When taking Jess, I experienced quite serious side effects that worsened over time, namely: severe pain in the joints, I could not go up to the second floor without crying, and my face became covered with severe pigmentation. After discontinuation, the pain and pigmentation went away, the same side effects occurred when taking Femoston 2/10. Lately I have been taking Belara and Diane.

In the fall, I developed rashes on my face; several specialists treated them, but they never made an accurate diagnosis. At first there was allergic dermatitis, then atopic and seborrheic, although my symptoms were not similar to any of these dermatitis. By chance, I saw photos on the Internet showing similar rashes as mine and an accurate description, it turns out it’s perioral dermatitis. Possible causes of this disease include hormonal problems. Is it possible that my problem arose while taking COCs, if there were already deteriorations in the skin before? And now the question is how to deal with them. Our dermatologists only prescribe corticosteroids, which make the problem worse and cause rashes to spread all over the face. Now I don’t take anything except folic acid, I wipe my skin with a decoction of celandine and lubricate it with black cumin oil. There are improvements, no rashes or redness are visible, but as soon as I stop doing this, it breaks out again. Perhaps you know a treatment regimen for this disease and is it even possible to cure it completely?

Answered by Berezovskaya E.P.

What you are describing is indeed a side effect of taking contraceptives. The same reaction can occur to steroid drugs, because contraceptives and steroids are one group. Also, it is necessary not to treat the skin with decoctions, but to understand that too aggressive care for it does not lead to good. The best thing to do is to find the optimal skin moisturizer. You have been addicted to all kinds of hormones for too long, so your problems are related to the liver's reaction to taking these hormones. The body needs to be given time (several months) to come to its senses. At the same time, it is important to eat right. Perioral dermatitis often occurs due to dental caries and periodontitis, so go to the dentist to have it checked.

Monophasic oral contraceptive with antiandrogenic properties

Active ingredients

Ethinylestradiol
- drospirenone

Release form, composition and packaging

(active) light pink, round, biconvex, engraved with the letters "DS" in a regular hexagon on one side; at the break - a white to almost white core and a light pink shell (24 pcs in a blister or 30 pcs in a flex cartridge).

Excipients: lactose monohydrate - 48.18 mg, corn starch - 28 mg, magnesium stearate - 0.8 mg.

Shell composition: hypromellose - 1.5168 mg, talc - 0.3036 mg, titanium dioxide - 1.1748 mg, red iron oxide dye - 0.0048 mg.

Film-coated tablets (placebo) white, round, biconvex, engraved with the letters "DP" in a regular hexagon on one side; at the break - a white to almost white core and a white shell (4 pieces in a blister).

Excipients: lactose monohydrate - 23.205 mg, microcrystalline cellulose - 54.21 mg, magnesium stearate - 0.585 mg.

Shell composition: hypromellose - 1.0112 mg, talc - 0.2024 mg, titanium dioxide - 0.7864 mg.

28 pcs. (24 active tablets and 4 placebo tablets) - blisters (1) - folding books (1) complete with a self-adhesive dosage calendar - film.
28 pcs. (24 active tablets and 4 placebo tablets) - blisters (1) - folding books (3) complete with a self-adhesive dosage calendar - film.
30 pcs. (30 active tablets) - flex cartridges (1) - blisters (1) - cardboard packs.
30 pcs. (30 active tablets) - flex cartridges (1) - blisters (3) - cardboard packs.
30 pcs. (30 active tablets) - flex cartridges (1) - blisters (1) - individual cardboard packs (1) complete with a Clyk dispenser - cardboard packs.

pharmachologic effect

The drug Jess is a combined hormonal contraceptive with antimineralocorticoid and antiandrogenic effects.

The contraceptive effect of combined oral contraceptives is based on the interaction of various factors, the most important of which include suppression of ovulation and changes in the properties of cervical secretion, as a result of which it becomes less permeable to sperm.

When used correctly, the Pearl index (the number of pregnancies per 100 women per year) is less than 1. If pills are missed or used incorrectly, the Pearl index may increase.

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

Drospirenone contained in the drug Jess has an antimineralocorticoid effect. Prevents weight gain and the appearance of edema associated with estrogen-induced fluid retention, which ensures good tolerability of the drug. Drospirenone has a positive effect on premenstrual syndrome (PMS). The clinical effectiveness of the drug Jess has been shown in alleviating the symptoms of severe PMS, such as severe psycho-emotional disorders, breast engorgement, headache, muscle and joint pain, weight gain and other symptoms associated with the menstrual cycle.

Drospirenone also has antiandrogenic activity and helps reduce acne, oily skin and hair. This action of drospirenone is similar to the action of natural drospirenone produced by the body.

Drospirenone does not have androgenic, estrogenic, glucocorticoid or antiglucocorticoid activity. All this, combined with antimineralocorticoid and antiandrogenic effects, provides drospirenone with a biochemical and pharmacological profile similar to natural progesterone.

When combined with ethinyl estradiol, drospirenone demonstrates a beneficial effect on the lipid profile, characterized by an increase in HDL.

The drug Jess can be used both in the usual mode (the “24+4” regimen: taking active tablets for 24 days, then taking inactive tablets for 4 days), and in the “flexible” mode.

The adapted extended (“flexible”) regimen for taking the drug Jess is based on the previously approved “24+4” regimen for taking the drug and consists in the fact that active tablets of the drug can be taken daily continuously for up to 120 days. Thus, the continuous period of taking active tablets can be 24-120 days, and the duration of the break in taking tablets should not exceed 4 days. A “flexible” regimen of administration is possible only if you have a Clyk dispenser and flex cartridges, which allow you to adhere to the regimen of taking the drug.

The results of a multicenter comparative open randomized study in parallel groups showed that the “flexible” regimen of taking the drug Jess, aimed at achieving a maximum duration of intervals without bleeding up to 120 days, allowed to reduce the total number of days of menstruation per year from 66 (“24+4” regimen). ) up to 41 days ("flexible" regimen).

Pharmacokinetics

Drospirenone

Suction

When taken orally, drospirenone is rapidly and almost completely absorbed. After a single oral dose, the Cmax of drospirenone in serum is reached after approximately 1-2 hours and is about 38 ng/ml. Bioavailability - 76-85%. Compared to taking the substance on an empty stomach, food intake does not affect the bioavailability of drospirenone.

Distribution

After oral administration, a biphasic decrease in the level of drospirenone in the serum is observed, with T 1/2, respectively, 1.6 ± 0.7 hours and 27 ± 7.5 hours. Drospirenone binds to serum and does not bind to sex hormone binding globulin (SHBG) or corticosteroid binding globulin globulin (CSG). Only 3-5% of the total serum concentration is present as free hormone. Ethinyl estradiol-induced increases in SHBG do not affect protein binding of drospirenone. The average apparent Vd is 3.7±1.2 l/kg.

The steady-state concentration during cyclic administration (C ss max) of drospirenone in serum is achieved between 7 and 14 days of treatment and is approximately 70 ng/ml. There was an increase in the concentration of drospirenone in the serum by approximately 2-3 times (due to cumulation), which was determined by the ratio of T 1/2 in the terminal phase and the dosing interval. A further increase in the serum concentration of drospirenone is observed between 1 and 6 cycles of administration, after which no increase in concentration is observed.

Metabolism

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

Removal

The rate of metabolic clearance of drospirenone in serum is 1.5±0.2 ml/min/kg. Unmodified drospirenone is excreted only in trace amounts. Drospirenone metabolites are excreted through the intestines and kidneys in a ratio of approximately 1.2:1.4. T 1/2 is approximately 40 hours.

Pharmacokinetics in special clinical situations

Css of drospirenone in serum in women with mild renal failure (creatinine clearance 50-80 ml/min) were comparable to the corresponding values ​​in women with normal renal function (creatinine clearance >80 ml/min). In women with moderate renal failure (creatinine clearance 30-50 ml/min), serum levels of drospirenone were on average 37% higher than in women with normal renal function. Drospirenone treatment was well tolerated in all groups. Drospirenone did not have a clinically significant effect on serum potassium concentrations. Pharmacokinetics in severe renal failure have not been studied.

Drospirenone is well tolerated in patients with mild to moderate hepatic impairment (Child-Pugh class B). Pharmacokinetics in severe hepatic impairment have not been studied.

Ethinyl estradiol

Suction

After oral administration, ethinyl estradiol is rapidly and completely absorbed. Cmax after a single oral dose is reached after 1-2 hours and is about 88-100 pg/ml. Absolute bioavailability due to presystemic conjugation and first-pass metabolism through the liver is approximately 60%. Concomitant food intake reduces the bioavailability of ethinyl estradiol in approximately 25% of those examined, while no such changes were observed in other study participants.

Distribution

The concentration of ethinyl estradiol in the serum decreases biphasically, T1/2 of the terminal phase is 24 hours. Ethinyl estradiol is significantly, but not specifically, associated with serum albumin (approximately 98.5%) and causes an increase in SHBG concentrations in the serum. The apparent Vd is about 5 l/kg. Steady-state concentration (C ss) is reached during the second half of the treatment cycle, with serum ethinyl estradiol levels increasing approximately 1.5-2.3 times.

Metabolism

Ethinyl estradiol undergoes significant first-pass metabolism in the intestine and liver. Ethinyl estradiol and its oxidative metabolites are primarily conjugated to glucuronides or sulfate. The rate of metabolic clearance of ethinyl estradiol is approximately 5 ml/min/kg.

Removal

Ethinyl estradiol is practically not excreted unchanged. Metabolites of ethinyl estradiol are excreted by the kidneys and through the intestines in a ratio of 4:6. T1/2 of metabolites - 24 hours.

Indications

- contraception;

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

- contraception and treatment of severe premenstrual syndrome.

Contraindications

Jess is contraindicated in the presence of any of the conditions listed below; If any of these conditions/diseases develop for the first time while taking the drug, the drug should be discontinued immediately:

- thrombosis (venous and arterial) and thromboembolism currently or in history (including deep vein thrombosis, pulmonary embolism, myocardial infarction), cerebrovascular disorders;

- conditions preceding thrombosis (including transient ischemic attacks, angina) currently or in history;

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

- presence of a high risk of venous or arterial thrombosis;

- migraine with focal neurological symptoms currently or in history;

— diabetes mellitus with vascular complications;

- liver failure and severe liver disease (until liver tests return to normal);

- liver tumors (benign or malignant) currently or in history;

- severe renal failure, acute renal failure;

- adrenal insufficiency;

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

- bleeding from the vagina of unknown origin;

— pregnancy or suspicion of it;

- period of breastfeeding;

- lactose intolerance, lactase deficiency, glucose-galactose malabsorption (the drug contains lactose monohydrate);

- hypersensitivity to any of the components of the drug Jess.

Use with caution

If any of the conditions/risk factors listed below currently exist, the potential risks and expected benefits of combined oral contraceptives should be carefully weighed in each individual case:

- risk factors for the development of thrombosis and thromboembolism (smoking; thrombosis, myocardial infarction or cerebrovascular accident at a young age in one of the immediate family; obesity; dyslipoproteinemia; arterial hypertension; migraine; heart valve disease; rhythm disturbance; prolonged immobilization; serious surgical interventions; extensive trauma);

- other diseases in which peripheral circulatory disorders may occur (diabetes mellitus; systemic lupus erythematosus; hemolytic uremic syndrome; Crohn's disease and ulcerative colitis; sickle cell anemia; phlebitis of the superficial veins);

- hereditary angioedema;

- hypertriglyceridemia;

- liver diseases;

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

- postpartum period.

