Oestrogel, transdermal gel 600 mcg/g 80 g

The active ingredient of the drug EstroGel^® – 17β-estradiol is chemically and biologically identical to endogenous human estradiol.

It has estrogenic effects on the main target organs: ovaries, endometrium, vaginal epithelium, mammary glands, urethra, hypothalamus, pituitary gland, liver – similar to the effects of endogenous estrogens in the follicular phase of the menstrual cycle.

Maintains estrogen deficiency in women during menopause and reduces the severity of menopausal disorders including hot flashes, excessive sweating at night, atrophic changes in the urinary tract (atrophic vulvovaginitis, dyspareunia, urinary incontinence) and psycho-emotional disorders.

The clinical effectiveness of Estrogel^® in treating menopausal symptoms is comparable to that of oral estrogen.

Estradiol helps reduce total cholesterol concentrations without changing the cholesterol/HDL ratio.

It has a procoagulant effect, increases the synthesis in the liver of vitamin K-dependent clotting factors (II, VII, IX, X), reduces the concentration of antithrombin III.

Estradiol prevents loss of bone mass associated with natural menopause or ovariectomy.

Estrogen deficiency in postmenopause is associated with decreased bone mineral density (BMD). The effect of estrogen on BMDM is dose-dependent and appears to continue for as long as hormone replacement therapy (HRT) is in place. After discontinuation of HRT, BMSCs begin to decline at the same rate as they did before the start of HRT.

The data from the randomized, placebo-controlled Women’s Health Initiative (WHI) study and a meta-analysis of clinical trials showed that MHT with estrogen alone or estrogen in combination with gestagens in healthy postmenopausal women reduces the risk of hip, spine, and other osteoporotic fractures. There is also limited evidence that MHT can prevent bone fractures in women with low BMD and/or established osteoporosis.

Indications

Active ingredient

Composition

Associates:

carbomer (carbopol 980) – 5 mg,

trolamine (triethanolamine) – 5 mg,

ethanol – 400 mg,

purified water – qs. to 1 g.

Interaction

The use of Estrogel® together with surfactants (e.g. sodium lauryl sulfate) or other substances that change the skin structure or barrier function may reduce its effectiveness. Therefore, strong detergents and detergents (e.g., those containing benzalkonium or benzethonium chloride), skin care products with high ethanol content (astringents, sunscreens) and keratolytic agents (e.g., salicylic or lactic acid) should be avoided.

The use of any concomitant medications that have a damaging effect on the skin (e.g., cytotoxic) should be avoided.

The metabolism of estradiol is accelerated with concomitant use with inducers of microsomal liver enzymes, such as antiepileptic drugs (phenobarbital, phenytoin, carbamazepine); some antibiotics and antiviral drugs (rifampicin, rifabutin, nevirapine, efavirenz); herbal medicines containing St. John’s wort.

Ritonavir and nelfinavir, also known as strong inhibitors, in contrast show inducing properties when used together with sex hormones.

Transdermal use avoids the “first pass” effect through the liver, so that the effect of MHT drugs with transdermal estrogen application may be less dependent on the action of microsomal enzyme inducers in the liver than with oral use.

The metabolism of estradiol is accelerated with concomitant use with tranquilizers (anxiolytics), narcotic analgesics, anesthetics. Concentrations of estradiol in plasma are also decreased when concomitant use with some antibiotics (penicillins and tetracyclines).

The effects of estradiol are enhanced with folic acid and thyroid hormone drugs.

In clinical practice, increased estrogen metabolism can lead to a weakened effect and changes in the nature of uterine bleeding.

Estradiol increases the effectiveness of hypolipidemic agents.

Estradiol weakens the effect of male sex hormone drugs, hypoglycemic, diuretic, hypotensive drugs and anticoagulants.

Directions for use

Estrogel® is administered externally, continuously or cyclically. Doses and duration of therapy are determined individually.

The usual starting dose of the drug is 2.5 g of gel once daily, corresponding to 1.5 mg of estradiol. In most patients, this dose is effective in relieving menopausal symptoms. If after one month of therapy the efficacy is not achieved, it is possible to increase the daily dose of the drug to a maximum of 5 g of gel corresponding to 3 mg of estradiol.

To initiate and continue therapy for menopausal symptoms, the minimum effective dose should be used for the minimum period of time.

For the prevention of osteoporosis in postmenopausal women the minimum effective dose in most patients is 2.5 g of Estrogel® once daily.

When using the product in a tube a plastic applicator-dispenser is used to determine the daily dose: 1 dose of the applicator corresponds to 2.5 g of gel (which corresponds to 1.5 mg of estradiol).

When used in a bottle, one press of the pump dispenser releases 1.25 g of gel (corresponding to 0.75 mg of estradiol) equal to half of the daily dose. The average daily dose is 2.5 g of gel (2 pressings on the pump).

