Jeanine Bean №21

Active ingredient and dosage form

Dragee: 1 pill contains dienogest 2 mg, ethinyl estradiol 30 mcg;
Excipients: lactose monohydrate, potato starch, gelatin, talc, Magnesium stearate, sucrose, sugar syrup, polyvidone K25, macrogol 35000, Calcium carbonate, titanium dioxide (E171), carnauba wax;
in a blister, 21 pcs.; in a pack of cardboard 1 or 3 blisters.

Mechanism of action

Monophasic combined progestogen-estrogenic contraceptive drug. Inhibits the secretion of pituitary gonadotropic hormones, inhibits the maturation of follicles and interferes with the process of ovulation. It increases the viscosity of cervical mucus, making it difficult for sperm to enter the uterus.
With the use of the drug, the menstrual cycle becomes more regular, less frequent painful menstruation, decreases the intensity of the menstrual flow, resulting in a reduced risk of developing iron deficiency anemia.
Zanin's progestin component, dienogest, is a progestogen and is a derivative of nortestosterone with antiandrogenic activity (which has been proven in clinical studies in patients with inflammatory acne). Dienogest increases the level of HDL in the blood.

Dienogest
Suction
After ingestion of 1 dragee, dienogest is rapidly and completely absorbed from the gastrointestinal tract. C_max is achieved after 2.5 h. The absolute bioavailability of dienogest is 96% and is stored in combination with ethinyl estradiol.
Distribution
About 10% of dienogest is in free-form plasma, approximately 90% is non-specifically bound to albumin. Dienogest does not bind to specific transport proteins - sex hormone-binding globulin (GSPH) and corticosteroid-binding globulin (GCL) - and, therefore, does not displace testosterone from its association with GSPG and cortisol from its association with GLC. It is unlikely that dienogest affects the physiological transport processes of endogenous steroids.
Dienogest slightly accumulates with daily intake. The average plasma concentration is about 30 ng / ml after three cycles of treatment.
Metabolism
The effect of "first pass" is negligible. Dienogest is metabolized primarily by hydroxylation, hydrogenation, conjugation and aromatization with the formation of inactive metabolites.
Removal
T_1/2 is about 9 hours with a single dose and about 10 hours with a multiple dose.
After a single dose of 1 dragee of Zhanin, the total clearance of dienogest is 3.6 l / h and slightly decreases to 2.8 l / h after three cycles of treatment.
The ratio of excretion of dienogest with urine and feces is 3.2 after ingestion of 0.1 mg of dienogest / kg body weight.
After ingestion, approximately 86% of the dose is eliminated in 6 days. Most of this amount (about 42%) is excreted during the first 24 hours, mainly with urine.
Ethinyl Estradiol
Suction
After taking the pills inside ethinyl estradiol is quickly and completely absorbed from the gastrointestinal tract.
C_max Ethinyl estradiol is reached in 1.5-4 hours after ingestion of 1 dragee and is 67 pg / ml and rises to 118 pg / ml after repeated administration. Exposed to the effect of "first pass", which leads to low absolute bioavailability (average 44%).
Distribution
About 1.5% of ethinyl estradiol is in free-form plasma, 98.5% is bound to albumin. Ethinyl estradiol stimulates the biosynthesis of SHBG and CGC, but does not bind to these transport proteins.
Metabolism
About 50-60% of ethinyl estradiol are subject to the "first pass" effect, turning into sulfate metabolites in the intestinal wall and liver.
Ethinyl estradiol is metabolized by hydroxylation followed by conjugation with glucuronic and / or sulfuric acids. Part of ethinyl estradiol conjugated with glucuronic acid, after excretion with bile, is subjected to enterohepatic recirculation.
Removal
T_1/2 it is 10 hours after a single dose of 1 pill and rises to 15 hours after three cycles of treatment.
With urine 30-50% of metabolites are excreted, with feces 30-40%.

Indications and usage

- hormonal contraception;
The drug is recommended for use in acne, seborrhea, hirsutism and androgenic alopecia.

