Pharmacological properties
Pharmacodynamics.
Dimethyl sulfoxide (DMSO). DMSO has anti-inflammatory, local analgesic and anti-edema effects. 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 the destruction of tissues.
DMSO has a local anesthetic effect, reducing the speed of conduction of excitatory impulses in peripheral neurons. The anti-edematous effect is explained by the inactivation of hydroxyl radicals and the consequent improvement of 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 exerts 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 is transformed in the skin into pantothenic acid - a vitamin of group B. Dexpanthenol has the same biological effectiveness as pantothenic acid. Pantothenic acid, which is part of coenzyme A, enters various reactions of formation and decay in all tissues and contributes to regeneration processes during wound healing and epithelization.
Pharmacokinetics
Dimethyl sulfoxide (DMSO). DMSO is present in human blood plasma as a natural substance in a concentration of about 40 ng/ml. After a single application of 1.5 g of Dolobene gel on the surface of the skin with an area of 400 cm 2, DMSO is absorbed with a half-life of 3-4 hours. 6 hours after application, the concentration in the blood plasma reaches a plateau (about 120 ng / ml), and remains at this level up to 12 hours after application. T ½ of DMSO from blood plasma is 11-14 hours. After 60 hours after the application, the desired endogenous concentration in the blood plasma is restored.
12-25% of DMSO is excreted during the first 24 hours and 37-48% during 7 days with urine unchanged as DMSO or as the main metabolite - dimethylsulfone (DMSO 2). 3.5-6% of the total dose of DMSO is exhaled by the lungs within 6-12 hours after application in the form of dimethyl sulfide (DMS).
Heparin. Penetration of heparin through healthy skin is dose-dependent and has been confirmed for dosages 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. Fast absorption of dexpanthenol was confirmed experimentally.
Indication
Injuries (including sports), hematomas, damage to muscles, periarticular structures or joints (without skin lesions); tendinitis, tendovaginitis, bursitis, shoulder scapular periarthritis and shoulder epicondylitis (the pathological basis of the clinical syndrome "tennis elbow"); acute neuralgia.
Application
The gel is applied in a thin layer (for example, a column 3 cm long is used for an area the size of which corresponds to the projection of the knee joint) on the affected areas and / or around them (in case of sores), evenly distributed over the surface of the skin with light rubbing movements 2-4 times a day. when applying bandages with gel DOLOBENE breathable dressing material is used only after the majority of the gel has penetrated the skin and the alcohol included 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. during phonophoresis, due to its good contact properties and the content of active substances, the drug 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 the therapy.
Contraindication
Increased sensitivity to the components of the drug; pronounced liver and kidney function disorders; ba; unstable hemodynamics; pronounced disorders of the cardiovascular system (severe angina pectoris, myocardial infarction, stroke, severe general atherosclerosis); bleeding trophic ulcers of the legs, open and / or infected wounds, hemorrhagic diathesis, purpura, thrombocytopenia, hemophilia, tendency to bleeding; comatose states, glaucoma, cataracts.
Side effects
From the side of the immune system: allergic skin reactions, in some cases allergic reactions of the immediate type are possible, such as urticaria and Quincke's edema.
From the side of the cardiovascular system: in some cases, when applied to large areas of the skin, cardiac disturbances are possible (the causal relationship has not been established).
From the side of the respiratory system: in some cases, when applied to large areas of the skin, disturbances from the side of the respiratory system are possible (the causal relationship is not determined).
From the side of the digestive system: a temporary smell of garlic from the mouth (caused by the action of dimethyl sulfide - a metabolite of dimethyl sulfoxide); change in taste sensations, which passes within a few minutes; in some cases, when applied to large areas of the skin - disturbances from the stomach, nausea, diarrhea (the causal relationship is not determined).
On the part of the skin: reactions of hypersensitivity to light.
General disorders: erythema, itching, burning, blisters, urticaria at the application site. These reactions usually disappear during treatment. Otherwise, the use of the drug should be stopped. In some cases, when applied to large areas of the skin, increased fatigue, headache, and chills are possible (the cause-and-effect relationship has not been determined).
Caused by the action of dimethyl sulfoxide: dizziness, insomnia, adynamia, dermatitis, bronchospasm, vomiting.
Due to the effect of dexpanthenol: contact dermatitis, allergic dermatitis, eczema, rash, skin irritation.
Caused by the effect of heparin: swelling of the skin, skin rash, hemorrhages, sometimes - the appearance of small pustules, blisters or blisters, which quickly disappear after the withdrawal 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 radiation, with dermatitis, dermatoses, postoperative scars, burns).
Other medicinal products should not be applied to the treated areas of the skin for several hours before and after applying the Dolobene gel.
In order to prevent unwanted effects, the drug should be applied to skin that has been cleansed of other drugs, cosmetics, and impurities.
Avoid contact with eyes.
Application of dimethyl sulfoxide can lead to the development of photosensitivity. In this regard, when using Dolobene gel, you should refrain from tanning and visiting the solarium. If hypersensitivity reactions occur, the use of the drug should be discontinued.
Application during pregnancy and lactation. The experience of using dimethylsulfoxide in pregnant women is still insufficient, so the use of the drug during pregnancy and breastfeeding is contraindicated. DMSO has been reported to be potentially teratogenic in animals.
Dimethyl sulfoxide penetrates into breast milk, so the use of the gel during breastfeeding is contraindicated.
The ability to influence the speed of reaction when driving vehicles or other mechanisms. Does not affect.
Children. The drug is not prescribed to children due to limited experience of use.
Interactions
The simultaneous use of other local medicines may be accompanied by an increase in their absorption.
Due to the ability of dimethylsulfoxide to increase both the specific activity and toxicity of some drugs, simultaneous application of other drugs for local use should be avoided.
The drug Dolobene, which contains dimethylsulfoxide, cannot be used with sulindac (NSAID) due to the possibility of severe toxic reactions (peripheral neuropathy).
The use of heparin can lead to a prolongation of the prothrombin time in patients who use oral anticoagulants. Dimethylsulfoxide enhances the effect of ethanol (alcohol inhibits the excretion of the drug) and insulin, acetylsalicylic acid, butadione; digitalis, quinidine, nitroglycerin, antibiotics (streptomycin, monomycin, etc.), sensitizes the body to anesthetics.
Overdose
There were no cases of overdose when using DOLOBENE.
Increased manifestations of hematoma and increased risk of bleeding with external use of heparin at a dose above 180,000 IU have been reported. Intestinal absorption of heparin is insignificant, so the appearance of signs of overdose with its accidental ingestion is unlikely.
Storage conditions
At a temperature not higher than 25 °C.