Detralex^® (Tablets, Suspension) Instructions for Use

ATC Code

C05CA53 (Diosmin in combination with other drugs)

Active Substance

Micronised purified flavonoid fraction (diosmin+flavonoids expressed as hesperidin)

Micronised purified flavonoid fraction (diosmin+flavonoids expressed as hesperidin) (Grouping name)

Clinical-Pharmacological Group

Venotonic and venoprotective drug

Pharmacotherapeutic Group

Angioprotectors; capillary stabilizing agents; bioflavonoids

Pharmacological Action

Mechanism of action

Detralex^® has venotonic and angioprotective properties.

The drug reduces venous distensibility and venous stasis, decreases capillary permeability and increases their resistance.

The results of clinical studies confirm the pharmacological activity of the drug in relation to venous hemodynamic parameters.

Pharmacodynamic effects

A statistically significant dose-dependent effect of Detralex^® was demonstrated for the following venous plethysmographic parameters: venous capacity, venous distensibility, venous emptying time.

In the treatment of chronic venous diseases, the optimal dose-effect ratio is observed when taking 1000 mg per day.

Detralex^® increases venous tone: a decrease in venous emptying time was shown using venous occlusion plethysmography.

In patients with signs of severe microcirculation disorders, after therapy with Detralex^®, a statistically significant increase in capillary resistance compared to placebo was noted when assessed by angiosterometry.

The therapeutic efficacy of Detralex^® has been proven in the treatment of chronic venous diseases of the lower extremities, as well as in the treatment of hemorrhoids.

Preclinical safety data

No toxic or lethal effects were observed in mice, rats and monkeys after single and repeated oral administration of the drug in high doses, and no behavioral, biological, anatomical or histological disorders were identified.

In studies on rats and rabbits, embryotoxic or teratogenic effects were not observed.

The drug does not affect fertility.

No mutagenic potential was detected in in vitro and in vivo studies.

Pharmacokinetics

Studies were conducted after oral administration of the drug with ¹⁴C-labeled diosmin and after a single oral administration of Detralex^® 500 mg to healthy volunteers.

Absorption

After a single oral dose of ¹⁴C-labeled diosmin, the absorption rate, calculated based on total urinary excretion, was 58%.

Distribution

C_max of the purified micronised flavonoid fraction after a single oral dose of Detralex^® 500 mg is reached in plasma within 12 hours (in the range from 8 to 24 hours).

Metabolism

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

Diosmin is metabolized to the aglycone diosmetin, which is then converted in enterocytes into circulating glucuronic acid derivatives and various phenolic acids, including hippuric acid.

Excretion

In the first 24 hours after a single oral dose, excretion occurs mainly in the urine, with 31% of the oral dose excreted during this period.

With complete excretion of the drug 109 ± 23%, 58 ± 20% of the administered dose is excreted in the urine, and 51±24% of the administered dose is excreted in the feces (the main part of the drug excreted in the feces is eliminated after 24 hours).

Based on the measurement of diosmetin concentration in blood plasma after a single oral dose of Detralex^® 500 mg, its T_1/2 is approximately 11 hours.

Indications

Detralex^® is indicated for use in adults for the treatment of symptoms of chronic venous diseases (relief and alleviation of symptoms).

Treatment of symptoms of venous-lymphatic insufficiency

• Pain;
• Cramps in the lower limbs;
• Sensation of heaviness and distension in the legs;
• “tired” legs.

Treatment of manifestations of venous-lymphatic insufficiency

• Swelling of the lower limbs;
• Trophic changes of the skin and subcutaneous tissue;
• Venous trophic ulcers.

Treatment of symptoms and manifestations of acute and chronic hemorrhoids.

ICD codes

Dosage Regimen

Tablets

Orally. The tablets should be swallowed whole with water.

The recommended dose for venous-lymphatic insufficiency is 2 tablets/day in 1 or 2 doses in the morning, afternoon and/or evening, with meals.

The duration of the course of treatment can be several months (up to 12 months). In case of recurrence of symptoms, on the recommendation of a doctor, the course of treatment can be repeated.

The recommended dose for acute hemorrhoids is 6 tablets/day (3 tablets in the morning and 3 tablets in the evening) for 4 days, then – 4 tablets/day (2 tablets in the morning and 2 tablets in the evening) for the next 3 days, with meals.

The recommended dose for chronic hemorrhoids is 2 tablets/day, with meals.

The safety and efficacy of Detralex^® in children under 18 years of age have not been established. Data are not available.

Suspension

Orally.

The tablets should be swallowed with water. The score on the tablet is intended solely for dividing to facilitate swallowing.

