Divigel - instructions for use, analogs, reviews and release forms (gel or ointment 0.1%) of the drug for the treatment of menopause, endometrial growth in IVF, planning and replacement therapy in women, including during pregnancy

In this article, you can read the instructions for using the drug Divigel. Presented are reviews of visitors to the site - consumers of this medication, as well as opinions of doctors of specialists on the use of Divigel in their practice. A big request is to actively add their feedback on the drug: the medicine helped or did not help get rid of the disease, which were observed complications and side effects, possibly not declared by the manufacturer in the annotation. Analogues of the Divigel in the presence of existing structural analogs.Use for the treatment of menopause, endometrial growth in IVF, planning and replacement therapy in women, including during pregnancy and lactation.

Divigel - an estrogen preparation for external use. The active ingredient, synthetic 17beta-estradiol, is chemically and biologically identical to endogenous human estradiol (formed in the body of women from the first menstruation to the menopause), produced by the ovaries. In the cells of the organs to which the action of hormones is directed, estrogens form a complex with specific receptors (found in various organs - in the uterus, vagina, urethra, mammary gland, liver, hypothalamus, pituitary); the receptor-ligand complex interacts with the estrogen-effector elements of the genome and specific intracellular proteins that induce the synthesis of i-RNA, proteins and the release of cytokines and growth factors.

Has a feminizing effect on the body. Stimulates the development of the uterus, fallopian tubes, vagina, stroma and ducts of the mammary glands, pigmentation in the nipple and genital area, the formation of secondary sex characteristics by the female type, the growth and closure of the epiphyses of long tubular bones.Rejection facilitates timely and regular endometrial bleeding, in high concentrations causes endometrial hyperplasia, suppresses lactation, inhibits bone resorption, stimulate the synthesis of several transport proteins (thyroxine-binding globulin, transcortin, transferrin, a protein that binds sex Gaumont) fibrinogen. Has procoagulant effect, induces the synthesis of hepatic vitamin K-dependent coagulation factors (2, 7, 9, 10), reduces the concentration of antithrombin 3.

Increases the concentration in the blood of thyroxine, iron, copper. Has antiatherosclerotic action, it increases the amount of HDL, LDL, and reduces cholesterol (triglycerides increases). Modulating Progesterone receptor sensitivity and sympathetic regulation of smooth muscle tone, stimulates transition intravascular fluid in the tissue and causes a compensatory delay sodium and water. In high doses, it prevents the degradation of endogenous catecholamines, competing for the active COMT receptors.

After menopause, only a small amount of estradiol (from estrone in the liver and adipose tissue) is formed in the body.The decrease in the content of estradiol produced in ovaries is accompanied in many women by vasomotor and thermoregulatory instability (blood flushes to the skin of the face), sleep disorders, and progressive atrophy of the urogenital system.

Due to estrogen deficiency, osteoporosis develops (mainly the spine). After ingestion, a greater amount of estradiol before being ingested is metabolized in the lumen (microflora) and intestinal wall, as well as in the liver (which leads to unphysiologically high concentrations of estrone in plasma, and with prolonged therapy to cumulation of estrone and estrone sulfate) . The effects of the accumulation of these metabolites in the body for a long time have not yet been elucidated. It is known that the oral use of estrogens causes an increase in the synthesis of proteins (including renin), which leads to an increase in blood pressure.

Composition

Estradiol (in the form of hemihydrate) + auxiliary substances.

Pharmacokinetics

When applying the gel, alcohol quickly evaporates, and estradiol penetrates through the skin, while most of it enters the systemic bloodstream at once,and a certain amount of estradiol is retained in the subcutaneous tissue and is released into the systemic bloodstream gradually. The bioavailability of Divigel is 82%. Transdermal application allows to avoid the first stage of hepatic metabolism, due to this fluctuations in the concentration of estrogen in blood plasma with the application of the Divigel are insignificant. It is excreted mainly by kidneys in the form of sulfates and glucuronides, in the urine there are also small amounts of estradiol, estrone and estriol.

Indications

• hormone replacement therapy with symptoms of estrogen deficiency;
• Treatment of climacteric syndrome associated with natural or artificial menopause, which developed as a result of surgical intervention.

Forms of release

Gel for external use (transdermal) 0.1% (sometimes mistakenly called ointment).

Instructions for use and how to use them

The divigel is prescribed for long-term and cyclic therapy. The initial dose, as a rule, is 1 g of gel (which corresponds to 1 mg of estradiol) per day, but is determined by the degree of symptom severity. Depending on the clinical picture, the dose can be changed after 2-3 cycles individually from 500 mg to 1.5 g of gel per day (corresponding to 500 μg to 1.5 mg of estradiol per day).

Patients with an intact (unoperated) uterus during treatment with Divigel are recommended to prescribe a progestogen (for example - medroxyprogesterone acetate, norethisterone, norethisterone acetate or dihydrogesterone) for 10-12 days per cycle. After the course of gestagen use, menstrual bleeding should occur. With extraordinary or prolonged uterine bleeding it is necessary to establish the cause of their occurrence.