Dosage

Reception mode "24+4"

The tablets should be taken in the order indicated on the package, at approximately the same time every day, with a small amount of water. The tablets are taken without interruption. Should be taken 1 tablet/day consistently for 28 days. Each subsequent package should be started the day after taking the last tablet from the previous package. Withdrawal bleeding usually begins on the 2-3rd day after starting the inactive (white) tablets and may not yet be completed before the next pack is started. You should always start taking pills from a new pack on the same day of the week, and withdrawal bleeding will occur on approximately the same days each month.

"Flexible" reception mode

The “flexible” mode of taking the drug Jess can only be used if you have a Clyk dispenser and flex cartridges. The drug should be taken 1 tablet daily at the same time with a small amount of liquid. The tablets should be taken continuously for at least 24 days. Between 25 and 120 days of using the drug Jess, at the patient’s discretion, a 4-day break from taking the pills can be taken. The break in taking pills should not exceed 4 days. A 4-day break from taking pills should be taken no later than 120 days of continuous pill taking. After each 4-day break from taking the pills, a new cycle begins with a minimum duration of 24 days and a maximum duration of 120 days. As a rule, withdrawal bleeding develops during the 4-day break from taking pills, but may not complete until the next pill is taken. If spotting/bleeding from the vagina appears for 3 consecutive days from days 25 to 120, it is recommended to take a 4-day break from taking the pills. This will reduce the total number of bleeding days.

Instructions for handling the packaging of the drug Jess for the “24+4” dosing regimen

The packaging of the drug Jess contains a blister containing 24 active hormone-containing light pink tablets and 4 inactive white, hormone-free tablets (last row). The package also includes an appointment calendar, consisting of 7 self-adhesive strips with the names of the days of the week marked on them. You should select the strip where the day of the week on which you plan to start taking the pills is indicated first. For example, if a woman starts taking the pill on Wednesday, she should use a strip that starts with "Wed."

The strip should be glued along the top of the package so that the designation of the first day is located above the tablet to which the arrow with the inscription “Start” is directed. This will show you which day of the week you should take each tablet.

Operating instructions for the Clyk dispenser

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

General description of the Clyk dispenser:

Side keys - press area to get a tablet;

Flex cartridge eject button - pressing this button removes the flex cartridge;

Tablet dispensing area - the part of the dispenser in which the dispensed tablets appear;

Tablet time indicator - shows the time of taking the tablet;

Display - displays the main screen and menu items;

"OK" button - pressing the button confirms the action, for example, starting a 4-day break from taking pills and changing the reminder sound.

Most important functions

Activating a new dispenser: The flex cartridge (containing 30 tablets) should be removed from the packaging and immediately inserted into the dispenser. The narrow end of the flex cartridge should be inserted into the dispenser so that the dispenser window (as well as the tablets in the flex cartridge) is clearly visible. The flex cartridge must be inserted all the way.

The dispenser will automatically record the time the first tablet was dispensed, setting this time as "Dose Time". Thus, a woman needs:

Make sure she unpacks and inserts the flex cartridge on the day she plans to start taking the pills;

Be sure that the time of dispensing the first tablet will be convenient for daily pill taking.

Every 24 hours, a signal will appear on the dispenser display indicating it is time to take the next tablet.

Removing the tablet

With one hand, simultaneously press both side keys to remove the tablet, which is obtained with the other hand.

Replacing the flex cartridge

During normal use, the flex cartridge can only be removed if it is empty; otherwise, you must follow the detailed operating instructions for the Clyk dispenser. An empty flex cartridge is removed by pressing the flex cartridge eject button. The dispenser retains all information about the current cycle and a new filled flex cartridge should be inserted according to the instructions above.

Before starting and during use, you should carefully read the detailed operating instructions for the Clyk dispenser included in the package with the drug.

Start taking the drug

If you have not taken any hormonal contraceptives in the previous month

Taking the drug Jess begins on the 1st day of the menstrual cycle (i.e. on the 1st day of menstrual bleeding), in this case additional contraceptive measures are not required. It is possible to start taking it on the 2-5th day of the menstrual cycle, but in this case it is recommended to additionally use a barrier method of contraception during the first 7 days of taking the tablets from the first package. The tablets should then be taken in the order indicated for the 24+4 or flexible dosing regimen.

When switching from other combined oral contraceptives, vaginal ring or contraceptive patch

It is preferable to start taking Jess the day after taking the last active tablet from the previous package, but in no case later than the next day after the usual 7-day break (for drugs containing 21 tablets) or after taking the last inactive tablet (for drugs containing containing 28 tablets per package). Taking Jess should begin on the day the vaginal ring or patch is removed, but no later than the day when a new ring is to be inserted or a new patch is applied.

When switching from contraceptives containing only gestagens ("mini-pills", injectable forms, implant), or from a gestagen-releasing intrauterine contraceptive

A woman can switch from taking the “mini-pill” to Jess on any day (without a break), from an implant or intrauterine contraceptive with progestogen - on the day of its removal, from an injectable contraceptive - on the day when the next injection is due. In all cases, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the pills.

After an abortion in the first trimester of pregnancy

A woman can start taking the drug 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 childbirth or abortion in the second trimester of pregnancy

Taking the drug can be started 21-28 days after a spontaneous or medical abortion or after childbirth, in the absence of breastfeeding. If use is started later, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the pills. However, if sexual intercourse has already taken place, pregnancy should be ruled out before starting to take Jess, or you should wait until your first menstruation.

Stopping taking Jess

You can stop taking the drug at any time. If a woman is not planning a pregnancy, or if a woman is contraindicated for pregnancy because she is taking medications that are potentially harmful to the fetus, other methods of contraception should be discussed with the doctor. If a woman is planning a pregnancy, it is recommended to stop taking the drug and wait for natural menstrual bleeding before trying to become pregnant. This will help you more accurately calculate your gestational age and delivery time.

Taking missed pills

Skipping inactive pills during the 24+4 regimen can be ignored. However, they should be thrown away to avoid accidentally prolonging the period of taking inactive tablets. The following recommendations apply only to skipping the 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 pill as soon as possible and take the next pill at the usual time.

If you are late in taking your pills more than 24 hours, contraceptive protection may be reduced. The more tablets are missed and the closer the missed tablets are to the phase of taking inactive white tablets when using the “24+4” regimen or to the period free from taking tablets against the backdrop of a “flexible” dosing regimen, the higher the likelihood of pregnancy.

In this case, you can be guided by the following two basic rules:

- taking the drug should never be interrupted for more than 7 days (please note that the recommended interval for taking inactive tablets is 4 days for the “24+4” dosing regimen, and for the “flexible” dosing regimen the interval without taking tablets is not must exceed 4 days);

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

The Clyk dispenser allows you to control the intake of pills and warns the woman about the need to use an additional method of contraception. The warning symbol "exclamation mark" appears on the display if you miss tablets or if you do not take tablets regularly for more than 7 days in a row. The "exclamation mark" disappears after 7 days of continuous dispensing of tablets. If more than one tablet is missed, it is recommended to consult a doctor.

In the case of the “24+4” reception mode, as well as in the “flexible” mode, if information from the Clyk dispenser is not available or there are doubts about its reliability, the following recommendations must be followed:

If you miss taking pills from the 1st to the 7th day

A woman should take the last missed pill as soon as she remembers, even if this means taking two pills at the same time. She continues to take her next pills at the usual time. In addition, over the next 7 days it is necessary to additionally use a barrier method of contraception (for example, a condom). If sexual intercourse took place within 7 days before missing a pill, the possibility of pregnancy should be taken into account.

If you miss taking pills from the 8th to the 14th day with the “24+4” regimen or if you miss taking pills from the 8th to the 24th day with the “flexible” regimen

A woman should take the last missed pill as soon as she remembers, even if this means taking two pills at the same time. She continues to take her next pills at the usual time.

Provided that a woman has taken her pills correctly for the 7 days preceding the first missed pill, there is no need to use additional contraceptive measures. Otherwise, as well as if two or more tablets are missed, it is necessary to additionally use barrier methods of contraception (for example, a condom) for 7 days, and with a “flexible” dosing regimen, barrier methods of contraception should be used until the continuous period of taking the tablets does not will reach 7 days.

If you miss taking pills from the 15th to 24th day with the “24+4” regimen or if you miss taking pills from the 25th to 120th day with the “flexible” regimen

The risk of reduced reliability is inevitable due to the approaching phase of taking inactive white tablets in the case of a “24+4” dosing regimen or a pill-free period with a “flexible” dosing regimen. You must strictly adhere to one of the following two options. Moreover, if during the 7 days preceding the first missed pill, all pills were taken correctly, there is no need to use additional contraceptive methods. Otherwise, you must use the first of the following regimens and additionally use a barrier method of contraception (for example, a condom) for 7 days.

1. A woman should take the last missed pill as soon as she remembers (even if this means taking two pills at the same time). For the 24+4 regimen: the following tablets are taken at the usual time until the active light pink tablets in the package run out, the 4 inactive white tablets should be discarded and the tablets from the next package should be started immediately. Withdrawal bleeding is unlikely until the active light pink tablets in the second pack are gone, but spotting and/or breakthrough bleeding may occur while taking the tablets. If using a “flexible” regimen, you should take at least 7 tablets without interruption (one tablet daily).

2. For the "24+4" regimen: the woman can also stop taking the active light pink tablets from the current package. Then you should take a break of no more than 4 days, including days you missed pills, and then start taking the drug from a new package. If a woman misses taking active light pink tablets and does not experience withdrawal bleeding while taking inactive white tablets, pregnancy must be ruled out. For a "flexible" dosing schedule, a woman can also take a 4-day pill-free period, including a missed pill day, to induce withdrawal bleeding, and then start a new cycle of dosing. If a woman misses a pill and does not experience withdrawal bleeding during the next pill-free period, the possibility of pregnancy should be considered.

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

If you have vomiting or diarrhea within 3-4 hours after taking the active light pink tablet, you should follow the recommendations for skipping tablets. If a woman does not want to change her usual dosing regimen and postpone the onset of menstruation to another day of the week, she should take an additional active light pink tablet.

How to change the time of onset of withdrawal bleeding or how to delay the onset of withdrawal bleeding during the “24+4” regimen

To delay the onset of withdrawal bleeding, the woman should continue taking tablets from the next pack of Jess, skipping the inactive tablets from the current pack. Thus, the cycle can be extended, if desired, for any period until the active light pink tablets from the second package run out, i.e. about 3 weeks later than usual. If you plan to start your next cycle earlier, you should stop taking the active light pink tablets from the second pack at any time, throw away the remaining active light pink tablets and start taking the white inactive tablets (for a maximum of 4 days), and then start taking the tablets from new packaging. In this case, withdrawal bleeding should begin approximately 2-3 days after taking the last light pink tablet from the previous package. While taking the drug from the second package, a woman may experience spotting and/or breakthrough uterine bleeding. Regular use of Jess is then resumed after the period of taking the inactive white tablets has ended.