The recommended dose for venous-lymphatic insufficiency is 1000 mg (1 tablet or 1 sachet) per day, preferably in the morning, with meals.

The duration of the course of treatment can be several months (up to 12 months). In case of recurrence of symptoms, on the recommendation of the attending physician, the course of treatment can be repeated.

The recommended dose for acute hemorrhoids is 3000 mg/day (1000 mg (1 tablet or 1 sachet) in the morning, 1000 mg (1 tablet or 1 sachet) in the afternoon and 1000 mg (1 tablet or 1 sachet) in the evening) for 4 days, then 2000 mg/day (1000 mg (1 tablet or 1 sachet) in the morning, 1000 mg (1 tablet or 1 sachet) in the evening) for the next 3 days, with meals.

The recommended dose for chronic hemorrhoids is 1000 mg (1 tablet or 1 sachet) per day at any convenient time of the day with meals.

The safety and efficacy of Detralex^® in children under 18 years of age have not been established. Data are not available.

Adverse Reactions

The side effects of Detralex^® observed during clinical studies were mild. Gastrointestinal disorders (diarrhea, dyspepsia, nausea, vomiting) were predominantly noted.

Tabulated summary of adverse reactions

Adverse reactions classified as possibly related to therapy with components of Detralex^®, based on clinical study data and post-registration experience, are listed below in the table by system organ class and absolute frequency of occurrence. Frequency is defined as follows: very common (≥1/10), common (≥1/100 and < 1/10), uncommon (≥1/1000 and < 1/100), rare (≥1/10,000 and < 1/1000), very rare (< 1/10,000), frequency not known (cannot be estimated from the available data).

Adverse reactions associated with the use of Detralex^®

* Post-registration experience

Reporting of suspected adverse reactions

It is important to report suspected adverse reactions after drug registration to ensure continuous monitoring of the benefit-risk balance of the drug. Healthcare professionals are encouraged to report any suspected adverse drug reactions through the national adverse reaction reporting systems of the member states of the Eurasian Economic Union.

Contraindications

• Hypersensitivity to the active substance or to any of the excipients included in the drug.

Use in Pregnancy and Lactation

Pregnancy

Data on the use of the purified micronised flavonoid fraction in pregnant women are absent or limited.

Animal studies have not revealed reproductive toxicity (see subsection “Preclinical safety data”).

As a precautionary measure, it is preferable not to use Detralex^® during pregnancy.

Breastfeeding period

It is unknown whether the purified micronised flavonoid fraction (metabolites) passes into human breast milk.

A risk to newborns and infants cannot be excluded. A decision should be made either to discontinue breastfeeding or to discontinue therapy with Detralex^®, taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.

Fertility

Reproductive toxicity studies did not show an effect on reproductive function in rats of both sexes (see subsection “Preclinical safety data”).

Pediatric Use

Use in children and adolescents under 18 years of age is contraindicated.

Special Precautions

In the treatment of hemorrhoids, the prescription of Detralex^® does not replace specific treatment for other diseases of the rectum and anal canal.

When using the drug independently, do not exceed the maximum periods and recommended doses indicated in the “Dosage Regimen” section.

If symptoms of hemorrhoids persist after the recommended course of therapy, you should be examined by a proctologist who will select further therapy.

In the presence of venous circulation disorders, the maximum treatment effect is achieved by combining therapy with a healthy (balanced) lifestyle: it is advisable to avoid prolonged exposure to the sun, prolonged standing, and it is recommended to reduce excess body weight.

Walking and, in some cases, wearing special stockings help improve blood circulation.

Patients with rare fructose intolerance should not take Detralex^® in the form of an oral suspension.

Effect on ability to drive vehicles and operate machinery

Studies of the effect of the flavonoid fraction on the ability to drive vehicles and operate machinery have not been conducted.

However, based on the overall safety profile of the flavonoid fraction, Detralex^® does not affect or does not have a significant effect on the ability to drive vehicles and operate machinery.

Overdose

Symptoms: data on cases of overdose with Detralex^® are limited. The most frequent adverse reactions in cases of overdose were gastrointestinal disorders (diarrhea, nausea, abdominal pain) and skin reactions (itching, rash).

Treatment: assistance in case of overdose should consist of eliminating clinical symptoms.

Drug Interactions

Interaction studies have not been conducted.

To date, no clinically significant drug interactions have been reported during the post-registration use of the drug.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 30°C (86°F).

Shelf Life

The shelf life for film-coated tablets is 4 years.

The shelf life for oral suspension is 3 years.

Do not use after the expiration date printed on the packaging.

Dispensing Status

The drug is available without a prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.