Instructions for use of JES® (YAZ®)

Jess® (Yaz®)

If any of the conditions/risk factors listed below currently exist, the potential risks and expected benefits of using COCs should be carefully weighed in each individual case 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.

— Risk of developing VTE and ATE

The results of epidemiological studies indicate a relationship between the use of COCs and an increased incidence of VTE and ATE (such as DVT, PE, myocardial infarction, cerebrovascular disorders). These diseases are rare.

An increased risk is present after initial use of COCs or resumption of use after a dosing interval of 4 weeks or more. Data from a large prospective study suggest that this increased risk is predominantly present during the first 3 months. COCs containing levonorgestrel, norgestimate or norethisterone as a progestogen component have the lowest risk of developing VTE. The risk of VTE when taking other COCs, including the combination of drospirenone + ethinyl estradiol, may be 2 times higher than the risk of developing this complication. The choice of using a COC with a higher risk of developing VTE should only be made after consultation with the woman to ensure that she fully understands the risk of VTE associated with the combination of drospirenone + ethinyl estradiol, the effect of the drug on her existing risk factors and what the risk The development of VTE is maximum in the first year of taking such drugs.

The overall risk of VTE in patients taking low-dose COCs (<0.05 mg ethinyl estradiol) is 2-3 times higher than in non-pregnant patients not taking COCs; however, this risk remains lower than the risk of VTE in patients taking COCs. pregnancy and childbirth.

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

VTE, manifested as DVT or PE, can occur with all COCs.

It is extremely rare when using COCs that thrombosis of other blood vessels occurs, for example, hepatic, mesenteric, renal, cerebral veins and arteries or retinal vessels.

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

Symptoms of PE include: difficulty or rapid breathing, sudden cough, including coughing up blood, sharp chest pain that may get worse with deep breaths, 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 common and less severe conditions (eg, respiratory tract infection).

ATE can lead to stroke, vascular occlusion, or myocardial infarction. Symptoms of a stroke include: sudden weakness or loss of sensation in the face, limbs, especially on one side of the body, sudden confusion, problems with speech and understanding, sudden loss of vision on one or both sides, 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 a seizure. Other signs of vascular occlusion: sudden pain, swelling and slight cyanosis of the extremities, “acute” abdomen.

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

ATE 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 Jess® is contraindicated (see section “Contraindications”).

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 old);

in the presence of:

— obesity (BMI more than 30 kg/m2);

- family history (for example, if there is a family history of venous or arterial thrombosis/thromboembolism in close relatives or parents under the age of 50 years). 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 COCs;

- in case of prolonged immobilization, serious surgery, any operation on the lower extremities, in the pelvic area or neurosurgical surgery, extensive severe trauma. In these situations, you should stop taking the COC (in the case of planned surgery, at least four weeks before it) and not resume it for two 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 VTE, especially in the presence of other risk factors.

- dislipoproteinemia;

- arterial hypertension;

- migraine;

— diseases of the heart valves;

- atrial fibrillation.

About 9-12 out of 10,000 women taking COCs containing drospirenone may develop VTE within a year, compared with about 6 in 10,000 women for COCs containing levonorgestrel.

The possible role of varicose veins and superficial thrombophlebitis in the development of VTE 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 COCs (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 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 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 COCs (<0.05 mg ethinyl estradiol).

— 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 COCs, but the relationship with COC use 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 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. Due to the fact that breast cancer is rare in women under 40 years of age, the increase in the number of breast cancer diagnoses in women who are currently or recently taking COCs is insignificant in relation to the overall risk of this disease. The observed increase in risk may be a consequence of earlier diagnosis of breast cancer in women using COCs, their biological effects, or a combination of both factors. Women who have 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 has been observed, which in some cases led to life-threatening intra-abdominal bleeding. In case of severe abdominal pain, liver enlargement or signs of intra-abdominal bleeding, 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. There is a theoretical risk of developing hyperkalemia in patients with impaired renal function with an initial potassium concentration at the upper limit of normal, while 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 the concentration of potassium in the blood plasma 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 COCs.

