Ovestin, tablets 2 mg 30 pcs

Pharmacotherapeutic group: Estrogens.

ATC code: G03CA04

Pharmacological properties

Pharmacodynamics

Ovestin® contains the natural female sex hormone estriol. Pre-menopausal and post-menopausal (natural or surgical) estriol is used to treat symptoms caused by estrogen deficiency.

Estriol has a selective effect primarily on the cervix, vagina, and vulva and is particularly effective for the treatment of urogenital symptoms caused by estrogen deficiency.

In cases of vaginal mucosal atrophy estriol causes increase of proliferation of vaginal and cervical epithelium, stimulates its blood supply, promotes restoration of epithelium, normal microflora and physiological pH of the vaginal environment, influences 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, since it is retained in the nuclei of endometrial cells for a short time and endometrial proliferation should not be expected if the recommended dosing regimen is followed. Because of this, cyclic use of progestagens is not necessary, postmenopausal bleeding cancellation does not occur.

Pharmacokinetics

After oral administration, estriol is quickly and almost completely absorbed in the gastrointestinal tract. The maximum concentration of unconjugated estriol in plasma is reached within 1 hour after ingestion.

About 90% of estriol is bound to plasma albumin, and, unlike other estrogens, estriol almost does not bind to sex hormone-binding globulin (HSPG). The metabolism of estriol consists mainly of conjugation and deconjugation during the intestinal-hepatic circulation. Estriol, the end product of metabolism, is excreted mainly with the urine in conjugated form. Only a small portion (±2%) is excreted with the feces, mainly as unconjugated estriol.

Indications

Active ingredient

Composition

Active Substance:

estriol 2.0 mg;

Associates:

colloidal silica 0.75 mg,

Potato starch 10.0 mg,

magnesium stearate 0.50 mg,

povidone 1.0 mg,

lactose monohydrate up to100.0 mg (about 87.75 mg),distilled water q.s.*

* – removed during manufacture.

How to take, the dosage

Interaction

Special Instructions

For the treatment of menopausal symptoms, MHT should be started only for symptoms that adversely affect quality of life. In all cases, the risks and benefits of treatment should be carefully evaluated at least once a year and MHT should be continued only for as long as the benefits outweigh the risks.

There is limited evidence for the development of risk of MHT in the treatment of premature menopause. Because of the low absolute risk in younger women, the benefit-risk ratio is more favorable than in older women.

Medical Assessment/Surveillance

A detailed individual and family history should be taken before starting or restarting on ZGT. Guided by the medical history, contraindications, and warnings for use, a clinical examination (including pelvic and breast exams) should be performed.

Periodic medical examinations are recommended during treatment, the frequency and nature of which are individualized. Women should be informed to report changes in their breasts to their physician (see “Breast Cancer” subsection below). Investigations, including appropriate imaging techniques such as mammography, should be performed according to currently accepted standards of examination and on a case-by-case basis.

Reasons for immediate discontinuation of therapy

The therapy should be discontinued if a contraindication is found and if the following conditions occur:

Jaundice or worsening of liver function.

Significant increase in blood pressure.

The occurrence of migraine-type headaches.

Pregnancy.

Endometrial hyperplasia and carcinoma

The daily dose of the drug should not exceed 1 suppository (0.5 mg estriol) to prevent endometrial stimulation. This maximum dose should not be used for more than 4 weeks. In addition, one epidemiologic study found that prolonged use of low-dose estriol administered orally but not intravaginally may increase the risk of endometrial cancer. The risk increases as the duration of treatment increases and returns to baseline values one year after discontinuation of the drug. Mostly, the risk of minimally invasive and highly differentiated tumors is increased. Vaginal bleeding in all cases requires evaluation. The patient should be informed to contact the attending physician if vaginal bleeding begins.

Breast cancer

Hormone replacement therapy (HRT) can increase mammographic density. This can make radiological detection of breast cancer more difficult. Clinical studies have shown that women treated with estriol are less likely to have increased mammographic density than women treated with other estrogens.

Generalized evidence suggests an increased risk of breast cancer in women receiving combined estrogen and progestagen therapy and possibly estrogen monotherapy.

In women receiving combined estrogen and progestagen therapy for more than 5 years, a 2-fold increase in breast cancer risk has been noted.

The increase in risk is significantly lower with estrogen monotherapy than with their combination with progestagens.

The level of risk depends on the duration of MHT.

It is not known whether Ovestin® poses the same risk. A recent population-based case-control study involving 3,345 women with invasive breast cancer and 3,454 women in a control group showed that estriol use, unlike other estrogens, was not associated with an increased risk of developing breast cancer. Therefore, it is important that the risk of developing breast cancer be discussed with the patient and correlated with the known benefits of MHT.

Ovarian cancer

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

Venous thromboembolism

MST is associated with a 1.3 to 3-fold increased risk of venous thromboembolism (VTE), that is, deep vein thrombosis or pulmonary embolism. The likelihood of VTE is higher during the first year of MST than at a later date. It is not known whether Ovestin® has the same risk.

Patients with confirmed thrombophilia have a high risk of VTE, and MST may further increase this risk. Because of this, MHT is contraindicated for these women (see Contraindications).

In general, estrogen intake, advanced age, major surgery, prolonged immobilization, obesity (BMI > 30 kg/m2), pregnancy/postpartum, systemic lupus erythematosus, and cancer are recognized risk factors for VTE. There is no consensus on the possible role of varicose veins in the development of VTE. VTE prophylaxis should be performed after any surgical intervention. If prolonged immobilization is associated with elective surgery, it is necessary to temporarily discontinue DHT 4-6 weeks prior to surgery. Treatment should be resumed after the woman begins to walk.

For women who are already receiving anticoagulant treatment, careful consideration of the benefit-risk ratio of ZGT is required.

If Ovestin® is prescribed as a “pre- and post-operative treatment…”, thrombosis prevention should be considered.

If there is no history of VTE, but if the patient’s immediate family has thrombosis at a young age, she may be offered a screening examination, discussing any limitations beforehand (screening can only identify a number of thrombophiliac disorders). If a thrombophilic defect is detected that does not match the disease in the relatives, or if a “severe” defect (e.g., antithrombin, protein S or protein C deficiency, or a combination of these defects) is detected, PHT is contraindicated.

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

Ischemic Heart Disease (CHD)

There are no results from randomized controlled trials suggesting that combined estrogen and progestogen therapy and estrogen monotherapy can prevent the development of myocardial infarction in women with and without CHD.

Estrogen monotherapy:

The risk of CHD does not increase with estrogen monotherapy in women with a removed uterus, according to randomized controlled trials.

The risk of coronary heart disease increases slightly with combined estrogen and progestagen ZGT in patients over age 60.

Ischemic stroke

Combined estrogen and progestogen therapy 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 and with time after menopause. However, the baseline risk of stroke is highly dependent on age, and the overall risk of stroke on MHT increases with age. The risk of hemorrhagic stroke does not increase with MHT.

Other conditions

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

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

Cognitive function is not improved on MHT. There is evidence of an increased risk of dementia in women who start combination therapy or continuous monotherapy after age 65.

Influence on ability to drive or operate machinery

There have been no effects of Ovestin® on concentration and attention.

Contraindications

Side effects

Overdose

Similarities