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Scientific Name(s): 3′,5,7-trihydroxy-4-methoxyflavone-7-rutinoside, 3′,5,7-trihydroxy-4′-methoxyflavone-7-ramnoglucoside, Diosmetin 7-O-rutinoside
Common Name(s): Diosmin, Diosmine

Medically reviewed by Last updated on Dec 22, 2022.

Clinical Overview


Diosmin has been widely used since 1969 as a phlebotonic and vascular protector for venous leg ulcers and hemorrhoids; however, clinical data to support these uses are limited. Most, but not all available clinical data support its use for chronic venous insufficiency (CVI) and hemorrhoid disease, both acute and chronic. Diosmin has also been used to improve postoperative cardiac function and outcomes in adults undergoing coronary artery bypass grafting (CABG) surgery, for pelvic congestion caused by pelvic varicose veins in men and women, and for varicoceles in men; however, few large-scale quality clinical trials support these uses.


Diosmin is commercially available in the United States and Europe as a nonprescription dietary supplement (ie, DiosVein). It is most often combined in a micronized form with hesperidin (diosmin 90% plus hesperidin 10%), referred to as micronized purified flavonoid fraction (MPFF), and marketed in the United States as Daflon 500 (diosmin 450 mg/hesperidin 50 mg). The usual diosmin dosage is 1,000 mg orally daily given in 2 divided doses for short durations (ie, 3 months or less). Cardiac surgery (preoperative): Starting 7 days prior to CABG, MPFF 3,000 mg daily for 4 days, then 1,000 mg for 3 days. Chronic venous insufficiency: Diosmin 1,000 mg/day for 60 days; MPFF 500 mg twice daily or 1,000 mg once daily for up to 6 months. Hemorrhoidal crisis: Loading dose of MPFF 1,000 mg 3 times daily for 4 days, then 1,000 mg twice daily for 3 days. Hemorrhoid management: MPFF 1,000 mg/day orally for 3 months. Hemorrhoidectomy: Starting on the sixth day after surgery, MPFF 1,500 mg twice daily after meals for 3 days, followed by 1,000 mg twice daily on days 4 to 7. Pelvic congestion/varicose veins: MPFF 1,000 mg once daily for up to 6 months; in women who do not respond, increase to 2,000 mg/day after 4 weeks. Varicoceles/Male infertility: MPFF 1,000 mg/day for 6 months.


The gel formulation is contraindicated for application to mucosa, dermal irritations, or wounds, and it should not be used to treat dermatitis, eczema, or urticaria. Diosmin is not recommended for use in children.


Avoid use. Diosmin is not recommended for use in pregnant or breast-feeding women.


Serum concentrations may be increased by coadministration of drugs metabolized by cytochrome P450 (CYP-450) 2E1 or 2C9, or by P-glycoprotein.

Adverse Reactions

The most common adverse effects are mild GI and autonomic disturbances (pruritus, erythema, dermatitis [hives, itching], stomach and epigastric pain, nausea, diarrhea, and dizziness); cardiac arrhythmias (tachycardia) and hemolytic anemia have also been documented. Rare excessive peripheral vasoconstriction and ischemic damage have been reported.


Extensive safety evaluations conducted with MPFF found no risk of toxicity.


In 1925, diosmin was first isolated from Scrophularia nodosa L. (figwort). It was introduced as a therapeutic agent in 1969 and has been widely used in Europe as a phlebotonic and vascular protector for the treatment of venous leg ulcers and hemorrhoids. Since 2005 it has been used to treat vascular diseases. Due to its potential anticancer effects, many researchers consider diosmin an alternative treatment for various cancers, including hepatocellular, colon, and urinary bladder cancers, with advantages being lower costs and fewer adverse reactions compared with chemotherapy.Ba-bai-ke-re 2011, Freag 2013, Silvestro 2013

Since 2000, micronized diosmin (90%) plus hesperidin (10%) as a fixed pharmaceutical product (MPFF) has been used extensively in Europe to treat blood vessel and lymphatic diseases.Ba-bai-ke-re 2011 It is most often used in the United States as the dietary supplement Daflon (diosmin 450 mg/hesperidin 50 mg).Bogucka-Kocka 2013