In patients in the postmenopausal period, the duration of the cycle can be increased to 3 months.

The gel is applied once a day to the clean skin of the lower part of the anterior wall of the abdomen, lumbar region, shoulders, forearms, or alternately to the right or left buttocks, alternating between the application sites. The area of ​​application should be equal to 1-2 palms. After applying the drug, you should wait a few minutes until the gel dries (2-3 minutes).

Place the application of the gel can not be rinsed for 1 hour. Avoid accidental contact with the eye. Wash hands immediately after applying the gel.

If you miss another gel application, you should do this as soon as possible, however, no later than within 12 hours from the moment of application of the drug according to the scheme.If more than 12 hours have passed, Divigel's application should be postponed until the next time. With irregular use of the drug (missed doses), menstrual-like uterine breakthrough bleeding may occur.

Side effect

• headache;
• migraine;
• dizziness;
• depression;
• increased blood pressure;
• thrombophlebitis;
• nausea, vomiting;
• gastric colic;
• flatulence;
• pain in the epigastric region;
• rash;
• skin irritation;
• hyperemia of the skin;
• contact dermatitis;
• scanty spotting;
• increase in the size of uterine leiomyoma;
• Endometrial hyperplasia (with appointment without combination with progesterone);
• carcinoma of the endometrium (in women with an intact uterus after menopause);
• sclerosis of the ovaries with prolonged use;
• change in libido;
• engorgement (stress and / or increase) of the mammary glands;
• increase in body weight;
• visual impairment (changes in the curvature of the cornea);
• Chloasma;
• vaginal candidiasis.

Contraindications

• breast cancer (diagnosed, suspected or in history);
• diagnosed or suspected estrogen-dependent malignant tumors of the ovaries, uterus, endometrium;
• benign and malignant neoplasms of the genital organs (cervical and uterine cancer, uterine myoma, vulvar cancer, ovarian cancer) in women under the age of 60;
• Benign neoplasm of the breast in women under the age of 60;
• vaginal bleeding of unclear etiology and a tendency to uterine bleeding;
• endometrial hyperplasia;
• tumors of the pituitary gland;
• diffuse connective tissue diseases;
• inflammatory diseases of female genital organs (salpingoophoritis, endometritis);
• hyperestrogenic stage of climacteric period;
• spontaneous thromboembolic diseases of veins (including in the anamnesis);
• deep vein thrombosis, pulmonary embolism (including anamnesis);
• thrombophlebitis and acute thrombophlebitis (including in the anamnesis);
• congenital hyperbilirubinemia (syndromes Gilbert, Dubin-Johnson, Rotor);
• liver tumors (hemangioma, liver cancer);
• disorders of cerebral circulation (ischemic stroke, hemorrhagic stroke);
• diabetes mellitus, retinopathy, angiopathy;
• sickle-cell anemia;
• disorders of fat metabolism;
• Cholestatic jaundice or severe cholestatic itching (incl.intensification of their manifestations during the previous pregnancy or on the background of taking steroid drugs);
• otosclerosis (including its exacerbation during pregnancy);
• hypersensitivity to estradiol and / or other components of the drug.

Divigel should not be applied to the mammary glands, face, genital area, or to irritated areas of the skin.

Application in pregnancy and lactation

The divigel is contraindicated in pregnancy and lactation.

Application in elderly patients

Experience in women over 65 is limited.

special instructions

Before starting or re-administering hormone replacement therapy (HRT), you must collect a complete personal and family history. A medical examination should be conducted to identify possible contraindications and to observe the necessary precautions when using the drug (including pelvic organs and mammary glands).

During the treatment it is recommended to conduct periodic examinations, the frequency and the set of methods included in it are determined for each case individually.Studies, including mammography, should be carried out in accordance with accepted norms and taking into account individual clinical features in each individual case.

At the time of HRT, all the benefits and risks of therapy should be carefully evaluated.

The patient should be under constant medical supervision in the event of any of the following diseases or conditions that were previously observed and / or aggravated during pregnancy or previous hormonal therapy: leiomyoma (uterine fibroids), endometriosis; history of thromboembolic disease or risk factors for their occurrence; risk factors for estrogen-dependent tumors (1st degree of heredity of breast cancer); arterial hypertension; violations of the liver (adenoma); diabetes mellitus with or without vascular lesions; cholelithiasis; migraine and / or (severe) headache; systemic lupus erythematosus; endometrial hyperplasia in the anamnesis; epilepsy; bronchial asthma; otosclerosis. It should be borne in mind that against the backdrop of treatment by Divigel, in rare cases, relapse or aggravation of the listed diseases is possible.

Therapy should be discontinued immediately if contraindications and / or in the following situations are detected: jaundice or impaired liver function; marked increase in blood pressure; new attacks of migraine headache; pregnancy.

When taking estrogens for a long time increases the risk of hyperplasia of the endometrium and carcinoma. To reduce the risk, it is necessary to combine estrogen therapy in women with a nonoperated uterus with progesterone for at least 12 days during the treatment cycle.

