Jeanine, 2 mg+0.03 mg 63 pcs

Pharmacodynamics

The contraceptive effect of Gynine is achieved through various complementary mechanisms, the most important of which are suppression of ovulation and changes in cervical mucus viscosity, making it impermeable to sperm.

When used correctly, the Perl Index (a measure of the number of pregnancies in 100 women taking the contraceptive in a year) is less than 1. If the pill is missed or used incorrectly, the Perl index may increase.

The gestagenic component of Janine, dienogest, has antiandrogenic activity, which has been confirmed by a number of clinical studies. In addition, dienogestr improves the lipid profile of the blood (increases the amount of HDL).

In women taking combined oral contraceptives menstrual cycle becomes more regular, painful menstruation is less often observed, the intensity and duration of bleeding decreases, and as a result the risk of iron deficiency anemia decreases. There is also evidence of a decreased risk of endometrial and ovarian cancer.

Pharmacokinetics

Dienogest

Absorption. When taken orally, dienogest is rapidly and completely absorbed; its Cmax in blood serum, equal to 51 ng/ml, is reached after approximately 2.5 hours. The bioavailability is approximately 96%.

Distribution. Dienogest is bound to serum albumin and does not bind to sex steroid-binding globulin (SBSG) and corticoid-binding globulin (CRG). Free is about 10% of the total serum concentration; about 90% is nonspecifically bound to serum albumin. Induction of HSPC synthesis by ethinylestradiol has no effect on dienogestin binding to serum albumin.

Metabolism. Dienogest is almost completely metabolized. Serum clearance after a single dose is approximately 3.6 l/h.

Elimation. T1/2 from plasma is about 8.5-10.8 hours. It is excreted in unchanged form by urine in insignificant amount; as metabolites – by kidneys and through the gastrointestinal tract in the ratio of about 3:1 with T1/2 – 14.4 hours.

The equilibrium concentration. The pharmacokinetics of dienogest is not affected by the serum HSPC level. Daily administration of the drug increases the level of the substance in the serum by approximately 1.5 times.

Ethinylestradiol

Absorption. After oral administration, ethinylestradiol is quickly and completely absorbed. Cmax in blood serum, equal to approximately 67 ng/ml, is reached in 1.5-4 hours. During absorption and first passage through the liver, ethinylestradiol is metabolized, resulting in an average bioavailability of about 44% when taken orally.

Distribution. Ethinylestradiol is almost completely (approximately 98%), although non-specific, bound to albumin. Ethinylestradiol induces the synthesis of HSPC. The apparent volume of distribution of ethinylestradiol is 2.8-8.6 L/kg.

Metabolism. Ethinylestradiol undergoes presystemic biotransformation both in the small intestinal mucosa and in the liver. The main metabolic pathway is aromatic hydroxylation. The blood plasma clearance rate is 2.3-7 ml/min/kg.

Evacuation. Decrease of ethinylestradiol concentration in blood serum has a biphasic character; the first phase is characterized by T1/2 about 1 h, the second – T1/2 10-20 h. It is not excreted from the body unchanged. Metabolites of ethinylestradiol are excreted in the urine and bile at a ratio of 4:6 with a T1/2 of about 24 hours.

The equilibrium concentration. The equilibrium concentration is reached during the second half of the treatment cycle.

Indications

Hormonal contraception.

Composition

1 dragee contains:

the active ingredient:

ethinylestradiol 0.03 mg,

Dienogest 2 mg,

excipients:

lactose monohydrate;

potato starch;

gelatin;

talc;

Magnesium stearate;

saccharose;

dextrose (glucose syrup);

macrogol 35000;

calcium carbonate;

p> povidone K25;

titanium dioxide (E171);

carnauba wax

How to take, the dosage

To be taken by mouth, with a small amount of water, daily at approximately the same time of the day, in the order indicated on the package. Take 1 tablet a day, continuously for 21 days. Taking the next package begins after a 7-day break in the reception of the dragee, during which there is usually a bleeding withdrawal. Bleeding usually begins on the 2nd or 3rd day after taking the last dose and may not end until the next dose.