Diosmin is a naturally occurring flavone glycoside that is isolated from various plants, especially citrus rinds, or derived from the flavonoid hesperidin.Bogucka-Kocka 2013, Lewinska 2015 It is rapidly hydrolyzed by the gut microbiome in the intestine to the active aglicone metabolite diosmetin, and is then absorbed. The volume of distribution of diosmin is 54.2 to 70 L, with a half-life documented at 22.9 to 40.1 hours and maximum plasma concentration (Cmax) of 322.9 to 511.1 ng/mL achieved 1 hour following an oral 10 mg/kg dose.Milano 2014 Diosmetin is extensively degraded into phenolic acids or their glycine conjugates and eliminated in the urine. Diosmetin-3-O-glucuronide is the major metabolite found in the plasma and urine, while 3,7-O-diglucuronide is present at low levels in plasma but not in urine; approximately half the dose is eliminated as unchanged diosmin or diosmetin in the feces.Milano 2014, Silvestro 2013

Diosmin is highly insoluble in water, which results in highly variable bioavailability among individuals. This necessitates a large oral standard dose of at least 500 mg twice daily. Improved bioavailability, absorption, and clinical efficacy have been observed with use of a micronized form (achieved by reducing particle size via the micronization process). In rats, a lyophilized formulation using phytosomal nanocarriers improved dissolution and intestinal permeation and therefore may offer a more stable option for drug dissolution.Freag 2013

Biologically, diosmin has demonstrated antioxidant, anticarcinogenic, antihyperglycemic, and antiulcer activities, as well as modulation of capillary permeability.Freag 2013, Silvestro 2013 Antioxidant and perhaps other activities provided a protective effect against streptozocin-induced diabetic neuropathy in rats.Jain 2014 Additionally, addition of diosmin to hesperidin increased antihyperalgesic effects in neuropathic pain models.Carballo-Villalobos 2016 In cyclophosphamide-treated rats, diosmin suppressed apoptosis and inflammation, preventing hepatic cell injury and death.Germoush 2016 As a phlebotonic and vascular protectant, diosmin's mechanism of action is attributed to the inhibition of metabolism of noradrenalin by the venous walls, which extends vascular smooth muscle contraction and increases vascular tonus. Diosmin exhibited a similar effect on lymphatic vessels.Bogucka-Kocka 2013

In Alzheimer disease mouse models, administration of diosmin resulted in reductions in physical measures of tau-hyperphosphorylation, amyloid-beta peptide levels, and cognitive impairment through glycogen synthase kinase-3– and transient receptor potential canonical 6–related mechanisms.Sawmiller 2016

Uses and Pharmacology

Anti-inflammatory and antioxidant activity

Clinical data

The impact of MPFF on the suspected underlying oxidative and inflammatory pathophysiology of chronic venous disease was explored in an experimental study of 89 women with primary varicose veins and diagnosed Clinical Etiological Anatomic Pathophysiologic (CEAP) stage C2 or C3 chronic venous disease. The influence of MPFF compared with no phlebotropic drug on the relationship between antioxidant enzyme balance, endothelin-1, and tumor necrosis factor alpha (TNF-alpha) levels was evaluated. Patients received MPFF (Detralex) 500 mg orally twice daily for at least 12 weeks. Compared with those patients not receiving phlebotropic treatment, administration of MPFF decreased the proinflammatory cytokines endothelin-1 and TNF-alpha and appeared to stabilize endothelin-1 during oxidative stress, especially in women who took MPFF for longer than 1 year.Pietrzycka 2015


Experimental data

In an experimental study identifying 5 CDK4 gene variations exhibiting highly deleterious effects on the CDK-4-cyclin D1 protein complex, diosmin demonstrated good binding affinity and interaction with one of the harmful mutated genes (Y18OH). This indicates that diosmin is a possible inhibitor of a harmful, single nucleotide polymorphism responsible for dysregulation of the CDK-4-cyclin D1 protein complex, which is common in many cancers.N 2015 Additionally, diosmin was the most cytotoxic and genotoxic of 3 citrus fruit flavonoids (ie, diosmin, naringin, hesperidin) tested in androgen-independent prostate cancer cells. Diosmin exhibited the highest inhibition of cancer cell proliferation (up to 30%), the highest augmentation of reactive oxygen species production (83%; P<0.001), a moderate increase in superoxide production (2.38-fold; P<0.001), potent induction of DNA double strand breaks and micronuclei production (2.64-fold increase and 5-fold increase, respectively; P<0.001), and the highest DNA damage. Diosmin was the only flavonoid of the 3 to induce apoptotic and necrotic cell death; however, it was the weakest inducer of DNA hypomethylation (P<0.05).Lewinska 2015

