Chronic Venous Disease:
Manage the Progression from Edema to Ulcer

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Pathophysiology of Chronic Venous Disease:
The Biochemical Metabolic Pathway

The Ongoing Presence of Inflammatory Molecules Can Lead to Disease Progression

The First and Only Prescription for Medical Management of CVD Available in the US

Vasculera manages the inflammatory molecules associated with venous hypertension

A Recommendation Supported by a Body of Clinical Evidence

Vasculera® is the only formulation of Micronized Purified Flavanoid Fraction (MPFF) available in the US, recommended in guidelines and supported by a body of evidence

2016 Recommendations

Hemodynamic pathophysiology leads to major cellular and enzymatic pathologic mechanisms

Inflammation is central to CVD

Management with MPFF

  • Modulates microvascular inflammation
  • Manages discomfort and edema in patients with C2 - C4 disease
  • Manages ulcers in patients with C5 - C6 disease

Diosmiplex is the only available formulation of 95% purified flavonoid in the U.S.

  • Dosed once daily
  • Addition of Alka-4 complex may address GI upset with the high dose of diosmin and potentially act as a buffer for the acidic environment

MPFF versus Placebo over 8 Weeks

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.

Vasculera, which contains MPFF, has been shown to improve the 8 symptoms of CVD. Each symptom was scored on a scale of 0-4, with 0 being no impact from the symptom, and 4 being highly impacted by the symptom. Symptom scores were compared from week 0 to week 4, and after week 8 on MPFF. The bars represent the difference in improvement from week 0 to 8 weeks after taking MPFF vs week 0 to week 8 on placebo. The change between week 0 to week 8 for MPFF was significant compared to placebo in 6 out of 8 symptoms of CVD, with greatest significance in reduction of swelling, heaviness and functional discomfort. Although there was a reduction in the symptom score for paresthesia and redness, the reduction when compared to placebo did not reach statistical significance.

Case Studies

Stasis Dermatitis


Venous Stasis Ulcer

Stasis Dermatitis

Frequently Asked Questions

The term "medical food" means a food which is formulated to be consumed or administered enterally (by mouth or feeding tube) under the supervision of a physician and which is intended for the specific dietary management of a disease or condition for which distinctive nutritional requirements, based on recognized scientific principles, are established by medical evaluation. (source: 21 U.S.C. sec. 360ee(b)(3). -- [from the Orphan Drug Act, 1988]

Since the components of Vasculera are natural molecules derived from foods, they are not classified as a drug. As required of all products classified as medical foods, the ingredients in Vasculera have been determined to be generally recognized as safe (GRAS), a food safety distinction at the FDA.

Vasculera is a 630mg diosmiplex tablet. Diosmiplex is a combination of purified diosmin (600mg) and alka4-complex (30mg).

Diosmin is a MPFF (micronized flavonoid fraction) derived from hesperidin found in oranges and other citrus fruit, with the highest concentration in the rinds (see the USDA flavonoid database). Flavonoids are healthy ingredients that give color to vegetables, fruits, cocoa, red wine and green tea. To get the same amount of diosmin packed into a single Vasculera tablet, you would need to eat about 140 oranges per day (rind included). Diosmin has been used in Europe as a prescription product for more than 30 years. Dozens of well-documented clinical studies support its effectiveness and safety.

Alka4-complex is an antacid. It works against acidity in the blood, which damages veins. Vasculera does not contain fructose, glucose, sucrose, lactose, gluten, maltodextrin, tree nuts, peanuts, or flavors and is suitable for vegans.

Diosmin is semi-synthetically produced from hesperidin, another flavonoid found in citrus. Diosmin is also found at low concentrations in oranges and some other citrus fruits in both the rind and juice (see the USDA flavonoid database). Alka4-complex is an antacid produced by mixing certain bases found in other products so that it can survive the harsh environment of stomach acid and be absorbed through the small intestine into the blood.

Half-life is the period of time it takes for half of an ingested dose to be eliminated from the body. The mean half-life for Vasculera is 31.5 hours. This justifies the once a day dosing.

Vasculera addresses the venous inflammation associated with chronic venous disease by decreasing leukocyte activation, downregulating VEGF expression and decreasing TNF-alpha.

Vasculera is indicated for the clinical dietary management of the metabolic processes of Chronic Venous Disease (CVD) under physician supervision. Vasculera has been recommended in guideline for the relief of symptoms across a range of CVD including hemorrhoids, varicose veins, spider veins, edema, lymphedema, traveler’s edema, stasis dermatitis, and venous ulcers.

A systematic review of the clinical literature concluded that the body of evidence supports the effectiveness of the main ingredient in Vasculera, MPFF on the symptoms of CVD. Guidelines from experts in international societies since 2008 have recommended the use of MPFF for the reduction of symptoms such as edema and the healing of venous ulcers. A recent peer-reviewed publication of the systematic review of the evidence and the recommendation of vascular experts can be found at:

The principle studies typically referenced to show the efficacy of diosmin in the management of hemorrhoids are:

  • Cospite M. Double-blind, placebo-controlled evaluation of clinical activity and safety of Daflon 500 mg in the treatment of acute hemorrhoids. Angiology. 1994 Jun; 45(6 Pt 2):566-73.
  • 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.
  • Thanapongsathorn W and Vajrabukka T. Clinical trial of oral diosmin (Daflon) in the treatment of hemorrhoids. Dis Colon Rectum. 1992.35;1085-8

Similar products have shown no serious adverse events reported in any study. Commonly reported side effects related to consumption of diosmin included gastrointestinal disturbances and headaches, which were generally mild and did not result in discontinuation. Please see Vasculera package insert for further information.

Vasculera is not for patients with hypersensitivity to any of its ingredients. Vasculera is not recommended for pregnant or lactating women. Drug interactions have been described with chlorzoxazone (Parafon Forte), diclofenac (Voltaren) and metronidazole (Flagyl). These reports were based on pharmacokinetic studies in healthy people, but have not been reported in clinical practice. If you believe you are having a drug interaction, tell your doctor right away.

The recommended intake of VASCULERA (diosmiplex) is 1 tablet per day for the dietary management of Chronic Venous Insufficiency (CVI), manifested as: varicose/spider veins, edema, stasis dermatitis and or venous ulcers. Results may appear in as little as one week but may not be seen for 4 to 8 weeks. For venous ulcers, results may not be seen for several months.

For hemorrhoidal disease, the recommended initial intake is 1 tablet 3 times daily for 4 days followed by 1 tablet twice daily for 9 days, or as directed by a physician. For hemorrhoidal discomfort persisting after resolution of the acute flare or for recurrent hemorrhoidal flares irrespective of persisting discomfort, a maintenance intake of one tablet of Vasculera daily is recommended.

Primus Care Direct is a hassle-free, mail-order pharmacy service that saves time for healthcare practitioners by helping to increase fill rates and eliminate call-backs for prior authorizations

In addition to convenience for practitioners, Primus Care Direct also guarantees patients get their Vasculera prescription for $49* (Medicare patients included). This is the lowest possible price available and includes free home delivery. If patients have insurance, they may pay even less.

*Offer based on 30-day supply at prescribed one tablet per day dose

Physician Resources

To learn more from experts in vascular disease, The Working Group in CVD, and for more resources on CVD, go to