Klimen tablets p / o, No. 21
Russian Pharmacy name:
Климен таблетки п/о, №21
HRT for menopausal disorders,
involutional changes in the skin and genitourinary tract,
depressive conditions in menopause, as well as symptoms of estrogen deficiency due to natural menopause or hypogonadism,
sterilization or primary ovarian dysfunction in women with an unremoved uterus;
prevention of postmenopausal osteoporosis;
normalization of irregular menstrual cycles;
treatment of primary or secondary amenorrhea.
The method of application and dosage regimen of a particular drug depends on its form of release and other factors. The optimal dosage regimen is determined by the doctor. It is necessary to strictly observe the compliance of the used dosage form of a particular drug with the indications for use and the dosage regimen.
For oral administration 1 time / day.
If the patient is still menstruating, treatment should be started on the 5th day of the menstrual cycle (the 1st day of menstrual bleeding corresponds to the 1st day of the menstrual cycle).
Patients with amenorrhea or very infrequent periods, as well as postmenopausal women, can start taking it at any time, provided that pregnancy is excluded.
Dragee of two types.
Dragee white (11 pcs. In a blister).
1 tablet
Active substance:
estradiol valerate - 2 mg
Excipients: lactose monohydrate, corn starch, povidone 25000 (K25), talc, magnesium stearate, sucrose, povidone 700000 (K700), macrogol 6000, calcium carbonate, wax.
Dragee pink (10 pcs. In a blister).
1 tablet
Active ingredients:
estradiol valerate - 2 mg
cyproterone acetate - 1 mg
Excipients: lactose monohydrate, corn starch, povidone 25000 (K25), talc, magnesium stearate, sucrose, povidone 700000 (K700), macrogol 6000, calcium carbonate, glycerol 85%, titanium dioxide, iron oxide red, iron oxide yellow, wax ...
Pregnancy and lactation;
vaginal bleeding of unknown origin;
a confirmed or suspected diagnosis of breast cancer;
confirmed or suspected diagnosis of hormone-dependent precancerous disease or hormone-dependent malignant tumors;
liver tumors, current or history (benign or malignant);
severe liver disease;
acute arterial thrombosis or thromboembolism (such as myocardial infarction, stroke);
deep vein thrombosis in the acute stage, current or history of thromboembolism;
severe hypertriglyceridemia;
hypersensitivity to components;
intolerance to lactose, fructose;
children and adolescents up to 18 years old.
Carefully
Arterial hypertension, congenital hyperbilirubinemia (Gilbert, Dubin-Johnson and Rotor syndromes), cholestatic jaundice or cholestatic pruritus during pregnancy, endometriosis, uterine fibroids, diabetes mellitus, epilepsy, chorea minor, bronchial asthma, migraine, porphyria.
Clinical and pharmacological group: Anti-climacteric drug with antiandrogenic properties
Pharmaco-therapeutic group: Anti-climacteric agent (estrogen + antiandrogen)
pharmachologic effect
The medicinal product contains estrogen - estradiol valerate, which in the human body turns into natural 17? - estradiol. It also contains a progesterone derivative - cyproterone acetate, which has a gestagenic, antigonadotropic and antiandrogenic effect.
Due to the composition and cyclic regimen of this combination (taking only estrogen for 11 days, then a combination of estrogen and gestagen for 10 days, and, finally, a 7-day break), in women with an unremoved uterus, when taken regularly, the menstrual cycle is established ...
Against the background of taking the drug, ovulation is not suppressed, and the production of hormones in the body itself does not practically change. It can be used by women of reproductive age to regulate the menstrual cycle, as well as by perimenopausal women for the treatment of irregular uterine bleeding.
Estradiol replenishes the estrogen deficiency in the female body after menopause and provides effective treatment for psycho-emotional and vegetative climacteric symptoms (such as hot flashes, increased sweating, sleep disturbances, increased nervous irritability, irritability, palpitations, cardialgia, dizziness, headache, decreased libido, muscle and joint pain); involution of the skin and mucous membranes, especially the mucous membranes of the genitourinary system (urinary incontinence, dryness and irritation of the vaginal mucosa, pain during intercourse).
Estradiol prevents bone loss caused by estrogen deficiency. This is mainly due to the suppression of osteoclast function and a shift in the process of bone remodeling towards bone formation. Long-term use of HRT has been shown to reduce the risk of peripheral bone fractures in postmenopausal women. With the abolition of HRT, the rate of bone loss is comparable to those characteristic of the period immediately after menopause. It has not been proven that, using HRT, it is possible to achieve the restoration of bone mass to the premenopausal level.
