Expiration date: 04/2025

Structure and Composition:

Dragee. 1 dragee contains:

0.03 mg ethinylestradiol

dienogest 2.0 mg

Excipients: lactose monohydrate, potato starch, gelatin, magnesium stearate, talc, sucrose, dextrose (glucose syrup) Macrogol 35000 calcium carbonate, povidone K25 titanium dioxide (E171) Carnauba wax

in blister 21 pcs. In the paper cartons 1 or 3 blisters.

Description pharmaceutical form:

White smooth pellet.

Characteristic:

Low-dose monophasic oral combined estrogen-progestin contraceptive drug. Due to the effect of antiandrogen progestin dienogest component contributes to clinical improvement in patients with inflamed acne (acne).

Pharmacokinetics:

dienogest

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

Distribution. Dienogest bound to albumin serum, and is not associated with binding globulin sex steroids (SHBG) and corticoid-binding globulin (CBG). The free form is about 10% of the total serum concentration of about 90% - non-specifically bound to serum albumin. Induction of synthesis of SHBG ethinylestradiol not affect binding to serum albumin dienogest.

Metabolism. Dienogest is almost completely metabolized. Clearance of serum after a single dose of about 3.6 l / h.

Withdrawal. T1 / 2 of the plasma is about 8,5-10,8 h unmodified form displayed in a small amount of urine as metabolites - kidneys and the digestive tract through a ratio of about 3:. 1 T1 / 2 - 14.4 hours.

The equilibrium concentration. Pharmacokinetics dienogest not affect SHBG serum. As a result, the level of daily dosing substance in serum increased about 1.5 times.

Ethinylestradiol

Absorption. After oral ethinyl estradiol is rapidly and completely absorbed. Serum Cmax of about 67 ng / ml, achieved after 1.5-4 hours. During the suction and the first passage through the liver is metabolized ethinylestradiol, whereby its oral bioavailability averages about 44%.

Distribution. Ethinyl estradiol is almost full (about 98%), while non-specifically binds to albumin. Ethinyl estradiol induces the synthesis of SHBG. The apparent volume of distribution of ethinylestradiol is 2,8-8,6 l / kg.

Metabolism. Ethinylestradiol presistemna undergoes biotransformation in the mucosa of the small intestine and in the liver. The main pathway - aromatic hydroxylation. The rate of clearance from the blood plasma of 2,3-7 ml / min / kg.

Withdrawal. The decrease in serum concentrations of ethinyl estradiol is a two-phase nature of the first phase is characterized by a T1 / 2 of about 1 hour, and the second -. T1 / 2 of 10-20 hours in an unmodified form of the organism is not displayed. Ethinylestradiol metabolites are excreted in the urine and bile in 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.

Description of the pharmacological actions:

Janine contraceptive effect achieved by mutually different mechanisms, the most important of which - ovulation suppression and the change in viscosity of the cervical mucus, whereby it becomes impenetrable to sperm.

When used properly, Pearl index (an indicator of the number of pregnancies in 100 women taking contraceptive during the year) is less than 1. When skipping pills or incorrect use Pearl Index may increase.

Jeanine progestogens component - dienogest - has anti-androgenic activity, as confirmed by the results of several clinical studies. Furthermore, dienogest improves blood lipid profile (increases the amount of HDL).

In women receiving combined oral contraceptives, menstrual cycle becomes more regular, more rarely observed painful menstruation, decreases the intensity and duration of bleeding, thus reducing the risk of iron deficiency anemia. Furthermore, there is evidence of reducing the risk of endometrial cancer and ovarian cancer.

Testimony:

Contraception.

Contraindications:

Janine should not be applied if any of the conditions listed below. If any of these conditions develop for the first time in patients receiving the drug should be immediately repealed:

• Hypersensitivity to any component of the drug Jeanine
  
• thrombosis (venous and arterial) and thromboembolism present or in history (including deep vein thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular accident)
  
• state prior thrombosis (including transient ischemic attack, angina) currently or history
  
• migraine with focal neurological symptoms in the present or in history
  
• diabetes with vascular complications
  
• expressed or multiple venous or arterial thrombosis risk factors, including complicated lesion valvular atrial fibrillation, cerebrovascular disease, or coronary artery
  
• uncontrolled hypertension
  
• major surgery with prolonged immobilization
  
• smoking at the age of 35 years
  
• pancreatitis with severe hypertriglyceridemia now or in history
  
• hepatic failure and severe liver disease (liver function tests before normalization)
  
• liver tumors (benign or malignant) currently or history
  
• hormone-dependent cancers identified (including genital or mammary glands) or are suspected
  
• vaginal bleeding of unknown origin
  
• pregnancy or suspected it
  
• lactation.
  