Cardiac surgery (preoperative)

Clinical data

A prospective, randomized controlled trial (N=43) investigated the effect of pretreatment with MPFF (Daflon) on postoperative cardiac function and outcomes in patients with left ventricular ejection fraction less than 0.5, greater than 70% stenosis of at least 2 coronary arteries, and New York Heart Association (NYHA) functional class status of 2.3 (European System for Cardiac Operative Risk Evaluation score [EuroSCORE] 3 to 5). Clinical staff were blinded to treatment allocation. Starting 7 days prior to CABG, patients received MPFF (3,000 mg daily for 4 days followed by 1,000 mg for 3 days) or placebo as part of their preoperative regimen. Postoperatively, both groups experienced a significant decrease in functional status, with patients in the MPFF group exhibiting a significantly greater improvement than placebo (P=0.02). Of the biomarkers studied, only levels of lactate dehydrogenase and cardiac troponin I were significantly lower in the MPFF group immediately after cardiopulmonary bypass (P=0.038 and P=0.003, respectively). One patient in the MPFF group died on the 19th postoperative day due to myocardial infarction.Sirlak 2010

Chronic venous insufficiency

Clinical data

A double-blind, randomized controlled dosing study in 174 patients with chronic venous disease compared the clinical acceptability of MPFF at the historical 500 mg twice-daily dosage with that of a once-daily regimen with a new 1,000 mg tablet. The study was conducted in 13 centers across Russia and Serbia. The study population was white, with the majority being female (83.3%), and 73.6% had at least one concomitant medical condition (33.9% menopause, 14.9% hypertension). Patients were classified according to CEAP stage (C0 to C4); the most frequent CEAP classification in the most affected leg was C2 (varicose veins; 38.5% of patients) and C3 (edema; 35.6% of patients). Of the 174 randomized patients, 171 completed the study, 87 patients (100%) in the twice-daily group and 84 patients (96.6%) in the once-daily group. A decrease in leg pain was observed in the 500 mg and 1,000 mg groups (mean change in visual analog scale [VAS] score of –4 cm and –4.2 cm, respectively). Adverse events were mild, with no severe treatment-emergent adverse events and no serious adverse events documented. Constipation, dyspepsia, and allergic dermatitis were considered treatment-related adverse effects in the 1,000 mg group, and 1 patient in the 500 mg group experienced a potential clinically important abnormal lab result (low hemoglobin).Kirienko 2016

A double-blind, randomized, placebo-controlled trial (N=136) compared the effectiveness of 3 venoactive agents for symptom relief in treatment-naive patients with CEAP stage C2 to C5 chronic venous disease; 81.1% of the study population was female. Water plethysmography of the lower extremity, tibiotarsal joint angle, and quality of life (measured via questionnaire designed for individuals with chronic venous disease) were assessed for 28 to 35 days after the start of treatment. The 3 venoactive treatment groups received diosmin 450 mg plus hesperidin 50 mg; aminaphthone 75 mg; or coumarin 15 mg plus troxerutin 90 mg every 12 hours; the duration of the intervention was not clearly stated. The diosmin and aminaphthone groups experienced improvements in quality of life, specifically for questionnaire items of "limb edema" and "pain/burning." However, there were no differences in lower limb absolute volumes or in tibiotarsal joint range with any of the treatments compared with baseline.Belczak 2014 Similar results were reported in a large, multinational, double-blind, randomized, controlled trial in symptomatic patients with CEAP stage C3 or C4 chronic venous disease (N=1,137). Patients were randomized to receive MPFF (Daflon 1,000 mg once daily for 4 months) or placebo. MPFF significantly reduced pain/leg heaviness and improved quality of life compared with placebo; however, statistical significance compared to baseline was not noted. Four patients in the MPFF group withdrew from the study because of adverse events (1 patient experienced pruritus, nausea, and brittle fingernails; 3 patients experienced abdominal pain, erysipelas, and depression).Rabe 2015