Dosage and administration

Jeanine is prescribed regularly to achieve a therapeutic effect and the required contraceptive protection. Irregular intake of Jeanine can lead to intermenstrual bleeding and impair therapeutic and contraceptive reliability.
Dragee should be taken in the order indicated on the package, every day at about the same time, drinking a small amount of water. Jeanine should be taken for 1 pill / day continuously for 21 days. Reception of each next package begins after a 7-day break, during which withdrawal bleeding is observed (menstrual-like bleeding). It usually starts 2-3 days from the reception of the last dragee and may not end before the start of taking a new package.
At not taking any hormonal contraceptives in the previous month Zhanin's intake begins on day 1 of the menstrual cycle (that is, on day 1 of menstrual bleeding). It is allowed to start taking on the 2-5 day of the menstrual cycle, but in this case it is recommended to use a barrier method of contraception during the first 7 days of taking pills from the first package.
At transition from combined oral contraceptives Zhanin's intake should be started the next day after taking the last dragee with the active ingredients of the previous drug, but in no case later than the next day after the usual 7-day break in taking (for drugs containing 21 dragees) or after taking the last inactive dragee (for preparations containing 28 pills in the package).
At transition from contraceptives containing only gestagens (mini-pili, injection forms, implant), Jeanine can begin to apply without interruption. At the transition from the "mini-pili" - any day without a break. At use of injectable contraceptives Jeanine is started from the day when the next injection should be given. At transition from implant - on the day of its removal. In all cases, you must use an additional barrier method of contraception during the first 7 days of taking pills.
After abortion in the first trimester of pregnancy a woman can start taking the drug immediately. In this case, the woman does not need additional methods of contraception.
After childbirth or abortion in the II trimester of pregnancy The drug should be started on days 21-28. If reception is started later, it is necessary to use an additional barrier method of contraception during the first 7 days of taking pills. However, if a woman lived in a sexual life between the birth or abortion and the beginning of Zanin's intake, then pregnancy should be excluded first or you should wait for the first menstruation.
Missed dragee a woman should take as soon as possible, the next dragee is taken at the usual time.
If the delay in taking pills less than 12 hours, the reliability of contraception is not reduced.
If the delay in taking pills was more than 12 hours, the reliability of contraception can be reduced. It should be borne in mind that pills should never be interrupted for more than 7 days, and that 7 days of continuous pills are required to achieve adequate suppression of the function of the hypothalamic-pituitary-ovarian system.
If the delay in the reception of the dragee is more than 12 hours (the interval since the reception of the last dragee is more than 36 hours) during first and second week taking the drug, the woman should take the last missed dragee as soon as she remembers (even if it means taking two dragees at the same time). The following dragee is taken at the usual time. Additionally, you should use a barrier method of contraception for the next 7 days. If a woman had sex life for a week before skipping the dragees, it is necessary to take into account the risk of pregnancy. The more pills are missed, and the closer this pass is to the 7-day break in taking pills, the higher the risk of pregnancy.
If the delay in the reception of the dragee is more than 12 hours (the interval since the reception of the last dragee is more than 36 hours) during time of the third week taking the drug, the woman should take the last missed dragee as soon as she remembers (even if it means taking two dragees at the same time). The following dragee is taken at the usual time. Additionally, you should use a barrier method of contraception for the next 7 days. In addition, the reception of drops from the new packaging should be started as soon as the current packaging ends, i.e. nonstop. Most likely, the woman will not have withdrawal bleeding until the end of the second package, but she may have spotting or breakthrough uterine bleeding on the days of taking pills.
If a woman misses pills, and then at the first normal free drug interval, she has no withdrawal bleeding, it is necessary to exclude pregnancy.
If a woman had vomiting within 3 to 4 hours after taking Jeanine, the absorption of the active substances may be incomplete. In this case, you should focus on the recommendations when skipping dragees. If a woman does not want to change the normal mode of taking the drug, she should take, if necessary, additional tablets (or several tablets) from another package.
In order to delay the onset of menstruation, the woman should continue to receive drops from the new package of Zhanin immediately after all the drops are taken from the previous one, without interruption in reception. Drops from this new package can be taken as long as the woman wants (until the package ends). While taking the drug from the second package, a woman may have spotting or breakthrough uterine bleeding. To resume taking Zanin from a new package should be after the usual 7-day break.
In order to postpone the beginning of menstruation to another day of the week, a woman should shorten the next break in the reception of dragees for as many days as she wants. The shorter the interval, the higher the risk that she will not have withdrawal bleeding and in the future there will be spotting and breakthrough bleeding while taking the second package (just as if she would like to delay the onset of menstruation).

