1 tablet contains:
ethinyl estradiol 0.03 mg,
dienogest 2 mg,
dextrose (glucose syrup);
titanium dioxide (E171);
Janine's contraceptive effect is carried out through various complementary mechanisms, the most important of which are the suppression of ovulation and the change in the viscosity of cervical mucus, as a result of which it becomes impermeable to sperm.
With proper use, the Pearl index (an indicator that reflects the number of pregnancies in 100 women taking contraceptives during the year) is less than 1. If the pill is missed or if used incorrectly, the Pearl index can increase.
The gestagenic component of Janine - dienogest - has antiandrogenic activity, which is confirmed by the results of a number of clinical studies. In addition, dienogest improves the lipid profile of the blood (increases the amount of HDL).
In women taking combined oral contraceptives, the menstrual cycle becomes more regular, less painful menstruation is observed, the intensity and duration of bleeding is reduced, resulting in a reduced risk of iron deficiency anemia. In addition, there is evidence of a reduced risk of developing endometrial cancer and ovarian cancer.
Absorption. When taken orally, the dienogest is rapidly and completely absorbed, its serum Cmax of 51 ng / ml is reached after about 2.5 hours. Bioavailability is approximately 96%.
Distribution. Dienogest binds to serum albumin and does not bind to sex steroid-binding globulin (SHGS) and corticoid-binding globulin (CSH). In free form is about 10% of the total concentration in the blood serum; about 90% are non-specifically related to serum albumin. Induction of ethinyl estradiol with SHG synthesis does not affect the binding of dienogest to serum albumin.
Metabolism. Dienogest is almost completely metabolized. Serum clearance after a single dose is approximately 3.6 l / h.
Breeding. T1 / 2 from plasma is about 8.5-10.8 hours. In unchanged form, excreted in the urine in a small amount; in the form of metabolites, by the kidneys and through the digestive tract in a ratio of about 3: 1 with T1 / 2 - 14.4 hours.
Equilibrium concentration. The pharmacokinetics of dienogest is not affected by the level of GPS in the serum. As a result of daily use of the drug, the level of substance in the serum increases by about 1.5 times.
Absorption. After oral administration, ethinyl estradiol is rapidly and completely absorbed. Serum Cmax, equal to approximately 67 ng / ml, is reached in 1.5–4 hours. During absorption and first passage through the liver, ethinyl estradiol is metabolized, as a result of which its oral bioavailability averages about 44%.
Distribution. Ethinyl estradiol is almost completely (approximately 98%), although non-specific, bound by albumin. Ethinyl estradiol induces the synthesis of GPS. The apparent volume of distribution of ethinyl estradiol is 2.8–8.6 l / kg.
Metabolism. Ethinyl estradiol undergoes a presystemic biotransformation both in the mucosa of the small intestine and in the liver. The main metabolic pathway is aromatic hydroxylation. The plasma clearance rate is 2.3–7 ml / min / kg.
Breeding. A decrease in the concentration of ethinyl estradiol in the blood serum is biphasic; the first phase is characterized by T1 / 2 for about 1 hour, the second - T1 / 2 of 10–20 hours. Unchanged from the body is not excreted. Ethinyl estradiol metabolites are excreted in the urine and bile in a ratio of 4: 6 with T1 / 2 for about 24 hours.
Equilibrium concentration. Equilibrium concentration is achieved during the second half of the treatment cycle.
Pregnancy and lactation
Zhanin® is not prescribed during pregnancy and during lactation.
If pregnancy is detected while taking Janine®, it should be immediately canceled. However, extensive epidemiological studies did not reveal any increased risk of developmental defects in children born to women who received sex hormones before pregnancy, or teratogenicity when sex hormones were taken by negligence in the early stages of pregnancy.
Taking combined oral contraceptives can reduce the amount of breast milk and change its composition, so their use is contraindicated in lactation. A small amount of sex steroids and / or their metabolites may be excreted in milk.