To postpone the onset of withdrawal bleeding on another day of the week, the woman should reduce the next period of taking inactive white tablets by the desired number of days. The shorter the interval, the higher the risk that she will not have withdrawal bleeding, and will subsequently have spotting and/or breakthrough bleeding while taking the pills from the second pack.

Additional information for special categories of patients

Children and teenagers

After menopause Jess is not indicated.

severe liver diseases until liver function tests return to normal.

Jess is contraindicated in women with or with acute renal failure.

Side effects

The following most common adverse reactions have been reported in women using the drug Jess in the “24+4” mode for the indications “Contraception” and “Contraception and treatment of moderate acne (acne vulgaris)”: nausea, pain in the mammary glands, irregular uterine bleeding, bleeding from the genital tract of unspecified origin. These adverse reactions occurred in more than 3% of women. In patients using Jess for the indication "Contraception and treatment of severe premenstrual syndrome", the following most common adverse reactions were reported (in more than 10% of women): nausea, pain in the mammary glands, irregular uterine bleeding.

Serious adverse reactions include arterial and venous thromboembolism, and for the “flexible” drug regimen, breast cancer and focal nodular hyperplasia of the liver are additionally noted.

Below is the frequency of adverse reactions reported during clinical studies of the drug Jess for the "24+4" regimen for the indications "Contraception" and "Contraception and treatment of moderate acne (acne vulgaris)" (n = 3565), for the indication " Contraception and treatment of severe premenstrual syndrome" (n=289), as well as a "flexible" regimen for taking the drug Jess (n=2738). Within each group, allocated depending on the frequency of occurrence of an undesirable reaction, adverse reactions are presented in order of decreasing severity. By frequency they are divided as follows: often (≥1/100 and<1/10), нечасто (≥1/1000 и <1/100) и редко (≥1/10 000 и <1/1000). Для дополнительных нежелательных реакций, выявленных только в процессе постмаркетинговых наблюдений, и для которых оценку частоты возникновения провести не представлялось возможным, указано "частота неизвестна".

Frequency of adverse reactions in clinical studies of the drug Jess ("24+4" and "flexible" dosage regimen*)

From the blood and lymphatic system: rarely - anemia, thrombocytopenia.

From the immune system: rarely - allergic reactions; frequency unknown - hypersensitivity.

Metabolism and nutrition: rarely - increased appetite, anorexia, hyperkalemia, hyponatremia.

From the mental side: often - emotional lability, depression, decreased libido; infrequently - nervousness, drowsiness; rarely - anorgasmia, insomnia.

From the nervous system: often - headache; infrequently - dizziness, paresthesia; rarely - vertigo, tremor.

From the side of the organ of vision: rarely - conjunctivitis, dry mucous membrane of the eyes.

From the cardiovascular system: often - migraine; infrequently – varicose veins, increased blood pressure; rarely tachycardia, phlebitis, epistaxis, fainting, venous thromboembolism, arterial thromboembolism.

From the gastrointestinal tract: often - nausea; uncommon - abdominal pain, vomiting, dyspepsia, flatulence, gastritis, diarrhea; rarely - bloating, feeling of heaviness in the abdomen, hiatal hernia, oral candidiasis, constipation, dry mouth.

From the liver and biliary tract: rarely - biliary dyskinesia, cholecystitis.

For the skin and subcutaneous tissues: uncommon - acne, itching, rash; rarely - chloasma, eczema, alopecia, acne dermatitis, dry skin, erythema nodosum, hypertrichosis, stretch marks, contact dermatitis, photodermatitis, skin nodules; frequency unknown - erythema multiforme.

From the musculoskeletal system: uncommon - back pain, pain in the limbs, muscle cramps.

From the genital organs and breast: often - pain in the mammary glands, metrorrhagia**, absence of menstrual-like bleeding; uncommon - vaginal candidiasis, pain in the pelvic area, enlarged mammary glands, fibrocystic formations in the mammary gland, spotting/bleeding from the genital tract**, discharge from the genital tract, hot flashes with a feeling of heat, vaginitis, painful menstrual-like bleeding , scanty menstrual-like bleeding, heavy menstrual-like bleeding, dryness of the vaginal mucosa, abnormal results of the Papanicolaou test; rarely - dyspareunia, vulvovaginitis, postcoital bleeding, withdrawal bleeding, breast hyperplasia, neoplasm in the mammary gland, cervical polyp, endometrial atrophy, ovarian cyst, uterine enlargement.

Laboratory and instrumental data: infrequently - weight gain; rarely - weight loss.

Others: uncommon - asthenia, increased sweating, edema (generalized edema, peripheral edema, facial edema); rarely - malaise.

* in cases where adverse reactions occurred with different frequencies during the use of the “24+4” and “flexible” modes, the highest frequency is indicated.

** The frequency of irregular bleeding decreases as the duration of use of the drug Jess increases.

Additional Information

Listed below are adverse reactions with a very rare incidence or delayed symptoms, which are believed to be associated with the use of drugs from the group of combined oral contraceptives.

Tumors

The incidence of breast cancer diagnosis in women taking combined oral contraceptives is slightly increased. Because breast cancer is rare in women under 40 years of age, the increase in breast cancer diagnoses in women taking combined oral contraceptives is small relative to the overall risk of this disease;

Liver tumors (benign and malignant).

Other states

Erythema nodosum, erythema multiforme (only for the “flexible” regimen of taking the drug);

Women with hypertriglyceridemia (increased risk of pancreatitis while taking combined oral contraceptives);

Increased blood pressure;

Conditions that develop or worsen while taking combined oral contraceptives, but their relationship has not been proven (jaundice and/or itching associated with cholestasis; cholelithiasis; porphyria; systemic lupus erythematosus; hemolytic uremic syndrome; Sydenham chorea; herpes during pregnancy; decreased hearing associated with otosclerosis);

In women with hereditary angioedema, estrogen may cause or worsen symptoms;

Liver dysfunction;

Change in tolerance to or effect on insulin resistance;

Crohn's disease, ulcerative colitis;

Chloasma;

Hypersensitivity (including symptoms such as rash, urticaria).

Interaction

Interaction of combined oral contraceptives with other drugs (enzyme inducers) may lead to breakthrough bleeding and/or decreased contraceptive effectiveness.

Overdose

No serious adverse events have been reported following overdose. Based on cumulative experience with combined oral contraceptives symptoms which may occur with an overdose of active tablets: nausea, vomiting, spotting or metrorrhagia.

Treatment: There is no specific antidote; symptomatic treatment should be carried out.

Drug interactions

The influence of other drugs on the drug Jess

Interaction with drugs that induce microsomal enzymes is possible, which may result in an increase in the clearance of sex hormones, which, in turn, can lead to breakthrough uterine bleeding and/or a decrease in the contraceptive effect.

Women who are treated with such drugs in addition to Jess are recommended to use a barrier method of contraception or choose another non-hormonal method of contraception. A barrier method of contraception should be used during the entire period of taking concomitant medications, as well as for 28 days after their discontinuation. If the period of use of the barrier method of contraception ends later than the active tablets in the Jess package, you should start taking Jess tablets from a new package without interruption in taking the active tablets.

Agents that increase the clearance of the drug Jess (weakening the effectiveness by inducing enzymes): phenytoin, barbiturates, primidone, carbamazepine, rifampicin and possibly also oxcarbazepine, topiramate, felbamate, griseofulvin, as well as preparations containing St. John's wort.

Agents with different effects on the clearance of the drug Jess: When used together with the drug Jess, many HIV or hepatitis C virus protease inhibitors and non-nucleoside reverse transcriptase inhibitors can both increase and decrease the concentration of estrogens or progestins in the blood plasma. In some cases, this effect may be clinically significant.

Drugs that reduce the clearance of combined oral contraceptives (enzyme inhibitors): strong and moderate inhibitors of CYP3A4, such as azole antifungals (eg, itraconazole, voriconazole, fluconazole), verapamil, macrolide antibiotics (eg, clarithromycin, erythromycin), diltiazem, and grapefruit juice may increase plasma concentrations of estrogen or progestin, or both .

Etoricoxib at doses of 60 and 120 mg/day, when coadministered with combined oral contraceptives containing 0.035 mg ethinyl estradiol, has been shown to increase plasma concentrations of ethinyl estradiol by 1.4 and 1.6 times, respectively.

The effect of Jess on other drugs

Combined oral contraceptives may affect the metabolism of other drugs, resulting in an increase (for example, cyclosporine) or a decrease (for example, lamotrigine) in their plasma and tissue concentrations.

In vitro, drospirenone is capable of weakly to moderate inhibition of the cytochrome P450 enzymes CYP1A1, CYP2C9, CYP2C19 and CYP3A4.

Based on in vivo interaction studies in female volunteers taking omeprazole, simvastatin or midazolam as marker substrates, it can be concluded that a clinically significant effect of drospirenone 3 mg on cytochrome P450-mediated drug metabolism is unlikely.

In vitro, ethinyl estradiol is a reversible inhibitor of CYP2C19, CYP1A1 and CYP1A2, and an irreversible inhibitor of CYP3A4/5, CYP2C8 and CYP2J2. In clinical studies, administration of a hormonal contraceptive containing ethinyl estradiol did not result in any increase or only a slight increase in plasma concentrations of CYP3A4 substrates (e.g., midazolam), whereas plasma concentrations of CYP1A2 substrates may increase slightly (e.g., theophylline ) or moderate (eg melatonin and tizanidine).

Other forms of interaction

In patients with unimpaired renal function, the combined use of drospirenone and ACE inhibitors or NSAIDs 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 must be monitored during the first cycle of taking the drug.

special instructions

If any of the conditions/risk factors listed below currently exist, the potential risks and expected benefits of combined oral contraceptives should be carefully weighed on an individual basis and discussed with the woman before she decides to start taking the drug. If any of these conditions or risk factors worsen, intensify, or appear for the first time, a woman should consult her doctor, who may decide whether to discontinue the drug.

Diseases of the cardiovascular system

The results of epidemiological studies indicate a relationship between the use of combined oral contraceptives and an increased incidence of venous and arterial thrombosis and thromboembolism (such as deep vein thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular diseases). These diseases are rare.

The risk of developing venous thromboembolism (VTE) is greatest in the first year of taking such drugs. An increased risk is present after initial use of oral contraceptives or resumption of use of the same or different combined oral contraceptives (after a dosing interval of 4 weeks or more). Data from a prospective study involving 3 groups of patients indicate that this increased risk is predominantly present during the first 3 months.

The overall risk of VTE in patients taking low-dose combined oral contraceptives (<50 мкг этинилэстрадиола), в 2-3 раза выше, чем у небеременных пациенток, которые не принимают комбинированные пероральные контрацептивы, тем не менее, этот риск остается более низким по сравнению с риском ВТЭ при беременности и родах. ВТЭ может угрожать жизни или привести к летальному исходу (в 1-2% случаев).

VTE, manifested as deep vein thrombosis or pulmonary embolism, can occur with the use of any combined oral contraceptives.

It is extremely rare when using combined oral contraceptives that thrombosis of other blood vessels occurs, for example, hepatic, mesenteric, renal, cerebral veins and arteries or retinal vessels. There is no consensus regarding the relationship between the occurrence of these events and the use of combined oral contraceptives.

