Климен®

General characteristics. Structure:

Active agents:
- 1 tablet coated white color contains 2,0 mg of oestradiol of valerate
- 1 tablet coated pink color contains 2,0 mg of oestradiol of valerate and 1,0 mg of a tsiproteron of acetate.
Excipients:
Lactoses monohydrate - 46,180 mg, starch corn - 26,200 mg, povidone To 25 - 3,000 mg, talc
- 2,400 mg, magnesium stearate - 0,220 mg; Excipients of a cover of white tablets:
sucrose - 33,980 mg, povidone of 700000 - 0,296 mg, a macrogoal of 6000 - 3,767 mg, calcium a carbonate of-14,711 mg, talc - 7,171 mg, wax mountain glikoliyevy - 0,075 mg Excipients of a cover of pink tablets:
sucrose - 33,551 mg, povidone of 700000 - 0,323 mg, a macrogoal of 6000 - 3,720 mg, calcium a carbonate of-14,576 mg, talc - 7,106 mg, глицерол 85% - 0,206 mg, titanium dioxide - 0,411 mg, dye ferrous oxide yellow - 0,012 mg, dye ferrous oxide red - 0,020 mg, wax mountain glikoliyevy -
0,075 mg

Description
Round tablets coated white color (11 tablets) and pink color (10 tablets).

Pharmacological properties:

Pharmacodynamics. Климен® contains estrogen - oestradiol valerate which in a human body turns into 17v-oestradiol identical developed by ovaries. Also is a part of the drug Klimen® derivative progesterone - a tsiproteron the acetate possessing gestagenny, anti-gonadotropic and anti-androgenic action.
Thanks to structure and the cyclic scheme of administration of drug Klimen® (reception only of estrogen within 11 days, then - combinations of estrogen and a gestagen within 10 days, and, at last, a 7-day break) at women with disturbances of a menstrual cycle at regular administration of drug the menstrual cycle is recovered.
Against the background of administration of drug of Klimen® there is no suppression of an ovulation, and production of hormones in the organism practically does not change. Климен® it can be applied by women of reproductive age to regulation of a menstrual cycle, and also women with disturbances of a menstrual cycle in the premonopauzny period.
Oestradiol fills shortage of estrogen in a female body after approach of a menopause and provides effective treatment of psychoemotional and vegetative climacteric symptoms (such as "inflows", the increased sweating, a sleep disorder, the increased nervous irritability, irritability, a heart consciousness, cardialgias, dizziness, a headache, decrease in a libido, muscular and joint pains); involution of skin and mucous membranes, especially mucous membranes of urinogenital system (an urine incontience, dryness and irritation mucous vaginas, morbidity at sexual contact).
Oestradiol prevents the decrease in bone weight caused by deficit of estrogen. Mainly it is connected with suppression of function of osteoclasts and maintenance of balance between processes of a resorption and formation of a bone. It was proved that prolonged use of drugs for the replacement hormonal therapy (RHT) allows to reduce risk of fractures of peripheral bones at women after approach of a menopause. At cancellation of ZGT rates of decrease in bone weight are comparable with the indicators characteristic of the period directly after a menopause. It is not proved that, applying ZGT, it is possible to achieve recovery of bone weight to premenopausal level.
ZGT also has salutary effect on the content of collagen in skin, as well as on its density, and also can slow down process of formation of wrinkles.
Besides, thanks to anti-androgenic properties of a tsiproteron of acetate, the drug Klimen® makes therapeutic impact on androgenzavisimy diseases, such as an acne, seborrhea, an androgenetichesky alopecia.
Administration of drug of Klimen® leads to decrease in concentration of the general cholesterol, lipoproteids of the low density (LPNP) and to increase in lipoproteids of the high density (LPVP) therefore LPVP/LPNP ratio considerably raises, and also concentration of triglycerides increases. Due to the lack of androgenic properties of a tsiproteron acetate practically does not interfere with impact of oestradiol on metabolism of lipids. Effect of the drug Klimen® is especially noticeable at women with the expressed atherogenous changes of a lipidic profile.
Addition of a tsiproteron of acetate within 10 days each cycle prevents development of a hyperplasia and endometrial cancer.
The observation researches give the grounds to believe that among women in a postmenopause when using ZGT the indicator of cancer cases of a large intestine decreases. The action mechanism is not clear so far.

