What is the recommended dose of Diosmin (micronized purified flavonoid fraction) plus Hesperidin for an adult patient with chronic venous insufficiency?

Diosmin plus Hesperidin Dosing for Chronic Venous Insufficiency

Standard Dosing Regimen

For chronic venous insufficiency manifested as varicose veins, edema, or stasis dermatitis, the recommended dose is 1000 mg daily (one 500 mg tablet twice daily or one 1000 mg tablet once daily). 1, 2

Evidence-Based Dosing by Clinical Presentation

For general CVI symptoms (varicose veins, edema, leg heaviness):

• Diosmin 450 mg + Hesperidin 50 mg (micronized purified flavonoid fraction): 1 tablet twice daily 1, 2, 3
• Results typically appear within 4-8 weeks of continuous therapy 1
• This dosing significantly decreases ankle/calf circumference and improves venous hemodynamic parameters compared to placebo 4, 2

For venous leg ulcers ≤10 cm diameter:

• Diosmin 450 mg + Hesperidin 50 mg: 1 tablet twice daily (total 1000 mg/day) plus standard compression therapy and local wound care 2
• Treatment duration: 2-6 months minimum 2
• Results may not be evident for several months 1
• This combination significantly increases complete healing rates compared to standard management alone 5, 2

For acute hemorrhoidal disease (grade 1-2):

• Initial phase: 3 tablets twice daily (3000 mg/day) for 4 days 1, 2
• Maintenance phase: 2 tablets twice daily (2000 mg/day) for 3-9 days 1, 2
• Long-term maintenance: 600 mg daily for recurrent symptoms 1

Critical Clinical Context

MPFF (micronized purified flavonoid fraction) is adjunctive therapy only—it cannot replace compression therapy or interventional treatment in moderate-to-severe disease. 5 The American Heart Association emphasizes that compression stockings (20-30 mmHg for CEAP C1-C3, 30-40 mmHg for C4-C6) remain mandatory initial treatment and must be continued for minimum 3 months before interventional therapy is considered 5

Treatment Algorithm Based on Disease Severity

CEAP C1-C3 (mild-to-moderate symptoms without skin changes):

• Start compression therapy 20-30 mmHg 5
• Add MPFF 1000 mg daily as adjunctive therapy 5, 2
• Continue for minimum 3 months before considering intervention 5

CEAP C4-C6 (skin changes, lipodermatosclerosis, or ulceration):

• Compression therapy 30-40 mmHg is mandatory 5
• MPFF 1000 mg daily as adjunctive therapy 5, 2
• Do not delay interventional therapy (thermal ablation) for prolonged compression trials—early intervention prevents progression 5
• For venous ulcers, MPFF plus standard management significantly increases healing rates over 2-6 months 5, 2

Formulation Considerations

The micronization of diosmin to particles <2 micrometers significantly improves absorption and clinical efficacy compared to non-micronized formulations. 2, 3 Studies demonstrate that micronized purified flavonoid fraction (90% diosmin + 10% hesperidin) produces more substantial improvement in clinical symptoms and venous hemodynamic parameters than non-micronized diosmin alone 3

Expected Outcomes and Monitoring

Plethysmographic improvements: MPFF 1000 mg daily significantly decreases venous capacitance, venous distensibility, and venous emptying time (P < 0.001) 4

Clinical symptom improvement: Significant reduction in leg pain, heaviness, fatigue, and edema within 2 months of therapy 4, 2

Ulcer healing: For venous ulcers ≤10 cm diameter, MPFF plus standard management accelerates complete healing compared to standard management alone over 2-6 months 5, 2

Safety Profile

MPFF has a tolerability profile similar to placebo. 2 The most frequently reported adverse events are gastrointestinal (nausea, indigestion) and autonomic in nature, occurring rarely and leading to treatment withdrawal in only 3 of 183 patients in controlled trials 4, 2

Common Pitfalls to Avoid

Do not use MPFF as monotherapy replacement for compression in patients with documented saphenofemoral junction reflux—this leads to 20-28% recurrence rates at 5 years. 5 The American College of Radiology explicitly states that compression stockings alone have no proven benefit in preventing post-thrombotic syndrome in recent randomized trials 5

Do not delay thermal ablation in CEAP C4-C6 disease for prolonged MPFF trials—early interventional treatment prevents progression. 5 MPFF serves as adjunctive medical therapy, not primary treatment for severe venous insufficiency with documented reflux 5

For patients with venous ulcers, do not expect rapid results—healing may require several months of continuous therapy at 1000 mg daily plus compression. 1, 2