Ovestin, pills 2mg, 30pcs

Composition

Active ingredient:

estriol 2.0 mg;

Auxiliary substances:

colloidal silicon dioxide 0.75 mg,

potato starch 10.0 mg,

magnesium stearate 0.50 mg,

povidone 1.0 mg,

lactose monohydrate up to 100.0 mg (about 87.75 mg), distilled water q. s. *

* – removed during production.

Pharmacological action

Pharmacotherapeutic group: Estrogens.

ATX code: G03CA04

Pharmacological properties

Pharmacodynamics

Ovestin ® contains the natural female sex hormone estriol. During the pre-menopausal and postmenopausal periods (natural or surgical), estriol is used to treat symptoms caused by estrogen deficiency.

Estriol has a selective effect mainly 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 increases the proliferation of the vaginal and cervical epithelium, stimulates its blood supply, helps restore the epithelium, normal microflora and physiological pH of the 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, since it is briefly retained in the nuclei of endometrial cells and if the recommended dosage regimen is followed, endometrial proliferation should not be expected. In this regard, cyclic use of progestogens is not necessary, and postmenopausal withdrawal bleeding does not occur.

Pharmacokinetics

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

About 90% of estriol binds to plasma albumin, and unlike other estrogens, estriol almost does not bind to sex hormone binding globulin (SHBG). Estriol metabolism consists mainly of conjugation and deconjugation during the intestinal-hepatic circulation. Estriol, the end product of metabolism, is mainly excreted in the urine in conjugated form. Only a small part (~2%) is excreted in the faeces, mainly in the form of unconjugated estriol.

Indications

• Atrophy of the mucous membranes of the lower genitourinary tract due to estrogen deficiency, in particular for the treatment of symptoms such as dyspareunia, dryness and itching of the vagina, for the prevention of recurrent infections of the vagina and lower genitourinary tract; for the treatment of urinary disorders (for example, increased frequency, dysuria) and moderate urinary incontinence;
• Pre-and postoperative treatment of vaginal surgery in the postmenopausal period;
• Menopausal disorders, such as hot flashes and night sweats;
• As an auxiliary diagnostic tool for obtaining an atrophic picture of the cervical smear;
• Infertility caused by the cervical factor.

Contraindications

• identified or suspected estrogen-tumors (breast cancer, endometrial cancer);
• vaginal bleeding of unknown etiology;
• confirmed venous thromboembolism (deep vein thrombosis, pulmonary embolism) within the last 2 years;
• venous thromboembolism history of thrombosis or, if not possible anticoagulant therapy;
• diabetes with angiopathy;
• sickle cell anemia;
• syndrome Dubin-Johnson,
• Rotor syndrome;
• cerebrovascular disease;
• pregnancy;
• lactation (breastfeeding);
• hypersensitivity to the active and/or auxiliary substances of the drug.

Caution should be exercised when prescribing the drug for the following conditions: :

• family hyperlipoproteinemia;
• increased risk of thromboembolic complications;
• systemic lupus erythematosus;
• prolonged immobilization, major surgery;
• severe liver disease;
• gallbladder disease in history (especially cholelithiasis);
• hepatic porphyria,
• severe itching, or cholestatic jaundice (including in the anamnesis during pregnancy);
• pancreatitis;
• endometriosis;
• leiomyoma;
• bronchial asthma;
• hypertension;
• hypercalcemia due to bone metastases of breast cancer;
• herpes in pregnancy;
• epilepsy;
• otosclerosis.