Pharmacokinetics. Oestradiol valerate Absorption
After oestradiol intake valerate is quickly and completely absorbed. During absorption and primary passing through a liver ester of hormone is split on oestradiol and valerianic acid. At the same time, oestradiol substantially is exposed to further metabolism, for example, in estrone, estriol and estrone sulfate. After oral administration bioavailability of oestradiol about 3%. Meal does not influence bioavailability of oestradiol.
Distribution
The maximum concentration of oestradiol in a blood plasma making about 30 pg/ml is usually reached in 4-9 hours after reception of tablets. In 24 hours after reception concentration of oestradiol in a blood plasma decreases to concentration approximately to 15 pg/ml.
Oestradiol contacts albumine and the globulin connecting sex hormones (GSP 11). The free fraction of oestradiol in a blood plasma makes about 1-1,5%, and the fraction of the substance connected by GSPG is in limits of 30 — 40%.
The seeming volume of distribution of oestradiol after single intravenous administration makes about 1 l/kg.
Metabolism
After hydrolysis of exogenous oestradiol of valerate, substance passes in the same ways of biotransformation, as endogenous oestradiol. Oestradiol is metabolized preferential in a liver, and also partially and in intestines, kidneys, skeletal muscles and target organs. These processes  are followed  by formation of estrone,  estriol,  katekholestrogen,   and also sulphatic and glyukuronidny conjugates of these connections, all from which have significantly smaller oestrogenic activity or have no oestrogenic activity at all.
Removal
The clearance of oestradiol from a blood plasma after single intravenous administration is characterized by high degree of variability in the range from 10 to 30 ml/min. A certain part of oestradiol is allocated with bile and is exposed to enterohepatic recirculation. Metabolites of oestradiol are removed mainly by kidneys in the form of sulfates and glucuronides.
Equilibrium concentration
Concentration of oestradiol in a blood plasma after repeated introduction is approximately twice higher, than after introduction of a single dose. On average, concentration of oestradiol is in a blood plasma ranging from 40 »ú/l (the minimum concentration) to 90 »ú/l (the maximum concentration). Concentration of estrone (weaker estrogen) approximately by 8 times, and concentration of estrone of sulfate — is about 150 times higher, than concentration of oestradiol. After the termination of administration of drug of Klimen® of concentration of oestradiol and estrone are returned to reference values within two-three days.
Tsiproterona acetate

Absorption
After intake with the broad range of doses of a tsiproteron acetate is quickly and completely absorbed. Absolute bioavailability after oral administration makes 88%.
Distribution
The maximum concentration of a tsiproteron of acetate in a blood plasma making about 30 ng/ml is reached in 1-2 hours after a single dose of 1 mg of a tsiproteron of acetate. After that two-phase decrease in concentration of a tsiproteron of acetate in a blood plasma with elimination half-lives 0,8 hours and 2,3 days, respectively is observed.
Tsiproterona acetate contacts almost only a seralbumin. Near 3,5k4 by % of the general concentration of a tsiproteron of acetate in a blood plasma it is not connected with protein. As linkng with proteins of plasma is not specific, changes of concentration of GSPG (the globulin connecting sex hormones) do not influence pharmacokinetics of a tsiproteron of acetate.