Symptoms of deep vein thrombosis (DVT) include: unilateral swelling of the lower extremity or along a vein in the lower extremity, pain or discomfort in the leg only when standing or walking, localized warmth in the affected lower extremity, redness or discoloration of the skin on the lower extremity .

Symptoms of pulmonary embolism (PE) include: difficulty or rapid breathing; sudden cough, incl. with hemoptysis; sharp pain in the chest, which may intensify with deep inspiration; sense of anxiety; severe dizziness; fast or irregular heartbeat. Some of these symptoms (eg, shortness of breath, cough) are nonspecific and may be misinterpreted as symptoms of other more or less severe events (eg, respiratory tract infection).

Arterial thromboembolism can lead to stroke, vascular occlusion, or myocardial infarction. Symptoms of a stroke: sudden weakness or loss of sensation in the face, arm or leg, especially on one side of the body, sudden confusion, problems with speech and comprehension; sudden unilateral or bilateral vision loss; sudden disturbance in gait, dizziness, loss of balance or coordination; 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, swelling and slight blue discoloration of the extremities, the “acute abdomen” symptom complex.

Symptoms of myocardial infarction include: pain, discomfort, pressure, heaviness, a feeling of squeezing or fullness in the chest, arm, or chest; discomfort radiating to the back, cheekbone, larynx, arm, stomach; cold sweat, nausea, vomiting or dizziness, severe weakness, anxiety or shortness of breath; fast or irregular heartbeat.

Arterial thromboembolism can be life-threatening or fatal.

In women with a combination of several risk factors or high severity of one of them, the possibility of their mutual reinforcement should be considered. In such cases, the degree of increase in risk may be higher than with a simple summation of factors. In this case, taking the drug Jess is contraindicated.

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

- with age;

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

- for obesity (BMI more than 30 kg/m2);

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

- with prolonged immobilization, major surgery, any leg surgery or major trauma. In these situations, it is advisable to stop using combined oral contraceptives (in the case of planned surgery, at least 4 weeks before it) and not to resume use for 2 weeks after the end of immobilization. Temporary immobilization (eg, air travel lasting more than 4 hours) may also be a risk factor for the development of venous thromboembolism, especially in the presence of other risk factors;

- with dislipoproteinemia;

- for arterial hypertension;

- for migraine;

- for diseases of the heart valves;

- with atrial fibrillation.

The use of any combined hormonal contraceptives increases the risk of developing VTE. The use of drugs containing levonorgestrel, norgestimate or norethisterone is associated with the lowest risk of developing VTE. The use of other drugs, such as Jess, may double the risk. The decision to use a drug other than the one with the lowest risk of developing VTE should only be made after discussion with the woman to ensure that she understands that the use of Jess is associated with the likelihood of developing VTE, and understands how her risk factors affect the likelihood of developing VTE , and also understands that in each first year of using the drug, her risk of developing VTE is greatest. There is evidence that the risk of developing VTE increases when taking combined hormonal contraceptives is resumed after a break of 4 weeks or more.

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

The increased risk of thromboembolism in the postpartum period should be taken into account.

Peripheral circulatory disorders may 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 combined oral contraceptives (which may precede cerebrovascular events) is grounds for immediate discontinuation of these drugs.

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

When assessing the risk-benefit ratio, it should be taken into account that adequate treatment of the relevant condition can reduce the associated risk of thrombosis. It should also be taken into account that the risk of thrombosis and thromboembolism during pregnancy is higher than when taking low-dose oral contraceptives (<50 мкг этинилэстрадиола).

Tumors

The most significant risk factor for developing cervical cancer is persistent human papillomavirus infection. There are reports of a slight increase in the risk of developing cervical cancer with long-term use of combined oral contraceptives, but the relationship with the use of combined oral contraceptives has not been proven. Controversy remains regarding the extent to which these findings are related to screening for cervical pathology or to sexual behavior (lower use of barrier methods of contraception).

A meta-analysis of 54 epidemiological studies found that there is a slightly increased relative risk of developing breast cancer diagnosed in women currently taking combined oral contraceptives (relative risk 1.24). The increased risk gradually disappears within 10 years of stopping these drugs. Because breast cancer is rare in women under 40 years of age, the increase in breast cancer diagnoses in women currently or recently taking combined oral contraceptives is small relative to the overall risk of breast cancer. The observed increased risk may be due to earlier diagnosis of breast cancer in women using combined oral contraceptives, the biological effects of oral contraceptives, or a combination of both factors. Women who have used combined oral contraceptives are diagnosed with earlier stages of breast cancer than women who have never used them.

In rare cases, during the use of combined oral contraceptives, the development of benign, and in extremely rare cases, malignant liver tumors, which in some cases led to life-threatening intra-abdominal bleeding, was observed. If severe abdominal pain, liver enlargement, or signs of intra-abdominal bleeding occur, this should be taken into account when making a differential diagnosis.

Tumors can be life-threatening or fatal.

Other states

Clinical studies have shown no effect of drospirenone on serum potassium concentrations in patients with mild to moderate renal failure. There is a theoretical risk of developing hyperkalemia in patients with impaired renal function with an initial potassium concentration at ULN who are simultaneously taking medications that lead to potassium retention in the body. In women with an increased risk of developing hyperkalemia, it is recommended to determine plasma potassium concentrations during the first cycle of taking Jess.

Women with hypertriglyceridemia (or a family history of this condition) may have an increased risk of developing pancreatitis while taking combined oral contraceptives.

Although slight increases in blood pressure have been described in many women taking combined oral contraceptives, clinically significant increases have rarely been reported. However, if a persistent, clinically significant increase in blood pressure develops while taking combined oral contraceptives, these drugs should be discontinued and treatment of arterial hypertension should be initiated. Taking combined oral contraceptives can be continued if normal blood pressure values ​​are achieved with antihypertensive therapy.

The following conditions have been reported to develop or worsen both during pregnancy and while taking combined oral contraceptives, but their relationship with taking combined oral contraceptives has not been proven: jaundice and/or pruritus associated with cholestasis; cholelithiasis; porphyria; systemic lupus erythematosus; hemolytic uremic syndrome; Sydenham's chorea; herpes during pregnancy; hearing loss associated with otosclerosis. Cases of worsening the course of endogenous depression, epilepsy, Crohn's disease and ulcerative colitis during the use of combined oral contraceptives have also been described.

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

Acute or chronic liver dysfunction may require discontinuation of combined oral contraceptives until liver function tests return to normal. Recurrent cholestatic jaundice, which develops for the first time during pregnancy or previous use of sex hormones, requires discontinuation of combined oral contraceptives.

Although combined oral contraceptives may have an effect on insulin resistance and glucose tolerance, there is no need to change the therapeutic regimen in diabetic patients using low-dose combined oral contraceptives (<50 мкг этинилэстрадиола). Тем не менее, женщин с сахарным диабетом следует тщательно наблюдать во время приема комбинированных пероральных контрацептивов.

Chloasma can sometimes develop, especially in women with a history of pregnancy chloasma. Women prone to chloasma should avoid prolonged exposure to the sun and ultraviolet radiation while taking combined oral contraceptives.

Laboratory tests

Taking combined oral contraceptives may affect the results of some laboratory tests, including liver, kidney, thyroid, adrenal function, plasma transport protein concentrations, carbohydrate metabolism, coagulation and fibrinolysis parameters. Changes usually do not go beyond normal values.

Drospirenone increases plasma renin and aldosterone activity, which is associated with its antimineralocorticoid effect.

Medical examinations

Before starting or resuming the use of the drug Jess, it is necessary to familiarize yourself with the woman’s life history, family history, conduct a thorough general medical examination (including measuring blood pressure, heart rate, determining BMI) and gynecological examination (including examination of the mammary glands and cytological examination of cervical mucus), and exclude pregnancy. The scope of additional studies and the frequency of follow-up examinations are determined individually. Typically, follow-up examinations should be carried out at least once every 6 months.

The woman should be warned that combined oral contraceptives do not protect against HIV infection (AIDS) and other sexually transmitted diseases.

Reduced efficiency

The effectiveness of combined oral contraceptives may be reduced in the following cases: when active light pink tablets are missed (when using the 24+4 regimen or light pink tablets when using the flexible regimen), vomiting and diarrhea, or as a result of drug interactions .

Poor control of the menstrual cycle

While taking combined oral contraceptives, irregular bleeding (spotting or breakthrough bleeding) may occur, especially during the first months of use for both regimens. With the “flexible” regimen, irregular bleeding may develop during the fixed period of use from days 1 to 24). Therefore, any irregular bleeding should be assessed only after an adaptation period of approximately three cycles (or 3 months with a flexible dosing regimen).

If irregular bleeding recurs or develops after previous regular cycles, a thorough diagnostic evaluation should be performed to rule out malignancy or pregnancy.

Some women may not develop withdrawal bleeding during a break from taking active light pink tablets (24+4 regimen). If the drug is taken as directed, it is unlikely that the woman is pregnant. However, if the drug has not been taken regularly before, or if there are no two withdrawal bleedings in a row, pregnancy should be ruled out before continuing to take the drug.

Against the background of a “flexible” regimen of taking the drug, withdrawal bleeding is not regular. Therefore, the absence of withdrawal bleeding cannot be used as a sign of an unintended pregnancy. In such cases, difficulties arise with timely diagnosis of pregnancy. This fact is of particular importance for women taking concomitant drugs with teratogenic effects. And although the onset of pregnancy with regular use of the drug Jess is unlikely, at the slightest suspicion of pregnancy you should perform a pregnancy test.

Preclinical safety data

Preclinical data from routine repeated-dose toxicity, genotoxicity, carcinogenicity and reproductive toxicity studies do not indicate a particular risk to humans. However, it should be remembered that sex hormones can promote the growth of certain hormone-dependent tissues and tumors.

Impact on the ability to drive vehicles and operate machinery

Not found.

Pregnancy and lactation

The use of the drug Jess is contraindicated during pregnancy and breastfeeding.

The possibility of pregnancy should not be excluded in any patient with preserved reproductive potential who has symptoms characteristic of pregnancy, especially in those who have not complied with the drug regimen.

Symptoms characteristic of pregnancy may include not only the absence of withdrawal bleeding during the 4-day period free from taking pills ("flexible" mode) or while taking white inactive pills ("24+4" mode), but also the appearance of 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 reasons.

Withdrawal bleeding when using the “flexible” regimen does not occur, as usual, every 4 weeks, but develops at intervals of up to 120 days, depending on when the patient chooses a 4-day break from taking pills. Therefore, the absence of withdrawal bleeding cannot be used as a sign of an unintended pregnancy. In such cases, difficulties arise with timely diagnosis of pregnancy. Although the onset of pregnancy with strict adherence to the regimen of taking the drug Jess is unlikely, if you suspect pregnancy, you should immediately stop taking the drug Jess, consult a doctor and perform a pregnancy test.

If the patient is planning a pregnancy, she can stop taking Jess at any time. If the patient is simultaneously taking drugs that are potentially dangerous to the fetus (teratogenic) and therefore needs to prevent pregnancy, the decision to stop taking Jess can only be made after consultation with a doctor.

If pregnancy is detected while taking Jess, the drug should be discontinued immediately. However, extensive epidemiological studies have not shown any increased risk of developmental defects in children born to women who received sex hormones (including combined oral contraceptives) before pregnancy, or teratogenicity when sex hormones were inadvertently taken in early pregnancy.

