Jess - instructions for use, doses, side effects, contraindications

Active tablets, film-coated: round, biconcave tablets covered with a film membrane, light pink in color. On one side of the tablet in the right hexagon is engraved "DS"View of the fracture: the core is from white to almost white, the shell is light pink.

Placebo-coated tablets: round, biconvex tablets covered with a film coat of white color. On one side of the tablet in the correct hexagon engraved "DP". View at the break: the core is white to almost white, the shell is white.

Pharmacotherapeutic group:contraceptive combination (estrogen + progestogen)

ATX: & nbsp

G.03.A.A.12 Drospirenone and ethinylestradiol

Pharmacodynamics:

Preparation Jess^® - Combined hormonal contraceptive with antimineralocorticoid and antiandrogenic action.The contraceptive effect of combined oral contraceptive drugs (COCs) is based on the interaction of various factors, the most important of which are suppression of ovulation and changes in the properties of the secretion of the cervix, resulting in it becoming impermeable to spermatozoa.

When used correctly, Perl's index (the number of pregnancies per 100 women per year) is less than 1. When missing tablets or improperly used, the Pearl index may increase.

In women taking COC, the menstrual cycle becomes more regular, less painful menstruation is observed, the intensity of bleeding decreases, which reduces the risk of anemia. In addition, according to epidemiological studies, the use of COC reduces the risk of developing endometrial cancer and ovarian cancer.

Drospirenone, contained in the preparation Jess ®, has antimineralocorticoid action. Prevents weight gain and the appearance of swelling associated with estrogen-induced fluid retention, which ensures a good tolerability of the drug. Drospirenone has a positive effect on premenstrual syndrome (PMS).The clinical efficacy of Jess® is shown to alleviate the symptoms of severe PMS, such as severe psychoemotional disorders, breast engorgement, headache, muscle and joint pain, weight gain and other symptoms associated with the menstrual cycle. Drospirenone also has anti-androgenic activity and reduces the symptoms of acne (acne), oiliness of the skin and hair. This action of drospirenone is similar to the action of natural progesterone, produced by the body.

Drospirenone does not have androgenic, estrogenic, glucocorticoid and antiglucocorticoid activity. All this in combination with antimineralocorticoid and antiandrogenic action provides drospirenone biochemical and pharmacological profile, similar to natural progesterone.

In combination with ethinyl estradiol, drospirenone shows a beneficial effect on the lipid profile, characterized by an increase in high-density lipoproteins.

The Jess® preparation can be used both in the usual mode ("24 + 4" reception mode: during 24 days taking active tablets, then for 4 days - taking inactive tablets) and in "flexible" mode.

Adaptable elongated mode ("flexible" mode) of the Jess preparation^® based on the previously approved regimen of the drug "24 + 4" and is that active tablets of the drug can be taken daily continuously for up to 120 days. Thus, the continuous period of active tablets intake can be 24-120 days, and the duration of interruption in taking the tablets should not exceed 4 days. "Flexible" mode of reception is possible only if there is a metering device. Click (Clyk) and flex cartridges, which allow you to comply with the regimen of the drug (see section "Method of administration and dose").

The results of a multicenter, comparative, open, randomized study in parallel groups showed that the "flexible" mode of Jess®, aimed at achieving a maximum duration of intervals without bleeding to 120 days, reduced the total number of menstruation days per year from 66 (24 + 4 ") to 41 days (" flexible "reception mode).

Pharmacokinetics:

Drospirenone

Absorption

When administered orally, drospirenone quickly and almost completely absorbed. After a single oral intake, the maximum concentration of drospirenone in the blood plasma, about 38 ng / ml, is reached after about 1-2 hours.Bioavailability ranges from 76 to 85%. Compared with taking the substance on an empty stomach, eating does not affect the bioavailability of drospirenone.

Distribution

After oral administration, there is a two-phase reduction in the concentration of drospirenone in the blood plasma, with half-lives of 1.6 ± 0.7 hours and 27.0 ± 7.5 hours, respectively. Drospirenone binds to serum albumin and does not bind to sex hormone binding globulin ), or a corticosteroid-binding globulin. Only 3-5% of the total concentration of the substance in the blood plasma is present as a free hormone. The increase in SHBG induced by ethinyl estradiol does not affect the binding of drospirenone to plasma proteins. The average apparent volume of distribution is 3.7 ± 1.2 l / kg.

Metabolism

After oral administration, drospirenone is extensively metabolized. Most metabolites in the plasma are represented by acid forms of drospirenone. Drospirenone is also a substrate for oxidative metabolism catalyzed by the cytochrome P450 isoenzyme CYP3A4.

Excretion from the body

The metabolic clearance rate of drospirenone in blood plasma is 1.5 ± 0.2 ml / min / kg.In unmodified form, drospirenone is excreted only in trace amounts. Metabolites of drospirenone are excreted through the intestine and kidneys in a ratio of approximately 1.2: 1.4. The elimination half-life when metabolites are excreted by the kidneys and through the intestine is approximately 40 h.

The equilibrium concentration

During the cyclic administration, the maximum equilibrium concentration of drospirenone in plasma is reached between 7 and 14 in the day of administration and is approximately 70 ng / ml. There was an increase in the concentration of drospirenone in the blood plasma by approximately 2-3 times (due to cumulation), which was due to the ratio of the half-life in the terminal phase and the dosing interval. A further increase in the concentration of drospirenone in the blood plasma is observed between 1 and 6 cycles of administration, after which no increase in the concentration is observed.

Special populations of patients

Influence of renal failure

Equilibrium concentrations of drospirenone in blood plasma in women with mild renal insufficiency (creatinine clearance 50-80 ml / min) were comparable with those in women with normal renal function (CC> 80 ml / min).In women with renal insufficiency of moderate severity (CK 30-50 ml / min), the concentration of drospirenone in the blood plasma was on average 37% higher than in women with normal renal function. Treatment with drospirenone was well tolerated in all groups. The intake of drospirenone did not have a clinically significant effect on the potassium concentration in the blood plasma. The pharmacokinetics of drospirenone in severe renal failure has not been studied.

Influence of hepatic impairment

Drospirenone is well tolerated by patients with mild to moderate hepatic insufficiency (class B on the Child-Pugh scale). Pharmacokinetics in severe hepatic insufficiency has not been studied.