Metabolism
Tsiproterona acetate is metabolized in various ways, including a hydroxylation and conjugation. The main metabolite in a blood plasma of the person is 15v-hydroxylic
derivative.
Removal
The clearance of a tsiproteron of acetate makes 3,6 ml/min. of plasma. Some part of the received dose is removed in an invariable view with bile. The most part of a dose is removed in the form of metabolites by kidneys and through intestines in the ratio 3:7, with an elimination half-life of 1,9 days. Metabolites are brought out of plasma with a similar elimination half-life, equal 1,7 days.
Equilibrium concentration
Owing to a long elimination half-life of a tsiproteron of acetate from plasma it is possible to expect that concentration of a tsiproteron of acetate during one cycle of administration of drug will increase in a blood plasma by 2-2,5 times.

Indications to use:

• The Replacement Hormonal Therapy (RHT) at symptoms of deficit of estrogen owing to approach of a natural menopause or a hypogonadism, surgical castration or primary insufficiency of ovaries at women with the kept uterus.
• Disturbances of a menstrual cycle.
• Primary or secondary amenorrhea.
• Prevention of post-menopausal osteoporosis at women with high risk of changes at intolerance or contraindications to use of other medicines intended for treatment of osteoporosis.

Route of administration and doses:

If at the patient periods still proceed, treatment should be begun for the 5th day of a menstrual cycle (1 - й day of menstrual bleeding corresponds 1 - му to day of a menstrual cycle).
Patients with an amenorrhea or very rare periods, and also women in a postmenopause, can begin administration of drug at any time provided that pregnancy is excluded (see the section "Pregnancy and Lactation").
Each packaging is counted on 21-day reception.
Daily during the first 11 days accept on one white tablet, and then within 10 days - daily on one pink tablet. After 21-day administration of drug the 7-day break in administration of drug during which there comes the menstrualnopodobny bleeding caused by drug withdrawal follows (within several days after reception of the last tablet).
After a 7-day break in administration of drug begin administration of drug of Klimen® from new packaging, taking the first pill of week on the same day, as the first tablet from the previous packaging.
Tablets are swallowed entirely, washing down with a small amount of liquid. Time of day when the woman accepts drug, does not matter, however, if she began to take a pill in any specific time, she has to adhere to this time further. If the woman forgot to take a pill, it can accept it within the next few 24 hours. If treatment is interrupted for longer time, developing of bleeding from a vagina is possible.

Features of use:

The drug Klimen® is not used for the purpose of contraception.
In the presence of symptoms of deficit of estrogen owing to approach of a natural menopause of ZGT in the cyclic mode it is carried out at women in the perimenopauzalny period (at women in the post-menopausal period carrying out ZGT in the continuous mode is shown)
In need of contraception, it is necessary to apply non-hormonal methods (except for calendar and temperature methods). At suspicion on pregnancy it is necessary to suspend reception of tablets until pregnancy is not excluded (see the section "Pregnancy and Lactation").
At existence or deterioration any of the states or risk factors provided below before beginning or continuing administration of drug of Klimen® it is necessary to estimate a ratio of individual risk and advantage of treatment.
Purpose of the drug Klimen® to the women having several risk factors of development of thrombosis or high degree of manifestation of one of risk factors contraindicated.

