How to use tablets, suppositories and Ovestin cream. The cost and analogues are cheaper. Ovestin: instructions for use of cream, suppositories and tablets

Photo of the drug

Latin name: Ovestin

ATX code: G03CA04

Active substance: Estriol

Analogs: Orniona, Estrocad, Estrovagin, Ovilol Clio, Elvagin

Manufacturer: Organon (Netherlands)

Description is valid on: 03.10.17

pharmachologic effect

Estrogen drug. An analogue of a natural female hormone. Replenishes estrogen deficiency in postmenopausal women and reduces postmenopausal symptoms. Most effective in the treatment of genitourinary disorders. With atrophy of the mucous membrane lower sections genitourinary tract estriol helps normalize the epithelium of the genitourinary tract and promotes recovery normal microflora and physiological pH in the vagina. Increases resistance epithelial cells genitourinary tract to infections and inflammation, reducing complaints such as pain during sexual intercourse, dryness, itching in the vagina, reduces the likelihood of vaginal infections and infections urinary tract, helps normalize urination, prevents urinary incontinence.

Unlike other estrogens, estriol has a short period of action, since it is retained in the nuclei of endometrial cells for a short period of time. It is assumed that a single daily dose does not cause endometrial proliferation. Therefore, cyclic administration of progestogen is not required and withdrawal bleeding does not occur. In addition, estriol has not been shown to increase mammographic density.

Pharmacokinetics

Suction

When the drug is used orally or topically, estriol is quickly and almost completely absorbed.

Cmax of estriol in plasma is achieved 1-2 hours after intravaginal use.

Distribution

In plasma, almost all (90%) estriol is associated with albumin and, unlike other estrogens, is practically not associated with sex hormone binding globulin (SHBG).

Removal

Excretion of estriol (in bound form) is carried out mainly by the kidneys; about 2% is excreted unchanged through the intestines. Excretion of metabolites in the urine begins within a few hours after administration of the drug and continues for 18 hours.

Indications

- replacement hormone therapy(HRT) for the treatment of atrophy of the mucous membrane of the lower genitourinary tract associated with estrogen deficiency;

— pre- and postoperative treatment of postmenopausal women during operations using vaginal access;

- With diagnostic purpose with unclear results of a cytological examination of the cervix (suspicion of a tumor process) against the background of atrophic changes.

Dosage regimen

Suppositories should be inserted into the vagina at night before bed.

At treatment of atrophy of the mucous membrane of the lower genitourinary tract Prescribe 1 suppository/day for the first weeks, followed by a gradual reduction in dose, based on symptom relief, until a maintenance dose is reached (i.e., 1 suppository 2 times a week).

At pre- and postoperative therapy postmenopausal women undergoing surgical interventions via vaginal access prescribe 1 suppository/day for 2 weeks before surgery; 1 suppository 2 times a week for 2 weeks after surgery.

WITH diagnostic purpose for unclear results of cytological examination of the cervix Prescribe 1 suppository every other day for a week before taking the next smear.

If a dose is missed, the missed dose must be administered on the same day as soon as the patient remembers it (the dose should not be administered 2 times a day). Subsequent applications are carried out in accordance with the usual dosage regimen.

When initiating or continuing treatment for postmenopausal symptoms, use the least amount of effective dose for the shortest period of time.

In women not receiving HRT or women who are transitioning from continuous oral combination drug for HRT, treatment with Ovestin ® can be started on any day. Women who are switching from a cyclic regimen of HRT medications should begin treatment with Ovestin ® 1 week after stopping HRT medications.

Side effect

As with any other drug that is applied to the surface of the mucous membranes, Ovestin ® suppositories can sometimes cause local irritation or itching.

Sometimes There may be sensitivity, tension, soreness, and an increase in the size of the mammary glands. These undesirable reactions are usually short-lived and passing, but at the same time may indicate the use of too high a dose.

There are also acyclic bloody issues, breakthrough bleeding, metrorrhagia.

With HRT using estrogen-progestagen-containing drugs, the following were also observed: side effects, the connection of which with the use of Ovestin has not been proven:

- benign and malignant estrogen-dependent neoplasia (endometrial and mammary gland cancer);

- venous thromboembolism (deep vein thrombosis of the legs or pelvis, pulmonary embolism) occurs more often with the use of HRT than without therapy;

- myocardial infarction, stroke;

— cholelithiasis;

- skin and subcutaneous diseases(chloasma, erythema multiforme, erythema nodosum, hemorrhagic purpura);

- dementia;

- increased libido.

