OVESTIN (Suppozitorii)

Active material: Theelol
When ATH: G03CA04
CCF: Estrogen drugs
ICD-10 codes (testimony): N95.1, N95.3, Z03
When CSF: 15.11.01
Manufacturer: N.V. ORGAN (Netherlands)

DOSAGE FORM, STRUCTURE AND PACKAGING

◊ Vaginal Suppositories from white to pale cream color, torpedo-shaped, surface and uniform longitudinal section.

Excipients: vitepsol S58.

5 PC. – packings Valium planimetric (3) – packs cardboard.

Pharmacological action

Estrogen drugs. An analogue of the natural female hormone. It restores estrogen deficiency in post-menopausal women and reduces the symptoms of menopause. Most effective in the treatment of urogenital disorders. When mucosal atrophy of the lower urinary tract estriol departments contributes to the normalization of the epithelium of the urinary tract and helps to restore the normal microflora and the physiological pH in the vagina. Increases resistance of epithelial cells in the urinary tract infection and inflammation, reducing such complaints, as soreness during intercourse, dryness, itching of the vagina, It reduces the occurrence of vaginal infections, urinary tract infections, It helps to normalize urination, prevents urinary incontinence.

In contrast to other estrogens, Estriol has a short duration of action, as in the nuclei of endometrial cells it is held for a short time. Expected, that a single dose daily dose does not cause endometrial proliferation. Therefore, no cyclic administration of progestogen and withdrawal bleeding occurs. Besides, shows, that estriol does not increase mammographic density.

Pharmacokinetics

Absorption

In applying the drug inside, as well as local estriol is rapidly and almost completely absorbed.

FROM_max estriol plasma achieved through 1 hours after ingestion and after 1-2 h after intravaginal application. With Values_max Estriol plasma after vaginal application of the above, than after oral administration.

Distribution

Binding to albumin is of plasma 90%.

Deduction

Withdrawal of estriol (in bound form) carried out, mainly, kidney; about 2% displayed through the intestines in unchanged form. Excretion of metabolites in the urine begins a few hours after treatment and continues 18 no.

Testimony

- Zamestitelynaya gormonalynaya therapy (AFE) for the treatment of mucosal atrophy of the lower genital tract, associated with estrogen deficiency;

- Before- and post-operative treatment of women in post-menopausal vaginal access for operations;

- For diagnostic purposes in the uncertain outcome of cervical cytology (suspicion of neoplastic process) against the background of atrophic changes.

Dosage regimen

Cuppozitorii should be introduced into the vagina at night before going to bed.

At treatment of mucosal atrophy of the lower genital tract appointed 1 suppository / day during the first week followed by gradual dose reduction, based on relieving symptoms, until a maintenance dose (ie. 1 suppozytoryy 2 times a week).

At before- and postoperative therapy in post-menopausal women, surgical interventions vaginal access appointed 1 suppository / day for 2 weeks before surgery; 1 suppozytoryy 2 times a week for two weeks after surgery.

FROM diagnostic purposes under unclear cytology cervix appointed 1 suppository a day for a week before taking the next smear.

When skipping doses missed dose must be entered on the same day, as soon as the patient remembers this (dose should not be administered 2 times / day). In further applications carried out in accordance with the ordinary dosing regimen.

At the beginning or at the post-menopausal symptoms continued treatment is necessary to apply the lowest effective dose for the shortest period of time.

Women, not receiving HRT, or women, which translates to continuous use of oral combined HRT, Ovestin drug treatment can begin at any day. Women, who switch from cyclic mode receiving HRT, We should begin drug treatment through Ovestin 1 week after cessation of treatment HRT.

Side effect

As in the case of any other drug, which is applied to mucosal surfaces, suppozitorii Ovestin^® can sometimes cause local irritation or itching.

Sometimes there may be a sensitivity, tension, soreness, enlargement of breasts. These adverse reactions are usually short-lived and passing, but at the same time may indicate the use of too high a dose.

Also recorded acyclic spotting, breakthrough bleeding, metrorragija.

When HRT with estrogen-progestogen-containing preparations have been observed as the following side effects, whose connection with Ovestin^® not proven:

- Benign and malignant estrogen-dependent neoplasia (endometrial cancer and breast);

- Venous thromboembolism (deep vein thrombosis of the legs or pelvis, pulmonary embolism) often occurs when using HRT, than in the absence of treatment;

- Myocardial infarction, stroke;

- Cholelithiasis;

- Skin and subcutaneous diseases (chloasma, erythema multiforme, uzlovataya эritema, gemorragicheskaya purpura);

- Dementia;

- Increased libido.

Contraindications

- Fixed, with a history of or suspected breast cancer;

- Diagnosed estrogen-dependent tumor or suspected them (eg, endometrial cancer);

- Vaginal bleeding of unknown etiology;

- Untreated endometrial hyperplasia;

- The presence of venous thrombosis in the present and in history;

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

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

- Porphyria;

- Installed sensitivity to the active agent or any of the excipients of the drug.

