Flebosmin

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT FLEBOSMIN (FLEBOSMIN)

Composition:

Active substance: micronized purified flavonoid fraction containing diosmin and flavonoids in the form of hesperidin;

One tablet contains 500 mg of micronized purified flavonoid fraction, comprising 450 mg of diosmin (90%) and 50 mg of flavonoids in the form of hesperidin (10%);

Excipients: gelatin, sodium starch glycolate (type A), microcrystalline cellulose, talc, magnesium stearate;

Film coating: sodium lauryl sulfate, Opadry orange 03G34105 (hypromellose, glycerin, titanium dioxide, iron oxide yellow, iron oxide red, polyethylene glycol 6000, magnesium stearate).

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: elongated film-coated tablets, pink-orange in color, with a score line on one side.

The score line is intended for tablet splitting to facilitate swallowing, but not to divide the tablet into two equal doses.

Pharmacotherapeutic group. Vasoprotectives. Capillary stabilizing agents. Bioflavonoids. Diosmin, combinations. ATC code C05CA53.

Pharmacological Properties

Pharmacodynamics

The medicinal product exerts a venotonic and angioprotective effect, reduces venous distensibility and venous stasis, improves microcirculation, decreases capillary permeability, and increases their resistance.

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 a daily dose of 1000 mg (2 tablets).

Venotonic activity
The medicinal product increases venous tone: a reduction in venous emptying time has been demonstrated using occlusive venous plethysmography.

Microcirculatory activity
Studies have demonstrated a statistically significant difference between administration of the medicinal product and placebo. In patients with symptoms of capillary fragility, treatment increased capillary resistance, as determined by angio-stereometry.

Pharmacokinetics

Absorption
After oral administration, diosmin is rapidly converted by intestinal microflora into the aglycone diosmetin, which is absorbed into systemic circulation. The oral bioavailability is approximately 57.9%.

Distribution
Diosmetin is widely distributed in tissues, with a volume of distribution of 62.1 L.

Metabolism
Diosmetin is rapidly and extensively metabolized to phlebotonic acids or their derivatives, conjugated with glycine, which are excreted in urine. The main metabolite in humans is hydroxyphenylpropionic acid, predominantly excreted in conjugated form. Minor metabolites include other phenolic acids corresponding to 1-hydroxy-4-methoxybenzoic acid, 3-methoxy-4-hydroxyphenylacetic acid, and 3,4-dihydroxybenzoic acid.

Elimination
Elimination in humans occurs relatively rapidly. In studies using radiolabeled diosmin, 34% of the dose was recovered in urine and feces within the first 24 hours, and approximately 86% within the first 48 hours.

Linearity/Non-linearity
The pharmacokinetics of diosmin are linear.

Clinical characteristics.

Indications.

Flébosmin is used in adults for:

• treatment of symptoms associated with mild venous insufficiency;
• relief of symptoms associated with hemorrhoids, such as pain or swelling around the anal area.

Contraindications.

Hypersensitivity to diosmin and other flavonoids or to any of the excipients.

Interaction with other medicinal products and other forms of interaction.

Diosmin may increase blood concentration and reduce elimination of metronidazole and diclofenac.

Diosmin may inhibit platelet aggregation (interfere with blood clotting). This may increase the risk of adverse reactions in patients taking anticoagulants.

Special precautions for use

The use of this medicinal product in acute haemorrhoids does not replace specific therapy and does not preclude the treatment of other proctological diseases. If symptoms do not resolve during a short course of treatment, a proctological examination should be performed and the therapy re-evaluated.

This medicinal product must not be used for prolonged periods without medical supervision.

If sudden, unusually severe symptoms occur, especially in one leg, with swelling, skin discoloration, sensation of tightness or warmth, and pain, immediate medical advice should be sought. These may be symptoms of deep vein thrombosis associated with underlying venous insufficiency.

Important information on excipients

Sodium. This medicinal product contains less than 1 mmol (23 mg)/dose of sodium, i.e. essentially "sodium-free".

Use during pregnancy or breastfeeding

Pregnancy

Data on the use of micronized purified flavonoid fraction in pregnant women are lacking or limited in quantity.

Animal studies have not shown reproductive toxicity.

As a precautionary measure, it is advisable to avoid using this medicinal product during pregnancy.

Breastfeeding

It is unknown whether the active substance or its metabolites are excreted in breast milk.

Risk to newborns/infants cannot be excluded.

The decision on whether to discontinue breastfeeding or to discontinue/abstain from treatment with this medicinal product should be made after considering the benefits of breastfeeding for the child and the benefits of treatment for the mother.

Fertility

Reproductive toxicity studies in animals showed no effect on fertility.

Ability to affect reaction speed when driving or operating machinery

Studies on the influence 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, this medicinal product has no effect or a negligible effect on this ability. If adverse reactions occur (see section "Adverse reactions"), caution is advised.

Method of administration and dosage.

For oral use in adults.

Venous insufficiency

2 tablets daily in two divided doses (1 tablet during the day and 1 tablet in the evening), taken with meals.

Symptom relief usually occurs within the first 2 weeks of treatment. If the patient's condition does not improve or worsens, the clinical situation should be reassessed.

If necessary, treatment may be continued at the same daily dose for 2–3 months.

Haemorrhoids

6 tablets daily for the first 4 days (2 tablets 3 times daily), then 4 tablets daily for the next 3 days (2 tablets twice daily). The recommended maintenance dose is 2 tablets daily.

For haemorrhoids, this medicinal product is indicated only for short-term use (see section "Special precautions"). If the patient's condition does not improve or worsens after the first week of treatment, the clinical situation should be reassessed.

Children

The safety and efficacy of Flébomin in children (under 18 years of age) have not been established. There are no data available on the use of this medicinal product in children.

Overdose.

Symptoms. There is limited information on cases of overdose with this medicinal product. The most commonly reported adverse reactions in cases of overdose were gastrointestinal reactions (such as diarrhoea, nausea, abdominal pain) and skin reactions (such as pruritus, rash).

Treatment: symptomatic.

Adverse Reactions

The following adverse reactions have been reported, categorized by frequency 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 the available data).

Nervous system disorders:
Rare: dizziness, headache, malaise.

Gastrointestinal disorders:
Common: diarrhea, dyspepsia, nausea, vomiting;
Uncommon: colitis;
Frequency not known: abdominal pain.

Skin and subcutaneous tissue disorders:
Rare: pruritus, rash, urticaria;
Frequency not known: isolated facial swelling, lips, eyelids, in exceptional cases – Quincke's edema.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after marketing authorization of the medicinal product is important. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients, as well as their legal representatives, should report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life.

5 years.

Storage conditions.

No special storage conditions are required for this medicinal product.

Keep out of reach of children.

Packaging.

10 film-coated tablets in a blister, 6 blisters in a cardboard box.

Supply category.

Over-the-counter (without prescription).

Manufacturer.

KERN PHARMA, S.L.

Manufacturer's address and place of business.

Poligono Industrial Colon II. Venus, 72 08228 Terrassa (Barcelona), Spain / Poligono Industrial Colon II. Venus, 72 08228 Terrassa (Barcelona), Spain.