CAREFULLY

You should carefully weigh the potential risks and expected benefits of the use of combined oral contraceptives in each individual case in the presence of the following diseases / conditions and risk factors:

• risk factors for thrombosis and thromboembolism: smoking obesity (dislipoproteinemia) hypertension migraine valvular disease prolonged immobilization, major surgery, major trauma genetic predisposition to thrombosis (thrombosis, myocardial infarction or cerebrovascular accident at a young age in any of the next of kin )
  
• Other diseases in which may occur peripheral circulatory disorders: diabetes mellitus, systemic lupus erythematosus, hemolytic uremic syndrome, Crohn's disease and ulcerative colitis sickle cell anemia, phlebitis of superficial veins
  
• hereditary angioedema
  
• hypertriglyceridemia
  
• liver disease
  
• the disease first appeared or worsen during pregnancy, or on the background of the previous use of sex hormones (such as jaundice, cholestasis, gallbladder disease, otosclerosis with hearing impairment, porphyria, herpes gestationis, Sydenham's chorea)
  
• postpartum period.
  

Application of pregnancy and breastfeeding:

Janine is not appointed during pregnancy and lactation.

If pregnancy is detected during the reception of Janine drug, it should be immediately abolished. However, extensive epidemiological studies have revealed no increased risk of defects in children born to women treated with hormones before pregnancy, or teratogenic effects when sex hormones were taken inadvertently in early pregnancy.

Admission combined oral contraceptives can reduce 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 derived from milk.

Side effect:

When receiving combined oral contraceptives may experience irregular bleeding (spotting or breakthrough bleeding), especially during the first months of use.

While taking the drug Jeanine observed in women and other undesirable effects listed in the table below. Within each group, selected depending on the frequency of undesirable effects, unwanted effects are shown in decreasing order of severity.

As the incidence of adverse effects is divided into parts (& ge1 / 100 and <1/10), infrequent (& ge1 / 1000 and <1/100) and rare (& ge1 / 10,000 and <1/1000). For additional undesirable effects identified only during postmarketing observations, and for which the frequency of an estimate can not be possible, given "the frequency is unknown."

In women receiving CCP, it reported on the development of the following undesirable effects (see also "Special Instructions" section.)

• Venous thromboembolic complications
  
• Arterial thromboembolic complications
  
• Cerebrovascular complications
  
• hypertension
  
• hypertriglyceridemia
  
• Changes in glucose tolerance or effect on peripheral tissue insulin resistance
  
• Liver tumors (benign or malignant)
  
• Liver dysfunction
  
• chloasma
  
• In women with hereditary angioedema exogenous estrogens may induce an exacerbation of symptoms
  
• The emergence or worsening of conditions for which the relationship with the CCP's certainly not proven: jaundice and / or pruritus related to cholestasis formation of stones in the gallbladder porphyria, systemic lupus erythematosus, hemolytic uremic syndrome, Sydenham's chorea herpes pregnant otosclerosis with hearing impairment, Crohn's disease, ulcerative colitis, cancer of the cervix.
  

In women who use the CCP, there is very little increase in the detection rate of breast cancer. Because breast cancer is rarely occurs in women under 40 years, from considering the overall risk of developing breast cancer, the additional number of cases is very small. The relationship with the CCP is not known. Additional information presented in the "Contraindications" and "Cautions".

Drug Interactions:

The interaction of oral contraceptives with other drugs may lead to breakthrough bleeding and / or reduce the contraceptive reliability. The literature reports the following types of interaction.

Effect on hepatic metabolism: use of drugs that induce hepatic microsomal enzymes which may lead to increased clearance of sex hormones. Such drugs include phenytoin, barbiturates, primidone, carbamazepine, rifampicin and there are suggestions concerning oxcarbazepine, topiramate, felbamate, griseofulvin and preparations containing St. John's wort.

HIV protease (such as ritonavir) and non-nucleoside reverse transcriptase inhibitors (e.g. nevirapine) and combinations thereof may also potentially affect hepatic metabolism.

Effect on the enterohepatic circulation: According to separate studies, some antibiotics (such as penicillins and tetracyclines) may reduce the enterohepatic circulation of estrogen, thereby decreasing the concentration of ethinyl estradiol.

During the designation of any of the above drugs, women should additionally use a barrier method of contraception (eg condom).

