Diosmin: benefits, dosage, contraindications
Scientific name(s)
Diosmin
Family or group:
Phytosubstances
Indications
Scoring methodology
EFSA approval.
Venous insufficiency ✪✪✪✪✪
Many clinical studies support the efficacy of diosmin, alone or in combination, for improving the symptoms of chronic venous insufficiency. The most studied product, Daflon 500 mg, combines 450 mg of micronized diosmin and 50 mg of other flavonoids, mainly hesperidin. Taken at 2 to 3 tablets per day for 2 to 6 months, it significantly reduces pain, heaviness, edema and cramps compared with placebo or baseline. In an observational study in patients with advanced chronic venous insufficiency, taking 1000 mg of a Micronized Purified Flavonoid Fraction (MPFF) for 6 months, in addition to compression therapy, reduced symptoms (edema, varicose veins, pain) and subcutaneous adipose tissue thickness, although the absence of a comparator group limits these findings. Research comparing diosmin alone and in combination with other flavonoids shows that micronized diosmin is more effective than the non-micronized form in reducing symptoms. However, in some cases, a non-micronized diosmin (Flebodia 600 mg) has demonstrated efficacy equivalent to Daflon 1000 mg. Overall, diosmin is a treatment of choice in chronic venous insufficiency, particularly in the micronized formulation.
Posologie
Oral
450 - 1000 mg
Micronized Purified Flavonoid Fraction
Synergies
Clinical Efficacy of Conservative Treatment with Micronized Purified Flavonoid Fraction in Female Patients with Pelvic Congestion Syndrome
Micronized purified flavonoid fraction-based conservative treatment of chronic venous disease in a real-world setting
Analysis of the effects of micronized purified flavonoid fraction versus placebo on symptoms and quality of life in patients suffering from chronic venous disease: from a prospective randomized trial
MPFF 1000 mg chewable once daily vs. MPFF 500 mg twice daily in chronic venous disease: the double-blind, randomized, non-inferiority CHEWY trial
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
Efficacy of a Low-Dose Diosmin Therapy on Improving Symptoms and Quality of Life in Patients with Chronic Venous Disease: Randomized, Double-Blind, Placebo-Controlled Trial
Hemorrhoids ✪✪✪✪✪
Clinical studies and a meta-analysis confirm the efficacy of the Micronized Purified Flavonoid Fraction (MPFF) containing 450 mg of diosmin and 50 mg of flavonoids (Daflon 500) in the management of internal hemorrhoids. Taken as three tablets twice daily for 4–5 days, followed by two tablets twice daily for 3 months, this treatment reduces acute bleeding in up to 92% of patients within 4 days and improves symptoms such as pain, anal discomfort, and discharge in just 2 days. Postoperatively, MPFF also accelerates recovery after hemorrhoidopexy or hemorrhoidectomy. A maintenance treatment with one tablet twice daily for 2–3 months reduces the relapse rate and improves persistent symptoms, including pain, itching, swelling, and bleeding. A combination of diosmin, troxerutin, and hesperidin showed promising results in acute hemorrhoidal attacks. Administered at tapering doses over 43 days, it significantly reduces pain (in 88% of patients), bleeding (64%), and anal itching (56%) compared with placebo. The protocol includes an initial 3-day phase with three sachets per day containing diosmin 300 mg, troxerutin 300 mg, and hesperidin 300 mg, followed by reduced doses for 40 days. Another combination with bulk-forming laxatives, including diosmin 600 mg three times a day for 4 days then 300 mg twice a day for 10 days with psyllium 11 g/day, modestly improves symptoms after 4 days, although it is less effective than MPFF.
Posologie
Orally
300 mg
Micronized Purified Flavonoid Fraction
Double-blind, placebo-controlled evaluation of clinical activity and safety of Daflon 500 mg in the treatment of acute hemorrhoids
Micronized Purified Flavonoid Fraction in Hemorrhoid Disease: A Systematic Review and Meta-Analysis
Micronized flavonoid therapy for internal hemorrhoids during pregnancy
Flavonoid mixture (diosmin, troxerutin, hesperidin) in the treatment of acute hemorrhoidal disease: a prospective, randomized, triple-blind, controlled trial
Leg ulcer ✪✪✪✪✪
Venous leg ulcers result from chronic venous insufficiency, where blood reflux and venous hypertension damage the skin tissues, causing painful open lesions. These ulcers, often located on the lower leg, are difficult to heal without appropriate treatment. Clinical studies show that taking two tablets per day of a Micronized Purified Flavonoid Fraction (MPFF, Daflon 500) containing 450 mg of diosmin and 50 mg of flavonoids, in addition to compression bandaging, doubles the number of patients achieving complete healing of ulcers up to 10 cm in diameter compared with placebo. Moreover, the time required for healing is significantly reduced. However, this combination did not show significant effects on ulcers larger than 10 cm in terms of surface reduction, symptoms, or healing rates.
