Ovestin vaginal suppositories 0.5 mg 15 pcs

Ovestin vaginal suppositories 0.5 mg 15 pcs

HRT for the treatment of symptoms of estrogen deficiency should be carried out only for symptoms that adversely affect the woman’s quality of life. At least once a year, a thorough assessment of the benefit-risk ratio should be carried out; continuation of therapy is justified only if the benefit of using the drug exceeds the risk. There is limited evidence of the risks associated with HRT in the treatment of premature menopause. Due to the low absolute risk in young women, the benefit-risk ratio is more favorable for them than for older women. Medical examination/observation: Before starting or resuming HRT after its interruption, it is necessary to collect a detailed individual and family history, conduct a general and gynecological examination (including examination of the mammary glands and pelvic organs). During the therapy period, it is recommended to conduct periodic medical examinations, the frequency and nature of which are determined individually. Women should be informed about the need to tell their doctor about possible changes in the mammary glands. Screenings, including appropriate imaging modalities such as mammography, should be performed according to currently accepted screening standards and on a case-by-case basis.

Reasons for immediate discontinuation of therapy: Therapy should be stopped immediately if contraindications are identified and if the following conditions occur: • jaundice or deterioration of liver function; • significant increase in blood pressure; • the occurrence of migraine-type headaches; • pregnancy.

Hyperplasia and endometrial cancer: In women with an intact uterus, long-term systemic estrogen monotherapy increases the risk of endometrial hyperplasia and cancer.

Indicators of systemic exposure to estriol contained in the drug Ovestin® (vaginal suppositories), when dosed twice a week, remain close to the normal range for the postmenopausal period. The addition of progestogen to treatment is not recommended.

The safety for the endometrium of long-term (more than 1 year) or repeated use of estrogens involving intravaginal administration has not been definitively established. Therefore, when repeating treatment, it is necessary to evaluate its effectiveness at least once a year.

Uncontrolled stimulation of estrogen can lead to precancerous or malignant transformation of residual endometriosis lesions. Therefore, caution is advised when using this drug in women who have had a hysterectomy for endometriosis, especially if they have residual endometriosis.

If bleeding or spotting occurs at any time during treatment, it is necessary to establish their cause. This may include an endometrial biopsy to rule out any endometrial malignancy.

To prevent stimulation of the endometrium, the daily dose of Ovestin® should not exceed 1 dose (0.5 mg estriol once a day). This maximum dose should not be used for more than 4 weeks.

One epidemiological study found that long-term treatment with low-dose oral estriol, as opposed to intravaginal estriol, may increase the risk of endometrial cancer. This risk increased with the duration of treatment and disappeared within one year after discontinuation of therapy. The increased risk concerned mainly less invasive and high-grade tumors.

Breast cancer (BC): Epidemiological data from a large meta-analysis indicate that there is no additional risk of developing breast cancer in women without a history of breast cancer when low-dose estrogen is administered intravaginally. There is no information about whether intravaginal use of low doses of estrogens provokes recurrence of breast cancer. HRT, especially combination therapy with estrogens and progestogens, leads to increased breast density on mammography, which may have a negative impact on radiological diagnosis of breast cancer. The results of clinical studies show that the likelihood of an increase in mammographic density in patients receiving estriol therapy was lower than in patients receiving other types of estrogens. Randomized placebo-controlled trials, including the Women's Health Initiative (WHI) study, have shown an increased risk of breast cancer in women receiving combined estrogen + progestogen HRT, which occurs after approximately 3 years of therapy.

Estrogen monotherapy: The WHI study did not find an increased risk of breast cancer in women with hysterectomies receiving estrogen-only HRT. Observational studies report a slight increase in the risk of diagnosing breast cancer, but it is significantly lower than in women using combined HRT.

Ovarian cancer: Ovarian cancer develops much less frequently than breast cancer. Long-term estrogen monotherapy (at least 5–10 years) was associated with a small increase in the risk of ovarian cancer. The results of some studies suggest that HRT with combination drugs has a similar or slightly lower risk. It is not known whether the risk of long-term use of low-potency estrogens (such as estriol) is different from that of monotherapy with other estrogens.

