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Active ingredients
Tibolon
Release form
Pills
Composition
Active ingredient: tibolone (tibolone) Concentration of the active substance (units): 2, 5 mg
Pharmacological effect
Anti-menopausal drug. When taken orally, tibolone is rapidly metabolized to form three compounds that determine the pharmaco-dynamic characteristics of the drug Livial. Two metabolites of tibolone (3α-hydroxytibolone and 3β-hydroxytibolone) have estrogen-like activity, while the third metabolite, the Δ4-isomer of tibolone, has gestagen-like and androgen-like activity. The Livial remedy compensates for the deficiency of estrogen and women and post-asparagus activity. hot flashes, night sweats, mood changes, depression, irritability, dryness and discomfort in the vagina, decreased libido). Livial prevents bone loss after menopause or removal of the ovaries.
Pharmacokinetics
Absorption and metabolismAfter intake, Tibolone is rapidly and completely absorbed. Due to rapid metabolism, Tibolone plasma levels are very low. The maximum plasma concentrations of Tibolone metabolites are reached 1–1.5 hours after taking the drug. Excretion Tibolone is released mainly as metabolites. A small amount is excreted in the urine, and most of it in the bile and feces. T1 / 2 metabolites is approximately 7 hours without subsequent accumulation.
Indications
- treatment of symptoms of estrogen deficiency in postmenopausal women; - prevention of osteoporosis in postmenopausal women who are at high risk of fractures, and with intolerance to other groups of drugs used to prevent osteoporosis.
Contraindications
Pregnancy and breastfeeding. Period less than a year after the last menstrual diagnosis. Diagnosed (including in the past - in history) breast cancer or suspicion of it. Diagnosed (including in history) malignant estrogen-dependent tumors (for example, endometrial cancer) or suspicion of them. endometrial hyperplasiaIdiopathic (in history) or existing venous thromboembolism (thrombophlebitis,pulmonary embolism) Any thromboembolic arterial disease in history (eg, angina pectoris, myocardial infarction, stroke, or transient ischemic attack) Cardiovascular failure in the stage of decompensation Acute liver disease or history of the liver, after which the liver function did not return to the liver, after which the liver function did not return to the heart, the liver function did not return to the heart rate, the liver function indicators did not return to the heart rate, the liver function indicators didn’t return to the heart rate, the liver function indicators did not return to the heart rate, the liver function indicators didn’t return to normal, after which the liver function didn’t return to the heart rate, the liver function or liver disease did not return to the speed of the liver. during pregnancy or with hormone therapy; Installed hypersensitivity to the drug. With caution to use, HRT may have some health risks that must be considered when deciding whether to start taking the drug or to continue its use. Before you start taking HRT, your doctor should familiarize yourself with your history, including family diseases that you have had, and carry out the necessary physical examination, including blood pressure (BP), pulse, body weight, etc .; breast examination; gynecological examination; carry out the necessary laboratory tests. In the future, you should undergo mandatory preventive check-ups, as recommended by the doctor, but at least once a year. It should be remembered that some conditions / diseases may progress or worsen under the influence of HRT. If you have or have previously experienced any of the following conditions / diseases, inform your physician in a timely manner: Leiomyoma (uterine fibroids) and / or endometriosis. Transferred thromboembolic disorders (diseases of veins and arteries). sisters) Arterial hypertension Liver disease now or in history (eg liver adenoma) Increased blood cholesterol Disorders of carbohydrate metabolism, diabetes mellitus as in the presence and in the absence of complicationsGellus disease Migraine or severe headacheSysthetic lupus erythematosus Endometrial hyperplasia in history Anesthesia EpilepsyBronchial asthmaRenitis failure
Precautionary measures
Do not exceed the recommended doses. With caution If any of the following conditions / diseases are present, observed before and / or worsened during pregnancy or previous hormone therapy, the patient should be under the close supervision of a physician.It should be taken into account that these conditions / diseases may recur or worsen during treatment with Livial, in particular: - leiomyoma (uterine fibroids) and / or endometriosis; - cardiovascular failure without signs of decompensation; - risk factors for estrogen-dependent tumors ( for example, the presence of breast cancer in the next of kin / mother, sisters /); - controlled arterial hypertension; - increased concentration of cholesterol in the blood; - carbohydrate metabolism disorders, diabetes mellitus as present, t ak and in the absence of complications; - cholelithiasis; - migraine or severe headache; - systemic lupus erythematosus; - endometrial hyperplasia; - epilepsy; - bronchial asthma; - renal failure; - otosclerosis not related to pregnancy or previous use of hormonal contraceptive drugs.
Use during pregnancy and lactation
Livial is contraindicated for use during pregnancy and lactation.
