Detralex

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT DETRALEX® (DETRALEX®)

Composition:

Active substance: micronized purified flavonoid fraction (diosmin + 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, magnesium stearate, microcrystalline cellulose, sodium starch glycolate (type A), talc, purified water;

Film coating: glycerin, macrogol 6000, magnesium stearate, hypromellose, iron oxide red (E 172), sodium lauryl sulfate, titanium dioxide (E 171), iron oxide yellow (E 172).

Pharmaceutical form. Film-coated tablets.

Main physicochemical characteristics: oval-shaped tablet with an orange-pink film coating.

Pharmacotherapeutic group.

Angioprotectors. Capillary-stabilizing agents. Bioflavonoids. Diosmin combinations.

ATC code C05C A53.

Pharmacological properties.

Pharmacodynamics.

Pharmacology.

Detralex® exerts a venotonic and angioprotective effect, reduces venous distensibility and venous stasis, improves microcirculation, decreases capillary permeability and increases their resistance, as well as enhances lymphatic drainage by increasing lymph 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 result is attributed to the protective effect on microcirculation exerted by flavonoids such as hesperidin, diosmetin, linarin, and isorhoifolin present in the fraction as hesperidin. 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 each individual component of the flavonoid fraction administered separately.

Clinical pharmacology.

The above-mentioned pharmacological properties 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 drainage time. The optimal dose–response relationship was achieved with administration of 2 tablets.

Venotonic activity.

Detralex® increases venous tone: venous occlusion plethysmography demonstrated a reduction in venous drainage time.

Microcirculatory activity.

Double-blind placebo-controlled studies demonstrated a statistically significant difference between drug administration 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 wall and venous valve leaflets.

In clinical practice.

Double-blind placebo-controlled studies have demonstrated the therapeutic efficacy of the drug 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 mainly via feces. On average, 14% of the administered dose is excreted in urine.

The elimination half-life is 11 hours.

The drug undergoes extensive metabolism, as confirmed by the presence of various phenolic acids in urine.

Clinical characteristics.

Indications.

Symptomatic treatment of venous and 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. During post-marketing use of the drug, no clinically significant interactions with medicinal products have been reported to date.

Special precautions for use

The use of this medicinal product in acute hemorrhoids does not replace specific treatment and does not preclude the management of other proctological disorders. If symptoms do not rapidly resolve during a short course of treatment, a proctological examination should be performed and the treatment regimen reassessed.

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

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

Excipients

Sodium content

Detraleks® contains less than 1 mmol of sodium (23 mg) per tablet, i.e. it is nearly 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 demonstrated reproductive toxicity.

As a precautionary measure, it is advisable to avoid using the drug during pregnancy.

Breastfeeding

It is unknown whether the active substance or its metabolites pass into 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 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, Detraleks® has no effect or has a negligible effect on this ability. If adverse reactions occur (see section "Adverse reactions"), caution should be exercised.

Dosage and Administration

For oral use.

For adults only.

Venous and lymphatic insufficiency

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

The usual recommended duration of treatment is up to 3 months. A longer duration of treatment, from 6 to 12 months, was well tolerated in clinical studies.

Hemorrhoidal disease

Treatment of acute hemorrhoidal episodes: 6 tablets daily for 4 days, followed by 4 tablets daily for the next 3 days. Take with meals. The daily dose should be divided into 2–3 doses.
Maintenance therapy: 2 tablets daily, with treatment duration up to 3 months.

Children

There are no data on the use of Detralex® 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 diarrhea, nausea, abdominal pain) and skin reactions (such as pruritus, rash).

Treatment

Treatment of overdose should be symptomatic.

Adverse Reactions.

During clinical trials, administration of micronized purified flavonoid fraction was associated with adverse effects of moderate intensity, primarily affecting the gastrointestinal tract (diarrhea, dyspepsia, nausea, vomiting).

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 (≥ 1/10,000, < 1/1000); very rare (< 1/10,000); frequency not known (cannot be estimated from the available data).

Of the nervous system: rare: dizziness, headache, malaise.

Of the gastrointestinal tract: common: diarrhea, dyspepsia, nausea, vomiting; uncommon: colitis; frequency not known*: abdominal pain.

Of the skin and subcutaneous tissue: rare: pruritus, rash, urticaria; frequency not known*: isolated facial swelling, lip swelling, eyelid swelling, in exceptional cases – Quincke's edema.

*Post-marketing observations.

Reporting of suspected adverse reactions. Reporting suspected adverse reactions after medicinal product authorization is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are required to report any suspected adverse reactions via the national reporting system.

Shelf life. 4 years.

Storage conditions.

No special storage conditions required. Keep out of reach and sight of children.

Packaging.

15 tablets per blister pack made of aluminum foil and PVC film; 2 or 4 blisters per cardboard box.

Availability. Over-the-counter (without prescription).

Manufacturer.

Laboratoires Servier Industrie / Les Laboratoires Servier Industrie.

Manufacturer's address.

905 route de Saran, 45520 Gidy, France.

Marketing Authorization Holder.

Les Laboratoires Servier.

Address of the Marketing Authorization Holder.

50, rue Carnot, 92284 Suresnes Cedex, France.

For any information regarding this medicinal product, please contact LLC "Servier Ukraine" by phone: (044) 490 3441, fax: (044) 490 3440.