The use of Estrogel® without the addition of gestagen is possible only in patients with a remote uterus.

Patients with an intact (not removed) uterus are recommended to be treated with Estrogel® with gestagen.

In the menopausal transition, treatment should be given for at least 3 consecutive weeks, followed by a break of 1 week, while gestagen is given orally for the last 12-14 days of the month.

In perimenopause, treatment can be given from day 1 to day 25 of the month at the same time as oral gestagen. During the one-week break, menstrual-like bleeding may occur due to a decrease in sex hormones. It is recommended to use only those gestagens that are approved for use at the same time as estrogens.

In postmenopause, treatment with estrogens in combination with gestagens is a continuous regimen.

Long-term estrogen monotherapy is indicated in women after hysterectomy. In women who have had a hysterectomy, the addition of gestagens in the absence of a history of endometriosis is not recommended.

Depending on the clinical symptomatology, a dose adjustment is performed after 2-3 cycles of treatment:

In women who have not previously used ZGT drugs and in women switching to Estrogel® From a combination ZHT drug with a continuous regimen, treatment with Estrogel® may be started on any day convenient for the patient. For women switching to Estrogel® from a continuous sequential regimen of ZGT, treatment should be started after completion of the previous regimen.

If a patient forgets to apply the gel, this should be done as soon as possible, but no later than 12 hours after application. If more than 12 hours have elapsed, application of Estrogel® should be delayed until the next time. Intermittent use (missed doses) may result in breakthrough bleeding and oozing.

Term of Use

Patients apply the gel by themselves, morning or evening, in a thin layer to clean, dry skin on the abdomen, lumbar area, shoulders or forearms until completely absorbed. The area of application should be at least the area of 2 palms.

Do not massage the area where the gel is applied. Avoid contact of the gel with the mammary glands and the mucosa of the vulva and the vagina.

Application is considered correct and effective if the gel is absorbed completely within 2-3 minutes.

If the sticky consistency persists for more than 5 min after application, then too little of the skin surface has been covered.

The Estrogel® product does not leave any spots.

You should wash your hands immediately after applying the gel.

Application of the product in a tube. Open the tube and pierce the metal membrane of the tube with the small puncher located on top of the tube’s cap. The desired dose is removed from the tube using the applicator bar.

1 dose corresponds to a column of extracted gel with a diameter corresponding to the diameter of the tube outlet, the length of which coincides with the recess on the applicator ruler. The recess has a line that allows dividing the daily dose in half. One tube of gel will hold 30 doses.

Application of the product in the bottle. It is necessary to remove the cap from the bottle and press down hard on the pump-dispenser with the other hand to collect the gel. The amount released the first time you press it may not be accurate. It is recommended to discard it. The bottle is designed for 64 squeezes. After 64 squeezes, the amount of gel released by one squeeze may be less than you need. Because of this, we do not recommend using the bottle after 64 pushes of the pump.

Special Instructions

When treating postmenopausal symptoms, MHT should be started only when symptoms adversely affect quality of life are present. A detailed risk-benefit assessment should be performed at least once a year, and ZGT should only be prescribed if the benefits outweigh the risks.

The data regarding the risks associated with MHT for the treatment of premature menopause are limited. However, given the low absolute risk of MHT in young women, the benefit-risk ratio in these women may be more favorable than in older women.

A complete personal and family history should be taken before initiating or re-prescribing MHT. A medical examination should be conducted to identify possible contraindications and to take the necessary precautions when taking the drug (including pelvic and mammary gland examinations). In the course of treatment, periodic examinations are recommended. The frequency and methods included are determined on a case-by-case basis. Examinations, including mammography, should be performed according to accepted norms and adapted to the individual clinical needs of each individual case.

The benefits and risks of therapy should be carefully evaluated during a patient’s use of OST medications.

Conditions that require monitoring

If any of the following conditions are present, have previously occurred, and/or have been exacerbated during pregnancy or prior hormone therapy, the patient should be under continued medical supervision. Note that these conditions may, in rare cases, recur or worsen during treatment with Estrogel®, in particular:

Synopsis

Features

Absorption and Distribution

When the gel is applied topically over a large skin surface, triethanolamine vaporizes and approximately 10% of estradiol is absorbed through the skin into the vascular system, regardless of the patient’s age. Daily application of Estrogel® at a dose of 2.5 g or 5 g per 400-750 cm2 leads to a gradual increase in estradiol and estrone concentrations and provides their Css in plasma after about 3-5 days at a ratio typical of the beginning of the middle follicular phase of the menstrual cycle.

