Detragel^® (Gel) Instructions for Use

Marketing Authorization Holder

Servier, JSC (Russia)

Manufactured By

Bosnalijek, JSC (Bosnia And Herzegovina)

Contact Information

SERVIER AO (Russia)

ATC Code

C05BA53 (Heparin in combination with other drugs)

Active Substances

Heparin sodium (Rec.INN registered by WHO)

Phospholipids (Grouping name)

Aescine (DCF adopted for use in France)

Dosage Form

Detragel®

Gel for external use 100 IU+10 mg+10 mg/1 g: tubes 40 g or 80 g

Dosage Form, Packaging, and Composition

Gel for external use transparent, light yellow in color, with a characteristic odor.

Excipients: isopropanol, glycerol 85%, trolamine, methylparaben, ethylparaben, propylparaben, carbomer-980, eau de cologne, rosemary oil, lavender oil, water.

40 g – aluminum tubes (1) – cardboard packs with first opening control.
80 g – aluminum tubes (1) – cardboard packs with first opening control.

Clinical-Pharmacological Group

Combination of a venotonic and a direct-acting anticoagulant for topical use

Pharmacotherapeutic Group

Angioprotectors; agents for the treatment of varicose veins; heparins or heparinoids for topical use

Pharmacological Action

Mechanism of action and pharmacodynamic effects

A combined drug that has a local anticoagulant, anti-inflammatory, venotonic and antiplatelet effect, reduces venous permeability, and improves microcirculation after a single application.

Detragel^® contains 3 active substances – Heparin sodium, Essential phospholipids and Aescin, which have pharmacodynamic and pharmacokinetic synergy.

Heparin sodium is a direct-acting anticoagulant; due to the inactivation of biogenic amines and blocking of lysosomal enzymes in the tissue, it exhibits an anti-inflammatory effect, accelerates the dissolution of microthrombi in the area of subcutaneous capillaries, prevents thrombus formation, and activates the fibrinolytic system; improves microcirculation, promotes regeneration of connective tissue by inhibiting the activity of hyaluronidase.

Essential phospholipids reduce blood viscosity due to their effect on fat metabolism and reduce platelet aggregation processes.

Aescin is a venotonic agent of plant origin. It prevents the activation of lysosomal enzymes that break down proteoglycan, increases the tone of the venous wall, and eliminates venous stasis; reduces the permeability and fragility of capillaries. Reduces exudation, reduces the effusion of fluid into tissues and accelerates the resorption of existing edema. Inhibits inflammation processes, improves microcirculation, and promotes tissue repair.

Clinical efficacy and safety

To date, there have been no reports of adverse effects on the mother and fetus when the drug was used by pregnant women.

The effect of the drug Detragel^® on microcirculation can be noted after a single application.

Pharmacokinetics

Absorption

Due to their hydrophilic and lipophilic properties, Essential phospholipids act as a carrier that ensures rapid penetration of other active substances through the skin (through sebaceous and sweat glands), which has been proven in radioisotope studies.

Heparin sodium, when applied topically, quickly penetrates the epidermis and accumulates in the upper layers of the skin. An insignificant amount of heparin sodium is absorbed from the skin surface into the systemic circulation (less than 0.2% of the total amount applied).

Distribution

C_max of heparin sodium in the blood is observed 8 hours after application to the skin.

Metabolism

After absorption, Heparin sodium is biotransformed in the liver and in the RES.

Excretion

Heparin sodium is excreted mainly in the urine. T_1/2 is 12 hours. Heparin does not cross the placental barrier and is not excreted in breast milk.

Indications

• Therapy of symptoms of chronic venous diseases;
• Varicose veins with symptoms such as pain, swelling, feeling of heaviness and fatigue in the legs, night cramps of the calf muscles and with signs such as telangiectasias (spider veins and reticular veins) and varicose veins;
• Superficial phlebitis, thrombophlebitis;
• Hematomas due to injuries, including sports sprains and bruises;
• Postoperative hematomas without violation of the integrity of the skin.

