Is There a Difference in the Clinical Efficacy of Diosmin and Micronized Purified Flavonoid Fraction for the Treatment of Chronic Venous Disorders? Review of Available Evidence

Figures & data

Figure 1 Flow Diagram of the Literature Review

Table 1 Summary of Randomized Trials Comparing Diosmin and Micronized Purified Flavonoid Fraction for the Treatment of Chronic Venous Disease

Study	Design	Study Groups	Study Objective	Duration	Inclusion Criteria	Primary Evaluation Criteria	Efficacy Results
Henriet (1995)^Citation17	Multicentric randomized double-blind study	Diosmin 600 (n=34) MPFF 500 (n=35)	To compare: Diosmin 600 mg once a day and MPFF 500 mg twice a day	28 days	Women 18 to 45 y suffering ≥6 months from functional symptoms of CVD (pain and/or heaviness in the lower limbs)	Weekly patient self-assessment (VAS) of pain/heaviness at D0, D7, D14, D21 and D28	Change from baseline of pain/heaviness assessed by patients significantly improved: p < 0.0001 at each time point from D7 to D28 No difference between groups
Maruszynski (2004)^Citation18	Multicentric randomized double-blind study	Diosmin 600 (n=59) MPFF 500 (n=60)	To compare: Diosmin 600 mg once a day and MPFF 500 mg twice a day	28 days	Women 20 to 60 y with CVD symptoms (C0-C3)	Weekly patient self-assessment (sum of individual scores of functional symptoms) at D0, D7, D14, D21 and D28	Significant decrease in symptoms in both groups No difference between treatment groups
Steinbruch (2020)^Citation19	Multicentric non-inferiority single-blind randomized study	Diosmin 600 (n=57) MPFF 1000 (n=57)	To assess the non-inferiority of diosmin 600 mg once a day compared to MPFF 1000 mg once a day	6 months	Patients with CVD symptoms (C0-C3) between 20 and 60 mm of a 100-mm VAS (patient self-assessment)	Self-assessment (VAS) at M0, M2, M4 and M6 of venous symptoms in CVD patients	Non-inferiority was demonstrated Significant improvement of symptoms from M2, maximal at M6, in both groups (p < 0.0001)

Abbreviations: CVD, chronic venous disease; D, day; M, month; MPFF, micronized purified flavonoid fraction; VAS, visual analog scale; y, years.

Table 2 Summary of Adverse Reactions Reported During the Randomized Trials

Study	Non-Micronized Diosmin 600 mg	MPFF 1000 mg
Henriet (1995)^Citation17	Vomiting and diarrhoea (n=1), gastralgia (n=1), headache (n=1) (n=3/34)	Gastralgia (n=3), constipation and abdominal meteorism (n=1), nausea (n=1) (n=5/35)
Maruszynski (2004)^Citation18	Calf, hand and feet oedema, body rash (n=NI/59)	Calf oedema, body rash, mouth dryness (n=NI/60)
Steinbruch (2020)^Citation19	Nausea (13.3%), dyspepsia (16.7%), diarrhoea (8.3%), headache (6.7%), vertigo (6.7%) (n=21/57)	Nausea (20%), dyspepsia (6.7%), diarrhoea (5.0%), headache (6.7%), vertigo (3.3%) (n=16/57)

Abbreviations n, Number of patients experiencing adverse reaction; NI, Not indicated; MPFF, micronized purified flavonoid fraction.

Henriet J. Insuffisance veineuse fonctionnelle: essai clinique comparatif d’une seule prise par jour de Diovenor 600 mg (600 mg de diosmine d’hémisynthèse) versus 2 prises par jour d’un mélange de 500 mg de flavonoïdes (900 mg de diosmine). [Functional venous insufficiency: comparative clinical trial of a single daily dose of DIOVENOR 600 mg (600 mg of hemisynthetic diosmin) versus two daily doses of a combination of 500 mg of flavonoids (900 mg of diosmin)]. Phlébologie (Annales Vasculaires). 1995;48:285–290.

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Maruszynski A. A double blind, randomized study evaluating the influence of semisynthetic diosmin, and purified, micronized flavonoid fraction (diosmin and hesperidin), on symptoms of chronic venous insufficiency of lower limb - a four week observation. Przeglad Flebologiczny. 2004;13:89–95.

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Steinbruch M, Nunes C, Gama R, et al. Is nonmicronized diosmin 600 mg as effective as micronized diosmin 900 mg plus hesperidin 100 mg on chronic venous disease symptoms? Results of a noninferiority study. Int J Vasc Med. 2020;2020:4237204.

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