Buy Divigel transderm gel. 0.1% 0.5g No. 28 in pharmacies

IVF is carried out under constant control, from patients visiting a doctor to achieving the goal - pregnancy through artificial insemination. For the result to be successful, the woman receives hormonal support. Before IVF, hormonal correction may be carried out to prepare the reproductive system for pregnancy. An analysis of the hormone estradiol must be carried out in advance and a transcript must be made. One of the hormone-containing drugs used in the complex of replacement therapy for IVF is Divigel . Hormone therapy is the most important stage of preparation; the expectant mother’s body must be completely ready to accept the embryo.

The task of doctors is to monitor the readiness of the woman’s reproductive system, on which the success of in vitro fertilization depends.

Pharmacological properties of the drug Divigel

An alcohol-based gel containing estradiol (estra-1,3,5(10)-triene-3,17β-diol) is a synthetic analogue of human endogenous estradiol with similar biological effects. The action of Divigel is similar to the action of estrogens when administered orally: it compensates for estrogen deficiency, reducing the severity of disorders caused by menopause and oophorectomy. With sequential use of Divigel and progestogen, 80–90% of women experience regular menstrual-like bleeding with an average duration of 5–6 days, which usually begins within 1–7 days after the last dose of progestogen. Breakthrough bleeding and/or light spotting occurs during treatment in approximately 4–5% of women. Amenorrhea in the first year of treatment is observed in 3–5% of women. Transdermal use of estradiol in combination with medroxyprogesterone acetate helps reduce total cholesterol levels without changing the cholesterol/HDL ratio. The effectiveness of Divigel in correcting decreased bone density in the postmenopausal period is the same as with the use of oral estrogen drugs. When the gel is applied to the skin, the alcohol evaporates and estradiol is quickly adsorbed, entering the systemic bloodstream. Applying Divigel to a skin surface area of ​​200 or 400 cm2 (approximately equivalent to the area of ​​one or two palms) does not affect the amount of estradiol absorbed, however, if Divigel is applied to a larger surface of the skin, the degree of absorption may change. A certain amount of estradiol accumulates in the subcutaneous fatty tissue, from where it is gradually released into the blood. Transdermal use avoids first-pass metabolism of the drug during its initial passage through the liver; for this reason, fluctuations in the concentration of estrogen in the blood plasma when using Divigel are significantly less pronounced than when taking estrogens orally. The maximum plasma concentration with transdermal use of estradiol at a dose of 1 mg is approximately 157 pmol/l, the average concentration in the interdose interval is 112 pmol/l, the minimum concentration is 82 pmol/l. The relative bioavailability of estradiol when used in the form of Divigel is 82% compared to an equivalent dose of estradiol valerate when administered orally.

Description

The active component of Divigel is a gonadosteroid of the estrogen class - estradiol, whose chemical structure is close to estradiol produced by the ovaries. Divigel is effective in case of insufficient production of this hormone by the gonads, which is the most active among female steroids and is formed from testosterone during enzymatic processes.

The effect of estradiol on the female and male body is enormous:

• stimulation of the development of a woman’s reproductive organs (uterus, fallopian tubes), mammary glands (ducts and stroma);
• pigmentation of the areola and genital area;
• feminization (female type of development of secondary sexual characteristics);
• growth of epiphyses of tubular bones;
• promotes rejection of the endometrioid layer of the uterus due to which regulation occurs;
• activates blood clotting factors;
• helps increase the concentration of thyroxine (thyroid hormone), copper, iron;
• has an antiatherosclerotic effect;
• reduces cholesterol concentration.

With a lack of estrogen, pathological conditions develop in which pregnancy is unlikely or impossible. Divigel is often prescribed for IVF to correct and normalize hormonal levels.

The form of Divigel is a gel-like product applied to the skin. After the evaporation of the alcohol component of the gel, the molecules of synthetic estradiol penetrate deep into the subcutaneous layer and enter the vascular bed. Part of the active substance accumulates in the fatty layer, from here it enters the blood. Due to the fact that Divigel is used as a local drug, and not systemic (in the form of an injection or tablet), it does not have a toxic effect on the liver.

