Janine, 0.03 mg+2 mg, film-coated tablets, 21 pcs.
If any of the conditions, diseases and risk factors listed below currently exist, 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. In the event of worsening, intensification or the first manifestation of any of these conditions, diseases or an increase in risk factors, the woman should consult with her doctor, who may decide whether to discontinue the drug.
Diseases of the cardiovascular system
The results of epidemiological studies indicate a relationship between the use of COCs and an increased 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 greatest in the first year of taking such drugs. An increased risk is present after initial use of combined oral contraceptives or resumption of use of the same or different combined oral contraceptives (after a dosing interval of 4 weeks or more). Data from a large prospective study involving 3 groups of patients indicate 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 (ethinyl estradiol content -
VTE, manifested as deep vein thrombosis, or pulmonary embolism can occur with the use of any combined oral contraceptives.
It is extremely rare that when using combined oral contraceptives, thrombosis of other blood vessels (for example, hepatic, mesenteric, renal, cerebral veins and arteries or retinal vessels) occurs. There is no consensus regarding 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 swelling of the lower extremity or along a vein in the leg, pain or discomfort in the leg only when standing up or when walking, localized warmth in the affected leg, redness or discoloration of the skin on the leg.
Symptoms of pulmonary embolism (PE) include: difficulty or rapid breathing; sudden cough, incl. with hemoptysis; sharp pain in the chest, which may intensify with deep inspiration; sense of anxiety; severe dizziness; fast or irregular heartbeat. Some of these symptoms (eg shortness of breath, cough) are non-specific and may be misinterpreted as signs of other more or less severe events (eg respiratory tract infection).
Arterial thromboembolism can lead to stroke, vascular occlusion, or myocardial infarction. Symptoms of a stroke include: sudden weakness or loss of feeling in the face, arm or leg, especially on one side of the body, sudden confusion, problems with speech and comprehension; sudden unilateral or bilateral vision loss; sudden disturbance in gait, dizziness, loss of balance or coordination; sudden, severe or prolonged headache for no apparent reason; loss of consciousness or fainting with or without an epileptic seizure. Other signs of vascular occlusion: sudden pain, swelling and slight blue discoloration of the extremities, acute abdomen.
Symptoms of myocardial infarction include: pain, discomfort, pressure, heaviness, a feeling of squeezing or fullness in the chest, arm, or behind the breastbone; discomfort radiating to the back, cheekbone, larynx, arm, stomach; cold sweat, nausea, vomiting or dizziness, severe weakness, anxiety or shortness of breath; fast or irregular heartbeat. Arterial thromboembolism can be fatal. The risk of developing thrombosis (venous and/or arterial) and thromboembolism increases:
- with age;
- in smokers (with an increase in the number of cigarettes or an increase in age, the risk increases, especially in women over 35 years of age).
In the presence of:
— obesity (body mass index more than 30 kg/m2);
- family history (for example, venous or arterial thromboembolism ever in close relatives or parents at a relatively young age). In the case of a hereditary or acquired predisposition, the woman should be examined by an appropriate specialist to decide on the possibility of taking combined oral contraceptives;
- prolonged immobilization, major surgery, any leg surgery or major 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 resume use for two weeks after the end of immobilization;
- dislipoproteinemia;
- arterial hypertension;
- migraine;
— diseases of the heart valves;
- atrial fibrillation.
The possible role of varicose veins and superficial thrombophlebitis in the development of venous thromboembolism remains controversial.
The increased risk of thromboembolism in the postpartum period should be taken into account.
Poor peripheral circulation may also occur in diabetes mellitus, systemic lupus erythematosus, hemolytic uremic syndrome, chronic inflammatory bowel disease (Crohn's disease or ulcerative colitis) and sickle cell anemia.
An increase in the frequency and severity of migraine during use of combined oral contraceptives (which may precede cerebrovascular events) may be grounds for immediate discontinuation of these drugs.
Biochemical indicators indicating a hereditary or acquired predisposition to venous or arterial thrombosis include the following: resistance to activated protein C, hyperhomocysteinemia, antithrombin III deficiency, protein C deficiency, protein S deficiency, antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant).
