Solvibene (Gel) Instructions for Use

Marketing Authorization Holder

Erkapharm, JSC (Russia)

Manufactured By

Tula Pharmaceutical Factory, LLC (Russia)

ATC Code

C05BA53 (Heparin in combination with other drugs)

Active Substances

Dexpanthenol (Rec.INN registered by WHO)

Heparin sodium (Rec.INN registered by WHO)

Dimethyl sulfoxide (Rec.INN registered by WHO)

Dosage Form

Solvibene

Gel for external use 500 IU+25 mg+150 mg/1 g: tube 45 g

Dosage Form, Packaging, and Composition

Gel for external use from transparent to slightly cloudy and from colorless to slightly yellowish.

Excipients: polyacrylic acid – 1.2 g, trometamol – 0.25 g, macrogolglycerol hydroxystearate – 1 g, isopropanol – 35 g, purified essential oil of Rosmarinus officinalis leaf (rosemary oil) – 0.2 g, purified essential oil of Pinus mugo needle – 0.25 g, purified essential oil of Cymbopogon winterianus herb (citronella oil) – 0.05 g, purified water – up to 100 g.

45 g – aluminum tubes (1) – cardboard packs.

Clinical-Pharmacological Group

A drug with antithrombotic and tissue regeneration-improving action for topical use

Pharmacotherapeutic Group

Drugs for external use for muscle and joint pain; other drugs for external use for muscle and joint pain

Pharmacological Action

A combined drug for external use, the action of which is due to its active ingredients.

Heparin is a direct-acting anticoagulant.

Due to the inactivation of biogenic amines and blocking of lysosomal enzymes in tissues, it has an anti-inflammatory effect; promotes the regeneration of connective tissue by inhibiting the activity of hyaluronidase.

It exerts a dose-dependent antithrombotic effect by enhancing the inhibitory activity of antithrombin III on the activation of prothrombin and thrombin.

The penetration of heparin through healthy skin is dose-dependent and confirmed for a dose starting from 300 IU/g.

It accelerates the dissolution of microthrombi in the area of subcutaneous capillaries; improves local blood flow.

When applied externally, it also has an anti-edema effect.

Dexpanthenol has anti-inflammatory and dermatoprotective effects.

When applied topically, it is transformed in the skin into pantothenic acid (a B-group vitamin).

The efficacy of dexpanthenol is comparable to that of pantothenic acid.

Pantothenic acid, as a component of coenzyme A, participates in various catabolic and anabolic processes in tissues; by improving granulation and epithelialization processes, it promotes the regeneration of damaged skin areas.

Dimethyl sulfoxide has anti-inflammatory, anti-edema, and local anesthetic effects, and has moderate fibrinolytic activity.

Anti-inflammatory activity is associated with several pharmacological effects, the most significant of which is the inactivation of hydroxyl radicals, which are produced in large quantities during the inflammatory process and have a destructive effect on tissues.

Dimethyl sulfoxide exerts a local anesthetic effect by reducing the conduction velocity of nociceptive impulses in peripheral neurons.

The anti-edema effect is provided by the inactivation of hydroxyl radicals and the improvement of the subcutaneous metabolic reaction at the site of drug application.

To a certain extent, the hygroscopic properties of dimethyl sulfoxide are also responsible for its anti-edema effect.

Dimethyl sulfoxide (from 50% and above) penetrates biological membranes, including the skin, promoting better and deeper penetration into the tissues of other drugs applied simultaneously with it.

Pharmacokinetics

Heparin sodium

When applied externally, it quickly penetrates the skin.

1 hour after applying the gel to the skin, the concentration in the underlying tissues is comparable to the concentration observed after intravenous (IV) administration of 5000 IU of heparin.

Heparin does not cross the placental barrier and is not excreted in breast milk.

Dexpanthenol

After resorption into the skin, it is converted into pantothenic acid (vitamin B₅), which, being an integral part of coenzyme A, participates in numerous metabolic processes.

Dimethyl sulfoxide

It enters the systemic circulation, the half-life of absorption is 3-4 hours.

Dimethyl sulfoxide penetrates into breast milk.

6 hours after application of the drug, C_max in blood plasma reaches 120 ng/ml and persists for up to 12 hours after application.