FROM caution

If there is any of the following conditions or a condition previously stated and / or worsened during pregnancy or previous hormone treatment carried out previously, such a patient should be under the direct supervision of a physician. It is necessary to take into account, that these conditions may recur or worsen during treatment with Ovestin, especially, if present:

- Leyomyoma (uterine fibroids) or endometriosis;

- Transferred thromboembolic disorders or existing risk factors such violations;

- Risk factors for estrogen-tumor, eg, 1-I have a degree heredity for breast cancer;

- Arterial hypertension;

- Benign tumors of the liver (eg, liver adenoma);

- Diabetes mellitus with or without vascular component;

- Cholelithiasis;

- Jaundice (incl. a history of previous pregnancy during);

- Liver failure;

- Migraine or severe headache;

- Systemic lupus erythematosus;

- A history of endometrial hyperplasia;

- Epilepsy;

- Asthma;

- Otosclerosis;

- Family hyperlipoproteinemia;

- Pancreatitis.

Pregnancy and lactation

The drug Ovestin^® contraindicated in pregnancy. In case of pregnancy during therapy with Ovestin^®, Treatment should be immediately canceled.

The results of most epidemiological studies, conducted to date regarding the unintended effects of estrogen on the fetus, showed no teratogenic or foetotoxic effects.

The drug Ovestin^® not recommended for breast-feeding. Estriol is excreted in breast milk and may reduce milk production.

Cautions

For the treatment of postmenopausal symptoms, HRT should be started only on the symptoms, which adversely affect the quality of life. In all cases, you must at least once a year to conduct a thorough assessment of the risks and benefits of treatment. HRT should be continued only for a time period, when the benefits exceed the risk.

Medical examination / observation

Before the start or resumption of HRT need to set detailed personal and family history. Based on history, contraindications and warnings for use of the drug, necessary to carry out a clinical examination, including examination of the pelvic organs and breast. During treatment, it is recommended to carry out periodic medical examinations, the frequency and nature of which are individual, but not less 1 per year. Women should be informed of the need to report your doctor about changes in the mammary glands. Research, including mammograms, must be performed in accordance with generally accepted standards of the survey.

Therapy should be discontinued in case of contraindications and / or when the following conditions:

- Jaundice, and / or deterioration of liver function;

- A significant increase in blood pressure;

- Renewal of a headache by type of migraine;

- Pregnancy;

- Endometrial hyperplasia;

- To prevent endometrial stimulation daily dose should not exceed 1 suppozytoryy (500 micrograms estriol). Do not use the maximum dosage over a 4 weeks.

Breast cancer

Based on the results of a randomized, placebo-controlled study on women's health initiative program (WHI) and epidemiological studies, Research involving millions of women (Eulogy), It reported an increased risk of breast cancer in women, taking estrogen, Estrogen-progestogen-containing combinations or tibolone for HRT for several years. For all HRT increased the risk becomes noticeable after several years of use and increases with duration of admission, but returns to baseline within a few (max. 5) years after cessation of treatment.

The study MWS relative risk of breast cancer when used conjugated equine estrogens (SEE) or estradiol (E2) It was higher, when added progestogen, as in the cyclic, and during continuous reception, regardless of the type of progestagen. We have not received confirmation of the change in the degree of risk in a variety of modes of administration.

In the WHI study, the use of a combined preparation of conjugated equine estrogen and medroxyprogesterone acetate (SEE + MRA) with continuous admission was associated with the occurrence of breast cancers, that were somewhat larger in size and more often had metastases in local lymph nodes when compared to placebo.

With regard Ovestin^® this risk is not known. In a recent population-based case-control study involving 3345 women with invasive breast cancer and 3454 Women in the control group was shown, that the use of estriol as opposed to other estrogen was not associated with an increased risk of developing breast cancer. In this regard, it is important to, that the patient was aware of the risk of developing breast cancer in relation to the known use of HRT.

Venous thromboembolism

HRT is associated with a higher relative risk of developing venous thromboembolism (VTЭ), ie. deep vein thrombosis or pulmonary embolism. In one randomized controlled trial and epidemiological studies found, that the risk for women, receiving HRT 2-3 times higher, than for patients, not receiving this treatment. Established, that for women, not using HRT, the number of cases of VTE, that may occur during the 5-year period, is about 3 cases per 1000 women aged 50-59 years 8 cases per 1000 women aged 60-69 years. In healthy women, applying HRT for 5 years, the number of additional cases of VTE over a 5 year period should make 2-6 cases (average 4) per 1000 women aged 50-59 years 5-15 cases (average 9) per 1000 women aged 60-69 years. VTE is most likely in the first year of HRT, than at a later date. With regard Ovestin^® this risk is unknown.

