Release forms and composition of the drug
Divigel for menopause, reviews of which among patients and doctors indicate its good therapeutic effect, is available in the form of a gel for external use in single-dose packages of 0.5 or 1 mg. A cardboard package may contain 28 or 91 packages. The official manufacturer of the medicine is Finnish.
The main active ingredient of the gel is estradiol hemihydrate (17β-estradiol), obtained synthetically, but its properties are closest to natural estradiol. 1 packet weighing 1 g contains 1 mg of 17β-estradiol.
The auxiliary components of the drug include:
- carbopol 974P, used as a gel structure former;
- trolamine – pH acidity regulator;
- propylene glycol – solvent and filler;
- ethyl alcohol (96%), which has a local irritant and antimicrobial effect;
- purified water (solvent).
Bottom line
The estrogen skin gel for hormone replacement therapy Divigel, which is produced in Finland, is very popular among women and doctors. It contains a synthetic analogue of the main female sex hormone estrogen. It is very convenient to use. A woman only needs to apply a dose of gel, which is packaged in a separate sachet, to the skin in the lower back, buttocks or lower abdomen once a day.
Since Divigel is a hormonal drug, it should be prescribed exclusively by a doctor after an examination. The drug has a number of contraindications. Therefore, it is important to first find out the genetic predisposition to certain diseases. Therapy must be carried out under the constant supervision of the attending physician. We wish you good health!
Pharmacological properties
Divigel is a drug for hormone replacement therapy. 17β-estradiol, an analogue of natural estradiol, is the most active steroidal female sex hormone.
In women of childbearing age, it is produced in the follicles of the ovaries. This process occurs under the influence of follicle-stimulating hormone (FSH). 98% of this substance is in a woman’s body in a bound state, and the remaining 2% is in an active form.
Under the influence of estradiol, the development of both primary and secondary sexual characteristics occurs:
- formation of the uterus, vagina;
- formation of connective tissue of the mammary glands;
- coloring of the nipple areola, hair growth;
- cyclic rejection of the endometrium (menstrual bleeding).
In addition, estradiol is involved in the following processes:
- the formation of the end parts of the tubular bones that form the joint;
- inhibition of the process of destruction and degradation of bone tissue;
- regulation of the tone of smooth muscles lining the walls of blood vessels and the cavities of internal organs, including the uterus;
- stimulating the production of globulins - blood proteins that transport nutrients;
- regulation of water and electrolyte balance in the body;
- blood clotting;
- increasing the concentration of HDL in the blood serum, inhibiting platelet aggregation (anti-atherosclerotic effect).
After menstruation stops during menopause, estrogen production decreases sharply.
This process is accompanied by the appearance of menopausal syndrome, expressed as follows:
- atrophy of the vaginal wall;
- dystrophic changes in the skin;
- stimulation of the sympathoadrenal system (sweating, flushing of the face, irritability, poor sleep and other symptoms);
- decreased bone density (osteoporosis);
- increased risk of atherosclerosis, ischemic heart disease and other disorders.
Reviews about Divigel
Divigel - reviews from doctors are proof of this - normalizes the regularity of bleeding, eliminates sleep disorders and other symptoms accompanying the onset of menopause , and also prevents the development of sclerosis and osteoporosis .
Another advantage of the drug, according to most doctors, is that, unlike oral medications estradiol in blood pressure .
The use of Divigel during IVF allows you to normalize the course of pregnancy and maintain the necessary balance of hormones in the body.
Reviews of women who have taken the drug, left on forums, indicate that the drug, although an effective remedy, still often provokes side effects, in particular, nausea and bloating.
Some women who used the gel while planning pregnancy note that Divigel suppresses ovulation , but after stopping the drug it is possible to get pregnant quite quickly. According to reviews, the chances of getting pregnant are significantly increased by Duphaston and Divigel, used as part of complex therapy .
Pharmacodynamics and pharmacokinetics
Divigel for menopause, reviews of which are mostly positive, unlike oral forms of release, is not accompanied by the primary passage of the active substance through the liver. The entry of estradiol into the general bloodstream is similar to the natural mechanism of hormone secretion by the ovaries.
As a result, the bioavailability of the drug increases (it is 82%), and the therapeutic level of the hormone corresponds to its physiological concentration in the blood. The gradual penetration of the active substance also reduces the risk of the formation of an “estrogenic peak” and accompanying side effects such as increased blood clotting and thrombosis.
After application to the skin, the distribution and metabolism of the drug occurs according to the following mechanism:
- Evaporating from the surface of the skin, alcohol destroys the lipids of the stratum corneum and promotes deep penetration of estradiol.
- The active component of the gel enters the circulatory system and is almost completely bound by transport proteins, and a small part of it remains in the subcutaneous tissues, which has a prolonged effect.
- The hormone penetrates target organs (mammary glands, genitals and others) and binds to receptors that have estradiol-sensitive elements.
- The resulting complex interacts with components of the cellular genome, specific proteins, which promotes the release of peptide molecules, growth factors and RNA synthesis.
- As a result, the process of feminization of the body and the mechanisms described above are activated.