Janine® is started:

If you have not taken any hormonal contraceptives in the previous month. Taking Jeanine® starts on the first day of the menstrual cycle (i.e., 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 use an additional barrier method of contraception during the first 7 days of taking tablets from the first package;

– when changing from other combined oral contraceptives (from vaginal ring, transdermal plaster). It is preferable to start Janine® the day after taking the last active dragee from the previous package, but in no case later than the day after the usual 7-day break (for products containing 21 drages) or after taking the last inactive dragee (for products containing 28 drages per package). When switching from a vaginal ring, transdermal patch, it is preferable to start taking Gynine® on the day the ring or patch is removed, but no later than the day the new ring or patch is to be inserted;

when switching from gestagen-only contraceptives (“mini-pills,” injectable forms, implant) or a gestagen-releasing intrauterine contraceptive (Mirena). A woman can change from a “mini-pili” to Jeanine® on any day (without a break), from an implant or intrauterine contraceptive with gestagen – on the day of its removal, from an injectable form – from the day when 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 may start taking the drug immediately. If this condition is met, the woman does not need additional contraceptive protection;

– after childbirth or abortion in the second trimester of pregnancy. It is recommended that the drug be started on day 21-28 after childbirth or a second trimester abortion. If it is started later, it is necessary to use additionally a barrier method of contraception during the first 7 days of taking the drops. If a woman has already been sexually active, pregnancy must be excluded before taking Gynin® or the first menstrual period must be awaited.

The use of missed pills. If the delay in taking the drug is less than 12 hours, contraceptive protection is not reduced. The woman should take the pills as soon as possible, and the next one should be taken at the usual time.

If the delay in taking the pills is more than 12 hours, contraceptive protection may be reduced. The following two basic rules may guide your contraceptive protection:

– taking the drug should never be interrupted for more than 7 days;

– 7 days of continuous taking of the dragee is required to achieve adequate suppression of hypothalamic-pituitary-ovarian regulation.

If the delay in taking the dragee is more than 12 hours (the interval since the last dragee was taken is more than 36 hours), the following advice may be given.

The first week of taking the drug

The woman should take the last missed dragee as soon as possible (even if this means taking two drages at the same time). The next dragee is taken at the usual time. In addition, a barrier method of contraception (e.g. condom) should be used for the next 7 days. If sexual intercourse took place during the week before skipping the pills, it is necessary to consider the possibility of pregnancy. The more pills missed and the closer the interruption in active ingredient intake, the greater the likelihood of pregnancy.

The second week of taking the drug

The woman should take the last missed dragee as soon as possible (even if that means taking two dragees at the same time). The next dragee is taken at the usual time.

As long as the woman has taken the pills correctly in the 7 days preceding the first missed pills, no additional contraceptive measures are necessary. Otherwise, and if two or more pills are missed, additional barrier methods of contraception (e.g., a condom) should be used for 7 days.

The third week of taking the drug

The risk of decreased reliability is inevitable because of the impending interruption of the pills.

The woman must strictly adhere to one of the following two options (if all the pills were taken correctly in the 7 days preceding the first missed pills, no additional contraceptive methods are necessary):

1. The woman should take the last missed dragee as soon as possible (even if this means taking two dragees at the same time). The next pill should be taken at the usual time until the pills from the current package run out. The next pack should be started immediately. Bleeding cancellation is unlikely until the second pack is finished, but there may be oozing and breakthrough bleeding while taking the pills.

2. A woman can also stop taking the pills from the current package. She should then take a break for 7 days, including the day she missed the dragee, and then start a new pack.

If a woman misses a dose and then has no bleeding cancellation during a break in the dragee, pregnancy must be ruled out.

Recommendations for vomiting and diarrhea

If a woman has had vomiting or diarrhea within 4 h of taking active pills, absorption may be incomplete and additional contraceptive measures should be taken. In these cases, the recommendations for skipping a dose of the dragee should be followed.