Contraindications for use

- established, known or suspected breast cancer;

- diagnosed or suspected estrogen-dependent tumors (for example, endometrial cancer);

- bleeding from the vagina unknown etiology;

- untreated endometrial hyperplasia;

- Availability venous thrombosis currently and in history;

- active or recent thromboembolic arterial disease (eg, angina, myocardial infarction);

- liver disease in the acute stage or a history of liver disease, after which liver function tests have not returned to normal;

- porphyria;

- installed increased sensitivity To active substance or to any of the excipients of the drug.

WITH caution

If any of the following conditions are present or the condition has previously been noted and/or worsened during previous pregnancies or previous hormonal treatment, then such a patient should be under the direct supervision of a physician. It must be taken into account that these conditions may recur or worsen during treatment with Ovestin ®, especially if:

- leiomyoma (uterine fibroids) or endometriosis;

— previous thromboembolic disorders or existing risk factors for such disorders;

- risk factors for estrogen-dependent tumors, for example, 1st degree of heredity for breast cancer;

— arterial hypertension;

— benign tumors liver (eg, liver adenoma);

— diabetes with the presence or absence of a vascular component;

- cholelithiasis;

- jaundice (including a history of jaundice during a previous pregnancy);

- liver failure;

- migraine or severe headache;

- systemic lupus erythematosus;

- history of endometrial hyperplasia;

- epilepsy;

- otosclerosis;

- familial hyperlipoproteinemia;

- pancreatitis.

Use during pregnancy and breastfeeding

Ovestin ® is contraindicated during pregnancy. If pregnancy occurs during therapy with Ovestin ® , treatment should be discontinued immediately.

The majority of epidemiological studies conducted to date regarding unintentional fetal exposure to estrogens indicate no teratogenic or fetotoxic effects.

Overdose

The acute toxicity of estriol in animals is very low. Overdose of the drug Ovestin ® with vaginal insertion unlikely. However, if hit large quantities the drug in the gastrointestinal tract may cause nausea, vomiting and cessation of bleeding in women.

Treatment: there is no specific antidote. If necessary, symptomatic treatment should be carried out.

Drug interactions

IN clinical practice There were no interactions observed between the drug Ovestin ® and other drugs.

The metabolism of estrogens may be enhanced when used in combination with compounds that induce enzymes involved in drug metabolism, in particular cytochrome P450 isoenzymes, such as anticonvulsants (phenobarbital, phenytoin, carbamazepine) and antimicrobial agents(rifampicin, rifabutin, nevirapine, efavirenz).

Ritonavir and nelfinavir exhibit inducing properties when used in combination with steroid hormones.

Herbal preparations containing St. John's wort (Hypericum perforatum) may induce estrogen metabolism.

Increased metabolism of estrogens may lead to a decrease in their clinical effect.

Estriol enhances the effect of lipid-lowering drugs.

Weakens the effects of male sex hormones, anticoagulants, antidepressants, diuretics, antihypertensives, hypoglycemic agents.

Means for general anesthesia, opioid analgesics, anxiolytics, some antihypertensive drugs, ethanol reduce the effectiveness of the drug.

Folic acid and thyroid medications enhance the effects of estriol.

Conditions for dispensing from pharmacies

The drug is approved for use as a means of OTC.

Storage conditions and periods

The drug should be stored in a dry place, protected from light and out of reach of children, at a temperature of 2° to 25°C. Shelf life - 3 years.

Use for liver dysfunction

The drug is contraindicated in patients with acute liver disease or a history of liver disease after which liver function tests have not returned to normal.

In case of liver failure, use the drug with caution.

Use for renal impairment

Estrogens can cause fluid retention, and therefore patients with impaired renal function should be closely monitored by a physician. IN terminal stage chronic renal failure it should be special control due to a possible increase in circulating levels active ingredients Ovestin.

special instructions

To treat postmenopausal 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. HRT should only be continued for a period of time when the benefit outweighs the risk.

Medical examination/observation

Before starting or resuming HRT, a detailed individual and family history should be established. Based on the medical history, contraindications and warnings for the use of the drug, it is necessary to 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 report changes in the mammary glands to their doctor. Tests, including mammography, must be performed in accordance with generally accepted screening standards.