Side effects

According to the monitoring of safety studies, there are the following adverse reactions: : From the digestive system: nausea. From the side of water-electrolyte metabolism: fluid retention. From the side of the reproductive system: – soreness and tension of the mammary glands;- intermenstrual bloody spotting from the vagina; – cervical hypersecretion. Side effects are usually transient and may also indicate an overdose of the drug. Other adverse reactions that have occurred with oestrogen monotherapy or combined oestrogen and progestogen therapy have been reported. : From the reproductive system: estrogen-dependent benign and malignant tumors, including endometrial cancer. From the digestive system: diseases of the gallbladder. From the skin: chloasma, erythema multiforme, erythema nodosum, vascular purpura. From the central nervous system: – headache; – dementia at the beginning of HRT in continuous mode after 65 years. There are data on the development of the risk of breast cancer, ovarian cancer, the risk of venous thromboembolism, the risk of coronary heart disease, and the risk of ischemic stroke.

Interaction

There were no cases of interaction of Ovestin® with other drugs. At the same time, there are data on the strengthening of the pharmacological effect of glucocorticosteroids, lipid-lowering agents when combined with estrogens. If necessary, the dose of glucocorticosteroids can be reduced. It is possible to weaken the effects of male sex hormone preparations, anticoagulants, antidepressants, diuretics, hypotensive and hypoglycemic drugs. Barbiturates, antiepileptic drugs (carbamazepine, phenytoin), anti-retroviral 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 concomitantly with steroid hormones. From a clinical point of view, an increase in estrogen metabolism can lead to a decrease in the effectiveness of Ovestin® 7 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 effects of estriol. Estriol can change the effectiveness of oral anticoagulants, increase the pharmacological effect of succinylcholine, theophylline, foleandomycin.

How to take, course of use and dosage

The drug is used internally. The daily oral dose should not exceed 8 mg. For atrophy of the lower genitourinary tract caused by estrogen deficiency: 4-8 mg per day for the first 4 weeks, followed by a gradual reduction in the dose in accordance with the symptoms until a maintenance dose of 1-2 mg per day is reached. 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 state of the endometrium or additionally use progestogens in therapy. Pre-and postoperative treatment for vaginal surgery in the postmenopausal period: 4-8 mg per day for 2 weeks before surgery,1-2 mg per day for 2 weeks after surgery. Treatment of menopausal disorders (hot flashes, night sweats): 4-8 mg for a week with a gradual dose reduction. For maintenance therapy, the minimum effective dose should be used for the least prolonged period of time. For infertility caused by a cervical factor: as a rule,1-2 mg is prescribed per day from the 6th to the 15th day of the menstrual cycle. However, in different patients, the daily dose may vary from 1 to 8 mg. The dose should be increased every month until the optimal effect on the cervical mucosa is achieved. Differential diagnosis in case of doubtful cervical smear of atrophic type: 2-4 mg per day for 7 days before taking the next smear. If a woman missed taking the next dose and the delay was no more than 12 hours, it is necessary to take it as soon as possible. If the delay is more than 12 hours, you should skip one appointment and continue to take the drug at the usual time. Tablets are taken with water, preferably at the same time of day every day. The daily dose should be taken in one dose. In women who have not previously received HRT or are taking HRT in a continuous combination regimen, treatment with Ovestin® can be started at any time. In women who have taken HRT intermittently, Ovestin® should be prescribed one week after the end of the cycle.

Overdose

Overdose causes nausea, vomiting, and vaginal bleeding. Treatment is symptomatic.

Special instructions

For the treatment of menopausal symptoms, HRT should only be initiated for symptoms that adversely affect the quality of life. In all cases, a thorough assessment of the risk and benefit of treatment should be carried out at least once a year, and HRT should only be continued for as long as the benefit outweighs the risk.

There is limited evidence for the development of HRT risk in the treatment of premature menopause. Because of the low absolute risk, younger women have a better benefit-risk ratio than older women.

Medical examination/follow-up

Before starting or resuming HRT, a detailed individual and family history should be collected. Based on the received 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 are individual. Women should be informed about the need to inform the doctor about changes in the mammary glands (see the section “Breast cancer” below). Studies, including appropriate imaging techniques such as mammography, should be conducted in accordance with currently accepted examination 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 a migraine-type headache.

Pregnancy.