HRT also has a beneficial effect on the collagen content of the skin, as well as on its density, and can also slow down the formation of wrinkles.
In addition, due to the antiandrogenic properties of cyproterone acetate, this combination has a therapeutic effect on androgen-dependent diseases such as acne, seborrhea, androgenetic alopecia.
Admission leads to a decrease in total cholesterol, LDL cholesterol and an increase in HDL, resulting in a significant increase in the HDL / LDL ratio, as well as an increase in triglyceride levels. Due to the lack of androgenic properties of cyproterone acetate, it practically does not interfere with the effect of estradiol on lipid metabolism.
The addition of cyproterone acetate for 10 days each cycle prevents the development of endometrial hyperplasia and cancer.
Pharmacokinetics
Estradiol valerate
After oral administration of estradiol, valerate is rapidly and completely absorbed. During absorption and the first passage through the liver, the ester of the hormone is broken down into estradiol and valeric acid. At the same time, estradiol undergoes significant further metabolism, for example into estrone, estriol and estrone sulfate. After oral administration, the bioavailability of estradiol is about 3%. Food intake does not affect the bioavailability of estradiol. Cmax of estradiol in serum, which is approximately 30 pg / ml, is usually achieved 4-9 hours after taking pills. 24 hours after administration, the serum estradiol concentration is reduced to a concentration of about 15 pg / ml. Estradiol binds to albumin and sex hormone binding globulin (SHBG). The free fraction of estradiol in serum is approximately 1-1.5%, and the fraction of the substance,associated SHBG, is in the range of 30-40%.
The apparent Vd of estradiol after a single intravenous administration is about 1 L / kg.
After hydrolysis of exogenous estradiol valerate, the substance passes through the same biotransformation pathways as endogenous estradiol. Estradiol is metabolized mainly in the liver, and also partially in the intestines, kidneys, skeletal muscles and target organs. These processes are accompanied by the formation of estrone, estriol, catechol estrogens, as well as sulfate and glucuronide conjugates of these compounds, all of which have significantly less estrogenic activity or have no estrogenic activity at all.
The clearance of estradiol from serum after a single intravenous administration is characterized by a high degree of variability in the range from 10 to 30 ml / min / kg. A certain part of estradiol is excreted in the bile and undergoes intestinal-hepatic recirculation. Estradiol metabolites are excreted mainly in the urine in the form of sulfates and glucuronides.
The concentration of estradiol in the blood serum after repeated administration is approximately two times higher than after the administration of a single dose. On average, the concentration of estradiol in serum ranges from 40 pg / L (minimum level) to 90 pg / L (maximum level). The concentration of estrone (weaker estrogen) is about 8 times, and the concentration of estrone sulfate is about 150 times higher than the concentration of estradiol. After stopping the intake of Klymene, the levels of estradiol and estrone return to their original values ??within two to three days.
Cyproterone acetate
After oral administration in a wide range of doses, cyproteran acetate is rapidly and completely absorbed. The absolute bioavailability after oral administration is 88%.
Cmax of cyproterone acetate in serum, which is about 30 ng / ml, is achieved within 1-2 hours after a single dose of 1 mg of cyproterone acetate.
Cyproterone acetate binds almost exclusively to serum albumin. About 3.5-4% of the total serum cyproterone acetate concentration is not protein bound. Since binding to plasma proteins is not specific, changes in SHBG levels do not affect the pharmacokinetics of cyproterone acetate. Cyproterone acetate is metabolized by a variety of pathways including hydroxylation and conjugation. The main metabolite in human serum is the 15?-hydroxyl derivative.
The serum clearance of cyproterone acetate is 3.6 ml / min / kg. Some of the dose received is excreted unchanged in the bile. Most of the dose is excreted in the form of metabolites along with urine and bile in a ratio of 3: 7, T1 / 2 1.9 days. The metabolites are excreted from the serum with a similar T1 / 2 equal to 1.7 days.
Due to the prolonged T1 / 2 of cyproterone acetate from serum, it can be expected that the concentration of cyproterone acetate in serum during one cycle of taking the drug will increase by 2-2.5 times.
Indications
HRT for menopausal disorders,
involutional changes in the skin and genitourinary tract,
depressive conditions in menopause, as well as symptoms of estrogen deficiency due to natural menopause or hypogonadism,
sterilization or primary ovarian dysfunction in women with an unremoved uterus;
prevention of postmenopausal osteoporosis;
normalization of irregular menstrual cycles;
treatment of primary or secondary amenorrhea.