Janine should not be used in the presence of any of the conditions listed below. If any of these conditions develops for the first time during administration, the drug should be immediately discontinued:
- hypersensitivity to any of the components of the drug Janine®;
- thrombosis (venous and arterial) and thromboembolism at present or in history (including deep vein thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular disorders);
- conditions preceding thrombosis (including transient ischemic attacks, angina pectoris) at present or in history;
- migraine with focal neurological symptoms at present or in history;
- diabetes mellitus with vascular complications;
- multiple or severe risk factors for venous or arterial thrombosis, including complicated lesions of the valvular apparatus of the heart, atrial fibrillation, diseases of the vessels of the brain or coronary arteries of the heart;
- uncontrolled arterial hypertension;
- serious surgery with prolonged immobilization;
- smoking over the age of 35;
- pancreatitis with severe hypertriglyceridemia at present or in history;
- liver failure and severe liver disease (until normalization of liver samples);
- liver tumors (benign or malignant) at present or in history;
- identified hormone-dependent malignant diseases (including genitals or mammary glands) or suspicion of them;
- vaginal bleeding of unknown origin;
- pregnancy or suspicion of it;
- lactation period.
- The potential risk and expected benefits of using combined oral contraceptives in each individual case should be carefully weighed in the presence of the following diseases / conditions and risk factors:
- risk factors for thrombosis and thromboembolism: smoking; obesity (dyslipoproteinemia); arterial hypertension; migraine; heart valve defects; prolonged immobilization, serious surgery, extensive trauma; hereditary predisposition to thrombosis (thrombosis, myocardial infarction or cerebrovascular accident at a young age in any of the next of kin);
- other diseases in which peripheral circulation disorders may occur: diabetes mellitus; systemic lupus erythematosus; hemolytic uremic syndrome; Crohn's disease and ulcerative colitis; sickle cell anemia; phlebitis of superficial veins;
- hereditary angioedema;
- liver disease
- diseases that first occurred or worsened during pregnancy or against the background of previous use of sex hormones (for example, jaundice, cholestasis, gallbladder disease, otosclerosis with hearing loss, porphyria, herpes pregnant, Sydenham chorea);
- the postpartum period.
From the digestive system: nausea, vomiting.
From the reproductive system: changes in vaginal secretion.
From the endocrine system: engorgement, tenderness of the mammary glands, secretion of them; changes in body weight, changes in libido.
From the side of the central nervous system: decreased mood, headache, migraine.
Other: chloasma, poor tolerance of contact lenses, fluid retention in the body, allergic reactions.
The interaction of oral contraceptives with other drugs can lead to breakthrough bleeding and / or a decrease in contraceptive reliability. The following types of interactions have been reported in the literature.
Effect on hepatic metabolism: the use of drugs that induce microsomal liver enzymes can lead to increased clearance of sex hormones. Such drugs include: phenytoin, barbiturates, primidone, carbamazepine, rifampicin; There are also suggestions regarding oxcarbazepine, topiramate, felbamate, griseofulvin, and St. John's wort preparations.
HIV proteases (e.g. ritonavir) and non-nucleoside reverse transcriptase inhibitors (e.g. nevirapine) and combinations thereof can also potentially affect hepatic metabolism.
Effect on the enterohepatic circulation: according to some studies, some antibiotics (e.g. penicillins and tetracycline) can reduce the enterohepatic circulation of estrogens, thereby lowering the concentration of ethinyl estradiol.
During the appointment of any of the above drugs, a woman should additionally use a barrier method of contraception (for example, a condom).
Substances that affect the metabolism of combined hormonal contraceptives (enzyme inhibitors). Dienogest is a substrate of cytochrome P450 (CYP) 3A4. Known CYP3A4 inhibitors, such as azole antifungal drugs (e.g. ketoconazole), cimetidine, verapamil, macrolides (e.g. erythromycin), diltiazem, antidepressants and grapefruit juice, can increase plasma levels of dienogest.