A Cochrane meta-analysis assessed efficacy data from 53 double-blind, randomized, controlled trials investigating the use of oral phlebotonics (rutosides, diosmin and hidrosmin, calcium dobesilate, Centella asiatica, aminaftone, Pycnogenol, and grape seed extract) for the treatment of signs and symptoms of lower extremity CVI. Ten trials investigated diosmin and/or hidrosmin (a standard mixture comprised mainly of mono- and di-O-beta-hydroxyethyl-diosmin). Study data were pooled in the absence of heterogeneity. Overall, the data supported the effectiveness of phlebotonics to reduce lower leg edema compared with placebo, based on moderate-quality evidence (N=1,245; n=839 for diosmin and hidrosmin). Subanalyses of only diosmin or hidrosmin pooled data showed significant improvement with treatment compared to placebo in edema, ankle perimeter circumference, trophic disorders, pain, lower leg cramps, heaviness, swelling in the lower legs, and global assessment by the participant. Dosages studied for diosmin included 1,000 mg/day for 60 days; MPFF was dosed at 500 mg twice daily or 1,000 mg once daily for up to 60 days. Overall, pooled adverse event data showed a greater incidence of adverse events with phlebotonics versus placebo (N=4,054); pooled data for diosmin and hidrosmin showed no difference compared with placebo.Martinez-Zapata 2016, Venosmil October 2014

An earlier meta-analysis of 10 randomized controlled trials (N=1,010) enrolling adults with venous insufficiency demonstrated similar results according to pooled data: venous ankle (malleolar) edema was significantly reduced with use of venoactive agents compared with placebo (P<0.0001). Mean reduction in ankle circumference was –0.8 cm with diosmin 90% plus hesperidin 10% (MPFF), –0.58 cm each for ruscus extract and hydroxyethylrutoside, –0.2 cm for diosmin alone, and –0.11 cm with placebo. However, subanalysis of each venoactive agent revealed that the effects of diosmin administered alone were not significantly different from placebo, whereas MPFF was statistically significantly superior to not only placebo but to the other products studied (P<0.0001).Allaert 2012

The effect of MPFF (Detralex) on venous trophic ulcers was assessed in a meta-analysis of 5 large randomized controlled trials conducted in Russia (N= 616). In these trials, 75% of patients had reflux in the superficial venous system alone or in both superficial and deep veins. The standard dose of 1,000 mg was administered for 2 months, or for 6 months when given as an adjunct to conventional therapy. Complete ulcer healing was achieved in 61.3% of diosmin-treated patients compared with 47.7% in control groups, and diosmin treatment led to shorter healing time (38% less than in the control group; mean of 16 weeks with diosmin vs 21 weeks with control). The benefit of diosmin treatment was present from week 8 of treatment. Subanalysis revealed that the benefit of MPFF was significant only in patients with an ulcer history of less than 5 years, in patients with mid-sized ulcers between 5 and 10 cm2, and in patients with ulcers that persisted for 6 to 12 months.Savel'ev 2006

A prospective trial compared the effect of MPFF (Daflon) with that of Pycnogenol in treating the signs and symptoms of severe CVI. Eighty-six patients with venous hypertension and microangiopathy were randomized to receive Pycnogenol 150 mg or 300 mg or Daflon 1,000 mg daily for 8 weeks. Compression stockings were not used. Significantly greater improvements in CVI signs, symptoms, and microcirculatory parameters were observed with Pycnogenol compared with Daflon (P<0.05). On average, edema, resting flux, and rate of ankle swelling were reduced twice as much with Pycnogenol compared with Daflon. It was unclear whether Daflon provided better improvement in any individual symptom compared to Pycnogenol. Both treatments were well tolerated, and no treatment-related adverse effects were reported.Cesarone 2006

Edema (posttraumatic)

Clinical data

Venotonic agents, including diosmin, have been reported to reduce calf and ankle swelling in patients with CVI. However, in one prospective, randomized controlled trial (N=81), adjunctive use of MPFF (Daflon 3,000 mg/day for 20 days) did not provide additional improvements to standard of care in adults experiencing acute posttraumatic edema subsequent to type II or III ankle sprain.Fotiadis 2011

In a randomized controlled trial conducted in China, warm acupuncture (combination of acupuncture and moxibustion) was compared with diosmin (control) for the treatment of breast cancer–related lymphedema in 30 women with unilateral, upper limb lymphedema symptoms resulting from modified radical mastectomy (with or without radiation therapy). Median time from surgery to initiation of treatment was 8.8 months; diosmin 900 mg orally 3 times daily or moxibustion was administered for 30 days. At both 1 week and 30 days, moxibustion significantly improved the overall effective index for upper limb lymphedema compared with diosmin (19.8% vs 8.42% [P<0.001] and 51.46% vs 26.27% [P<0.00001], respectively). Additionally, subjective quality-of-life ratings were significantly better with moxibustion than with diosmin (P<0.05). No adverse events were noted during treatment.Yao 2016