Generally recognized risk factors for VTE is the appropriate individual or family history, obesity, high (BMI>30 kg / m²) and systemic lupus erythematosus. There is no consensus regarding the role of varicose veins in VTE.

Patients with a history of VTE or defined thromboembolic states have an increased risk of VTE. HRT may increase the risk. For, predisposition to prevent the formation of thrombi, the careful collection of personal and family history of thromboembolism or recurrent spontaneous abortion. Until then, until a thorough evaluation of thromboembolic factors, should not start treatment with anticoagulants or conduct HRT. With regard to women, who are already receiving treatment with anticoagulants, It requires careful consideration of the benefit / risk of HRT.

The risk of VTE may be increased after prolonged immobilization of the patient, major trauma, large volume surgery. After surgery, you need to pay particular attention to preventive measures for the prevention of VTE. Where, When the duration of immobilization after elective surgery inevitable, especially, after abdominal surgery or orthopedic surgery on the lower extremities, possibly, necessary to provide for the temporary cessation of HRT 4-6 weeks before surgery. If the drug Ovestin^® used as indicated “before- and post-operative treatment of women in post-menopausal vaginal access for operations” necessary to provide a prophylactic treatment to prevent thrombosis.

If, after the start of treatment Ovestin^® developing VTE, the drug treatment should be discontinued. Patients should be informed of the need for immediate treatment to the doctor, if they feel the potential thromboembolic symptom (eg, painful swelling of the feet, sudden chest pain, breathlessness).

CHD

In randomized controlled trials have not received confirmation of the positive effect of continuous administration of combinations of conjugated estrogens and medroxyprogesterone acetate (MPA) on the cardiovascular system. In two large clinical studies, WHI and HERS (A study of the heart and estrogen-progestin replacement therapy) It confirmed the likelihood of a possible increased risk of cardiovascular disease in the first year of application and the absence of the common good.

For other HRT there are only limited data, therefore there is no certainty, these results also apply to other drugs for HRT.

In a large randomized trial (WHI) It was found, that as a side effect can be considered at increased risk of ischemic stroke in healthy women during treatment with continuous reception a combination of conjugated estrogens and MPA. For women, who do not use HRT, the number of cases of stroke, which may occur during the 5-year period, is about 3 cases per 1000 women aged 50-59 years 11 cases per 1000 women aged 60-69 years. Established, that for women, who use conjugated estrogens and MPA for 5 years, It increases the number of additional cases in the 0-3 case (average 1) per 1000 patients aged 50-59 years 1-9 cases (average 4) per 1000 patients aged 60-69 years. Unknown, Does the increased risk to other HRT.

Ovarian Cancer

Prolonged (no less 5-10 years) monotherapy эstrogenami (how HRT) Women, undergoing surgery on the uterus, It is associated with an increased risk of ovarian cancer, that was found in several epidemiological studies. Not shown, that long-term combination HRT or estrogen monotherapy low-level (eg, Ovestin^®) It has a different risk.

Other conditions

Estrogens may cause fluid retention, and therefore patients with impaired renal function and cardiovascular insufficiency must be carefully monitored by a doctor. In end-stage renal disease should be under special control in connection with a possible increase in the level of circulating active ingredients Ovestin^®.

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

Do not produced convincing evidence of improving cognitive function. The WHI trial produced evidence of an increased risk of possible dementia in women, start applying continuous combination of conjugated estrogens and MPA continuously after 65 years. Unknown, Whether these findings apply to younger women, We are in postmenopausal women, using other drugs for HRT.

If you have a vaginal infection concomitant specific treatment is recommended.

Overdose

The acute toxicity of estriol in animals is very low. Overdose Ovestin^® vaginal administration is unlikely. But, In the event that large quantities of the drug in the gastrointestinal tract may develop nausea, vomiting, and stop bleeding in women.

Treatment: No specific antidote. If necessary, symptomatic treatment.

Drug Interactions

In clinical practice were observed interaction between the drug Ovestin^® and other drugs.

The metabolism of estrogens may be increased when used in combination with compounds, enzymes which induce, involved in the metabolism of drugs, especially, yzofermentы cytochrome P450, eg, such as anticonvulsants (phenobarbital, phenytoin, Carbamazepine) and antimicrobials (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 estrogen metabolism may lead to a decrease in their clinical effect.

Estriol increases the effects of lipid-lowering drugs.

Reduces the effects of male sex hormones, antykoahulyantov, Antidepressants, diuretic, antihypertensive, hypoglycemic agents.

General anesthetics, opioid analgesics, anxiolytics, Some antihypertensives, Ethanol reduces the effectiveness of the drug.

Folic acid and thyroid medications increase the action of estriol.

Conditions of supply of pharmacies

The drug is resolved to application as an agent Valium holidays.

Conditions and terms

The drug should be stored in a dry, protected from light and away from children at a temperature of 2 ° to 25 ° C. Shelf life – 3 year.