Existing data on the results of using the drug 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 currently no significant epidemiological data on the drug Jess.

Taking combined oral contraceptives may reduce the amount of breast milk and change its composition, so their use is not recommended until you stop breastfeeding. Small amounts of sex hormones and/or their metabolites can pass into breast milk and affect the newborn's body.

Use in childhood

Children and teenagers Jess is indicated only after menarche. Available data do not suggest dose adjustment in this group of patients.

For impaired renal function

Jess is contraindicated in women with severe renal failure or with Storage conditions and periods

The drug should be stored out of the reach of children at a temperature not exceeding 30°C. Shelf life - 5 years (blister with 28 tablets), 3 years (flex cartridge with 30 tablets).

Jess Plus (ethinyl estradiol + drospirenone + calcium levomefolate) is a tablet contraceptive, one of the properties of which is low doses of active ingredients, which in this case should be considered as an advantage. The drug consists of active and auxiliary (calcium levomefolate) tablets. The contraceptive effect is due mainly to inhibition of the ovulatory process and changes in the rheological properties of cervical secretion in the direction of increasing its viscosity. The result of using Jess Plus is the regularization of the monthly cycle, relief of painful sensations, a decrease in the intensity of bleeding during menstruation, as well as a reduction in its duration (the latter entails another beneficial effect - reducing the risk of anemia). In the medical literature there is information about a reduction in the risk of developing malignant neoplasms of the endometrium and ovaries while taking tablet contraceptives in general and Jess Plus in particular. Drospirenone acts as an antagonist of cortisol and corticosterone, preventing the development of swelling caused by hormonal imbalance. The latter circumstance causes a decrease in body weight with the use of Jess Plus. Drospirenone is also an antiandrogen, reducing the likelihood of developing acne and reducing the oiliness of hair and skin. This fact is recommended to be taken into account when choosing a contraceptive for a woman with edema caused by hormonal imbalance, as well as acne and seborrhea. In fact, if we take into account the biochemical and pharmacological characteristics, drospirenone acts in the body as endogenous progesterone.

Calcium levomefolate is absorbed in the body better than folic acid. It is indicated for pregnant and lactating women to compensate for folate deficiency (during this period, women have an increased need for these substances). Additional intake of calcium levomefolate into the body can reduce the risk of developing defects in the fetus during an unexpected pregnancy or pregnancy that occurs immediately after stopping the use of contraceptives. The pharmacokinetic characteristics of the drug components vary somewhat. All three ingredients are quickly and completely absorbed in the digestive tract. However, while the bioavailability of drospirenone is practically not affected by the presence of food masses in the intestines, the same cannot be said about ethinyl estradiol. Jess Plus should be taken in strict accordance with what is indicated on the packaging and in the instructions for use. The key to reliable contraception is regularity of use and equal time intervals between doses. One package is enough for 28 days, after which you should start taking the next package. It is necessary to carefully weigh the possible risk and expected prospects for using the drug in the presence of the following risk factors:

Cardiovascular pathology;

Neoplasms (including malignant);

Kidney and liver failure.

The drug is contraindicated during pregnancy and breastfeeding. It is not recommended to use it as a means of teenage contraception.

Pharmacology

Jess ® Plus is a low-dose monophasic oral combined estrogen-progestogen contraceptive drug, including active tablets and auxiliary vitamin tablets containing calcium levomefolate.

The contraceptive effect of Jess ® Plus is mainly achieved by suppressing ovulation and increasing the viscosity of cervical mucus.

In women taking combined oral contraceptives (COCs), the cycle becomes more regular, the pain, intensity and duration of menstrual bleeding decrease, resulting in a reduced risk of iron deficiency anemia. There is also evidence of a reduced risk of endometrial and ovarian cancer.

Drospirenone, contained in the drug Jess ® Plus, has an antimineralocorticoid effect and helps prevent hormone-dependent fluid retention, which can manifest itself in weight loss and a decrease in the likelihood of peripheral edema. Drospirenone also has antiandrogenic activity and helps reduce acne (blackheads), oily skin and hair. This effect of drospirenone is similar to the effect of natural progesterone produced in the female body. This should be taken into account when choosing a contraceptive, especially for women with hormone-dependent fluid retention, as well as women with acne and seborrhea. When used correctly, the Pearl index (an indicator reflecting the number of pregnancies in 100 women using a contraceptive during the year) is less than 1. If pills are missed or used incorrectly, the Pearl index may increase.

The acid form of calcium levomefolate is structurally identical to naturally occurring L-5-methyltetrahydrofolate (L-5-methyl-THF), the main folate form found in food. The average concentration in the blood plasma of people who do not consume foods fortified with folic acid is about 15 nmol/l.

Levomefolate, unlike folic acid, is a biologically active form of folate. Thanks to this, it is absorbed better than folic acid. Levomefolate is indicated to meet the increased need and ensure the necessary folate content in a woman’s body during pregnancy and lactation. The addition of levomefolate calcium to an oral contraceptive reduces the risk of developing a neural tube defect if a woman becomes unexpectedly pregnant immediately after stopping contraception (or, in very rare cases, when using oral contraception).

Pharmacokinetics

Drospirenone

Suction

After oral administration, drospirenone is rapidly and almost completely absorbed. After a single oral dose, the Cmax of drospirenone in the blood plasma, equal to 35 ng/ml, is achieved after 1-2 hours. Bioavailability ranges from 76 to 85%. Compared to taking drospirenone on an empty stomach, food intake does not affect its bioavailability.

Distribution

Drospirenone binds to serum albumin and does not bind to sex hormone binding globulin (SHBG) or corticosteroid binding globulin (CBG). Only 3-5% of the total serum concentration is present as free hormone. The increase in SHBG induced by ethinyl estradiol does not affect the binding of drospirenone to plasma proteins. The average apparent Vd is 3.7±1.2 l/kg.

During the first course of use of the drug, the equilibrium state of drospirenone with a plasma concentration of about 60 ng/ml is achieved from the 7th to the 14th day of use of the drug. There was an increase in the concentration of drospirenone in the blood plasma by approximately 2-3 times (due to cumulation), which was determined by the ratio of T 1/2 in the terminal phase and the dosing interval. A further increase in the concentration of drospirenone in the blood plasma is observed after 1-6 courses of use of the drug, after which no increase in concentration is observed.

Metabolism

After oral administration, drospirenone is extensively metabolized. Most metabolites in plasma are represented by acidic forms of drospirenone, which are formed without the involvement of the cytochrome P450 system. Cytochrome P450 isoenzyme 3A4 is involved to a minimal extent in the metabolism of drospirenone. Drospirenone is able to reduce the concentration of the enzyme in the blood plasma and the activity of isoenzymes 1A1, 2C9 and 2C19 of cytochrome P450 in vitro.

Removal

After oral administration, a two-phase decrease in the level of the drug in the serum is observed, with T 1/2, respectively, 1.6 ± 0.7 hours and 27 ± 7.5 hours. The rate of metabolic clearance of drospirenone in blood plasma is 1.5 ± 0.2 ml/min/kg. Unmodified drospirenone is excreted only in trace amounts. Drospirenone metabolites are excreted through the gastrointestinal tract and kidneys in a ratio of approximately 1.2:1.4. T1/2 of metabolites - about 40 hours.

The concentration of drospirenone in the blood plasma when reaching a steady state was comparable in women with mild renal impairment (creatinine clearance 50-80 ml/min) and in women with preserved renal function (creatinine clearance more than 80 ml/min). However, in women with moderate renal impairment (creatinine clearance 30-50 ml/min), the average plasma concentration of drospirenone was 37% higher than in patients with preserved renal function. There were no changes in the concentration of potassium in the blood plasma when using drospirenone.

In women with moderate liver dysfunction (class B on the Child-Pugh scale), AUC is comparable to the corresponding indicator in healthy women with similar Cmax values ​​​​in the absorption and distribution phases. T1/2 of drospirenone in patients with moderate liver dysfunction was 1.8 times higher than in healthy volunteers with intact liver function.

In patients with moderate liver dysfunction, a decrease in the clearance of drospirenone by about 50% was observed compared to women with preserved liver function, while there were no differences in the concentration of potassium in the blood plasma in the studied groups. There were no changes in potassium concentration even in the case of a combination of factors predisposing to its increase (concomitant diabetes mellitus or treatment with spironolactone).

Ethinyl estradiol

Suction

After oral administration, ethinyl estradiol is rapidly and completely absorbed. Cmax is about 33 pg/ml, achieved within 1-2 hours. The drug undergoes first-pass metabolism in the liver, its bioavailability when taken orally is on average about 60%. Simultaneous ingestion of food in some cases is accompanied by a decrease in the bioavailability of ethinyl estradiol by 25%.

Distribution

Ethinyl estradiol has a nonspecific but strong binding to plasma albumin (about 98.5%) and induces an increase in plasma concentrations of SHBG. The estimated V d is about 5 l/kg.

An equilibrium state is achieved in the second half of the course of treatment, the concentration of ethinyl estradiol in the blood plasma increases by approximately 1.4-2.1 times.

Metabolism

Ethinyl estradiol undergoes presystemic conjugation in the liver and in the mucosa of the small intestine. The main route of metabolism of ethinyl estradiol is aromatic hydroxylation with the formation of numerous metabolites that are in both bound and unbound states. The rate of elimination of ethinyl estradiol is about 5 ml/min/kg.

Removal

The concentration of ethinyl estradiol in the blood plasma decreases in 2 phases, T1/2 of ethinyl estradiol in the second phase is about 24 hours. Ethinyl estradiol is excreted only in the form of metabolites by the kidneys and through the gastrointestinal tract in a ratio of 4:6.

Pharmacokinetics in special clinical situations

The effect of ethnicity on pharmacokinetic parameters was studied in single and multiple dose studies of drospirenone and ethinyl estradiol in healthy Caucasian and Japanese women. The influence of ethnicity on the pharmacokinetic parameters of drospirenone and ethinyl estradiol has not been established.

Calcium levomefolate

Suction

After oral administration of calcium, levomefolate is rapidly absorbed and included in the body's folate pool. After a single oral dose of 451 mcg of calcium levomefolate, after 0.5-1.5 hours, Cmax becomes 50 nmol/l higher than the initial concentration.

Distribution

The pharmacokinetics of folates has a two-phase character: a pool of folates with fast and slow metabolism is determined. The rapidly metabolized pool likely represents newly absorbed folate, which is consistent with the T1/2 of levomefolate calcium, which is about 4-5 hours after a single oral dose of 451 mcg. The slow metabolizing pool reflects the conversion of folate polyglutamate, whose T1/2 is about 100 days. External folates and folates passing through the enterohepatic cycle ensure the maintenance of a constant concentration of L-5-methyl-THF in the body.

L-5-methyl-THF represents the main form of existence of folates in the body, in which they are delivered to peripheral tissues to participate in cellular folate metabolism.

The equilibrium state of L-5-methyl-THF in the blood plasma after oral administration of 451 mcg of calcium levomefolate is achieved after 8-16 weeks and depends on its initial concentration. In red blood cells, C ss is achieved at a later date due to the lifespan of red blood cells, which is about 120 days.

