Description overdue on 08/11/2014

• Composition
• Product form
• Pharmacological action
• Pharmacodynamics and pharmacokinetics
• Indications
• Contraindications
• Side effects
• Instructions on Divigel: Dosage and Administration
• Overdose
• Cooperation
• Terms of sale
• Storage conditions
• Shelf life
• Cautions
• With alcohol
• During pregnancy (and lactation)
• Reviews
• Price, where to buy

Composition

In composition of the gel Divigel includes:

• Estradiol   (Oestradiolum) at a dose of 500 mg or 1 g;
• Carbomer 974P   (Carbomerum 974P);
• triethanolamine   (Triethanolamine);
• propylene glycol   (Propylen Glycol);
• ethanol 96%   (Aethanolum 96%);
• Purified water (Aqua Purificata).

Product form

The drug is available in the form of a transdermal gel for the treatment of symptoms estrogen deficit. Opalescent gel has the form of a homogeneous mass and packed in laminated bags of aluminum foil №28. Contents active substance in one package - 500 mg or 1 gram.

Pharmacological action

Divigel belongs to the category of drugs that are used for correction of disorders caused by the onset of menopause And it has on the body expressed estrogenic   action.

The therapeutic effect of its application is determined activity Estradiol - estrogen   means identical in their properties, chemical, biological and pharmacological parameters endogenous estradiol Which is produced in a woman's body Ovarian follicular unit Starting with the appearance of the first menstrual   bleeding and up to menopause .

According to the accepted classification of drugs Estradiol   It belongs to the pharmacological groups:

• Estrogens .   progestins ; their antagonists   and   homologues .
• Antineoplastic hormonal agents   antagonists hormones .

Action substances intended to compensate for deficits Well enskih sex hormones   and stimulating activity Estrogen   receptors localized in the target cells.

Pharmacodynamics and pharmacokinetics

Synthetically produced Estradiol   - A white powder with a crystalline structure which is virtually insoluble in water, poorly soluble in oils of vegetable origin, however, is highly soluble in alcohols . acetone . dietilendiokside   and other organic solvents.

Estradiol   has the ability to penetrate by diffusion into the target cell, which subsequently is transported to the cell nucleus forms a bond with specific estrogenic   receptors and forms ligand-receptor complex .

Receptors estrogen   They are found in different tissues, but its greatest amount is contained in female genital mutilation : In particular uterus . the hypothalamic-pituitary the System . liver . vagina . ovary . mammary glands And bones .

Educated ligand-receptor complex:

• reacted with estrogen effector   elements genome ;
• interacts with specific intracellular proteins ;
• stimulates the synthesis of matrix (information) RNA ;
• stimulates protein synthesis ;
• promotes the release of Cytokine ;
• It stimulates growth factors.

Like other Estrogens . Estradiol   It contributes to the feminization of the body. Thus, the active ingredient Divigel 17-beta-Estradiol :

• exerts stimulatory action on development female genital mutilation . from oedinitelnoy tissue , In which the are located specific elements of one or another organ female reproductive system (the so-called stroma ), And also ductal Breast ;
• stimulate pigmentation in nipples and genitals ;
• stimulates formation secondary sexual characteristics   the female type;
• It stimulates growth and development   bony epiphysis   (end sections of the tubular bones of the skeleton);
• It ensures the timely rejection lining the the uterus from the inside of the mucous membrane ( endometrial );
• assures regularity   menstrual bleeding ;
• inhibits the production of breast milk;
• oppresses bone resorption   (the process of destruction of bone tissue);
• has procoagulant   action;
• accelerates the recovery of the normal amount leukocytes   in conditions provoked by radiation injury and characterized by oppression bone marrow hematopoiesis .

Increased concentration Estradiol   provokes endometrial hyperplasia   (ie, its proliferation by activation of the structural elements of tissue neoplasms); It stimulates the production of specific transport proteins ( globulin Binding circulating blood thyroxine   (TSvG), androgen-binding globulin, kortikosteroidsvyazyvayuschego globulin transferrin ); It stimulates the production of plasma protein fibrinogen .