Ethinylestradiol

Absorption

After oral administration ethinyl estradiol quickly and completely absorbed. The maximum concentration in the blood plasma after a single oral intake is achieved after 1-2 hours and is about 88-100 pg / ml. Absolute bioavailability as a result of presystemic conjugation and metabolism of the first passage is approximately 60%. Concomitant ingestion reduces the bioavailability of ethinylestradiol in about 25% of those surveyed, while in other subjects no similar changes were noted.

Distribution

The concentration of ethinylestradiol in the blood plasma is reduced biphasic, the terminal phase is characterized by a half-life period of approximately 24 hours. Ethinylestradiol to a significant extent, but not specifically, is associated with serum albumin (approximately 98.5%) and causes an increase in the concentration of SHBG in the blood plasma. The apparent volume of distribution is about 5 l / kg.

Metabolism

Ethinyl estradiol undergoes significant primary metabolism in the intestine and liver. Ethinylestradiol and its oxidative metabolites are primarily conjugated to glucuronides or sulfate. The metabolic clearance rate of ethinylestradiol is about 5 ml / min / kg.

Excretion from the body

Ethinyl estradiol is not practically excreted unchanged. Metabolites of ethinyl estradiol are excreted by the kidneys and through the intestine in a ratio of 4: 6. The half-life of metabolites is approximately 24 hours.

The equilibrium concentration

The state of equilibrium concentration is reached during the second half of the cycle, while the concentration of ethinyl estradiol in the blood plasma increases approximately 1.5-2.3 times.

Preclinical safety data

Preclinical data obtained from routine studies to detect toxicity with multiple doses of the drug, as well as genotoxicity, carcinogenic potential, and toxicity to the reproductive system, do not indicate a particular risk to humans. Nevertheless, it should be remembered that sex hormones can promote the growth of some hormone-dependent tissues and tumors.

Indications:

- Contraception;

- contraception and treatment of moderate forms of acne (acne vulgaris);

- contraception and treatment of severe premenstrual syndrome (PMS).

Contraindications:

Jess® is contraindicated in the presence of any of the conditions / diseases listed below. If any of these conditions / diseases develop for the first time on the background of admission, the drug should be immediately withdrawn:

- Thrombosis (venous and arterial) and thromboembolism at present or in the anamnesis (including deep vein thrombosis, pulmonary embolism, myocardial infarction), cerebrovascular disorders;

- conditions preceding thrombosis (including transient ischemic attacks, angina pectoris) at present or in the anamnesis;

- identified acquired or hereditary predisposition to venous or arterial thrombosis, including resistance to activated protein C, antithrombin deficiency III, Protein C Deficiency, Protein Deficiency S, hyperhomocysteinemia, antibodies to phospholipids (antibodies to cardiolipin, lupus anticoagulant);

- the presence of a high risk of venous or arterial thrombosis (see section "Special instructions");

- Migraine with focal neurologic symptoms at present or in the anamnesis;

- diabetes mellitus with vascular complications;

- hepatic failure and severe liver disease (before the normalization of liver function);

- liver tumors (benign or malignant) at present or in the anamnesis;

- severe renal failure, acute renal failure;

- adrenal insufficiency;

- identified hormone-dependent malignant diseases (including genital organs or mammary glands) or suspected of them;

- bleeding from the vagina of unknown origin;

- pregnancy or suspected of it;

- the period of breastfeeding;

- hypersensitivity to any of the components of Jess®;

- lactose intolerance, lactase deficiency, glucose-galactose malabsorption (lactose monohydrate is included in the formulation).

Carefully:

If any of the conditions / risk factors indicated below are currently available, the potential risk and the expected benefit of using combined oral contraceptives in each individual case should be carefully weighed:

- risk factors for thrombosis and thromboembolism: smoking; thrombosis, myocardial infarction or cerebrovascular accident at a young age in someone of the next of kin; obesity; dyslipoproteinemia; arterial hypertension; migraine; heart valve diseases; heart rhythm disorder; long-term immobilization; serious surgical interventions; extensive trauma;

- other diseases in which there may be violations of peripheral circulation: diabetes mellitus; systemic lupus erythematosus; hemolytic uremic syndrome; Crohn's disease and nonspecific ulcerative colitis; sickle-cell anemia; and phlebitis of superficial veins;

- hereditary angioedema;

- hypertriglyceridemia;

- liver disease;

- diseases that first appeared or worsened during pregnancy or against the background of previous reception of sex hormones (for example, jaundice, cholestasis, cholelithiasis, otosclerosis with hearing impairment, porphyria, herpes pregnant, Sydenham's chorea);

- Pan osseous period.

Pregnancy and lactation:

The use of Jess ® is contraindicated during pregnancy and during breastfeeding.

The possibility of pregnancy should not be excluded in any patient with a preserved reproductive potential in the presence of symptoms characteristic of pregnancy, especially in those who did not comply with the regimen of the drug.

Of the symptoms characteristic of pregnancy, not only the absence of bleeding from the "cancellation" during the 4-day tablet-free period ("flexible" regimen) or against the background of taking white inactive tablets (regimen "24 + 4"), but also the appearance of the morning weakness, vomiting or swelling of the mammary glands, although these symptoms do not develop in all women and, in addition, they can be caused by other causes.

Bleeding "cancellation" when applying the "flexible" regimen does not occur, as usual, every 4 weeks, but develops with an interval of up to 120 days, depending on when the patient chooses a 4-day break in taking the tablets.Therefore, the absence of bleeding "cancellation" can not be used as a sign of an unforeseen pregnancy. In such cases, there are difficulties with timely diagnosis of pregnancy. Although the onset of pregnancy with a clear adherence to the Jets® regimen is unlikely, if pregnancy is suspected, immediately stop taking Jes®, consult a doctor and perform a pregnancy test.

If the patient is planning a pregnancy, she may stop taking Jes® at any time. If the patient simultaneously takes potentially harmful to the fetus (teratogenic) drugs and therefore needs a pregnancy prevention, the decision on the possibility of stopping the Jess® drug can be taken only after consulting a doctor.

If the pregnancy is detected during the JES® drug, the drug should be immediately discontinued. However, extensive epidemiological studies have not revealed any increased risk of developmental defects in children born to women who received sex hormones (including COCs) prior to pregnancy, or teratogenicity, when sex hormones were mistaken for early pregnancy.

