Dolobene® [Heparin, Dexpanthenol, Dimethyl Sulfoxide]

Pharmacological properties

Pharmacodynamics

Dimethyl sulfoxide (DMSO). DMSO has an anti-inflammatory, local analgesic and decongestant effect. The anti-inflammatory effect is based on several pharmacological effects, the main of which is the inactivation of hydroxyl radicals, which are formed in large quantities during inflammation and lead to tissue destruction.

DMSO has a local anesthetic effect, reducing the speed of the exciting pulses in peripheral neurons. The decongestant effect is explained by the inactivation of hydroxyl radicals and the consequent improvement in metabolic processes in the focus of inflammation. The hygroscopic properties of DMSO are also partly responsible for this.

Heparin. Heparin competitively inhibits the activity of hyaluronidase, which, in turn, prevents excessive degeneration of connective tissue during inflammation. Thus, heparin has an anti-inflammatory effect and promotes healing. In addition, heparin has a dose-dependent antithrombotic effect, significantly increasing the inhibitory effect of antithrombin III on the activation of prothrombin and thrombin.

Dexpanthenol. When applied topically, dexpanthenol turns into skin in pantothenic acid - a vitamin of group B. Dexpanthenol has the same biological effectiveness as pantothenic acid. Pantothenic acid, which is part of coenzyme A, in all tissues enters various reactions of formation and decomposition and contributes to the passage of regeneration processes during wound healing and epithelization.

Pharmacokinetics

Dimethyl sulfoxide (DMSO). DMSO is present in human blood plasma as a natural substance at a concentration of about 40 ng / ml. After a single application of 1.5 g of Dolobene gel on a 400 cm skin surface² DMSO is absorbed with a half-life of 3-4 hours. After 6 hours after application, the plasma concentration reaches a plateau (about 120 ng / ml), and remains at this level until 12 hours after application. T_½ DMSO from blood plasma is 11-14 hours. After 60 hours after application, an endogenous plasma concentration is again reached.

12–25% DMSO is excreted during the first 24 hours and 37–48% within 7 days with urine unchanged as DMSO or as the main metabolite, dimethyl sulfone (DMSO₂) 3.5–6% of the total dose of DMSO is exhaled by the lungs for 6–12 hours after application in the form of dimethyl sulfide (DMS).

Heparin. The penetration of heparin through healthy skin is dose-dependent and confirmed for dosing from 300 IU / h.

There are no data on the pharmacokinetics of heparin after its application to the skin.

Dexpanthenol. Dexpanthenol is absorbed faster than pantothenic acid. The rapid absorption of dexpanthenol was confirmed experimentally.

Indications

• Injuries (including sports), hematomas, damage to muscles, periarticular structures or joints (without skin lesions); tendonitis, tendovaginitis, bursitis, humeroscapular periarthritis and shoulder epicondylitis (pathological basis of the clinical syndrome “tennis player’s elbow”); acute neuralgia.

Application

The gel is applied in a thin layer (for example, a column of gel 3 cm long is applied to an area the size of which corresponds to the projection of the knee joint) on the affected areas and / or around them (with abrasions), evenly distributed over the skin surface with light rubbing movements 2–4 times a day. when applying dressings with dolobene gel, a breathable dressing is used only after the majority of the gel has penetrated the skin and the alcohol contained in the preparation has evaporated (several minutes). when using iontophoresis, the gel is applied under the cathode, taking into account the anionic properties of heparin, which is part of dolobene.with phonophoresis, the drug, due to its good contact properties and active substance content, complements the physiotherapeutic effect of ultrasonic waves. the duration of the dolobene treatment course is individual and depends on the severity of the course of the disease, as well as on the effectiveness of therapy.

Contraindications

Hypersensitivity to the components of the drug; severe impaired liver and kidney function; ba; unstable hemodynamics; severe disorders of the cardiovascular system (severe angina pectoris, myocardial infarction, stroke, severe general atherosclerosis); trophic ulcers of the legs that bleed, open and / or infected wounds, hemorrhagic diathesis, purpura, thrombocytopenia, hemophilia, tendency to bleed; coma, glaucoma, cataract.

