Jes

General characteristics. Structure:

• Active agents
Ethinylestradiol (in a look бетадекс a clathrate)   0,02 mg
Drospirenon of 3,00 mg
• Excipients
Lactoses monohydrate, starch corn, magnesium stearate
Tablet cover: gipromelloza, talc, titanium dioxide, dye ferrous oxide red.
Each tablet of placebo film coated contains: Tablet kernel:
• Active agents: absence
• Excipients:
Lactoses monohydrate, starch corn, povidone, magnesium stearate tablet Cover: gipromelloza, talc, titanium dioxide.

Description. Active tablets film coated: round biconvex tablets film coated, light pink color. On one party of a tablet in the correct hexagon "DS" is engraved. A look on a break: a kernel from white till almost white color, a cover - light pink.
Placebo tablets film coated: round biconvex tablets film coated white color. On one party of a tablet in the correct hexagon "DP" is engraved. A look on a break: a kernel from white till almost white color, a cover - white.

Pharmacological properties:

Pharmacodynamics. Jes - a hormonal contraceptive with antimineralkortikoidny and anti-androgenic action.
The contraceptive effect of the combined oral contraceptives is based on interaction of various factors suppression of an ovulation and change of properties of a cervical secret therefore it becomes low-permeable for spermatozoa concern to the most important of which.
At the correct use Perl's index (number of pregnancies on 100 women a year) makes less than 1. At the admission of tablets or the wrong use Perl's index can increase.
At the women accepting the combined oral contraceptives, the menstrual cycle becomes more regular, painful periods are less often observed, intensity of bleeding decreases that reduces risk of development of anemia. Besides, according to epidemiological researches, at use of the combined oral contraceptives the risk of development of endometrial cancer and ovarian cancer decreases.
Drospirenon who is contained in drug Jes possesses antimineralokortikoidny action. Prevents increase in body weight and emergence of the hypostases connected with the liquid delay caused by estrogen that provides very good tolerance of drug. Drospirenon makes positive impact on a premenstrual syndrome (PMS). Clinical performance of Jes in relief of symptoms of a severe form of PMS, such as the expressed psychoemotional disturbances, nagrubany mammary glands, a headache, the muscle and joints pain, increase in weight and other symptoms associated with a menstrual cycle is shown. In the USA the severe form of PMS is designated by the term "premenstrual dysphoric syndrome".
Drospirenon also has anti-androgenic activity and promotes reduction of symptoms of an acne (eels), fat content of skin and hair. This action of a drospirenon is similar to effect of the natural progesterone produced by an organism.
Drospirenon has no androgenic, oestrogenic, glucocorticoid and anti-glucocorticoid activity. All this in combination with antimineralokortikoidny and anti-androgenic action, provides to a drospirenon the biochemical and pharmacological profile similar to natural progesterone.
In combination with ethinylestradiol дроспиренон shows a favorable effect on the lipidic profile which is characterized by increase in LPVP.