VTE: Systemic HRT is associated with a 1.3- to 3-fold increase in the risk of developing VTE (deep vein thrombosis or pulmonary embolism). The likelihood of developing VTE is higher during the first year of HRT use than at a later date. In patients with a confirmed thrombophilic condition, the risk of VTE is high, and HRT may further increase this risk, and therefore HRT is contraindicated in such women. Generally recognized risk factors for VTE include estrogen use, older age, major surgery, prolonged immobilization, obesity (BMI > 30 kg/m2), pregnancy/puerperium, systemic lupus erythematosus and cancer. There is no consensus regarding the possible role of varicose veins in the development of VTE. After any surgical intervention, VTE prophylaxis is necessary. In case of prolonged immobilization due to planned surgery, HRT should be temporarily discontinued 4-6 weeks before surgery and resumed only after the woman has regained full mobility. In the absence of a woman's history of VTE, but in the presence of thrombosis at the age of less than 50 years in close relatives, it is recommended to conduct a screening examination, having previously discussed all its limitations (screening can only identify a number of thrombophilic disorders). If a disorder is detected that does not correspond to the disease in relatives, or if a “severe” defect is detected (for example, deficiency of antithrombin III, protein S or protein C, or a combination of these defects), HRT with estriol is contraindicated. For women receiving long-term anticoagulant treatment, careful consideration of the benefit-risk profile of HRT is required. If VTE develops, drug therapy should be discontinued immediately. A woman should be informed of the need to immediately consult a doctor if possible signs of thromboembolic complications appear (for example, swelling or tenderness along the vein of the lower extremity, sudden chest pain, shortness of breath, etc.).

Coronary artery disease (CHD): There is no evidence from randomized controlled clinical trials that combination HRT or estrogen monotherapy can prevent myocardial infarction in women with and without CAD.

Estrogen monotherapy: According to randomized controlled clinical trials in women with a history of hysterectomy, the risk of coronary artery disease is not increased with estrogen monotherapy. The absolute risk of coronary heart disease increases slightly with HRT with combined (estrogen + progestogen) drugs in patients over 60 years of age.

Ischemic stroke: Systemic HRT with combination drugs and estrogen monotherapy are associated with a 1.5-fold increase in the risk of ischemic stroke. The relative risk does not change with age or time after menopause. However, the baseline risk of stroke is highly dependent on age, and the overall risk of ischemic stroke with HRT increases with age. The risk of hemorrhagic stroke does not increase with HRT.

Concomitant use of drugs for the treatment of hepatitis C: Information about increased ALT levels in patients receiving combination therapy with ombitasvir/paritaprevir/ritonavir and dasabuvir with or without ribavirin and in combination with estrogen (see section "Interactions with other drugs").

Other states:

• Estrogens can cause fluid retention, so patients with impaired renal function or cardiovascular insufficiency should be closely monitored by a physician.

• Women with pre-existing hypertriglyceridemia during estrogen therapy or hormone replacement therapy should be closely monitored by a physician, as rare cases of significant increases in plasma triglyceride leading to pancreatitis have been reported during estrogen therapy in this type of setting.

• Estrogens increase the concentration of thyroxine-binding globulin (TBG), which leads to an increase in the total level of circulating thyroid hormones, as assessed by the concentration of protein-bound iodine (PBI), T4 concentration (by chromatography or radioimmunoassay), or T3 concentration (by radioimmunoassay) . The concentrations of free T4 and T3 do not change. There may be an increase in the levels of other binding proteins in the blood plasma, such as corticosteroid binding globulin (CBG), sex hormone binding globulin (SHBG), which leads to an increase in the concentration of circulating corticosteroids and sex hormones, respectively. The concentrations of free or biologically active forms of hormones remain unchanged. Possible increases in levels of other plasma proteins (angiotensinogen/renin substrate, alpha-1-antitrypsin, ceruloplasmin).

• Cognitive function does not improve with HRT. There is evidence of an increased risk of developing dementia in women when starting HRT with combination drugs or continuous estrogen monotherapy after 65 years.

• The use of estriol leads to a slight decrease in follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The effect of estriol on other endocrine laboratory test results is unknown.

• Constant breast tension or excessive secretion of cervical mucus are signs of too high a dose of estriol.

Effect on the ability to drive vehicles and machinery: The drug Ovestin® does not affect the ability to drive vehicles or engage in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Instructions for use OVESTIN® (OVESTIN)

To treat menopausal symptoms, HRT should only be started for symptoms that adversely affect quality of life. In all cases, it is necessary to conduct a thorough assessment of the risks and benefits of treatment at least once a year, and HRT should be continued only for a period of time until the benefits outweigh the risks.

Before starting or resuming HRT, a detailed individual and family history should be established. Based on the obtained medical history, contraindications and warnings for use, it is necessary to conduct a clinical examination (including examination of the pelvic organs and mammary glands). During treatment, it is recommended to conduct periodic medical examinations, the frequency and nature of which vary from person to person. Women should be informed about the need to report changes in the mammary glands to their doctor. Tests, including mammography, must be performed in accordance with currently accepted screening standards.