Side effects

On the part of the immune system: allergic skin reactions, in some cases immediate allergic reactions are possible, such as urticaria and angioedema.

From the cardiovascular system: in some cases, when applied to large areas of the skin, disturbances from the heart are possible (a causal relationship has not been established).

On the part of the respiratory system: in some cases, when applied to large areas of the skin, violations of the respiratory system are possible (a causal relationship has not been determined).

From the digestive system: temporary smell of garlic from the mouth (due to the action of dimethyl sulfide - a metabolite of dimethyl sulfoxide); a change in taste that lasts for several minutes; in some cases, when applied to large areas of the skin - disorders of the stomach, nausea, diarrhea (causal relationship not defined).

On the part of the skin: hypersensitivity reactions to the action of light.

Common disorders: erythema, itching, burning, blisters, urticaria at the site of application. These reactions usually disappear during treatment. Otherwise, the use of the drug should be discontinued. In some cases, when applied to large areas of the skin, increased fatigue, headache, and chills are possible (a causal relationship has not been determined).

Due to the action of dimethyl sulfoxide: dizziness, insomnia, adynamia, dermatitis, bronchospasm, vomiting.

Due to the action of dexpanthenol: contact dermatitis, allergic dermatitis, eczema, rash, skin irritation.

Due to the action of heparin: swelling of the skin, skin rash, hemorrhage, sometimes - the appearance of small pustules, vesicles or blisters that quickly disappear after discontinuation of the drug.

special instructions

The drug contains isopropyl alcohol, therefore, in order to avoid painful reactions, it should not be applied to mucous membranes, an open wound surface or damaged skin (for example, after irradiation, with dermatitis, dermatoses, postoperative scars, burns).

Other drugs should not be applied to treated skin for several hours before and after application of Dolobene gel.

In order to prevent the appearance of undesirable effects, the drug must be applied to the skin cleansed of other drugs, cosmetics and contaminants.

Eye contact should be avoided.

Application of dimethyl sulfoxide can lead to the development of photosensitization. In this regard, when applying the Dolobene gel, you should refrain from tanning and visiting the solarium. If hypersensitivity reactions occur, the use of the drug should be discontinued.

Use during pregnancy or lactation. Experience in the use of dimethyl sulfoxide in pregnant women is still not enough, so the use of the drug during pregnancy and lactation is contraindicated. Potential teratogenic effects of DMSO in animals have been reported.

Dimethyl sulfoxide passes into breast milk, so the use of the gel during lactation is contraindicated.

The ability to influence the reaction rate when driving vehicles or other mechanisms. Does not affect.

Children. The drug is not prescribed for children due to limited experience in use.

Interactions

The simultaneous use of other local medicines may be accompanied by increased absorption.

Due to the ability of dimethyl sulfoxide to enhance both the specific activity and toxicity of certain drugs, the simultaneous application of other drugs for local use should be avoided.

The drug Dolobene containing dimethyl sulfoxide cannot be used with sulindac (NSAIDs) because of the possibility of severe toxic reactions (peripheral neuropathy).

The use of heparin can lead to an increase in prothrombin time in patients taking oral anticoagulants. Dimethyl sulfoxide enhances the action of ethanol (alcohol inhibits the excretion of the drug) and insulin, acetylsalicylic acid, butadione; digitalis drugs, quinidine, nitroglycerin, antibiotics (streptomycin, monomycin, etc.), the body sensitizes to drugs for anesthesia.

Overdose

When using dolobene, overdose cases were not observed.

An increase in hematoma manifestations and an increased risk of bleeding with external use of heparin at a dose above 180,000 IU have been reported. Intestinal absorption of heparin is negligible, so the appearance of signs of an overdose if it is accidentally swallowed is unlikely.

Storage conditions

At a temperature not exceeding 25 ° c.

Medicinal product information for healthcare professionals.