Clinical data

A multicenter, double-blind, randomized dosing study (N=162) compared the clinical acceptability of a dosing regimen (3 g/day for 4 days followed by 2 g/day for 3 days) using MPFF 1,000 mg tablets versus MPFF 500 mg tablets in adults who had experienced an episode of symptomatic acute hemorrhoids within the past 5 days. Mean age of participants was 42 years, and more than 50% of patients reported at least one concomitant medical condition (eg, hypertension, constipation). Both the 1,000 mg tablet and the 500 mg tablet were associated with a significant reduction in anal pain (mean change in VAS score of –2.4 and –2.17 cm, respectively; P<0.001 for both) and improvement in bleeding (46.8% and 54.2%, respectively). Lab results in the 500 mg group showed high gamma-glutamyltransferase, low protein, and low hemoglobin; 3 cases of low prothrombin time were reported, 1 case in the 1,000 mg group and 2 cases in the 500 mg group. The incidence of adverse events was 19% and 12% in the 1,000 mg and 500 mg groups, respectively. The most frequently reported adverse events were headache, diarrhea, and nausea.Shelygin 2016

A Cochrane review of randomized controlled trials evaluating the use of phlebotonics (including diosmin) for treatment of symptomatic or asymptomatic hemorrhoidal disease demonstrated benefit of phlebotonics in the management of pruritus, bleeding, bleeding posthemorrhoidectomy, and discharge and leakage, and for overall symptom improvement compared with controls. Of the 2,344 patients in the included trials, more than 480 patients received diosmin and MPFF. Subanalysis of efficacy for individual agents was not performed.Perera 2012 The most recent diosmin study included in the Perera et al 2012 meta-analysis was an observer-blinded, randomized, placebo-controlled trial (N=86) in which patients undergoing Milligan-Morgan open hemorrhoidectomy received MPFF administered at the following dosage starting on the sixth day after surgery: 1,500 mg 2 times daily after meals for 3 days, followed by 1,000 mg twice daily on days 4 to 7. Treatment with MPFF resulted in a significantly shorter hospital stay after surgery (P<0.05) and better proctoscopic appearance (P<0.001) compared with placebo.Ba-bai-ke-re 2011

In a randomized comparator trial of 60 Italian adults with grade 2 or higher hemorrhoids who had experienced an acute hemorrhoidal crisis, improvements in bleeding intensity and pain severity were observed after 7 days of treatment with both MPFF (Daflon 1,000 mg every 8 hours [ie, 6 tablets daily]) and Emospid (a standardized mixture of extracts from Vitis vinifera, Centella asiatica, and Vaccinium myrtillus; 1 tablet every 8 hours [ie, 3 tablets daily]). These improvements were comparable between the 2 treatments; however, improvements observed with MPFF for all other parameters (ie, itching, pain, tenesm, relative sphincterial tone, stool mucus, and defecation disorders) were inferior to those observed with Emospid. Overall, 87.5% and 50% of patients taking Emospid and MPFF, respectively, improved by 1 grade on the hemorrhoidal scale; however, the global evaluation scores for MPFF were about 25% to 50% inferior to Emospid. Compliance was lower for MPFF, likely due to the higher number of tablets required. No clinically significant adverse effects were associated with either treatment.Di Pierro 2011

Short- and long-term outcomes of hemorrhoid management with MPFF were compared with those of sclerotherapy in a 2-year, randomized controlled trial in patients with first- or second-degree hemorrhoids (N=126). Patients received MPFF 1,000 mg/day orally for 3 months, or sclerotherapy with submucosal injection of polidocanol 3%. Average anoscopic and symptom scores decreased in both groups throughout the first year (P<0.05); at the end of week 4, both scores were significantly lower in the MPFF group compared with sclerotherapy (P=0.009 and P=0.034, respectively). However, during the second year, there was a more significant increase in both scores with MPFF compared to sclerotherapy (P<0.001 for both scores). Subjective symptoms were scored as "cured" or "improved" by 32% of patients in the MPFF group and by 71.6% in the sclerotherapy group (P=0.012); bleeding rates decreased in the first month only in patients taking MPFF. No complications occurred with MPFF, while 2 cases of severe pain occurred in the sclerotherapy group.Yuksel 2008

