Ovestin® (Ovestin®)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceEstriolEstriol
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    • Dosage form: & nbspVaginal suppositories
    Composition:

    Active substance:

    Estriol 0.5 mg.

    Excipients:

    ATitepsol S58 2.4995 g.

    Description:

    Suppositories in the form of a torpedo from white to light cream color.

    The surface and the longitudinal section are uniform.

    Pharmacotherapeutic group:Estrogen
    ATX: & nbsp

    G.03.C.A   Natural and semi-synthetic estrogens

    G.03.C.A.04   Estriol

    Pharmacodynamics:
    Ovestin® contains estriol - an analog of the natural female hormone. He replenishes the estrogen deficiency in postmenopausal women and weakens postmenopausal symptoms. The most effective estrirol in the treatment of urogenital disorders. In the case of atrophy of the mucous membrane of the lower sections of the genito-urinary tract estriol It helps normalize the epithelium of the genito-urinary tract and helps restore normal microflora and physiological pH in the vagina.As a result, it increases the resistance of the epithelial cells of the urogenital tract to infection and inflammation, reducing complaints such as soreness in intercourse, dryness, itching in the vagina, reduces the likelihood of vaginal infections and urinary tract infections, helps normalize urination, and prevents incontinence.

    Unlike other estrogens, estriol has a short period of action, since in the nuclei of endometrial cells it is retained for a short period of time. It is assumed that a single dose of a daily dose does not cause endometrial proliferation. Therefore, cyclic progestogen administration is not required and no withdrawal bleeding occurs. In addition, it is shown that estriol does not increase mammographic density.

    Pharmacokinetics:

    Intravaginal administration of estriol provides optimal bioavailability at the site of action. Estriol is also absorbed and enters the total blood flow, which is manifested by a rapid increase in the concentration of unbound estriol in plasma. The maximum plasma concentration is observed 1-2 hours after the administration.

    In plasma, almost the whole (90%) estriol is associated with albumin and, unlike other estrogens, is virtually unrelated to the globulin binding sex hormones. Metabolism of estriol is mainly in the transition to a conjugated and unconjugated state with intestinal hepatic circulation.

    Estriol, being the final product of metabolism, is mostly excreted in urine in a bound form. Only a small part (± 2%) is excreted with feces, mainly as unbound estriol. The half-life is approximately 6-9 hours.

    After vaginal administration, 0.5 mg of estriol, the maximum concentration of Cmax is about 100 pg / ml, the minimum concentration of Cmin - about 25 pg / ml, and the average concentration of CWed about 70 pg / ml. After 3 weeks of daily administration of 0.5 mg of vaginal estriol, the value of CWed decreased to 40 pg / ml.

    Indications:

    - Replacement hormone therapy (HRT) for the treatment of mucosal atrophy of the lower genito-urinary tract associated with estrogen deficiency in postmenopausal women;

    - pre- and postoperative therapy of women in the postmenopausal period, with surgical interventions for vaginal access;

    - as an auxiliary means of diagnosis in obtaining an atrophic picture of the cervical smear.

    Contraindications:

    - An established, history of or suspected breast cancer;

    - diagnosed estrogen-dependent tumors or suspected of them (eg, endometrial cancer);

    bleeding from the vagina of an unclear etiology;

    - untreated endometrial hyperplasia;

    - presence of venous thrombosis at present and in anamnesis (deep vein thrombosis, pulmonary thromboembolism);

    - confirmed thrombophilia (eg deficiency of protein C, protein S or antithrombin (see section "Special instructions"));

    - Thrombosis (venous and arterial) and thromboembolism at present or in the anamnesis (including deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke), cerebrovascular disorders; conditions preceding thrombosis (including transient ischemic attacks, angina pectoris) at present or in the anamnesis;

    - liver disease in the acute stage or liver disease in history, after which the liver function indicators did not return to normal;

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

    - porphyria.

    Carefully:

    With caution (under close medical supervision), Ovestin® should be used if any of the following diseases or conditions are present, or these conditions or conditions were noted earlier and / or worsened during previous pregnancies or previous hormonal treatments (as they may relapse 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, the first degree of heredity for breast cancer;

    - arterial hypertension;

    - benign liver tumors (eg, liver adenoma);

    - diabetes mellitus with or without diabetic angiopathy;

    - cholelithiasis;

    - jaundice (including anamnesis during previous pregnancy);

    - liver failure;

    - migraine or (severe) headache;

    - systemic lupus erythematosus;

    - Endometrial hyperplasia in the anamnesis (see section "Special instructions");

    - epilepsy;

    - bronchial asthma;

    otosclerosis;

    - familial hyperlipoproteinemia;

    - pancreatitis.

    Pregnancy and lactation:

    The drug Ovestin® is contraindicated during pregnancy. In case of pregnancy during therapy with Ovestin ®, treatment should be immediately canceled. The results of most epidemiological studies conducted so far on the unintended impact of estrogen on the fetus indicate the absence of teratogenic or fetotoxic effects.