Dosage and administration
Blisters with Livial are marked with days of the week. Start taking the drug with the pill, marked the current day. For example, if the reception day coincides with Monday, then it is necessary to take a pill marked Monday from the top row of the blister. Then take the pills according to the days of the week. From the next blister, pills are taken without any passes or breaks. Do not allow admission gaps between blisters or packs. The drug Livial should not be taken in the period before the expiration of 12 months after the last natural menstruation. If you start taking Livial before the specified time, then the likelihood of irregular bleeding from the vagina increases. In case of any side effects, consult a doctor immediately. If you forgot to take the drug Livial If you forgot to take the pill, then take it as soon as you think about it, but no later than 12 hours. If you have delayed taking the pill for more than 12 hours, then skip it. Do not take double the dose to replenish the missed individual dose.
Side effects
Lower abdominal pain Vaginal bleeding / bleeding Strengthening vaginal mucous discharge Weight gain Soreness in the mammary glands Strengthening hair growth, including on the face Discomfort in the vagina, for example, discharge, itching and irritation of Acne. Mastinium.Dementia (mental impairment, expressed in loss of memory). Other possible side effects may be; Dizziness, headache, migraine Depression Skin rashes or itching of the skin effects, including those not mentioned in this manual, which appeared during the administration of Livial. During HRT, the following can be diagnosed: Proliferation of the endometrium. gland cancer, other benign and malignant hormone-dependent tumors Venous thromboembolism Myocardial infarction and / or strokeGelliferous disease Skin diseases (with the appearance of skin rashes, depigmentation, red stripes on the skin)
Overdose
The following symptoms are possible: feeling of indisposition, nausea, vaginal bleeding.
Interaction with other drugs
Livial increases blood fibrinolytic activity, which can lead to increased anticoagulant action of anticoagulants, in particular of warfarin, therefore, the dose of warfarin should be adjusted accordingly for MHO. Simultaneous use of the drug Livial and anticoagulants must be controlled, especially at the beginning and at the end of treatment with Livial. There is only limited information regarding the pharmacokinetic interaction with treatment with tibolone. An in vivo study demonstrated that combined use with tibolone to a small extent affects the pharmacokinetics of the cytochrome P450 3A4 substrate midazolam. Based on this, drug interactions with other CYP3A4 substrates are possible. Medicinal products — CYP3A4 inducers, such as barbiturates, carbamazepine, hydantoins, and rifampicin, can increase Tibolone metabolism and thus affect its therapeutic effect. Drugs containing Hypericum perforatum (Hypericum perforatum) can enhance the metabolism of estrogens and progestins through induction of the CYP3A4 isoenzyme. Increased metabolism of estrogens and progestins can lead to a decrease in their clinical effect and a change in the profile of uterine bleeding.
special instructions
The drug Livial is not intended for use as a contraceptive and does not protect against unwanted pregnancy. The decision to start taking Livial should be based on an evaluation of the “benefit / risk” ratio taking into account all individual risk factors, and for women over 60 years old, you should also take The increased risk of stroke is considered. For the treatment of postmenopausal symptoms, Livial should only be prescribed for symptoms that adversely affect the quality of life. In all cases, it is necessary to conduct a thorough assessment of the risk and benefits of therapy at least once a year, and therapy with Livial should be continued only during the period of time when the benefits of therapy exceed the risk. It is necessary to carefully evaluate the risk of stroke, breast cancer and cancer endometrium in every woman with an intact uterus, taking into account all individual risk factors, the incidence and characteristics of both types of cancer and stroke in terms of curability, morbidity and mortality. Evidence of in relative risk associated with HRT or use of tibolone for the treatment of premature menopause is limited. However, the benefit / risk ratio in women with premature menopause may be more favorable than in older women due to the lower absolute risk level in younger women. Medical examination / observation Before initiating or resuming Livial therapy, an individual and family medical history. Physical examination (including examination of the pelvic organs and mammary glands) should be carried out taking into account the data of anamnesis, absolute and relative contraindications. During therapy, preventive follow-up examinations are recommended, the frequency and nature of which are determined by the patient's individual characteristics, but at least 1 time in 6 months. In particular, the woman should be informed about the need to report to the doctor about changes in the mammary glands. Surveys, including appropriate imaging methods, such as mammography, should be conducted in accordance with the current examination scheme adapted to the clinical needs of each patient.but at least 1 time in 6 months. The reasons for the immediate cancellation of therapy and immediate treatment to the doctor Therapy should be stopped if a contraindication is detected and / or in the following conditions / diseases: - jaundice or deterioration of liver function; - sudden increase in blood pressure, different from the usual indicators AD, characteristic for the patient; - the occurrence of migraine-type headache. Hyperplasia and endometrial cancer. Data from randomized controlled clinical studies are contradictory, but the data from observational studies had an increased risk of endometrial hyperplasia or cancer in women prinimayuschihpreparat Livial. These studies have shown that the risk of developing endometrial cancer increases with increasing duration of drug use. Tibolone may increase the thickness measured by transvaginal ultrasound. Breakthrough bleeding and bleeding may occur during the first months of treatment. If bleeding / bleeding occurs during the use of the drug Livial, which lasts more than 6 months from the start of taking the drug or