Under the influence of enzymes (cytochrome p450, catechol methyltransferase, sulfotransferase), the active substance of the drug is broken down in the body to methoxyestrogens, which are excreted mainly with bile through the intestines. Its accumulation is not observed with repeated exposure to the body.
Transdermal administration of 17β-estradiol leads to an increase in the level of the hormone in the blood to the values indicated in the table below.
Index | Content in blood serum, pmol per 1 l | |
0.5 mg estradiol | 1 mg estradiol | |
Maximum concentration | 143 | 247 |
Average concentration | 75 | 124 |
Minimum level | 92 | 101 |
Combination with alcohol
While using Divigel, a woman should avoid drinking all alcoholic beverages. Even a small dose of alcohol that enters the body simultaneously with sex hormones leads to more intense activity of the adrenal glands and gonads. It can also cause disruption of the woman’s endocrine system.
Whatever the outcome, alcohol reduces the therapeutic effect of hormonal medications. In some women, the simultaneous use of hormonal drugs and any type of alcohol leads to severe headaches, seizures, the development of thrombophlebitis or exacerbation of peptic ulcers.
Indications for use
The indication for the use of Divigel is the need for hormone replacement therapy in the following cases:
- after removal of the uterus or treatment of malignant tumors using radiotherapy;
- premature onset of menopause;
- planning pregnancy (to increase the thickness of the endometrium);
- cessation of menstruation for more than 6 months in women of reproductive age (secondary amenorrhea);
- early appearance of signs of menopausal syndrome;
- genitourinary disorders;
- increased risk of osteoporosis and cardiovascular disease in women;
- prevention of late metabolic disorders in menopause.
Complex hormone therapy for menopause
In some conditions, women are prescribed complex hormone replacement therapy:
- the patient has endometriosis;
- for the purpose of preventing fibroids;
- the results of blood tests for hormones showed low levels of progesterone;
- in case of early menopause;
- surgical menopause occurred as a result of removal of the uterus with or without appendages.
The woman is additionally prescribed progestin drugs compatible with Divigel. Progestogens are artificial analogues of the female sex hormone progesterone.
Divigel has good compatibility with the Belgian progestin drug Utrozhestan. It contains a microdose of progesterone obtained from the wild yam plant. The medicine is available in two forms: vaginal suppositories or capsules of 100 mg and 200 mg. Utrozhestan for menopause is taken daily without interruption.
This treatment regimen allows you to constantly maintain a sufficient amount of progesterone in the body. The woman's menopausal symptoms will decrease in intensity.
Vaginal suppositories have less negative effects on the female body than capsules. Therefore, for ladies with diseases of the gastrointestinal tract and liver, gynecologists prescribe complex therapy together with vaginal suppositories, including Divigel and Utrozhestan.
Contraindications
Divigel, which restores estrogen levels during menopause, also has contraindications. According to patient reviews, one of its significant advantages is the absence of passage through the gastrointestinal tract, good tolerability and ease of use.
The drug should not be used in the presence of the following pathologies:
- malignant tumors of the breast, liver or genital organs, currently present or previously in the anamnesis;
- bleeding from the genital tract for an unknown reason;
- pathological growth of the inner layer of tissue lining the uterus (endometrial hyperplasia);
- genetic predisposition to thrombosis, diagnosed venous thrombosis, as well as recent thromboembolic complications;
- acute liver pathologies, manifestations of bile stagnation - jaundice, skin itching, including those that occurred during the last pregnancy, when the level of estradiol increases, or while taking hormonal medications;
- hereditary metabolic disorders - porphyria, hyperbilirubinemia.
The medicine is also contraindicated in pregnant and nursing mothers, patients with increased individual sensitivity to estradiol and other components of the gel. If pregnancy occurs during treatment, you should immediately stop using it.
Use during pregnancy and lactation
Pregnancy and breastfeeding are contraindications to the drug.
If pregnancy occurs during the course of treatment, stop using the gel immediately. However, the final decision on the need for further use of Divigel when diagnosing pregnancy is made by the attending physician.
Epidemiological studies have shown that accidental use of estrogen in early pregnancy does not provoke teratogenic or fetotoxic effects .
The use of the gel during lactation is prohibited.
Instructions for use, dosage of the drug
The gel can be applied to the skin of the following areas of the body:
- lower part of the anterior abdominal wall;
- lumbar region of the back;
- shoulders and forearms;
- buttocks (alternately left and right).
These places must be alternated daily. The gel is not used on the skin of the face, mammary glands and genitals. Avoid getting it on damaged or irritated areas, as well as in the eyes and mucous membranes.
The procedure for applying the gel is as follows:
- Open the single-use package.
- Apply the drug to one of the above areas of the body, approximately 1-2 palms in area.
Divigel during menopause should not be applied to mucous membranes. In case of accidental contact, wash off the gel with water. - Leave the gel for several minutes until it dries completely.
- Wash your hands with soap. Do not wash off the gel from the skin surface for at least 1 hour.
The daily dosage is selected individually and averages 1 g of gel per day. The initial dose is 0.5 g. Therapy can be carried out periodically (in a course) or continuously over a long period of time. To reduce the risk of side effects, the minimum dosage that produces a therapeutic effect should be used.