Although slight increases in blood pressure have been described in many women taking COCs, clinically significant increases have been reported rarely. However, if a persistent clinically significant increase in blood pressure develops while taking a COC, the COC should be discontinued and treatment for hypertension should be initiated. COCs can be continued if normal blood pressure levels 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; cholelithiasis; porphyria; systemic lupus erythematosus; hemolytic-uremic syndrome; 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 COCs 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 COCs 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 COC use.

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

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

— Laboratory tests

Taking COCs may affect the results of some laboratory tests, including indicators of liver, kidney, thyroid, adrenal function, the concentration of transport proteins in the blood plasma, indicators of carbohydrate metabolism, parameters of coagulation and fibrinolysis. 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 measurement of blood pressure, heart rate, determination of body mass index) and gynecological examination (including breast examination and cytological examination of the cervical epithelium ), 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.

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

Reduced efficiency

The effectiveness of COCs may be reduced in the following cases: if hormone-containing (light pink) tablets are missed, with vomiting and diarrhea, or as a result of drug interactions.

Insufficient menstrual control

While taking COCs, irregular bleeding may occur (“spotting” and/or “breakthrough” bleeding), especially during the first months of use. Therefore, any irregular bleeding should be assessed only after an adaptation period of about 3 cycles of the drug.

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 hormone-containing (light pink) tablets; pregnancy should be ruled out before continuing to take the drug. This is of particular importance for women taking concomitant drugs with teratogenic effects. And although the onset of pregnancy while regularly taking Jess® is unlikely, at the slightest suspicion of pregnancy a pregnancy test should be performed.

Jess (Jazz)

Tablets based on estradiol. One tablet contains 20 mcg ethinyl estradiol and 3 mcg drospirenone. One package of the drug contains 28 tablets, of which 24 tablets are active, and 4 are placebo (neutral drug without drug effects). Active tablets are round, biconvex, light pink in appearance. On one side of the tablet, “DS” is engraved in a regular hexagon. The placebo tablets are white and have “DP” engraved on them.

The contraceptive effect is ensured by a complex of factors, among which the most significant is the suppression of ovulation. Also, as a result of Jess’s action, the cervical mucus changes, which loses its ability to pass sperm.

Positive side effects of taking Jess:

• regularity of the menstrual cycle;
• reducing the intensity of bleeding, reducing pain;
• reducing the risk of iron deficiency anemia;
• reducing the risk of developing endometrial and ovarian cancer;
• antiandrogenic effect, which is expressed in reducing the appearance of acne (blackheads), reducing the level of oily skin and hair.

Drospirenone, a synthetic analogue of progesterone, plays a very important role. It neutralizes the possible negative effects of estrogens and is similar in its biochemical and pharmacological profile to natural progesterone. For example, drospirenone counteracts weight gain, fluid retention in the body and the occurrence of edema; it also reduces the symptoms of PMS (premenstrual syndrome). The combination of ethinyl estradiol and drospirenone ensures very good tolerability of the drug.

Indications for prescribing Jess are:

• the need for a contraceptive with antimineralocorticoid and antiandrogenic effects;
• moderate manifestation of acne, increased oiliness of the skin of the face and scalp;
• treatment of severe premenstrual syndrome (PMS).

Contraindications:

• thrombosis (venous and arterial) and thromboembolism - if they are currently diagnosed or have occurred in history), as well as conditions that precede thrombosis (ischemic attacks, angina pectoris);
• migraine;
• diabetes mellitus with vascular complications;
• disorders of the cardiovascular system: lesions of the valvular apparatus of the heart, heart rhythm disturbances, diseases of the cerebral vessels or coronary arteries, hypertension;
• pancreatitis;
• liver failure and severe liver disease;
• benign or malignant neoplasms in the liver;
• renal failure;
• hormone-dependent malignant diseases or suspicion of them;
• vaginal bleeding of unknown origin.