Existing data on the results of taking Jess ® during pregnancy are limited, which does not allow us to draw any conclusions about the effect of the drug on the course of pregnancy, the health of the newborn and the fetus. There are no significant epidemiological data on Jess® at this time.

Admission COC can reduce the amount of breast milk and change its composition, so their use is not recommended until the termination of breastfeeding. A small amount of sex hormones and / or their metabolites can penetrate into breast milk and affect the body of the newborn.

Dosing and Administration:

How to take jes®

Reception mode "24 + 4"

Tablets should be taken in the order indicated by the arrows on the package, daily at approximately the same time, with a small amount of water. Tablets are taken without interruption in admission. One tablet per day should be taken consecutively for 28 days. The taking of tablets from each subsequent package should begin the day after the last tablet from the previous package was taken. Bleeding "cancellation", as a rule,begins on the 2-3 day after the start of the reception of white inactive tablets and may not be completed before taking the tablets from the next package. Receiving tablets from a new package should always start on the same day of the week, and bleeding "cancellations" will occur approximately on the same days of each month.

"Flexible" mode of reception

"Flexible" regimen of the Jess ® preparation can be used only with a dosimeter Click (Clyk) and flex cartridges.

Every day at the same time should take one tablet, squeezed a small amount of liquid.

Tablets should be taken continuously, for at least 24 days.

Between 25 and 120 days of using the Jae® drug, the patient's decision can be made with a 4-day break in taking the tablets.

A break in taking the tablets should not exceed 4 days.

A 4-day break in taking the tablets should be made no later than 120 days of continuous intake of tablets.

After each 4-day break in taking the tablets, a new cycle begins with a minimum duration of 24 days and a maximum duration of 120 days.

As a rule, bleeding "cancellation" develops during a 4-day break in taking the tablets, but may not end until the moment you need to take the next pill.

If during the period from 25 to 120 days for 3 consecutive days appear "smearing" bloody discharge / bleeding from the vagina, it is recommended to take a 4-day break in taking the tablets. This will reduce the total number of days of bleeding.

Brief instructions for operating the dispenser Click (Clyk)

Before starting and during operation, you should carefully read the detailed operating instructions for the dispenser.

General description of the dispenser Click (Clyk):

Side keys

Pressing area for tablet.

Flex-cartridge eject button

Press this button to eject the flex cartridge.

Tablet dispensing area

Part of the dispenser in which the pills are dispensed.

Tablet reception time indicator

Shows the time of taking the pill.

Display

Displays the main screen and menu items.

OK button

Pressing the button confirms the action, for example, the beginning of the 4-day break in taking the tablets and changing the reminder sound.

The most important functions

Activation of the new dispenser: Flexible cartridge (containing 30 tablets) should be removed from the package and IMMEDIATELY inserted into the dispenser.Insert the narrow end of the flex cartridge into the dispenser so that the dispenser window (as well as the tablets in the flex cartridge) can be easily seen (see Figure 1). The flex cartridge MUST be inserted completely.

Fig. 1. Preparation for use of the dispenser. Click (Clyk).

The dispenser will automatically record the time of issuing the first tablet, setting this time as Reception Time. Thus, a woman must:

> be sure that she unpacks and inserts the flex cartridge on the day she plans to start taking the tablets;

> be sure that the time of issuing the first tablet will be convenient for daily intake of tablets.

Every 24 hours, the signal on the arrival of the next tablet will appear on the dispenser display.

Extraction of the tablet

With one hand, simultaneously press both side keys to remove the tablet, which will be received by the other hand.

Replacing the flex cartridge

In normal use, the flex cartridge can only be removed if it is empty, otherwise follow the instructions of the detailed operating instructions for the dispenser. Click (Clyk). An empty flex-cartridge is removed by pressing the flex-cartridge eject button.The dispenser saves all information about the current cycle, and a new filled-in flex cartridge must be inserted in accordance with the instructions above.

Before and during the application, you should carefully read the detailed operating instructions for the dosimeter Click (Clyk), enclosed in the package with the drug.

How to start taking jes®

- In the absence of taking any hormonal contraceptives in the previous month

The Jess® drug should be taken on the first day of the menstrual cycle (ie on the first day of menstrual bleeding), in which case no additional contraceptive measures are required. It is acceptable to start taking the menstrual cycle for 2-5 days, but in this case it is recommended to use the barrier method of contraception during the first 7 days of taking the tablets from the first package. Then the tablets should be taken in the order indicated for the reception mode "24 + 4" or "flexible" reception mode.

- When switching from other combined contraceptive drugs (COC, vaginal ring or transdermal patch)

It is preferable to start taking Jes® on the day after taking the last active tablet from the previous package,but not in any case not later than the next day after the usual 7-day break (for preparations containing 21 tablets) or after taking the last inactive tablet (for preparations containing 28 tablets in the package).

Jace drug intake^® should begin on the day of removal of the vaginal ring or patch, but no later than the day when a new ring is to be inserted or a new patch is stuck.

- When switching from contraceptive preparations containing only gestagens ("mini-pili", injectable forms, implant), or with the progestative-releasing progestogen of the intrauterine contraceptive

A woman can switch from a "mini-drink" to a JES® drug on any day (without a break); from the implant or intrauterine contraceptive with gestagen - on the day of its removal; with an injection contraceptive - the day the next injection is to be made. In all cases, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the tablets.

- After abortion in the first trimester of pregnancy

A woman can start taking the medication immediately after a spontaneous or medical abortion in the first trimester of pregnancy.If this condition is met, the woman does not need additional contraceptive measures.

- After abortion in the second trimester of pregnancy or childbirth

The drug can be taken 21-28 days after a spontaneous or medical abortion or after childbirth without breastfeeding. If the reception is started later, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the tablets. However, if sexual intercourse has already occurred, pregnancy should be ruled out before the Jess® drug is taken or it is necessary to wait for the first menstruation.

- Discontinuation of Jess ®

You can stop taking the drug at any time. If a woman does not plan a pregnancy or a woman is contraindicated in pregnancy, because she is taking potentially dangerous preparations for the fetus, you need to discuss other methods of contraception with your doctor.

If a woman is planning a pregnancy, it is recommended to stop taking the drug and wait for a natural menstrual bleeding, and then try to get pregnant. This will help to more accurately calculate the duration of pregnancy and the time of delivery.