Pharmacokinetics

• Drospirenon Absorbtion
At oral administration дроспиренон quickly and almost it is completely absorbed. After a single dose inside the maximum concentration of a drospirenon in serum, equal about 35 ng/ml, is reached approximately in 1-2 hours. Bioavailability fluctuates from 76 to 85%. In comparison with substance reception next the heart, meal does not influence bioavailability of a drospirenon.
Distribution
After oral administration two-phase decrease in level of drug in serum, with elimination half-lives, respectively, 1,6±0,7 hours and 27,0±7,5 hours is observed. Drospirenon contacts a seralbumin and the corticosteroid-the connecting globulin (CCG) does not contact the globulin, connecting sexual steroids (G,CSS), or. Only 3-5% of the general concentration of substance in serum are present at quality of a free steroid. The increase in GSPS induced by ethinylestradiol does not influence binding of a drospirenon proteins of serum. The average seeming volume of distribution makes 3,7±1,2 l/kg.
Metabolism
After oral administration дроспиренон it is extensively metabolized. The majority of metabolites in plasma are presented by acid forms of a drospirenon.
Removal from an organism
Speed of metabolic clearance of a drospirenon in serum makes 1,5±0,2 ml/min. In not changed look дроспиренон it is excreted only in trace quantities. Metabolites of a drospirenon are excreted with excrements and urine in the ratio about 1,2:1,4. The elimination half-life at excretion of metabolites with urine and excrements makes about 40 hours.
Equilibrium concentration
During cyclic treatment the maximum equilibrium concentration of a drospirenon in serum is reached between the 7 and 14 day of treatment and makes about 60 ng/ml. Increase in concentration of a drospirenon in serum approximately by 2-3 times was noted (due to cumulation) that was caused by an elimination half-life ratio in a terminal phase and a dosing interval. Further increase in serumal concentration of a drospirenon is noted between 1 and 6 cycles of reception then increase in concentration is not observed.
Special populations of patients
Influence of a renal failure
Equilibrium concentration of a drospirenon in serum at women with a slight renal failure (clearance of creatinine = 50-80 ml/min.) were comparable with the corresponding indicators at women with normal function of kidneys (C. territory> of 80 ml/min.). At women with a moderate renal failure (C. the territory = 30-50 ml/min.) the serumal level of a drospirenon was on average 37% higher, than at women with normal function of kidneys. Treatment drospirenony was well transferred in all groups. Reception of a drospirenon did not exert clinically significant impact on potassium concentration in serum. The pharmacokinetics at a heavy renal failure was not studied.
Influence of a liver failure
Drospirenon is well had by patients with a slight or moderate liver failure (a class B on a scale of Chayld-Pyyu). The pharmacokinetics at a heavy liver failure was not studied.
•  Ethinylestradiol Absorption
After oral administration ethinylestradiol is quickly and completely absorbed. The peak of serumal concentration after a single dose is inside reached in 1 - 2 hour and makes about 88 - 100 pg/ml. Absolute bioavailability as a result of a presistemny konjyugirovaniye and metabolism of the first passage makes about 60%. The accompanying meal reduces bioavailability of ethinylestradiol approximately at 25% inspected whereas at other subjects of similar changes it was not noted.
Distribution
Concentration of ethinylestradiol in serum decreases dvukhfazno, the terminal phase is characterized by an elimination half-life, components are about 24 hours old. Ethinylestradiol very substantially, but not specifically, is connected with a seralbumin (about 98,5%) and causes increase of concentration of GSPS in serum. The seeming volume of distribution makes about 5 l/kg.
Metabolism
Ethinylestradiol is exposed to a presistemny konjyugirovaniye in mucous a small intestine and in a liver. Ethinylestradiol is initially metabolized by an aromatic hydroxylation, at the same time the various hydroxylated and metilirovanny metabolites presented both in the form of free metabolites, and in the form of conjugates with glucuronic and sulfuric acids are formed. Ethinylestradiol is completely metabolized. Speed of metabolic clearance of ethinylestradiol makes about 5 ml/min.
Removal from an organism
Ethinylestradiol is practically not excreted in not changed look. Metabolites of ethinylestradiol are excreted with urine and bile in the ratio 4:6. The elimination half-life for excretion of metabolites makes about 1 days.
Equilibrium concentration
The condition of equilibrium concentration is reached during the second half of a cycle of treatment, and the serumal level of ethinylestradiol increases approximately in 1,4k2,1 time.
Preclinical data on safety
The preclinical data obtained during the standard researches regarding detection of toxicity at multiple dose of doses of drug, and also genotoxicity, cancerogenic potential and toxicity for reproductive system do not indicate existence of extra risk for the person. Nevertheless, it is necessary to remember that sexual steroids can promote growth of some hormonedependent fabrics and tumors.

Indications to use:

• Contraception
• Contraception and treatment of a moderate form of eels (acne vulgaris)
• Contraception and treatment of a severe form of a premenstrual syndrome (PMS).

Route of administration and doses:

Pill should be taken in the order specified on packaging, every day approximately at the same time with a small amount of water. A pill is taken without interruption in reception. It is necessary to accept on one tablet a day consistently within 28 days. Each subsequent packaging should be begun next day after reception of the last tablet from the previous packaging. Cancellation bleeding, as a rule, begins for 2-3 day after the beginning of reception of inactive tablets and can not come to the end prior to the following packaging yet.
How to begin reception Jes
• In the absence of reception of any hormonal contraceptives last month.
Reception Jes begins in the first day of a menstrual cycle (i.e. in the first day of menstrual bleeding). The beginning of reception for 2-5 day of a menstrual cycle is allowed, but in this case it is recommended to use in addition a barrier method of contraception during the first 7 days of reception of tablets from the first packaging.
• Upon transition from other combined oral contraceptives, a vaginal ring or a contraceptive plaster.
It is preferable to begin reception Jes next day after reception of the last active tablet from the previous packaging, but by no means no later than the next day after a usual 7-day break (for the drugs containing 21 tablets) or after reception of the last inactive tablet (for the drugs containing 28 tablets in packaging). Reception Jes should be begun in day of removal of a vaginal ring or plaster, but no later than day when the new ring has to be entered or the new plaster is pasted.
• Upon transition from the contraceptives containing only gestagena ("mini-drank", injection forms, an implant), or from the intrauterine contraceptive (Mirren) releasing гестаген.
The woman can pass with mini-saw on Jes in any day (without interruption), from an implant or an intrauterine contraceptive with gestageny - in day of its removal, from an injection contraceptive - in day when the following injection has to be made. In all cases it is necessary to use in addition barrier method of contraception during the first 7 days of reception of tablets.
• After abortion in the first trimester of pregnancy.
The woman can begin administration of drug immediately. At observance of this condition the woman does not need additional measures of contraception.
•  After the delivery or abortion in the second trimester of pregnancy.
It is recommended to begin administration of drug for 21 - 28 days after the delivery or abortion in the second trimester of pregnancy. If reception is begun later, it is necessary to use in addition barrier method of contraception during the first 7 days of reception of tablets. However if the woman already led sex life, prior to Jes's reception pregnancy has to be excluded or it is necessary to wait for the first periods.
Reception of the passed tablets
The admission of inactive tablets can be ignored. Nevertheless, they should be thrown out accidentally not to prolong the period of reception of inactive tablets. The following recommendations belong only to the admission of active tablets:
If delay in administration of drug made less than 24 hours, contraceptive protection does not decrease. The woman has to take the passed pill as soon as possible, and following to accept in usual time.
If delay in reception of tablets made more than 24 hours, contraceptive protection can be reduced. Than more tablets are passed, and the admission of tablets is closer to a phase of reception of inactive tablets, the probability of pregnancy is higher.
At the same time it is possible to be guided by the following two basic rules:
• administration of drug never has to be interrupted, more than for 7 days (please, pay attention that the recommended interval of reception of inactive tablets makes 4 days).
• for achievement of adequate suppression гипоталамо - pituitary and ovarian system 7 days of continuous reception of tablets are required.
Respectively, if delay in reception of active tablets made more than 24 hours, it is possible to recommend the following:
• With 1 - го till the 7th day:
The woman has to take the last passed pill at once as soon as she remembers it even if it means reception of two tablets at the same time. She continues to take the following pill in usual time. Besides, during the next 7 days it is necessary to use in addition a barrier method of contraception (for example, condom). If the sexual contact took place within 7 days before the admission of a tablet, it is necessary to consider a possibility of approach of pregnancy.
• From the 8th to the 14th day
The woman has to take the last passed pill at once as soon as she remembers it even if it means reception of two tablets at the same time. She continues to take the following pill in usual time.
Provided that the woman took a pill correctly within 7 days preceding the first passed tablet there is no need for use of additional measures of contraception. Otherwise, and also at the admission of two and more tablets it is necessary to use in addition barrier methods of contraception (for example, condom) within 7 days.
• From the 15th to the 24th day
The risk of decrease in reliability is inevitable because of the coming phase of reception of inactive tablets. The woman has to adhere strictly to one of two following options. At the same time, if in 7 days preceding the first passed tablet all pill was taken correctly, there is no need to use additional contraceptive methods. Otherwise she needs to use the first of the following schemes and in addition to use a barrier method of contraception (for example, condom) within 7 days.
1. The woman has to take the last passed pill as soon as possible as soon as she remembers (even if it means, reception of two tablets at the same time). The following takes a pill in usual time, active tablets in packaging will not end yet. Four inactive tablets should be thrown out and to immediately begin reception of tablets from the following packaging. Bleeding of cancellation is improbable, active tablets in the second packaging will not end yet, but the smearing allocations and breakthrough bleedings can be noted during reception of tablets.
2. The woman can also interrupt reception of tablets from the current packaging. Then it has to take a break no more than 4 days, including days of the admission of tablets, and then begin administration of drug from new packaging.
If the woman passed active tablets, and during reception of inactive tablets of bleeding of cancellation did not come, it is necessary to exclude pregnancy.
Recommendations at gastrointestinal frustration
At heavy gastrointestinal frustration absorption can be incomplete therefore it is necessary to take additional contraceptive measures.
If within 4 hours after reception of an active tablet there is vomiting, it is necessary to be guided by recommendations at the admission of tablets. If the woman does not want to change the usual scheme of reception and to move the beginning of periods the next day of week, the additional active pill should be taken from other packaging.
How to change menstrual cycles or how to delay approach of periods
To delay approach of periods, the woman should continue reception of tablets from the following packaging Jes, having passed inactive tablets from the current packaging. Thus, the cycle can be prolonged, at will, for any term, active tablets from the second packaging will not end yet. Against the background of administration of drug from the second packaging at the woman the smearing allocations or breakthrough uterine bleedings can be noted. Regular reception Jes then is resumed after the termination of a phase of reception of inactive tablets.
To move the beginning of periods the next day of week, the woman should reduce the following phase of reception of inactive tablets by the desirable number of days. The interval is shorter, the risk is higher that it will have no cancellation bleeding, and further there will be smearing allocations and breakthrough bleedings during reception of the second packaging.
Additional information for special categories of patients
Children and teenagers
Drug Jes is shown only after approach of menarche. The available data do not assume dose adjustment at this group of patients.
Patients of advanced age
It is not applicable. Drug Jes is not shown after approach of a menopause. Patients with disturbances from a liver
Drug Jes is contraindicated to women with a serious illness of a liver until indicators of function of a liver do not return to normal. See also sections of "Contraindication" and "Pharmacological Properties".
Patients with disturbances from kidneys
Drug Jes is contraindicated to women with a heavy renal failure or with an acute renal failure. See also sections of "Contraindication" and "Pharmacological Properties".