From the digestive system: nausea, vomiting.
From the reproductive system: changes in vaginal secretion.
On the part of the endocrine system: engorgement, tenderness of the mammary glands, secretion from them; changes in body weight, changes in libido.
From the side of the central nervous system: decrease in mood, headache, migraine.
Other: chloasma, poor tolerance of contact lenses, fluid retention in the body, allergic reactions.

- the presence of thrombosis (venous and arterial) at present or in history (for example, deep vein thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular disorders);
- Presence or current history of conditions preceding thrombosis (for example, transient ischemic attacks, angina);
- diabetes with vascular complications;
- the presence of severe or multiple risk factors for venous or arterial thrombosis;
- the presence or history of jaundice or severe forms of liver disease (as long as the liver tests are not normalized);
- the presence at present or in the history of benign or malignant tumors of the liver;
- identified hormone-dependent malignant diseases of the genital or mammary glands or suspicion of them;
- vaginal bleeding of unknown origin;
- pregnancy or suspicion of it;
- hypersensitivity to the drug.

Epidemiological studies did not reveal an increased risk of teratogenic effects in children whose mothers took sex hormones before pregnancy or through negligence in the early stages of pregnancy.However, taking Jeanine is contraindicated during pregnancy.
Taking combined contraceptives can reduce the amount of breast milk and change its composition. Therefore, it is not recommended to prescribe Jeanine when breastfeeding. A small amount of sex hormones and / or their metabolites may be excreted in breast milk, but there is no evidence of their negative impact on the newborn.

