Pharmacodynamics and pharmacokinetics
The drug Livial exhibits estrogenic, progestogenic, and also weak androgenic activity. Helps stabilize the hypothalamic-pituitary system during menopause, induces a decrease in the production of gonadotropic hormones .
In the postmenopausal , it delays the destruction of bone tissue, weakens symptoms of menopausal syndrome such as headaches, increased sweating, and “flushes” of blood to the face.
Positively affects general mood and libido, due to an increase in the concentration of peripheral and central opioids . It does not have a stimulating effect on endometrial proliferation, while at the same time stimulating the vaginal mucosa. Suppresses the ovulation in fertile women.
Prevents the development of the disease - osteoporosis , lowers the content of calcium and phosphates in the blood serum.
Tibolone is highly absorbable. The absorption process after oral administration is rapid and complete.
The transformation occurs in the liver with the release of active and inactive metabolic products.
The concentration of Tibolone in the blood plasma is quite low and reaches its peak 60-90 minutes after internal administration.
T1/2 of drug metabolites is about 7 hours, without subsequent accumulation in the body.
It is excreted, mainly in the form of metabolites, via the kidneys. A small part is excreted in feces and bile.
Pharmacological properties of the drug Livial
Pharmacodynamics. Livial stabilizes the hypothalamic-pituitary system during menopause, when the functioning of the ovaries ceases. This central effect is manifested due to a combination of hormonal (estrogenic, progestogenic and weak androgenic) properties of the drug. Livial in a daily dose of 2.5 mg inhibits the secretion of gonadotropins in postmenopausal women and inhibits ovulation in women of reproductive age. At the indicated dose, Livial does not stimulate the endometrium in postmenopausal women. Only a few patients showed slight proliferation of the endometrium, the severity of which did not change with increasing duration of drug use. There is also a stimulating effect of Livial on the vaginal mucosa. Livial at the indicated dose has been proven to prevent bone loss in the postmenopausal period. The severity of menopausal disorders, especially vasomotor ones, such as hot flashes and sweating, is reduced. Livial has a positive effect on libido and mood. Some metabolites of Livial may enhance the biological effects of this drug. Pharmacokinetics. After oral administration, tibolone is rapidly and almost completely absorbed from the gastrointestinal tract. The maximum concentration in the blood is reached after 4 hours. About 96% of tibolone in the bloodstream is bound to protein. Cumulation of neither tibolone nor its metabolites in the body is noted. In tissues, tibolone is metabolized to derivative compounds that determine the tissue specificity of the drug's action. In particular, in the endometrium, tibolone is metabolized by the enzyme 3β-hydroxysteroid dehydrogenase/isomerase to the E4 isomer, which has a progestogenic effect. On the contrary, in bone tissue the drug is metabolized to 3α/3β-OH-tibolone, which has an exclusively estrogenic effect. The half-life of tibolone is 45 hours, and its hydroxymetabolites are 6 hours. Tibolone is metabolized mainly by conjugation and deconjugation during the enterohepatic circulation to form compounds that are excreted in urine (30–35%) and feces (65–70%) .
Contraindications
- breastfeeding period;
- pregnancy period;
- vaginal bleeding of unknown etiology;
- a period of time less than 12 months since the last menstruation;
- diagnosed or suspected malignant breast tumor (including history);
- untreated endometrial hyperplasia
- diagnosed or suspected estrogen-dependent malignancies , in particular endometrial cancer and others (including a history);
- thromboembolism and thrombosis (arterial or venous) present at the present time or in the past (including thrombophlebitis and deep vein thrombosis, myocardial infarction, pulmonary embolism, hemorrhagic or ischemic cerebrovascular pathologies );
- pre-thrombotic conditions (including angina pectoris and transient ischemic attacks ), currently occurring or observed in the past;
- confirmed thrombophilic pathologies (including deficiency of antithrombin; C or S proteins);
- cardiovascular failure in the stage of decompensation;
- numerous or pronounced causes of the possible development of arterial or venous thrombosis (including uncontrolled arterial hypertension, atrial fibrillation, heart valve damage with complications, infective endocarditis, major operations with prolonged immobilization, obesity , extensive trauma);
- liver failure;
- acute liver pathology or previous liver disease that led to changes in its function;
- discovered or previously diagnosed benign or malignant liver tumors (including liver adenoma );
- otosclerosis that developed while taking hormonal contraceptives or during the previous stage of pregnancy;
- porphyria;
- rare hereditary pathologies (including lactase deficiency, galactose intolerance, glucose-galactose malabsorption);
- hypersensitivity to the components of Livial.