Therapy should be discontinued if a contraindication is identified and if the following conditions occur:

• jaundice or impaired liver function, significant increase in blood pressure, resumption of migraine-type headaches, pregnancy, endometrial hyperplasia.

When used intravaginally to prevent stimulation of the endometrium, the daily dose should not exceed 0.5 mg of estriol (1 application of cream or 1 suppository). This maximum dose should not be used for more than 4 weeks.

Breast cancer

Based on randomized, placebo-controlled, Women's Health Initiative (WHI) trials, and epidemiological studies including the Million Women Study (MWS), an increased risk of breast cancer was reported in women taking estrogens, estrogen-progestogen combinations, or tribolone. for HRT for several years. For all HRT, the increased risk becomes noticeable after several years of use and increases with duration of use, but returns to baseline levels a few (maximum 5) years after stopping treatment.

In the MWS study, the relative risk of mammary cancer with conjugated equine estrogens (CEE) or estradiol (E2) was higher when a progestogen was added, both cyclically and continuously, and regardless of the type of progestogen. There is no evidence of differences in risk between different routes of administration.

In the WHI study, a continuous combination of conjugated equine estrogen and medroxyprogesterone acetate (CEE + MPA) was associated with mammary tumors that were slightly larger and more likely to have local lymph node metastases compared with placebo.

It is unknown whether such a risk is associated with the use of Ovestin. A recent population-based case-control study of 3345 women with invasive breast cancer and 3454 controls showed that estriol use, unlike other estrogens, was not associated with an increased risk of breast cancer. Therefore, when deciding whether to use HRT, it is very important to carefully assess the risk of developing breast cancer and the benefits of therapy.

Venous thromboembolism (VTE)

HRT is associated with a higher relative risk of developing VTE - deep vein thrombosis or pulmonary embolism. One randomized controlled trial and epidemiological studies have found that the risk for women receiving HRT is 2-3 times higher than for non-users. It is unknown whether the use of Ovestin is associated with the same risk.

Commonly recognized risk factors for VTE include personal or family history, severe obesity (BMI >30 kg/m2) and systemic lupus erythematosus. There is no consensus regarding the possible role of varicose veins in the development of VTE.

Patients with a history of VTE or known thromboembolic conditions are at increased risk of VTE. HRT may increase this risk. In order to exclude a predisposition to blood clots, it is necessary to examine an individual and family history of thromboembolism or recurrent spontaneous miscarriage. Until a thorough assessment of thromboembolic factors has been carried out, the initiation of anticoagulant treatment or the use of HRT in such patients should be considered a contraindication. For women already receiving anticoagulant treatment, careful consideration of the benefit-risk balance of HRT is required.

The risk of VTE may increase with prolonged immobilization of the patient, extensive trauma, or a large volume of surgical intervention. After surgery, special attention should be paid to preventive measures to prevent VTE. In cases where prolonged immobilization is unavoidable after elective surgery (especially after abdominal surgery or orthopedic surgery on the lower extremities), if possible, temporary cessation of HRT should be considered 4-6 weeks before surgery. If the drug Ovestin is used for indications related to pre- and postoperative therapy, then it is necessary to provide preventive treatment to prevent thrombosis.

If VTE develops after starting treatment with Ovestin, treatment should be discontinued. Patients should be advised to seek immediate medical attention if they experience a symptom of a potential thromboembolism (eg, painful leg swelling, sudden chest pain, shortness of breath).

Cardiac ischemia

Randomized controlled trials have not confirmed the positive effect of continuous use of a combination of conjugated estrogens and medroxyprogesterone acetate on the state of the cardiovascular system. Two large clinical trials (WHI and HERS, i.e. Heart Study and Estrogen-Progestogen Replacement Therapy) showed a possible increase in the risk of cardiovascular disease during the first year of use and did not show an overall benefit. For other HRT drugs, only limited data are available from randomized controlled trials assessing effects on cardiovascular disease incidence or mortality in such patients. Therefore, it is not certain that these results also apply to other HRT drugs.

Stroke

It was found that there is an increased risk of ischemic stroke in healthy women during treatment with continuous use of a combination of conjugated estrogens and medroxyprogesterone acetate. It is unknown whether this risk applies to other HRT drugs, including Ovestin.

Ovarian cancer

Long-term (at least 5-10 years) use of estrogen-only HRT in women who have had uterine surgery has been associated with an increased risk of ovarian cancer in several epidemiological studies. There is no certainty that long-term use of combined HRT or low-potency estrogens (for example, Ovestin) is characterized by a different degree of risk than the use of drugs containing only estrogen.