Use of the drug Divigel

The dose of the drug is set individually, the recommended dose is 0.5–1.5 mg/day, the dose can be adjusted in the future. The course of treatment is cyclical or continuous. Typically the initial dose is 1 mg estradiol (1 g gel) per day. With an intact uterus, it is recommended to carry out cyclic courses with the simultaneous administration of progestins for 10–12 days of each cycle (to prevent endometrial hyperplasia). After a course of gestagen, menstrual-like bleeding should begin. In case of extraordinary or prolonged uterine bleeding, the cause of its occurrence should be determined. In postmenopausal patients, the cycle duration can be 3 months. A daily dose of Divigel is rubbed into the skin of the lower part of the anterior wall of the abdomen or applied in turn to the skin of the buttocks over an area the size of 1–2 palms, alternating the right and left sides. After rubbing, the skin should dry for a few minutes.

Indications

There are two main indications for using Divigel:

1. Insufficient thickness of the endometrium. With IVF, an embryo is implanted into the uterus, which must attach securely to the endometrium, only then will pregnancy occur. The uterine layer should have a thickness of 7 millimeters or more; if it is less, the embryo will not be able to implant and it will end in a miscarriage. Divigel is prescribed for endometrial thickness of 5 millimeters or less.
2. Deficiency of endogenous estradiol (that is, the one produced by the woman’s body).

In addition to artificial insemination programs, Divigel is used in postmenopausal women to prevent osteoporosis.

Contraindications to the use of the drug Divigel

Diagnosed, suspected or past breast cancer; diagnosed or suspected estrogen-dependent tumors (for example, endometrial cancer); vaginal bleeding of unknown etiology; untreated endometrial hyperplasia; thrombosis and thromboembolism (deep vein thrombosis, pulmonary embolism, myocardial infarction) within the last 2 years, a history of repeated thromboembolism; acute or chronic liver diseases (including a history) with changes in liver function tests; hypersensitivity to the components of the drug; During pregnancy and breastfeeding; porphyria.

Special instructions for the use of the drug Divigel

Before starting or resuming hormone replacement therapy, it is necessary to conduct a complete medical examination of the patient (including examination of the pelvic organs and mammary glands). During treatment, periodic control examinations should be carried out, the scope of which (including mammography) is determined individually. Divigel should not be applied to the skin of the chest (especially the mammary glands), face, perineum, or damaged skin. Avoid getting the gel into your eyes. After applying the drug, wash your hands thoroughly. If the patient missed the time for applying the gel, it can be used only in the first 12 hours after the miss; if the gel was not applied at this time, the drug should be skipped and the next dose should be applied as scheduled. It must be remembered that during such omissions the patient may experience bleeding. Patients with endometriosis, endometrial hyperplasia, diseases of the cardiovascular system, cerebrovascular accidents, a history of thromboembolism, hypercoagulability phenomena, hypertension (arterial hypertension), a family history of breast cancer, impaired liver or kidney function, require careful monitoring during estrogen treatment. porphyria, uterine leiomyoma, epilepsy, asthma, diabetes mellitus, otosclerosis and multiple sclerosis, cholelithiasis, systemic lupus erythematosus. The drug should be discontinued immediately if liver dysfunction develops (including jaundice), a marked increase in blood pressure, attacks of migraine-like headaches, or pregnancy.

Side effects

Divigel is well tolerated by patients in most cases.

But since the product contains an active hormonal element, the following adverse reactions may occasionally occur:

• tissue swelling (minor);
• headache or migraine;
• irritability, episodic psycho-emotional instability;
• increased blood pressure;
• increased heart rate;
• decreased libido;
• vaginal discharge of an atypical nature;
• weight gain;
• loss of appetite;
• dyspeptic disorders;
• hives or other skin rashes;
• liver dysfunction;
• cholestasis (decreased bile secretion or cessation of bile secretion).