In a prospective, double-blind, randomized controlled trial of adults experiencing a first episode of acute hemorrhoids (N=90), evolution of pain (P<0.001), edema (P<0.001), and bleeding (P=0.021) were significantly improved with MPFF 500 mg (6 tablets daily for 4 days, then 4 tablets daily for 3 days) compared with placebo. Mean time from onset of acute hemorrhoidal episode was 45.3 hours. Symptoms and signs at baseline, in decreasing order of frequency, included pain, edema, bleeding, prolapse, itching, and mucus leakage; edema was more prevalent in patients randomized to the diosmin group. One patient in the diosmin group experienced self-limiting adverse mild abdominal discomfort.Jiang 2006 In contrast, a double-blind, randomized, controlled trial (N=570) that evaluated blood tests, medical examination, proctoscopy, and patient self-assessed symptom scoring (for bleeding, pain, discharge, pruritus, and erythema) in patients with acute hemorrhoids found no differences among MPFF (Daflon 3,000 mg/day for 4 days, then 2,000 mg/day for 3 days), Cissus quadrangularis L., or placebo in terms of therapeutic efficacy.Panpimanmas 2010

Pelvic congestion

Clinical data

A noncontrolled study investigated the effect of MPFF (1,000 mg once daily for 1 month) on secondary varicose small pelvic veins in 24 male and female adults with at least a 1-year history of acute iliac thrombosis with impaired urination, possibly associated with pain and/or, in women, dyspareunia. Compared with baseline, MPFF significantly improved varicose vein diameter (P<0.0001); decreased the number of patients experiencing retrograde blood flow (P=0.02), urination disorders (from 24 to 9, a 63% improvement; P=0.03), and pelvic pain (from 8 to 1; P=0.04); and decreased the number of cases of bilateral varicose veins (from 10 to 2; P=0.037).Tsukanov 2016 In another noncontrolled study, women with isolated pelvic varicose veins (n=65) and those with additional gonadal varicose veins (n=20) received MPFF (Daflon) 1,000 mg/day for 8 weeks. A reduction in pelvic pain was observed in both groups from weeks 2 to 4 of treatment and continued up to week 8 in the pelvic varicose veins group. After 4 weeks, the dose was increased to 2,000 mg/day in women who did not respond; this increased dosage resulted in a reduction of pain in women with pelvic varicose veins only. Self-assessed pain during the 14-week follow-up period after MPFF treatment revealed almost complete relief of pelvic pain in the pelvic varicose veins group; in contrast, those with pelvic varicose veins in addition to gonadal varicose veins reported an increase in pain similar to pretreatment levels. Of the 57 women in the pelvic varicose veins only group who continued MPFF long-term over 60 months, 7 took MPFF prophylactically while the other 50 took it as needed when symptoms (eg, pelvic pain, dyspareunia, coital and postcoital pain) occurred. The duration of administration over the long-term follow-up period ranged from 2 to 3.2 months and usually did not exceed 3 courses of therapy per year. Except for a few cases of gastric dyspepsia, no adverse effects were noted.Gavrilov 2015

In a placebo-controlled, randomized crossover trial, 20 multiparous women diagnosed with pelvic congestion syndrome and who had experienced pelvic pain for more than 12 months despite various medical treatments (eg, oral contraceptives, nonsteroidal anti-inflammatory drugs) were randomized to receive MPFF (Daflon 500 mg twice daily for 6 months) or a vitamin pill, and were then switched to the alternate treatment for 6 more months. Pelvic scores improved during the second and third months of treatment with MPFF, compared with baseline and the vitamin pill; improvements became significant at the end of the sixth month (P<0.05). Similar results were observed after the crossover.Simsek 2007

Proctitis (radiation induced)

Animal data

The efficacy of MPFF in the management of acute radiation-induced proctitis was assessed in a rat model. Rats administered MPFF (Daflon) 100 mg/kg/day starting the day before irradiation and continuing to day 15 after irradiation showed a statistically significant decrease in inflammation, with less glandular distortion, less mucosal inflammation, and less infiltration of crypt epithelia by inflammatory cells compared with irradiated rats given placebo (sodium chloride 0.9% solution).Sezer 2011