Venous thromboembolism
In a number of controlled randomized, and also epidemiological researches the increased relative risk of development of a venous thromboembolism (VTE) against the background of administration of drug of Klimen®, i.e. a deep vein thrombosis or an embolism of a pulmonary artery is revealed. Therefore, at purpose of the drug Klimen® to women with risk factors of VTE the ratio of risk and advantage of treatment has to be carefully weighed and discussed with the patient.
Risk factors of development of VTE are included by the individual and family anamnesis (existence of VTE at the immediate family at rather young age can indicate genetic predisposition), the revealed predisposition to venous or arterial thrombosis, including resistance to the activated protein With, deficit of antithrombin III, deficit of a protein With, deficit of a protein of S, a gipergomotsisteinemiya, antibodies to phospholipids (antibodies to cardiolipin, lupoid anticoagulant), and also the multiple or expressed risk factors of venous or arterial thrombosis, including the complicated defeats of the valve device of heart, fibrillation of auricles, diseases of vessels of a brain or coronary arteries; uncontrollable arterial hypertension, smoking is aged more senior than 35 years, obesity with a body weight index> 30 kg/sq.m. The risk of VTE also increases with age. The question of a possible role of a varicosity in development of VTE remains disputable.
The risk of VTE can temporarily increase at a long immobilization, "big" planned and traumatologic operations or a massive injury. Depending on the reason or duration of an immobilization it is necessary to resolve an issue of expediency of the temporary termination of administration of drug of Klimen®
It is necessary to stop immediately treatment at emergence of symptoms of trombotichesky disturbances or at suspicion on their emergence.
Arterial thromboembolism
During the randomized controlled researches at prolonged use of the combined conjugated horse estrogen (CHE) and a medroksiprogesterona of acetate the evidence of positive influence on cardiovascular system was not obtained. In large-scale clinical trials of this connection possible increase of risk of the coronary heart disease (CHD) in the first year of use with the subsequent lack of positive effect was revealed. In one large clinical trial when using only KLE was found potential reduction of cases of the coronary heart disease (CHD) among women at the age of 50-59 years in the absence of the cumulative positive effect among cumulative population of a research. As secondary result in two large-scale clinical trials with use of KLE as monotherapy or in combination with MPA 30-40% increase of risk of development of a stroke were revealed. It is unknown whether this increased risk extends to other drugs for ZGT, in particular, Klimen® containing other types of estrogen and progestogens or to not peroral routes of administration.

Endometrial cancer
At long monotherapy by estrogen the risk of development of a hyperplasia or endometrial cancer increases. Researches confirmed that addition of gestagen interferes with increase in risk of a hyperplasia and endometrial cancer.
Breast cancer
According to clinical tests and to results of the observation researches increase in relative risk of development of a breast cancer in the women using drugs for ZGT within several years was revealed. It can be connected with earlier diagnosis, acceleration of growth of already available tumor against the background of ZGT or a combination of both factors. The relative risk increases with increase in duration of use, but can be absent or be reduced at treatment only estrogen. This increase is comparable to increase in risk of developing of cancer of mammary glands at women at later approach of a natural menopause, and also at obesity and an alcohol abuse. The increased risk gradually decreases to usual level within the first several years after the termination of administration of drugs for ZGT to which Klimen® belongs.
Assumptions concerning increase in risk of development of a breast cancer are made on the basis of results of more than 50 epidemiological researches.
There is a risk of distribution of RMZh out of limits of a mammary gland.
In two large-scale randomized researches with KLE separately or at a constant combination to MPA the settlement indicators of risk equal 0,77 were received (95% a confidence interval: 0,59 - 1,01) or 1,24 (95% confidence interval: 1,01 - 1,54) after about 6 years of use of this combination. It is unknown whether this increased risk as well extends to other products for ZGT, in particular, on Klimen®.
Drugs for ZGT to which Klimen® belongs, increases the mammography density of mammary glands that in certain cases can exert a negative impact on radiological detection of a breast cancer.
Liver tumors
Against the background of use of sex hormones to which also means for ZGT belong were in rare instances observed high-quality, and is even more rare - malignant tumors of a liver. In some cases these tumors led to the intra belly bleeding posing a threat for life. At pains in an upper part of a stomach, the increased liver or symptoms of intra belly bleeding at differential diagnosis it is necessary to consider probability of existence of a tumor of a liver.
Cholelithiasis
It is known that estrogen increases a bile litogennost. Some women are predisposed to development of cholelithiasis at treatment with use of estrogen.
Dementia
There are limited data showing increase in probability of risk of dementia at the women beginning reception of gormonozamestitelny therapy at the age of 65 years is more senior. The risk can be reduced if administration of drugs of ZGT is begun in an early menopause as it was observed in researches. It is unknown whether it extends to other drugs ZGT to which Klimen® belongs.