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

- jaundice and/or deterioration of liver function;

- significant increase in blood pressure;

- resumption of migraine-type headaches;

- pregnancy.

Endometrial hyperplasia

To prevent endometrial stimulation daily dose should not exceed 1 suppository (500 mcg estriol). This should not be used maximum dose for more than 4 weeks.

Breast cancer

Based on the results of a randomized, placebo-controlled trial in the Initiative program women's health(WHI) and epidemiological studies including the Million Women Study (MWS), reported increased risk breast cancer in women who have taken estrogens, estrogen-progestogen-containing combinations, or tibolone 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 original level several (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, regardless of the type of progestogen. No confirmation was received of a change in the degree of risk when in various ways introduction.

In the WHI study, continuous use of a combination of conjugated equine estrogen and medroxyprogesterone acetate (CEE + MPA) was associated with the occurrence of cancerous tumors breasts, which were slightly larger in size and more often had metastases in local lymph nodes compared to placebo.

Regarding Ovestin similar risk not known. In a recent population-based case-control study of 3345 women with invasive cancer breast 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 developing breast cancer. In this regard, it is important that the patient is aware of the risk of developing breast cancer in relation to known benefits HRT.

Venous thromboembolism

HRT is associated with a higher relative risk of developing venous thromboembolism (VTE), i.e. deep vein thrombosis or pulmonary embolism. One randomized controlled trial and epidemiological studies found that the risk for women receiving HRT was 2-3 times higher than for patients not receiving such treatment. For women not using HRT, the incidence of VTE that is likely to occur over a 5-year period is estimated to be approximately 3 in every 1,000 women aged 50-59 years and 8 in every 1,000 women aged 60-69. years. U healthy women using HRT for 5 years, the number of additional cases of VTE over a 5-year period should be 2-6 cases (average 4) per 1000 women aged 50-59 years and 5-15 cases (average 9) per every 1000 women aged 60-69 years. VTE is more likely to occur during the first year of HRT than in later years. late dates. In relation to Ovestin, such a risk is unknown.

Generally accepted risk factors for VTE are a relevant individual or family history, high obesity (BMI>30 kg/m2) and SLE. There is no consensus on the role varicose veins 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, a careful individual and family history of thromboembolism or recurrent spontaneous miscarriage is necessary. Anticoagulant treatment or HRT should not be initiated until a thorough assessment of thromboembolic factors has been carried out. For women already receiving anticoagulant treatment, careful consideration of the benefit/risk 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 it is necessary to pay Special attention preventive measures to prevent VTE. In cases where prolonged immobilization is unavoidable after elective surgery, especially after abdominal surgery or orthopedic surgery lower limbs If possible, it is necessary to temporarily discontinue HRT 4-6 weeks before surgery. If Ovestin ® is used for the indication “pre- and postoperative treatment of postmenopausal women during operations with vaginal access,” it is necessary to provide preventive treatment to prevent thrombosis.

If VTE develops after starting treatment with Ovestin ®, then treatment with the drug must be stopped. 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).

Randomized controlled trials have not provided evidence of a positive effect of continuous use of a combination of conjugated estrogens and medroxyprogesterone acetate (MPA) on the condition of cardio-vascular system. Two large clinical trials, the WHI and the HERS (Heart and Estrogen-Progestin Replacement Therapy Study), confirmed the possibility possible increase risk of occurrence cardiovascular diseases during the first year of use and lack of overall benefit.

There are only limited data available for other HRT medications, so it is not certain that these results also apply to other HRT medications.

Stroke

A large randomized trial (WHI) found that an increased risk may be considered as a side effect ischemic stroke in healthy women during treatment with continuous use of a combination of conjugated estrogens and MPA. For women who do not use HRT, the number of strokes that may occur over a 5-year period is about 3 in every 1000 women aged 50-59 years and 11 in every 1000 women aged 60-69 years. It has been found that for women who use conjugated estrogens and MRAs for 5 years, the number of additional cases increases by 0-3 cases (average 1) for every 1000 patients aged 50-59 years and 1-9 cases (average 4 ) for every 1000 patients aged 60-69 years. It is unknown whether the increased risk also applies to other HRT drugs.