Instructions for handling the packaging of Jess^® for reception mode "24 + 4"

A blister is glued into the Jess® package, which contains 24 active hormone-containing light pink tablets and 4 inactive white, hormone-free tablets (last row). The packaging also includes a self-adhesive reception calendar consisting of 7 self-adhesive strips with the names of the days of the week marked on them. It is necessary to choose the strip where the first day of the week is indicated, in which it is planned to start taking the tablets. For example, if a woman starts taking pills on Wednesday, you need to use a strip that starts with "Wed." (see Figure 1).

The strip is glued along the top of the package so that the designation of the first day is above the tablet on which the arrow with the inscription "Start" is pointing (Fig. 2).

Thus, it will be seen on which day of the week you should take each pill (Figure 3).

Acceptance of missed tablets

Passing inactive white tablets on the background of the "24 + 4" reception mode can be ignored. Nevertheless, they should be thrown away, so as not to accidentally prolong the period of intake of inactive tablets. The following recommendations apply only to the omission of active light pink tablets:

- If the delay in taking the drug was less than 24 hours, Contraceptive protection is not reduced. A woman should take the missed tablet as soon as possible, and take the following tablets at the usual time.

- If the delay in taking the tablets was more than 24 hours, contraceptive protection can be reduced. The larger tablets is omitted, and the closer to the phase skip tablets White tablets reception inactive mode when using "24 + 4" or an available period from the reception of pills in the background "flexible" reception mode, the higher the chance of pregnancy.

In this case, you can follow the following two basic rules:

- the drug should never be interrupted for more than 7 days (please note that the recommended interval receiving inactive white tablets is 4 days for the reception mode "24 + 4" and for "flexible" reception modes - interval without reception tablets should not exceed 4 days);

- to achieve adequate suppression of the hypothalamic-pituitary-ovarian system, 7 days of continuous tablet intake are required.

Dozer Click (Clyk) allows you to control the taking of tablets and warns a woman about the need to use an additional method of contraception.The warning symbol "exclamation point" appears on the display when skipping tablets or when taking tablets irregularly for more than 7 consecutive days. "Exclamation mark" disappears after 7 days of continuous dispensing of tablets by a dispenser. If more than one pill is missed, it is recommended that you consult your doctor.

In the case of the reception mode "24 + 4", and also in the "flexible" mode, if information from the clicker Click (Сlyk) is not available or there are doubts about its reliability, it is necessary to adhere to the following recommendations:

- If you skip during the 1st to 7th day of taking tablets:

A woman should take the last missed pill right away, as soon as she remembers it, even if it means taking two pills at the same time. The following tablets she continues to take at the usual time. In addition, during the next 7 days, the barrier method of contraception (for example, a condom) needs to be additionally used. If sexual intercourse has occurred within 7 days before passing the pill, you should consider the possibility of pregnancy.

- If you skip during the 8th to 14th day of taking the tablets with the "24 + 4" reception mode OR

- If you miss during the 8 to 24 day of taking tablets with a "flexible" reception mode:

A woman should take the last missed pill right away, as soon as she remembers it, even if it means taking two pills at the same time. The following tablets she continues to take at the usual time.

Provided that the woman took the tablets correctly for 7 days preceding the first missed tablet, there is no need for additional contraceptive measures. Otherwise, as well as when two or more tablets are missed, barrier methods of contraception (for example, a condom) should be used additionally for 7 days, and in case of "flexible" mode of reception, barrier methods of contraception should be used until the continuous period of admission tablets will not reach 7 days.

- When skipped during the 15th to 24th day of taking tablets under the regime reception "24 + 4" OR

- If you miss during the 25 to 120 day of taking tablets with a "flexible" mode of reception:

The risk of a decrease in reliability is inevitable due to the approaching period of taking inactive white tablets in case of application of the "24 + 4" reception mode or tablet-free period with "flexible" reception mode. One must strictly adhere to one of the following two options.In this case, if in 7 days preceding the first missed tablet, all the tablets were taken correctly, there is no need to apply additional contraceptive methods. Otherwise, the woman should apply the first of the following schemes and additionally use the barrier method of contraception (for example, a condom) for 7 days.

1. The woman should take the last missed tablet as soon as possible, as soon as she remembers (even if it means taking two tablets at the same time). For the mode "24 + 4": the following tablets are taken at the usual time, until the active light pink tablets in the package run out, 4 inactive white tablets should be discarded and immediately begin taking the tablets from the next package. Bleeding "cancellation" is unlikely until the active light pink tablets in the second package run out, but "smearing" discharge and / or "breakthrough" bleeding may occur during taking the tablets.

In the case of a "flexible" regimen, you must take at least 7 tablets (one tablet daily) without taking a break.

2. For the mode "24 + 4": a woman can also interrupt the intake of active light pink tablets from the current package.Then she should take a break no more than 4 days, including the days of skipping the tablets, and then start taking the drug from the new package.

If a woman missed the reception of active light pink tablets and during the reception of inactive white pills bleeding "cancellation" did not come, you need to exclude pregnancy.

For the "flexible" reception mode: a woman can also take a 4-day break in taking the pills, including the day the tablet is missed, to cause the bleeding of the "cancellation", and then begin a new cycle of taking the drug. If the woman missed taking the pills and in the next period of the pills break there was no bleeding of the "cancellation", the possibility of pregnancy should be taken into account.

Recommendations for gastrointestinal disorders

In severe gastrointestinal disorders, absorption may be incomplete, therefore additional contraceptive measures should be taken.

If within 3-4 hours after taking an active light pink tablet was vomiting or diarrhea, you should focus on the recommendations when skipping tablets. If a woman does not want to change her usual schedule of taking and transfer the onset of menstruation on another day of the week, an additional active light pink pill should be taken.

How to change the time of bleeding "cancellation" or how to delay the onset of bleeding "cancellation" against the background of the reception mode "24 + 4"

To delay the onset of the bleeding "cancellation", a woman should continue taking the tablets from the next packaging of the JES® product, skipping the inactive white tablets from the current package. Thus, the cycle can be extended at will for any period until the active light-pink tablets run out of the second package, that is, about 3 weeks later than usual.