Features of use:

If any of the states/risk factors provided below are available now, then it is necessary to weigh carefully potential risk and the expected advantage of use of the combined oral contraceptives in each individual case and to discuss it with the woman before she decides to begin administration of drug. In case of weighting, strengthening or the first manifestation of any of these states or risk factors, the woman has to consult with the doctor who can make the decision on need of drug withdrawal.

•  Diseases of cardiovascular system
Results of epidemiological researches indicate existence of interrelation between use of the CPC and increase in frequency of development of venous and arterial thromboses and thromboembolisms (such as deep vein thrombosis, thromboembolism of a pulmonary artery, myocardial infarction, cerebrovascular disturbances) at reception of the combined oral contraceptives. These diseases are noted seldom. The risk of development of a venous thromboembolism (VTE) is maximum in the first year of reception of such drugs. The increased risk is present after initial use of the combined oral contraceptives or resuming of use same or the different combined oral contraceptives (after a break between  administrations of drug in 4 weeks and more).  Data of a large prospective research with participation of 3 groups of patients show that this increased risk is present preferential within the first 3 months.
The general risk of a venous thromboembolism (VTE) at the patients accepting the low-dosed combined oral contraceptives (<50 mkg of ethinylestradiol) is two-three times higher, than at nonpregnant patients who do not accept the CPC, nevertheless, this risk remains lower in comparison with risk of VTE at pregnancy and childbirth.
VTE can threaten life or lead to a lethal outcome (in 1-2% of cases). The venous thromboembolism (VTE) which is shown as a deep vein thrombosis, or an embolism of a pulmonary artery can occur when using of any combined oral contraceptives.
Extremely seldom when using of the combined oral contraceptives there is thrombosis of other blood vessels, for example, of hepatic, mesenteric, renal, brain veins and arteries or vessels of a retina. A consensus concerning communication between emergence of these events and use of the combined oral contraceptives is absent.
Symptoms of the deep vein thrombosis (DVT) include the following: unilateral hypostasis of the lower extremity or along a vein on a leg, pain or discomfort in a leg only in vertical position or when walking, local temperature increase in the affected leg, reddening or change of coloring of integuments on a leg. Symptoms of a thromboembolism of a pulmonary artery (TELA) consist in the following: the complicated or hurried breathing; sudden cough, including with a pneumorrhagia; an acute pain in a thorax which can amplify at a deep breath; feeling of alarm; severe dizziness; the speeded-up or irregular heartbeat. Some of these symptoms (for example, "short wind", "cough") are nonspecific and can be interpreted incorrectly as signs of other more or less heavy events (for example, respiratory infection).
The arterial thromboembolism can lead to a stroke, occlusion of vessels or a myocardial infarction. Symptoms of a stroke are as follows: sudden weakness or anesthesia of the person, hand or leg, especially on the one hand bodies, sudden confusion of consciousness, problem with the speech and understanding; sudden one - or bilateral loss of sight; sudden disturbance of gait, dizziness, loss of balance or coordination of movements; sudden, heavy or long headache for no apparent reason; a loss of consciousness or a syncope with an epileptic seizure or without it. Other signs of occlusion of vessels: sudden pain, puffiness and weak posineniye of extremities, acute abdomen.
Symptoms of a myocardial infarction include: pain, discomfort, pressure, weight, feeling of compression or a raspiraniye in a breast, in a hand or behind a breast; discomfort with irradiation in a back, a cheekbone, a throat, a hand, a stomach; cold sweat, nausea, vomiting or dizziness, strong weakness, alarm or asthma; the speeded-up or irregular heartbeat. The arterial thromboembolism can threaten life or lead to a lethal outcome. The risk of development of thrombosis (venous and/or arterial) and thromboembolisms increases:
- with age;
- at smokers (with increase in quantity of cigarettes or increase in age the risk increases, especially at women 35 years are more senior);
in the presence:
- obesity (index of body weight of more than 30 kg/sq.m);
- the family anamnesis (for example, a venous or arterial thromboembolism ever at close relatives or parents at rather young age). In case of the hereditary or acquired predisposition, the woman has to be examined by the corresponding specialist for the solution of a question of a possibility of reception of the combined oral contraceptives;
- long immobilization, serious surgical intervention, any operation standing or extensive injury. In these situations it is desirable to stop use of the combined oral contraceptives (in case of the planned operation, at least, in four weeks prior to it) and not to resume reception within two weeks after the termination of an immobilization;
- dislipoproteinemiya;
- arterial hypertension;
- migraines;
- diseases of valves of heart;
- fibrillations of auricles.
The question of a possible role of a varicosity and superficial thrombophlebitis in development of a venous thromboembolism remains disputable.