Other states

Estrogens can cause fluid retention and therefore patients with impaired renal function and cardiovascular insufficiency should be closely monitored. Patients with end-stage chronic renal failure should be closely monitored as circulating levels of the active substances of Ovestin are expected to increase.

Estriol is a weak gonadotropin inhibitor and has no other significant effects on the endocrine system.

There has been no convincing evidence of improvement in cognitive function with HRT.

In case of vaginal infections, concomitant specific treatment is recommended.

Ovestin 2 mg 30 pcs. pills

pharmachologic effect

Estrogen drug.

Composition and release form Ovestin 2 mg 30 pcs. pills

Tablets - 1 tablet:

• Active ingredients: estriol - 2 mg;
• Excipients: colloidal silicon dioxide - 0.75 mg, potato starch - 10 mg, magnesium stearate - 0.5 mg, povidone - 1 mg, lactose monohydrate - up to 100 mg (about 87.75 mg), distilled water - qs (removed during the production process).

30 pcs. - blisters (1) - cardboard packs.

Description of the dosage form

Tablets are white, round, flat, 6 mm in diameter, with a bevel and a score, with the engraving “DG” above the score and the number “8” below the score, on one side of the tablet.

Directions for use and doses

The drug is administered orally. The daily dose should not exceed 8 mg. The daily dose should be taken in one dose.

The tablets are taken with water, preferably at the same time of day.

For atrophy of the lower genitourinary tract caused by estrogen deficiency, 4-8 mg/day is prescribed for the first 4 weeks, followed by a gradual dose reduction in accordance with symptoms until a maintenance dose of 1-2 mg/day is achieved. The lowest effective dose should be used. In the case of long-term treatment in women with an intact uterus, it is necessary to monitor the condition of the endometrium or additionally use progestogens in therapy.

For pre- and postoperative treatment during vaginal surgery in the postmenopausal period - 4-8 mg/day for 2 weeks before surgery, 1-2 mg/day for 2 weeks after surgery.

In the treatment of menopausal disorders (“hot flashes”, night sweats) - 4-8 mg for a week with a gradual reduction in dose. For maintenance therapy, the minimum effective dose should be used for the shortest period of time.

For infertility caused by a cervical factor, 1-2 mg/day is usually prescribed from the 6th to the 15th day of the menstrual cycle. However, in different patients the daily dose can vary from 1 mg to 8 mg. The dose should be increased every month until the optimal effect on the cervical mucosa is achieved.

Differential diagnosis in the case of a questionable cervical smear of the atrophic type - 2-4 mg/day 7 days before taking the next smear.

If a woman misses the next dose and the delay is no more than 12 hours, she must take the pill as soon as possible. If the delay is more than 12 hours, you should skip one dose and then take the drug at the usual time.

In women who have not previously received HRT or have taken HRT in a continuous combination regimen, treatment with Ovestin® can be started at any time. In women taking HRT on an intermittent basis, Ovestin® should be prescribed one week after completion of the cycle.

Pharmacodynamics

Ovestin® contains the natural female sex hormone estriol. In the period preceding menopause and postmenopause (natural or surgical), estriol is used to treat symptoms caused by estrogen deficiency. Estriol has a selective effect primarily on the cervix, vagina, vulva and is especially effective for the treatment of urogenital symptoms caused by estrogen deficiency. In cases of atrophy of the vaginal mucosa, estriol causes increased proliferation of the epithelium of the vagina and cervix, stimulates its blood supply, helps restore the epithelium, normal microflora and physiological vaginal environment, and affects the quality and quantity of cervical mucus. As a result, the resistance of epithelial cells to infection and inflammation increases.

Unlike other estrogens, estriol has a short-term effect because it is retained for a short time in the nuclei of endometrial cells, and endometrial proliferation should not be expected if the recommended dosage regimen is followed. In this regard, cyclic use of progestogens is not necessary; postmenopausal withdrawal bleeding does not occur.

Pharmacokinetics

Suction

After oral administration, estriol is quickly and almost completely absorbed from the gastrointestinal tract. Cmax of unconjugated estriol in plasma is achieved within 1 hour after administration.

Distribution

About 90% of estriol is bound to plasma albumin, and, unlike other estrogens, estriol has almost no binding to sex hormone binding globulin (SHBG).

Metabolism

The metabolism of estriol consists mainly of conjugation and deconjugation during the enterohepatic circulation.

Removal

Estriol, the end product of metabolism, is excreted mainly in the urine in conjugated form. Only a small portion (±2%) is excreted in the feces, mainly in the form of unconjugated estriol.