Endometrial hyperplasia and carcinoma

To prevent endometrial stimulation, the daily dose of the drug should not exceed 1 suppository (0.5 mg of estriol). Do not use this maximum dose 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 as the duration of treatment increases and returns to baseline values one year after discontinuation of the drug. In general, the risk of minimally invasive and highly differentiated tumors increases. Vaginal bleeding in all cases requires examination. The patient should be informed about the need to contact the attending physician in case of vaginal bleeding.

Breast cancer

Hormone Replacement therapy (HRT) can increase mammographic density. This may complicate radiological detection of breast cancer. Clinical studies have shown that the likelihood of increased mammographic density is lower in women treated with estriol than in women treated with other estrogens.

Summary evidence suggests an increased risk of breast cancer in women receiving combined estrogen and progestogen therapy, and possibly estrogen monotherapy.

Women who received combined therapy with estrogens and progestogens for more than 5 years had a 2-fold increase in the risk of breast cancer.

The risk increase is significantly lower with oestrogen monotherapy 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. In a recent population-based case-control study involving 3345 women with invasive breast cancer and 3454 women in the control group, it was shown that the use of estriol, unlike other estrogens, was not associated with an increased risk of breast cancer. Therefore, it is important that the risk of breast cancer is discussed with the patient and correlated with the known benefits of HRT.

Ovarian cancer

Ovarian cancer develops significantly less frequently than breast cancer. Long-term oestrogen 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 way or slightly. It is not known whether the risk of long-term use of low-level estrogens (such as Ovestin®) differs from that of monotherapy with other estrogens.

Venous thromboembolism

HRT is associated with a 1.3 — to 3-fold increased risk of venous thromboembolism (VTE), i. e. deep vein thrombosis or pulmonary embolism. The probability of developing VTE is higher during the first year of HRT use than in later periods. It is not known whether Ovestin ® has the same risk.

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 the section “Contraindications”).

Commonly recognized risk factors for VTE include estrogen use, advanced age, extensive surgery, prolonged immobilization, obesity (BMI > 30 kg / m2), pregnancy/postpartum period, systemic lupus erythematosus, and cancer. There is no consensus on the possible role of varicose veins in the development of VTE. After any surgical intervention, it is necessary to carry out VTE prevention. If prolonged immobilization is associated with elective surgery, HRT should be temporarily discontinued 4-6 weeks before surgery. Treatment should be resumed after the woman starts walking.

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

If Ovestin® is prescribed as a “pre – and postoperative treatment… “, prevention of thrombosis should be considered.

In the absence of VTE in the anamnesis, but in the presence of thrombosis at a young age in the next of kin of the patient, she can be offered to conduct a screening examination, having previously discussed all its limitations (screening allows you to identify only 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, a 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 with the drug should be discontinued. Patients should be informed about the need to see a doctor immediately if they feel possible signs of thromboembolism (for example, painful swelling of the leg, sudden chest pain, shortness of breath).

Coronary heart disease (CHD)

In randomized controlled trials, there were no results that would indicate that combination therapy with estrogens and progestogens and monotherapy with estrogens can prevent the development of myocardial infarction in women with and without coronary heart disease.

Estrogen monotherapy:

According to randomized controlled trials, women with a removed uterus do not have an increased risk of coronary heart disease with oestrogen monotherapy.

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

Ischemic stroke

Combined 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 and with time after menopause. However, the initial risk of stroke is highly age-dependent, 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 carefully monitored.

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

Cognitive function does not improve with HRT. There is evidence of an increased risk of dementia in women who start using combination therapy or monotherapy on a continuous basis after 65 years.

Influence on the ability to drive a car and other mechanisms

No effect of Ovestin on concentration or attention was observed.

Form of production

Tablets

Storage conditions

At a temperature of 2 °C to 30 °C in a dry place protected from light. Keep out of reach of children.

Shelf life

3 years

Active ingredient

Estriol

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For postmenopausal women

Indications

Estrogen deficiency, Menopause