Livial should be prescribed with caution:
- with uterine fibroids (leiomyoma) and/or endometriosis;
- with an increased risk of developing estrogen-dependent tumors (for example, breast cancer found in close relatives);
- with cardiovascular failure without symptoms of decompensation;
- with controlled arterial hypertension;
- with elevated blood cholesterol levels;
- with cholelithiasis;
- for diabetes mellitus;
- with systemic lupus erythematosus;
- for severe headaches or migraines;
- for epilepsy;
- with a history endometrial hyperplasia
- with renal failure;
- for bronchial asthma;
- for otosclerosis that is not associated with taking hormonal contraceptives or pregnancy.
The presence of any of these pathologies, observed previously or currently, is a risk factor for their exacerbation or relapse during the use of Livial. In the presence of such conditions, the patient must be under constant supervision of the attending physician.
Livial®
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 assessment of the benefit/risk ratio, taking into account all individual risk factors, and in women over 60 years of age, the increased risk of stroke should also be taken into account.
For the treatment of postmenopausal symptoms, Livial should be prescribed only for symptoms that adversely affect 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 therapy with Livial should be continued only for a period of time when the benefits of therapy outweigh the risks.
It is necessary to carefully assess the risk of stroke, the risk of developing breast cancer and endometrial cancer in each woman with an intact uterus (see section “Side effects”), 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 the relative risk associated with hormone replacement therapy (HRT) or tibolone use 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 low level
absolute risk in younger women.
Medical examination/observation
Before starting or resuming therapy, individual and family medical history.
Physical examination (including examination of the pelvic organs and mammary glands) should be carried out taking into account medical history, absolute and relative contraindications. During therapy, preventive repeat examinations are recommended, the frequency and nature of which are determined by the individual characteristics of the patient, but at least once every 6 months. In particular, the woman should be informed about the need to inform the doctor about changes in the mammary glands.
Examinations, including appropriate imaging modalities such as mammography, should be performed according to a currently accepted examination regimen, adapted to the clinical needs of each patient, but at least every 6 months.
Reasons for immediate discontinuation of therapy and immediate consultation with a doctor
Therapy should be discontinued if a contraindication is identified and/or in the following conditions/diseases:
- jaundice or deterioration of liver function;
- a sudden increase in blood pressure that differs from the patient’s usual blood pressure readings;
- the occurrence of migraine-type headaches.
Hyperplasia and endometrial cancer
Data from randomized controlled clinical trials are conflicting, but data from observational studies have shown an increased risk of developing endometrial hyperplasia or cancer in women taking Livial® (see also section "Side effects"). These studies showed that the risk of developing endometrial cancer increases with the duration of drug use.
Tibolone may increase endometrial thickness as measured by transvaginal ultrasound.
During the first months of treatment, breakthrough bleeding and spotting may occur.
If spotting/bleeding occurs during the use of Livial®, which
- lasts more than 6 months from the start of taking the drug,
- begin 6 months after starting use of the drug Livial and continue even after the patient has stopped using the drug Livial®, you must consult a doctor - this may be a sign of endometrial hyperplasia.
Mammary cancer
Data from various clinical studies from the point of view of evidence-based medicine regarding the risk of developing breast cancer when taking tibolone are contradictory, and further research is required.
According to the Million Women Study, a significant increase in the risk of developing breast cancer was identified when using a dose of 2.5 mg (see section “Side Effects”). This risk became apparent after several years of use of the drug and increased with increasing duration of use, returning to the baseline level several years (usually five years) after discontinuation of the drug.
These results were not confirmed in a study using the General Practice Database (GPRD).
Ovarian cancer
Ovarian cancer is much less common than breast cancer. Long-term (at least 5-10 years) estrogen replacement monotherapy was associated with a slight increase in the risk of developing ovarian cancer.
Some studies, including the Women's Health Initiative study, suggest that long-term HRT combination therapy may have a similar or slightly lower risk.
The Million Women Study showed that the relative risk of ovarian cancer with tibolone was similar to the risk associated with other types of HRT.
