The drug Livial® is not intended for use as a contraceptive and does not protect against unwanted pregnancy.
The decision to start taking the drug Livial® should be based on an assessment of the "benefit / risk" ratio, taking into account all individual risk factors, and in women over 60 years of age, the risk of developing strokes should also be taken into account.
For the treatment of postmenopausal symptoms, Livial is necessary appoint only for symptoms that adversely affect the quality of life. In all cases, a careful assessment of the risks and benefits of therapy should be carried out at least once a year, and Liviral® should be continued only at a time when the benefits of therapy exceed the risk.
It is necessary to carefully evaluate the risk stroke risk, the risk of developing breast cancer and endometrial cancer in every woman with an intact uterus (see the "Side effect" section), considering all individual risk factors, incidence and features of both cancers and stroke in terms of healing, morbidity and mortality .
Evidence of relative risk, associated with hormone replacement therapy (HRT) or the use of tibolone for the treatment of premature menopause, are limited. However, the benefit / risk ratio in women with premature menopause may be more favorable than in women older age, because of the low level of absolute risk in younger women.
Medical Examination / Surveillance
Before the initiation or resumption of therapy, individual and family medical history.
Physical examination (including examination of pelvic organs and mammary glands) should be performed taking into account the history, absolute and relative contraindications. During the therapy, preventive repeated examinations are recommended, the frequency and nature of which are determined by the individual characteristics of the patient, but not less than once in 6 months.In particular, a woman should be informed about the need to inform the doctor about changes in the mammary glands.
Surveys, including relevant methods of visualization, for example, mammography, should be carried out in accordance with the current survey scheme, adapted to the clinical needs of each patient, but at least once every 6 months.
Reasons for immediate withdrawal of therapy and immediate medical attention
Therapy should be discontinued in case of detection of contraindications and / or in the following conditions / diseases:
- jaundice or worsening of liver function;
- sudden increase of arterial pressure, which differs from the usual indices of blood pressure, characteristic for the patient;
- occurrence of a headache type migraine.
Hyperplasia and endometrial cancer
Data from randomized controlled clinical trials are controversial, but observational studies have shown an increased risk of developing hyperplasia or endometrial cancer in women taking Livial® (see also "Side effect").These studies have shown that the risk of developing endometrial cancer increases with increasing duration of the drug.
Tibolon can increase the thickness Endometrium, measured by transvaginal ultrasound.
During the first months of treatment, observed "breakthrough" bleeding and spotting.
When bloody discharge / bleeding during the use of the drug Livial®, which
- last more than 6 months from the beginning reception of the drug,
- begin 6 months after the start of the drug Livial and continue even after the patient stopped using the drug Livial®, you need to see a doctor - this may be a sign of hyperplasia of the endometrium.
Mammary cancer
Data from different clinical trials with the viewpoints of evidence-based medicine regarding the risk of developing breast cancer when taking tibolone are controversial, and further research is required.
According to the "Study of a million women "there was a significant increase in the risk of developing breast cancer with a dose of 2.5 mg (see the" Side effect "section).This risk became apparent after several years of application of the drug and increased with increasing duration of application, returning to the baseline in a few years (more often in five years) after discontinuation of the drug.
These results were not confirmed in the course of the study using the General Practice Research Database (GPRD),
Ovarian Cancer
Ovarian cancer is widespread less than breast cancer. Long-term (at least 5-10 years) estrogen replacement monotherapy was associated with a slight increase in the risk of ovarian cancer.
Some studies, including study "Health Initiative women " (WHI) [Women's Health Initiative], suggest that prolonged therapy with combined drugs for HRT may have a similar or slightly lower risk.
In the "Study of a million women" was It was shown that the relative risk of developing ovarian cancer with tibolone was similar to the risk associated with the use of other types of HRT.
Venous thromboembolism
Preparations for HRT containing only estrogens, or combined HRT preparations containing estrogen and progestogen may increase the risk of venous thromboembolism (VTE) (i.e.deep vein thrombosis or pulmonary embolism) 1.3-3 times, especially during the first year of use of HRT preparations (see "Side effect" section).