There are the following features of the use of this drug:
- patients who do not have surgical interventions on the uterus are simultaneously prescribed gestagens, which are taken for at least 12-14 days during the monthly cycle;
- women who have not previously been treated with hormonal drugs can start using the gel any day;
- patients who have previously taken similar drugs must complete the previous course of treatment;
- occasional (irregular) use of the gel can lead to spotting vaginal discharge and heavy uterine bleeding.
Divigel price, where to buy
You can buy Divigel on the Russian market for: 360-400 rubles for a package of 28 gel packets containing 500 mg estradiol; 670-750 rubles for a package of 28 gel packets containing 1 g of estradiol.
In Ukraine, the average price of Divigel is: 120-130 UAH for transdermal gel 500 mg (28 pieces); 200-220 UAH for transdermal gel 1 g (28 pieces).
- Online pharmacies in RussiaRussia
- Online pharmacies in UkraineUkraine
- Online pharmacies in KazakhstanKazakhstan
ZdravCity
- Divigel gel transderm.
0.1% 1g 28 pcs. Orion 965 rub. order
Pharmacy Dialogue
- Divigel (0.1% 1.0g gel pack. No. 28)Orion
1020 rub. order
- Divigel (0.1% 0.5g gel pack. No. 28)Orion
RUR 756 order
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Pharmacy24
- Divigel 0.1% 1 g N28 gel Orion Corporation, Finland
401 UAH order - Divigel 0.1% 0.5 g No. 28 gel Orion Corporation, Finland
247 UAH order
PaniPharmacy
- Divigel gel Divigel gel 0.1% 1g No. 28 Finland, Orion
510 UAH order
- Divigel gel Divigel gel 0.1% 0.5g No. 28 Finland, Orion
305 UAH. order
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Side effects
Divigel for menopause, reviews of which indicate its effectiveness in hormonal imbalances, can cause the following side effects:
- cardiovascular system - rapid or heavy heartbeat, arterial hypertension, inflammation of the venous walls, small-spotted capillary hemorrhages in the skin, under it or in the mucous membranes, the formation of blood clots in the veins of the lower extremities, myocardial infarction, stroke (in rare cases);
- genitourinary organs - disruption of the menstrual cycle, pathological growth of tissue and endometrial cancer, severe pain during menstruation, increased signs of premenstrual syndrome, inflammation of the vulva and vagina, fibroids, increased or delayed urination, urinary incontinence, inflammation of the bladder, the appearance of blood in the urine;
- respiratory system – feeling of lack of air, inflammation of the nasal mucosa;
- digestive and hepatobiliary system - nausea, vomiting, increased flatulence, increased appetite, stool disorders, abdominal pain, bile stagnation, jaundice, deterioration of liver function;
- skin – itching, irritation, pain at the site of application of the drug, dryness, acne, hair loss or increased hair growth, pathological changes in the nail plates, possible dermatitis and eczema, local increased pigmentation of the skin, formation of dense nodules;
- metabolic disorders - edema, weight gain or loss, abnormal increase in blood cholesterol;
- nervous system and psyche - headache, dizziness, sensitivity disorders (feelings of goosebumps, crawling, burning, tingling), tremors, increased nervousness or agitation, depression, muscle spasms, sleep disturbances, changeable mood, decreased concentration and attention, increased risk dementia for women over 65 years of age;
- other systems and organs - the formation of benign tumors, enlargement and pain in the mammary glands, increased sweating, fever, general malaise, allergic reactions, Quincke's edema, blurred vision, dry eye syndrome, joint pathologies, breast or ovarian cancer (the risk increases in 2 times when using estradiol for 5 years or more).
Bloody vaginal discharge is usually temporary, can last several months and does not require discontinuation of the drug. If other side effects occur, stop taking and consult a doctor. Divigel does not affect the ability to drive a car or operate high-risk mechanisms.
Why is Divigel prescribed?
Well, in extreme cases, when you really can’t get pregnant, then of course this kind of medication can really help! The endometrium “gets fat” under the influence of female hormones estrogen. They are produced by follicles at the end of the early follicular phase of the menstrual cycle. If the level of estrogen in the body increases, then the endometrium also grows.
To stimulate endometrial growth, doctors prescribe the use of an artificial analogue of the hormone estrogen. Divigel increases the amount of estrogen, which in turn leads to thickening of the endometrium.
This drug can only be taken if doctors diagnose you with hypoplasia. Part of the drug enters the bloodstream through the skin, while part is gradually released from the subcutaneous tissue. When treated correctly, the drug rarely causes side effects. In some cases, when taking Divigel, patients may complain of headaches, unscheduled vaginal bleeding, and nausea.
An overdose of the drug causes bloating, nausea, vomiting, irritability and anxiety. In short, all this is bullshit, not Divigel. My endometrium has not grown in two courses, and I also have chest pains and I have gained extra weight. Divigel contains endogenous estradiol, similar in structure and biological activity to human endogenous estradiol. About 3-5% of women report amenorrhea in the first year of therapy.
