Velledien tabs 2.5mg #28

Velledien instruction

You can buy Velledien here

Composition

Each tablet contains:
Active substance:
Tibolone - 2.50 mg;
Excipients:
lactose monohydrate - 69.44 mg, microcrystalline cellulose - 17.36 mg, ascorbyl palmitate - 0.20 mg, corn starch - 10.00 mg, magnesium stearate - 0.50 mg.
Description:
Round, flat-cylindrical tablets of white color.
Pharmacotherapeutic group
other estrogens.
ATX code: G03CX01

Pharmacodynamics

The drug selectively regulates estrogen-like activity in tissues and is a tissue-selective regulator. Its pharmacodynamic properties are determined by the action of three pharmacologically active metabolites of tibolone: ​​3-alpha-hydroxy-tibolone and 3-beta-hydroxy-tibolone possess estrogen-like activity; the delta-4-isomer is characteristic of progestagen-like and weak androgen-like activity. The drug compensates for the estrogen deficiency in the postmenopausal period, alleviating the symptoms associated with their deficiency - "hot flashes", depression, increased sweating at night, and headache. A positive effect on libido and mood (increases the concentration of central and peripheral opioids). It has a trophic effect on the mucous membrane of the vagina, without causing proliferation of the endometrium. It prevents bone loss after menopause or removal of the ovaries. Reduces the concentration of phosphate and calcium in the blood plasma.

Pharmacokinetics

After ingestion, tibolone is rapidly and rapidly absorbed. Eating does not have a significant effect on the absorption of the drug.
As a result of the rapid metabolism of tibolone, its plasma concentration is very low. The concentration of delta 4-isomer in the blood plasma is also very low, so a number of pharmacokinetic parameters cannot be determined. The maximum plasma concentrations of metabolites 3 alpha-hydroxy-tibolone (3a-OH) and Zbeta-hydroxy-tibolone (3-in-OH) are higher, but no cumulation occurs.
Excretion of tibolone occurs mainly in the form of conjugated metabolites (mainly sulphated). A part of taken tibolone is excreted by the kidneys, the most part - through the intestines.
Tibolone pharmacokinetic parameters are independent of renal function.

Indications for use

• Treatment of symptoms of estrogen deficiency in postmenopausal women (no earlier than 1 year after the last menstruation at the onset of natural menopause or immediately after surgical menopause);
• prevention of postmenopausal osteoporosis in women with a high risk of fractures with intolerance or contraindications to the use of other drugs for the treatment of osteoporosis.

Contraindications for Velledien

    Pregnancy and breastfeeding period;
    diagnosed (including, in the anamnesis) breast cancer or suspicion of it and diagnosed (including, in the anamnesis) estrogen-dependent malignant tumors (for example, endometrial cancer) or suspicion of them;
    bleeding from the vagina of unknown etiology;
    thrombosis (venous and arterial) and thromboembolism at present or in history (including thrombosis and deep vein thrombophlebitis, thromboembolism of the pulmonary artery), coronary heart disease, myocardial infarction, ischemic and hemorrhagic cerebrovascular disorders;
    conditions preceding thrombosis (including transient ischemic attacks, angina pectoris at present or in history);
    identified susceptibility to venous or arterial thrombosis, including resistance to activated protein C, deficiency of protein C, deficiency of protein S or antithrombin III, antibodies to phospholipids (antibodies to cardiolipin, lupus anticoagulant);
    multiple or pronounced risk factors for venous or arterial thrombosis, including complicated lesions of the cardiac valve apparatus, atrial fibrillation, vascular diseases of the brain or coronary arteries; uncontrolled arterial hypertension;
    extended surgical intervention with prolonged immobilization,
    extensive injury, smoking over the age of 35, obesity with a body mass index of> 30 kg / m2;
    • malignant or benign tumors (including liver adenoma); currently or in history;
    a history of liver failure, acute liver disease, or liver disease, after which liver function tests did not return to normal;
    hypersensitivity to Velledien or any of its components;
    porphyria;
    otosclerosis that occurred during a previous pregnancy or when using hormonal contraceptive drugs in history;
    chronic heart failure (FC III-IV), cerebrovascular disorders;
    period less than 1 year after the last menstruation;
    untreated endometrial hyperplasia;
    rare hereditary diseases: galactose intolerance, lactase deficiency, or glucose-galactose malabsorption.