Against the background of increasing concentrations Estradiol :

• increasing the concentration in the blood iron, thyroxine, copper   etc.;
• increased production in the tissues liver   having K-vitamin   dependent factors which are responsible for blood clotting ;
• are reduced quantitative indicators the content of in the system of blood clotting a specific protein Antithrombin III ;
• prevented the degradation of endogenous catecholamines adrenaline   and noradrenaline   (a similar effect is achieved by competing   Estradiol   for receptor activity enzyme COMT - catechol-O-methyltransferase ).

Other important qualities Estradiol   They include the fact that it prevents the development of atherosclerosis ; enhances the level of HDL in the blood; It reduces the performance of LDL contained in blood; and reduces the performance of the blood cholesterol   while increasing the level of triglycerides .

The substance changes the sensitivity of the receptors progesterone The parameters of sympathetic tone regulation smooth muscle It stimulates movement of the liquid portion plasma   in tissue as well as a compensatory fluid retention and sodium ions.

After the onset of Menopause   a woman's ovaries cease production Estradiol . From now on a major role in its formation played by the liver and adipose tissue.

The decline in the level of the synthesized ovaries Estradiol   It leads to the development and thermoregulatory vasomotor instability, which in turn is expressed as "hot flushes" of blood to the face, sleep disorders and progressive atrophy genito-urinary organs .

Another unpleasant consequence of the reduction estrogen   It is osteoporosis   - Are chronically a progressive the exchange disease, which is accompanied by increased fragility and a violation of architectonics of bones (in the period of Menopause   It mainly affects the spine).

After ingestion of a significant amount of Estradiol , Even before addition, how it gets into circulatory system Metabolized by intestinal microflora in the lumen and walls of the intestine and in the liver.

This leads to the fact that the concentration of estrone   plasma unphysiological increases. With long-term treatment of the same estrone   and estrone sulfate   begin to accumulate in the body.

The consequences of the accumulation of these metabolites Estradiol   for a long period of time yet remain poorly understood. What is known is that oral estrogen drugs   provokes an increase fusion proteins   (in particular, Renin ). The result is a significant increase in performance Blood Pressure .

Divigel - transdermal gel is alcohol-based. After applying the the drug on the integuments, contained therein alcohol quickly enough volatilizes, as well Estradiol Which serves as the active substance, penetrates the skin   at circulatory system .

Application Divigel on the skin site area is equal to one or two hands (about 200-400 sq. Cm), no effect on the amount of absorbable   Estradiol . However, increasing the area of ​​application reduces the suction performance.

In some ways Estradiol   delays in the subcutaneous tissues, where then gradually begins to be released in bloodstream . Transdermal delivery using the gel avoids the initial stage of hepatic metabolism, so fluctuations in plasma concentrations of Estrogen   when used insignificant.

Metabolism 17-beta-Estradiol   similar to the naturally produced by metabolism estrogen . Getting in bloodstream The substance is almost entirely associated with the transport protein. Indicator bioavailability Estradiol   when taking it inside is almost 100%.

After reception of per os it is subjected to effect of "first passage" medication through liver Where biotransformed to have less activity products - estriol   and of estrone .

Next estradiol secretes bile into the lumen   small intestine   and again absorbed. Finally, it loses its activity in liver by oxidation.

Emissions of biological degradation Estradiol   excreted primarily kidney   in the form of sulphates and glucuronide . Minor concentrations Estradiol . estrone   and estriol   It is also found in the urine.

During the course of treatment with Divigel ratios estradiol / estrone range from 0 4 to 0, 7. Indicator gel bioavailability is about 82%.

Applying to the skin the gel at a dose of 1 mg 17-beta-Estradiol   (1 gram of gel, respectively) creates a maximum plasma concentration of 157 pmol / l. The index average plasma concentration of the dosing period is 112 pmol / l. Indicator average free plasma concentrations, respectively, - 82 pmol / l.

Cumulation is not marked.

Indications

Divigel recommended for use in replacement hormone replacement therapy patients with symptoms es trogennoy failure of different nature backgrounds.

The drug is used to treat menopausal syndrome That developed as a result of:

• the natural extinction of the body and attack Menopause ;
• surgical menopause Including menopause after ovariectomy   (surgery to remove one or both ovaries), or radiation castration .

Divigel also shown as a prophylactic agent to prevent the development of osteoporosis   in postclimacteric period and in as supportive pregnancy   and its normal flow of funds in the IVF .