These problems are usually not pronounced and are eliminated by adjusting the dose of Divigel by the attending physician or discontinuing the drug.

Interactions of the drug Divigel

Estrogens reduce the effectiveness of antihypertensive, antidiabetic agents and anticoagulants. Barbiturates, carbamazepine, rifampicin, griseofulvin and other activators of microsomal liver enzymes reduce the level of estradiol in the blood plasma. Ritonavir and nelfinavir, when used simultaneously with estrogens, may have an inducing effect. Preparations of St. John's wort can enhance the metabolism of estrogens and progestogens. Due to the lack of the effect of primary passage through the liver when using transdermal agents, the effect of liver enzyme inducers on metabolism is less pronounced.

Divigel gel 0.1% in sachet 1g No. 28

Name

Divigel.

Description

Colorless opalescent homogeneous gel.

Main active ingredient

Estradiol.

Release form

Transdermal gel.

Dosage

0.1% 1 g.

special instructions

pharmachologic effect

Sex hormones. Estrogens. ATC code G03CA03.

Pharmacodynamics

The active substance of the Divigel gel is synthetic 17β-estradiol, chemically and biologically identical to endogenous human estradiol. It compensates for the loss of estrogen synthesis in women during menopause and alleviates menopausal symptoms. Estrogens prevent bone loss that occurs during menopause or after oophorectomy. Clinical Study Information Relief of Estrogen Deficiency Symptoms and Bleeding Relief of menopausal symptoms was achieved within the first weeks of treatment. Prevention of osteoporosis Estrogen deficiency during menopause is associated with increased bone turnover and decreased bone mass. The effect of estrogens on bone mineral density is dose-dependent. Protection is effective as long as treatment continues. After stopping hormone replacement therapy (HRT), bone mass decreases at the same rate as in women not receiving this therapy. Evidence from the Women's Health Initiative (WHI) and meta-analytic studies suggests that the use of hormone replacement therapy (estrogen replacement alone or in combination with a progestogen) in healthy women reduces the risk of hip, vertebral, and other fractures. fractures caused by osteoporosis. Hormone replacement therapy may also prevent fractures in women with low bone density and/or established osteoporosis, but research data are limited.

Pharmacokinetics

Divigel is an alcohol-based estradiol gel. When Divigel is applied to the skin, the alcohol quickly evaporates and estradiol is absorbed through the skin, entering the circulatory system. With external use of estradiol, changes in the concentration of estrogen in plasma are insignificant, since some of the estradiol is still retained in the subcutaneous tissues, from where it is gradually released into the circulatory system. Transdermal application avoids the first stage of hepatic metabolism. With transdermal application of a dose of Divigel (0.5, 1 and 1.5 mg estradiol), the concentration of estrogen in plasma is as follows: Dose of Divigel Cmax (pmol/l) Average (pmol1/1) Cmin (pmo1/1) 0.5 mg 143 75 92 1.0 mg 247 124 101 1.5 mg 582 210 152 During treatment with Divigel, the estradiol-estrone ratio remains at 0.4-0.7, whereas with oral estrogen this ratio usually drops to less than 0 ,2. The bioavailability rate is 82% compared to an equivalent oral dose of estradiol valerate. The metabolism and excretion of estradiol when administered transdermally is similar to that of natural estrogens.

Indications for use

Hormone replacement therapy for symptoms of estrogen deficiency in postmenopausal women. For the prevention of osteoporosis in postmenopausal women at high risk of fractures when other drugs for the treatment of osteoporosis are contraindicated or inappropriate. Experience with the use of HRT drugs in women over 65 years of age is limited.

