorectal conditions: the "thermosphincteric reflex". J Clin Gastroenterol 1993 Jun; 16 (4): 304-8