Diosmin

BRAND NAMES

Diosmin is marketed under many brand names worldwide, either alone or more commonly in combination with Hesperidin. Some well‑known examples include Daflon (micronized purified flavonoid fraction of diosmin + hesperidin) and various brands such as Venex, Microsmin Forte, Venusmin in India.

MECHANISM OF ACTION

Although the exact mechanism is not fully delineated, diosmin exerts a venotonic and vasoprotective effect by increasing venous tone, reducing capillary permeability and improving lymphatic drainage. It also shows anti‑inflammatory and antioxidant properties, and appears to prolong the effect of noradrenaline on the vein wall, improving venous return and reducing stasis.

PHARMACOKINETICS:

Absorption         

After oral administration, diosmin (or its aglycone metabolite diosmetin) is absorbed from the gastrointestinal tract; micronized formulations show improved bioavailability.

Distribution

It is distributed with a volume of distribution around ~60 L in humans, and preferential accumulation has been observed in venous tissue.

Metabolism

Diosmin is extensively metabolised; it is converted to diosmetin and further to phenolic acids and glucuronide conjugates.

Excretion

The majority of the dose is excreted via faeces; urinary excretion is relatively small (~14% in one study) and elimination half‑life has been reported around 11 hours in some formulations.

PHARMACODYNAMICS

Diosmin is a veno‑active flavonoid that supports circulatory health by enhancing venous tone and elasticity, improving micro‑ and lymphatic circulation, and reducing capillary permeability, which is why it is commonly used by individuals with chronic venous disease and has been shown to improve quality of life. In addition to these vascular effects, it exhibits antioxidant activity by scavenging free radicals and lowering oxidative‑stress biomarkers such as isoprostane precursors. Furthermore, a clinical study found that three months of diosmin therapy (2 × 600 mg daily) significantly reduced plasma levels of pro‑inflammatory and angiogenic markers including TNF‑α, VEGF‑A, VEGF‑C, IL‑6 and FGF2, while also leaving patients with less leg oedema and smaller mean leg circumference. The data suggest that diosmin modulates inflammatory and angiogenic mechanisms underlying venous insufficiency, contributing to symptomatic relief and improved leg‑physiology.

ADMINISTRATION

Diosmin is administered orally in the form of tablets or capsules. It is available as a stand-alone supplement or, more commonly, as a Micronised Purified Flavonoid Fraction (MPFF) in combination with hesperidin. It is generally recommended to take diosmin with food to improve absorption and minimize stomach discomfort.

DOSAGE AND STRENGTH

Diosmin is most commonly available as a micronised purified flavonoid fraction (MPFF), which typically contains 90% diosmin plus 10% hesperidin—common tablet strengths include 500 mg (equivalent to 450 mg diosmin + 50 mg hesperidin) or 1,000 mg (equivalent to 900 mg diosmin + 100 mg hesperidin). The dose prescribed varies depending on the specific condition being treated.

DRUG INTERACTIONS

Diosmin has several potential drug interactions, primarily due to its effects on blood clotting and the liver enzymes (Cytochrome P450) that metabolize many medications. 

Key Drug Interactions of Diosmin

Anticoagulants and Antiplatelets: Diosmin may slow blood clotting and inhibit platelet aggregation, increasing the risk of bruising and bleeding when taken with medications that also slow blood clotting.

• Examples: Warfarin (Coumadin), heparin, aspirin, clopidogrel (Plavix), NSAIDs (e.g., ibuprofen, naproxen, diclofenac).

• Clinical Note: A case report documented spontaneous intraventricular hemorrhage in a patient taking both warfarin and diosmin long-term.

Medications Changed by the Liver (CYP450 substrates): Diosmin can inhibit certain liver enzymes, particularly CYP3A4, CYP2C9, and CYP2E1, which can decrease how quickly the body breaks down these medications, potentially increasing their effects and side effects.

Examples:

• Carbamazepine (Tegretol, an anticonvulsant): Increased effects and side effects of carbamazepine.

• Diclofenac (Voltaren, an NSAID): Increased effects and side effects of diclofenac.

FOOD INTERACTIONS

There are no well‑documented or clinically significant food‑drug interactions for diosmin; it may be taken with or without food.

CONTRAINDICATIONS

The gel form of Diosmin must not be applied to mucous membranes, broken skin, or areas of inflammation such as dermatitis, eczema or urticaria. Furthermore, its use in children is not recommended due to insufficient safety and efficacy data.

SIDE EFFECTS

• Abdominal discomfort and loose stools

• Headache and light-headedness

• Skin eruptions and itching

• Muscle soreness

• Irregularities in heart rhythm

• Dizziness

OVER DOSE

An overdose of diosmin is likely to result in intensified common side effects, primarily gastrointestinal upset (nausea, vomiting, diarrhea, abdominal pain) and headaches or dizziness. 

In case of an overdose:

• Seek immediate medical attention.

• Stop taking the medication.

• Management will involve treating the clinical symptoms (symptomatic treatment).

TOXICITY

Diosmin is considered to have very low toxicity and is generally well-tolerated by most people when taken at recommended doses. The lethal dose 50% (LD50) in animal studies is high (greater than 3 g/kg in rats), indicating a wide safety margin.