Varicoceles/Male infertility

Clinical data

In a prospective, randomized, placebo-controlled trial in men with scrotal varicoceles and normal sperm count (N=40), pain, percentage of motile sperm, duration of left spermatic vein reflux, and sonographic grade of left varicocele improved significantly with administration of MPFF (Daflon 1,000 mg/day for 12 months) compared with baseline and placebo. Mean pain scores decreased significantly within the first month with MPFF (VAS score change from 5.25 to 1.8; P<0.01) and continued to improve through month 12, with a final mean score of 0.95 (P<0.01). No significant changes in mean pain scores were observed in the placebo group, with pretreatment and 12-month mean pain scores of 5.1 and 5.15, respectively. Additionally, MPFF provided a significant improvement in the percentage of total motile sperm at 6 months compared with baseline (P=0.038). Duration of reflux in the left spermatic vein was also significantly lower than baseline at months 1, 3, and 6 (P=0.04, P=0.025, and P=0.015, respectively), which resulted in a significant decrease in sonographic grade of left varicocele. No correlation was noted between pretreatment duration of pain or varicocele grade and posttreatment pain. No adverse effects were observed.Söylemez 2012

Vascular reperfusion

In 2 case reports of infants born with spinal muscular atrophy and severe vascular perfusion abnormalities, diosmin was used in combination with aspirin, heparin, pentoxifylline, and local antiseptics as empiric treatment to improve the outcome of a novel clinical feature, digital necrosis. Improvement in symptoms as well as survival occurred in both cases, the result of invasive ventilation and proactive supportive care.Araujo 2009


Diosmin is usually given for a short duration (3 months or less) at 1,000 mg/day (500 mg twice daily).Freag 2013, Milano 2014 It is often formulated in combination with hesperidin in a micronized form (MPFF [ie, Daflon]; diosmin 90% plus hesperidin 10%).

Cardiac surgery (preoperative)

Starting 7 days prior to CABG, MPFF 3,000 mg (6 tablets) daily for 4 days, then 1,000 mg (2 tablets) for 3 days as part of the preoperative regimen improved postoperative functional status in patients with a left ventricular ejection fraction less than 0.5, greater than 70% stenosis of at least 2 coronary arteries, and NYHA functional class status of 2.3 (EuroSCORE 3 to 5).Sirlak 2010

Chronic venous insufficiency

Diosmin 1,000 mg/day for 60 days; MPFF 500 mg twice daily or 1,000 mg once daily for up to 6 months.Martinez-Zapata 2016, Savel'ev 2006 A once-daily MPFF 1,000 mg tablet regimen has also been used successfully for up to 4 months.Kirienko 2016, Rabe 2015, Savel'ev 2006 However, some data indicate that the effects of diosmin administered as a single ingredient (versus the MPFF formula) may not be different from placebo.Allaert 2012

Manufacturer product labeling suggests 200 mg 3 times daily orally for short-term (2 to 3 months) relief of edema and symptoms related to CVI in adults.Venosmil October 2014

Hemorrhoidal crisis

For acute attacks, a loading dose of 1,000 mg 3 times daily for 4 days, followed by 1,000 mg twice daily for 3 days.Jiang 2006, Milano 2014, Panpimanmas 2010, Shelygin 2016 Another study observed improvements in bleeding intensity and pain severity after 7 days in patients receiving 1,000 mg every 8 hours.Di Pierro 2011

Hemorrhoid management

MPFF 1,000 mg/day orally for 3 months improved short- and long-term anoscopic and symptom scores for up to 2 years in patients with first- or second-degree hemorrhoids.Yuksel 2008


Starting on the sixth day after surgery, MPFF was administered at 1,500 mg 2 times daily after meals for 3 days, followed by 1,000 mg twice daily on days 4 to 7. Better proctoscopic appearance was achieved with MPFF compared with placebo in patients who had undergone Milligan-Morgan open hemorrhoidectomy for the treatment of prolapsed hemorrhoids.Ba-bai-ke-re 2011

Pelvic congestion/varicose veins

MPFF 1,000 mg once daily for 1 month improved varicose small pelvic vein diameter; decreased the number of patients experiencing retrograde blood flow, urination disorders, and pelvic pain; and decreased the number of cases of bilateral varicose veins in male and female adults with at least a 1-year history of acute iliac thrombosis with impaired urination.Tsukanov 2016 MPFF 1,000 mg/day for 8 weeks reduced pelvic pain in women with isolated pelvic varicose veins and in women with additional gonadal varicose veins; an increase in dosage to 2,000 mg/day after 4 weeks in women who did not respond to the 1,000 mg/day dosage resulted in a reduction of pain in women with pelvic varicose veins only.Gavrilov 2015 MPFF 500 mg twice daily for 6 months improved pelvic scores in multiparous women diagnosed with pelvic congestion syndrome who had experienced pelvic pain for more than 12 months despite various medical treatments.Simsek 2007

