Dolonit-Mosfarma (Gel) Instructions for Use

Marketing Authorization Holder

Moscow Pharmaceutical Factory CJS (Russia)

Contact Information

MOSCOW PHARMACEUTICAL FACTORY CJSC (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

Dolonit-Mosfarma

Gel for external use 50,000 IU+2.5 g+15 g/100 g: tubes 30 g or 50 g

Dosage Form, Packaging, and Composition

Gel for external use colorless, transparent or slightly opalescent, homogeneous, with a characteristic odor.

Excipients: carbomer homopolymer type C – 1 g, trometamol – 0.2 g, macrogol glyceryl hydroxystearate – 0.9 g, ethanol 95% – 38.06 g, rosemary oil – 0.2 g, Scots pine oil – 0.25 g, lemon oil – 0.05 g, purified water – up to 100 g.

30 g – aluminum tubes (1) – cardboard boxes.
50 g – aluminum tubes (1) – cardboard boxes.

Clinical-Pharmacological Group

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

Pharmacotherapeutic Group

Direct-acting anticoagulant for topical use + other drugs

Pharmacological Action

The action of the drug is due to its active substances: dimethyl sulfoxide, heparin sodium, and dexpanthenol.

Dimethyl sulfoxide (DMSO)

DMSO has anti-inflammatory, anti-edema, and local analgesic action.

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.

DMSO exerts a local analgesic effect by reducing the conduction velocity of nociceptive (pain) 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 some extent, the hygroscopic properties of DMSO are also responsible for its anti-edema action.

DMSO (from 50% and more) penetrates biological membranes, including the skin, promoting better and deeper penetration into the tissues of other drugs applied simultaneously.

Heparin sodium

Heparin sodium, which is part of the drug, is a direct-acting anticoagulant; due to the inactivation of biogenic amines in the tissue, it exhibits a distinct anti-inflammatory effect and improves local blood circulation. Heparin sodium inhibits the action of hyaluronidase and thus effectively promotes the regeneration of connective tissue.

Heparin sodium exhibits a dose-dependent antithrombotic effect by enhancing the inhibitory activity of antithrombin III on the activation of prothrombin and thrombin. The penetration of heparin sodium through healthy skin is dose-dependent and confirmed for dosages starting from 300 IU/g.

Dexpanthenol

Dexpanthenol exhibits anti-inflammatory and dermatoprotective action, stimulates regeneration processes. After absorption, it is converted into pantothenic acid, which is involved in numerous metabolic processes as a component of coenzyme A; by improving granulation and epithelialization processes, it promotes the regeneration of damaged skin areas.

Pharmacokinetics

Dimethyl sulfoxide (DMSO)

DMSO enters the systemic circulation, the half-life of absorption is 3-4 hours. DMSO penetrates into breast milk. It is eliminated mainly in the urine.

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 DMSO in blood plasma reaches the physiological level of 40 ng/ml.

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

3.5-6.0% of all DMSO is excreted through the lungs as dimethyl sulfide, 6-12 hours after application of the drug.

When applying 1 g of DMSO 3 times/day for 5 days, its average content at the site of application to the skin 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 DMSO in blood plasma is 0.5 µg/g.

T_1/2 of DMSO from blood plasma is 11-14 hours.

Heparin sodium

Heparin sodium quickly penetrates the skin; already within the first hour after application of the gel, the concentration in the underlying tissues corresponds to concentrations that are achieved after IV administration of 5000 IU of heparin. Heparin sodium does not cross the placental barrier and does not enter breast milk.

Dexpanthenol

With external use, Dexpanthenol is transformed in the skin into pantothenic acid, which has a lower rate and degree of transdermal penetration than dexpanthenol.

Indications

• Edema, hematomas, and inflammations of soft tissues, muscles, tendons, tendon sheaths, and ligaments after contusions, compressions, injuries;
• Closed injuries, bruises;
• Joint injuries with ligament damage;
• Scapulohumeral periarthritis and humeral epicondylitis (“tennis elbow”), tendinitis (inflammation of tendons), tenosynovitis (inflammation of tendon sheaths), bursitis (inflammation of the joint synovial bursa);
• Acute neuralgia.

ICD codes

Dosage Regimen

The drug is applied in a thin surface layer to the skin over the area of affected soft tissues, joints, or tendons (edema, hematoma, inflammation, injury) and evenly distributed with light rubbing movements.

To cover the entire surface of a bruised knee, it is usually sufficient to squeeze out 3-4 cm of gel from the tube.

The procedure is repeated 2-4 times/day for 7 days or until the symptoms of the disease, such as pain, swelling, edema, inflammation, disappear.

