Livial®

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%) .

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.

Use of the drug Livial

The Livial package contains 28 white tablets. The tablets should be swallowed without chewing, preferably at the same time of day. The dose of the drug is 1 tablet per day. Improvement is usually achieved within a few weeks, but the best results are observed with treatment for at least 3 months. At the recommended dose, taking Livial may last longer. The first pill to be taken is from the top row, surrounded by a frame, which is marked with the day corresponding to the day you start taking Livial. The following tablets are taken 1 tablet per day in the direction of the arrow on the package until all tablets have been taken.

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.

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.

Contraindications

• The period is less than a year after the last menstruation;
• Thrombosis (arterial or venous) and thromboembolism currently or in history (including thrombophlebitis and deep vein thrombosis, pulmonary embolism, hemorrhagic or ischemic cerebrovascular disorders, myocardial infarction);
• Diagnosed (including a history of) malignant estrogen-dependent tumors (for example, endometrial cancer) or suspected of them;
• Diagnosed (including a history of) breast cancer or suspicion of it;
• Diagnosed thrombophilic conditions (eg, protein S, protein C or antithrombin deficiency);
• Untreated endometrial hyperplasia;
• Bleeding from the vagina of unknown etiology;
• Conditions preceding thrombosis (including angina pectoris and transient ischemic attacks), currently or in history;
• Cardiovascular failure in the stage of decompensation;
• Numerous or pronounced risk factors for the development of arterial or venous thrombosis (including atrial fibrillation, subacute bacterial endocarditis and complicated lesions of the valvular apparatus of the heart, uncontrolled arterial hypertension, extended surgical intervention accompanied by prolonged immobilization, extensive trauma, obesity (with a body mass index of more than 30 kg/m2 );
• Liver failure;
• Acute liver disease or a history of liver disease, after which liver function tests have not returned to normal;
• Benign or malignant liver tumors (including liver adenoma) currently or in history;
• Porphyria;
• Otosclerosis that developed during the use of hormonal contraceptives in history or during a previous pregnancy;
• Rare hereditary diseases: galactose intolerance, glucose-galactose malabsorption or lactase deficiency;
• Pregnancy and lactation (breastfeeding);
• Established hypersensitivity to the components of the drug.

Livial should be taken with caution if any of the following diseases/conditions currently exist, have previously occurred, and/or have been aggravated during previous hormone therapy or pregnancy:

• Cardiovascular failure without signs of decompensation;
• Endometriosis and/or leiomyoma (uterine fibroids);
• Presence of risk factors for estrogen-dependent tumors (for example, genetic predisposition);
• Increased concentration of cholesterol in the blood;
• Controlled arterial hypertension;
• severe headache or migraine;
• Diabetes mellitus, carbohydrate metabolism disorders (regardless of the presence or absence of complications);
• Cholelithiasis;
• History of endometrial hyperplasia;
• Systemic lupus erythematosus;
• Epilepsy;
• Kidney failure;
• Bronchial asthma;
• Otosclerosis not associated with previous use of hormonal contraceptives or pregnancy.

When using Livial in these cases, the woman should be under close medical supervision. It should be taken into account that when taking the drug, these diseases/conditions may worsen or recur.

Special instructions for the use of Livial

Livial is not intended for use as a contraceptive. Taking doses higher than recommended may cause vaginal bleeding. If it is necessary to use the drug in higher doses, additional use of progestogen in courses of 10 days every 3 months is recommended. It is not recommended to start taking Livial before 1 year after the last natural menstruation. If you start taking it earlier, irregular bleeding from the vagina may appear. When switching to Livial after using another hormone replacement agent, it is recommended to first induce withdrawal bleeding by using a progestogen to eliminate possibly existing endometrial hyperplasia. During long-term use of steroid hormones, periodic medical examination is recommended. Livial should be discontinued if signs of thromboembolism appear, laboratory tests of liver function change, or cholestatic jaundice develops. Patients with any of the following pathological conditions should be constantly monitored: impaired renal function, epilepsy or migraine (or a history of these diseases), since taking steroid hormones may contribute to fluid retention in the body; hypercholesterolemia, since while taking Livial there were cases of changes in the lipid profile of the blood serum; disorders of carbohydrate metabolism, since Livial can reduce glucose tolerance and increase the need for insulin or other antidiabetic drugs.

LIVIAL

special instructions

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/monitoring Prior to initiation or resumption of therapy, individual and family medical history.

Physical examination (including pelvic examination 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 that 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 famous

thrombophilic conditions have an increased risk of developing VTE, and taking Livial® may increase this risk, therefore the use of the drug in this patient population is contraindicated (see section "Contraindications").

Risk factors for the development of VTE are the use of estrogens, old age, extensive surgery, prolonged immobilization, obesity .

(body mass index (BMI) >30 kg/m ), 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").

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.

Drug interactions

Livial may increase the fibrinolytic activity of the blood, which increases the risk of enhancing the anticoagulant effect of anticoagulants, in particular warfarin. Therefore, the dose of warfarin should be adjusted accordingly. The simultaneous use of Livial with anticoagulants should be under medical supervision.

Medicines that are inducers of CYP3A4 (carbamazepine, barbiturates, rifampicin and hydantoins) can increase the metabolism of tibolone, affecting its therapeutic effect.

Preparations containing St. John's wort (Hypericum perforatum) can enhance the metabolism of estrogens and progestins, which may result in a decrease in their clinical effect and a change in the profile of uterine bleeding.

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 1800 rub. order

ZdravCity

• Livial tablets 2.5 mg 28 pcs.Organon

  RUB 2,344 order