Ovarian cancer

Long-term (at least 5-10 years) estrogen monotherapy (as HRT) in women who have undergone uterine surgery is associated with increased risk development of ovarian cancer, which has been found in several epidemiological studies. It has not been proven that long-term combined HRT or monotherapy with low-active estrogens (for example, Ovestin ®) has any other risk.

Other states

Estrogens can cause fluid retention, and therefore patients with impaired renal function and cardiovascular failure must be under close medical supervision. In the terminal stage of chronic renal failure, there should be special monitoring due to a possible increase in the level of circulating active components of Ovestin.

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

There was no convincing evidence of improvement in cognitive function. The WHI trial provided evidence of an increased risk of possible dementia in women who started using a combination of conjugated estrogens and MPA continuously. continuous mode after 65 years. It is unknown whether these results apply to younger postmenopausal women using other HRT medications.

Ovestin drug contains the natural female hormone estriol, which is a hormone short acting, which means it does not stimulate proliferative processes in the endometrium. The drug promotes the regeneration of the epithelium of the vaginal mucosa, restoration of the pH environment and natural microflora of the vagina, all this increases local immunity and prevents the development of pathological flora.

Indications for use

Mode of application

Preparation for surgery with transvaginal access, women of menopausal age: 1 suppository daily, starting 2 weeks before surgery and one suppository 2 times a week, for 14 days after surgery. Tablets are used according to the following scheme: 4-8 mg 14 days before surgery and 1-2 mg 14 days in postoperative period. The cream is administered according to the same scheme: 14 days before surgery once a day, in the postoperative period - 2 times a week.

For pathological menopause: 4-8 mg, with a gradual reduction in dose as the condition improves.
For diagnosis, if the results of a vaginal smear for cytology are unclear: 1 suppository every other day for 1 week before taking the next smear. Cream, according to the same scheme as the candles.
For infertility associated with the cervical factor: 1–2 mg per day from the 6th to the 15th day of the menstrual cycle, sometimes the dose is increased to 8 mg per day.
If you miss the next dose of the drug, if the interval between doses is no more than 36 hours, you must take the missed dose and then continue taking the drug according to the regimen. If more than 36 hours have passed, you just need to continue taking the drug according to the regimen.

Side effects

Contraindications

Pregnancy

Interaction with other drugs

Overdose

Release form

Storage conditions

Compound

Ovestin candles:
Active substance: estriol - 0.5 mg
Additional substances: vitepsol S 58.

Cream Ovestin:
Active substance: estriol - 1 mg/g.
Additional substances: octyldodecanol, cetyl palmitate, glycerin, cetyl alcohol, stearyl alcohol, polysorbate, sorbitan stearate, lactic acid, chlorhexidine hydrochloride, sodium hydroxide, prepared water.

Additionally

Main settings

In this article you can read the instructions for using hormonal drugs Ovestin. Feedback from site visitors - consumers - is presented of this medicine, as well as the opinions of specialist doctors on the use of Ovestin in their practice. We kindly ask you to actively add your reviews about the drug: whether the medicine helped or did not help get rid of the disease, what complications and side effects were observed, perhaps not stated by the manufacturer in the annotation. Ovestin analogues in the presence of existing structural analogues. Use for the treatment of itching, infertility, hot flashes and other menopausal disorders in adults, children, as well as during pregnancy and lactation. Interaction of the drug with alcohol.

Ovestin- estrogen drug. Estriol (the active ingredient of the drug Ovestin) is a natural estrogen. 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, Ovestin 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, affects the quality and quantity 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 a short time is 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; postmenopausal withdrawal bleeding does not occur.

Compound

Estriol + excipients.

Pharmacokinetics

When the drug is used orally or topically, estriol is quickly and almost completely absorbed. Binding to plasma albumin is 90%. Excretion of estriol (in bound form) is carried out mainly by the kidneys; about 2% is excreted unchanged through the intestines.

Indications

• hormone replacement therapy (HRT) to treat atrophy of the mucous membrane of the lower genitourinary tract associated with 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 of postmenopausal women;
• climacteric disorders (hot flashes and night sweats);
• infertility caused by cervical factor;
• for diagnostic purposes in case of unclear results of a cytological examination of the cervix (suspicion of a tumor process) against the background of atrophic changes.

Release forms

Vaginal suppositories 0.5 mg.

Vaginal cream (sometimes mistakenly called ointment).

Tablets 2 mg.