Posologie
Oral administration
450 mg
Micronized Purified Flavonoid Fraction
Efficacy of Daflon 500 mg in venous leg ulcer healing: a double-blind, randomized, placebo-controlled trial in 107 patients
Benefit of a 2-month treatment with a micronized, purified flavonoid fraction on venous ulcer healing: a randomized, double-blind, placebo-controlled trial
Venous thromboses ✪✪✪✪✪
In a clinical study, the addition of 600 mg of diosmin daily to rivaroxaban and compression stockings for 12 months significantly reduced the incidence of post-thrombotic syndrome in patients with femoropopliteal deep vein thrombosis (DVT) compared with standard treatment alone.nnDiosmin also accelerated venous recanalization and slowed the progression of chronic venous disease, while improving patients' quality of life, measured by the CIVIQ-20 score.nn
Posologie
Oral administration
600 mg
Micronized Purified Flavonoid Fraction
Properties
Venotonic
Diosmin improves vascular health by strengthening venous tone and reducing blood stasis. It acts by increasing intracellular cAMP levels via inhibition of phosphodiesterase, which reduces the production of inflammatory prostaglandins (PGE2, PGF2) and thromboxanes (A2, B2). It also decreases the expression of endothelial adhesion molecules, reducing neutrophil infiltration and the formation of free radicals. In a clinical study of patients with chronic venous insufficiency, administration of diosmin (Daflon 500 mg) for 60 days significantly reduced symptoms such as edema and pain, while improving capillary permeability and lymphatic drainage. These anti-inflammatory and pro-angiogenic effects also promote healing of venous ulcers.
Usages associés
Anti-inflammatory
Diosmin reduces inflammation by modulating pro-inflammatory mediators and limiting oxidative damage. It inhibits phosphodiesterase, increasing intracellular cAMP levels, which decreases the production of prostaglandins (PGE2, PGF2) and thromboxanes (A2, B2).
Hepatoprotective
Diosmin and its metabolite, diosmetin, exhibit promising hepatoprotective properties. Diosmetin acts as a direct antioxidant, increasing glutathione (GSH) levels and reducing lipid peroxidation, thereby limiting damage to the liver. Preclinical studies have shown that diosmin protects the liver against the toxic effects of heavy metals, such as cadmium and lead. It attenuates liver injury by reducing inflammation and oxidative stress induced by these substances. These mechanisms include a decrease in pro-inflammatory cytokines and an improvement in antioxidant markers such as superoxide dismutase (SOD) and glutathione.
Safe dosage
Adult: 450 mg - 1350 mg (Micronized Purified Flavonoid Fraction)
Diosmin is generally used alone or in combination with other flavonoids, at doses of 450 to 1350 mg per day for 1 to 6 months, depending on the indication.nn
Interactions
Médicaments
Diclofenac: moderate interaction
Diosmin could increase the blood levels and clinical effects of diclofenac by inhibiting its metabolism. A human pharmacokinetic study showed that taking diosmin (Venex 500, 500 mg/day) for 9 days before a 100 mg oral dose of diclofenac increased the latter's plasma concentrations while reducing its clearance. This effect is thought to be related to inhibition of cytochrome P450 2C9 (CYP2C9), which is responsible for diclofenac metabolism.
Fexofenadine: moderate interaction
Diosmin could increase the blood concentrations and clinical effects of fexofenadine. A human pharmacokinetic study showed that taking diosmin (Venex, 500 mg/day) for 10 days before oral administration of fexofenadine 120 mg increased its plasma levels by 49% and reduced its apparent oral clearance by 41%. These effects appear to be related to inhibition of intestinal P-glycoprotein by diosmin, with no impact on the kidney or the liver. Other pharmacokinetic parameters, such as time to reach maximum plasma concentration and half-life, are not affected.
Carbamazepine: moderate interaction
Diosmin could reduce the therapeutic effects of carbamazepine while increasing the risk of seizures. A human pharmacokinetic study showed that taking diosmin (Venex, 500 mg/day) for 10 days before a 200 mg oral dose of carbamazepine increased carbamazepine plasma concentrations by 58% while decreasing its clearance by 42%. Additionally, formation of carbamazepine's active metabolite was reduced, likely due to inhibition of cytochrome P450 3A4 (CYP3A4) by diosmin.
Precautions
Pregnant women: use with caution
Diosmin is taken during pregnancy at doses up to 900 mg per day, in combination with hesperidin, for a maximum of 30 days. However, its use in the third trimester may be associated with placental insufficiency.nn
Breastfeeding women: use with caution
During breastfeeding, diosmin does not appear to affect infants' growth or feeding, but medical advice is recommended before use.nn