Varicoceles/Male infertility

MPFF 1,000 mg/day for 12 months in men with scrotal varicoceles and normal sperm count improved pain, percentage of motile sperm, duration of left spermatic vein reflux, and sonographic grade of left varicocele.Söylemez 2012

Pregnancy / Lactation

Avoid use. Diosmin is not intended for use in pregnant or breast-feeding women unless the benefit outweighs the risk of therapy. Clinical data are limited; however, in a safety and efficacy study of MPFF for the treatment of internal hemorrhoids of pregnancy (N=50), MPFF was found to be safe, acceptable, and effective when used for a median of 8 weeks before delivery and for 4 weeks afterwards. Pregnancy, fetal development, birth weight, infant growth, and feeding were not affected by treatment.Diosvein 2006


Chlorzoxazone: Serum levels of chlorzoxazone, a CYP2E1 substrate, may be increased in the presence of diosmin.Rajnarayana 2008

Diclofenac sodium: Bioavailability and serum levels of diclofenac sodium, a CYP2C9 substrate, may be increased in the presence of diosmin.Rajnarayana 2007

Fexofenadine: Bioavailability and serum levels of fexofenadine, a P-glycoprotein substrate, may be increased in the presence of diosmin.Bedada 2016

Adverse Reactions

The most common adverse effects reported with use of diosmin are mild GI and autonomic disturbances (eg, pruritus, erythema, dermatitis (hives, itching), stomach and epigastric pain, nausea, diarrhea, dizziness), which have been reported in up to 10% of cases. Cardiac arrhythmias (tachycardia) and hemolytic anemia have also been documented.Ba-bai-ke-re 2011, Milano 2014 In one study, 4 patients receiving MPFF 1,000 mg once daily for 4 months withdrew because of adverse events (ie, 1 patient experienced pruritus, nausea, and brittle fingernails; 3 patients experienced abdominal pain, erysipelas, and depression).Rabe 2015 In a dosing study, mild constipation, dyspepsia, and allergic dermatitis were observed in the 1,000 mg once daily group, and one patient in the 500 mg twice daily group experienced a potential clinically relevant abnormal lab result (low hemoglobin).Kirienko 2016

Rare excessive peripheral vasoconstriction and ischemic damage have been reported in 2 cases, presenting as diffuse myalgias and elevated creatine phosphokinase in a 55-year-old white woman, and as elevated lactic dehydrogenase levels in a 79-year-old white man. Both patients were taking multiple medications for concomitant conditions; however, based on physiological response to diosmin discontinuation and/or rechallenge, the patients' reactions were considered "probably" and "possibly" associated with diosmin therapy, respectively. Diosmin 450 mg twice daily and diosmin 900 mg 3 times daily were the respective diosmin regimens employed.Milano 2014

Spontaneous intraventricular hemorrhage in a 77-year-old woman who had started therapy (warfarin and aspirin) for atrial fibrillation 6 weeks previously was thought to be related to chronic microcirculatory hypertension and inhibition of platelet aggregation due to the woman's long-term (several years') use of diosmin. The woman presented with a severe bitemporal headache and an international normalized ratio of 1.8, then developed syndrome of inappropriate secretion of antidiuretic hormone (SIADH) during her hospital stay. She was discharged without neurological deficits. The authors noted, as a confounder to their diosmin theory, that the antiplatelet effects of daily aspirin therapy, when combined with anticoagulation, can more than double the frequency of intracranial hemorrhage.Kumar 2011


Extensive safety evaluations conducted with diosmin/hesperidin found no risk of toxicity.Ba-bai-ke-re 2011 In animal studies, the acute median lethal dose for hidrosmin (a standard mixture composed mainly of mono- and di-O-beta-hydroxyethyl-diosmin) was very high (greater than 5,000 mg/kg) with respect to the clinical dose of 10 mg/kg/day. No signs of teratogenicity or embryotoxicity were observed at doses 3 to 600 times the clinically recommended therapeutic range.Venosmil October 2014



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