Dosage regimen
The method of application and dosage regimen of a particular drug depends on its form of release and other factors. The optimal dosage regimen is determined by the doctor. It is necessary to strictly observe the compliance of the used dosage form of a particular drug with the indications for use and the dosage regimen.
For oral administration 1 time / day.
If the patient is still menstruating, treatment should be started on the 5th day of the menstrual cycle (the 1st day of menstrual bleeding corresponds to the 1st day of the menstrual cycle).
Patients with amenorrhea or very infrequent periods, as well as postmenopausal women, can start taking it at any time, provided that pregnancy is excluded.
Side effect
From the side of the organ of vision: visual impairment, intolerance to contact lenses.
From the reproductive system and mammary glands: changes in the frequency and intensity of uterine bleeding, breakthrough bleeding, intermenstrual spotting (usually weakened during therapy), dysmenorrhea, changes in vaginal discharge, a condition similar to premenstrual syndrome; soreness, tension and / or enlargement of the mammary glands.
From the gastrointestinal tract: dyspepsia, bloating, nausea, vomiting, abdominal pain.
From the immune system: hypersensitivity reactions.
From the side of metabolism : an increase or decrease in body weight.
From the musculoskeletal system: muscle cramps.
On the part of the skin and subcutaneous tissue: skin rash, pruritus, chloasma, erythema nodosum.
From the side of the central nervous system: headache, migraine, dizziness.
On the part of the cardiovascular system: palpitations.
Contraindications for use
Pregnancy and lactation;
vaginal bleeding of unknown origin;
a confirmed or suspected diagnosis of breast cancer;
confirmed or suspected diagnosis of hormone-dependent precancerous disease or hormone-dependent malignant tumors;
liver tumors, current or history (benign or malignant);
severe liver disease;
acute arterial thrombosis or thromboembolism (such as myocardial infarction, stroke);
deep vein thrombosis in the acute stage, current or history of thromboembolism;
severe hypertriglyceridemia;
hypersensitivity to components;
intolerance to lactose, fructose;
children and adolescents up to 18 years old.
Carefully
Arterial hypertension, congenital hyperbilirubinemia (Gilbert, Dubin-Johnson and Rotor syndromes), cholestatic jaundice or cholestatic pruritus during pregnancy, endometriosis, uterine fibroids, diabetes mellitus, epilepsy, chorea minor, bronchial asthma, migraine, porphyria.
Application during pregnancy and lactation
Contraindicated during pregnancy and lactation (breastfeeding).
Application for violations of liver function
Contraindicated in liver tumors currently or in history (benign or malignant), in severe liver disease.
Application in children
The use is contraindicated in children and adolescents under 18 years of age.
special instructions
Not used for contraceptive purposes.
If contraception is necessary, non-hormonal methods should be used (with the exception of the calendar and temperature methods). If you suspect pregnancy, you should stop taking until the pregnancy is ruled out.
In the presence or worsening of any of the conditions or risk factors listed below, before starting or continuing HRT, the ratio of individual risk and benefit of treatment should be assessed.
When prescribing HRT for women with risk factors for VTE, the ratio of risk and benefit of treatment should be carefully weighed and discussed with the patient.
Treatment should be stopped immediately if symptoms of thrombotic disorders appear or if they are suspected.
With prolonged estrogen monotherapy, the risk of developing endometrial hyperplasia or carcinoma increases. Studies have confirmed that the addition of gestagens reduces the risk of endometrial hyperplasia and cancer.
HRT increases the mammographic density of the mammary glands, which in some cases can have a negative effect on X-ray detection of breast cancer.
Against the background of the use of sex steroids, which include drugs for HRT, in rare cases, benign, and even less often, malignant liver tumors were observed. In some cases, these tumors have resulted in life-threatening intra-abdominal bleeding. In case of pain in the upper abdomen, an enlarged liver, or signs of intra-abdominal bleeding, differential diagnosis should take into account the likelihood of a liver tumor.
»звестно, что эстрогены увеличивают литогенность желчи. Ќекоторые женщины предрасположены к развитию желчнокаменной болезни при лечении с использованием эстрогенов.
?ругие состо¤ни¤
—ледует немедленно прекратить лечение, при по¤влении впервые мигренеподобных или частых и необычайно сильных головных бол¤х, а также при по¤влении других симптомов - возможных предвестников тромботического инсульта головного мозга.