The latter is due to the fact that the conduct of the procedure in vitro fertilization   It implies the need for hormonal stimulation ovarian function . This in turn leads to a change in hormonal levels of the female organism and influences the course pregnancy .

In order for pregnancy   took place without complications, the patient being prescribed hormone drugs: Djufaston . Proginova , A transdermal patch   "CLIMAR" , Divigel and injection progesterone   (when its concentration in the blood drops).

Divigel appointed strictly individually at the dosage selected by the attending physician at the clinic, which was conducted fertilization procedure .

Before the procedure in vitro fertilization   use of the drug is recommended to start in about two weeks before the transfer embryo   in the uterus, after which the gel is applied to continue for several more weeks.

As progesterone . Estradiol   It is extremely important for the offensive pregnancy   hormone. With pregnancy , Ensuing natural by, he, like rule, produced by the body in normal quantities.

With IVF the Required level Estradiol   (Thousands of 5-10 pmol / L) is maintained by means of various hormones.

In the event of pregnancy   Divigel stop taking gradually. This is due to the fact that the abrupt withdrawal threatened miscarriage.

The drug is recommended for use, and women planning pregnancy . However, when planning Divigel pregnancy   It can be assigned only to women who have been diagnosed endometrial hypoplasia That is, the inner lining of the uterus is thinned.

Transdermal Gel is used for stimulation   Ovulation . In some cases, it is advisable to appointment at a time and Divigel proginova. Treatment regimens picks physician based on the individual characteristics of the patient.

Contraindications

Contraindications to the appointment of a transdermal gel are:

• hypersensitivity estradiol and / or some of the constituent components of the drug support;
• diagnosed, suspected or marked by history mammary cancer ;
• Diagnosed, anticipated or marked in history estrogen-dependent malignant tumors in the ovaries . uterus   or endometrium ;
• availability benign tumors   in the field of reproductive system and / or the breast (e.g. hysteromyoma ) In women younger than 60 years;
• uterine bleeding   uncertain nature of origin, and a predisposition to them;
• hyperplastic processes endometrial ;
• are hypophyseal tumor ;
• diffuse connective tissue diseases;
• the presence of female genital diseases, inflammatory character wearing (eg salpingo-oophoritis   or endometritis );
• characterized increase the concentration of estrogen phase of menopause ;
• venous thromboembolic disease Wearing spontaneous (including disease, marked in history);
• pathology, accompanied thrombosis in the deep veins   (also in cases when those pathologies noted history);
• thrombophlebitis   (including acute form, including history);
• congenital disease characterized by elevated levels of bilirubin in the blood (including a simple family cholehemia .   enzimopaticheskaya jaundice .   Rotor syndrome );
• presence of tumors in the liver (e.g. hemangioma   or   liver cancer );
• pathologies associated with ischemic attack (for example, ischemic   or hemorrhagic stroke );
• sickle cell anemia ;
• disease caused by disturbance of lipid metabolism;
• diabetes , including diabetes Complicated by retinopathy, and / or angiopathy ;
• intrahepatic cholestasis   (cholestatic jaundice), and / or expressed cholestatic itching   (including reinforced preceding pregnancy or reception steroid medicinal preparations);
• middle ear disease It caused by abnormal growth of bone therein (including their exacerbation during pregnancy).

With extreme caution Divigel prescribed to patients who are noted:

• bronchial asthma ;
• attacks migraine ;
• seizures ;
• steady   high blood pressure ;
• heart . hepatic   and / or renal failure ;
• coronary artery disease ;
• edematous syndrome ;
• shotty breast ;
• porphyrin disease .

Side effects

In some cases Divigel can cause the development of undesirable side reactions.

Disorders of the central and peripheral nervous system can be expressed as:

• headaches ;
• attacks migraine ;
• dizziness;
• of depressive states;
• trochaic hyperkinesis   (chorea).

Violations by function hearts   and vascular system   expressed as:

• improve performance Blood Pressure ;
• thrombophlebitis .

The digestive system often reacts to drug use:

• nausea;
• vomiting;
• stomach cramps;
• flatulence;
• painful sensations in the epigastric region.

On the part of the reproductive system are not excluded:

• bleeding from the vagina, which are indiscriminate in nature ( metrorrhagia );
• meager vaginal discharge;
• overgrowth   leiomyoma   ( fibroids ) Of the uterus;
• overgrowth endometrial   (notes, as a rule, if you do not complete the assignment Divigel progesterone );
• hysterocarcinoma   (as rule, develops y women with an intact uterus   after the menopause );
• sclerotic ovarian syndrome   (long-term use of the drug);
• change libido .