If you plan an earlier start of the next cycle, you should at any time complete the reception of active light pink tablets from the second package, discard the remaining active light pink tablets and start taking white inactive tablets (maximum for 4 days), and then start taking the tablets from new packaging. In this case, approximately 2-3 days after the last light pink pill is taken from the previous package, bleeding of the "cancellation" should begin. Against the background of taking the drug from the second package, a woman can be noted "smearing" and / or "breakthrough" uterine bleeding.The regular administration of Jess® is then resumed after the end of the inactive white tablets.

To transfer the onset of the bleeding "cancellation" to another day of the week, the woman should shorten the next period of taking inactive white tablets for the desired number of days. The shorter the interval, the higher the risk that it will not have a bleeding "cancellation", and thereafter there will be "smearing" discharge and / or "breakthrough" bleeding during taking the tablets from the second package.

Use in specific categories of patients

Children and teens

Jess ® is indicated only after menarche. The available data do not suggest correction of the dose in this group of patients.

Older patients

Not applicable. Jess® is not indicated after menopause.

Patients with impaired hepatic function

Jess® is contraindicated in women with severe liver disease until the functional liver test results are normal (see also the sections "Contraindications" and "Pharmacological properties").

Patients with impaired renal function

Jess® is contraindicated in women with severe renal failure or with acuterenal insufficiency (see also the sections "Contraindications" and "Pharmacological properties").

Side effects:

The following most common adverse reactions have been reported in women using JES® in the "24 + 4" mode as indicated by "Contraception" and "Contraception and treatment of moderate form of acne (acne vulgaris)": nausea, pain in the mammary glands, irregular uterine bleeding, bleeding from the genital tract, unspecified genesis." These adverse reactions were found in more than 3% of women.

In patients using the JES® preparation, "Contraception and treatment of severe premenstrual syndrome, the following most common adverse reactions have been reported (more than 10% of women): nausea, mammary gland, irregular uterine bleeding.

Severe adverse reactions are arterial and venous thromboembolism, and for "flexible" regimen of the drug additionally noted breast cancer and focal nodular hyperplasia of the liver.

Table 1 below shows the incidence of adverse reactions reported was reported in the clinical trials of Jess ® for the "24 + 4" regimen according to "Contraception" and "Contraception and treatment of moderate form of acne (acne vulgaris) "(N = 3565), according to the indication" Contraception and treatment of severe premenstrual syndrome "(N = 289), as well as" flexible "regimen of Dzec® (N = 2738).

Within the limits of each group, isolated depending on the incidence of the undesired reaction, undesirable reactions are presented in order of decreasing severity. In frequency, they are divided into frequent (≥1 / 100 and <1/10), infrequent (≥1 / 1000 and <1/100) and rare (≥1 / 10000 and <1/1000). For additional unwanted reactions revealed only in the process of post-registration observations, and for which it was not possible to estimate the frequency of occurrence, "frequency is unknown" is indicated.

Table №1. The incidence of adverse reactions in clinical trials of Jess® ("24 + 4" and "flexible" regimens *)

System-Organic grade (MedDRA version: 9.1)	Often (>1/100 - <1/10)	Infrequently (>1/1000 - <1/100)	Rarely (>1/10 000 - <1/1000)	Frequency unknown
Infectious and parasitic diseases			Candidiasis
Violations of the blood and lymphatic system			Anemia Thrombocythemia
Immune system disorders			Allergic reaction	Hypersensitivity
Disorders from the metabolism and nutrition			Increased appetite Anorexia Hyperkalemia Hyponatremia
Disorders of the psyche	Emotional lability Depression Decreased libido	Nervousness Drowsiness	Anorgasmia Insomnia
Disturbances from the nervous system	Head pain	Dizziness Paresthesia	Vertigo Tremor
Disturbances on the part of the organ of sight			Conjunctivitis Dry eye mucosa
Heart Disease			Tachycardia
Vascular disorders	Migraine	Varicose expansion veins Increased blood pressure	Phlebitis New bleeding Fainting Venous thromboembolism (VTE) Arterial thromboembolism (ATE)
Disorders from the gastrointestinal tract	Nausea	Will in the belly Vomiting Dyspepsia Flatulence Gastritis Diarrhea	Bloating Feeling of heaviness in the abdomen Hernia of the esophageal opening of the diaphragm Candidiasis of the mouth Constipation Dry mouth
Disturbances from the liver and bile ducts			Biliary dyskinesia Cholecystitis
Disturbances from the skin and subcutaneous tissues		Acne Itching Rash	Chloasma Eczema Alopecia Dermatitis acne Dryness of the skin Knotty erythema Hypertrichosis Stria Contact dermatitis Photodermatitis Cutaneous Nodule	Multi-form erythema
Disturbances from musculoskeletal and connective tissue		Backache Pain in the limb Muscular convulsions
Violations of the genitals and mammary gland	Pain in the mammary glands Metrorrhagia ** Absence of menstrual like bleeding	Vaginal candidiasis Pain in the pelvic area Increase mammary glands Fibrous-cystic lesions in the mammary gland Bloody discharge / bleeding from the genital tract ** Discharge from the genital tract "Tides" with sensation of heat Vaginitis Painful menstrual bleeding Scanty menstrual bleeding Abundant menstrual bleeding Dryness of the mucous membrane of the vagina Pathological results of the Pap test	Dyspareunia Vulvovaginitis Postcoital bleeding Bleeding "cancellation" Hyperplasia of the breast Neoplasm in the mammary gland Cervical polyp Atrophy of the endometrium Ovarian cyst Increase uterus
General disorders and disorders at the site of administration		Asthenia Reinforced sweating Edema (generalized puffiness, peripheral edema, edema of the face)	Malaise
Laboratory and instrumental data		Weight gain	Weight loss

* In cases where adverse reactions occurred with an equal frequency against the background of the application of the "24 + 4" and "flexible" regimes, the highest frequency was indicated;

** the frequency of irregular bleeding decreases as the duration of administration of the Jess® drug increases.

For more information about venous and arterial thromboembolism, migraine, breast cancer and focal nodular liver hyperplasia, see also "Contraindications" and "Special instructions".

Additional Information:

Listed below are adverse reactions with a very rare incidence or with delayed symptoms that are believed to be associated with taking drugs from the COC group (see also "Contraindications" and "Special instructions").