Changing the start day of the menstrual cycle

In order to delay the start of menstruation, a woman should continue taking the new Gironin® pack of pills as soon as she has taken all the pills in the previous pack, without interruption. This new pack can be taken as long as the woman wishes (until the pack runs out). While taking the second package, a woman may experience menses or breakthrough uterine bleeding. Resume taking Jeanine® from the new pack after the usual 7-day break.

In order to postpone the day her period starts to another day of the week, a woman should be advised to shorten her immediate break from taking the dragee by as many days as she wants. The shorter the interval, the greater the risk that she will not have a bleeding withdrawal and will subsequently have oozing and breakthrough bleeding while taking the second pack (just like when she would like to delay the start of her period).

Further information for special types of patients

Children and adolescents. Jeanine® is indicated only after the onset of menarche.

Patients who are elderly. Not applicable. Jeanine® is not indicated after the onset of menopause.

Patients with liver disorders. Jeanine® is contraindicated in women with severe liver disease until liver function returns to normal (see also Contraindications).

Patients with renal impairment. Jeanine® has not been specifically studied in patients with renal impairment. The available data do not suggest a change in treatment in such patients.

Interaction

Interactions between oral contraceptives and other drugs can lead to breakthrough bleeding and/or decreased contraceptive reliability. The following types of interactions have been reported in the literature.

Influence on hepatic metabolism: the use of drugs that induce microsomal liver enzymes may lead to increased clearance of sex hormones. These drugs include: phenytoin, barbiturates, primidone, carbamazepine, rifampicin; there are also suggestions for oxcarbazepine, topiramate, felbamate, griseofulvin, and St John’s wort.

HIV proteases (e.g. ritonavir) and non-nucleoside reverse transcriptase inhibitors (e.g. nevirapine) and their combinations also have the potential to affect hepatic metabolism.

Influence on intestinal hepatic circulation: Some antibiotics (e.g., penicillins and tetracyclines) may decrease intestinal hepatic circulation of estrogen, thereby lowering the concentration of ethinylestradiol, according to individual studies.

When prescribing any of the above drugs, a woman should additionally use a barrier method of contraception (for example, a condom).

The substances affecting the metabolism of combined hormonal contraceptives (enzyme inhibitors). Dienogest is a substrate of cytochrome P450 (CYP)3A4. Known CYP3A4 inhibitors such as azole antifungals (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 for 28 days after their withdrawal, an additional barrier method of contraception should be used.

When taking antibiotics (except rifampicin and griseofulvin) and for 7 days after their withdrawal, an additional barrier method of contraception should be used. If the period of using a barrier method of contraception ends later than the pills in the package, you should move on to the next package without the usual break in the intake of pills.

The oral combination contraceptives may affect the metabolism of other drugs, resulting in higher (e.g., cyclosporine) or lower (e.g., lamotrigine) plasma and tissue concentrations.

Special Instructions

If any of the conditions, diseases, and risk factors listed below are present, 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, diseases, or increased risk factors aggravate, worsen, or first appear, the woman should consult her doctor, who may decide whether to discontinue the medication.

Cardiovascular disease

. Epidemiologic studies suggest an association between MTCT use and an increased incidence of venous and arterial thrombosis and thromboembolism (such as deep vein thrombosis, pulmonary embolism, myocardial infarction, and cerebrovascular events) with combined oral contraceptive use. These diseases are rare.

The risk of venous thromboembolism (VTE) is highest in the first year of taking these drugs. An increased risk is present after initial use of combined oral contraceptives or renewed use of the same or different combined oral contraceptives (after a gap of 4 weeks or more between doses). Data from a large prospective study involving 3 groups of patients show 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 (ethinylestradiol content –

VTE manifesting as deep vein thrombosis or pulmonary embolism can occur with any combined oral contraceptive.