Directions for use and doses

Divigel is a gel for transdermal use intended for long-term or cyclic treatment. The usual starting dose is 1 g of gel per day, which corresponds to 1 mg of estradiol. The duration of use and dose are selected by the doctor, taking into account the individual characteristics of the patient (depending on the clinical condition after 2-3 cycles, the dose can be adjusted: from 0.5 g to 1.5 g of gel per day, which corresponds to from 0.5 to 1 .5 mg estradiol per day). In patients with an intact uterus, it is necessary to combine Divigel with an adequate dose of progesterone according to the duration of administration, for example, 12-14 days in a row for a month or constantly to prevent the development of estrogen-stimulated endometrial hyperplasia. A dose of Divigel is applied once a day to the skin of the lower part of the anterior abdominal wall, or alternately to the right or left buttocks. The application area is equal in size to 1-2 palms. Divigel should not be applied to the mammary glands, face, genitals, or irritated areas of the skin. After applying the drug, you need to let the gel dry. Avoid accidental contact of Divigel with your eyes; wash your hands immediately after applying the gel. If the patient forgot to apply the gel on time, it is necessary to do this as quickly as possible, but no later than within 12 hours from the moment of applying the drug according to the established schedule. If more than 12 hours have passed, then applying Divigel should be postponed until the next time. If the drug is not used regularly, menstrual-like uterine bleeding may occur.

Use during pregnancy and lactation

The use of Divigel during pregnancy is not indicated. If pregnancy occurs, you must immediately stop taking the drug. The results of epidemiological studies indicate that unintentional use of estrogens during pregnancy does not have teratogenic or embryotoxic effects. The use of Divigel during breastfeeding is not indicated.

Impact on the ability to drive vehicles and other mechanisms

The drug does not affect the ability to drive vehicles or other potentially dangerous mechanisms.

