Pharmacological properties
Pharmacodynamics.
Dimethyl sulfoxide (DMSO). DMSO has anti-inflammatory, local analgesic and anti-edematous effects. The anti-inflammatory effect is based on several pharmacological effects, the main of which is the inactivation of hydroxyl radicals, which during inflammation are formed in large quantities and lead to tissue destruction.
DMSO has a local analgesic effect by reducing the speed of excitatory impulses in peripheral neurons. The anti-edematous effect is explained by the inactivation of hydroxyl radicals and the resulting improvement in metabolic processes at the site 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 is converted in the skin into pantothenic acid, a B vitamin. Dexpanthenol has the same biological effectiveness as pantothenic acid. Pantothenic acid, which is part of coenzyme A, enters various formation and breakdown reactions in all tissues and promotes regeneration processes during wound healing and epithelization.
Pharmacokinetics
Dimethyl sulfoxide (DMSO). DMSO is present in human plasma as a natural substance at a concentration of about 40 ng/ml. After a single application of 1.5 g of Dolobene gel to a skin surface area of 400 cm2, 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 until 12 hours after application. T½ of DMSO from blood plasma is 11–14 hours. 60 hours after application, endogenous concentration in blood plasma is again achieved.
12–25% of DMSO is excreted within the first 24 hours and 37–48% within 7 days in the urine either unchanged as DMSO or as the main metabolite, dimethyl sulfone (DMSO2). 3.5–6% of the total DMSO dose is exhaled by the lungs within 6–12 hours after application as dimethyl sulfide (DMS).
Heparin. The penetration of heparin through healthy skin is dose dependent and has been confirmed for dosages of 300 IU/h.
There are no pharmacokinetic data for heparin after application to the skin.
Dexpanthenol. Dexpanthenol is absorbed faster than pantothenic acid. The rapid absorption of dexpanthenol has been confirmed experimentally.
Mechanism of action
The overall effect of the drug is determined by the effects of each individual component.
Heparin
Competitively inhibits hyaluronidase, due to which the activity of connective tissue degeneration during inflammation is reduced. This weakens the severity of local inflammatory processes and accelerates healing in their foci. Acts as an antithrombotic agent, enhancing the inhibitory effect of antithrombin III on the activation of prothrombin and thrombin. This effect is dose dependent.
Dexpanthenol
When applied to the skin, it is transformed into vitamin B5 (pantothenic acid). It has all the properties of this vitamin: it participates in metabolic processes, improves granulation and epithelization in damaged areas of the skin, thus providing a wound-healing effect.
Dimethyl sulfoxide
Inactivates hydroxyl radicals, which are synthesized during inflammation and destroy tissue, thus exhibiting an anti-inflammatory effect. Inactivation of these substances improves local metabolism, which reduces swelling at the site of inflammation. The substance reduces the speed of impulse transmission along peripheral nerves responsible for pain sensitivity. This determines its analgesic effect. In addition, dimethyl sulfoxide improves the penetration of other components of the drug into tissues.
A complete analogue of the drug is Fitobene gel, which has the same effects as Dolobene gel. The advantage of the drug in comparison with monocomponent analogues lies in its versatile action.
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 (for abrasions), evenly distributed over the surface of the skin with light rubbing movements 2-4 times a day. When applying dressings with dolobene gel, a breathable dressing material is used only after most of the gel has penetrated into 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 the dolobene. during phonophoresis, the drug, due to its good contact properties and content of active substances, complements the physiotherapeutic effect of ultrasonic waves. The duration of treatment for dolobene is individual and depends on the severity of the disease, as well as on the effectiveness of therapy.
Side effects
From the immune system: allergic skin reactions; in some cases, immediate allergic reactions, such as urticaria and angioedema, are possible.
From the cardiovascular system: in some cases, when applied to large areas of skin, cardiac disorders are possible (a cause-and-effect relationship has not been established).
From the respiratory system: in some cases, when applied to large areas of the skin, disturbances from the respiratory system are possible (a cause-and-effect relationship has not been determined).
From the digestive system: temporary odor of garlic from the mouth (due to the action of dimethyl sulfide, a metabolite of dimethyl sulfoxide); a change in taste that goes away within a few minutes; in some cases, when applied to large areas of skin - stomach disorders, nausea, diarrhea (cause-and-effect relationship has not been determined).
Skin: hypersensitivity reactions to light.
General disorders: erythema, itching, burning, blisters, urticaria at the site of application. These reactions usually disappear during treatment. Otherwise, use of the drug should be discontinued. In some cases, when applied to large areas of the skin, increased fatigue, headache, chills are possible (cause-and-effect relationship has not been determined).
Caused by the action of dimethyl sulfoxide: dizziness, insomnia, adynamia, dermatitis, bronchospasm, vomiting.