Instructions for use and dosage

Candles

The suppositories should be inserted into the vagina at night before bedtime.

When treating atrophy of the mucous membrane of the lower genitourinary tract, 1 suppository per day is prescribed for the first weeks, followed by a gradual reduction in the dose, based on symptom relief, until a maintenance dose is reached (i.e., 1 suppository 2 times a week).

For pre- and postoperative therapy of postmenopausal women, during surgical interventions via vaginal access, 1 suppository per day is prescribed for 2 weeks before surgery; 1 suppository 2 times a week for 2 weeks after surgery.

For diagnostic purposes, if the results of a cytological examination of the cervix are unclear, 1 suppository is prescribed every other day for a week before taking the next smear.

If a dose is missed, the missed dose must be administered on the same day as soon as the patient remembers (the dose should not be administered 2 times a day). Subsequent applications are carried out in accordance with the usual dosage regimen.

When initiating or continuing treatment of postmenopausal symptoms, use the lowest effective dose for the shortest possible duration.

In women not receiving hormone replacement therapy (HRT), or women who are switching from continuous use of an oral combination drug for HRT, treatment with Ovestin can be started on any day. Women who are switching from a cyclic regimen of HRT should begin treatment with Ovestin 1 week after discontinuation of HRT.

Cream

The cream should be inserted into the vagina using a calibrated applicator at night (before going to bed).

1 application (applicator filled to the ring mark) contains 500 mg of cream, which corresponds to 500 mcg of estriol.

When treating atrophy of the mucous membrane of the lower genitourinary tract - 1 application per day for the first weeks (maximum 4 weeks), followed by a gradual reduction in dose, based on symptom relief, until a maintenance dose is reached (i.e. 1 application 2 times a week) .

For pre- and postoperative therapy of postmenopausal women, for surgical interventions via vaginal access - 1 application per day for 2 weeks before surgery; 1 application 2 times a week for 2 weeks after surgery.

For diagnostic purposes in case of unclear results of cytological examination of the cervix - 1 application every other day for a week before taking the next smear.

Instructions for use for patients

1. The cream is inserted into the vagina at night (before bedtime).

2. Remove the cap from the tube, turn the cap over and use a sharp rod to open the tube.

3. Screw the applicator onto the tube.

4. Squeeze the tube to fill the applicator with cream until the piston stops.

5. Unscrew the applicator from the tube and close the tube with the cap.

6. In a lying position, the end of the applicator is inserted deep into the vagina and slowly press the piston all the way, introducing the cream.

After administering the drug, remove the piston from the cylinder and wash the cylinder and piston warm water with soap. Detergents should not be used. After this, the cylinder and piston are rinsed generously with clean water.

Do not immerse the applicator in hot or boiling water.

Pills

The drug is administered orally. The daily dose should not exceed 8 mg.

For atrophy of the lower genitourinary tract caused by estrogen deficiency, 4-8 mg per day is prescribed for the first 4 weeks, followed by a gradual reduction in the dose in accordance with symptoms until a maintenance dose of 1-2 mg per day is achieved.

For pre- and postoperative treatment during 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.

In the 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 infertility caused by the cervical factor, as a rule, 1-2 mg per day is 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.

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.

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

The daily dose should be taken in 1 dose.

Side effect

• intermenstrual bloody spotting from the vagina;
• cervical hypersecretion;
• soreness and tension of the mammary glands;
• jaundice;
• nausea;
• skin rash;
• increased blood pressure;
• headache.

Contraindications

• identified or suspected estrogen-dependent tumors (breast cancer, endometrial cancer);
• vaginal bleeding of unknown etiology;
• 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;
• diabetes mellitus with angiopathy;
• sickle cell anemia;
• Dubin-Johnson syndrome;
• Rotor syndrome;
• cerebrovascular accident;
• pregnancy;
• lactation period (breastfeeding);
• hypersensitivity to the active and/or excipients of the drug.

The drug should be prescribed with caution in the following conditions:

• familial hyperlipoproteinemia;
• increased risk of thromboembolic complications;
• systemic lupus erythematosus;
• prolonged immobilization, serious surgical interventions;
• severe liver disease;
• history of gallbladder disease (especially cholelithiasis);
• hepatic porphyria;
• severe itching or cholestatic jaundice (including a history of previous pregnancy);
• pancreatitis;
• endometriosis;
• leiomyoma;
• bronchial asthma;
• arterial hypertension;
• hypercalcemia caused by bone metastases of breast cancer;
• herpes during pregnancy;
• epilepsy;
• otosclerosis.