    Ovestin ® is not recommended during breastfeeding. Estriol is excreted in breast milk and can reduce the formation of milk.

    Dosing and Administration:

    Ovestin® suppositories should be injected into the vagina at nighttime before bedtime.

    - In the treatment of atrophy of the mucous membrane of the lower sections of the genito-urinary tract:

    1 suppository per day during the first weeks, followed by a gradual dose reduction, based on alleviating the symptoms, until a maintenance dose is reached (i.e., 1 suppository twice a week).

    - Pre- and postoperative therapy of women in the postmenopausal period, with surgical interventions by vaginal access:

    1 suppository per day for 2 weeks before surgery; 1 suppository twice a week for 2 weeks after surgery.

    - With a diagnostic purpose for unclear results of cervical cervical examination:

    1 suppository every other day for a week before taking the next smear. The missed dose should be entered on the same day as soon as the patient remembers it (the dose should not be administered twice a day). In the future, the applications are carried out in accordance with the usual dosing scheme.

    At the onset or continuation of the treatment of postmenopausal symptoms, the lowest effective dose in the flownore of the shortest period of time.

    In women who do not receive HRT, or women who are transferred from a continuous oral intake of the combined drug for HRT, Ovestin® can be started on any given day. Women who switch from cyclic mode reception of drugs for HRT, should begin treatment with Ovestin ® through odaysa week after the withdrawal of HRT.

    Side effects:

    As with any other drug that is applied on the surface of the mucous membranes, Ovestin® suppositories can sometimes cause local irritation or itching.Sometimes there may be sensitivity, tension, tenderness, increase in the size of the mammary glands. These undesirable reactions are usually short and transitory, but at the same time may indicate the use of too high a dose.

    Also occur: acyclic spotting, bleeding "breakthrough", metrorrhagia.

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

    Disorders from the liver and bile ducts:

    - Cholelithiasis.

    Benign, malignant and unspecified neoplasms (including cysts and polyps):

    - Benign and malignant estrogen-dependent neoplasias, incl. endometrial cancer (for more information, see "Contraindications" and "Special instructions").

    Disorders of the psyche:

    - Dementia at the onset of HRT in continuous mode after 65 years (see section "Special instructions").

    Violations of the genitals and breast:

    - Increased libido.

    Disturbances from the skin and subcutaneous tissues:

    - Chloasma, erythema multiforme, erythema nodosum, hemorrhagic purpura.

    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, the risk of ischemic stroke (for details, see "Special instructions").

    Overdose:

    Acute toxicity of estriol in animals is very low. Overdosage with Ovestin ® for vaginal administration is unlikely. However, in the event that large amounts enter the gastrointestinal tract, nausea, vomiting and cessation of bleeding in women may develop.

    The specific antidote is not known. If necessary, symptomatic treatment should be performed.

    Interaction:

    In clinical practice, no interaction between the drug Ovestin ® and other drugs.

    Estrogen metabolism can be enhanced when used in combination with compounds that induce enzymes involved in the metabolism of drugs, in particular cytochrome P450 enzymes, for example, such as anticonvulsants (for example, phenobarbital, phenytoin, carbamazepine) and antimicrobial agents (for example, 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), can induce estrogen metabolism.

    Elevated estrogen metabolism can lead to a decrease in their clinical effect.

    Estriol enhances the action of lipid-lowering drugs; weakens the effects of male sex hormones, anticoagulants, antidepressants, diuretic, hypotensive, hypoglycemic drugs.

    Medicines for general anesthesia, narcotic analgesics, anxiolytics, certain antihypertensive drugs, ethanol reduce the effectiveness of the drug.

    Folic acid and thyroid medications enhance the effects of estriol.
    Special instructions:

    - For the treatment of climacteric symptoms, HRT should be started only with regard to symptoms that adversely affect the quality of life. In all cases, at least once a year, a thorough assessment of the risks and benefits of treatment and HRT should be continued only for as long as the benefit exceeds the risk.

    - There is limited evidence of the development of HRT risk in the treatment of premature menopause. In view of the low absolute risk in younger women, the benefit-risk ratio is more favorable for them than for the elderly.

    Medical Examination / Surveillance

    - Before starting or resuming HRT, you need to collect a detailed individual and family history. Guided by the received anamnesis, contraindications and warnings on 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 are individual. Women should be informed of the need to inform the doctor about changes in the mammary glands (see below section "Breast Cancer"). Studies, including appropriate imaging techniques, such as mammography, should be performed in accordance with current survey standards and, depending on each case.

    Reasons for immediate withdrawal of therapy

    Therapy should be discontinued in case of a contraindication and if the following conditions occur:

    - Jaundice or impaired liver function;

    - Significant increase in blood pressure;

    - The onset of a migraine headache;

    - Pregnancy.

    Hyperplasia of the endometrium and carcinoma

    - To prevent endometrial stimulation, the daily dose of the drug should not exceed 1 suppository (0.5 mg estriol). Do not use this maximum dose for more than 4 weeks. In addition, in one epidemiological study, it was found that prolonged use of estriol in low doses, administered orally but not intravaginally, may increase the risk of endometrial cancer. The risk increases as the duration of treatment increases and returns to the baseline values ​​one year after the drug was discontinued. In general, the risk of minimally invasive and highly differentiated tumors increases. Vaginal bleeding in all cases requires examination. The patient should be informed of the need to contact the doctor in case of the onset of vaginal bleeding.