Caused by the action of dexpanthenol: contact dermatitis, allergic dermatitis, eczema, rash, skin irritation.
Caused by the action of heparin: swelling of the skin, skin rash, hemorrhages, sometimes the appearance of small pustules, vesicles or blisters, which quickly disappear after discontinuation of the drug.
special instructions
The drug contains isopropyl alcohol, so in order to avoid painful reactions it should not be applied to mucous membranes, open wound surfaces or damaged skin (for example, after irradiation, with dermatitis, dermatoses, postoperative scars, burns).
Other medications should not be applied to the treated areas of the skin for several hours before and after the application of Dolobene gel.
In order to prevent the occurrence of undesirable effects, the drug must be applied to skin cleansed of other medications, cosmetics and contaminants.
Contact with eyes should be avoided.
Application of dimethyl sulfoxide may lead to the development of photosensitivity. In this regard, when using Dolobene gel, you should refrain from sunbathing and visiting a solarium. If hypersensitivity reactions occur, use of the drug should be discontinued.
Use during pregnancy or breastfeeding. There is still insufficient experience with the use of dimethyl sulfoxide in pregnant women, therefore the use of the drug during pregnancy and lactation is contraindicated. Potential teratogenic effects of DMSO have been reported in animals.
Dimethyl sulfoxide passes into breast milk, so the use of the gel during breastfeeding is contraindicated.
The ability to influence reaction speed when driving vehicles or other mechanisms. Does not affect.
Children. The drug is not prescribed to children due to limited experience with use.
Contraindications
The use of the drug is prohibited in the following cases:
- severe impairment of the kidneys and/or liver;
- bronchial asthma;
- severe cardiovascular pathology, especially accompanied by unstable hemodynamics;
- violation of the integrity of the skin at the site of application, including bleeding trophic ulcers and infected wounds;
- tendency to bleeding and bleeding disorders: hemorrhagic purpura and diathesis, hemophilia, thrombocytopenia;
- cataract, glaucoma;
- comatose states;
- pregnancy and breastfeeding;
- age up to 5 years;
- simultaneous use with the drug Sulindac;
- simultaneous use with other external drugs;
- individual hypersensitivity to any of the components of the drug.
There is no reliable data indicating the safety of the gel in pregnant women. Potential teratogenic effects of dimethyl sulfoxide have been reported. This substance also passes into breast milk, so if you need to use the medicine, breastfeeding should be stopped.
Interactions
The simultaneous use of other local drugs 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 topical drugs should be avoided.
The drug Dolobene, containing dimethyl sulfoxide, cannot be used with sulindac (NSAID) due to the possibility of severe toxic reactions (peripheral neuropathy).
The use of heparin may lead to prolongation of prothrombin time in patients taking oral anticoagulants. Dimethyl sulfoxide enhances the effect of ethanol (alcohol inhibits the elimination of the drug) and insulin, acetylsalicylic acid, butadione; digitalis preparations, quinidine, nitroglycerin, antibiotics (streptomycin, monomycin, etc.), the body is sensitized to anesthesia.
Features of application and interaction
Dolobene gel, which can be purchased without a prescription, is not recommended for use simultaneously with other external medications, as it may enhance their absorption.
Concomitant use with the drug Sulindac can lead to the development of peripheral neuropathies.
When used during treatment with oral anticoagulants, prothrombin time may be prolonged. Simultaneous use with alcohol is not recommended: the drug enhances the effects of ethanol, and alcohol slows down the excretion of Dolobene. The medicine also enhances the effects of insulin, butadione and aspirin, streptomycin antibacterial agents, digitalis preparations, nitroglycerin and quinidine, and also sensitizes the body to anesthesia.
Before using Dolobene, the manufacturer recommends cleansing the skin of organic contaminants, as well as cosmetics and other external products. Do not apply any other medicine to the area where Dolobene will be used two hours before and two hours after its use.
The product contains isopropyl alcohol, so applying the gel to areas where the integrity of the skin is damaged is prohibited. Also, you should not apply the medicine to skin with dermatitis or dermatoses, burns, postoperative scars and radiation injuries.
When using Dolobene, care should be taken not to get it into the eyes or onto the mucous membranes of the respiratory and digestive organs, as well as the genitals.
The drug may cause photosensitivity. While using the medicine, you should avoid sunbathing and visiting solariums.
Note!
The description of the drug Dolobene gel tube 50g on this page is a simplified author’s version of the apteka911 website, created on the basis of the instructions for use.
Before purchasing or using the drug, you should consult your doctor and read the manufacturer's original instructions (attached to each package of the drug). Information about the drug is provided for informational purposes only and should not be used as a guide to self-medication. Only a doctor can decide to prescribe the drug, as well as determine the dose and methods of its use.