Carefully

If any of the conditions / diseases listed below are present, observed previously and / or exacerbated during pregnancy or previous hormone therapy, the patient should be under the close supervision of a physician. It should be borne in mind that these conditions / diseases may recur or worsen during the treatment with Velledien, in particular:
    leiomyoma (uterine fibroma) or endometriosis;
    cardiovascular failure without signs of decompensation;
    the presence of risk factors for estrogen-dependent tumors (for example, breast cancer in first-degree relatives);
    controlled arterial hypertension;
    hypercholesterolemia;
    carbohydrate metabolism disorders, diabetes, both in the presence and in the absence of complications;
    cholelithiasis ;
    migraine or severe headache;
    systemic lupus erythematosus;
    endometrial hyperplasia in history;
    epilepsy;
    bronchial asthma;
    renal failure;
    otosclerosis, not associated with pregnancy or prior use of hormonal contraceptive drugs.

Use during pregnancy and breastfeeding

The drug is contraindicated during pregnancy and during breastfeeding.

Dosage and administration

The drug Velledien ingested 1 tablet per day, without chewing, drinking water, preferably at the same time, continuously. The first is taken a pill from the top row cell, marked by the day of the week, corresponding to the day of the beginning of the reception. All other tablets are taken sequentially from the cells in the direction of the arrow on the calendar package, until all the tablets are taken.

Start taking the drug Velledien

For the treatment of postmenopausal symptoms, the drug Velledien should be used only for symptoms that adversely affect the quality of life of a woman. Reception of the drug Velledien begin no earlier than 12 months after the last menstruation at the onset of natural menopause. Patients with menopause due to surgery can begin taking the drug right away. In all cases, at least 1 time in 6 months, it is necessary to conduct a thorough assessment of the risks and benefits of treatment and to continue the use of the drug during the period of time when the benefits of therapy outweigh the risks.
Switch to taking the drug Velledien after another drug for hormone replacement therapy (HRT)
Women with an intact uterus, when switching to taking the drug Velledien after using another HRT drug containing only estrogens, are advised to first induce menstrual-like “withdrawal” bleeding by applying progestogen to eliminate likely existing endometrial hyperplasia.
When switching from a drug for HRT with a cyclic regimen, Velledien should be taken the next day after the completion of the use of progestogen.
If the transition is carried out with a combined HRT drug with a continuous regimen, Velledien can be taken at any time.

Violation of the regimen

A missed pill, if less than 12 hours have passed since the admission, a woman should take it as soon as possible on the same day. The next pill is taken at the usual time of day.
If the delay in taking the pill is more than 12 hours (the interval from the moment of taking the last pill is more than 36 hours), you do not need to take the missed pill, and the next pill must be drunk at regular times.

Side effects of Velledien

To determine the incidence of side effects of Velledien used the following classification:
    Very often (> 1/10)
    Often (> 1/100 and <1/10)
    Infrequently (> 1/1 000 and <1/100)
    Rarely (> 1/10 000 and <1/1 000)
    Very rarely (> 1/10 000).
Disturbances from the gastrointestinal tract: often - pain in the lower abdomen.
Violations of the skin and subcutaneous tissues: often - increased hair growth, including on the face; infrequently - acne.
Disorders of the reproductive system and mammary glands: often - vaginal discharge, increase in endometrial thickness, bleeding or bleeding from the vagina, pain in the mammary glands, genital itching, vulvovaginal candidiasis, pain in the pelvic region, cervical dysplasia, vulvovaginitis; infrequently, mycosis, breast engorgement, nipple soreness.
Laboratory and instrumental data: infrequently - weight gain; deviations of the cervical smear results (deviation from the normal values ​​of the cytological characteristics of the cervical epithelium).
Most of the side effects were mild. The incidence of cervical disease (cervical cancer) did not increase when Tibolone was taken compared with placebo.
Other possible side effects may be (frequency not set):
    dizziness, headache, migraine;
    depression;
    skin rashes, itchy skin, seborrheic dermatitis;
    visual impairment (including blurred vision);
    gastrointestinal disorders (diarrhea, flatulence);
    fluid retention, peripheral edema;
    pain in the joints and muscles;
    abnormal liver function (including increased transaminase activity).

Risk of developing breast cancer

In women receiving combined therapy (estrogen / progestogen) drugs for more than 5 years, there has been a twofold increase in the diagnosis of breast cancer.
Any increased risk in patients receiving only estrogen or tibolone is significantly lower than the risk observed in patients receiving therapy with combined (estrogen / gestagen) drugs.
The level of risk depends on the duration of use (see section "Special instructions").

Risk of endometrial cancer

The risk of endometrial cancer is about 5 cases per 1000 women with an unremoved uterus who do not receive HRT or tibolone.
The highest risk of endometrial cancer was observed in a randomized, placebo-controlled study that included women who were not initially examined for endometrial pathology, so the study design was close to the clinical practice conditions (LIFT study, mean age 68 years). In this study, there were no cases of endometrial cancer diagnosed in the placebo group (n = 1746) after follow-up for 2.9 years, compared with 4 cases of endometrial cancer in the tibolone group (n = 1746), which corresponds to diagnosis 0 , 8 additional cases of endometrial cancer per 1000 women who received tibolone for 1 year in this study (see section “Special Instructions”).