Indications for use Ovestin 2 mg 30 pcs. pills

• atrophy of the mucous membrane of the lower genitourinary tract due to estrogen deficiency, in particular to treat symptoms such as dyspareunia, vaginal dryness and itching, to prevent recurrent infections of the vagina and lower genitourinary tract; for the treatment of urinary disorders (for example, frequency, dysuria) and moderate urinary incontinence;
• pre- and postoperative treatment during vaginal surgery in the postmenopausal period;
• menopausal disorders such as hot flashes, night sweats;
• as an auxiliary diagnostic tool when obtaining an atrophic picture of a cervical smear;
• infertility caused by cervical factor.

Contraindications

• pregnancy;
• lactation period;
• hypersensitivity to the active and (or) excipients of the drug;
• known, known or suspected breast cancer;
• identified or suspected estrogen-dependent tumors (endometrial cancer);
• vaginal bleeding of unknown etiology;
• untreated endometrial hyperplasia;
• confirmed venous thromboembolism (deep vein thrombosis, pulmonary thromboembolism) within the last 2 years;
• a history of venous thromboembolism or thrombosis, if anticoagulant therapy is not carried out;
• confirmed thrombophilias (eg, protein C, protein S, or antithrombin deficiency;
• thrombosis (venous and arterial) and thromboembolism currently or in history (including deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke), cerebrovascular disorders; conditions preceding thrombosis (including transient ischemic attacks, angina) currently or in history;
• acute liver disease or a history of liver disease after which liver function tests have not returned to normal;
• porphyria;
• diabetes mellitus with diabetic angiopathy;
• sickle cell anemia;
• Dubin-Johnson syndrome;
• cerebrovascular accident;
• Rotor syndrome;
• rare hereditary diseases with galactose intolerance, lactase deficiency or glucose-galactose malabsorption.

Ovestin® should be used with caution (under close medical supervision) if any of the following diseases or conditions are present, or these diseases or conditions have previously been noted and/or worsened during previous pregnancies or previous hormonal treatment (as they may recur or worsen during treatment with Ovestin®):

• familial hyperlipoproteinemia;
• risk factors for thromboembolism;
• risk factors for estrogen-dependent tumors, for example, 1st degree of heredity for breast cancer;
• systemic lupus erythematosus;
• prolonged immobilization, serious surgical interventions;
• severe liver disease (for example, adenoma);
• history of gallbladder disease (especially cholelithiasis);
• hepatic porphyria;
• diabetes mellitus without diabetic angiopathy;
• severe itching or cholestatic jaundice (including a history of previous pregnancy);
• migraine or severe headache;
• pancreatitis;
• endometriosis;
• leiomyoma (uterine fibroids);
• history of endometrial hyperplasia;
• bronchial asthma;
• arterial hypertension;
• hypercalcemia caused by bone metastases of breast cancer;
• herpes during pregnancy;
• epilepsy;
• otosclerosis.

Application of Ovestin 2 mg 30 pcs. pills during pregnancy and breastfeeding

The drug is contraindicated for use during pregnancy and lactation (breastfeeding).

special instructions

To treat menopausal symptoms, HRT should only be prescribed for symptoms that adversely affect quality of life. In all cases, a thorough assessment of the risks and benefits of treatment should be carried out at least once a year and HRT should be continued only as long as the benefits outweigh the risks.

There is limited evidence of the risks of HRT when treating premature menopause. Due to the lower absolute risk in younger women, the benefit-risk ratio is more favorable in them than in older women.

Medical examination/observation

Before starting or resuming HRT, a detailed individual and family history should be obtained. Guided by the obtained medical history, contraindications and warnings for use, it is necessary to conduct a clinical examination, including examination of the pelvic organs and mammary glands. During treatment, it is recommended to conduct periodic medical examinations, the frequency and nature of which vary from person to person. Women should be informed about the need to report changes in the mammary glands to their doctor. Investigations, including appropriate imaging modalities such as mammography, should be performed in accordance with currently accepted screening standards and on a case-by-case basis.

Reasons for immediate discontinuation of therapy

Therapy should be discontinued if contraindications are identified and if the following conditions occur:

• jaundice or worsening liver function;
• significant increase in blood pressure;
• the occurrence of migraine-type headaches;
• pregnancy.

Endometrial hyperplasia and carcinoma

To prevent stimulation of the endometrium, the daily dose of the drug should not be divided into several doses and should not exceed 8 mg of estriol. In addition, one epidemiological study found that long-term use of low-dose estriol may increase the risk of endometrial cancer. The risk increases with the duration of treatment and returns to baseline values ​​one year after discontinuation of the drug. Basically, the risk of minimally invasive and well-differentiated tumors increases.