Unfortunately, not every woman is able to get pregnant according to her first desire. There can be many reasons; they are determined by the doctor after a thorough examination and tests. The optimal condition of this tissue is maintained by a special hormone - estrogen. There is no need to be upset if you have been diagnosed with this: the thickness of the endometrium can increase if treated correctly.
If the thickness of the endometrium is less than 5 mm, the probability of pregnancy does not exceed 1%. Therefore, women are prescribed Divigel. Divigel is prescribed to women with estrogen deficiency of various etiologies. Indications for use: Divigel is used to treat women with symptoms associated with estrogen deficiency during artificial or natural menopause.
Overdose
With percutaneous administration, an overdose is unlikely.
When taking estradiol orally, an overdose manifests itself in the form of the following symptoms:
- pain in the mammary glands;
- the appearance of a feeling of anxiety;
- increased irritability;
- nausea, vomiting;
- uterine bleeding between menstruation.
To eliminate the symptoms of overdose, it is necessary to wash the drug off the skin and stop using it.
Gel Divigel
Instructions for medical use of the drug
Description of pharmacological action
Estrogen preparation for external use. The active ingredient, synthetic 17β-estradiol, is chemically and biologically identical to endogenous human estradiol (produced in the body of women from the first menstruation until 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 gland); the receptor-ligand complex interacts with estrogen effector elements of the genome and specific intracellular proteins that induce the synthesis of mRNA, 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 area of the nipples and genitals, the formation of secondary sexual characteristics of the female type, the growth and closure of the epiphyses of long tubular bones. Promotes timely endometrial rejection and regular bleeding, in high concentrations causes endometrial hyperplasia, suppresses lactation, inhibits bone resorption, stimulates the synthesis of a number of transport proteins (thyroxine-binding globulin, transcortin, transferrin, sex hormone-binding protein), fibrinogen. It has a procoagulant effect, induces the synthesis of vitamin K-dependent blood coagulation factors (II, VII, IX, X) in the liver, and reduces the concentration of antithrombin III. Increases blood concentrations of thyroxine, iron, copper. It has an anti-atherosclerotic effect, increases HDL content, reduces LDL and cholesterol (triglyceride levels increase). Modulates the sensitivity of receptors to progesterone and sympathetic regulation of smooth muscle tone, stimulates the transition of intravascular fluid into tissues and causes compensatory retention of sodium and water. In high doses, it prevents the degradation of endogenous catecholamines by competing for active COMT receptors. After menopause, only a small amount of estradiol is produced in the body (from estrone found in the liver and adipose tissue). A decrease in the content of estradiol produced in the ovaries is accompanied in many women by vasomotor and thermoregulatory instability (flushes to the facial skin), sleep disorders, as well as progressive atrophy of the genitourinary system. Osteoporosis (mainly of the spine) develops due to estrogen deficiency. After oral administration, larger amounts of estradiol are metabolized in the lumen (microflora) and intestinal wall, as well as in the liver, before entering the bloodstream (leading to non-physiologically high concentrations of estrone in plasma, and with long-term therapy, to the accumulation of estrone and estrone sulfate) . The consequences of the accumulation of these metabolites in the body over a long period of time have not yet been clarified. It is known that oral administration of estrogens causes an increase in protein synthesis (including renin), which leads to an increase in blood pressure.
Indications for use
- hormone replacement therapy for symptoms of estrogen deficiency; - treatment of climacteric syndrome associated with natural or artificial menopause that develops as a result of surgical intervention.
Release form
transdermal gel 0.1%; package (bag) 1 g, box (box) 28; transdermal gel 0.1%; package (bag) 1 g, box (box) 91; transdermal gel 0.1%; package (bag) 0.5 g, box (box) 28; transdermal gel 0.1%; package (bag) 0.5 g, box (box) 91; transdermal gel 1 mg; package (sachet) rich ball 1 g, cardboard pack 28; transdermal gel 1 mg; sachet 1 g, cardboard pack 91; transdermal gel 0.5 mg; package (sachet) rich ball 1 g, cardboard pack 28; transdermal gel 0.5 mg; sachet 1 g, cardboard pack 91; Warehouse Transdermal gel 1 g active ingredient estradiol 1 mg (looks like estradiol hemihydrate) other ingredients: carbomer (carbopol 974 R); trolamine; propylene glycol; ethyl alcohol (96%); purified water - up to 1.0 g in multi-ball bags of 0.5 or 1 g; There are 28 or 91 packages in a box.