Tumors

- The frequency of diagnosing breast cancer in women taking COC is slightly increased. Due to the fact that breast cancer is rarely seen in women under 40, the increase in the number of diagnoses of breast cancer in women taking COC is insignificant in relation to the overall risk of this disease;

- liver tumors (benign and malignant).

Other states

- Nodular erythema, erythema multiforme (only for "flexible" regimen);

- women with hypertriglyceridemia (increased risk of pancreatitis while taking COC);

- increased blood pressure;

- conditions developing or worsening during the administration of COCs, but their relationship is not proven: jaundice and / or pruritus associated with cholestasis; cholelithiasis; porphyria; systemic lupus erythematosus; hemolytic-uremic syndrome; Sydengam's chorea: herpes during pregnancy; hearing loss associated with otosclerosis;

- in women with hereditary angioedema, estrogen administration may cause or aggravate its symptoms;

- impaired liver function;

- change in glucose tolerance or influence on insulin resistance;

- Crohn's disease, ulcerative colitis;

- Chloasma;

- Hypersensitivity (including symptoms such as rash, hives).

Interaction

The interaction of COC with other drugs (enzyme inducers) can lead to "breakthrough" bleeding and / or a decrease in contraceptive effectiveness (see "Interaction with Other Drugs").

Overdose:

No serious violations were reported in case of an overdose. Pre-clinical studies also showed no significant adverse effects from overdose.

Symptoms that may occur with an overdose: nausea, vomiting, spotting spotting from the vagina or metrorrhagia.

There is no specific antidote, symptomatic treatment should be performed.

Interaction:

The effect of other drugs on Jess ®

It is possible to interact with drugs that induce microsomal enzymes, as a result of which the clearance of sex hormones can increase, which in turn can lead to "breakthrough" uterine bleeding and / or a reduction in the contraceptive effect. Women who receive treatment with these drugs in addition to the JES® drug are advised to use a barrier method of contraception or choose a different non-hormonal contraceptive method. The barrier method of contraception should be used during the entire period of taking concomitant medications, and also within 28 days after their withdrawal.If the period of application of the barrier method of contraception ends later than the active tablets in the Jes® package, you should start taking the JES® tablets from the new package without interruption in taking active pills.

- Substances that increase the clearance of the Jess® preparation (weakening the efficiency by induction of enzymes): phenytoin, barbiturates, primidon, carbamazepine, rifampicin and, possibly, also oxcarbazepine, topiramate, felbamate, griseofulvin, as well as preparations containing St. John's wort pitted.

- Substances with different effects on the clearance of Jess ®

When combined with Jess®, many HIV protease inhibitors or hepatitis C virus and non-nucleoside reverse transcriptase inhibitors can both increase and decrease the concentration of estrogens or progestins in the blood plasma. In some cases, such an effect may be clinically significant.

- Substances that reduce the clearance of COCs (andMr.enzyme healers)

Strong and moderate inhibitors CYP3A4, such as azole antimycotics (for example, and azole, voriconazole, fluconazole), verapamil, macrolides (for example, clarithromycin, erythromycin), diltiazem and grapefruit juice can increase plasma concentrations of estrogen or progestin, or both.

It was shown that etorikoksib in doses of 60 and 120 mg / day, when taken together with COC containing 0.035 mg of ethinylestradiol, increases the concentration of ethinyl estradiol in blood plasma by 1.4 and 1.6 times, respectively.

The effect of Jess ® on other drugs

COCs can affect the metabolism of other drugs, leading to an increase (for example, ciclosporin) or decrease (for example, lamotrigine) of their concentration in blood plasma and tissues.

In vitro Drospirenone is able to weakly or moderately inhibit cytochrome P450 enzymes CYP1A1, CYP2C9, CYP2C19 and CYP3A4.

Based on interaction studies in vivo women volunteers who took omeprazole, simvastatin or midazolam as marker substrates, it can be concluded that the clinically significant effect of 3 mg of drospirenone on the metabolism of medications mediated by cytochrome P450 enzymes is unlikely.

In vitro ethinyl estradiol is a reversible inhibitor CYP2C19, CYP1A1 and CYP1A2, as well as an irreversible inhibitor CYP3A4/5, CYP2C8 and CYP2J2. In clinical trials, the appointment of a hormonal contraceptive containing ethinyl estradiol, did not lead to any increase or led only to a slight increase in the concentrations of substrates CYP3A4 in cryopyrosis (for example, midazolam), whereas plasma concentrations of substrates CYP1A2 may grow weakly (for example, theophylline) or moderately (for example, melatonin and tizanidine).

Other forms of interaction

In patients with intact renal function, the combined use of drospirenone and angiotensin-converting enzyme inhibitors or notsteroidal anti-inflammatory drugs does not have a significant effect on the concentration of potassium in the blood plasma. However, the combined use of Jess ® with aldosterone antagonists or potassium-sparing diuretics has not been studied. In such cases, the concentration of potassium in the blood plasma should be monitored during the first cycle of taking the drug (see section "Special instructions").

Special instructions:

If any of the conditions / risk factors listed below are currently available, the potential risk and expected benefits of using COCs in each individual case should be carefully weighed and discussed with the woman before she decides to start taking the drug.In case of weighting, strengthening, or the first manifestation of any of these conditions or risk factors, a woman should consult with her doctor who can decide whether to cancel the drug.

Diseases of the cardiovascular system

Epidemiological studies indicate a relationship between the use of COCs and increased incidence of venous and arterial thrombosis and thromboembolism (such as deep vein thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular disorders). These diseases are rare.

The risk of developing venous thromboembolism (VTE) is maximal in the first year of taking such drugs. The increased risk is present after the initial use of COC or the resumption of the use of the same or different COCs (after a break between doses of 4 weeks or more). These prospective study involving 3 groups of patients suggest that this increased risk is present mainly in the first 3 months.

The overall risk of VTE in patients receiving low-dose COCs (<0.05 mg ethinylestradiol) is 2-3 times higherthan in non-pregnant patients who do not take COC, however, this risk remains lower compared to the risk of VTE during pregnancy and childbirth. VTE may be life threatening or fatal (in 1-2% of cases).

VTE, manifested as deep vein thrombosis or pulmonary embolism, may occur with any COCs.

Very rarely, when using COC, thrombosis occurs in other blood vessels, for example, liver, mesenteric, renal, cerebral veins and arteries or retinal vessels. A common opinion regarding the relationship between the onset of these diseases and the use of COC is absent.