Substances that affect the metabolism of combined hormonal contraceptives (enzyme inhibitors). Dienogest is a substrate of cytochrome P450 (CYP) 3A4. Known inhibitors of CYP3A4, such as azole antifungals (e.g. ketoconazole), cimetidine, verapamil, macrolides (e.g. erythromycin), diltiazem, antidepressants and grapefruit juice may increase plasma levels of dienogest.

When taking drugs affecting the microsomal enzymes and for 28 days after their removal should additionally use a barrier method of contraception.

While antibiotics (except rifampicin and griseofulvin) and for 7 days after their removal should additionally use a barrier method of contraception. If the period of use of barrier methods of protection ends later than tablets in a package, you need to move on to the next pack without the usual break in taking pills.

Combination oral contraceptives may affect the metabolism of other drugs, which leads to an increase (e.g. cyclosporin), or reducing (e.g. lamotrigine) concentrations in plasma and tissues.

Dosage and administration:

Inside, a small amount of water every day about the same time of day, in the order indicated on the package. Take 1 tablet a day, continuously for 21 days. Receiving the next pack is started after a 7-day break in taking pills, during which usually occurs withdrawal bleeding. Bleeding usually begins 2-3 days after receiving the last pellet and can not end before receiving a new package.

Admission Jeanine begin:

• Without taking any hormonal contraceptive use in the preceding month. Janine Reception begins on the first day of the menstrual cycle (ie the first day of menstrual bleeding). Shall start receiving the 2-5 th day of the menstrual cycle, but in this case it is recommended to additionally use a barrier method of contraception during the first 7 days of tablet-taking from the first package
  
• The transition to the other combined oral contraceptives (with the vaginal ring, transdermal patch). Preferably start accepting Janine the next day after taking the last active pills from the previous package, but in any case not later than the day after the usual 7-day break (for products containing 21 pills), or after the last inactive pills (for products containing 28 pills in the package). In the transition from a vaginal ring, transdermal patch preferably start taking Jeanine day remove the ring or patch, but not later than the day when it should be inserted a new ring or pasted a new patch
  
• The transition from contraceptives containing only progestin ( "mini-pill", an injectable form, implant) or progestogen-releasing intrauterine device (Mirena). A woman can go to the "mini-pill" on Jeanine any day (without a break), with the implant or intrauterine device with progestin - the date of its removal from the injection mold - the day when the next injection should have to be made. In all cases, you must use an additional barrier method of contraception during the first 7 days of tablet
  
• After the abortion I trimester of pregnancy. The woman may start taking the drug immediately. Subject to this condition the woman does not need extra contraceptive protection
  
• After delivery or abortion in the II trimester of pregnancy. It is recommended to start taking the drug at 21-28 days after delivery or abortion in the II trimester of pregnancy. If the reception is started later, you must use an additional barrier method of contraception during the first 7 days of tablet-taking. If a woman has been sexually active, before you start taking Jeanine pregnancy should be excluded or must wait for the first menstrual period.
  

Admission missed pills. If the delay in receiving the drug was less than 12 hours, contraceptive protection is not reduced. The woman should take pills as soon as possible, should be taken at the usual time.

If the delay in taking pills made more than 12 hours, contraceptive protection may be reduced. It is possible to be guided by the following two basic rules:

• Receiving the drug should never be interrupted for more than 7 days
  
• To achieve adequate suppression of the hypothalamic-pituitary-ovarian regulation required 7 days of continuous reception dragees.
  

If the delay in taking pills made more than 12 hours (interval from the receipt of the last pills for more than 36 h), the following advice can be given.

The first week of taking the drug

The woman should take the last missed pills as soon as possible (even if this means taking two pills at once). Next take the pills at the usual time. In addition to be used a barrier method of contraception (eg a condom) for the next 7 days. If intercourse took place during the week before skipping pills, you need to take into account the chance of pregnancy. The larger and closer missed pills break in the reception of active substance, the greater the chance of pregnancy.

The second week of taking the drug

The woman should take the last missed pills as soon as possible (even if this means taking two pills at once). Next take the pills at the usual time.

Provided that the woman has taken pills correctly in the 7 days preceding the first missed pills, there is no need to use additional contraceptive measures. Otherwise, as well as skipping of two or more must be added dragees barrier methods of contraception (e.g. condom) for 7 days.

The third week of taking the drug

The risk of reduced reliability is imminent because of the forthcoming break in taking pills.

