Estrovagin sup vag 0.5 mg x10 180702

Estrovagin sup vag 0.5 mg x10

Estrovagin sup vag 0.5 mg x10 Altaivitamins, ATX code: G03CA04 (Estriol) Active substance: estriol (estriol) Ph.Eur. European Pharmacopoeia

Dosage form

ESTROVAGIN

vaginal suppositories. 500 mcg: 10 pcs.reg. No.: LP-000720 dated 09/20/11 - Valid

Release form, composition and packaging

Vaginal suppositories 1 sup.

estriol 500 mcg, Clinical-pharmacological group: Estrogenic drug Pharmaco-therapeutic group: Estrogen The scientific information provided is general and cannot be used to make a decision about the possibility of using a specific drug.

pharmachologic effect

Estrogen, an analogue of the 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 of the lower genitourinary tract, estriol helps normalize the epithelium of the genitourinary tract and helps restore normal microflora and physiological pH in the vagina. Increases the resistance of epithelial cells of the 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 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

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.

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

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

Indications

HRT for the treatment of atrophy of the mucous membrane of the lower urinary and genital tract associated with estrogen deficiency, pre- and postoperative treatment of postmenopausal women during operations with vaginal access, for diagnostic purposes with unclear results of a cytological examination of the cervix (suspicion of a tumor process) against the background atrophic changes.

ICD-10 codes

Dosage regimen

Administer intravaginally. The dose is 500 mcg/day. The regimen of use is determined individually, depending on the indications and clinical situation.

Side effect

Possible: sensitivity, tension, pain, increased size of the mammary glands, acyclic bleeding, breakthrough bleeding, metrorrhagia may be noted.

Contraindications for use

Known, history or suspected breast cancer, diagnosed or suspected estrogen-dependent tumors (for example, endometrial cancer), vaginal bleeding of unknown etiology, untreated endometrial hyperplasia, current and history of venous thrombosis, active or recent thromboembolic arterial disease (for example, angina pectoris, myocardial infarction), acute liver disease or a history of liver disease after which liver function tests have not returned to normal, porphyria, known hypersensitivity to the active substance or to any of the excipients of the drug.

Use during pregnancy and breastfeeding

Use during pregnancy is contraindicated. If pregnancy occurs during estriol therapy, 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.

Use during lactation (breastfeeding) is not recommended. Estriol is excreted in breast milk and may reduce milk production.

special instructions

During treatment with estriol, a relapse or worsening of the following diseases and conditions is possible: 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 liver tumors (for example, hepatic adenoma), diabetes mellitus with or without a vascular component, cholelithiasis, jaundice (including a history of previous pregnancy), liver failure, migraine or severe headache, systemic lupus erythematosus , history of endometrial hyperplasia, epilepsy, asthma, otosclerosis, familial hyperlipoproteinemia, pancreatitis.

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.

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 headaches, pregnancy.

The risk of breast cancer with intravaginal use of estriol is unknown. It was shown that the use of estriol, unlike other estrogens, was not associated with an increased risk of developing breast cancer.

If estriol is used for the indication “pre- and postoperative treatment of postmenopausal women during operations with vaginal access,” prophylactic treatment must be provided to prevent thrombosis.

If VTE develops after starting estriol use, treatment should be discontinued.

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

Drug interactions

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 (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.

General anesthesia, opioid analgesics, anxiolytics, some antihypertensive drugs, and ethanol reduce the effectiveness of the drug.

Folic acid and thyroid medications enhance the effects of estriol.

Estrovagin®

HRT for the treatment of symptoms of estrogen deficiency should be carried out only for symptoms that adversely affect the woman’s quality of life. At least once a year, a thorough assessment of the benefit-risk ratio should be carried out; continuation of therapy is justified only if the benefit of using the drug exceeds the risk. There is limited evidence of the risks associated with HRT in the treatment of premature menopause. Due to the low absolute risk in younger women, the benefit-risk ratio is more favorable for them than for older women.

Medical examination/observation

Before starting or resuming HRT after its interruption, it is necessary to collect a detailed individual and family history, conduct a general and gynecological examination (including examination of the mammary glands and pelvic organs). During the therapy period, it is recommended to conduct periodic medical examinations, the frequency and nature of which are determined individually. The woman should be informed about the need to inform the doctor about possible changes in the mammary glands. Screenings, including appropriate imaging modalities such as mammography, should be performed according to currently accepted screening standards and on a case-by-case basis.

Reasons for immediate discontinuation of therapy

Therapy should be stopped immediately if contraindications are identified and if the following conditions occur:

- jaundice or deterioration of liver function;

- significant increase in blood pressure;

- the occurrence of migraine-type headaches;

- pregnancy.