Use during pregnancy and breastfeeding

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

special instructions

Before starting hormone replacement therapy, it is necessary to conduct a full medical examination.

During treatment, regular examinations (including breast examination, mammography) should be carried out every 6 months in accordance with accepted medical practice.

It is necessary to exclude a history of thromboembolism or repeated spontaneous abortions, which indicates thrombophilia. The risk of thromboembolism increases with prolonged immobilization, severe injuries and surgical interventions. In these cases, it is necessary to temporarily interrupt hormone replacement therapy (4-6 weeks before surgery)

The use of estriol does not lead to an increase in breast density. And it is possible that estriol use does not increase the risk of breast cancer.

Cases of venous thromboembolism (deep vein thrombosis of the leg, pelvic vein thrombosis and pulmonary thromboembolism) are observed more often in women receiving hormone replacement therapy.

Drug interactions

There have been no cases of interaction of the drug Ovestin with other drugs.

There is known data on the enhancement of the pharmacological effect of glucocorticosteroids (GCS), lipid-lowering drugs in joint use 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 and antiepileptic drugs (carbamazepine, phenytoin) increase the metabolism of steroid hormones.

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

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

Ovestin may alter the effectiveness of oral anticoagulants.

Estriol may increase pharmacological effect succinlycholine, theophylline, foleandomycin.

Analogues of the drug Ovestin

Structural analogues according to active substance:

• Ovipol Clio;
• Elvagin;
• Estriol;
• Estrovagin;
• Estrocad.

If there are no analogues of the drug for the active substance, you can follow the links below to the diseases for which the corresponding drug helps, and look at the available analogues for the therapeutic effect.

Estrogen drug

Active substance

Estriol

Release form, composition and packaging

◊ Vaginal cream in the form of a homogeneous mass of creamy consistency from white to almost white, with a specific smell.

Excipients: octyldodecanol - 50 mg, cetyl palmitate - 15 mg, glycerol - 120 mg, cetyl alcohol - 36.7 mg, stearyl alcohol - 88.4 mg, polysorbate 60 - 32.4 mg, sorbitan stearate - 7.6 mg, lactic acid - 4 mg, dihydrochloride - 0.1 mg, sodium hydroxide - up to pH 4, purified water - up to 1000 mg.

15 g - aluminum tubes (1) complete with applicator - cardboard packs.

pharmachologic effect

The drug Ovestin contains estriol, an analogue of the natural female hormone. It replenishes estrogen deficiency in postmenopausal women and reduces postmenopausal symptoms. Estriol is most effective in the treatment of genitourinary disorders. In case of atrophy of the mucous membrane of the lower parts of the genitourinary tract, estriol helps to normalize the epithelium of the genitourinary tract and helps restore normal microflora and physiological pH in the vagina. As a result, it increases the resistance of epithelial cells of the genitourinary tract to infection and inflammation, reducing complaints such as pain during sexual intercourse, dryness, itching in the vagina, reduces the likelihood of vaginal infections and urinary tract infections, helps normalize urination and prevents urinary incontinence.

Unlike other estrogens, estriol has a short period of action, since it is retained in the nuclei of endometrial cells for a short period of time. It is assumed that a single daily dose does not cause endometrial proliferation. Therefore, cyclic administration of progestogen is not required and withdrawal bleeding does not occur. In addition, estriol has not been shown to increase mammographic density.

Pharmacokinetics

Suction

Intravaginal administration of estriol ensures optimal bioavailability at the site of action. Estriol is also absorbed and enters the general bloodstream, which is manifested by a rapid increase in the concentration of unbound estriol in. Cmax in plasma is observed 1-2 hours after administration.

After vaginal administration of 0.5 mg estriol, the maximum concentration C max is approximately 100 pg/ml, the minimum concentration C min is approximately 25 pg/ml, and the average concentration C av is approximately 70 pg/ml. After 3 weeks of daily application of 0.5 mg vaginal estriol, the C av value decreased to 40 pg/ml.

Distribution

In plasma, almost all (90%) estriol is associated with and, unlike other estrogens, practically not associated with sex hormone-binding globulin.