60 hours after application, the concentration of dimethyl sulfoxide in blood plasma reaches the physiological level of 40 ng/ml.

It is excreted mainly by the kidneys.

12-25% of the absorbed dimethyl sulfoxide is excreted within the first 24 hours and 37-48% is excreted within 7 days unchanged or as a metabolite (dimethyl sulfone).

3.5-6% of dimethyl sulfoxide is excreted through the lungs as dimethyl sulfide 6-12 hours after application of the drug.

When using dimethyl sulfoxide at a dose of 1 g 3 times/day for 5 days, its average content at the skin application site is 3 mg/g, the average content in the underlying muscle tissues and synovial membrane at the site of the synovial joint is 7-10 µg/ml, in the synovial fluid – 0.8 µg/g.

The concentration of dimethyl sulfoxide in blood plasma is 0.5 µg/g.

T_1/2 of dimethyl sulfoxide is 11-14 hours.

Indications

Edema, hematomas, and inflammation of soft tissues, muscles, tendons, tendon sheaths after bruises, compressions, injuries (including sports injuries); scapulohumeral periarthritis, epicondylitis of the humerus (“tennis elbow”), tendinitis, tenosynovitis, bursitis, neuralgias.

ICD codes

Dosage Regimen

The drug is applied externally.

The gel is applied in a thin layer to clean, dry skin over the affected area and distributed evenly with light rubbing movements, 1-4 times/day.

The duration of treatment depends on the severity of symptoms and the severity of the disease.

Usually, the drug is used for 7-10 days or until the symptoms of the disease (pain, swelling, inflammation) disappear.

When using the drug under a bandage, apply the gel and wait a few minutes for it to be absorbed by the skin and for the isopropanol to evaporate.

Then an occlusive dressing can be applied.

The drug can be used for iontophoresis.

The gel is applied under the cathode.

The drug can be used as a contact gel in ultrasound therapy (phonophoresis).

The active ingredients of the gel complement the therapeutic effect of ultrasonic waves.

Adverse Reactions

Local reactions: skin reactions (redness, itching, burning sensation at the site of gel application) are possible, which usually disappear during further treatment.

Allergic reactions sometimes – skin manifestations, including urticaria; in isolated cases – angioedema.

Other in rare cases – garlic odor from the mouth (caused by dimethyl sulfide, which is a metabolite of dimethyl sulfoxide), possible change in taste sensations (disappear a few minutes after applying the gel); when applying the drug to large areas of the body, extremely rarely – nausea, diarrhea, difficulty breathing, headache, chills.

Contraindications

Severe hepatic insufficiency; severe renal insufficiency; bronchial asthma; severe disorders of the cardiovascular system (including stable angina pectoris CCS Class IV, myocardial infarction, stroke, severe generalized atherosclerosis); open wounds at the site of drug application; pregnancy; lactation period; children under 5 years of age; hypersensitivity to heparin, dimethyl sulfoxide, dexpanthenol and other components of the drug.

Use in Pregnancy and Lactation

The use of the drug is contraindicated during pregnancy due to the lack of clinical study data.

The use of the drug during breastfeeding is contraindicated, because Dimethyl sulfoxide is excreted in breast milk.

Use in Hepatic Impairment

The use of the drug is contraindicated in severe hepatic impairment.

Use in Renal Impairment

The use of the drug is contraindicated in severe renal impairment.

Pediatric Use

The use of the drug is contraindicated in children under 5 years of age.

Special Precautions

Before applying the gel, the skin should be thoroughly cleaned of other medicines, cosmetics, or any chemicals.

The drug should not be applied to the mucous membranes of the eyes, nasal and oral cavities, open wounds, or damaged skin areas (due to radiation, severe sunburn, postoperative scars).

During treatment with the drug, skin photosensitivity may increase, so during the period of gel application, intense sunbathing and visiting a solarium should be limited.

If skin allergic reactions occur, treatment should be discontinued.

Effect on the ability to drive vehicles and mechanisms

The drug does not affect the ability to drive vehicles and engage in other activities requiring increased concentration and speed of psychomotor reactions.

Drug Interactions

With simultaneous external application, the drug may enhance the penetration of other drugs through the skin.

With simultaneous use of the drug with medicines containing sulindac (NSAID), the development of peripheral neuropathy is possible.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Over-the-Counter

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.