In extremely rare cases, thrombosis of other blood vessels (e.g., hepatic, mesenteric, renal, cerebral veins and arteries, or retinal vessels) occurs with combined oral contraceptives. There is no consensus on the association between the occurrence of these events and the use of combined oral contraceptives.

The symptoms of deep vein thrombosis (DVT) include the following: unilateral swelling of the lower extremity or along a vein in the leg, pain or discomfort in the leg only when upright or walking, localized temperature rise in the affected leg, redness or discoloration of the skin on the leg.

The symptoms of pulmonary artery thromboembolism (TELA) are: difficulty or rapid breathing; sudden cough, including with hemoptysis; sharp pain in the chest, which may increase with deep breaths; anxiety; severe dizziness; and rapid or irregular heartbeat. Some of these symptoms (e.g., shortness of breath, coughing) are nonspecific and may be misinterpreted as signs of other more or less severe events (e.g., respiratory infection).

Arterial thromboembolism can lead to stroke, vascular occlusion or myocardial infarction. Symptoms of stroke include: 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 one- or two-sided loss of vision; sudden gait disturbance, dizziness, loss of balance or coordination of movements; sudden, severe or prolonged headache for no apparent reason; loss of consciousness or fainting with or without an epileptic seizure. Other signs of vascular occlusion: sudden pain, swelling and mild bruising of the extremities, acute abdomen.

Symptoms of myocardial infarction include: pain, discomfort, pressure, heaviness, compression, or tumescence in the chest, arm, or behind the sternum; discomfort radiating to the back, cheekbone, throat, 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 is increased:

– with age;

– in smokers (the risk increases with more cigarettes or greater age, especially in women over 35).

If there is:

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

– family history (e.g. venous or arterial thromboembolism ever in a close relative or parent at a relatively young age). If there is an inherited or acquired predisposition, the woman should be evaluated by an appropriate specialist to decide whether she should take the combined oral contraceptive;

Long-term immobilization, major surgery, any leg surgery or extensive 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 taking them for two weeks after the end of immobilization;

– dyslipoproteinemia;

– arterial hypertension;

– migraine;

– heart valve disease;

– atrial fibrillation.

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

The increased risk of thromboembolism in the postpartum period should be considered.

Peripheral circulatory disorders may also be seen in diabetes mellitus, systemic lupus erythematosus, hemolytic uremic syndrome, chronic inflammatory bowel disease (Crohn’s disease or nonspecific ulcerative colitis) and sickle cell anemia.

An increase in the frequency and severity of migraines during use of combined oral contraceptives (which may precede cerebrovascular disorders) may be grounds for immediate discontinuation of these drugs.

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

When evaluating the risk-benefit ratio, it should be considered that adequate treatment of the condition in question can reduce the associated risk of thrombosis. Also consider that the risk of thrombosis and thromboembolism in pregnancy is higher than with low-dose oral contraceptives (ethinyl estradiol content –

Tumors

The most significant risk factor for cervical cancer is persistent papillomavirus infection. There have been reports of some increased risk of cervical cancer with long-term use of combined oral contraceptives. However, the association with taking combined oral contraceptives has not been proven. There remains controversy about the extent to which these findings are related to screening for cervical abnormalities or to patterns of sexual behavior (less frequent use of barrier methods of contraception).

A meta-analysis of 54 epidemiological studies found that there is a slightly increased relative risk of breast cancer diagnosed in women who used combined oral contraceptives (relative risk of 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 the combined oral contraceptives is small relative to the overall risk of the disease. Its association with taking combined oral contraceptives has not been proven. The observed increase in risk may also be a consequence of earlier diagnosis of breast cancer in women who use the combined oral contraceptives. Women who have ever used combined oral contraceptives are found to have earlier stages of breast cancer than women who have never used them.

In rare cases, the development of liver tumors has been observed during the use of combined oral contraceptives, which in some cases led to life-threatening intra-abdominal bleeding. If severe abdominal pain, liver enlargement, or signs of intra-abdominal bleeding occur, this should be considered when making a differential diagnosis.