Hyperplasia and endometrial cancer

To prevent endometrial stimulation, the daily dose of estriol should not exceed 1 suppository (0.5 mg estriol) per day. This maximum dose should not be used for more than 4 weeks. One epidemiological study found that long-term, low-dose oral estriol 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. Basically, the risk of developing minimally invasive and highly differentiated tumors increases. If spotting/bleeding from the vagina occurs, an appropriate examination is necessary. The patient should be informed of the need to notify the attending physician if bleeding begins.

Mammary cancer

Long-term use of HRT increases the risk of breast cancer in women receiving combination therapy with estrogen and progestogen and, possibly, estrogen monotherapy. In women receiving combined estrogen + progestogen therapy 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 a progestogen. Limited data indicate that there is no risk of developing breast cancer with the use of estriol.

HRT, in particular combination drugs, can increase the density of mammographic images. This may complicate radiological detection of breast cancer.

Ovarian cancer

Ovarian cancer develops much less frequently than breast cancer. Long-term estrogen monotherapy (for at least 5 to 10 years) was associated with a small increase in the risk of ovarian cancer. Some studies suggest that HRT with combination drugs has a similar or slightly lower risk. It is not known whether the risk of long-term use of low-potency estrogens (such as estriol) is different from that of monotherapy with other estrogens.

Venous thromboembolism (VTE)

HRT is associated with an increase in the risk of developing VTE (deep vein thrombosis or pulmonary embolism) by 1.3-3 times. The likelihood of developing VTE is higher during the first year of HRT use than at a later date. In patients with a confirmed thrombophilic condition, the risk of VTE is high, and HRT may further increase this risk. Therefore, HRT is contraindicated in such women.

Generally recognized risk factors for VTE include estrogen use, older age, major surgery, prolonged immobilization, obesity (BMI >30 kg/m2), pregnancy/puerperium, systemic lupus erythematosus, and cancer. There is no consensus regarding the possible role of varicose veins and the development of VTE. After any surgical intervention, VTE prophylaxis is necessary. In case of prolonged immobilization due to planned surgery, HRT should be temporarily discontinued 4-6 weeks before surgery and resumed only after the woman has regained full mobility.

In the absence of a woman's history of VTE, but in the presence of thrombosis at the age of less than 50 years in close relatives, it is recommended to conduct a screening examination, having previously discussed all its limitations (screening can only identify a number of thrombophilic disorders). If a disorder is detected that does not correspond to the disease in relatives, or if a “severe” defect is detected (for example, deficiency of antithrombin III, protein S or protein C, or a combination of these defects), HRT with estriol is contraindicated.

For women receiving long-term anticoagulant treatment, careful consideration of the benefit-risk profile of HRT is required.

If VTE develops, drug therapy should be discontinued immediately. A woman should be informed of the need to immediately consult a doctor if possible signs of thromboembolic complications appear (for example, swelling or tenderness along the vein of the lower extremity, sudden chest pain, shortness of breath, etc.).

Coronary heart disease (CHD)

In randomized controlled clinical trials, there was no evidence that HRT with combination drugs or estrogen monotherapy can prevent the development of myocardial infarction in women with and without coronary artery disease.

Estrogen monotherapy

According to randomized controlled clinical trials, in women with a history of hysterectomy, the risk of coronary artery disease is not increased with estrogen monotherapy. The absolute risk of coronary heart disease increases slightly with HRT with combined (estrogen + gestagen) drugs in patients over 60 years of age.

Ischemic stroke

HRT with combination drugs and estrogen monotherapy is associated with a 1.5-fold increase in the risk of ischemic stroke. The relative risk does not change with age and time after menopause. However, the baseline risk of stroke is highly dependent on age, and the overall risk of ischemic 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 chronic heart and kidney failure should be under close medical supervision.

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

Women with pre-existing hypertriglyceridemia should be closely monitored because, in rare cases, estrogen HRT has caused a significant increase in plasma triglyceride concentrations, leading to the development of pancreatitis.

Estrogens cause an increase in the concentration of thyroxine-binding globulin, which leads to an increase in total circulating thyroid hormone, measured as total protein-bound iodine; T4 concentration or T3 concentration.

The concentration of other plasma proteins (angiotensin-renin substrate, alpha-1-antitrypsin, ceruloplasmin) may also increase.

Cognitive function does not improve with HRT. There is evidence of an increased risk of developing dementia in women who start HRT with combination drugs or continuous estrogen monotherapy after 65 years.

Estrovagin