Venous thromboembolism
HRT preparations containing only estrogens, or combined HRT preparations containing estrogen and a progestin, may increase the risk of venous thromboembolism (VTE) (i.e. deep vein thrombosis or pulmonary embolism) by 1.3-3 times, in especially during the first year of using drugs for HRT (see section “Side effects”).
In an epidemiological study using UK databases, the risk of VTE associated with tibolone was lower than the risk associated with conventional HRT, but due to the fact that only a small proportion of women were taking tibolone at that time, a minor risk cannot be ruled out. increased risk compared to women who did not take tibolone. Patients with known thrombophilic conditions have an increased risk of developing VTE, and taking Livial® may increase this risk, so use of the drug in this patient population is contraindicated (see section "Contraindications").
Risk factors for VTE include estrogen use, older age, major surgery, prolonged immobilization, obesity (body mass index (BMI) >30 kg/m2), pregnancy and the postpartum period, systemic lupus erythematosus and cancer.
In patients after surgical interventions, special attention should be paid to preventive measures to prevent VTE in the postoperative period. If prolonged immobilization is necessary after surgery, it is recommended to temporarily stop taking Livial® 4-6 weeks before surgery. Treatment should not be resumed until the woman regains motor activity. Women who do not have a history of VTE, but who have first-degree relatives with a history of thrombosis at a young age, may be offered screening (the woman should be informed that screening detects only a subset of thrombophilic conditions). If a thrombophilic condition is identified that is separate from thrombosis in relatives, or a serious disorder (for example, antithrombin III deficiency ,
protein S, protein C or a combination of disorders), taking Livial® is contraindicated.
For women already receiving anticoagulant treatment, careful consideration of the benefit/risk of using HRT or tibolone is required.
If VTE develops after starting treatment, the drug should be discontinued.
Patients should be advised to seek immediate medical attention if symptoms of potential thromboembolism occur (eg, pain and unilateral swelling of the lower extremity, sudden chest pain, shortness of breath).
Coronary heart disease (CHD)
Randomized controlled trials did not provide evidence of protection against myocardial infarction in women with or without coronary artery disease who received combined HRT (estrogen/progestogen) or HRT preparations containing only estrogen.
Epidemiological studies using the GPRD did not provide evidence of protection against myocardial infarction in postmenopausal women who received tibolone.
Ischemic stroke
Therapy with Livial® increases the risk of ischemic stroke, starting from the first year of use (see section “Side effects”). The absolute risk of stroke is strictly dependent on age, and, therefore, this effect of tibolone is greater with increasing age.
If you experience unexplained migraine-like headaches with or without visual disturbances, you should consult a doctor as soon as possible. In this case, you should not take the drug until your doctor confirms that it is safe to continue HRT, since such headaches can be an early diagnostic sign of a possible stroke.
Other states
- According to available data, treatment with Livial® led to a significant dose-dependent reduction in HDL (high-density lipoprotein) cholesterol (from - 16.7% at a 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 the concentration of total cholesterol and VLDL cholesterol (very low density lipoprotein) was not dose dependent.
LDL (low-density lipoprotein) cholesterol concentrations did not change. The clinical significance of these data is not yet known.
- Estrogens can cause fluid retention, so patients with heart or kidney failure should be closely monitored by a physician.
- Women with pre-existing hypertriglyceridemia should be closely monitored by a physician during therapy with Livial®, as cases of significant increases in concentrations
plasma triglycerides, which contribute to the development of pancreatitis, have been observed during estrogen therapy for this condition.
- Treatment with Livial® leads to a very small decrease in thyroxine-binding globulin (TBG) and total T4. Concentration
the general technical specification does not change.
Livial® reduces the concentration
of sex hormone binding globulin (SHBG), while
the concentrations
of corticosteroid binding globulin (CBG) and circulating cortisol do not change.
— The use of HRT drugs does not improve cognitive function.
There is evidence of an increased risk of possible development of dementia in women when starting continuous therapy with combined HRT drugs or HRT drugs containing only estrogens after the age of 65 years (see section "Side effects").
Side effects
Digestive system:
- lower abdominal pain;
- dyspeptic disorders ( flatulence, diarrhea );
- liver dysfunction.
Central nervous system:
- dizziness;
- migraine;
- headache;
- depression.
Endocrine system:
- weight changes;
- pretibial edema.
Reproductive system:
- thickening of the endometrium;
- vaginal discharge;
- bleeding or spotting from the vagina;
- genital itching;
- soreness of the mammary glands;
- vulvovaginal candidiasis;
- cervical dysplasia;
- pain in the pelvic area;
- vulvovaginitis.