If no distinct improvement occurs within 7 days of treatment, the patient should consult a doctor.

When applying bandages with the gel, the air-permeable dressing material is applied only after most of the gel has penetrated the skin and the alcohol has evaporated (a few minutes).

Dolonit-Mosfarma and iontophoresis

The drug can be used for iontophoresis. Heparin sodium contained in the drug is an anion in solution. Applying the drug under the cathode promotes increased penetration of heparin sodium into the affected area, and Dimethyl sulfoxide exhibits a synergistic action with the effect of electric current (analgesia, reduction of local edema).

It should be remembered that the electric current treatment itself can cause local skin irritation reactions. Therefore, it is necessary to carefully follow the instructions of the device manufacturers so that the use of the drug does not enhance local reactions.

Attention should always be paid to the sufficiency of covering the electrodes with a moist sponge.

Dolonit-Mosfarma and ultrasound (phonophoresis)

This drug is a good contact gel for ultrasound therapy (phonophoresis). The active substances of the gel (Dimethyl sulfoxide and Heparin sodium) complement the therapeutic effect of ultrasonic waves.

Adverse Reactions

The drug is usually well tolerated, however, in isolated cases, local skin reactions (redness, itching, and burning sensation at the application site) are possible, which usually gradually disappear during treatment.

Sometimes, due to the content of DMSO or other components of the drug, a general skin allergic reaction with urticaria and angioedema may occur.

In rare cases, during the use of the drug, some patients may develop a garlic odor from the mouth, which is due to the presence of dimethyl sulfide, a metabolite of dimethyl sulfoxide. This odor indicates good absorption of dimethyl sulfoxide. In some patients, after applying the gel, a change in taste sensations may appear, which disappears after a few minutes.

Extremely rarely, when applying the drug to large areas of the body, nausea, diarrhea, difficulty breathing, headache, and chills may occur.

Contraindications

• Hypersensitivity to any of the components of the gel (active/excipient substances);
• Severe impairment of liver and/or kidney function;
• Bronchial asthma;
• Severe disorders of the cardiovascular system (Canadian Cardiovascular Society functional class IV angina pectoris, myocardial infarction, stroke, severe generalized atherosclerosis);
• Pregnancy;
• Breastfeeding period;
• Children under 5 years of age.

The drug should not be applied to mucous membranes (eyes, nose, mouth), open wounds, or damaged skin (for example, condition after radiation or severe sunburns, fresh postoperative scars).

Use in Pregnancy and Lactation

Since there are no research data on the use of the drug in pregnant women, its use during pregnancy is contraindicated.

Dimethyl sulfoxide penetrates into breast milk, therefore, breastfeeding should be discontinued during the use of the drug.

Use in Hepatic Impairment

The use of the drug is contraindicated in severe impairment of liver function.

Use in Renal Impairment

The use of the drug is contraindicated in severe impairment of kidney function.

Pediatric Use

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

Special Precautions

The drug is used economically, quickly penetrates the skin and does not leave a greasy layer on the skin or stains on linen. Due to the contained alcohol (ethanol), which evaporates after applying the gel, a pleasant cooling sensation is felt at the site of application of the drug. The pleasant cooling effect is enhanced if the gel is stored in the refrigerator, and also if the drug is used in hot weather (due to increased evaporation of alcohol).

The area of skin to which the drug is applied should be cleaned of dirt, cosmetics, other medicines, and chemicals.

When using bandages, it is necessary to wait a few minutes after applying the gel for the main mass of the gel to be absorbed and the ethyl alcohol (ethanol) to evaporate. This is especially important in cases where a poorly air-permeable bandage is used.

During treatment with the drug, skin photosensitivity may increase, so during its use, intense sunbathing and visiting a solarium should be limited.

In case of skin reactions, treatment should be discontinued.

Due to the high absorption of dimethyl sulfoxide, Dolonit-Mosfarma should not be used in combination with other ointments and gels.

It should be remembered that getting the drug on open wounds causes a pain reaction, because the gel contains ethyl alcohol (ethanol).

Effect on the ability to drive vehicles and mechanisms

When applied to the skin, the drug does not affect the ability to drive vehicles and engage in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Overdose

Cases of overdose and poisoning with the drug have not been described.

Drug Interactions

Topical application of other drugs simultaneously with Dolonit-Mosfarma promotes a sharp increase in their permeability through the skin.

With simultaneous use with the non-steroidal anti-inflammatory drug sulindac, the development of peripheral neuropathy is possible (due to the presence of dimethyl sulfoxide in the composition of Dolonit-Mosfarma).

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 the drug 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.