Risk of ischemic stroke

The relative risk of developing ischemic stroke does not depend on the age or duration of Velledien intake, but the absolute risk strongly depends on age. The overall risk of ischemic stroke in women taking Tibolone will increase with age (see “Special Instructions”).
A randomized controlled trial of 2.9 years established a 2.2-fold increase in the risk of stroke in women (mean age 68 years) who took Tibolone 1.25 mg (28/2249) compared with placebo (13/2257) . Most (80%) strokes were ischemic.
The absolute risk of developing a stroke strongly depends on age. So the absolute risk for 5 years is 3 cases per 1000 women aged 50-59 years and 11 cases per 1000 women aged 60-69 years.
For women taking tibolone for 5 years, we can expect about 4 additional cases per 1000 patients aged 50–59 years and 13 additional cases per 1000 patients aged 60–69 years.
Other adverse events associated with the use of drugs for HRT containing only estrogen and HRT with combined (estrogen / progestogen) drugs for HRT were also noted:
• Prolonged use of drugs for hormone therapy containing only estrogen and combined (estrogen / stagenic) drugs was associated with a slight increase in the risk of ovarian cancer. According to the “Research of a Million Women”, HRT for 5 years resulted in 1 additional case of cancer per 2500 patients. This study showed that the relative risk of ovarian cancer when taking Tibolone is similar to the risk of using other drugs for HRT.
• Tibolone intake is associated with an increase in the relative risk of venous thromboembolism (VTE), i.e. deep vein thrombosis and pulmonary thromboembolism, 1.3-3 times. This phenomenon occurs more often during the first year of the drug use (see section "Special Instructions").
• There is a slight increase in the risk of coronary heart disease (CHD) in patients over 60 years of age who are receiving HRT combined (estrogen / gestagen) drugs. There is no reason to believe that the risk of myocardial infarction while taking tibolone is different from the risk of using other types of HRT.
• Diseases of the gallbladder (cholelithiasis, cholecystitis).
• Skin diseases: chloasma, erythema multiforme, erythema nodosum,
vascular purpura.
• Dementia at the start of treatment at the age of 65 years (see “Special instructions”).
• Pancreatitis.
• Increased blood pressure.

Overdose

The acute toxicity of tibolone in animals is very low, so toxic symptoms can not be expected, even if the patient took several tablets at the same time. In cases of acute overdose, nausea, vomiting and vaginal bleeding may develop. The antidote is unknown. Recommended symptomatic therapy.

Interaction with other drugs

Tibolone increases blood fibrinolytic activity, which can lead to increased anticoagulant action of anticoagulants, in particular warfarin, therefore, the dose of warfarin should be adjusted accordingly to INR (international normalized ratio).
The simultaneous use of tibolone and anticoagulants must be controlled, especially at the beginning and at the end of treatment with tibolone.
There is only limited information regarding pharmacokinetic interactions in the treatment of tibolone. An in vivo study demonstrated that co-administration 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. CYP3A4 drug inducers (barbiturates, carbamazepine, hydantoin derivatives, rifampicin), while being applied, can increase Tibolone metabolism and, therefore, affect its therapeutic effect.
Drugs containing Hypericum perforatum (Hypericum perforatum) can increase the metabolism of estrogens and progestogens through the induction of CYP3A4 isoenzyme. Increased metabolism of estrogens and progestogens can lead to a decrease in their clinical effect and a change in the profile of uterine bleeding.

special instructions

Velledien is not intended for use as a contraceptive and does not protect against unwanted pregnancy.
The decision to start taking Velledien should be based on the “benefit / risk” ratio, taking into account all individual risk factors, and in women over 60 years old, the increased risk of developing strokes should also be taken into account.
For the treatment of postmenopausal symptoms, the drug Velledien should be prescribed only in relation to 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 the use of the drug Velledien should be continued only when the benefits of therapy exceed the risk.
It is necessary to carefully evaluate the risk of developing stroke, the risk of developing breast cancer and endometrial cancer in every woman with an intact uterus (see the section “Side Effects”), taking into account all individual risk factors, the incidence and characteristics of both types of cancer and stroke in terms of cure. morbidity and mortality.
Evidence of the relative risk associated with hormone replacement therapy (HRT) or the 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

An individual and family medical history should be collected before starting or resuming Velledien.
A woman needs to see a doctor - this may be a sign of endometrial hyperplasia.