Pharmacodynamics
An estrogenic drug for external stagnation. The active ingredient is synthetic 17β-estradiol, chemically and biologically identical to endogenous human estradiol (which is established in the body of women from the first menstruation until menopause), so is shaking with ovaries. In cellular organs where the action of hormones is directed, estrogens create a complex with specific receptors (detected in various organs - in the mother, sow, raspberry, mammary gland, liver, hypothalamus, hypothalamus physics); the receptor-ligand complex interacts with estrogen-effector genome elements and specific internal cellular proteins, inducing the synthesis of i-RNA, proteins and the development of cytokines and growth factors. Delivers a feminizing infusion to the body. Stimulates the development of the uterus, fallopian tubes, pustule, stroma and mammary duct, pigmentation in the area of the nipples and organs, the formation of secondary signs of the female type, the growth and closure of the epiphyses of other tubular parts. origin. It relieves the temporary rupture of the endometrium and regular bleeding, in high concentrations it causes hyperplasia of the endometrium, suppresses lactation, suppresses the resorption of cystic tissue, stimulates the synthesis of a number of transport proteins (and roxin-binding globulin, transcortin, transferrin, protein, which is associated with the homonymous state), fibrinogen. It has a procoagulant effect, inducing the synthesis in the liver of vitamin K-dependent laryngeal factors (II, VII, IX, X), reducing the concentration of antithrombin III. Promotes blood concentrations of thyroxine, saliva, and copper. It has an anti-atherosclerotic effect, increasing LDL and cholesterol (the level of triglycerides increases). Modulates the sensitivity of receptors to progesterone and sympathizes with the regulation of smooth muscle tone, stimulates the transition of the intravascular line in the tissue and promotes compensatory retention of sodium and water. At high doses, the degradation of endogenous catecholamines, which compete for active COMT receptors, occurs. After menopause, only a small amount of estradiol is established in the body (from the part that is found in the liver and in adipose tissue). A decrease in estradiol secreted in the ovaries is accompanied in rich women by varicose veins and thermoregulatory instability (blood flow to the skin of the face), sleep disorders, as well as progressive organ atrophy iv sechostate system. As a result of estrogen deficiency, osteoporosis develops (head ridge). After taking a large amount of estradiol, it is first absorbed into the bloodstream, metabolized in the lumen (microflora) and intestinal tract, as well as in the liver (which leads to non-physiologically high concentrations estrone in plasma, and with trival therapy - before cumulation of estrone and estrone sulfate) . The evidence of the accumulation of these metabolites in the body over time has not yet been elucidated. It appears that oral administration of estrogens promotes protein synthesis (including renin), which leads to increased arterial pressure.
Pharmacokinetics
Soaking and distribution When the gel is applied, the alcohol quickly evaporates, and estradiol penetrates through the skin, whereby a large part is absorbed into the systemic bloodstream immediately, and some of the estradiol is trapped in the skin. and cellulose is released into the systemic bloodstream step by step. When applied to an area of 200-400 cm2 (the size of one or two sides) it does not cover the amount of absorbed estradiol. However, if the Divigel is applied over a large area, the level of penetration is significantly reduced. The bioavailability of the drug becomes 82%. With transdermal stagnation of divigel at a dose of 1 mg estradiol (1 g of divigel), Cmax in blood plasma becomes approximately 157 pmol / l, the average concentration is 112 pmol / l, the minimum concentration is 82 pmol / l. Doesn't accumulate. Metabolism and elimination Transdermal application eliminates the first stage of hepatic metabolism, which therefore increases the concentration of estrogen in the blood plasma when the gel is frozen. The metabolism of 17β-estradiol is similar to the metabolism of natural estrogens. In the blood, it is closely associated with the carrier protein. It undergoes a “first pass” effect through the liver and is metabolized to fewer active products—estron and estriol. It is seen from the stomach into the lumen of the small intestine and is reabsorbed. The remaining activity is lost as a result of oxidation in the liver. During the hour of treatment with the virus, the ratio of estradiols/estrons is maintained at 0.4-0.7. Excreted mainly in the form of sulfates and glucuronides; small amounts of estradiol, esterone and estriol are also found.
Use during pregnancy
The product is contraindicated before use during gestation and during lactation.
Use for renal impairment
Caution is indicated in case of nitric deficiency.
Other special occasions at reception
Caution is indicated in case of liver failure.
Contraindications for use
— Cancer of the breast (diagnosis, suspicion or history); — Diagnosed or suspected estrogen-related malignant tumors of the ovaries, uterus, endometrium; — Good and bad new development of organs (cancer of the cervix and uterine body, uterine fibroids, vulvar cancer, ovarian cancer) in women under 60 years of age; — Good new mammary ducts in females up to 60 years of age; — Vaginal bleeding of unknown etiology and predisposition to uterine bleeding; — Endometrial hyperplasia; — Pituitary swellings; — Diffuse illness of the tissue; — Inflammatory illness of female organs (salpingo-oophoritis, endometritis); — Hyperestrogenic stage of menopause; — Spontaneous thromboembolic venous disease (including history); — Deep vein thrombosis, pulmonary embolism (including history); — Thrombophlebitis and acute thrombophlebitis (including history); — Congenital hyperbolic rubinemia (Gilbert, Dubin-Johnson, Rotor syndromes); — Swollen liver (hemangioma, liver cancer); — Damage to cerebral blood flow (ischemic stroke, hemorrhagic stroke); — Blood diabetes, retinopathy, angiopathy; — Sickle-cell anemia; — Destruction of fat metabolism; — Cholestatic diarrhea or severe cholestatic itching (including intensification of their manifestations during the hour of advanced pregnancy or against the background of taking steroid drugs); — Otosclerosis (including congestion under the hour of pregnancy); — Increased sensitivity to estradiol and/or other components of the drug. With caution: bronchial asthma, migraine, epilepsy, arterial hypertension, heart failure, IHS, hepatic and/or nitric insufficiency, swelling, endometriosis, fibrocystic mastopathy, porf Ireland. Evidence of stagnation in women over 65 years of age. Divigel should not be applied to the breasts, skin, genital area, as well as to razed areas of the skin.