Relative contraindications, which must be considered individually and taken into account when prescribing a contraceptive, are:

• smoking;
• thrombosis;
• myocardial infarction;
• diseases associated with cerebrovascular accidents that were observed in one of the closest relatives at a young age;
• obesity;
• high blood pressure (hypertension);
• migraine;
• heart valve diseases, heart rhythm disturbances;
• prolonged immobility, for example due to injury;
• upcoming surgery,
• diabetes.

During pregnancy and lactation, Jess should not be taken. If pregnancy is detected while taking a contraceptive, the drug should be stopped. However, it must be emphasized that large-scale clinical studies have not found any negative effects on the fetus in cases where sex hormones were taken through carelessness or due to ignorance about pregnancy in the early stages. Therefore, if such a situation arises, there is no need to panic - it is enough to simply cancel oral contraception and continue to monitor the pregnancy as usual.

Side effects of Jess may be as follows:

• periodic bleeding between menstruation (often observed in the first 2-3 months of use);
• development of thrombosis and thromboembolism.

Reception scheme

The tablets are taken sequentially, in the order indicated on the package, for 28 days, one tablet per day. Each subsequent package should be started the day after taking the last tablet from the previous package. Menstrual-like bleeding usually begins 2–3 days after starting placebo tablets and may not stop by the time you start taking the next pack of tablets.

Start of reception:

• If you have not taken any hormonal contraceptives in the previous month, the first Jess tablet is taken on the first day of the menstrual cycle, that is, on the first day of menstrual bleeding. It is possible to start taking it on days 2–5 of the menstrual cycle, but in this case it is recommended to additionally use barrier non-hormonal contraceptives for a week.
• When switching from other combined oral contraceptives, it is recommended to start taking Jess the next day after taking the last active tablet from the previous package. You can take a break between drugs, but it should not be more than seven days - for drugs whose packaging contains 21 tablets. If the drug contains 28 tablets, then you need to take the first Jess tablet the next day after taking the last inactive tablet of the previous drug.
• When switching from a vaginal ring or contraceptive patch, it is recommended to start taking Jess 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.
• The transition from the mini-pill to Jess can be done any day, without interruption.
• The transition to Jess from an implant or intrauterine contraceptive (Mirena) with gestagen is carried out on the day of its removal.
• The transition to Jess from an injectable contraceptive is carried out on the day when the next injection is due. Note! In cases of switching from a mini-pill, intrauterine contraceptive, implant, or injectable contraceptive within a week, it is necessary to additionally use a barrier method of contraception.

After an abortion in the first trimester of pregnancy, you can start taking Jess immediately. There is no need for additional non-hormonal methods of contraception in this case.

After an abortion performed in the second trimester of pregnancy, it is recommended to start taking Jess on days 21–28. If reception is started later, it is necessary to additionally use a barrier method of contraception for a week. Also, if you start taking the drug later, you must make sure that the woman is not pregnant. This is done using ultrasound. If it is not possible to do an ultrasound, it is better to wait until your first menstruation.

After childbirth, you should proceed in the same way as after an abortion performed in the second trimester.

If you forget to take an inactive pill, you can ignore this omission. But the missed inactive tablet must be thrown away so as not to accidentally extend the period of taking tablets from one package.

If you forget to take an active pill, your further actions depend on how many hours you are late and in what period this happened.

If the gap in taking the drug is less than 12 hours, the contraceptive effect is not reduced. It is necessary to take the missed pill as soon as possible and continue to take pills based on your usual schedule.

If the missed period is more than 12 hours, the contraceptive effect may be reduced. The more pills you skip, and the closer the missed pills are to the placebo phase, the higher the chance of pregnancy.

In such a situation, you must always remember two fundamental rules:

1. Taking Jess should not be interrupted for more than 4 days.
2. The contraceptive effect is achieved after 7 days of continuous pill taking.