    Mammary cancer

    - Replacement hormonal therapy can increase mammographic density. This can complicate radiological detection of breast cancer. Clinical studies have shown that the probability of an increase in mammographic density is lower in women receiving estriol than in women receiving treatment with other estrogens.

    - Generalized evidence suggests an increased risk of breast cancer in women receiving combined therapy with estrogens and progestogens and, possibly, estrogen monotherapy.

    - Women who receive combined therapy with estrogens and progestogens for more than 5 years have an increase in the risk of breast cancer by 2 times.

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

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

    - It is not known whether Ovestin® is the same risk. In a recent population-based case-control study involving 3345 women with invasive breast cancer and 3,454 women in the control group, estriol, 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 has been discussed with the patient and is correlated with the known benefit of HRT.

    Ovarian Cancer

    - Ovarian cancer is much less common than breast cancer. Prolonged monotherapy with estrogen (at least 5-10 years) was associated with a slight increase in the risk of ovarian cancer. The results of some studies indicate that combined HRT may increase the risk of ovarian cancer in a similar way or slightly. It is unknown whether the risk of long-term use of low-level estrogen (such as Ovestin®) is different from that of monotherapy with other estrogens.

    Venous thromboembolism

    - HRT is associated with an increased risk of venous thromboembolism (VTE), i.e. deep vein thrombosis or pulmonary embolism, in 1,3-3 times. The likelihood of developing VTE is higher during the first year of HRT use than at a later date. It is not known whether Ovestin® has the same risk.

    - In patients with confirmed thrombophilia, the risk of VTE is high, and HRT can additionally increase it. In connection with these women, HRT is contraindicated (see the section "Contraindications").

    - Usually recognized risk factors for VTE are estrogen intake, advanced age, extensive surgical interventions, 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 prevent VTE. If prolonged immobilization is associated with a planned operation, it is necessary to temporarily cancel HRT 4-6 weeks before the operation. 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 appointed as a "pre- and post-operative treatment ...", thrombosis prophylaxis should be considered.

    - In the absence of VTE in the anamnesis, but in the presence of thrombosis at a young age at the next of kin of the patient, she can be offered to conduct a screening survey, having previously discussed all of its limitations (screening can reveal only a number of thrombophilic disorders).If there is a thrombophilic defect that does not correspond to the disease in relatives, or if a "severe" defect (eg, an antithrombin deficiency, protein S or protein C deficiency, or a combination of these defects is found), HRT is contraindicated.

    - If after the start of treatment with Ovestin®, VTE develops, then treatment should be stopped. Patients should be informed of the need to seek immediate medical attention if they feel any signs of thromboembolism (eg, painful leg swelling, sudden chest pain, shortness of breath).

    Ischemic heart disease (CHD)

    - In randomized controlled trials, no results have been obtained that would indicate that combination therapy with estrogens and progestogens and estrogen monotherapy can prevent the development of myocardial infarction in women with and without IHD.

    Monotherapy with estrogen

    - According to randomized controlled trials in women with a deleted uterus, the risk of CHD with estrogen alone does not increase.

    - The risk of coronary heart disease increases slightly with combined HRT estrogens and progestogens in patients older than 60 years.

    Ischemic stroke

    - Combined therapy with estrogens and progestogens and estrogen monotherapy are associated with an increased risk of ischemic stroke by a factor of 1.5. The relative risk with age and with time after the onset of menopause does not change. However, the initial risk of stroke largely depends on age, and the overall risk of stroke with HRT increases with age. The risk of hemorrhagic stroke with HRT is not increased.

    Other states

    - Estrogens can cause fluid retention, and therefore patients with impaired renal function and cardiovascular failure 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. A certificate of an increased risk of dementia in women who started using combined therapy or monotherapy in continuous mode after 65 years of age has been obtained.

    Effect on the ability to drive transp. cf. and fur:

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

    Form release / dosage:Vaginal suppositories, 0.5 mg.
    Packaging:

    For 5 suppositories in a double-sided contour pack of PVC / PE. 3 contour packs together with instructions for use are placed in a cardboard box.

    Storage conditions:

    At a temperature of 2-25 ° C in a dry place, protected from light and inaccessible to children.

    Shelf life:

    3 years.

    Do not use after the expiration date.

    Terms of leave from pharmacies:Without recipe
    Registration number:П N013327 / 01
    Date of registration:06.11.2007 / 10.01.2017
    Expiration Date:Unlimited
    The owner of the registration certificate:Aspen Pharma Trading LimitedAspen Pharma Trading Limited
    Manufacturer: & nbsp
    ORGANON, N.V. Netherlands
    Representation: & nbspAspen Hells Ltd.Aspen Hells Ltd.
    Information update date: & nbsp21.05.2017
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