Other conditions

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

While small increases in BP 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 BP develops while taking combined oral contraceptives, the medications should be stopped and treatment for arterial hypertension should be initiated. The combined oral contraceptives may be continued if normal BP is achieved with hypotensive therapy.

The following conditions have been reported to develop or worsen both during pregnancy and while taking combined oral contraceptives, but their association with taking combined oral contraceptives has not been proven: Jaundice and/or pruritus associated with cholestasis; gallstone formation; porphyria; systemic lupus erythematosus; hemolytic uremic syndrome; Sydenham’s chorea; herpes of pregnancy; hearing loss associated with otosclerosis. Cases of Crohn’s disease and nonspecific ulcerative colitis have also been described with combined oral contraceptives.

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

Acute or chronic liver dysfunction may require withdrawal of combined oral contraceptives until liver function values 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.

While combined oral contraceptives may affect insulin resistance and glucose tolerance, there is no need to change the therapeutic regimen in diabetic patients using low-dose combined oral contraceptives (ethinylestradiol content –

Occasionally, chloasma may develop, especially in women with a history of pregnancy chloasma. Women who are prone to chloasma should avoid prolonged sun exposure and exposure to UV radiation while taking combined oral contraceptives.

Preclinical safety data

Preclinical data from standard multiple-dose toxicity studies, as well as genotoxicity, carcinogenic potential, and reproductive toxicity, do not indicate any particular risk to humans. However, it should be remembered that sex steroids can promote the growth of some hormone-dependent tissues and tumors.

Laboratory tests

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

The efficacy of combined oral contraceptives may be reduced in the following cases: skipping pills, vomiting and diarrhea, or as a result of drug interactions.

The effect on the menstrual cycle

The combined oral contraceptives may cause irregular bleeding (spotting or breakthrough bleeding), especially during the first months of use. Therefore, any irregular bleeding should be evaluated only after an adjustment period of about three cycles.

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

Some women may not develop withdrawal bleeding during a break in the pill. If the combined oral contraceptives have been taken as directed, it is unlikely that the woman is pregnant. However, if the combined oral contraceptives have been taken irregularly before, or if there have not been two consecutive bleeding withdrawals, pregnancy must be ruled out before continuing the medication.

Medical examinations

. Before starting or resuming treatment with Jeanine® , a woman’s medical history, family history, a thorough general medical (including blood pressure, heart rate, BMI) and gynecological examination, including breast examination and cytology of cervical smears (Papanicolae test), should be performed to rule out pregnancy. The scope of additional examinations and the frequency of follow-up examinations are determined on an individual basis. Normally, follow-up examinations should be performed at least once a year.

The woman should be warned that drugs like Jeanine® do not protect against HIV infection (AIDS) and other sexually transmitted diseases.

Contraindications

Janine should not be used for any of the conditions listed below. If any of these conditions develop for the first time while taking the drug, it should be stopped immediately:

Side effects

Digestive system disorders: nausea, vomiting.

Perior genital system: changes in vaginal secretion.

Endocrine system disorders: breast engorgement, painfulness, secretion of mammary glands; changes in body weight, changes in libido.

CNS disorders: decreased mood, headache, migraine.

Others: chloasma, poor tolerance of contact lenses, fluid retention in the body, allergic reactions.

Overdose

Symptoms: nausea, vomiting, slight vaginal bleeding (in girls).

Treatment: symptomatic therapy is carried out. There is no specific antidote.

Pregnancy use

Janine® is not prescribed during pregnancy and while breastfeeding.

If pregnancy is detected while taking Jeanine® , it should be stopped immediately. However, extensive epidemiological studies have found no increased risk of developmental defects in children born to women who received sex hormones before pregnancy or teratogenic effects when sex hormones were inadvertently taken early in pregnancy.

The use of combined oral contraceptives may decrease the amount of breast milk and change its composition, so their use is contraindicated during lactation. A small amount of sex steroids and/or their metabolites may be excreted with milk.