A woman should strictly stick to one of the following options (if the 7 days preceding the first missed pills, all the pills are taken correctly, there is no need to use additional contraceptive methods):

1. The woman should take the last missed pills as soon as possible (even if this means taking two pills at once). Next take the pills at the usual time until the end of the current package of pills. The next pack should be started immediately. Withdrawal bleeding is unlikely until the end of the second pack, but may experience spotting and breakthrough bleeding during the tablet-taking.
   
2. The woman may also interrupt the reception of pills from the current package. Then she should take a break for 7 days, including the day of skipping pills, and then start receiving new packaging.
   

If a woman misses pills, and then during a break in taking pills she had no withdrawal bleeding, pregnancy must be excluded.

Recommendations in case of vomiting and diarrhea

If a woman has had vomiting or diarrhea within up to 4 hours after taking the active pills, absorption may not be complete, and should be additional contraceptive measures are taken. In these cases should be guided by the recommendations in the pass of tablet-taking.

Changing the date of the beginning of the menstrual cycle

In order to delay the onset of menstruation, the woman should continue taking pills from a new package Jeanine immediately after taking all the pills from the previous one, without a break in the reception. Drops of this new packaging may be taken for as long as the woman wants (as long as the packaging is not finished). Against the background of the drug from the second package, women may experience spotting or breakthrough uterine bleeding. Resume Jeanine reception from a new package follows the usual 7-day break.

In order to move the first day of menstruation to another day of the week, the woman should be advised to shorten the next break in taking pills for as many days, as much as she wants. The shorter the interval, the higher the risk that she will not have withdrawal bleeding will continue to spotting and breakthrough bleeding while taking second pack (just as when she wanted to delay the onset of menses).

Additional information for special categories of patients

Children and adolescents. The drug Jeanine shown only after menarche.

Elderly patients. Not applicable. The drug Jeanine not shown after menopause.

Patients with disorders of the liver. Jeanine drug is contraindicated in women with severe liver disease as long as liver function tests have not come back to normal (see. Also "Contraindications").

Patients with disorders of the kidneys. The drug Jeanine not specifically studied in patients with disorders of the kidneys. Available data do not suggest changes in the treatment of such patients.

Overdose:

Symptoms include nausea, vomiting, spotting or metrorrhagia. Serious violations were reported in overdose.

Treatment: symptomatic treatment. No specific antidote.

Special instructions:

If any of the conditions, diseases, and the risk factors listed below are currently available, you should carefully weigh the potential risks and expected benefits of the use of combined oral contraceptives in each individual case and discussed with the woman before she decides to start taking the drug. In the case of aggravation, or amplification of the first manifestations of any of these conditions, diseases or increased risk factors, women should consult their doctor, who can decide whether to cancel the drug.

Diseases of the cardiovascular system

Epidemiological studies indicate a relationship between the use of PDAs and increased incidence of venous and arterial thrombosis and thromboembolism (such as deep vein thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular accident) while taking combined oral contraceptives. These diseases are rare.

The risk of developing venous thromboembolism (VTE) is greatest in the first year of receiving such drugs. The increased risk is present after the initial use of combined oral contraceptives, or the resumption of use of the same or different combined oral contraceptive (after an interval between doses of the drug in 4 weeks or more). These large prospective study with three patients groups show that this increased risk is present preferably within the first 3 months.

The overall risk of VTE in patients receiving low-dose combined oral contraceptives (ethinylestradiol content - <50 micrograms) is 2-3 times higher than in non-pregnant patients who are not taking combined oral contraceptives, however, the risk is lower than that the risk of VTE in pregnancy and childbirth. VTE can be fatal (in 1-2% of cases).

VTE, which manifests itself as a deep vein thrombosis or pulmonary embolism may occur with the use of any combined oral contraceptive.

Very rarely using COCs arises other vascular thrombosis (for example hepatic, mesenteric, renal, and cerebral arteries veins or the retinal vessels). There is no consensus about the connection between the occurrence of these events and the use of combined oral contraceptives available.

Symptoms of deep vein thrombosis (DVT) include: unilateral swelling of the lower limbs or along a vein in the leg, pain or discomfort in the leg in an upright position or walking, the local temperature rise in the affected leg, redness or discoloration of the skin on the foot.

Symptoms of pulmonary embolism (PE) are the following: difficulty breathing or shortness of sudden cough, including Hemoptysis with acute chest pain, which may be aggravated by deep inspiration anxiety severe dizziness fast or irregular heartbeat. Some of these symptoms (such as shortness of breath, cough) are non-specific and can be misinterpreted - as signs of other more or less severe events (eg respiratory tract infection).

Arterial thrombosis can lead to stroke, heart attack or vascular occlusion.