When taking drugs that affect microsomal enzymes, and within 28 days after their withdrawal, the barrier method of contraception should be additionally used.
While taking antibiotics (with the exception of rifampicin and griseofulvin) and within 7 days after their withdrawal, the barrier method of contraception should be additionally used. If the period of use of the barrier method of protection ends later than the tablets in the package, you need to move on to the next package without the usual break in taking dragees.
Oral combined contraceptives can affect the metabolism of other drugs, which leads to an increase (for example cyclosporine) or a decrease (for example lamotrigine) in their concentration in plasma and tissues.
How to take, course of administration and dosage
Inside, with a small amount of water, daily at about the same time of day, in the order indicated on the package. Take 1 tablet per day, continuously for 21 days. Reception of the next package begins after a 7-day break in taking dragees, during which withdrawal bleeding usually occurs. Bleeding, as a rule, begins on the 2nd – 3rd day after taking the last dragee and may not end until the start of taking a new package.
Reception Zhanina® begin:
- in the absence of any hormonal contraceptives in the previous month. Reception of Janine® begins on the first day of the menstrual cycle (i.e. on the first day of menstrual bleeding). It is allowed to start taking on the 2nd – 5th day of the menstrual cycle, but in this case it is recommended to additionally use the barrier method of contraception during the first 7 days of taking the dragee from the first package;
- during the transition from other combined oral contraceptives (from the vaginal ring, transdermal patch). It is preferable to start taking Janine® the day after taking the last active dragee from the previous package, but in no case later than the next day after the usual 7-day break (for drugs containing 21 dragees), or after taking the last inactive dragee (for drugs containing 28 tablets in a package). When switching from a vaginal ring, transdermal patch, it is preferable to start taking Janine® on the day the ring or patch is removed, but no later than the day when a new ring is to be inserted or a new patch is glued;
- during the transition from contraceptives containing only progestogens ("mini-drank", injectable forms, implant), or an intrauterine contraceptive-releasing progestogen (Mirena). A woman can switch from “mini-drinking” to Janine® any day (without a break), from an implant or an intrauterine contraceptive with gestagen - on the day of its removal, from the injection form - from the day the next injection should have been made. In all cases, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the dragee;
- after an abortion in the first trimester of pregnancy. A woman can start taking the drug immediately. Subject to this condition, a woman does not need additional contraceptive protection;
- 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 the reception is started later, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the dragee. If a woman has already lived sexually, pregnancy should be ruled out before the start of taking Janine® or it is necessary to wait for the first menstruation.
Reception of missed dragees. If the delay in taking the drug was less than 12 hours, contraceptive protection does not decrease. A woman should take the dragee as soon as possible, the following is taken at the usual time.
If the delay in taking dragees was more than 12 hours, contraceptive protection can be reduced. In this case, one can be guided by the following two basic rules:
- the drug should never be interrupted for more than 7 days;
- to achieve adequate suppression of the hypothalamic-pituitary-ovarian regulation, 7 days of continuous use of dragees are required.
If the delay in taking the dragee was more than 12 hours (the interval since the last dragee was taken was more than 36 hours), the following tips can be given.
The first week of taking the drug
A woman should take the last missed dragee as soon as possible (even if this means taking two dragees at the same time). The following dragees are taken at normal times. Additionally, a barrier method of contraception (such as a condom) should be used over the next 7 days. If sexual intercourse took place during the week before skipping a dragee, the probability of pregnancy should be considered. The more dragees missed and the closer the break in taking active substances, the greater the likelihood of pregnancy.
The second week of taking the drug
A woman should take the last missed dragee as soon as possible (even if this means taking two dragees at the same time). The following dragees are taken at normal times.
Provided that the woman took the dragee correctly within 7 days preceding the first missed dragee, there is no need to use additional contraceptive measures. Otherwise, as well as when skipping two or more tablets, it is necessary to additionally use barrier methods of contraception (such as a condom) for 7 days.