Metabolism and excretion

The metabolism of estriol consists mainly of the transition to a conjugated and unconjugated state during the enterohepatic circulation.

Estriol, being the end product of metabolism, is mainly excreted in the urine in bound form. Only a small portion (±2%) is excreted in the feces, mainly as unbound estriol. T 1/2 is approximately 6-9 hours.

Indications

— hormone replacement therapy (HRT) for the treatment of atrophy of the mucous membrane of the lower genitourinary tract associated with estrogen deficiency in postmenopausal women;

— pre- and postoperative treatment of postmenopausal women during surgical interventions via vaginal access;

- How aid diagnosis upon receipt of an atrophic picture of a cervical smear.

Contraindications

- established, known or suspected breast cancer;

- diagnosed or suspected estrogen-dependent tumors (for example, endometrial cancer);

- bleeding from the vagina of unknown etiology;

- untreated endometrial hyperplasia;

- presence of venous thrombosis currently and in history (deep vein thrombosis, pulmonary thromboembolism);

- confirmed thrombophilias (for example, deficiency of protein C, protein S or antithrombin (see section "Special instructions"));

- thrombosis (venous and arterial) and thromboembolism currently or in history (including deep vein thrombosis, thromboembolism pulmonary artery, myocardial infarction, stroke), cerebrovascular disorders; conditions preceding thrombosis (including transient ischemic attacks, angina) currently or in history;

- liver disease in the acute stage or a history of liver disease, after which liver function tests have not returned to normal;

- porphyria;

- established hypersensitivity to the active substance or to any of the excipients of the drug.

Carefully

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):

Leiomyoma (uterine fibroids) or endometriosis;

Risk factors for thromboembolism (see section "Special instructions");

Risk factors for estrogen-dependent tumors, for example, 1st degree of heredity for breast cancer;

Arterial hypertension;

Benign liver tumors (for example, liver adenoma);

Diabetes mellitus with or without diabetic angiopathy;

Cholelithiasis;

Jaundice (including a history during a previous pregnancy);

Liver failure;

Migraine or (severe) headache;

Systemic lupus erythematosus;

History of endometrial hyperplasia (see section "Special instructions");

Epilepsy;

Bronchial asthma;

Otosclerosis;

Familial hyperlipoproteinemia;

Pancreatitis.

Dosage

Ovestin cream should be inserted into the vagina using a calibrated applicator at night before bed.

1 application (applicator filled to the ring mark) contains 0.5 g of cream, which corresponds to 0.5 mg of estriol.

At treatment of atrophy of the mucous membrane of the lower parts of the genitourinary tract - 1 application/day for the first weeks (maximum 4 weeks), followed by a gradual dose reduction based on symptom relief until a maintenance dose is reached (i.e. 1 application twice a week).

At pre- and postoperative therapy of postmenopausal women during surgical interventions via vaginal access- 1 application/day for 2 weeks before surgery; 1 application 2 times a week for 2 weeks after surgery.

WITH diagnostic purpose in case of unclear results of cytological examination of the cervix - 1 application every other day for a week before taking the next smear.

If a dose is missed, the missed dose must be administered on the same day as soon as the patient remembers it (the dose should not be administered 2 times a day). Subsequent applications are carried out in accordance with the usual dosage regimen.

When initiating or continuing treatment of menopausal symptoms, the lowest effective dose should be used for the shortest period of time.

In women not receiving HRT, or women who are switching from continuous use of an oral combination drug for HRT, treatment with Ovestin can be started on any day. Women who are switching from a cyclic regimen of HRT medications should begin treatment with Ovestin cream 1 week after stopping HRT medications.

Instructions for use for patients

1. The cream is inserted into the vagina at night before bed.

2. Remove the cap from the tube, turn the cap over and use a sharp rod to open the tube.

3. Screw the applicator onto the tube.

4. Squeeze the tube to fill the applicator with cream until the piston stops.

5. Unscrew the applicator from the tube and close the tube with the cap.

6. In the “lying down” position, the cream is injected, the end of the applicator is inserted deep into the vagina and slowly press the piston all the way, introducing the cream.

After administering the drug, remove the piston from the cylinder and wash the cylinder and piston with warm water and soap. Detergents should not be used. After this, the cylinder and piston are rinsed generously with clean water.

Do not immerse the applicator in hot or boiling water.