Metabolism

L-5-methyl-THF is the main transported form of folate in plasma. When comparing 451 mcg calcium levomefolate and 400 mcg folic acid, similar metabolic mechanisms were established for other significant folates. Folate coenzymes are involved in 3 main coupled metabolic cycles in the cytoplasm of cells. These cycles are necessary for the synthesis of thymidine and purines, precursors of DNA and RNA acids, as well as for the synthesis of methionine from homocysteine ​​and the conversion of serine to glycine.

Removal

L-5-methyl-THF is excreted by the kidneys unchanged and in the form of metabolites, as well as through the gastrointestinal tract.

Release form

Film-coated tablets (active combination) are pink, round, biconvex, on one side with “Z+” embossed in a regular hexagon (24 pcs. in a blister).

Excipients: lactose monohydrate - 45.329 mg, microcrystalline cellulose - 24.8 mg, croscarmellose sodium - 3.2 mg, hyprolose (5 cP) - 1.6 mg, magnesium stearate - 1.6 mg.

Shell composition: pink varnish - 2 mg or (alternatively): hypromellose (5 cP) - 1.0112 mg, macrogol 6000 - 202.4 mcg, talc - 202.4 mcg, titanium dioxide - 558 mcg, red iron oxide dye - 26 mcg.

Film-coated tablets (vitamin supplements) are light orange, round, biconvex, on one side with “M+” embossed in a regular hexagon (4 pieces in a blister).

Excipients: lactose monohydrate - 48.349 mg, microcrystalline cellulose - 24.8 mg, croscarmellose sodium - 3.2 mg, hyprolose (5 cP) - 1.6 mg, magnesium stearate - 1.6 mg.

Shell composition: light orange varnish - 2 mg or (alternatively): hypromellose (5 cP) - 1.0112 mg, macrogol 6000 - 202.4 mcg, talc - 202.4 mcg, titanium dioxide - 572.3 mcg, iron oxide yellow dye - 8.9 mcg, dye iron oxide red - 2.8 mcg.

28 pcs. (set: 24 active combined tablets and 4 auxiliary vitamin tablets) - contour cell packaging (blisters) (1) - folding books (1) complete with a block of self-adhesive stickers for designing an appointment calendar - film.
28 pcs. (set: 24 active combined tablets and 4 auxiliary vitamin tablets) - contour cell packaging (blisters) (1) - clamshell books (3) complete with a block of self-adhesive stickers for designing an appointment calendar - film.

Dosage

The tablets should be taken orally in the order indicated on the package, every day at the same time, without chewing, with a small amount of water. Take 1 tablet/day continuously for 28 days. Taking tablets from the next package begins immediately after completing the previous one.

Withdrawal bleeding usually begins 2-3 days after starting to take the inactive pills and may not stop before you start taking the next pack of pills.

Start taking the drug

If you have not taken any hormonal contraceptives in the previous month

The drug should be taken on the 1st day of the menstrual cycle (i.e. on the 1st day of menstrual bleeding). It is possible to start taking it on the 2-5th day of the menstrual cycle, but in this case it is recommended to additionally use a barrier method of contraception during the first 7 days of taking the tablets from the first package.

When switching from other combined oral contraceptives, vaginal ring or contraceptive patch

It is preferable to start taking the drug the day after taking the last active tablet from the previous package, but in no case later than the next day after the usual 7-day break (for drugs containing 21 tablets) or after taking the last inactive tablet (for drugs containing 28 tablets per package). Taking Jess ® Plus should begin on the day the vaginal ring or patch is removed, but no later than the day when a new ring is to be inserted or a new patch is applied.

When switching from contraceptives containing only gestagens (mini-pills, injectable forms, implant), or from a gestagen-releasing intrauterine contraceptive (Mirena)

A woman can switch from taking the “mini-pill” to Jess ® Plus on any day (without a break), from an implant or intrauterine contraceptive with gestagen - on the day of its removal, from an injectable contraceptive - on the day when the next injection is due. In all cases, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the pills.

After an abortion in the first trimester of pregnancy

A woman can start taking the drug immediately. If this condition is met, the woman does not need additional contraceptive measures.

After childbirth or abortion in the second trimester of pregnancy

It is recommended to start taking the drug on the 21-28th day after childbirth or abortion in the second trimester of pregnancy. If use is started later, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the pills. However, if a woman has already been sexually active, pregnancy should be ruled out or she must wait until her first menstruation before starting to take Jess ® Plus.

Taking missed pills

Skipping inactive tablets can be ignored. However, they should be thrown away to avoid accidentally prolonging the period of taking inactive tablets. The following recommendations apply only to skipping active tablets.

If the delay in taking the drug is less than 24 hours, contraceptive protection is not reduced. A woman should take the missed pill as soon as possible and take the next pill at the usual time.

If the delay in taking the pills is more than 24 hours, contraceptive protection may be reduced. The more pills you skip and the closer the missed pills are to the inactive pill phase, the higher the chance of pregnancy.

In this case, you can be guided by the following two basic rules:

• The drug should never be interrupted for more than 7 days (please note that the recommended interval for taking inactive tablets is 4 days);
• To achieve adequate suppression of the hypothalamic-pituitary-ovarian axis, 7 days of continuous tablet use are required.

Accordingly, if the delay in taking active tablets is more than 24 hours, the following can be recommended:

From 1st to 7th day

A woman should take the last missed pill as soon as she remembers, even if this means taking two pills at the same time. She continues to take her next pills at the usual time. In addition, over the next 7 days it is necessary to additionally use a barrier method of contraception (for example, a condom). If sexual intercourse took place within 7 days before missing a pill, the possibility of pregnancy should be taken into account.

From 8th to 14th day

A woman should take the last missed pill as soon as she remembers, even if this means taking two pills at the same time. She continues to take her next pills at the usual time.

Provided that a woman has taken her pills correctly for the 7 days preceding the first missed pill, there is no need to use additional contraceptive measures. Otherwise, as well as if you miss two or more tablets, you must additionally use barrier methods of contraception (for example, a condom) for 7 days.

From the 15th to the 24th day

The risk of reduced reliability is inevitable due to the approaching phase of taking inactive tablets. A woman must strictly adhere to one of the following two options. Moreover, if during the 7 days preceding the first missed pill, all pills were taken correctly, there is no need to use additional contraceptive methods. Otherwise, you must use the first of the following regimens and additionally use a barrier method of contraception (for example, a condom) for 7 days.

1. A woman should take the last missed pill as soon as she remembers (even if this means taking two pills at the same time). The following tablets are taken at the usual time until the active tablets in the pack are gone. The four inactive tablets should be discarded and the next pack of tablets should be started immediately. Withdrawal bleeding is unlikely until the active tablets in the second pack are gone, but spotting and breakthrough bleeding may occur while taking the tablets.

2. A woman can also stop taking pills from the current package. Then she should take a break of no more than 4 days, including days of missing pills, and then start taking the drug from a new package.

If a woman has missed active pills and there is no withdrawal bleeding while taking inactive pills, pregnancy must be ruled out.

If vomiting or diarrhea occurs within 4 hours of taking the tablets, absorption may not be complete and additional measures should be taken to protect against unwanted pregnancy.

Overdose

No cases of overdose of the drug Jess ® Plus have been reported.

Symptoms that may occur in case of overdose: nausea, vomiting, spotting vaginal discharge or metrorrhagia (more often in young women).

Treatment: there is no specific antidote; symptomatic treatment should be carried out. Calcium levomefolate and its metabolites are identical to folates that are part of natural products, the daily consumption of which does not harm the body. Taking levomefolate calcium at a dose of 17 mg/day (the dose is 37 times higher than that contained in 1 tablet of Jess ® Plus) for 12 weeks was well tolerated.

Interaction

Interaction of oral contraceptives with other drugs may lead to breakthrough uterine bleeding and/or decreased contraceptive reliability.

Interaction leading to a decrease in the effectiveness of the drug Jess ® Plus

Effect on hepatic metabolism: the use of drugs that induce liver microsomal enzymes can lead to an increase in the clearance of sex hormones. Such drugs include: phenytoin, barbiturates, primidone, carbamazepine, rifampicin, possibly also oxcarbazepine, topiramate, felbamate, griseofulvin and preparations containing St. John's wort. HIV protease inhibitors (eg, ritonavir) and non-nucleoside reverse transcriptase inhibitors (eg, nevirapine) and combinations thereof also have the potential to affect hepatic metabolism.

Effect on enterohepatic recirculation: Some antibiotics (eg, penicillins and tetracyclines) may reduce the enterohepatic recirculation of estrogens, thereby reducing ethinyl estradiol concentrations, according to individual studies.

While taking medications that affect microsomal liver enzymes, and for 28 days after their discontinuation, a barrier method of contraception should be additionally used.

While taking antibiotics (except for rifampicin and griseofulvin) and for 7 days after their discontinuation, a barrier method of contraception should be additionally used. If the period of use of the barrier method of contraception ends later than the hormone-containing pink tablets in the package, you should skip taking the remaining auxiliary light orange tablets and start taking the drug Jess ® Plus from a new package without interruption in taking the tablets.

Interactions that reduce the effectiveness of calcium levomefolate

Effect on folate metabolism: Some drugs reduce blood folate concentrations or reduce the effectiveness of levomefolate calcium by inhibiting the enzyme dihydrofolate reductase (eg, methotrexate, trimethoprim, sulfasalazine, and triamterene) or by reducing folate absorption (eg, cholestyramine) or through unknown mechanisms (eg, cholestyramine). for example, antiepileptic drugs: carbamazepine, phenytoin, phenobarbital, primidone and valproic acid).

Effect on the metabolism of CPC (enzyme inhibitors)

The main metabolites of drospirenone are formed in plasma without the participation of the cytochrome P450 system. Therefore, the effect of inhibitors of the cytochrome P450 system on the metabolism of drospirenone is unlikely.

Effect of CPC or calcium levomefolate on the activity of other drugs

COCs can affect the metabolism of other drugs, leading to an increase (for example, cyclosporine) or a decrease (for example, lamotrigine) in their plasma and tissue concentrations.

Based on interaction studies, as well as studies in female volunteers taking omeprazole, simvastatin and midazolam as test substrates, it can be concluded that the effect of drospirenone 3 mg on the metabolism of other drugs is unlikely.

Folates may alter the pharmacokinetics or pharmacodynamics of some drugs that affect folate metabolism, such as antiepileptic drugs (phenytoin), methotrexate or pyrimethamine, which may be accompanied by a decrease (mostly reversible, provided the dose of the drug affecting folate metabolism is increased) of their therapeutic effect. The administration of folate during treatment with such drugs is recommended mainly to reduce the toxicity of the latter.

Side effects

The most common adverse reactions reported in connection with the use of the drug Jess ® are the following:

• nausea, pain in the mammary glands, irregular uterine bleeding, bleeding from the genital tract of unspecified origin (more than 3% of women using the drug for the indications “Contraception” and “Contraception and treatment of moderate acne /acne vulgaris/”);
• nausea, pain in the mammary glands, irregular uterine bleeding (in more than 10% of women using the drug for the indication “Contraception and treatment of severe premenstrual syndrome”).