The third week of taking the drug
The risk of a decrease in reliability is inevitable due to the upcoming break in taking dragees.
A woman should strictly adhere to one of the following two options (if in the 7 days preceding the first missed tablet, all tablets were taken correctly, there is no need to use additional contraceptive methods):
1. A woman should take the last missed dragee as soon as possible (even if this means taking two dragees at the same time). The next dragee is taken at the usual time until the dragee from the current package runs out. The next packaging should be started immediately. Cancellation bleeding is unlikely until the second package is over, but spotting and breakthrough bleeding may occur while taking the dragee.
2. A woman can also stop taking dragees from the current package. Then she should take a break for 7 days, including the day of the pass of the dragee, and then start accepting new packaging.
If a woman missed taking dragees and then during a break in taking dragees, she does not have withdrawal bleeding, pregnancy must be excluded.
Recommendations for vomiting and diarrhea
If a woman has vomiting or diarrhea within 4 hours after taking an active pill, absorption may not be complete and additional contraceptive measures should be taken. In these cases, you should be guided by the recommendations when skipping a dragee.
Change in the day the menstrual cycle begins
In order to delay the onset of menstruation, a woman should continue taking dragees from the new Janine® package immediately after all dragees from the previous one were taken, without interruption in admission. Dragees from this new package can be taken as long as the woman wants (until the package is finished). Against the background of taking the drug from the second package, a woman may have spotting or breakthrough uterine bleeding. To resume taking Janine® from a new pack should be after a normal 7-day break.
In order to transfer the day the menstruation begins to another day of the week, a woman should be advised to shorten the next break in taking dragees for as many days as she wants. The shorter the interval, the higher the risk that she will not have withdrawal bleeding and there will subsequently be spotting and breakthrough bleeding during the second pack (as well as in the case when she would like to delay the onset of menstruation).
Additional information for special patient categories
Children and teens. The drug Janine® is indicated only after the onset of menarche.
Elderly patients. Not applicable. Zhanin® is not indicated after menopause.
Patients with impaired liver function. The drug Janine® is contraindicated in women with severe liver diseases until liver function indicators return to normal (see also the section "Contraindications").
Patients with impaired renal function. The drug Janine® has not been specifically studied in patients with impaired renal function. Available data do not suggest treatment changes in such patients.
Symptoms: nausea, vomiting, slight vaginal bleeding (in girls).
Treatment: conduct symptomatic therapy. There is no specific antidote.
If any of the conditions, diseases, and risk factors listed below are present, then the potential risk and expected benefits of using combined oral contraceptives in each individual case should be carefully weighed and discussed with a woman before she decides to start taking the drug. In the event of a worsening, intensification, or first manifestation of any of these conditions, diseases, or an increase in risk factors, a woman should consult her doctor, who can decide whether to discontinue the drug.
Diseases of the cardiovascular system
The results of epidemiological studies indicate a relationship between the use of CPC and an increase in the 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 maximum in the first year of taking such drugs. An increased risk is present after the initial use of combined oral contraceptives or the resumption of the use of the same or different combined oral contraceptives (after a break between doses of 4 weeks or more). Data from a large prospective study involving 3 groups of patients show that this increased risk is present mainly during the first 3 months.
The general risk of VTE in patients taking low-dose combined oral contraceptives (ethinyl estradiol content -
VTE, which manifests itself as deep vein thrombosis, or pulmonary embolism can occur with any combination of oral contraceptives.
Very rarely, when using combined oral contraceptives, thrombosis of other blood vessels (for example, hepatic, mesenteric, renal, cerebral veins and arteries or vessels of the retina) occurs. There is no consensus on the relationship between the occurrence of these events and the use of combined oral contraceptives.