Other states
It is necessary to stop immediately treatment at emergence for the first time of the arisen migrenepodobny or frequent and extraordinary severe headaches, and also at emergence of other symptoms - possible harbingers of a trombotichesky stroke of a brain.
The interrelation between administration of drug of Klimen® and development of clinically expressed arterial hypertension is not established. At the women accepting drugs for ZGT to which the drug Klimen® belongs small increase in arterial pressure, clinically significant increase is described (over 140/90 mm рт.ст) it is noted seldom. However, in some cases, at development against the background of administration of drug of Klimen® of persistent clinically significant arterial hypertension drug withdrawal can be considered.
At not heavy abnormal liver functions, including various forms of a hyperbilirubinemia, such as syndrome the Cudgel Johnson or a syndrome of the Rotor, are necessary observation of the doctor, and also periodic researches of function of a liver. At deterioration in indicators of function of a liver the drug Klimen® should be cancelled.
At a recurrence of cholestatic jaundice or cholestatic itch, observed for the first time during pregnancy or the previous treatment by sex steroid hormones, it is necessary to stop administration of drug of Klimen® immediately.
Special observation of women with moderately increased concentration of triglycerides is necessary. In similar cases use of the drug Klimen® can cause further increase in concentration of triglycerides in blood that increases risk of acute pancreatitis.
Though administration of drug of Klimen® can influence peripheral insulin resistance and tolerance to glucose, need to change the scheme of treatment of patients with a diabetes mellitus at drug use usually does not arise. Nevertheless, women with a diabetes mellitus at use of the drug Klimen® have to be under observation.
At some patients under the influence of the drug Klimen® undesirable manifestations of stimulation by estrogen, for example, of bleeding from a vagina can develop. Frequent or persistent bleedings from a vagina against the background of treatment are the indication for an endometria research.
If treatment of irregular menstrual cycles does not yield results, it is necessary to conduct examination for an exception of a disease of organic character.
Under the influence of estrogen myomatous nodes of a uterus can increase in sizes. In this case treatment has to be stopped.
It is recommended to stop treatment at development of a recurrence of endometriosis against the background of administration of drug of Klimen®.
In case of identification of a prolaktinoma, the patient has to be under fixed medical observation (including periodic definition of concentration of prolactin).
In certain cases the hloazma, especially at women with hloazmy pregnant women in the anamnesis can be observed. During use of the drug Klimen® of the woman with tendency to emergence of a hloazma have to avoid long stay in the sun or ultraviolet radiation.
The following states can arise or be aggravated against the background of administration of drugs for ZGT to which Klimen® belongs. Though their interrelation with administration of drug of Klimen® is not proved, women with these states at use of the drug Klimen® have to be under observation of the doctor: epilepsy; benign diseases of a mammary gland; bronchial asthma; migraine; porphyria; otosclerosis; system lupus erythematosus, hysterical chorea. At women with hereditary forms of a Quincke's disease exogenous estrogen can cause or worsen symptoms of a Quincke's disease.
Additional information
Women have no data on need of dose adjustment up to 65 years. At use of the drug Klimen® for women 65 years are more senior it is necessary to take information provided in the section "Special Instructions" into account.

Use of the drug Klimen® for women with abnormal liver functions was not studied.
Use of the drug Klimen® for women with renal failures was not studied. The available data indicate lack of need of dose adjustment at such patients.