Before using Zhanin, it is necessary to conduct a general medical examination (including the mammary glands and cytological examination of cervical mucus), to exclude pregnancy, disorders of the blood coagulation system. With prolonged use of the drug, prophylactic control examinations should be carried out every 6 months.
If there are risk factors, the potential risk and expected benefits of the therapy should be carefully evaluated and discussed with the woman before she decides to start taking the drug. When weighting, amplification, or at the first manifestation of risk factors may require the abolition of the drug.
When taking combined contraceptive drugs may develop venous thromboembolism (VTE), manifested in the form of deep vein thrombosis and / or pulmonary thromboembolism. The approximate frequency of VTE when taking oral contraceptives with a low dose of estrogen (less than 50 μg of ethinyl estradiol) is up to 4 per 10,000 women per year compared to 0.5–3 per 10,000 women per year for women who do not take contraceptives.The frequency of VTE when taking combined oral contraceptives is less than the frequency of VTE associated with pregnancy (6 per 10,000 pregnant women per year).
In women taking combined contraceptive drugs, extremely rare cases of thrombosis of other blood vessels (hepatic, mesenteric, renal arteries and veins, retinal arteries and veins) have been described. The relationship of these cases with the reception of combined oral contraceptives has not been proven.
The patient should be informed that if symptoms of venous or arterial thrombosis develop, one should immediately consult a doctor. These symptoms include unilateral pain in the leg and / or swelling, sudden severe chest pain with or without irradiation to the left hand, sudden shortness of breath, sudden coughing, any unusual, severe, prolonged headache, increased frequency and severity of migraine, sudden partial or complete loss of vision, diplopia, slurred speech or aphasia, dizziness, collapse with / or partial seizure, weakness or a very significant loss of sensation that suddenly appears on one side or in one part of the body, motor Novel disorders, acute stomach syndrome.
It should be borne in mind that the risk of venous or arterial thrombosis and / or thromboembolism increases with age; in smokers (with an increase in the number of cigarettes or an increase in age, the risk further increases, especially in women over 35); in the presence of a family history; obesity (body mass index more than 30 kg / m²); dyslipoproteinemia; hypertension; valvular heart disease; atrial fibrillation; prolonged immobilization; serious surgery; any surgery on the legs or extensive trauma. In these situations, it is advisable to stop using Zhanin (in the case of the planned operation, at least 4 weeks before it) and not to resume reception within 2 weeks after the end of immobilization.
You should consider the increased risk of thromboembolism in the postpartum period.
Circulatory disorders can also be observed in diabetes mellitus, systemic lupus erythematosus, hemolytic uremic syndrome, Crohn's disease, UC, sickle cell anemia.
It should also take into account biochemical parameters that may indicate a predisposition to thrombosis: resistance to activated protein C, hyperhomocysteinemia, deficiency of antithrombin III, protein C, protein S, the presence of antiphospholipid antibodies (antibodies to cardiolipin, lupus anticoagulant).
The relationship between the development of cervical cancer, breast cancer and taking combined oral contraceptives has not been proven.
In rare cases, against the background of the use of sex hormones, the development of liver tumors was observed. In cases of enlarged liver, the appearance of severe abdominal pain or signs of intraperitoneal bleeding, this should be considered when making a differential diagnosis.
The relationship between taking combined oral contraceptives and arterial hypertension has not been established. If a persistent arterial hypertension occurs, Jeanine should be canceled and appropriate anti-hypertensive therapy should be prescribed. Admission contraceptive can be continued after the normalization of blood pressure.
In the event of an abnormal liver function, it may be necessary to cancel Zanin temporarily until laboratory values ​​are normalized. With the development of cholestatic jaundice or cholestatic itching (first occurred during pregnancy or previous intake of sex hormones) Jeanine should be canceled.
It should be borne in mind that while taking Zanin, chloasma may develop, especially in women with a history of pregnant chloasma. This category of patients should avoid UV radiation.
Although combined oral contraceptives have an effect on insulin resistance and glucose tolerance, there is usually no need to correct the dose of hypoglycemic drugs in diabetic patients. However, patients in this category should be under close medical supervision.
In women with hypertriglyceridemia or a family history, there is an increased risk of developing acute pancreatitis when taking Zanin.
It should be borne in mind that while taking Zanin, the following conditions may worsen, but their connection with taking the drug has not been proven: jaundice and / or itching,associated with cholestasis ; the formation of gallstones; porphyria; systemic lupus erythematosus; hemolytic uremic syndrome; chorea; herpes pregnant; hearing loss associated with otosclerosis.
While taking Jeanine, occasional bleeding (spotting or breakthrough bleeding) may sometimes occur, especially during the first months of therapy. Therefore, the assessment of any irregular bleeding should be carried out only after an adaptation period of approximately 3 cycles.
If irregular bleeding recurs or develops after previous regular cycles, non-hormonal causes should be considered and adequate diagnostic measures taken to exclude malignant neoplasms or pregnancy. These may include diagnostic curettage.
In some cases, withdrawal bleeding may not develop during a break in taking the pills. If Jeanine was taken according to directions, it is unlikely that the woman is pregnant. However, in case of irregular pills or in the absence of two menstrual bleeding in a row, pregnancy should be excluded before continuing to take the drug.
A woman should be informed that taking Zhanin does not protect against HIV infection and other sexually transmitted diseases.
Reception of Zhanin can influence biochemical indicators of the function of the liver, thyroid gland, adrenal glands and kidneys,as well as plasma transport protein levels (corticosteroid-binding globulin, lipid / lipoprotein fractions, carbohydrate metabolism, coagulation and fibrinolysis).

Symptoms: nausea, vomiting, slight vaginal bleeding (in girls).
Treatment: conduct symptomatic therapy. There is no specific antidote.

With simultaneous application Jeanine with drugs that induce hepatic microsomal enzymes (hydantoins, barbiturates, primidone, Carbamazepine and rifampicin, but also possible with oxcarbazepine, topiramate , felbamate and griseofulvin) increases clearance of dienogest and ethinyl estradiol, which can lead to a decrease in contraceptive reliability. Typically, the maximum increase in enzyme activity is observed not earlier than 2-3 weeks after the start of taking these drugs, but may persist for at least 4 weeks after they are canceled.
With simultaneous use of Zhanin with ampicillins and tetracyclines there is a decrease in the level of ethinyl estradiol.
It should be borne in mind that women taking any of the above short-course drugs, in addition to Zhanin, should use barrier methods of contraception during concomitant use of the drug and within 7 days after their cancellation.
When taking rifampicin and for 28 days after its cancellation, a barrier method of contraception should be used in addition to Zhanin.If the concomitant administration of the drug is started at the end of taking Zanin's package, the next package of Zhanin should be started without the usual interruption in reception.

The drug should be stored at a temperature not higher than 25 ° C.

- 3 years.