Side effects
On the side of the central nervous system and peripheral nervous system: headache, migraine, confusion, depression, chorea. On the side of the cardiovascular system: displacement of the arterial pressure, thrombophlebitis. On the side of the herbal system: boredom, vomiting, cunt sticks, flatulence, epigastric pain, cholestatic diarrhea, cholelithiasis. Allergic reactions: at the site of application - sagging, skin irritation, skin hyperemia, contact dermatitis. On the side of the reproductive system: metrorrhagia, scanty bloody vision, increased size of uterine leiomyoma, endometrial hyperplasia (when recognized without a combination with progesterone), endometrial carcinoma (in women with intact uterus after menopause), ovarian sclerosis with severe stasation, changes in libido. On the side of the endocrine system: engorgement (tension or increase) of breast tissue, increased body weight, decreased tolerance to carbohydrates. On the side of the exchange of substances: adding sodium, calcium and water (absorbents) during dry stagnation; attacks of porphyria. Others: impaired vision (change in corneal curvature), chloasma, melasma, vaginal candidiasis.
Directions for use and doses
Transdermal. Divigel can be used for trival and cyclic therapy. The initial starting dose is 1.0 mg estradiol (1.0 g gel per day) per dose, but choosing an initial dose can be based on the severity of symptoms. Depending on the clinical picture, the dose may be changed after 2-3 cycles individually to 0.5 to 1.5 g per day, which is equivalent to 0.5 to 1.5 mg estradiol per dose. Patsynts of the wtaknoye (uninitiated) by the matcoure of the pіd hour of Lіkuvannya Divigel is recommended to recognize the gestagen (the Medoxyprogesterone Acetate, Noretisteron, Noretisteron Abo Digydrogestron) for 10-12 days in the skin of the cycle. After a course of gestagen ingestion, menstrual-like bleeding may occur. In case of persistent or persistent uterine bleeding, it is easy to establish the cause of their guilt. In postmenopausal patients, the duration of the cycle may be increased to 3 months. The gel should be applied 1 time to the clean skin of the lower part of the front wall of the abdomen, transverse area, shoulders, forearm or across the right or left buttock, carefully marking the area of application. The area of application must be increased by 1-2 dolons. After applying the drug, rub a small amount of liquid until the gel dries (2-3 minutes). The area where the gel is applied cannot be rinsed for 1 hour. There is evidence of a drop in the gel in the eyes. Wash your hands immediately after applying the gel. If the patient forgot to apply the gel, the next step will be to start working, but no later than 12 years from the time the drug was applied. If more than 12 years have passed, then the application to the engine must be put aside until the next time. If you do not take the drug regularly (missed doses), menstrual-like uterine bleeding may occur.
Overdose
Symptoms: pain in the mammary glands or in the pelvic area, bloating, anxiety, twitchiness, boredom, vomiting, and in some episodes - metrorrhagia. Treatment: carrying out symptomatic therapy. Symptoms appear with a reduced dose or with administration of the drug.
Interactions with other drugs
Estradiol promotes the effectiveness of hypolipidemic conditions; weakens the effect of human hormone preparations; hypoglycemic, diuretic, antihypertensive drugs and anticoagulants; reduces glucose tolerance (correction of the dose of hypoglycemic drugs). The metabolism of estradiol is accelerated when taken simultaneously with barbiturates, tranquilizers (anxiolytics), opioid analgesics, anesthesia drugs, some anti-epileptic drugs (carbamazepine, phenytoin), inducers microsomal liver enzymes; rosemary preparations to replace the herb with St. John's wort (St. John's herb). The concentration of estradiol in the blood also decreases with one-hour administration of phenylbutazone and certain antibiotics (ampicillin, rifampicin, rifabutin) and antiviral drugs (nevirapine, efavirenz), which This is due to changes in intestinal microflora. The action of estradiol progresses against the background of taking folic acid and thyroid medications.