It is necessary to consider the increased risk of development of thromboembolisms in a puerperal period.
Disturbances of peripheric circulation can be also noted at a diabetes mellitus, a system lupus erythematosus, a hemolitic uraemic syndrome, chronic inflammatory diseases of intestines (a disease Krone or nonspecific ulcer colitis) and a sickemia.
Increase in frequency and weight of migraine during use of the combined oral contraceptives (that can precede cerebrovascular disturbances) can be the basis for the immediate termination of reception of these drugs.
The following belongs to the biochemical indicators indicating the hereditary or acquired predisposition to venous or arterial thrombosis: resistance to the activated protein C, a gipergomotsisteinemiya, a lack of antithrombin-III, a lack of protein C, a lack of protein S, anti-phospholipidic antibodies (anti-cardiolipin antibodies, lupus anticoagulant).
At assessment of a ratio of risk and advantage, it is necessary to consider that adequate treatment of the corresponding state can reduce the related risk of thrombosis. Also it is necessary to consider that the risk of thromboses and thromboembolisms at pregnancy is higher, than at reception of the low-dosed oral contraceptives (<0,05 mg of ethinylestradiol).

•  Tumors
The most essential risk factor of development of cancer of neck of uterus, the persistent human papillomavirus infection is. There are messages on some increase in risk of development of cancer of neck of uterus at prolonged use of the combined oral contraceptives. Communication with reception of the combined oral contraceptives is not proved. Contradictions concerning in what degree these finds are connected with screening regarding pathology of a neck of uterus or with features of a sexual behavior (more rare use of barrier methods of contraception) remain.
Meta-analysis of 54 epidemiological researches showed that there is a little increased relative risk of development of the breast cancer diagnosed for the women accepting the combined oral contraceptives now (relative risk 1,24). The increased risk gradually disappears within 10 years after the termination of reception of these drugs. Because the breast cancer is noted seldom at women to 40 years, increase in number of diagnoses of a breast cancer at the women accepting the combined oral contraceptives now or accepting recently is insignificant in relation to the general risk of this disease. Observed increase in risk can be a consequence of earlier diagnosis of a breast cancer at the women applying the combined oral contraceptives, biological effect of oral contraceptives or a combination of both factors. At the women using the combined oral contraceptives clinically less expressed breast cancer, than at women, never their applying comes to light.
In rare instances against the background of use of the combined oral contraceptives development high-quality, and in extremely rare - malignant tumors of a liver which in some cases led to life-threatening intra belly bleeding was observed. In case of severe pains in a stomach, increases in a liver or symptoms of intra belly bleeding it should be considered when carrying out the differential diagnosis.
Tumors can threaten life or lead to a lethal outcome. •  Other states
Clinical trials showed lack of influence of a drospirenon on potassium concentration in blood serum at patients with a slight and moderate renal failure. There is a theoretical risk of development of a hyperpotassemia in the patients with disturbance of renal function at initial potassium concentration on the upper bound of norm who are at the same time accepting the medicines leading to a potassium delay in an organism. Nevertheless, at women with the increased risk of development of a hyperpotassemia it is recommended to define potassium concentration of plasma during the first cycle of administration of drug Jes.
At women with a gipertriglitseridemiya (or existence of this state in the family anamnesis) increase in risk of development of pancreatitis is possible during reception of the combined oral contraceptives.
Though small increase in arterial pressure was described at many women accepting the combined oral contraceptives, clinically significant increases were noted seldom. Nevertheless, if during reception of the combined oral contraceptives permanent, clinically significant increase in arterial pressure develops, it is necessary to cancel these drugs and to begin treatment of arterial hypertension. Reception of the combined oral contraceptives can be continued if by means of hypotensive therapy normal values of arterial pressure are reached.
The following states as it was reported, develop or worsen both during pregnancy, and at reception of the combined oral contraceptives, but their communication with reception of the combined oral contraceptives is not proved: jaundice and/or the itch connected with a cholestasia; formation of stones in a gall bladder; porphyria; system lupus erythematosus; hemolitic uraemic syndrome; Sydenham's chorea; herpes of pregnant women; the hearing loss connected with an otosclerosis. Disease cases Krone and nonspecific ulcer colitis against the background of use of the combined oral contraceptives are also described.
At women with hereditary forms of a Quincke's disease exogenous estrogen can cause or worsen symptoms of a Quincke's disease.
Acute or chronic abnormal liver functions can demand cancellation of the combined oral contraceptives until indicators of function of a liver do not return to norm. Recurrent cholestatic jaundice which develops for the first time in time of pregnancy or previous reception of sex hormones demands the termination of reception of the combined oral contraceptives.
Though the combined oral contraceptives can exert impact on resistance to insulin and tolerance to glucose, the patients with a diabetes mellitus using the low-dosed   combined   oral   contraceptives have no need of change of the therapeutic mode   (<0,05   mg of ethinylestradiol). Nevertheless, women with a diabetes mellitus have to be observed carefully during reception of the combined oral contraceptives.
The hloazma can sometimes develop, especially women with existence in the anamnesis have hloazma of pregnant women. Women with tendency to a hloazma during reception of the combined oral contraceptives have to avoid long stay to the sun and influences of ultraviolet radiation.