Precautionary measures

Hormone replacement therapy to treat postmenopausal symptoms should only be used for symptoms that adversely affect quality of life. The risk-benefit ratio must be carefully assessed and HRT can be continued as long as the expected benefit outweighs the risk. Medical examination and long-term follow-up Before starting or restarting hormone replacement therapy, a complete personal and family history should be obtained. A medical examination should be conducted to identify possible contraindications and observe the necessary precautions when using the drug (including the pelvic organs and mammary glands). During the treatment process, periodic examinations are recommended. The frequency and set of methods included in it are determined for each specific case individually. A woman should tell her doctor about changes in her breasts (see section “Breast Cancer”). Studies, including mammography, should be carried out in accordance with accepted standards and taking into account individual clinical characteristics in each individual case. Conditions that require close monitoring The patient should be under constant medical supervision in case of any of the following diseases or conditions that were previously observed and/or aggravated during pregnancy or previous hormonal therapy. It should be borne in mind that during treatment with Divigel, in rare cases, a relapse or exacerbation of the listed diseases is possible: leiomyoma (uterine fibroids) or endometriosis; history of thromboembolic diseases or risk factors for their occurrence; risk factors for estrogen-dependent tumors (1st degree of heredity of breast cancer); arterial hypertension; liver dysfunction (eg, adenoma); diabetes mellitus with or without vascular lesions; cholelithiasis; migraine and/or (severe) headache; systemic lupus erythematosus; history of endometrial hyperplasia; epilepsy; bronchial asthma; otosclerosis; hereditary angioedema. Reasons for immediate discontinuation of therapy Therapy should be stopped immediately if contraindications are found and/or in the following cases: jaundice or deterioration of liver function; marked increase in blood pressure; new attacks of migraine-like headaches; pregnancy. Endometrial hyperplasia and carcinoma With long-term use of estrogen replacement therapy in women with a non-removed uterus, the risk of developing endometrial hyperplasia and carcinoma increases. This increase in risk, depending on the duration of use and dose of estrogens, in patients taking only estrogens is from 2 to 12 times higher than in patients not taking estrogens (see section "Side effects"). The increased risk may persist for at least 10 years after discontinuation of therapy. Long-term combination therapy with estrogen and progestogen or the addition of progestogen to estrogen therapy for at least 12 days per month or 28 days per treatment cycle may prevent increased risk in women with a hysterectomy. If breakthrough bleeding and/or spotting occurs after several months of use or after discontinuation of therapy, studies should be carried out to identify the causes of their occurrence. Investigations may include endometrial biopsy (to rule out endometrial malignancy). For women with a hysterectomy due to endometriosis (especially in cases of residual endometriosis), the addition of a progestogen to estrogen replacement therapy is recommended, due to premalignant or malignant transformation of endometriosis lesions with estrogen stimulation. Breast cancer The risk of developing breast cancer depending on the duration of HRT is increased in women taking combined estrogen-progestogen therapy and possibly taking estrogen replacement therapy only. Combination estrogen-progestogen therapy Evidence from randomized, placebo-controlled Women's Health Initiative (WHI) trials and epidemiological studies suggests that use of combined estrogen-progestogen hormone replacement therapy increases the risk of breast cancer. This effect takes approximately 3 years to appear (see Side Effects section) Estrogen replacement therapy only Data from the Women's Health Initiative (WHI) studies suggest that estrogen replacement therapy does not increase the risk of breast cancer in women with the uterus removed. Observational studies have reported a small increase in the risk of developing breast cancer, but the increase is significantly lower compared with users of estrogen-progestogen combination therapy (see section "Side effects"). This risk appears within several years of using the drug and returns to its original level within several (no more than 5) years after stopping treatment. HRT and especially estrogen-progestogen combination therapy increases breast tissue density, which interferes with radiological diagnosis of breast cancer. Ovarian cancer Ovarian cancer is less common than breast cancer. Epidemiological evidence from a large meta-analysis suggests a slightly increased risk of ovarian cancer in women taking estrogen replacement therapy alone or combined estrogen-progestogen HRT. This risk appears within 5 years of using the drug and decreases some time after stopping treatment. Some other studies, including those from the Women's Health Initiative (WHI), suggest that combined HRT may be associated with a similar or slightly lower risk (see Side Effects section). Venous thromboembolism HRT is associated with a 1.3-3 times higher risk of developing venous thromboembolism, i.e. deep vein thrombosis and pulmonary embolism. The likelihood is higher in the first year of HRT than in subsequent years (see section “Side effects”). Patients with thrombophilic disorders have an increased risk of venous thromboembolism and the use of HRT may increase this risk. Therefore, the use of HRT in this group of patients is contraindicated (see section “Contraindications”). The main risk factors for venous thromboembolism are estrogen use, older age, major surgery, prolonged immobilization, increased weight (body mass index > 30 kg/m2), pregnancy/puerperium, systemic lupus erythematosus and cancer. There is no clear opinion about the significance of varicose veins in the manifestation of venous thromboembolism. Just like all patients, it is necessary to prevent venous thromboembolism after surgery. If long-term immobilization of the patient is necessary after surgery, HRT should be stopped 4-6 weeks before planned surgery. Therapy can be resumed only after bed rest is discontinued. Women who do not have a history of venous thromboembolism, but who have had thrombosis in a first-degree relative, may be offered screening after careful review of restrictions (screening reveals only part of the predisposing causes of thrombosis). If a predisposing cause of thrombosis is identified that is different from that of other family members or is serious (antithrombin deficiency, protein C or S deficiency, many other reasons), the use of HRT is contraindicated. It is necessary to carefully evaluate the risk-benefit ratio in the case of chronic use of anticoagulants. If venous thromboembolism occurs at the beginning of treatment, you must stop taking the drug. If symptoms of venous thromboembolism (eg, painful swelling of the legs, sudden chest pain, shortness of breath) occur, patients should consult a doctor immediately. Coronary artery disease Randomized controlled trials have not demonstrated that estrogen-progestogen combination therapy or estrogen replacement therapy alone protect against myocardial infarction in women with or without coronary artery disease. Estrogen-progestogen combination therapy During estrogen-progestogen combination therapy, the relative risk of developing coronary heart disease is slightly increased. The risk of developing coronary heart disease depends on age. The incidence of additional risk from combined estrogen-progestogen therapy in healthy women very close to menopause is small, but increases with age. Estrogen replacement therapy alone Data from randomized controlled trials have not shown an increased risk of coronary heart disease in women with a hysterectomy when using estrogen replacement therapy alone. Ischemic stroke HRT (estrogen replacement alone or estrogen-progestogen combination therapy) is associated with a 1.5 times higher relative risk of ischemic stroke. The relative risk does not change with age or time after menopause. Since the risk depends on age, the overall risk of stroke in women taking HRT increases with age (see section "Side effects"). Other Conditions Estrogens cause fluid retention in the body. Patients with cardiac problems or impaired renal function should be under constant medical supervision. Patients with elevated levels of triglycerides in the blood while taking estrogen replacement therapy or other HRT should be under constant medical supervision. In rare cases, taking estrogen in this group of patients caused a sharp increase in triglyceride levels in the blood, which can cause the development of pancreatitis. Estrogens increase thyronine-binding globulin (TBG) levels, resulting in increased circulating levels of thyroid hormone as measured by protein-bound iodine, T4 concentration (column or radioimmunoassay), or T3 concentration (radioimmunoassay). The increase in T3 levels decreases, which reflects increased TSH, the concentrations of free T4 and T3 do not change. Serum concentrations of other binding proteins, such as corticosteroid binding globulin (CBG), sex hormone binding globulin (SHBG), may increase, resulting in increased concentrations of circulating corticosteroids and sex steroid hormones, respectively. Concentrations of free or biologically active hormone remain unchanged. The concentration of other plasma proteins may increase (angiotensin/renin substrate, alpha-1-trypsin, ceruloplasmin). In rare cases, chloasma may develop, especially in women with a history of chloasma during pregnancy. Women at increased risk of developing chloasma are advised to avoid exposure to sunlight or ultraviolet light. HRT does not improve cognitive function. There is some evidence that starting combined HRT may increase the risk of dementia in women over 65 years of age. This product contains propylene glycol, which may cause skin irritation.