Special instructions for use
Before starting or re-initiating replacement hormonal therapy, it is necessary to obtain a further personal and family history. Follow up with medical attention to identify possible contraindications and monitor any necessary companions when taking the drug (including the pelvic organs and chest organs). During the treatment process, it is recommended to carry out periodic irritations, the frequency and set of methods that are included before are determined for the specific skin condition individually. Follow-up, including mammography, should be carried out in accordance with accepted standards and with the understanding of individual clinical features in the skin lesion. Before starting HRT, you should carefully evaluate all the benefits and risks of therapy. The patient must be under the constant supervision of a physician in case of any illness or condition that was previously avoided and/or aggravated during pregnancy or prior hormonal therapy: leiomyoma (f uterine fibroids), endometriosis; thromboembolic illnesses in the past or risk factors for their culpability; factors for the risk of estrogen-dependent puffiness (1st stage of decline in breast cancer); arterial hypertension; impaired liver function (adenoma); blood diabetes with or without blood vessels; cholelithiasis; migraine and/or (severe) headache; systemic Chervona Vovchanka; history of endometrial hyperplasia; epilepsy; bronchial asthma; otosclerosis. The mother's trace is on the lookout for aphid treatment in rare cases, a possible relapse or worsening illness. Therapy should be carefully administered in case of emergency, if contraindications are identified and / or in urgent situations: chronic fatigue or impaired liver function; expression of AT displacement; new attacks of migraine-like headache; Vaginism. When taking estrogens over a period of time, there is a risk of developing endometrial hyperplasia and carcinoma. To reduce the risk, it is necessary to combine estrogen therapy in women with an intact uterus with progesterone for at least 12 days during the treatment cycle. In cases where severe bleeding and/or minor bleeding is seen after several months, we will then conduct an investigation to identify the reasons for their occurrence. Follow-up may include endometrial biopsy (to exclude endometrial malignancy). For women with a damaged uterus due to endometriosis (especially in cases of excessive endometriosis), it is recommended to supplement with progesterone before estrogen therapy, due to premalignant or malignant transformation of the uterus of endometriosis. estrogenic stimulation. With prolonged use of HRT, the risk of development of breast cancer increases. According to epidemiological studies, among women aged 50 to 70 years, breast cancer is diagnosed in 45 cases per 1000. It has been established that among women who are taking or have recently taken HRT, the total number of additional incidences of mammary cancer in the breeding period becomes 1-3 (in the average - 2) additional incidences per 1000 individuals, which can be eliminated HRT for 5 days; 3-9 (in the middle - 6) episodes per 1000 women, to stop HRT for 10 years and 5-20 (in the middle - 12) episodes per 1000 women, to stop HRT for 15 years. The development of such a rhiziku was revealed mainly in women of thin or normal stature. In women of advanced status (high risk of breast cancer), HRT does not further promote the development of breast cancer. The additional risk for the development of breast cancer appears due to increased pain in taking HRT and turns to exit approximately 5 days after treatment. Combinations of estrogen-progestagen HRT have a similar or greater risk in those treated with estrogen therapy. In women who stopped HRT, the risk of development of thromboembolic vein diseases (thrombosis of the deep veins of the lower ends and leg veins) was increased by 2-3 times in equal numbers with women who did not stop HRT. The prevalence is higher in the first period of HRT, and lower in the later years. The main risk factors for thromboembolic complications: individual or family history, severe obesity (body mass index more than 30 kg/m2), systemic bloodworm. Patients with a history of thromboembolism or recent spontaneous pregnancy loss should undergo further investigation to exclude the possibility of thrombophlebitis. The use of HRT in this form may emerge after a new assessment of factors in the development of thrombophlebitis and the initiation of anticoagulant therapy. The risk progresses with severe immobilization, major injuries or major surgical procedures. HRT should be administered 4-6 days before planned surgical operations on the abdominal organs or orthopedic operations on the lower ends. The bath can be renewed after the dryness has been completely restored. If thromboembolic symptoms develop (pain in the chest, dyspnea), you may need to discontinue HRT. Estrogens cause the loss of fluid in the body. Patients with impaired function are at least under the constant supervision of a doctor due to the increase in the level of estradiol and its metabolites in the blood. Estrogens increase sensitivity to insulin and increase its elimination. If you are suffering from blood diabetes in the first month of HRT indications, constant control of the level of glucose in the blood. The intake of estrogens increases the risk of surgically confirmed gum disease. In rare cases of a sharp increase in the level of triglycerides in the blood against the background of taking estrogens, pancreatitis may develop. Estrogens increase the level of thyroid-binding globulin, increasing the level of circulating thyroid hormones. There is no trace of the gel being stained on the mammary glands and mucous membranes of the vulva and groin. Involvement in the development of water vehicles and caravan mechanisms. Therapy for the engine should not be discouraged in the opportunity to engage in potentially unsafe types of activities that require increased respect and fluidity of psychomotor reactions. ій.
Storage conditions
List B.: At a temperature not exceeding 25 ° C.
Best before date
36 months
ATX classification:
G Genitourinary system and sex hormones
G03 Sex hormones and modulators of the reproductive system
G03C Estrogens
G03CA Natural and semi-synthetic estrogens
G03CA03 Estradiol
special instructions
The drug is prescribed with caution in the following cases:
- liver, heart and kidney failure, liver pathologies;
- benign tumors of various locations (including uterine fibroids);
- cancer in close relatives;
- diabetes;
- epilepsy;
- cholelithiasis;
- migraine;
- systemic connective tissue diseases;
- bronchial asthma;
- IHD;
- sickle cell anemia.
Patients using Divigel for a long time require annual diagnostics (blood tests, mammography, ultrasound of the mammary glands and pelvic organs, other studies, the scope of which is determined individually) to reduce the risk of negative phenomena.
Divigel for menopause, reviews of which indicate a small number of side effects, with prolonged use increases the risk of malignant formations.