Symptoms of deep vein thrombosis (DVT) include the following: unilateral edema of the lower limb or along the vein on the lower extremity, pain or discomfort in the lower extremity only in the vertical position or walking, local temperature increase in the affected lower limb, redness or discoloration of the skin lower limb.

Symptoms of thromboembolism of the pulmonary artery (PE) are as follows: shortness of breath or rapid breathing; sudden cough,including hemoptysis; acute pain in the chest, which can increase with a deep breath; sense of anxiety; severe dizziness; rapid or irregular heartbeat. Some of these symptoms (eg, dyspnea, cough) are non-specific and can be misinterpreted as signs of other more or less severe conditions / diseases (eg, respiratory tract infection).

Arterial thromboembolism can lead to stroke, vascular occlusion or myocardial infarction.

Symptoms of stroke are as follows: sudden weakness or loss of sensitivity of the face, limbs, especially on one side of the body, sudden confusion, problems with speech and understanding; sudden one- or two-sided loss of vision; sudden gait disturbance, dizziness, loss of balance or coordination of movements; sudden, severe or prolonged headache for no apparent reason; loss of consciousness or fainting with or without an epileptic seizure.

Other signs of vascular occlusion: sudden pain, puffiness and weak blueing of the extremities, "sharp" abdomen.

Symptoms of myocardial infarction include: pain, discomfort, pressure, heaviness, a feeling of constriction or raspiraniya in the chest, in the hand or behind the breastbone; discomfort with irradiation in the back, cheekbone, larynx, hand, stomach; cold sweats, nausea, vomiting or dizziness, severe weakness, anxiety, or shortness of breath; rapid or irregular heartbeat.

Arterial thromboembolism can be life threatening or fatal.

Women with a combination of several risk factors or high severity of one of them should consider the possibility of their mutual reinforcement. In such cases, the degree of risk increase may be higher than with a simple summation of factors. In this case, taking Jess^® contraindicated (see section "Contraindications").

The risk of developing thrombosis (venous and / or arterial) and thromboembolism increases:

- with age;

- smokers (with the increase in the number of cigarettes or an increase in the age of the risk increases, especially in women older than 35 years);

in the presence of:

- obesity (body mass index more than 30 kg / m²);

- family history (for example, venous or arterial thromboembolism ever at close relatives or parents at a relatively young age).In the case of a hereditary or acquired predisposition, a woman should be examined by an appropriate specialist to decide on the possibility of taking COC;

- prolonged immobilization, serious surgical intervention, any operation on the lower limb or extensive trauma. In these situations, it is desirable to stop using COCs (in the case of a planned operation at least 4 weeks before) and not to resume taking two weeks after the end of immobilization. Temporary immobilization (for example, air travel lasting more than 4 hours) may also be a risk factor for venous thromboembolism, especially if there are other risk factors;

- dyslipoproteinemia;

- arterial hypertension;

- migraine;

- heart valve diseases;

- atrial fibrillation.

The use of any combination hormonal contraceptives increases the risk of developing VTE. The use of drugs containing levonorgestrel, norgestimate or norethisterone is associated with the lowest risk of VTE development. The use of other drugs, such as Jess®, can lead to a twofold increase in risk.The decision to use a drug other than the lowest risk of developing VTE should be taken only after discussion with the woman to make sure that she understands that the use of Jess® is accompanied by the probability of developing VTE, understands how its risk factors affect the likelihood of development VTE, and also understands that in every first year of the drug use, the risk of developing VTE for it is greatest. There is evidence that the risk of developing VTE increases with the resumption of taking combined hormonal contraceptives after a 4-week or more interruption in admission.

The question of the possible role of varicose veins and superficial thrombophlebitis in the development of venous thromboembolism remains controversial.

You should consider the increased risk of thromboembolism in the postpartum period.

Violations of peripheral circulation can also occur in diabetes mellitus, systemic lupus erythematosus, hemolytic-uremic syndrome, chronic inflammatory bowel disease (Crohn's disease or ulcerative colitis) and sickle cell anemia.

An increase in the frequency and severity of migraine during the use of COCs (which may precede cerebrovascular disorders) is the basis for the immediate discontinuation of these medications.

Biochemical indicators indicating a hereditary or acquired predisposition to venous or arterial thrombosis include the following: resistance to activated protein C, hyperhomocysteinemia, antithrombin III deficiency, protein C deficiency, protein deficiency S, antiphospholipid antibodies (antibodies to cardiolipin, lupus anticoagulant).

When assessing the relationship between risk and benefit, it should be borne in mind that adequate treatment of the relevant condition can reduce the risk of thrombosis associated with it. It should also be taken into account that the risk of thrombosis and thromboembolism in pregnancy is higher than when taking low-dose COCs (<0.05 mg of ethinyl estradiol).

Tumors

The most significant risk factor for developing cervical cancer is persistent papillomavirus infection. There are reports of a slight increase in the risk of developing cervical cancer with prolonged use of COCs, but there is no evidence of a relationship with COC use.There are contradictions as to the extent to which these findings are associated with screening for cervical pathology or with peculiarities of sexual behavior (more rare use of barrier methods of contraception).

A meta-analysis of 54 epidemiological studies showed that there is a slightly increased relative risk of developing breast cancer diagnosed in women currently taking COC (relative risk 1.24). Increased risk gradually disappears within 10 years after discontinuation of these drugs. Due to the fact that breast cancer is rarely seen in women under 40 years of age, an increase in the number of diagnoses of breast cancer in women who are currently taking COCs or who have recently taken COC is insignificant in relation to the overall risk of this disease. The observed increase in risk may be the result of an earlier diagnosis of breast cancer in women using COC, their biological effect, or a combination of both. Women who used COC have earlier stages of breast cancer than women who have never used them.

In rare cases, against the background of the use of COC, there was a development of benign, and in very rare cases, malignant liver tumors, which in some cases led to angiographygiving birth to life abdominal hemorrhage. In the event of severe pain in the abdomen, liver enlargement, or signs of intra-abdominal bleeding, this should be taken into account when making a differential diagnosis.

Tumors can endanger life or lead to death.