ICD codes

Dosage Regimen

Externally. Apply a thin layer to the problem area of the skin and distribute evenly with light massaging movements. The gel should be applied to the lower limbs from the bottom up.

In case of phlebitis/thrombophlebitis, rubbing the gel should be avoided.

If necessary, the gel can be applied under elastic stockings or bandages.

After application, hands should be washed thoroughly.

Unless otherwise recommended by a doctor, a 1-5 cm strip of gel (depending on the indication for use and the area of the treated surface) is applied in a thin layer to the skin on the affected area 2-3 times/day daily until the symptoms disappear.

The standard duration of the course of treatment is no more than 15 days. A longer course of treatment is possible.

Patients should be informed that they should not exceed the recommended dose and duration of use of the drug.

Children

The safety and efficacy of the drug Detragel^® in children aged 0 to 18 years have not been established to date. Data are not available.

Adverse Reactions

Side effects are presented with the following gradation: 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 unknown (cannot be estimated from the available data).

Respiratory system disorders very rare – bronchospasm.

Skin and subcutaneous tissue disorders very rare – delayed-type allergic reactions (contact dermatitis), immediate-type allergic reactions (skin rash, skin itching, urticaria).

Reporting of suspected adverse reactions

It is important to report suspected adverse reactions after registration of the drug in order to ensure continuous monitoring of the benefit-risk ratio of the drug. Healthcare professionals and pharmaceutical specialists are recommended 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 heparin sodium, essential phospholipids, aescin or to any of the excipients included in the drug;
• Hemorrhagic diathesis (including thrombocytopenic purpura, hemophilia);
• Violation of the integrity of the skin at the site of application of the drug (open wounds, ulcerative-necrotic lesions);
• Burns, eczema, skin infections at the site of application of the drug;
• Use on mucous membranes.

Use in Pregnancy and Lactation

Pregnancy

Reproductive toxicity studies in animals have not revealed any effect on embryo or fetal development.

Heparin sodium does not cross the placental barrier.

Use during pregnancy is possible only in cases where the expected benefit of therapy for the mother outweighs the potential risk to the fetus.

Breastfeeding period

Heparin sodium is not excreted in breast milk.

Use during breastfeeding is possible only in cases where the expected benefit of therapy for the mother outweighs the potential risk to the child.

Pediatric Use

There is no experience with the use of the drug in children under 18 years of age.

Special Precautions

Application of the gel to mucous membranes is contraindicated. Contact with eyes should be avoided.

In case of development of allergic reactions (including delayed ones), the use of the drug should be stopped immediately and appropriate treatment should be prescribed.

If during the use of the drug there is a worsening of symptoms (pain, swelling, redness, inflammatory changes), it is necessary to consult a doctor immediately, as this may be a sign of a more serious disease.

Topical agents can cause sensitization (especially with prolonged use). In case of sensitization development, the use of the drug Detragel^® should be discontinued and, if necessary, appropriate therapy should be prescribed.

With prolonged use of the drug on large areas of the skin and simultaneous use of indirect anticoagulants (including warfarin, acenocoumarol), prothrombin time and blood clotting time should be monitored.

It is not recommended to use the drug Detragel^® for deep vein thrombosis.

Use in pediatrics

There is no experience with the use of the drug in children under 18 years of age.

Excipients

The drug Detragel^® contains methylparaben, ethylparaben and propylparaben, which can cause allergic reactions (including delayed ones).

Effect on ability to drive vehicles and mechanisms

No studies have been conducted on the effect of the drug on the ability to drive vehicles and work with mechanisms.

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Overdose

There are no data on drug overdose.

Treatment in case of overdose, the effect of heparin can be neutralized with a solution of protamine sulfate.

Drug Interactions

Currently, there are no data on interaction with other medicinal products.

The drug should not be applied to the same area of the skin simultaneously with other topical medicinal products.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 3 years. Do not use after the expiration date.

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.