•  Laboratory tests
Reception of the combined oral contraceptives can influence results of some laboratory tests, including indicators of function of a liver, kidneys, a thyroid gland, adrenal glands, level of transport proteins in plasma, indicators of carbohydrate metabolism, parameters of coagulation and a fibrinolysis. Changes usually do not overstep the bounds of normal values. Drospirenon increases activity of a renin of plasma and Aldosteronum that is connected with its antimineralokortikoidny effect.

Medical examinations
Before the beginning or resuming of use of drug Jes it is necessary to study the anamnesis of life, the family anamnesis of the woman, to carry out careful all-medical (including measurement of the ABP, heart rate, definition of an index of body weight) and gynecologic inspection (including a research of mammary glands and a cytologic research of cervical slime), to exclude pregnancy. The volume of additional researches and frequency of control surveys is defined individually. Usually control examinations should be conducted at least 1 time a year.
It is necessary to warn the woman that the combined oral contraceptives do not protect from HIV infection (AIDS) and other diseases, sexually transmitted!

Decrease in efficiency
Efficiency of the combined peroral contraceptive drugs can be reduced in the following cases: at the admission of active tablets (light pink), at vomiting and diarrhea or as a result of medicinal interaction.
Insufficient control of a menstrual cycle
Against the background of reception of the combined oral contraceptives the irregular bleedings (smearing bloody allocations or breakthrough bleedings), especially within the first months of use can be noted. Therefore, assessment of any irregular bleedings has to be carried out only after the period of adaptation making about three cycles.
If irregular bleedings repeat or develop after the previous regular cycles, it is necessary to conduct careful examination for an exception of malignant new growths or pregnancy.
At some women during a break in reception of active tablets (light pink)
cancellation bleeding can not develop. If the combined oral contraceptives were accepted as directed, it is improbable that the woman is pregnant. Nevertheless, if before the combined oral contraceptives were accepted irregularly or if there are no in a row two bleedings of cancellation, before continuation of administration of drug pregnancy has to be excluded.

Influence on ability to drive the car and the equipment.

It is not revealed.

Side effects:

It was reported about the following most widespread side reactions at the women applying Jes according to indications "Contraception" and "Contraception and treatment of a moderate  form of eels   (acne vulgaris)":  nausea,        mammary gland pain, irregular uterine bleedings, bleedings from a genital tract of not specified genesis. These side reactions occurred more than at 3% of women. At the patients applying Jes according to the indication "Contraception and treatment of a severe form of a premenstrual syndrome" more was reported about the following most widespread side reactions (than at 10% of women): nausea, mammary gland pain, irregular uterine bleedings.

Serious side reactions are an arterial and venous thromboembolism.
In the table the frequency of undesirable reactions about which it was reported during clinical trials of drug Jes according to indications "Contraception" and "Contraception and treatment of a moderate form of eels (acne vulgaris)" (N=3565), and also according to the indication "Contraception and treatment of a severe form of a premenstrual syndrome" (N=289) is specified below. Within each group allocated depending on the frequency of emergence of undesirable reaction, undesirable reactions are presented as reduction of their weight. On frequency they are divided on frequent (> 1/100 and <1/10), infrequent (> 1/1000 and <1/100) and rare (> 1/10000 and <1/1000). For the additional undesirable reactions revealed only in the course of post-marketing observations and for which to carry out assessment of frequency of emergence it was not represented possible, it is specified "frequency is not known".

