Avenue

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT AVE**NUE® (AVENUE)

Composition:

Active substances: diosmin, hesperidin;

One tablet contains 500 mg of micronized purified flavonoid fraction (calculated as 100% anhydrous substance), containing 450 mg diosmin (90%) and 50 mg flavonoids as hesperidin (10%);

Excipients: polyvinyl alcohol, microcrystalline cellulose, sodium starch glycolate (type A), talc, magnesium stearate, Opadry II 85F34486 Pink (polyvinyl alcohol, titanium dioxide (E 171), polyethylene glycol (macrogol), talc, iron oxide red (E 172), iron oxide yellow (E 172)).

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: oval-shaped, biconvex tablets with a score line on one side, film-coated, light pink in color with a slight brownish tint.

Pharmacotherapeutic group. Capillary stabilizing agents. Bioflavonoids. Diosmin, combinations. ATC code C05C A53.

Pharmacological Properties.

Pharmacodynamics.

Pharmacology.

Avenue® exerts venotonic and angioprotective effects, reduces venous distensibility and venous stasis, improves microcirculation, decreases capillary permeability and increases their resistance, as well as enhances lymphatic drainage by increasing lymphatic outflow.

Preclinical Pharmacology.

Experimental studies in animals using the "ischemia/reperfusion" model demonstrated that administration of micronized purified flavonoid fraction is more effective in reducing vascular wall permeability and plasma extravasation compared to plain diosmin. This effect is attributed to the protective action on microcirculation exerted by flavonoids such as hesperidin, diosmetin, linarin, and isorhoifolin, which are components of the fraction and expressed as hesperidin equivalents. The reduction in vascular wall permeability and plasma extravasation observed with the micronized purified flavonoid fraction was more pronounced than that observed with plain diosmin or with each individual component of the flavonoid fraction administered separately.

Clinical Pharmacology.

The pharmacological properties described above have been confirmed in double-blind placebo-controlled studies using methods capable of assessing the drug's effect on venous hemodynamics.

Dose–response relationship.

A statistically significant dose-dependent effect of the medicinal product was established according to the following venous plethysmographic parameters: venous volume, venous distensibility, and venous emptying time. The optimal dose–response relationship was achieved with administration of 2 tablets.

Venotonic activity.

Micronized purified flavonoid fraction increases venous tone: venous occlusion plethysmography demonstrated a reduction in venous emptying time.

Microcirculatory activity.

Double-blind placebo-controlled studies demonstrated a statistically significant difference between the use of the drug and placebo. In patients with symptoms of capillary fragility, treatment increased capillary resistance, as determined by angioscopy.

The drug also reduces leukocyte–endothelium interaction and leukocyte adhesion in postcapillary venules. This reduces the damaging effects of inflammatory mediators on venous walls and venous valve leaflets.

In clinical practice.

Double-blind placebo-controlled studies have demonstrated the therapeutic efficacy of micronized purified flavonoid fraction in phlebology for the treatment of functional and organic chronic venous insufficiency of the lower limbs, as well as in proctology for the treatment of hemorrhoids.

Pharmacokinetics.

Elimination of the active substance occurs primarily via feces. On average, 14% of the administered dose is excreted in urine.

The elimination half-life is 11 hours.

The drug is actively metabolized, as confirmed by the presence of various phenolic acids in urine.

Clinical characteristics.

Indications.

Symptomatic treatment of venous-lymphatic insufficiency (leg heaviness, pain, nocturnal cramps, edema, trophic disorders, including varicose ulcers).

Symptomatic treatment of hemorrhoids.

Contraindications.

Hypersensitivity to the active substance or to any of the excipients.

Interaction with other medicinal products and other forms of interaction.

Studies on interactions have not been conducted. However, despite extensive post-marketing experience with diosmin, no interactions with other medicinal products have been reported to date.

Special precautions for use.

The use of this medicinal product in acute haemorrhoids does not replace specific therapy and does not interfere with the treatment of other proctological diseases. If symptoms do not rapidly resolve during short-term treatment, a proctological examination should be performed and the treatment regimen reassessed.

In disorders of venous circulation, therapy is more effective when combined with adherence to the following lifestyle recommendations:

• avoid excessive sun exposure, prolonged standing, and excess body weight;
• walk regularly and, in some cases, wear special compression stockings to improve circulation.

This medicinal product contains less than 1 mmol/dose of sodium (23 mg), i.e. it is practically sodium-free.

Use during pregnancy or breastfeeding.

Pregnancy.

Avenue® should be used with caution in pregnant women. Consult a physician prior to use.

Studies have shown no teratogenic effects, and adverse effects have not been reported.

Breastfeeding.

Due to the lack of data on penetration into breast milk, use during breastfeeding should be avoided.

Fertility.

Reproductive toxicity studies in animals showed no effect on fertility.

Ability to affect reaction speed when driving or operating machinery.

Studies on the effect of the flavonoid fraction on the ability to drive or operate machinery have not been conducted. However, based on the overall safety profile of the flavonoid fraction, Avenue® has no effect or has a negligible effect on this ability. Nevertheless, caution should be exercised if adverse reactions occur (see section "Adverse reactions").

Dosage and Administration.

For oral use.

To be prescribed to adults.

Venous and lymphatic insufficiency.

The recommended dose is 2 tablets daily: 1 tablet during the day and 1 tablet in the evening with meals. After one week of treatment, 2 tablets daily may be taken once daily with food.

Haemorrhoidal disease.

Treatment of acute haemorrhoidal attacks: 6 tablets daily for 4 days, followed by 4 tablets daily for the next 3 days. Administer during meals. The daily dose should be divided into 2–3 doses. Maintenance therapy: 2 tablets daily.

The duration of therapy should be determined by the physician depending on the indication and course of the disease.

Children.

There are no data on the use of Avene® in children.

Overdose.

Cases of overdose have not been reported.

Adverse Reactions

During clinical studies with micronized purified flavonoid fraction, adverse effects of moderate intensity were observed, mainly affecting the gastrointestinal tract (diarrhea, dyspepsia, nausea, vomiting).

The following adverse reactions have been reported, listed by frequency categories as follows: very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1000, < 1/100); rare (≥ 1/10000, < 1/1000); very rare (< 1/10000); frequency not known (cannot be estimated from available data).

* Post-marketing observations.

Shelf life. 4 years.

Do not use the medicinal product after the expiry date stated on the packaging.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 ºC. Keep out of reach of children.

Packaging.

10 tablets per blister. 3 or 5 blisters per carton.

Pharmaceutical category. Over-the-counter (without prescription).

Manufacturer.

JSC "Farmak".

Manufacturer's address and place of business.

74, Kyrylivska Street, Kyiv, 04080, Ukraine.