It reaches its maximum 5 years after starting the drug. Thus, endometrial cancer is observed 2-12 times more often in women using hormonal drugs. After discontinuation of therapy, the increased likelihood of malignant processes may persist for 10 years.
The risk of thromboembolism when taking estrogen increases by 1.3-3 times, and ischemic stroke by 1.5 times.
What should you remember when taking it?
Before starting the Divigel course, read the instructions for use when planning pregnancy. As part of replacement therapy, a family and complete personal history is required. As part of therapy, periodic re-examinations are recommended. This list includes a mammogram, a complete blood count, and a liver check.
If the patient uses the drug on an irregular basis, breakthrough uterine bleeding of a menstrual type may occur. In addition, doctors warn that long-term use or violation of the optimal dosage increases the likelihood of endometrial hyperplasia, breast cancer and carcinoma. Although such effects have been observed extremely rarely, it is strongly recommended to consult with your doctor before each course of taking the drug.
Do not spread the gel on the vaginal mucosa and mammary glands. An increase in the effect of estradiol is observed with parallel use of drugs for the thyroid gland, as well as medications with a high concentration of folic acid.
Drug interactions
The pharmacokinetics of the active component of Divigel is enhanced by simultaneous use of the following medications:
- barbiturates (Phenobarbital, Veronal, Barbamil and others);
- tranquilizers (Diazepam, Amizil, Grandaxin);
- folic acid;
- antiviral agents Ritonavir and Nelfinavir;
- drugs containing thyroid hormones;
- narcotic painkillers (Codeine, Morphine and others);
- anesthetics;
- medications that increase the activity of liver enzymes (Rifampicin, Phenobarbital and others);
- antiepileptic drugs (valproate, Diphenin, Clonazepam and others);
- medicines containing St. John's wort.
A decrease in the therapeutic effect is observed when taking drugs such as:
- antibacterial drugs (Ampicillin, Rifabutin and others);
- antivirals (Nevirapine, Efavirenz);
- some NSAIDs (Phenylbutazone and its analogues).
On the other hand, estradiol enhances the therapeutic effect of drugs used to reduce the concentration of lipid fractions in the blood, and also reduces the activity of diuretics, antihypertensive drugs and anticoagulants (Aspirin, Warfarin and others).
Interaction of Divigel with other drugs
Hormonal gel Divigel affects the action of other medications. As a rule, a woman of menopausal age already has chronic diseases that require regular medication.
Before you start using Divigel, you need to find out how its active substance 17beta-estradiol interacts with other medications:
- It reduces the therapeutic effect of medications from the following groups: antidiabetic, antithrombotic, diuretic, blood pressure-lowering, progesterone.
- Enhances the therapeutic effect of stanins - medications designed to reduce the level of bad cholesterol in a woman.
During menopause, it is better to prevent an increase in the amount of bad cholesterol by taking estrogen-containing drugs than stanins, which have a large list of side effects. For this purpose, it is enough for a woman to take 1 mg of estrogen per day. In addition, products containing estrogen will reduce the intensity of menopausal symptoms or completely eliminate them.
Hormone therapy with Divigel.
The therapeutic effect of Divigel is reduced by the following medications:
- medicines containing St. John's wort;
- antiepileptic drugs;
- tranquilizers;
- barbiturates;
- anesthetics;
- opioid analgesics.
While drugs for the treatment of thyroid diseases and folic acid, on the contrary, enhance the effect of 17beta-estradiol.
Analogs
The following drugs are analogues of Divigel in terms of the content of the active component and method of administration:
- vaginal cream Ovestin;
- Estrogel gel;
- transdermal therapeutic system Klimara.
Price in pharmacies in Moscow, St. Petersburg, regions
The average price for Divigel in 1 g packets (pack of 28 packets) is:
- in Moscow – 900 rubles;
- in St. Petersburg – 850 rubles;
- in the regions – 800-1200 rubles.
The drug Divigel is used for menopause, which occurs with signs of disorders of the cardiovascular, nervous, endocrine and other systems. Before prescribing it, the doctor must collect detailed information about previous diseases, diagnose existing pathologies and data on the presence of family diseases.
According to patient reviews, the drug has virtually no significant side effects and effectively increases estrogen levels, reducing menopausal symptoms.
Article design: Vladimir the Great
Who is the drug contraindicated for?
Divigel, as a hormonal agent, has a rather impressive list of contraindications:
- venous thrombosis;
- thrombophlebitis;
- pulmonary emboli;
- diabetes;
- lipid metabolism disorders;
- anemia;
- cerebral atherosclerosis;
- previous strokes;
- endometrial hyperplasia, endometriosis;
- uterine bleeding for unknown reasons;
- benign and malignant neoplasms of any location;
- cholestatic jaundice;
- intolerance to some component of the drug.
It is important to take hormone replacement therapy seriously, and before prescribing medications, inform your doctor about previous illnesses and existing chronic diseases. During therapy, it is necessary to undergo medical examinations every six months.
This way the woman will prevent the development of diseases or complications. The drug is not prescribed to women over 65 years of age.