System and organ classes                                     Often Infrequently Seldom      Frequency is not known
(MedDRA 12.0 version) 
Mental                           Differences of mood  Reduction or
frustration                        a depression / suppressed   loss libido2
                                                 mood   
Nervous system                        Migraine   
Disturbances with                                                                                                 Venous or
parties of vessels                                                                                               arterial
                                                                                                                       thromboembolism
Gastrointestinal
path                                         Nausea   
Skin and hypodermic fabrics                                                                                 of Multiformnaya erythema
Reproductive system
and mammary glands            of Bol in milk zhelezakh1,
                                              irregular uterine
                                                krovotecheniya1,
                                             bleedings from sexual
                                              ways of not specified   
                                                        genesis

The undesirable phenomena were codified with use of the MedDRA dictionary (the Medical Dictionary of Regulatory Activity). Various terms of MedDRA reflecting the same symptom were grouped together and submitted as the only side reaction, in order to avoid easing or degradation of true effect.
* - Approximate frequency following the results of the epidemiological researches covering group of the combined oral contraceptives. Frequency bordered on very rare.
- "The venous or arterial thromboembolism" includes the following nosological units: occlusion of peripheral deep veins, fibrinferments and embolism / occlusion of pulmonary vessels, fibrinferments, embolism and heart attack / myocardial infarction / cerebral heart attack and hemorrhagic stroke.

1 Frequency of cases during the researches estimating PMS was very frequent> 10/100

2 Frequency of cases during the researches estimating PMS was frequent> 1/100

For a venous and arterial thromboembolism, migraine see also "Contraindications" and "Special instructions".
Additional information:
Side reactions with very rare frequency of emergence or with the delayed symptoms which as believe, can be connected with administration of drugs from group of the oral combined contraceptives are listed below (see also "Contraindications" and "Special instructions").

Tumors
• Frequency of diagnosing of a breast cancer at the women accepting the combined oral contraceptives is a little increased. Because the breast cancer is noted seldom at women to 40 years, increase in number of diagnoses of a breast cancer at the women accepting the combined oral contraceptives is insignificant in relation to the general risk of this disease.
• Liver tumors (high-quality and malignant).

Other states
• Knotty erythema.
• Women with a gipertriglitseridemiya (the increased risk of pancreatitis during reception of the combined oral contraceptives).
• Hypertensia.
• The states developing or worsening during reception of the combined oral contraceptives, but their communication is not proved: jaundice and/or the itch connected with a cholestasia; formation of stones in a gall bladder; porphyria; system lupus erythematosus; hemolitic uraemic syndrome; Sydenham's chorea; herpes of pregnant women; the hearing loss connected with an otosclerosis.
• At women with a hereditary Quincke's disease reception of estrogen can cause or aggravate its symptoms.
• Abnormal liver functions.
• Changes in tolerance to glucose or influence on resistance to insulin.
• Disease Krone, nonspecific ulcer colitis.
• Hloazma.
• Hypersensitivity (including such symptoms as rash, urticaria).

Interaction
Interaction of oral contraceptives with other medicines (inductors of enzymes, some antibiotics) can lead to breakthrough bleedings and/or decrease in contraceptive efficiency (see. "Interaction with other medicines").

Interaction with other medicines:

Interaction of oral contraceptives with other medicines can lead to breakthrough bleedings and/or decrease in contraceptive reliability. The women accepting these drugs have to use temporarily barrier methods of contraception in addition to drug Jes, or choose other method of contraception.
Influence on hepatic metabolism: use of the drugs inducing microsomal enzymes of a liver can lead to increase of clearance of sex hormones. Treat such medicines: Phenytoinum, barbiturates, Primidonum, carbamazepine, rifampicin; also there are assumptions concerning an okskarbazepin, a topiramata, a felbamata, the griseofulvin and drugs containing a St. John's Wort.
HIV proteases (for example, ритонавир) and nenukleozidny inhibitors of the return transcriptase (for example, not Virapinum) and their combinations also potentially can influence hepatic metabolism.
Influence on enterohepatic circulation: according to separate researches, some antibiotics (for example, penicillin and tetracycline) can reduce enterohepatic circulation of estrogen, thereby, lowering concentration of ethinylestradiol.
During administration of drugs, influencing microsomal enzymes, and within 28 days after their cancellation it is necessary to use a barrier method of contraception in addition.
During reception of antibiotics (such as ampitsillina and tetracyclines) and within 7 days after their cancellation it is necessary to use a barrier method of contraception in addition. If during these 7 days of use of a barrier method of contraception active (light pink) tablets come to an end, then it is necessary to miss reception of tablets of placebo (white) of the current packaging and to begin reception of tablets from the following packaging Jes. The main metabolites of a drospirenon are formed in plasma without participation of system of P450 cytochrome. Therefore influence of inhibitors of system of P450 cytochrome on metabolism of a drospirenon is a little probable.
The oral combined contraceptives can influence metabolism of other drugs that leads to increase (for example, cyclosporine) or to decrease (for example, ламотриджин) their concentration in plasma and fabrics.
On the basis of researches of interaction in vitro, and also the research in vivo at the female volunteers accepting омепразол, симвастатин and midazolam as markers it is possible to conclude that influence of a drospirenon in a dose of 3 mg on metabolism of other medicines it is improbable.
The women receiving Jes along with other drugs which can increase the serumal level of potassium have a theoretical possibility of increase in serumal level of potassium. APF inhibitors, antagonists of receptors of angiotensin-II, some antiinflammatory drugs, kaliysberegayushchy diuretics and antagonists of Aldosteronum belong to these drugs. However, in the researches estimating interaction of a drospirenon with APF inhibitors or indometacin reliable distinction between serumal potassium concentration in comparison with placebo was not revealed. Nevertheless, at the women accepting drugs which can increase the serumal level of potassium it is recommended to define potassium concentration of serum during the first cycle of administration of drug Jes.
For identification of possible interactions it is necessary to study application instructions of the corresponding medicines.