When Estrogel® was administered to 17 postmenopausal women once/daily by application to the back surface of one arm from wrist to shoulder for 14 days Cmaxsub>max of estradiol and estrone in plasma on day 12 of administration was 117 pg/mL and 128 pg/mL, respectively. The mean plasma estradiol and estrone concentrations over a 24-hour time interval after administration of Estrogel® at a dose of 2.5 g on day 12 of administration were 76.8 pg/mL and 95.7 pg/mL, respectively.

Metabolism and excretion

Estradiol is metabolized primarily in the liver to estriol, estrone, and their conjugated metabolites (glucuronides, sulfates). These metabolites undergo intrahepatic recirculation. After discontinuation of treatment, estradiol concentrations return to baseline after approximately 76 h.

Contraindications

With caution: the drug should be used in diseases and conditions such as: uterine myoma; endometriosis; a history of endometrial hyperplasia; presence of estrogen-dependent tumor risk factors (breast cancer in first-line relatives); presence of risk factors for thromboembolic disorders; arterial hypertension; liver diseases (includingAdenoma) with normal liver function tests; gallbladder disease (incl. cholelithiasis); diabetes with or without diabetic angiopathy; migraine or severe headache; systemic lupus erythematosus; epilepsy; bronchial asthma; otosclerosis, chronic heart failure; renal failure; CHD; sickle cell anemia; history of chloasma; history of hypertriglyceridemia; pancreatitis; hereditary angioedema.

There is limited experience with treatment in women over 65 years of age.

Side effects

Possible side effects of MHT are described below. The frequency of side effects is defined as follows: frequently (>1/100; < 1/10), infrequently (>1/1000; < 1/100), rarely (>1/10 000; < 1/1000).

In immune system disorders: rarely – anaphylactic reactions (in women with a history of allergic reactions).

Metabolism and nutrition: rarely – impaired glucose tolerance.

Mental disorders: infrequently – depression, mood swings; rarely – changes in libido.

Nervous system disorders: frequent – headache; infrequent – migraine, dizziness; rare – exacerbation of epilepsy.

Cardiovascular system: infrequent – venous thromboembolism; rarely – increased BP.

Gastrointestinal disorders:often – nausea, abdominal pain; infrequently – flatulence, vomiting.

Hepatic and biliary tract disorders: rarely – abnormal liver function tests.

Skin and subcutaneous tissue: infrequent – skin itching; rarely – skin discoloration, acne.

From the genitals and mammary gland: often – mammary gland edema, mammary gland pain, breast enlargement, dysmenorrhea, menorrhagia, metrorrhagia, leukorrhea, endometrial hyperplasia; infrequent – benign tumors of the breast, increased uterine size, uterine myoma, vaginitis, candidiasis vaginitis; rare – galactorrhea.

Others:often – changes in body weight (decrease or increase), fluid retention with peripheral edema; infrequently – asthenia.

Other adverse reactions, identified with estrogen-gestagen therapy:

Risk of breast cancer

Women who have used combined estrogen-gestogen drugs for more than 5 years have a 2-fold increased risk of being diagnosed with breast cancer. At carrying out mGT only with estrogens the risk of development of a breast cancer is considerably lower, than at carrying out mGT with combined oestrogens and gestagens. The magnitude of the risk of breast cancer depends on the duration of MHT.

Risk of endometrial cancer

In postmenopausal women with an intact uterus

The incidence of endometrial cancer is about 5 cases for every 1,000 women with an intact uterus who are not on ZGT.

In women with an intact uterus, estrogen-only MHT is not recommended because it increases the risk of developing endometrial cancer.

Depending on the duration of estrogen-only use and the dose, the increased risk of endometrial cancer in epidemiological studies ranged from 5 to 55 additional cases diagnosed in every 1,000 women aged 50 to 65 years.

The addition of gestagen for at least 12 days of the cycle to estrogen-only therapy may prevent this increased risk. The WHI study found no increased risk of endometrial cancer (RR 1.0 (0.8-1.2)) with combined estrogen-gestagen drugs for five years when ZHG (sequential or continuous) was given.

Ovarian cancer

Long-term estrogen-only and combined estrogen-gestagen MHT was associated with a small increase in risk of ovarian cancer. The WHI study found 1 additional case of ovarian cancer per 2,500 women while on MHT for five years.

Risk of venous thromboembolism

. Women who receive MHT have an increased risk of venous thromboembolism (VTE), particularly deep vein thrombosis or pulmonary embolism, compared with women who did not receive MHT by 1.3 to 3 times. The likelihood of VTE is higher in the first year of ZGT than in subsequent years.

Overdose

Symptoms of acute overdose have not been reported. Breast pain or excessive cervical secretion production may indicate an overdose of the drug.

Symptoms of estrogen overdose may include nausea and bleeding withdrawal.

Treatment:There is no specific antidote; the drug should be withdrawn and symptomatic therapy should be given.

Pregnancy use