If the delay in taking active tablets is more than 12 hours (that is, more than 36 hours have passed since the last active tablet was taken), then depending on the period of the cycle, the following actions can be recommended:

From 1st to 7th day

Take the missed tablet immediately, even if this means taking two tablets at the same time. Then continue taking Jess according to your usual schedule. During the week it is necessary to additionally use a barrier method of contraception. If you had sexual intercourse within seven days before missing the pill, there is a possibility of pregnancy.

From 8th to 14th day

Take the missed tablet immediately, even if this means taking two tablets at the same time. Then continue taking Jess according to your usual schedule. If during the 7 days preceding the first missed pill, the dosage schedule was strictly followed, then there is no need to use additional contraceptive measures. Otherwise, as well as if two or more tablets are missed, the contraceptive effect is reduced. Therefore, it is recommended to use barrier methods of contraception for a week.

From the 15th to the 24th day

The contraceptive effect decreases as the period of taking inactive pills approaches. If during the week before missing the pill the dosage schedule was strictly followed, then you can follow one of the following regimens. There is no need for additional contraceptive measures. If the dosage schedule was violated, then it is necessary to use the first regimen and, in addition to this, barrier contraceptives for a week.

Possible dosage regimens.

1. Take the last missed tablet as soon as possible, even if this means taking two tablets at the same time. Next, Jess is taken according to the usual schedule - until the active tablets in the package run out. The four inactive tablets should be ignored and immediately proceed to the tablets in the next pack. In this case, menstrual-like bleeding is unlikely until the active tablets in the second package run out. But there may be spotting and breakthrough bleeding while taking the pills.
2. Stop taking pills from the current package and take a break for no more than four days, including days you missed pills. Next, you begin taking the drug from the new package. If bleeding does not occur during the break, pregnancy must be ruled out.

In cases where gastrointestinal disorders occur, absorption of the drug may be incomplete - therefore, additional contraceptive measures should be taken. If vomiting occurs within 4 hours after taking an active tablet, you should follow the recommendations for skipping tablets.

Instructions for use of JES® (YAZ®)

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 approximately 35 ng/ml. Bioavailability - 76-85%. Compared to taking the substance on an empty stomach, food intake does not affect the bioavailability of drospirenone.

Distribution

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

During cyclic treatment, Cssmax of drospirenone in serum is achieved between 7 and 14 days of treatment and is approximately 60 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 T1/2 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.

Removal

After oral administration, a biphasic decrease in the level of drospirenone in the serum is observed, with T1/2, respectively, 1.6 ± 0.7 hours and 27 ± 7.5 hours. 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 in feces and urine in a ratio of approximately 1.2:

• 1.4. T1/2 - 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 nocturnal 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 by 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 subjects, while no such changes were observed in other subjects.

Distribution

Ethinyl estradiol is significantly, but not specifically, bound to serum albumin (approximately 98.5%) and causes an increase in serum SHG concentrations. The apparent Vd is about 5 l/kg. Css is achieved during the second half of the treatment cycle, with serum ethinyl estradiol levels increasing approximately 1.4-2.1 times.

Metabolism

Ethinyl estradiol undergoes presystemic conjugation in the mucous membrane of the small intestine and in the liver. Ethinyl estradiol is primarily metabolized by aromatic hydroxylation, resulting in the formation of a variety of hydroxylated and methylated metabolites, presented both as free metabolites and as conjugates with glucuronic and sulfuric acids. Ethinyl estradiol is completely metabolized. The rate of metabolic clearance of ethinyl estradiol is approximately 5 ml/min/kg.

Removal

The concentration of ethinyl estradiol in the serum decreases biphasically, T1/2 of the terminal phase is 24 hours. Ethinyl estradiol is practically not excreted unchanged. Ethinyl estradiol metabolites are excreted in urine and bile in a ratio of 4:

• 6. T1/2 of metabolites - 24 hours.