For women with an intact uterus, the following precautions are recommended:

• the entire daily dose must be taken at once;
• the patient should be informed of the need to contact the attending physician if vaginal bleeding begins (this symptom in all cases requires examination);
• with long-term treatment, the condition of the endometrium must be assessed at least once a year or progestogens must be prescribed for at least 12-14 days of each calendar month.

When deciding whether to control the condition of the endometrium or to prescribe progestogens, the increased risk of breast cancer with combined therapy with estrogens and progestogens should be taken into account. There is currently no evidence that estrogen monotherapy increases the risk of breast cancer.

Mammary cancer

Hormone replacement therapy may increase mammographic density. This can make radiological detection of breast cancer more difficult. Clinical studies have shown that the likelihood of developing increased mammographic density was lower in patients treated with estriol than in patients treated with other estrogens.

Composite evidence suggests an increased risk of breast cancer in women receiving combination therapy with estrogens and progestogens and possibly estrogen monotherapy.

In women receiving combination therapy with estrogens and progestogens for more than 5 years, a 2-fold increase in the risk of breast cancer was noted.

With estrogen monotherapy, any increase in risk is significantly lower than when combined with progestogens.

The level of risk depends on the duration of HRT.

It is not known whether Ovestin® poses the same risk. A recent population-based case-control study of 3345 women with invasive breast cancer and 3454 controls showed that estriol use, unlike other estrogens, was not associated with an increased risk of breast cancer. It is therefore important that the risk of developing breast cancer is discussed with the patient and weighed against the known benefits of HRT.

Ovarian cancer

Ovarian cancer develops much less frequently than breast cancer. Long-term estrogen monotherapy (at least 5–10 years) was associated with a small increase in the risk of ovarian cancer. Some studies suggest that combined HRT may increase the risk of ovarian cancer in a similar or small way. It is not known whether the risk of long-term use of low-potency estrogens (such as Ovestin®) differs from that of monotherapy with other estrogens.

Venous thromboembolism

HRT is associated with an increased risk of venous thromboembolism (VTE), i.e. deep vein thrombosis or pulmonary embolism, 1.3-3 times. VTE is more likely to occur during the first year of HRT use than later in life. A similar risk is not known for Ovestin®.

In patients with confirmed thrombophilia, the risk of VTE is high, and HRT may further increase this risk. In this regard, HRT is contraindicated for such women.

Commonly recognized risk factors for VTE include estrogen use, older age, major surgery, prolonged immobilization, obesity (BMI >30 kg/m2), pregnancy/puerperium, systemic lupus erythematosus, and cancer. There is no consensus regarding the possible role of varicose veins in the development of VTE. After any surgical intervention, VTE prophylaxis is necessary. If prolonged immobilization is associated with elective surgery, it is necessary to temporarily discontinue HRT 4-6 weeks before surgery. Treatment should be resumed after the woman begins to walk.

If Ovestin® is prescribed as pre- and postoperative treatment, the issue of thrombosis prophylaxis should be considered.

In the absence of a history of VTE, but in the presence of thrombosis at a young age in the patient’s closest relatives, she can be offered a screening examination, having previously discussed all its limitations (screening can only identify a number of thrombophilic disorders). If a thrombophilic defect is detected that does not correspond to the disease in relatives, or if a “severe” defect is detected (for example, deficiency of antithrombin, protein S or protein C, or a combination of these defects), HRT is contraindicated.

For women already receiving anticoagulant treatment, careful consideration of the benefit-risk balance of HRT is required.

If VTE develops after starting treatment with Ovestin®, then treatment with the drug must be discontinued. Patients should be informed to seek immediate medical attention if they experience possible signs of thromboembolism (eg, painful leg swelling, sudden chest pain, shortness of breath).

Coronary heart disease (CHD)

There are no results from randomized controlled trials that indicate that combination therapy with estrogens and progestogens and estrogen monotherapy can prevent the development of myocardial infarction in women with and without coronary artery disease.

Estrogen monotherapy:

• According to randomized controlled trials, the risk of coronary heart disease in women with a removed uterus does not increase with estrogen monotherapy.

The risk of coronary artery disease increases slightly with combined HRT with estrogens and progestogens in patients over 60 years of age.

Ischemic stroke

Combination therapy with estrogens and progestogens and monotherapy with estrogens are associated with a 1.5-fold increase in the risk of ischemic stroke. The relative risk does not change with age or time after menopause. However, the baseline risk of stroke is highly dependent on age, and the overall risk of stroke with HRT increases with age. The risk of hemorrhagic stroke does not increase with HRT.

Other states

Estrogens can cause fluid retention, so patients with impaired renal function and cardiovascular insufficiency should be closely monitored by a physician.