In the event of breakthrough bleeding and / or scanty bleeding after a few months of taking Divigel, research should be conducted to identify the causes of their occurrence. Studies may include endometrial biopsy (to exclude malignancy of the endometrium).

Women with a distant uterus due to endometriosis (especially in cases of residual endometriosis) are recommended to add progesterone to estrogen-dependent therapy, due to the pre-malignant or malignant transformation of foci of endometriosis with estrogen stimulation.

With prolonged use of HRT, the risk of developing breast cancer increases.The increase in this risk is found mainly in women of lean or normal physique. In women of full physique (high predisposition to breast cancer) HRT does not increase the risk of developing breast cancer in addition.

An additional risk of developing breast cancer appears with an increase in the duration of HRT and returns to baseline for approximately 5 years after discontinuation of treatment.

Combined estrogen-progestogen ZGT causes a similar or higher risk compared with estrogen therapy.

In women receiving HRT, the risk of developing thromboembolic diseases of the veins (deep vein thrombosis of the lower extremities and pulmonary veins) was increased 2-3 times compared with women who did not receive HRT. Probability is higher in the first year of HRT than in subsequent years.

The main risk factors for thromboembolic complications: individual or family history, pronounced obesity (body mass index more than 30 kg / m2), systemic lupus erythematosus.

Patients with a history of thromboembolism or recent spontaneous miscarriages should conduct additional studies to exclude a predisposition to thrombophlebitis.The use of HRT in this case should be initiated after a full assessment of risk factors for thrombophlebitis and the initiation of anticoagulant therapy. The risk increases with prolonged immobilization, extensive injuries or extensive surgical interventions. HRT should be discontinued 4 to 6 weeks before the planned surgical operations on the abdominal organs or orthopedic operations on the lower limbs. Treatment can be resumed after a complete recovery of motor ability. With the development of thromboembolic symptoms (sudden pain in the chest, dyspnoea), it may be necessary to cancel HRT.

Estrogens cause fluid retention in the body. Patients with impaired renal function should be under constant medical supervision due to an increase in the level of estradiol and its metabolites in the blood.

Estrogens increase sensitivity to insulin and increase its excretion. Patients with diabetes mellitus in the early months of HRT are shown constant monitoring of blood glucose.

Admission of estrogen increases the risk of a surgically confirmed cholelithiasis.

In rare cases of a sharp increase in the level of triglycerides in the blood against the background of taking Divigel, development of pancreatitis is possible.

Estrogens increase the level of thyroid-binding globulin, increasing the level of the circulating hormones of the thyroid gland.

You should avoid getting the gel on the mammary glands and mucous membranes of the vulva and vagina.

Impact on the ability to drive vehicles and manage mechanisms

Therapy by Divigel does not affect the ability to engage in potentially dangerous activities requiring increased attention and speed of psychomotor reactions.

Drug Interactions

Estradiol increases the effectiveness of lipid-lowering drugs; weaken the effect of drugs of male sex hormones; hypoglycemic, diuretic, antihypertensive drugs and anticoagulants; reduces tolerance to glucose (dosage correction of hypoglycemic drugs).

Metabolism Divigel is accelerated by simultaneous admission with barbiturates, tranquilizers (anxiolytics), opioid analgesics, means for anesthesia,some antiepileptic drugs (carbamazepine, phenytoin), inducers of microsomal liver enzymes; herbal preparations containing the herb of St. John's wort (St. John's herb).

The concentration of estradiol in the blood also decreases with the simultaneous use of phenylbutazone and certain antibiotics (ampicillin, rifampicin, rifabutin) and antiviral drugs (nevirapine, efavirenz), which is associated with changes in the intestinal microflora.

The effect of estradiol increases with folic acid and thyroid medications.

Analogues of the medicinal product Divigel

Structural analogs for the active substance:

• Derremiril;
• Climara;
• Estimax;
• Estrogele;
• Estrofem.

Analogues for the pharmacological group (estrogens and gestagens):

• Ginepristone;
• Gynoflor E;
• Daillah;
• Depot Provera;
• Jess;
• Jess Plus;
• Diane 35;
• Divina;
• Dimia;
• Duphaston;
• Evra;
• Janine;
• The individual;
• Clira;
• Climadinone;
• Clinonorm;
• Clomiphene;
• Clostilbite;
• Lactineth;
• Levonorgestrel;
• Lindineth;
• Logest;
• Marvelon;
• Mifepristone;
• NovaRing;
• Novinet;
• Norkolut;
• Norplant;
• Ovestin;
• Provera;
• Progesterone;
• Proginova;
• Projest;
• Regulon;
• Rigevidone;
• Silhouettes;
• Tamoxifen;
• Three Mercy;
• Three regol;
• Utrozhestan;
• Femoston;
• Charozette;
• Escapel;
• Estriol;
• Ethinylestradiol;
• Yarina;
• Yarina Plus.

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