Interaction with other drugs

There is evidence in the literature that estrogens may reduce the effect of antihypertensive and antidiabetic drugs and anticoagulants. Concomitant use of drugs that induce liver enzymes (barbiturates, phenytoin, carbamazepine, griseofulvin, rifampicin, rifabutin, nevirapine and efavirenz) may reduce the level of estradiol in the blood plasma. Ritonavir and nelfinavir, although they are strong inhibitors, when used simultaneously with estrogens, on the contrary, have an inducing effect. Herbal preparations containing St. John's wort can enhance the metabolism of estrogens and progestogens. When administered transdermally, the drug bypasses the “first pass” effect through the liver; accordingly, transdermally applied estrogens and progestogens are less affected by enzyme inducers than hormones taken orally. Clinically, increased metabolism of estrogens and progestogens can lead to a decrease in effect and a change in the nature of vaginal bleeding.

Contraindications

breast cancer (diagnosed, suspected or history); diagnosed or suspected estrogen-dependent malignant tumors (for example, endometrial cancer); vaginal bleeding of unknown etiology; untreated endometrial hyperplasia; idiopathic venous thromboembolism (diagnosed or history, such as deep vein thrombosis or pulmonary embolism); thrombophilic disorders (for example, protein C deficiency, antithrombin deficiency (see section “Special instructions”)); diagnosed arterial thromboembolism (eg, angina, myocardial infarction); acute liver disease or a history of liver disease, after which liver function tests have not returned to normal; hypersensitivity to estradiol and/or other components of the drug; porphyria.

Compound

One sachet contains: active ingredient – ​​0.5 mg or 1.0 mg of estradiol (in the form of estradiol hemihydrate). excipients - carbomer (carbopol 974 R), triethanolamine, propylene glycol, ethanol (96%), purified water.

Overdose

Symptoms: pain in the mammary glands, bloating, anxiety, irritability. Treatment: drug withdrawal or dose reduction.