Serious adverse reactions include arterial and venous thromboembolism. Below is the frequency of adverse reactions reported during clinical studies of Jess ® and Jess ® Plus for the indication “Contraception”, as well as for the indication “Contraception and treatment of moderate acne (acne vulgaris)” (n=3565) and “Contraception” and treatment of severe premenstrual syndrome" (n=289) for the drug Jess ®. Within each group, allocated depending on the frequency of occurrence, adverse reactions are presented in order of decreasing severity. The incidence of adverse events was classified as follows: frequent (≥1/100 and<1/10), нечастые (≥1/1000 и <1/100) и редкие (≥1/10 000 и <1/1000). Для дополнительных побочных реакций, выявленных только в процессе постмаркетинговых наблюдений, и для которых оценку частоты возникновения провести не представлялось возможным, указано "частота неизвестна".

From the side of the central nervous system: often - migraine.

Mental disorders: often - mood swings, depression/depressed mood; infrequently - decrease or loss of libido 2.

From the cardiovascular system: rarely - venous or arterial thromboembolism (approximate frequency based on the results of epidemiological studies covering a group of combined oral contraceptives. The frequency bordered on very rare. The term includes the following nosological units: peripheral deep vein occlusion, thrombosis and embolism/ pulmonary vascular occlusion, thrombosis, embolism and infarction, myocardial infarction, cerebral infarction and hemorrhagic stroke).

From the digestive system: often - nausea 1.

From the skin: frequency unknown - erythema multiforme.

From the reproductive system and mammary glands: often - pain in the mammary glands 1, irregular uterine bleeding 1, bleeding from the genital tract of unspecified origin.

Adverse events were classified using the MedDRA (Medical Dictionary of Regulatory Activities) dictionary. Different MedDRA terms reflecting the same symptom were grouped together and presented as a single adverse reaction to avoid diluting or diluting the true effect.

1—Incidence rates in studies evaluating PMS were very common >10/100.

2 - Incidence in studies evaluating PMS was common >1/100.

For more information about venous and arterial thromboembolic complications, see “Contraindications” and “Special Instructions”.

Listed below are adverse reactions with a very rare incidence or with delayed symptoms, which are believed to be associated with taking drugs from the group of oral combined contraceptives (for more information, see “Contraindications” and “Special Instructions”).

• The incidence of breast cancer diagnosis in women taking combined oral contraceptives is slightly increased. Because breast cancer is rare in women under 40 years of age, the increase in breast cancer diagnoses in women taking combined oral contraceptives is small relative to the overall risk of this disease;
• liver tumors (benign and malignant).

Other states

• erythema nodosum;
• hypertriglyceridemia (increased risk of pancreatitis while taking combined oral contraceptives);
• increased blood pressure;
• conditions that develop or worsen while taking combined oral contraceptives, but their relationship has not been proven: jaundice and/or itching associated with cholestasis; formation of gallstones, porphyria, systemic lupus erythematosus, hemolytic-uremic syndrome, Sydenham's chorea, herpes of pregnancy, hearing loss associated with otosclerosis;
• in women with hereditary angioedema, taking estrogens may cause or aggravate its symptoms;
• liver dysfunction;
• changes in glucose tolerance or effects on peripheral insulin resistance;
• Crohn's disease, ulcerative colitis;
• chloasma;
• hypersensitivity (including symptoms such as rash, urticaria).

Interaction

Interaction of oral contraceptives with other drugs (enzyme inducers, some antibiotics) may lead to breakthrough bleeding and/or decreased contraceptive effectiveness.

Indications

• contraception intended primarily for women with symptoms of hormone-dependent fluid retention in the body;
• contraception and treatment of moderate acne (acne vulgaris);
• contraception in women with folate deficiency;
• contraception and treatment of severe premenstrual syndrome.

Contraindications

Jess ® Plus is contraindicated in the presence of any of the conditions/diseases listed below. If any of these conditions/diseases develop for the first time while taking the drug, the drug should be discontinued immediately.

• thrombosis (venous and arterial) and thromboembolism currently or in history (including deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke), cerebrovascular disorders;
• conditions preceding thrombosis (including transient ischemic attacks, angina) currently or in history;
• the presence of multiple or severe risk factors for venous or arterial thrombosis;
• migraine with focal neurological symptoms currently or in history;
• diabetes mellitus with vascular complications;
• liver failure and severe liver diseases (until normalization of liver tests);
• severe and/or acute renal failure;
• liver tumors (benign or malignant) currently or in history;
• identified hormone-dependent malignant neoplasms (including genital organs or mammary glands) or suspicion of them;
• bleeding from the vagina of unknown origin;
• pregnancy or suspicion of it;
• breastfeeding period;
• rare hereditary lactose intolerance, lactase deficiency or glucose-galactose malabsorption (due to lactose content);
• hypersensitivity or intolerance to any of the components of the drug Jess ® Plus.

Carefully

The potential risk and expected benefit of using the drug Jess ® Plus should be assessed in each individual case in the presence of the following diseases/conditions and risk factors:

• risk factors for the development of thrombosis and thromboembolism: smoking, obesity, dyslipoproteinemia, controlled arterial hypertension, migraine without focal neurological symptoms, uncomplicated valvular heart disease, hereditary predisposition to thrombosis (thrombosis, myocardial infarction or cerebrovascular accident at a young age in someone close to relatives);
• other diseases in which peripheral circulatory disorders may occur: diabetes mellitus without vascular complications, systemic lupus erythematosus, hemolytic-uremic syndrome, Crohn's disease and ulcerative colitis, sickle cell anemia, phlebitis of the superficial veins;
• hereditary angioedema;
• hypertriglyceridemia;
• liver diseases that are not contraindicated;
• diseases that first appeared or worsened during pregnancy or against the background of previous use of sex hormones (for example, jaundice and/or itching associated with cholestasis, cholelithiasis, otosclerosis with hearing impairment, porphyria, herpes of pregnancy, Sydenham's chorea);
• postpartum period.

Features of application

Use during pregnancy and breastfeeding

The drug is contraindicated during pregnancy. If pregnancy is detected while taking Jess ® Plus, the drug should be discontinued immediately. Data on the results of taking the drug Jess ® Plus during pregnancy are limited and do not allow us to draw any conclusions about the negative impact of the drug on pregnancy, the health of the fetus and newborn child. At the same time, extensive epidemiological studies have not revealed an increased risk of developmental defects in children born to women who took COCs before pregnancy or teratogenic effects in cases of inadvertent use of COCs in early pregnancy. Specific epidemiological studies have not been conducted regarding the drug Jess ® Plus.

The drug is contraindicated during breastfeeding. Taking COCs can reduce the amount of breast milk and change its composition, so their use is not recommended until you stop breastfeeding. Small amounts of sex hormones and/or their metabolites may be excreted in milk, but there is no evidence of their negative effects on the health of the child.

Use for liver dysfunction

The drug is contraindicated for use in women with severe liver dysfunction.

Use for renal impairment

The drug is contraindicated for use in women with severe renal impairment and acute renal failure.

Use in children

The effectiveness and safety of Jess ® Plus as a contraceptive have been studied in women of reproductive age. It is assumed that the effectiveness and safety of the drug in post-pubertal age up to 18 years are similar to those in women after 18 years. The use of the drug before menarche is not indicated.

Use in elderly patients

The drug Jess ® Plus is not used after menopause.

special instructions

If any of the conditions, diseases and risk factors listed below currently exist, the potential risks and expected benefits of using Jess ® Plus should be carefully weighed in each individual case and discussed with the woman before she decides to start taking drug of this drug.

Diseases of the cardiovascular system

The results of epidemiological studies indicate a relationship between the use of COCs and an increased incidence of venous and arterial thrombosis and thromboembolism (such as deep vein thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular disorders) when taking combined oral contraceptives. These diseases are rare.

The risk of developing venous thromboembolism (VTE) is greatest in the first year of taking such drugs. An increased risk is present after initial use of combined oral contraceptives or resumption of use of the same or different combined oral contraceptives (after a dosing interval of 4 weeks or more). Data from a large prospective study involving 3 groups of patients suggest that this increased risk is predominantly present during the first 3 months.

The overall risk of VTE in patients taking low-dose combined oral contraceptives (< 50 мкг этинилэстрадиола) в 2-3 раза выше, чем у небеременных пациенток, которые не принимают КПК, тем не менее, этот риск остается более низким по сравнению с риском ВТЭ при беременности и родах.

VTE can be life-threatening or fatal (in 1-2% of cases).

VTE, manifested as deep vein thrombosis or pulmonary embolism, can occur with the use of any combined oral contraceptives.

It is extremely rare that when using combined oral contraceptives, thrombosis of other blood vessels occurs, for example, hepatic, mesenteric, renal, cerebral veins and arteries or retinal vessels. There is no consensus regarding the relationship between the occurrence of these events and the use of combined oral contraceptives.

Symptoms of deep vein thrombosis (DVT): unilateral swelling of the lower extremity or along a vein of the lower extremity, pain or discomfort in the lower extremity only in an upright position or when walking, local increase in temperature in the affected lower extremity, redness or discoloration of the skin on the lower extremity.

Symptoms of pulmonary embolism (PE): difficulty or rapid breathing; sudden cough, incl. with hemoptysis; sharp pain in the chest, which may intensify with deep inspiration; sense of anxiety; severe dizziness; fast or irregular heartbeat. Some of these symptoms (eg, shortness of breath, cough) are nonspecific and may be misinterpreted as signs of other more or less severe events (eg, respiratory tract infection).

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

Symptoms of a stroke: sudden weakness or loss of sensation in the face, upper or lower extremities, especially on one side of the body, sudden confusion, problems with speech and comprehension; sudden unilateral or bilateral vision loss; sudden disturbance in gait, dizziness, loss of balance or coordination; 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, swelling and slight blue discoloration of the extremities, acute abdomen.

Symptoms of myocardial infarction: pain, discomfort, pressure, heaviness, a feeling of squeezing or fullness in the chest, arm or chest; discomfort radiating to the back, cheekbone, larynx, arm, stomach; cold sweat, nausea, vomiting or dizziness, severe weakness, anxiety or shortness of breath; fast or irregular heartbeat.

Arterial thromboembolism can be life-threatening or fatal.

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

• with age;
• in smokers (with increasing number of cigarettes or increasing age, the risk increases, especially in women over 35 years of age);

in the presence of:

• obesity (BMI more than 30 kg/m2);
• family history (for example, venous or arterial thromboembolism ever in close relatives or parents at a relatively young age). In the case of a hereditary or acquired predisposition, the woman should be examined by an appropriate specialist to decide on the possibility of taking the drug Jess ® Plus;
• prolonged immobilization, major surgery, any operation on the lower extremities or major trauma. In these situations, it is advisable to stop using the drug Jess ® Plus (in the case of a planned operation, at least four weeks before it) and not to resume taking it for two weeks after the end of immobilization;
• dyslipoproteinemia;
• arterial hypertension;
• migraine;
• heart valve diseases;
• atrial fibrillation.

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

The increased risk of thromboembolism in the postpartum period should be taken into account.

Peripheral circulatory disorders may 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 migraines during use of Jess ® Plus (which may precede cerebrovascular events) may be grounds for immediate discontinuation of this drug.

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 S deficiency, antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant).

When assessing the risk-benefit ratio, it should be taken into account that adequate treatment of the relevant condition may reduce the associated risk of thrombosis. It should also be taken into account that the risk of thrombosis and thromboembolism during pregnancy is higher than when taking low-dose oral contraceptives (< 50 мкг этинилэстрадиола).