Estriol is a weak gonadotropin antagonist and has no other significant effects on the endocrine system.

Cognitive function does not improve with HRT. Evidence was obtained of an increased risk of developing dementia in women who began using combination therapy or monotherapy in a continuous regimen after 65 years.

Impact on the ability to drive vehicles and operate machinery

There was no effect of the drug Ovestin® on concentration and attention.

Overdose

Symptoms: nausea, vomiting and vaginal bleeding.

Treatment: symptomatic therapy.

Side effects Ovestin 2 mg 30 pcs. pills

According to monitoring safety studies, there are adverse reactions presented below.

From the digestive system: nausea.

From the side of water-electrolyte metabolism: fluid retention.

From the reproductive system: soreness and tension of the mammary glands; intermenstrual bloody spotting from the vagina; cervical hypersecretion.

Adverse reactions are usually transient and may also indicate an overdose of the drug.

Other adverse reactions have been reported during estrogen monotherapy or combination therapy with estrogens and progestogens.

From the reproductive system: estrogen-dependent benign and malignant tumors, incl. endometrial cancer.

From the digestive system: gallbladder diseases.

From the skin: chloasma, erythema multiforme, erythema nodosum, vascular purpura.

From the central nervous system: headache; dementia when starting continuous HRT after 65 years.

There is data on the development of the risk of breast cancer, ovarian cancer, the risk of venous thromboembolism, the risk of coronary artery disease, and the risk of ischemic stroke.

Drug interactions

There have been no cases of interaction between the drug Ovestin® and other drugs. At the same time, there is evidence of an increase in the pharmacological effect of GCS and lipid-lowering drugs when used together with estrogens. If necessary, the dose of GCS can be reduced.

The effects of male sex hormones, anticoagulants, antidepressants, diuretics, antihypertensive and hypoglycemic drugs may be weakened.

Barbiturates, antiepileptic drugs (carbamazepine, phenytoin), antiretroviral drugs nevirapine and efavirenz, herbal preparations containing St. John's wort (Hypericum Perforatum) increase the metabolism of steroid hormones. Ritonavir and nelfinavir exhibit inducing properties when used simultaneously with steroid hormones. From a clinical point of view, an increase in estrogen metabolism can lead to a decrease in the effectiveness of Ovestin® and a change in the nature of uterine bleeding.

Antibiotics (griseofulvin, ampicillin, rifampicin), drugs for general anesthesia, narcotic analgesics, anxiolytics, antiepileptic drugs, some antihypertensive drugs, ethanol reduce the effectiveness of estrogens.

Folic acid and thyroid hormone preparations enhance the effect of estriol.

Estriol can change the effectiveness of oral anticoagulants and increase the pharmacological effect of succinylcholine, theophylline, foleandomycin.

Ovestin®

— To treat menopausal symptoms, HRT should only be started for symptoms that adversely affect quality of life. In all cases, a thorough assessment of the risks and benefits of treatment should be carried out at least once a year and HRT should be continued only as long as the benefits outweigh the risks.

— There is limited evidence of the risk of HRT when treating premature menopause. Because younger women have a lower absolute risk, their benefit-risk ratio is more favorable than that of older women.

Medical examination/observation

— Before starting or resuming HRT, it is necessary to obtain a detailed individual and family history. Guided by the obtained medical history, contraindications and warnings for the use of the drug, it is necessary to conduct a clinical examination, including examination of the pelvic organs and mammary glands. During treatment, it is recommended to conduct periodic medical examinations, the frequency and nature of which vary from person to person, but at least once a year. Women should be informed about the need to tell their doctor about changes in the mammary glands (see section “Breast cancer” below). Investigations, including appropriate imaging modalities such as mammography, should be performed in accordance with currently accepted screening standards and on a case-by-case basis.

Reasons for immediate discontinuation of therapy

Therapy should be discontinued if a contraindication is identified and if the following conditions occur:

- Jaundice or deterioration of liver function;

- Significant increase in blood pressure;

— The occurrence of migraine-type headaches;

- Pregnancy.

Endometrial hyperplasia and carcinoma

— To prevent stimulation of the endometrium, the daily dose of the drug should not exceed 1 application (0.5 mg estriol). This maximum dose should not be used for more than 4 weeks. In addition, one epidemiological study found that long-term use of low-dose estriol, administered orally but not intravaginally, may increase the risk of endometrial cancer. The risk increases with the duration of treatment and returns to baseline values ​​one year after discontinuation of the drug. The risk of minimally invasive and well-differentiated tumors mainly increases. Vaginal bleeding in all cases requires examination. The patient should be informed of the need to contact the attending physician if vaginal bleeding begins.