Symptoms of deep vein thrombosis (DVT) include the following: unilateral edema of the lower extremity or along the vein in the leg, pain or discomfort in the leg only in an upright position or when walking, local temperature increase in the affected leg, redness or discoloration of the skin of the leg.
Symptoms of pulmonary embolism (pulmonary embolism) are as follows: shortness of breath or rapid breathing; sudden cough, incl. with hemoptysis; acute pain in the chest, which may intensify with a deep breath; sense of anxiety; severe dizziness; rapid or irregular heartbeat. Some of these symptoms (e.g. shortness of breath, cough) are nonspecific and may be misinterpreted as signs of other more or less severe events (e.g., respiratory tract infection).
Arterial thromboembolism can lead to stroke, vascular occlusion, or myocardial infarction. Symptoms of a stroke are as follows: sudden weakness or loss of sensation of the face, arm or leg, especially on one side of the body, sudden confusion, problems with speech and understanding; sudden one- or two-sided loss of vision; sudden disturbance of gait, dizziness, loss of balance or coordination of movements; sudden, severe or prolonged headache for no apparent reason; loss of consciousness or fainting with or without an epileptic seizure. Other signs of vascular occlusion: sudden pain, swelling and weak blueness of the limbs, acute abdomen.
Symptoms of myocardial infarction include: pain, discomfort, pressure, heaviness, a feeling of constriction or fullness in the chest, in the arm, or behind the sternum; discomfort with irradiation in the back, cheekbone, larynx, arm, stomach; cold sweat, nausea, vomiting, or dizziness, severe weakness, anxiety, or shortness of breath; rapid or irregular heartbeat. Arterial thromboembolism can be fatal. The risk of 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 (body mass index more than 30 kg / m2);
- family history (e.g., venous or arterial thromboembolism at any time with close relatives or parents at a relatively young age). In the case of a hereditary or acquired predisposition, a woman should be examined by an appropriate specialist to decide on the possibility of taking combined oral contraceptives;
- prolonged immobilization, serious surgery, any leg surgery or extensive injury. In these situations, it is advisable to stop the use of combined oral contraceptives (in the case of the planned operation, at least 4 weeks before it) and not to resume taking within two weeks after the end of the immobilization;
- arterial hypertension;
- heart valve disease;
- Atrial fibrillation.
The possible role of varicose veins and superficial thrombophlebitis in the development of venous thromboembolism remains a controversial issue.
You should take into account the increased risk of developing thromboembolism in the postpartum period.
Peripheral circulation disorder can also occur in diabetes mellitus, systemic lupus erythematosus, hemolytic uremic syndrome, chronic inflammatory bowel disease (Crohn's disease or ulcerative colitis) and sickle cell anemia.
An increase in the frequency and severity of migraine during the use of combined oral contraceptives (which may precede cerebrovascular disorders) may be the reason for the immediate termination 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, lack of antithrombin III, lack of protein C, lack of protein S, antiphospholipid antibodies (anticardiolipin antibodies, anticoagulant).
When assessing the ratio of risk and benefit, it should be borne in mind that adequate treatment of an appropriate condition can reduce the risk of thrombosis associated with it. It should also be borne in mind that the risk of thrombosis and thromboembolism during pregnancy is higher than when taking low-dose oral contraceptives (the content of ethinyl estradiol -
The most significant risk factor for cervical cancer is persistent human papillomavirus infection. There are reports of a slight increase in the risk of developing cervical cancer with prolonged use of combined oral contraceptives. However, the connection with the use of combined oral contraceptives has not been proven. Contradictions remain regarding the extent to which these data are associated with screening for cervical pathology or with features of sexual behavior (a more rare use of barrier methods of contraception).