The most significant risk factor for developing cervical cancer is persistent human papillomavirus infection. There are reports of a slight increase in the risk of developing cervical cancer with long-term use of COCs. However, the connection with taking COCs has not been proven. The possibility of the relationship of these data with screening for cervical diseases and with characteristics of sexual behavior (less frequent use of barrier methods of contraception) is discussed.

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 COCs (relative risk 1.24). The increased risk gradually disappears within 10 years of stopping these drugs. Because breast cancer is rare in women under 40 years of age, the increase in breast cancer diagnoses in women who are currently or recently taking COCs is small relative to the overall risk of breast cancer. Its connection with the use of COCs has not been proven. The observed increased risk may be a consequence of careful monitoring and earlier diagnosis of breast cancer in women using COCs. Women who have ever used COCs are diagnosed with earlier stages of breast cancer than women who have never used them.

In rare cases, during the use of COCs, the development of benign, and in extremely rare cases, malignant liver tumors was observed, which in some patients led to life-threatening intra-abdominal bleeding.

If severe abdominal pain, liver enlargement, or signs of intra-abdominal bleeding occur, this should be taken into account when making a differential diagnosis.

Tumors can be life-threatening or fatal.

Other states

Clinical studies have shown no effect of drospirenone on plasma potassium concentrations in patients with mild to moderate renal failure. However, in patients with impaired renal function and an initial potassium concentration at the upper limit of normal, the risk of developing hyperkalemia cannot be excluded while taking medications that lead to potassium retention in the body.

Women with hypertriglyceridemia (or a family history of this condition) may have an increased risk of developing pancreatitis while taking COCs.

Although slight increases in blood pressure have been described in many women taking COCs, clinically significant increases have rarely been observed. However, if a persistent, clinically significant increase in blood pressure develops while taking Jess ® Plus, this drug should be discontinued and treatment of arterial hypertension should be started. The drug can be continued if normal blood pressure values ​​are achieved with antihypertensive therapy.

The following conditions have been reported to develop or worsen both during pregnancy and while taking COCs, but their relationship with COC use has not been proven: jaundice and/or pruritus associated with cholestasis; formation of gallstones; porphyria; systemic lupus erythematosus: hemolytic-uremic syndrome; Sydenham's chorea; herpes during pregnancy; hearing loss associated with otosclerosis. Cases of Crohn's disease and ulcerative colitis have also been described with the use of COCs.

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

Acute or chronic liver dysfunction may require discontinuation of Jess ® Plus until liver function tests return to normal. Recurrent cholestatic jaundice, which develops for the first time during pregnancy or previous use of sex hormones, requires discontinuation of the drug Jess ® Plus.

Although COCs may have an effect on insulin resistance and glucose tolerance, there is no need to change the therapeutic regimen in diabetic patients using Jess ® Plus. However, women with diabetes should be closely monitored while taking this drug.

Chloasma can sometimes develop, especially in women with a history of chloasma during pregnancy. Women with a tendency to chloasma while taking Jess ® Plus should avoid prolonged exposure to the sun and exposure to ultraviolet radiation.

Folates may mask a lack of vitamin B12.

Preclinical safety data

Preclinical data from routine repeated-dose toxicity, genotoxicity, carcinogenicity and reproductive toxicity studies do not indicate a particular risk to humans. However, it should be remembered that sex hormones can promote the growth of certain hormone-dependent tissues and tumors.

Preclinical data from routine studies of levomefolate calcium for repeated-dose toxicity, genotoxicity and reproductive toxicity do not indicate a particular risk to humans.

Laboratory tests

Taking Jess ® Plus may affect the results of some laboratory tests, including indicators of liver, kidney, thyroid, adrenal function, the concentration of transport proteins in plasma, indicators of carbohydrate metabolism, parameters of blood coagulation and fibrinolysis. Changes usually do not go beyond normal values. Drospirenone increases plasma renin activity and aldosterone concentrations, which is associated with its antimineralocorticoid effect.

There is a theoretical possibility of increasing the concentration of potassium in the blood plasma in women receiving the drug Jess ® Plus simultaneously with other drugs that can increase the content of potassium in the blood plasma. These drugs include angiotensin II receptor antagonists, potassium-sparing diuretics, and aldosterone antagonists. However, in studies evaluating the interaction of drospirenone with ACE inhibitors or indomethacin, there was no significant difference in plasma potassium concentrations compared with placebo.

Reduced efficiency

The effectiveness of Jess ® Plus may be reduced in the following cases: if you miss pills, with vomiting and diarrhea, or as a result of drug interactions.

Frequency and severity of menstrual-like bleeding

While taking the drug Jess ® Plus, irregular (acyclic) spotting and bleeding from the vagina (spotting or “breakthrough” uterine bleeding) may occur, especially during the first months of use. Therefore, any irregular bleeding should be assessed after an adaptation period of approximately 3 cycles.

If irregular bleeding recurs or develops after previous regular cycles, careful evaluation should be performed to rule out malignancy or pregnancy.

Some women may not develop withdrawal bleeding while off the pill. If Jess ® Plus was taken as recommended, it is unlikely that the woman is pregnant. However, if Jess ® Plus is not used regularly and there are no two withdrawal bleedings in a row, the drug cannot be continued until pregnancy has been ruled out.

Medical examinations

Before starting or resuming use of the drug, it is necessary to familiarize yourself with the woman’s life history, family history, conduct a thorough physical examination (including measuring blood pressure, heart rate, determining the BMI index, examining the mammary glands), gynecological examination, cytological examination of the cervix (Papanicolaou test), exclude pregnancy. When resuming taking the drug Jess ® Plus, the volume of additional studies and the frequency of control examinations are determined individually, but at least once every 6 months.

The woman should be warned that Jess ® Plus does not protect against HIV infection and other sexually transmitted diseases.

Impact on the ability to drive vehicles and operate machinery

There have been no reported cases of adverse effects of the drug Jess ® Plus on the speed of psychomotor reactions; No studies have been conducted to study the effect of the drug on the speed of psychomotor reactions.

The balance of female and male hormones in the body affects the condition of the skin. A lack of estrogen reduces its elasticity, and an excess of androgen increases the oiliness of the skin. Birth control pills Jess help restore balance. Their regular use helps in the fight against acne and acne.

The effectiveness of hormonal contraceptives in the fight against acne

Teenage acne is a common occurrence, but at a later age their occurrence may indicate an acquired disease of internal organs, malfunction of the genitourinary system and hormonal imbalances. In the latter case, the rashes are presented in the form of cystic acne - purulent reddish tubercles. Treatment involves restoring balance through the use of hormonal drugs.

These include Jess tablets - combined contraceptives that contain two active substances, female sex hormones:

• gestagen drospirenone;
• estrogen.

Jess pills are ideal for women whose skin is prone to oily skin and acne due to excess testosterone. If the cause of the appearance is indeed an excess of male sex hormones, the pills will have the necessary effect. Drospirenone has pronounced antiandrogenic properties.

By regulating the level of testosterone in a woman’s body, Jess tablets reduce the amount of subcutaneous fat and, accordingly, acne.

Low-dose Jess tablets help cope with a small degree of inflammation: mild to moderate acne. But if the medicine is chosen correctly, with constant use, pimples and blackheads (comedones) completely disappear.

The principle of action of the drug

The mechanism of action of birth control pills is to suppress ovulation. There is no ovulation - there are no surges in sex hormones, which can cause acne. Read more about the connection between the occurrence of acne during ovulation.

Ovulation is suppressed with the help of drospirenone. It performs the following tasks:

• suppresses fat production in the subcutaneous layers of epithelial tissue;
• restores normal functioning of the sebaceous glands and narrows pores;
• removes excess water from the body, reducing swelling.

Taken together, the above actions can reduce the number of acne and cure them completely. But only if the appearance of rashes is associated with an imbalance of hormones. The use of the drug, as a rule, is not a panacea, but an additional assistant in the fight against acne.

How to properly use Jess for acne?

Those who decide to take hormonal contraceptives not for protection, but to combat acne, should be aware of the risks posed by their improper use. Only by following the requirements for taking pills can you achieve the desired result.

The course of taking Jess is typical for oral contraceptives:

• The tablets are taken once a day at the same time.
• Course duration is 28 days, reference menstrual cycle. There are no breaks in admission. After all 28 tablets have been consumed, they will begin to drink the next pack.
• The package contains 28 pills, 24 of which contain active ingredients, and the other 4 are dummy pills (placebo). 2-3 days after taking the white pills, the woman gets her period.
• On day 29, taking the pills is resumed, but from a different package (regardless of whether there is still spotting or not).

Jess' appointment for girls over 21 years of age is prescribed by gynecologists and endocrinologists after examination and tests. Despite the fact that the pills are sold without a prescription, before taking them, you should consult a doctor to find out whether it is advisable to use these particular pills and whether they will help in the fight against acne.

Only when taken regularly do oral contraceptives maintain the necessary hormonal levels. After canceling them, all existing problems will return again. That's why it's so important to find the root cause and eliminate it.

If a gynecologist or dermatologist prescribes the use of the drug, you must take at least 3-6 courses, i.e. 3-6 months. In the second or third month, the effect of oral contraceptives on the skin will become noticeable. The number of rashes will decrease or the acne will disappear completely. However, it is important to remember that long-term use of contraceptives can adversely affect your health.

If desired, hormonal birth control can be combined with other acne medications. They can be easily combined with external use products: acne gels and creams, homemade masks. Read more about other remedies for getting rid of acne -.

You need to use oral contraceptives against acne wisely: start and stop taking the pills correctly, so as not to provoke severe inflammation after taking the drug. In this video you will learn about this in detail:

Advantages and disadvantages of the drug

The advantage of Jess is that the drug is highly effective in the fight against acne (provided that the cause of their appearance is indeed hormonal fluctuations in the body).

The disadvantages of these tablets are their contraindications and side effects.

Adverse reactions

Jess tablets contain a small amount of active substances (hormones), and this reduces the likelihood of negative consequences and reactions from taking them. But the following may still occur:

• headaches and migraines;
• frequent mood swings, irritability, depression;
• decreased libido and vaginal dryness during sexual intercourse;
• nausea;
• vaginal candidiasis (thrush);
• soreness and sensitivity of the mammary glands;
• scanty menstrual-like discharge;
• an increase in the number of acne lesions - on the forehead and chin. Such processes are possible at the beginning of taking the medicine, but disappear when hormonal levels have normalized.

If acne not only does not disappear after taking Jess for a long time, but also increases, changes in shape and texture, this means one thing: the pills are prescribed incorrectly. They need to be abandoned or replaced by other means.

Contraindications

When taking hormonal contraception for acne, it is important to be aware of the risks posed by using it incorrectly. Even such a mild drug as Jess has its contraindications for use. This includes pathologies such as:

• diabetes;
• liver and kidney diseases;
• problems with the heart and blood vessels (risk of blood clots);
• malignant or hormone-dependent tumors.

Experienced smokers, pregnant and lactating women, as well as teenage girls should stop taking hormonal pills. About treating teenage acne.

Cost and analogues

Like other oral contraceptives, Jess is distinguished by its relatively high price. They are not the most expensive, but not the cheapest either. A package of pills will cost 800-1000 rubles (depending on where the pills were purchased).