Medical examination and consultation
Before the beginning or resuming of administration of drug of Klimen® it is necessary to get acquainted in detail with a case history of the patient and to conduct physical and gynecologic examination. Frequency and the nature of such inspections have to be based on the existing norms of medical practice at the necessary accounting of specific features of each patient (but at least 1 time in 6 months) and have to include measurement of arterial pressure, assessment of a condition of mammary glands, abdominal organs and a small pelvis, including a cytologic research of an epithelium of a neck of uterus.
Influence on results of laboratory researches
Reception of sex hormones can influence biochemical indicators of function of a liver, thyroid gland, adrenal glands and kidneys, the content in plasma of transport proteins, such as kortikosteroidsvyazyvayushchy globulin and lipid/lipoprotein fractions, indicators of carbohydrate metabolism, coagulation and a fibrinolysis.
Influence on ability to manage vehicles and mechanisms
It is not revealed.

Side effects:

At administration of drug of Klimen® undesirable effects which communication with reception of this drug cannot be can be noted neither it is confirmed, nor disproved.

Disturbances from organs of sight
Infrequently (> 1/1000 and <1/100)
Vision disorders
Seldom (<1/1000)
Intolerance of contact lenses (unpleasant feelings at their carrying)
Disturbances from digestive tract
Often (> 1/100)
Nausea, abdominal pain
Infrequently (> 1/1000 and <1/100)
Dispeptic frustration
Seldom (<1/1000)
Vomiting, abdominal distention
Disturbances from immune system
Infrequently (> 1/1000 and <1/100)
Hypersensitivity reactions
Disturbances from a metabolism and food
Often (> 1/100)
Increase or decrease in body weight
Disturbances from a musculoskeletal system
Seldom (<1/1000)
Muscular spasms
Disturbances from a nervous system
Often (> 1/100)
Headache
Infrequently (> 1/1000 and <1/100)
Dizziness
Seldom (<1/1000)
Migraine
Mental disorders
Infrequently (> 1/1000 and <1/100)
Decrease in mood
Seldom (<1/1000)
Uneasiness, decrease or increase in a libido
Disturbances from cardiovascular system
Infrequently (> 1/1000 and <1/100)
Heart consciousness
Disturbances from reproductive system and mammary glands
Often (> 1/100)
Uterine bleedings and bleedings from a vagina (frequency of irregular bleedings usually decreases during long
Infrequently (> 1/1000 and <1/100)
Mammary gland pain, nagrubaniye of mammary glands
Seldom (<1/1000)
Dysmenorrhea, allocations from a vagina, increase in mammary glands, a predmenstrualnopodobny syndrome
Disturbances from skin and hypodermic fabrics
Often (> 1/100)
Rash, itch
Infrequently (> 1/1000 and <1/100)
Knotty erythema, small tortoiseshell
Seldom (<1/1000)
Hirsutism, acne
General symptoms
Infrequently (> 1/1000 and <1/100)
Hypostases (including the century swelled)
Seldom (<1/1000)
Increased fatigue

At administration of drug development of thromboses and thromboembolisms is in rare instances possible (see also "Special instructions"), cholecystitis cases (were noted from biliary tract) and increases in arterial pressure (from cardiovascular system), a recurrence
cholestatic jaundice (from digestive tract), a hloazma (from skin and hypodermic fabrics).
At women with hereditary forms of a Quincke's disease exogenous estrogen can cause or worsen symptoms of a Quincke's disease.

Interaction with other medicines:

If the patient accepted hormonal contraceptives, at the beginning of ZGT it is necessary to stop their use. If necessary the patient should recommend non-hormonal methods of contraception.
Prolonged treatment by drugs - inductors of microsomal enzymes of a liver (for example, some anticonvulsant and germicides) can increase clearance of sex hormones and reduce their clinical performance. Similar property was revealed to induce microsomal enzymes of a liver at hydantoins, barbiturates, Primidonum, carbamazepine and rifampicin, existence of this feature is also supposed at an okskarbazepin, a topiramat, a felbamat and griseofulvin. The maximum induction of microsomal enzymes is usually observed not earlier, than in 2-3 weeks, but then it can remain still, at least, within 4 weeks after the termination of administration of drug. Changes (increase or decrease) of concentration of etrogen and gestagen in a blood plasma were observed in cases of joint appointment with inhibitors of microsomal enzymes of a liver, such as ритонавир and нелфинавир. The drugs containing the St. John's Wort which is made a hole can stimulate exchange of estrogen and gestagen.
In rare instances against the background of the accompanying reception of some antimicrobic drugs (for example, penicillinic and tetracycline groups) decrease in concentration of oestradiol was observed.
The substances which substantially are exposed to conjugation (for example, paracetamol), can increase bioavailability of oestradiol owing to competitive inhibition of system of conjugation in the course of absorption.
Owing to influence of ZGT on tolerance to glucose the need for peroral hypoglycemic means or insulin in some cases can change.
Overconsumption of alcohol during ZGT can lead to increase in concentration of the circulating oestradiol.

Contraindications:

Administration of drug of Klimen® in the presence of any of the listed below states/diseases is contraindicated. If any of these circumstances arises during drug Klimen® use, then it is necessary to stop drug use immediately.
• Pregnancy and lactation.
• Bleeding from a vagina of not clear etiology.
• The confirmed or estimated diagnosis of a breast cancer.
• The confirmed or estimated diagnosis of a hormonedependent precancerous disease or hormonedependent malignant tumor.
• Liver tumors now or in the anamnesis (high-quality or malignant).
• Serious illness of a liver.
• Fibrinferments (arterial and venous) and thromboembolisms now or in the anamnesis (including, thrombosis, thrombophlebitis of deep veins; thromboembolism of a pulmonary artery, myocardial infarction, stroke, cerebrovascular disturbances);
• Existence of high risk of venous and arterial thromboses. The revealed predisposition to venous or arterial thrombosis, including resistance to
to the activated protein With, deficit of antithrombin III, deficit of a protein With, deficit of a protein of S, a gipergomotsisteinemiya, antibodies to phospholipids (antibodies to cardiolipin, lupoid anticoagulant).
• The states preceding thrombosis (including the tranzitorny ischemic attacks, stenocardia), now or in the anamnesis.
• The expressed gipertriglitseridemiya.
• Hypersensitivity to drug Klimen® components.

• Lactose intolerance, fructose. Deficit of lactase, invertase/isomaltase, glyukozo-galaktozny malabsorption.
• Children's and teenage age up to 18 years.

Use with care
It is necessary to appoint the drug Klimen® with care at the following diseases: arterial hypertension, inborn hyperbilirubinemias (Gilbert's syndromes, the Cudgel Johnson and the Rotor), acute and chronic diseases of a liver easy and moderate severity at normal indicators of functional trials of a liver and gall bladder, a cholestatic itch during the previous pregnancy, epilepsy, endometriosis, a hysteromyoma, a diabetes mellitus, a hysterical chorea, bronchial asthma, an endometria hyperplasia in an anmneza; existence of risk factors of developing of estrogenzavisimy tumors (relatives of the first line of relationship with a breast cancer); migraine; porphyria.
Pregnancy and lactation
Use of drug at pregnancy and breastfeeding is contraindicated. If pregnancy develops in time of administration of drug of Klimen®, then administration of drug should be cancelled immediately.
A small amount of sex hormones can be allocated with maternal milk.

Overdose:

The risk of serious side effects at accidental administration of drug of Klimen® in the dose which is repeatedly exceeding a daily therapeutic dose is not revealed. There is no specific antidote, a symptomatic treatment.

Storage conditions:

To store at a temperature not above 30 °C. To store in the place, unavailable to children. Period of validity of 5 years. Not to apply after the period of validity specified on packaging!

Issue conditions:

According to the recipe

Packaging:

Tablets coated white color and tablet coated pink color. On 11 white and 10 pink tablets in the blister from a polyvinyl chloride film and color aluminum foil. On 1 or 3 blisters together with the application instruction and a self-adhesive calendar place in a cardboard pack.