Allergic manifestations:
- skin itching;
- seborrheic dermatitis;
- rash.
Other:
- visual impairment;
- fluid retention;
- pain in muscles and joints.
Contraindications to the use of the drug Livial
During pregnancy and breastfeeding; diagnosed hormone-dependent tumor or suspicion of its presence (breast cancer, endometrial cancer); cardiovascular or cerebrovascular disorders (thrombophlebitis, thromboembolic disorders currently or in history); vaginal bleeding of unknown etiology; development or exacerbation of otosclerosis during pregnancy or taking steroids; liver dysfunction; hypersensitivity to lactose and other ingredients of the drug.
Livial, instructions for use (Method and dosage)
The instructions for Livial recommend 1 tablet of the drug as a daily dose. There is no need to adjust the dose of the drug, taking into account the patient’s age. They try to take the tablet at the same time of day, swallowing it whole and washing it down with water.
The drug Livial is available in blisters, on the bottom of which are marked with the days of the week. The day you start taking the pills should coincide with the day marked on the blister.
For example, when taking the first pill on Monday, you should take the pill from the top row of the blister labeled “Monday” (Mon). Further administration of the drug is carried out sequentially (along the rows of tablets) in accordance with the labeling and the day of administration, including subsequent blisters.
During therapy, try not to miss the next dose of the drug and not take breaks in treatment, unless this is first recommended by the doctor.
If you accidentally miss your daily dose of Livial, the next tablet should be taken as early as possible within 12 hours.
After 12 hours, you should skip this dose and take the next tablet in the blister at the usual time. Do not take a double dose of the drug to compensate for a missed dose.
Interaction
The drug Livial may enhance the effects of anticoagulants ; therefore, the dose of the latter is subject to adjustment.
Barbiturates, hydantoins, Carbamazepine, Rifampicin can increase the metabolism of Tibolone.
Medicines containing St. John's wort (Hypericum perforatum ) increase the metabolism of progestins and estrogens.
Drug interactions Livial
The metabolism of tibolone may be accelerated and, therefore, its activity may be reduced when taken concomitantly with compounds that induce enzymatic systems. While taking Livial, sensitivity to anticoagulants may increase due to increased fibrinolytic activity of the blood (decreased fibrinogen levels; increased concentrations of antithrombin III, plasminogen and fibrinolytic activity of blood plasma). Changes in these parameters are caused by any steroid hormones; these parameters return to baseline after drug discontinuation.
special instructions
The drug is not used as a contraceptive.
Livial is recommended to be prescribed no earlier than 12 months after the last menstruation (natural menopause). In case of surgical menopause, the drug is prescribed immediately after surgery.
It is not recommended to exceed the daily dose of Livial (1 tablet) due to the risk of bleeding from the vagina.
During therapy, medical monitoring of the condition of patients suffering from epilepsy, migraine, diabetes mellitus, hypercholesterolemia, and renal dysfunction (including a history of it) is necessary.
Livial's analogs
Level 4 ATX code matches:
Ladybone
Among the frequently prescribed hormone replacement therapy drugs for menopause, there are analogues of Livial:
- Angelique;
- Femoston;
- Climodien;
- Cycloproginova;
- Klimonorm;
- Divina;
- Proginova , etc.
When searching for an effective drug during the postmenopausal , people often discuss the following topics: - which is better Angelique or Livial; Femoston or Ladybon , etc.
It is worth noting that hormone replacement therapy for menopause can only be prescribed by an experienced gynecologist, after conducting a detailed examination and collecting an anamnesis.
Therefore, it is impossible to give an unambiguous answer as to which of the existing drugs is better: Livial, Angelique, Proginova and others. Hormonal therapy is selected individually for each patient, and is carried out under the constant supervision of a doctor in compliance with all his recommendations.
Livial price, where to buy
The price of Livial tablets 2.5 mg No. 28 in Russia ranges from 1,400 rubles to 2,000 rubles.
The drug Livial (2.5 mg No. 28) can be bought in Moscow for approximately 1,750 rubles.
- Online pharmacies in RussiaRussia
LuxPharma* special offer
- Livial tab.
2.5 mg No. 28 RUR 1,470 order
ZdravCity
- Livial tablets 2.5 mg 28 pcsOrganon
RUB 2,559 order