Side effects

As with any other drug that is applied to the surface of the mucous membranes, Ovestin cream can sometimes cause local irritation or itching.

Sometimes There may be sensitivity, tension, soreness, and an increase in the size of the mammary glands. These undesirable reactions are usually short-lived and passing, but at the same time may indicate the use of too high a dose.

Acyclic spotting, breakthrough bleeding, and metrorrhagia are also noted.

Others reported adverse reactions that arose during estrogen monotherapy or combination therapy with estrogens and progestogens.

From the liver and biliary tract: cholelithiasis.

Benign, malignant and unspecified neoplasms (including cysts and polyps): benign and malignant estrogen-dependent neoplasia, incl. endometrial cancer ( Additional information see sections "Contraindications" and "Special instructions").

Mental disorders: dementia when starting continuous HRT after 65 years (see section "Special instructions").

From the genital organs and breast: increased libido.

For the skin and subcutaneous tissues: chloasma, erythema multiforme, erythema nodosum, hemorrhagic purpura.

There is data on the development of the risk of breast cancer, ovarian cancer, the risk of venous thromboembolism, the risk of coronary heart disease, the risk of ischemic stroke ( detailed information presented in the "Special Instructions" section).

Overdose

The acute toxicity of estriol in animals is very low. An overdose of Ovestin when administered vaginally is unlikely. However, if large quantities of the drug enter the gastrointestinal tract, nausea, vomiting and cessation of bleeding in women may develop.

Treatment: there is no specific antidote. If necessary, symptomatic treatment should be carried out.

Drug interactions

In clinical practice, there has been no interaction between the drug Ovestin and other drugs.

The metabolism of estrogens may be enhanced when used in combination with compounds that induce enzymes involved in drug metabolism, particularly cytochrome P450 isoenzymes, such as anticonvulsants (e.g., phenytoin, carbamazepine) and antimicrobial agents (e.g., rifampicin, rifabutin, nevirapine, efavirenz).

Ritonavir and nelfinavir exhibit inducing properties when used in combination with steroid hormones.

Herbal preparations containing St. John's wort (Hypericum perforatum) may induce estrogen metabolism.

Increased metabolism of estrogens may lead to a decrease in their clinical effect.

Estriol enhances the effect of lipid-lowering drugs; weakens the effects of male sex hormones, antidepressants, diuretic, antihypertensive, hypoglycemic drugs.

Medicines for general anesthesia, narcotic analgesics, anxiolytics, some antihypertensives medicines, ethanol reduce the effectiveness of the drug.

And thyroid medications enhance the effects of estriol.

special instructions

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 development 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, a detailed individual and family history should be established. Based on the 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 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 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/or if the following conditions occur:

Jaundice and/or deterioration of liver function;

Significant increase in blood pressure;

Renewal of migraine-type headaches;

Pregnancy.

Endometrial hyperplasia and carcinoma

To prevent endometrial stimulation, 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 estriol in low doses, taken 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 researches showed that the likelihood of an increase in mammographic density is lower in women treated with estriol than in women 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, 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 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 unknown whether the risk differs between long-term use low-active estrogens (such as Ovestin) from those with 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. 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 this risk. In this regard, HRT is contraindicated for such women (see section “Contraindications”).

Commonly recognized risk factors for VTE are estrogen use, elderly age, major surgery, prolonged immobilization, obesity (BMI >30 kg/m2), pregnancy/postpartum period, 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 planned operation, 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 balance of HRT is required.

If the drug Ovestin is prescribed as a 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 in at a young age The patient's closest relatives can offer her 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, treatment should be discontinued. Patients should be informed of the need to immediately contact a doctor if they feel possible signs thromboembolism (eg, painful swelling of the leg, 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 in women with a removed uterus risk of ischemic heart disease 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 total risk The incidence of stroke during 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.

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.

The drug contains cetyl alcohol and stearyl alcohol, which can cause local skin reactions(eg contact dermatitis).

Impact on the ability to drive vehicles and operate machinery

The effect of the drug Ovestin on concentration and attention was not noted.

Pregnancy and lactation

The drug Ovestin is contraindicated during pregnancy. If pregnancy occurs during therapy with Ovestin, treatment should be discontinued immediately. The majority of epidemiological studies conducted to date regarding unintentional fetal exposure to estrogens indicate no teratogenic or fetotoxic effects.

For impaired renal function

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