Contraindications:

Drug Jes should not be used in the presence of any of the states which are listed below. If any of these states develop for the first time against the background of reception, drug has to be immediately cancelled.
• Fibrinferments (venous and arterial) and thromboembolisms now or in the anamnesis (including, a deep vein thrombosis, a thromboembolism of a pulmonary artery, a myocardial infarction), cerebrovascular disturbances.
• The states preceding thrombosis (including, the tranzitorny ischemic attacks, stenocardia) now or in the anamnesis.
• Migraine with focal neurologic symptoms now or in the anamnesis
• A diabetes mellitus with vascular complications.
• 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; serious surgical intervention with a long immobilization; smoking is aged more senior than 35 years.
• A liver failure and a serious illness of a liver (until hepatic tests do not return to normal).
• Liver tumors (high-quality or malignant) now or in the anamnesis.
• Heavy renal failure, acute renal failure.
• Adrenal insufficiency
• The revealed hormonedependent malignant diseases (including generative organs or mammary glands) or suspicion of them.
• Vaginal bleeding of not clear genesis.
• Pregnancy or suspicion on it.
• Feeding period breast.
• Hypersensitivity to any of drug components Jes.

Use with care
If any of the states/risk factors provided below are available now, then it is necessary to weigh carefully potential risk and the expected advantage of use of the combined oral contraceptives in each individual case:
• Risk factors of development of thrombosis and thromboembolisms: smoking; thromboses, a myocardial infarction or disturbance of cerebral circulation at young age at any of the immediate family; obesity; dislipoproteinemiya; arterial hypertension; migraine; diseases of valves of heart; disturbance of a cordial rhythm; long immobilization; serious surgical interventions; extensive injury
• Other diseases at which disturbances of peripheric circulation can be noted: diabetes mellitus; system lupus erythematosus; hemolitic uraemic syndrome; disease Krone and nonspecific ulcer colitis; sickemia; and also phlebitis of superficial veins
• Hereditary Quincke's disease
• Gipertriglitseridemiya
• Liver diseases
• The diseases which for the first time arose or aggravated during pregnancy or against the background of the previous reception of sex hormones (for example, jaundice, a cholestasia, a cholelithiasis, an otosclerosis with deterioration in hearing, a porphyria, herpes of pregnant women, Sydenham's trochee)
• Puerperal period Pregnancy and lactation
Jes is not appointed during pregnancy and during feeding by a breast.
If pregnancy comes to light during administration of drug Jes, drug should be cancelled at once. However extensive epidemiological researches did not reveal any increased risk of defects of development in the children born by the women receiving sexual steroids (including the combined oral contraceptives) before pregnancy or teratogenic action when sexual steroids were accepted on imprudence in early durations of gestation.
The existing data on results of administration of drug Jes during pregnancy are limited that does not allow to draw any conclusions on influence of drug on the course of pregnancy, health of the newborn and a fruit. Any significant epidemiological data on drug Jes are absent now.
Reception of the combined oral contraceptives can reduce amount of breast milk and change its structure therefore, their use is not recommended before the breastfeeding termination. A small amount of sexual steroids and/or their metabolites can be removed with milk.

Overdose:

About serious violations at overdose it was not reported. On the basis of total experience of use of the combined oral contraceptives symptoms which can be noted at overdose by active tablets: nausea, vomiting, the smearing bloody allocations or a metrorrhagia.
There is no specific antidote, it is necessary to carry out a symptomatic treatment.

Storage conditions:

To store in the dry place 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 a period of validity!

Issue conditions:

According to the recipe

Packaging:

Tablets are film coated. On 28 tablets (24 active tablets and 4 tablets of placebo) in the blister. 1 blister is pasted in the book folding bed cardboard. 1 or 3 books folding beds together with a self-adhesive calendar of reception and the application instruction are sealed in a transparent film.