Other states

Clinical studies have shown no effect of drospirenone on the potassium concentration in blood plasma in patients with mild and moderate renal insufficiency. There is a theoretical risk of developing hyperkalemia in patients with impaired renal function with an initial potassium concentration at the upper limit of the norm, simultaneously taking drugs, leading to a delay in potassium in the body. In women with an increased risk of developing hyperkalemia, it is recommended to determine the concentration of potassium in blood plasma during the first cycle of taking Jets®.

In women with hypertriglyceridemia (or the presence of this condition in a family history), an increased risk of developing pancreatitis during COC administration is possible.

Although a small increase in blood pressure was described in many women taking COC, clinically significant increases were rarely seen. However, if a persistent clinically significant increase in blood pressure develops during the administration of COCs, these drugs should be discontinued and treatment of hypertension should begin. Reception of COCs can be continued if normal blood pressure values are achieved with the help of antihypertensive therapy. The following conditions have been reported to develop or worsen, both during pregnancy and when taking COC, but their relationship with COCs has not been proven: jaundice and / or pruritus associated with cholestasis; cholelithiasis; porphyria: systemic lupus erythematosus; hemolytic-uremic syndrome; chorea; herpes during pregnancy; hearing loss associated with otosclerosis. Also, cases of worsening of the course of endogenous depression, epilepsy, Crohn's disease and ulcerative colitis are described along with the use of COCs.

In women with hereditary forms of angioedema, exogenous estrogens can cause or worsen symptoms of angioedema.

Acute or chronic liver dysfunction may require cancellation of the COC until the functional liver test results return to normal. Recurrent cholestatic jaundice, which develops for the first time during pregnancy or previous reception of sex hormones, requires discontinuation of COCs.

Although COCs may have an effect on insulin resistance and glucose tolerance, there is no need to change the dose of hypoglycemic drugs in diabetic patients using low-dose COCs (<0.05 mg ethinylestradiol). Nevertheless, women with diabetes should be carefully observed while taking COC.

Sometimes chloasma can develop, especially in women with a history of pregnancy chloasma. Women with a tendency to chloasma while taking COC should avoid prolonged exposure to the sun and exposure to ultraviolet radiation.

Laboratory Tests

Admission COC can affect the results of some laboratory tests, including indicators of liver function, kidney function, thyroid gland, adrenal gland, transport protein concentration in blood plasma, carbohydrate metabolism, coagulation and fibrinolysis parameters.Changes usually do not go beyond the limits of normal values. Drospirenone increases the activity of plasma renin and aldosterone, which is associated with its antimineralocorticoid action.

Medical examinations

Before starting or resuming the use of JEs®, you need to familiarize yourself with the history of life, the family history of the woman, and conduct a thorough medical examination (including measuring blood pressure, heart rate, body mass index) and gynecological examination (including breast examination and cytology of cervical scraping uterus), to exclude pregnancy. The volume of additional studies and the frequency of follow-up visits are determined individually. Usually, follow-up examinations should be conducted at least once every 6 months.

A woman should be warned that COCs do not protect against HIV infection (AIDS) and other sexually transmitted diseases.

Decreased efficiency

The effectiveness of COCs can be reduced in the following cases: when active pale pink tablets are missed (when using the "24 + 4" mode or light pink tablets in case of "flexible" mode)when vomiting and diarrhea or as a result of drug interactions.

Insufficient control of the menstrual cycle

When taking COC, irregular bleeding (spotting spotting and / or breakthrough bleeding) can occur, especially during the first months of use for both regimens. With a "flexible" regimen, irregular bleeding can develop during a fixed period of admission (from 1 to 24 days). Therefore, any irregular bleeding should be assessed only after an adaptation period of approximately three cycles (or 3 months with a "flexible" regimen).

If irregular bleeding recurs or develops after previous regular cycles, a thorough diagnostic examination should be performed to exclude malignant neoplasms or pregnancy.

Some women during the break in taking active light pink tablets ("24 + 4") may not develop a bleeding "cancellation". If the drug was taken as directed, it is unlikely that a woman is pregnant. Nevertheless, if before this drug was taken irregularly, or if there are no consecutive two bleeding "cancellations", the continuation of the drug should be excluded from pregnancy.

Against the background of a "flexible" regimen of taking the drug, bleeding "cancellations" are not regular. Therefore, the absence of bleeding "cancellation" can not be used as a sign of an unforeseen pregnancy. In such cases, there are difficulties with timely diagnosis of pregnancy. This fact is especially important for women taking concomitant drugs with teratogenic effect. And although the onset of pregnancy against the background of regular use of the drug Jess ® is unlikely, with the slightest suspicion of pregnancy, a pregnancy test should be performed.

Effect on the ability to drive transp. cf. and fur:

Not found.

Form release / dosage:

Tablets, film-coated, 3.00 mg + 0.02 mg.

Packaging:

For 28 tablets (24 active tablets and 4 tablets) in a blister of polyvinyl chloride and aluminum foil. 1 blister is pasted into a clamshell cardboard, 1 or 3 clamshell books along with a self-adhesive calendar of reception and instructions for use are sealed in a transparent film.

For 30 active tablets in a flex polymer cartridge. 1 flex-cartridge in a blister of polyamide / polyethylene and aluminum foil.1 or 3 blisters with a flexo cartridge together with instructions for medical use in a pack of cardboard, or 1 blister with a flexo cartridge together with instructions for medical use in an individual pack of cardboard and a dosimeter Click (Clyk) with instructions for use in an individual pack of cardboard, in a pack of cardboard.

Storage conditions:

Store at a temperature not exceeding 30 ° C.

Keep out of the reach of children.

Shelf life:

5 years (blister with 28 tablets);

3 years (flex-cartridge with 30 tablets). *

Do not use after the expiration date!

* The shelf life of the kit may be limited by the activation date of the dispenser included in the kit. Click (Clyk) and thus less than 3 years. The shelf life of tablets in the flex cartridge remains unchanged (3 years).

Terms of leave from pharmacies:On prescription

Registration number:LSR-008842/08

Date of registration:10.11.2008 / 14.04.2016

Expiration Date:Unlimited

The owner of the registration certificate:Bayer Pharma AGBayer Pharma AG Germany

Manufacturer: & nbsp

BAYER PHARMA, AG Germany

BAYER WEIMAR, GmbH & Co. KG. KG Germany

Representation: & nbspBAYER, AOBAYER, AO

Information update date: & nbsp24.01.2016

Illustrated instructions

Instructions

Jess® (Yaz®)