Mammary cancer

Evidence from evidence-based clinical trials
regarding the risk of developing breast cancer when taking tibolone is controversial and further research is needed.
According to the “Research of a Million Women”, a significant increase in the risk of developing breast cancer was revealed with the use of tibolone 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 after a few years (more often 5 years) after stopping the use of the drug.
These results were not confirmed during the study using the General Practitioner Practice (GPRD) 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 combination drugs for HRT may 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 the use of other types of HRT.

Venous thromboembolism

HRT preparations containing only estrogen, or combined HRT drugs containing estrogen and progestogen, may increase the risk of VTE (deep vein thrombosis or pulmonary embolism) 1.3 times, especially during the first year of the use of drugs for HRT .
Data on the increased risk of developing VTE when using tibolone are insufficient, however, 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 Velledien can increase this risk, therefore the use of the drug in this population of patients is contraindicated.
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.
Particular attention should be paid to preventive measures to prevent the development of thrombosis, VTE in the postoperative period. It is recommended that discontinuation of therapy with Velledien for 4-6 weeks before surgery, if in the future long-term adherence to bed rest is expected. Treatment should not be resumed until the woman has restored physical activity.
Women who have a history of VTE are absent, but who have first-degree relatives with a history of thrombosis at a young age, may be offered screening (a woman should be informed that only part of thrombophilic conditions are detected during screening). If a thrombophilic condition is detected, which is isolated from thrombosis in relatives, or a serious disorder (for example, a deficiency of antithrombin III, protein S, protein C, or a combination of disorders), taking the drug Velledien is contraindicated.
Before prescribing tibolone to women receiving anticoagulants, the physician should carefully evaluate the benefit / risk ratio of HRT or tibolone.
If, after the start of treatment, VTE develops, the drug should be stopped. A woman should be informed of the need to immediately consult a doctor if symptoms of potential thromboembolism appear (pain and unilateral edema of the lower limb, sudden chest pain, shortness of breath).

Coronary heart disease

In randomized controlled trials, there is no evidence of protection against myocardial infarction in women with or without coronary artery disease who received HRT with a combination of drugs (estrogen / gestagen) or drugs for HRT containing only estrogen. In epidemiological studies using the GPRD database, there was no evidence of protection against myocardial infarction in postmenopausal women who received Tibolone.
Velledien or any other drugs for HRT should not be used for the prevention of cardiovascular diseases.

Ischemic stroke

Taking tibolone increases the risk of ischemic stroke, starting from the first year of use.
The absolute risk of stroke is strictly dependent on age, and, consequently, this effect of tibolone is greater, the greater the age.
If you experience unexplained migraine-like headaches with or without visual impairment, you should consult a doctor as soon as possible. In this case, you can not take the drug until the doctor confirms the safety of continuing HRT, since these headaches can be an early diagnostic sign of a possible stroke.

Other states

• According to the available data, the use of tibolone led to a significant
dose-dependent reduction of HDL cholesterol (high density lipoprotein) (from 16.7% at a dose of 1.25 mg to 21.8% at a dose of 2.5 mg after two years
applications).
• The total concentration of triglycerides and lipoproteins has decreased. The decrease in total cholesterol and VLDL (very low density lipoprotein) cholesterol was not dose-dependent. The concentration of LDL cholesterol (low density lipoprotein) did not change. The clinical significance of this data is not yet known.
• Estrogens can cause fluid retention, so patients with heart or kidney failure should be closely monitored.
the doctor.
• Women with existing hypertriglyceridemia should be under
careful observation of the physician during tibolone therapy, as rare
cases of a significant increase in plasma triglyceride concentrations contributing to the development of pancreatitis were noted during estrogen therapy in this condition.
• Taking tibolone can cause a slight decrease in plasma concentration of thyroxin-binding globulin (TSH) and total T4. The concentration of total T3 does not change. Tibolone reduces the concentration of sex hormone-binding globulin (SHBG), but does not affect the concentration of corticosteroid-binding globulin (CGS) and free cortisol.
• The use of drugs for HRT does not improve cognitive function. There is evidence of an increased risk of possible development of dementia in women at the start of continuous therapy with drugs for hormonal hormone therapy containing only estrogens after the age of 65.

Impact on the ability to drive vehicles, machinery

No effect of tibolone on the concentration of attention and ability to drive vehicles and other mechanisms was noted.

Release form

2.5 mg tablets. On 28 tablets in the blister from PVC / Al foil. 1 blister together with
the application instruction is placed in a pack cardboard.

Storage conditions

Store at a temperature not higher than 25 ° С.
Keep out of the reach of children.
Shelf life - 3 years.
Do not use the drug after the expiration date.

Terms of sell

You don't need a prescription to buy Velledien.