A meta-analysis of 54 epidemiological studies showed that there is a slightly increased relative risk of developing breast cancer diagnosed in women who used combined oral contraceptives (relative risk - 1.24). The increased risk gradually disappears within 10 years after stopping taking these drugs. Due to the fact that breast cancer is rare in women under 40 years of age, an increase in the number of breast cancer diagnoses in women who are currently taking combined oral contraceptives or who have recently taken is insignificant in relation to the overall risk of this disease. Its connection with the use of combined oral contraceptives has not been proven. The observed increased risk may also be a consequence of an earlier diagnosis of breast cancer in women, using combined oral contraceptives. Women who have ever used combined oral contraceptives have earlier stages of breast cancer than women who have never used them.
In rare cases, against the background of the use of combined oral contraceptives, the development of liver tumors was observed, which in some cases led to life-threatening intraperitoneal bleeding. In the case of severe pain in the abdomen, liver enlargement, or signs of intra-abdominal bleeding, this should be considered when making a differential diagnosis.
Women with hypertriglyceridemia (or the presence of this condition in a family history) may increase the risk of developing pancreatitis while taking combined oral contraceptives.
Although a slight increase in blood pressure has been described in many women taking combined oral contraceptives, a clinically significant increase has been rare. Nevertheless, 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 started. 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 when taking combined oral contraceptives, but their relationship with taking combined oral contraceptives 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. Cases of Crohn’s disease and ulcerative colitis with the use of combined oral contraceptives have also been described.
In women with hereditary forms of angioedema, exogenous estrogens can cause or worsen symptoms of angioedema.
Acute or chronic liver dysfunction may require discontinuation of combined oral contraceptives until liver function returns to normal. Recurrent cholestatic jaundice, which develops for the first time during pregnancy or the previous intake of sex hormones, requires stopping the use of combined oral contraceptives.
Although combined oral contraceptives may affect insulin resistance and glucose tolerance, there is no need to change the therapeutic regimen in patients with diabetes using low-dose combined oral contraceptives (ethinyl estradiol -
Sometimes chloasma can develop, especially in women with a history of pregnant chloasma. Women with a tendency to chloasma while taking combined oral contraceptives should avoid prolonged exposure to the sun and exposure to UV radiation.
Preclinical Safety Data
Preclinical data obtained in the course of standard studies to detect toxicity with multiple doses of the drug, as well as genotoxicity, carcinogenic potential and toxicity to the reproductive system, do not indicate a particular risk to humans. However, it should be remembered that sex steroids can contribute to the growth of some hormone-dependent tissues and tumors.
Taking combined oral contraceptives may affect the results of some laboratory tests, including liver, kidney, thyroid, adrenal gland function, plasma transport protein levels, carbohydrate metabolism, coagulation and fibrinolysis parameters. Changes usually do not go beyond the normal range.
The effectiveness of combined oral contraceptive drugs can be reduced in the following cases: with missed tablets, vomiting and diarrhea, or as a result of drug interactions.
Effect on the menstrual cycle
Irregular bleeding (spotting spotting or breakthrough bleeding) may occur with combined oral contraceptives, especially during the first months of use. Therefore, any irregular bleeding should be evaluated only after an adaptation period of approximately three cycles.
If irregular bleeding recurs or develops after previous regular cycles, a thorough examination should be performed to exclude malignant neoplasms or pregnancy.
Some women may not develop withdrawal bleeding during a break in taking the pills. If combined oral contraceptives were taken as directed, it is unlikely that the woman is pregnant. However, if before that combined oral contraceptives were taken irregularly or two consecutive bleeding was absent in a row, pregnancy should be excluded before continuing with the drug.
Before starting or resuming taking Janine®, it is necessary to familiarize yourself with the woman’s history of life, the family history of the woman, conduct a thorough general medical (including measurement of blood pressure, heart rate, determination of body mass index) and gynecological examination, including examination of the mammary glands and cytological examination of scraping from the cervix (test according to Papanicolaou), exclude pregnancy. The volume of additional studies and the frequency of control examinations is determined individually. Typically, control examinations should be carried out at least 1 time per year.
A woman should be warned that drugs like Janine® do not protect against HIV infection (AIDS) and other sexually transmitted diseases.