starts after 6 months after starting the drug Livial and continue even after the patient has discontinued the use of the drug Livial, you must turn to Chu - this may be a sign of endometrial hyperplasia. Breast cancer The data from different clinical studies from the point of view of evidence-based medicine regarding the risk of developing breast cancer when taking Tibolone is contradictory, and further research is required. According to a study of a million women, a significant increase in the risk of developing cancer was found. mammary gland when using a dose of 2.5 mg. This risk became apparent after several years of use of the drug and increased with an increase in the duration of use, returning to the initial level several years later (more often 5 years) after stopping the use of the drug. These results were not confirmed during the study using the General (medical) Database Practice (GPRD) [General Practice Research Database]. Ovarian cancer Ovarian cancer is much less common than breast cancer.Long-term (at least 5-10 years) estrogen replacement therapy was associated with a slight increase in the risk of ovarian cancer. Some studies, including the Women's Health Initiative (WHI) study, suggest that long-term therapy with combined drugs for hormone therapy have a similar or slightly lower risk. In a study of a million women, it was shown that the relative risk of developing ovarian cancer when using tibolone was similar to the risk associated with Other types of HRT. Venous thromboembolism Preparations for HRT containing only estrogen, or combination drugs for HRT containing estrogen and gestagen may increase the risk of venous thromboembolism (VTE) (ie, deep vein thrombosis or pulmonary embolism) 1.3-3. times, especially during the first year of use of drugs for hormone therapy. According to an epidemiological study using UK databases, the risk of developing VTE associated with taking tibolone was lower than the risk associated with normal T, but due to the fact that at that time only a small proportion of women took tibolone, a slight increase in risk compared with women who did not take tibolone cannot be ruled out. Patients with known thrombophilic conditions have an increased risk of developing VTE, and taking Livial can To increase this risk, therefore, the use of the drug in this population of patients is contraindicated. The risk factors for the development of VTE are the use of estrogens, old age, extensive surgery, long-term immobi ization, obesity (body mass index (BMI)> 30 kg / m2), pregnancy and the postpartum period, systemic lupus erythematosus and rak.U patients after surgery is necessary to pay special attention to preventive measures for the prevention of venous thromboembolism in the postoperative period. If necessary, prolonged immobilization after surgery recommended a temporary cessation of taking the drug Livial 4-6 weeks before the operation. Treatment should not be resumed until the woman recovers to physical activity. Women who have no history of VTE but who have first-degree relatives with a history of thrombosis at a young age may be screened (a woman should be informed that only part of thrombophilic conditions are detected during screening).If a thrombophilic condition is found that is isolated from thrombosis in relatives or a serious disorder (for example, antithrombin, protein S, protein C or a combination of disorders), taking Livial is contraindicated. For women who are already receiving anticoagulant treatment, careful consideration of the ratio benefit / risk of using HRT or tibolone. If VTE develops after the start of treatment, the drug should be stopped. Patients should be informed of the need to immediately see a doctor if symptoms of potential thromboembolism appear (for example, pain and unilateral edema of the lower limb, sudden chest pain, shortness of breath). Coronary heart disease (CHD) No evidence of protection against heart attack has been obtained in randomized controlled studies myocardium in women with the presence or absence of coronary artery disease who received hormone therapy with combined drugs (estrogen / progestogen) or drugs for hormone therapy containing only estrogen. In epidemiological ecological research using the GPRD database was not obtained evidence of protection against myocardial infarction in postmenopausal women who received tibolon.Ishemichesky insultTerapiya drug Livial increases the risk of ischemic stroke from the first year of application. The absolute risk of stroke is strictly dependent on age, and, consequently, this effect of tibolone is greater, the greater the age. In case of unexplained migraine-like headaches with or without visual impairment, it is necessary to consult a doctor as soon as possible. In this case, you should not take the drug until the doctor confirms the safety of continuing HRT, since such headaches can be an early diagnostic sign of a possible stroke. Other conditions According to available data, treatment with Livial resulted in a significant dose-related decrease in HDL cholesterol (with -16.7% with dose of 1.25 mg to -21.8% at a dose of 2.5 mg after 2 years of use). The total concentration of triglycerides and lipoprotein also decreased. The decrease in total cholesterol and VLDL cholesterol was not dose-dependent. Concentrations of LDL cholesterol did not change.The clinical significance of these data is not yet known. Estrogens can cause fluid retention, so patients with cardiac or renal failure should be under the close supervision of a physician. Women with existing hypertriglyceridemia should be under the close supervision of a physician during therapy with Livial, because rare cases of a significant increase in plasma triglycerides, contributing to the development of pancreatitis, were observed during estrogen therapy in this condition. Treatment with Livial results in a very small decrease in thyroxin-binding globulin (TSH) and total T4. The level of total T3 does not change. Livial decreases the level of the sex hormone-binding globulin (SHBG), whereas the levels of corticosteroid-binding globulin (CGC) and circulating cortisol do not change. The use of drugs for HRT does not improve cognitive function. There is evidence of an increased risk of the possible development of dementia in women, at the beginning of continuous therapy with combination drugs for HRT or drugs for HRT containing only estrogen, after the age of 65.