According to the epidemiological studies using UK databases, the risk of developing VTE associated with taking tibolone was lower than that associated with conventional HRT, but due to the fact that at that time only a small proportion of women were taking tibolone, we can not exclude a slight increase in risk compared to women who did not take tibolone. Patients with known thrombophilic conditions have a higherwThe risk of developing VTE and taking Liviaz® can increase this risk, so the use of the drug by this population of patients is contraindicated (see section "Contraindications").
Risk factors for VTE are estrogen use, advanced age, extensive surgery, prolonged immobilization, obesity (body mass index (BMI)> 30 kg /m2), pregnancy and the postpartum period, systemic lupus erythematosus and cancer.
Patients after surgical interventions should pay special attention to preventive measures to prevent VTE in the postoperative period.If prolonged immobilization is required after the operation, a temporary discontinuation of Livial® is recommended 4 to 6 weeks before surgery. Treatment should not be resumed until the woman's motor activity is restored. Women who have no history of VTE, but who have relatives of the first degree of kinship who have a history of thrombosis at a young age, may be offered screening (should inform the woman that screening reveals only a part of thrombophilic conditions). If a thrombophilic condition is identified that is isolated from the thrombosis of relatives, or a serious disorder (eg, an antithrombin III deficiency, protein S, protein C or a combination of disorders), the drug Livial® is contraindicated.
With regard to women who are already are treated with anticoagulants, careful consideration of the benefit / risk ratio of HRT or tibolone is required.
If after the start of treatment VTE develops, the drug should be discontinued.
Patients should be informed of the the need for immediate medical attention if symptoms of potential thromboembolism appear (for example,pain and unilateral swelling of the lower limb, sudden pain in the chest, shortness of breath).
Ischemic heart disease (CHD)
In a randomized controlled studies have not received evidence of protection against myocardial infarction in women with or without CHD who received HRT with combined drugs (estrogen / progestogen) or estrogen-only preparations for HRT.
In epidemiological studies using the base GPRD did not have evidence of protection against myocardial infarction myocardium in postmenopausal women, who received tibolone.
Ischemic stroke
Therapy with LIVIAL® increases risk of ischemic stroke, starting from the first year application (see the section " action "). Absolute risk the occurrence of a stroke is strictly dependent on age, and, consequently, this effect Tibolon the more, the more age.
When inexplicable migraine-like headaches with or without visual impairment is necessary as much as possible contact a doctor sooner. In this case do not take the drug until the doctor will not confirm the safety continuation of HRT, since such headaches can be early diagnostic sign of a possible stroke.
Other states
- According to available data, treatment with Liviaz® resulted in significant dose-dependent lowering HDL cholesterol (high density lipoproteins) (c - 16.7% at a dose of 1.25 mg to-21.8% with dose 2.5 mg after 2 years of use).
- Also, the total concentration triglycerides and lipoprotein.
Decrease in the concentration of total cholesterol and cholesterol VLDLP (very low density lipoproteins) was not dose-dependent.
Concentrations of LDL cholesterol (low-density lipoproteins) did not change. The clinical significance of these data is still unknown.
- Estrogens can cause a delay fluid, so patients with cardiac or renal insufficiency should be under the close supervision of a physician.
- Women with existing Hypertriglyceridemia should be carefully monitored by a physician during therapy with Liavial®, as rare cases of a significant increase concentrations triglycerides in plasma blood, promoting the development of pancreatitis, were observed during estrogen therapy in this condition.
- Treatment with the drug Livial® leads to a very small decrease in thyroxine-binding globulin (TSH) and total T4. Concentration general terms of reference does not change. Livial® reduces concentration globulin binding sex hormones (SHBG), whereas concentrations corticosteroid-binding globulin (CSG) and circulating cortisol is not are changing.
- The use of drugs for HRT is not improves cognitive function.
There is evidence of increased risk the possible development of dementia in women, with the onset of continuous therapy with combined preparations for HRT or with hormone replacement drugs containing estrogens only, after the age of 65 (see "Side effect").