Side effect

During the first months of therapy, breakthrough bleeding, spotting, tenderness, or breast enlargement may occur. These symptoms are temporary and disappear during therapy. Side effects that were observed during clinical trials are presented, as well as side effects that were reported during the post-registration period. Side effects can be expected in 76% of patients. During clinical trials, more than 10% of patients experienced side effects such as injection site reactions and chest pain. Benign and malignant estrogen-dependent tumors, for example, endometrial cancer. Venous thromboembolism, i.e., deep vein thrombosis of the legs or pelvic vein thrombosis and pulmonary embolism; more often observed in patients receiving hormone replacement therapy compared to those not receiving this therapy. For detailed information, see the “Contraindications” and “Special Instructions” sections. Myocardial infarction and stroke. Gallbladder diseases. Skin and subcutaneous tissue disorders: chloasma, erythema multiforme and nodosum, vascular purpura. Dementia may develop over the age of 65 (see section “Special instructions”). Risk of Breast Cancer Using estrogen-progestogen combination therapy for more than 5 years doubles the risk of developing breast cancer. The increased risk of breast cancer in patients taking estrogen alone is much lower than in patients taking estrogen-progestogen combination therapy. The risk depends on the duration of therapy (see section "Special instructions"). Results from a large randomized placebo-controlled trial (WHI) and epidemiological study (MWS): Million Women study (MWS) - estimated increase in breast cancer risk after five years of use. Risk of developing endometrial cancer Postmenopausal women with a hysterectomy 5 out of every 1000 women with a hysterectomy who do not take HRT are at risk of developing endometrial cancer. Women with a non-removed uterus are not recommended to use HRT, which contains only estrogens, as this therapy increases the risk of developing endometrial cancer (see section “Special instructions”). In epidemiological studies, the increase in risk of endometrial cancer depending on the duration of estrogen-only use and its dosage was from 5 to 55 additional diagnosed cases per 1000 women aged 50 to 65 years. Adding a progestogen to estrogen replacement therapy for at least 12 days per cycle may prevent the increased risk. In the Million Women Study, use of combined HRT (cyclic or continuous) for 5 years did not increase the risk of endometrial cancer (risk ratio 1.0

0.8-1.2

). Risk of Ovarian Cancer Use of estrogen replacement alone or combined estrogen-progestogen HRT has been associated with a slightly increased risk of being diagnosed with ovarian cancer (see Precautions section). A meta-analysis of 52 epidemiological studies reported an increased risk of developing ovarian cancer in women taking HRT compared with those women who had never taken HRT (hazard ratio 1.43, 95% confidence interval 1.31–1.56 ). In women aged 50 to 54 years, use of HRT for 5 years causes approximately 1 additional case in 2000 women. Among women aged 50 to 54 years who do not take HRT, approximately 2 in 2,000 women will be diagnosed with ovarian cancer within 5 years. Risk of venous thromboembolism HRT is associated with a 1.3-3 times higher relative risk of developing venous thromboembolism, i.e. deep vein thrombosis and pulmonary embolism. These disorders most often can develop during the first year of using HRT (see section “Special instructions”). Risk of developing coronary heart disease In women over 60 years of age who take combined estrogen-progestogen HRT, the risk of developing coronary heart disease is slightly increased (see section "Special instructions"). Risk of ischemic stroke The relative risk of ischemic stroke increases 1.5 times in patients who use both estrogen monotherapy and combined estrogen-progestogen therapy. The risk of hemorrhagic stroke does not increase while using HRT. The relative risk does not depend on age or duration of use, but since the risk depends on age, the overall risk of stroke in women taking HRT increases with age (see section "Special instructions").

Storage conditions

Store at a temperature not exceeding 25 °C. Keep out of the reach of children!

Buy Divigel gel d/nar.prim.0.1% in sachet 1g in pack No. 28 in the pharmacy

Price for Divigel gel d/nar. approx. 0.1% in sachet 1g in pack No. 28

Instructions for use for Divigel gel d/nar.prim.0.1% in sachet 1g in pack No. 28