Violations by Endocrine   It is manifested by symptoms such as:

• engorgement, increase in voltage and / or increase in size of pectoral glands ;
• weight gain;
• decline in tolerance carbohydrates .

Violations of the liver and biliary system are shown:

• cholestatic jaundice ;
• cholelithiasis   (cholelithiasis);
• attacks porphyrin disease .

On the side water-salt balance   are possible delay is of sodium and of calcium and of water, which in turn at long application Divigel provokes the development of in a female patient of edemas.

Because the gel is used as an external agent, in place of its application in some patients may appear the symptoms allergies : rash , Increased irritability and redness of the skin . contact dermatitis .

By the other things byproduct symptoms include visually impaired I lead a change of its curvature, education chloasma . melasma   (melasma), vaginal candidiasis .

Instructions on Divigel: Dosage and Administration

Transdermal drug Divigel - a tool that may be used for long-term and cyclical therapy.

The standard starting dose is 1 mg Estradiol   per day, which corresponds to one gram of the gel, however, the initial dosage may be somewhat different depending on the severity of symptoms.

After two-three courses therapy using Divigel initial dose may be changed depending from how varies clinical picture y particular patient.

The optimal dose is selected individually and is usually from 0, 5 to 1, 5 mg Estradiol   per day.

The decision as to what day of the cycle should begin receiving also receives the doctor.

Patients with intact (non-operated), uterus   the period of treatment is further appointed progestin preparations . Their accept from 10 to 12 days in each cycle.

After completing the course application gestogena the patient must undergo menstrualnopodobnoe bleeding . If the woman is extraordinary or prolonged uterine bleeding It is required to establish the cause of their origin.

It should be remembered, that in the postmenopausal   duration of one menstrual cycle   It may be increased to three months.

Application Instruction Divigel recommends applying the drug to clean skin in the lower part of the front wall of the abdomen, waist, arms, forearms, or alternately to each of the buttocks once daily, preferably at the same time. At the same time the application site should be alternated daily.

The optimum is considered to be Floor area applying, equal to the area the one-two palms. After applying the gel is allowed to dry for a few minutes (usually only two or three minutes).

Place the application can not be washed and rinsed for one hour.

In cases where the patient forgets to apply the gel, it is advisable to carry out the procedure immediately when it will remember, but not later than within 12 hours from the time of the drug on schedule.

If same after skipping passed more than 12 hours, drawing of of the drug lay their until the next times.

Irregular use of Divigel (frequent omissions doses) can cause breakthrough menstrualnopobodnyh uterine bleeding .

Overdose

If you exceed the recommended dosage instructions may develop the following symptoms:

• breast tenderness;
• bloating;
• abdominal pelvic region;
• increased anxiety;
• irritability;
• nausea;
• vomiting;
• metrorrhagia .

The appearance of one or more of the above symptoms require symptomatic treatment.

Typically, unpleasant symptoms disappear after dose adjustment towards its reduction or after discontinuation.

Cooperation

Estradiol at simultaneous reception with these drugs is capable of to provoke the:

• increase in efficiency lipid-lowering drugs ;
• the weakening of the therapeutic effect of drugs containing male sex hormones ;
• the weakening of the therapeutic effect hypoglycemic agents ;
• the weakening of the therapeutic effect diuretics ;
• antihypertensive drugs ;
• anticoagulants .

Estradiol   barbiturates . anxiolytics . opioid .   (eg, carbamazepine or phenytoin ); microsomal liver enzymes ;

  Estradiol     rifampicin .   . ampicillin   etc.). .

Estradiol   folic acid   and drugs Thyroid .

Terms of sale

Storage conditions

Shelf life

Cautions

  and .

dementia .

Breast

ovulation about . ovary .

estrogen   pregnancy  

contraceptive   contraceptives .

Gestation   and lactation  

pregnancy   pregnancy  

  Estrogen   pregnancy   teratogenicity   or .

Menopause   and osteoporosis .

Estradiol   Blood Pressure .

IVF   pregnancy  

pregnancy Ovulation Djufaston   combination therapy .