Mammary cancer

— Hormone replacement therapy may increase mammographic density. This can make radiological detection of breast cancer more difficult. Clinical studies have shown that the likelihood of an increase in mammographic density is lower in women treated with estriol than in women treated with other estrogens.

— Pooled evidence suggests an increased risk of breast cancer in women receiving combination therapy with estrogens and progestogens and possibly estrogen monotherapy.

— In women receiving combination therapy with estrogens and progestogens for more than 5 years, there was a 2-fold increase in the risk of breast cancer.

— With estrogen monotherapy, the increase in risk is significantly lower than when combined with progestogens.

— The level of risk depends on the duration of HRT.

— A similar risk is not known for the drug Ovestin®. A recent population-based case-control study of 3345 women with invasive breast cancer and 3454 controls showed that estriol use, unlike other estrogens, was not associated with an increased risk of breast cancer. It is therefore important that the risk of developing breast cancer is discussed with the patient and weighed against the known benefits of HRT.

Ovarian cancer

— Ovarian cancer develops much less frequently than breast cancer. Long-term estrogen monotherapy (at least 5–10 years) was associated with a small increase in the risk of ovarian cancer. Some studies suggest that combined HRT may increase the risk of ovarian cancer in a similar or small way. It is not known whether the risk of long-term use of low-potency estrogens (such as Ovestin®) differs from that of monotherapy with other estrogens.

Venous thromboembolism

— HRT is associated with an increased risk of developing venous thromboembolism (VTE), i.e. deep vein thrombosis or pulmonary embolism, 1.3-3 times. The likelihood of developing VTE is higher during the first year of HRT use than at a later date. A similar risk is not known for Ovestin®.

— In patients with confirmed thrombophilia, the risk of VTE is high, and HRT may further increase it. In this regard, HRT is contraindicated for such women (see section “Contraindications”).

— Commonly recognized risk factors for VTE include estrogen use, older age, major surgery, prolonged immobilization, obesity (BMI >30 kg/m2), pregnancy/puerperium, systemic lupus erythematosus and cancer. There is no consensus regarding the possible role of varicose veins in the development of VTE. After any surgical intervention, VTE prophylaxis is necessary. If prolonged immobilization is associated with elective surgery, it is necessary to temporarily discontinue HRT 4-6 weeks before surgery. Treatment should be resumed after the woman begins to walk.

— For women already receiving anticoagulant treatment, careful consideration of the benefit-risk ratio of HRT is required.

— If the drug Ovestin® is prescribed as “pre- and postoperative treatment...”, the issue of preventing thrombosis should be considered.

— In the absence of a history of VTE, but in the presence of thrombosis at a young age in the patient’s closest relatives, she can be offered a screening examination, having previously discussed all its limitations (screening can only identify a number of thrombophilic disorders). If a thrombophilic defect is detected that does not correspond to the disease in relatives, or if a “severe” defect is detected (for example, deficiency of antithrombin, protein S or protein C, or a combination of these defects), HRT is contraindicated.

— If VTE develops after starting treatment with Ovestin®, then treatment should be stopped. Patients should be informed to seek immediate medical attention if they experience possible signs of thromboembolism (eg, painful leg swelling, sudden chest pain, shortness of breath).

Coronary heart disease (CHD)

— Randomized controlled trials did not provide results that would indicate that combination therapy with estrogens and progestogens and estrogen monotherapy can prevent the development of myocardial infarction in women with and without coronary artery disease.

Estrogen monotherapy

— According to randomized controlled trials in women with a removed uterus, the risk of coronary heart disease does not increase with estrogen monotherapy.

— The risk of coronary heart disease increases slightly with combined HRT with estrogens and progestogens in patients over 60 years of age.

Ischemic stroke

— Combination therapy with estrogens and progestogens and monotherapy with estrogens are associated with a 1.5-fold increase in the risk of ischemic stroke. The relative risk does not change with age or time after menopause. However, the baseline risk of stroke is highly dependent on age, and the overall risk of stroke with HRT increases with age. The risk of hemorrhagic stroke does not increase with HRT.

Other states

- Estrogens can cause fluid retention, and therefore patients with impaired renal function and cardiovascular insufficiency should be closely monitored.

— Estriol is a weak gonadotropin antagonist and does not have other significant effects on the endocrine system.

— Cognitive function does not improve with HRT. Evidence was obtained of an increased risk of developing dementia in women who began using combination therapy or monotherapy in a continuous regimen after 65 years.

The drug contains cetyl alcohol and stearic alcohol, which can cause local skin reactions (for example, contact dermatitis).