Ovestin, vaginal suppositories 0.5mg, 15pcs

Composition

Active ingredient:

Estriol 0.5 mg

Auxiliary substances:

Vitepsol S58 2,4995 g

Pharmacological action

Ovestin contains estriol, an analog of the natural female hormone. It makes up for estrogen deficiency in postmenopausal women and reduces postmenopausal symptoms. Estriol is most effective in the treatment of genitourinary disorders. In the case of atrophy of the mucous membrane of the lower parts of the genitourinary tract, estriol contributes to the normalization of 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 the epithelial cells of the genitourinary tract to infection and inflammation, reducing complaints such as soreness during sexual intercourse, dryness and itching in the vagina, reduces the likelihood of vaginal infections and urinary tract infections, helps to 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 use of progestogen is not required and withdrawal bleeding does not occur. In addition, estriol has not been shown to increase mammographic density.

Pharmacokinetics

Intravaginal use of estriol provides 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 plasma. The maximum plasma concentration is observed 1-2 hours after use.

In plasma, almost all (90%) of estriol is bound to albumin and, unlike other estrogens, it is practically not bound to globulin, which binds sex hormones. The metabolism of estriol consists mainly in the transition to a conjugated and unconjugated state during the intestinal-hepatic circulation. Estriol, being the end product of metabolism, is mainly excreted in the urine in a bound form. Only a small part (± 2%) is excreted in the faeces, mainly in the form of unbound estriol. The elimination half-life is approximately 6-9 hours.

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

Indications

• Hormone replacement therapy (HRT) for the treatment of lower genitourinary tract mucosal atrophy associated with estrogen deficiency in postmenopausal women.
• Pre-and postoperative therapy of postmenopausal women during surgical interventions with vaginal access.
• As an auxiliary diagnostic tool for obtaining an atrophic picture of the cervical smear.

Use during pregnancy and lactation

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

Contraindications

• Established, pre-existing, or suspected breast cancer.
• Diagnosed or suspected estrogen-dependent tumors (for example, endometrial cancer).
• Vaginal bleeding of unclear etiology.
• Untreated endometrial hyperplasia.
• The presence of venous thrombosis at the present time and in the anamnesis (deep vein thrombosis, pulmonary thromboembolism).
• Confirmed thrombophilia (such as protein C, protein S, or antithrombin deficiency).
• 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.
• Acute liver disease or a history of liver disease after which liver function indicators have not returned to normal.
• Established hypersensitivity to the Active ingredient or to any of the excipients of the drug.
• Porphyria.

With caution

Ovestin® should be used with caution (under close medical supervision) if any of the following diseases or conditions are present, or if these diseases or conditions have previously been reported and / or worsened during previous pregnancies or hormone treatment (as they may recur or worsen during treatment with Ovestin®):

• Leiomyoma (uterine fibroids) or endometriosis.
• Risk factors for thromboembolism.
• Risk factors for estrogen-dependent tumors, such as grade 1 inheritance for breast cancer.
• Arterial hypertension.
• Benign liver tumors (for example, liver adenoma).
• Diabetes mellitus with or without diabetic angiopathy.
• Cholelithiasis.
• Jaundice (including a history of previous pregnancy).
• Liver failure.
• Migraine or (severe) headache.
• Systemic lupus erythematosus.
• A history of endometrial hyperplasia.
• Epilepsy.
• Bronchial asthma.
• Otosclerosis.
• Familial hyperlipoproteinemia.
• Pancreatitis.

Side effects

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 adverse reactions are usually short-lived and transient, but at the same time may indicate the use of too high a dose.

Also found: acyclic spotting, bleeding “breakthrough”, metrorrhagia.

Other adverse reactions have been reported with oestrogen monotherapy or combined oestrogen and progestogen therapy.

Liver and biliary tract disorders:

– Cholelithiasis.

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

– Benign and malignant estrogen-dependent neoplasms, including endometrial cancer.

Mental disorders:

– Dementia at the beginning of HRT in continuous mode after 65 years (see the section “Special instructions”).

Genital and breast disorders:

– Increased libido.

Skin and subcutaneous tissue disorders:

– 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, and the risk of ischemic stroke.

Interaction

In clinical practice, there was no interaction between the drug Ovestin® and other drugs. The metabolism of estrogens can be enhanced when they are used in combination with compounds that induce enzymes involved in drug metabolism, in particular cytochrome P450 enzymes, such as anticonvulsants (for example, phenobarbital, phenytoin, carbamazepine) and antimicrobials (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. Increased estrogen metabolism can lead to a decrease in their clinical effect. Estriol enhances the effect of lipid-lowering drugs and weakens the effects of male sex hormones, anticoagulants, antidepressants, diuretics, hypotensive, hypoglycemic drugs. General anesthesia medications, narcotic analgesics, anxiolytics, certain antihypertensive medications, and ethanol reduce the effectiveness of the drug. Folic acid and thyroid medications enhance the effect of estriol.

How to take, course of use and dosage

Ovestin suppositories should be inserted into the vagina at night before going to bed.

• In the treatment of atrophy of the mucous membrane of the lower parts of the genitourinary tract:

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

• Pre-and postoperative therapy of postmenopausal women during surgical interventions with vaginal access:

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

• For diagnostic purposes with unclear results of cytological examination of the cervix:

1 suppository every other day for a week before taking the next smear.

The missed dose should be administered on the same day, as soon as the patient remembers it (the dose should not be administered twice a day). Further applications are carried out in accordance with the usual dosage scheme.

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

In women who are not receiving HRT, or who are being transferred from continuous oral use of a combined HRT drug, treatment with Ovestin® can be started on any day.Women who are switching from a cyclic HRT regimen should start treatment with Ovestin® one week after discontinuing HRT medications.

Overdose

Acute toxicity of estriol in animals is very low. Overdose of Ovestin® with vaginal use is unlikely. However, if large amounts enter the gastrointestinal tract, women may develop nausea, vomiting, and stop bleeding. The specific antidote is unknown. If necessary, symptomatic treatment should be performed.

Special instructions

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.
• 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.

No effect on the ability to drive a car or other mechanisms of action of Ovestin® on concentration and attention was observed.

Form of production

Vaginal suppositories 0.5 mg. 5 suppositories in a double-sided contour cell package made of PVC/PE. 3 contour packages together with the 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.

Keep out of reach of children.

Shelf

life is 3 years. Do not use after the expiration date.

Active ingredient

Estriol

Dosage form

vaginal suppositories

Purpose

For postmenopausal women

Indications

Estrogen deficiency, Menopause