ѕри нет¤желых нарушени¤х функции печени, в том числе различных формах гипербилирубинемии, таких как синдром ?убина-?жонсона или синдром –отора, необходимы наблюдение врача, а также периодические исследовани¤ функции печени. ѕри ухудшении показателей функции печени «v“ следует отменить.
ѕри рецидиве холестатической желтухи или холестатического зуда, наблюдавшихс¤ в первый раз во врем¤ беременности или предшествующего лечени¤ половыми стероидными гормонами, необходимо немедленно прекратить «v“.
Ќеобходимо особое наблюдение за женщинами с умеренно-повышенным уровнем триглицеридов. ¬ подобных случа¤х применение «v“ может вызвать дальнейшее возрастание уровн¤ триглицеридов в крови, что повышает риск острого панкреатита .
’от¤ «v“ может вли¤ть на периферическую инсулинорезистентность и толерантность к глюкозе, необходимости измен¤ть схему лечени¤ больных сахарным диабетом при проведении «v“, обычно не возникает. “ем не менее, женщины, страдающие сахарным диабетом, при проведении «v“ должны находитьс¤ под наблюдением.
” некоторых пациенток под действием «v“ могут развитьс¤ нежелательные про¤влени¤ стимул¤ции эстрогенами, например патологическое маточное кровотечение. „астые или персистирующие патологические маточные кровотечени¤ на фоне лечени¤ ¤вл¤ютс¤ показанием дл¤ исследовани¤ эндометри¤.
?сли лечение нерегул¤рных менструальных циклов не даст результатов, следует провести обследование дл¤ исключени¤ заболевани¤ органического характера.
ѕод вли¤нием эстрогенов миомы матки могут увеличитьс¤ в размерах. ¬ этом случае лечение должно быть прекращено.
–екомендуетс¤ прекратить лечение при развитии рецидива эндометриоза на фоне «v“. ѕри подозрении на наличие пролактиномы перед началом лечени¤ следует исключить это заболевание.
¬ некоторых случа¤х может наблюдатьс¤ хлоазма, особенно у женщин с хлоазмой беременных в анамнезе. ¬о врем¤ проведени¤ «v“ женщины со склонностью к возникновению хлоазмы должны избегать длительного пребывани¤ на солнце или ультрафиолетового излучени¤.
—ледующие состо¤ни¤ могут могут возникать или усугубл¤тьс¤ на фоне «v“. ’от¤ их взаимосв¤зь с «v“ не доказана, женщины с этими состо¤ни¤ми при проведении «v“ должны находитьс¤ под наблюдением врача: эпилепси¤; доброкачественна¤ опухоль молочной железы; бронхиальна¤ астма; мигрень; порфири¤; отосклероз; системна¤ красна¤ волчанка, мала¤ хоре¤.
ѕрием половых стероидов может вли¤ть на биохимические показатели функции печени, щитовидной железы, надпочечников и почек, на содержание в плазме транспортных белков, таких как кортикостероидсв¤зывающий глобулин и липидные/липопротсиновые фракции, показатели углеводного обмена, коагул¤ции и фибринолиза.
Ћекарственное взаимодействие
ѕри начале «v“ необходимо прекратить применение гормональных контрацептивов. ѕри необходимости пациентке следует рекомендовать негормональные контрацептивы.
?лительное лечение препаратами, индуцирующими ферменты печени (например, некоторыми противосудорожными и антимикробными препаратами) может увеличивать клиренс половых гормонов и снижать их клиническую эффективность. ѕодобное свойство индуцировать ферменты печени было обнаружено у гидантоинов, барбитуратов, примидона, карбамазепина и рифампицина, наличие этой особенности также предполагаетс¤ у окскарбазепина, топирамата, фелбамата и гризеофульвина. ћаксимальна¤ индукци¤ ферментов обычно наблюдаетс¤ не раньше, чем через 2-3 недели, но затем она может сохран¤тьс¤ еще, по крайней мере, в течение 4 недель после прекращени¤ приема препарата.
In rare cases, against the background of concomitant use of certain antibiotics (for example, the penicillin and tetracycline groups), a decrease in the level of estradiol was observed.
Substances that undergo significant conjugation (for example, paracetamol ) can increase the bioavailability of estradiol due to competitive inhibition of the conjugation system during absorption.
Due to the effect of HRT on glucose tolerance, in some cases, the need for oral hypoglycemic agents or insulin may change .
Excessive alcohol consumption during HRT can lead to an increase in circulating estradiol levels.