When assessing the risk-benefit ratio, it should be taken into account that adequate treatment of the relevant condition may reduce the associated risk of thrombosis. It should also be taken into account that the risk of thrombosis and thromboembolism during pregnancy is higher than when taking low-dose oral contraceptives (ethinyl estradiol content -
Tumors
The most significant risk factor for developing cervical cancer is persistent human papillomavirus infection. There are reports of a slight increase in the risk of developing cervical cancer with long-term use of combined oral contraceptives. However, the connection with the use of combined oral contraceptives has not been proven. Controversy remains regarding the extent to which these findings are related to screening for cervical pathology or to sexual behavior (lower use of barrier methods of contraception).
A meta-analysis of 54 epidemiological studies found 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 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 combined oral contraceptives is small relative to the overall risk of breast cancer. Its connection with the use of combined oral contraceptives has not been proven. The observed increased risk may also be a consequence of earlier diagnosis of breast cancer in women using combined oral contraceptives. Women who have ever used combined oral contraceptives are diagnosed with earlier stages of breast cancer than women who have never used them.
In rare cases, during the use of combined oral contraceptives, the development of liver tumors has been observed, which in some cases led to life-threatening intra-abdominal bleeding. In case of severe abdominal pain, liver enlargement or signs of intra-abdominal bleeding, this should be taken into account when making a differential diagnosis.
Other states
Women with hypertriglyceridemia (or a family history of this condition) may have an increased risk of developing pancreatitis while taking combined oral contraceptives.
Although slight increases in blood pressure 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 blood pressure develops while taking combined oral contraceptives, these drugs should be discontinued and treatment of arterial hypertension should be initiated. 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 while taking combined oral contraceptives, but their association with combined oral contraceptives has not been proven: jaundice and/or pruritus associated with cholestasis; formation of gallstones; porphyria; systemic lupus erythematosus; hemolytic uremic syndrome; chorea; herpes during pregnancy; hearing loss associated with otosclerosis. Cases of Crohn's disease and ulcerative colitis have also been described during the use of 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 discontinuation of combined oral contraceptives until liver function tests return to normal. Recurrent cholestatic jaundice, which develops for the first time during pregnancy or previous use of sex hormones, requires discontinuation of combined oral contraceptives.
Although combined oral contraceptives may have an effect on insulin resistance and glucose tolerance, there is no need to change the therapeutic regimen in diabetic patients using low-dose combined oral contraceptives (ethinyl estradiol content -
Chloasma can sometimes develop, especially in women with a history of pregnancy chloasma. Women prone to chloasma should avoid prolonged sun exposure and exposure to UV radiation while taking combined oral contraceptives.
Preclinical safety data
Preclinical data from routine repeated-dose toxicity, genotoxicity, carcinogenicity and reproductive toxicity studies do not indicate a particular risk to humans. However, it should be remembered that sex steroids can promote the growth of certain hormone-dependent tissues and tumors.
Laboratory tests
Taking combined oral contraceptives may affect the results of some laboratory tests, including liver, kidney, thyroid, adrenal function, plasma transport protein levels, carbohydrate metabolism, coagulation and fibrinolysis parameters. Changes usually do not go beyond normal values.
Reduced efficiency
The effectiveness of combined oral contraceptives may be reduced in the following cases: missed pills, vomiting and diarrhea, or as a result of drug interactions.
Effect on the menstrual cycle
While taking combined oral contraceptives, irregular bleeding (spotting or breakthrough bleeding) may occur, especially during the first months of use. Therefore, any irregular bleeding should be assessed only after an adaptation period of approximately three cycles.
If irregular bleeding recurs or develops after previous regular cycles, careful evaluation should be performed to rule out malignancy or pregnancy.
Some women may not develop withdrawal bleeding during a pill-free break. If combined oral contraceptives are taken as directed, the woman is unlikely to be pregnant. However, if combined oral contraceptives have previously been taken irregularly or there are no two withdrawal bleedings in a row, pregnancy should be excluded before continuing to take the drug.
Medical examinations
Before starting or resuming taking the drug Zhanine ®, it is necessary to familiarize yourself with the woman’s life history, family history, conduct a thorough general medical examination (including measurement of blood pressure, heart rate, determination of body mass index) and gynecological examination, including examination of the mammary glands and cytological examination of scrapings from the cervix (test Papanicolaou test), exclude pregnancy. The scope of additional studies and the frequency of follow-up examinations are determined individually. Typically, follow-up examinations should be carried out at least once a year.
The woman should be warned that drugs such as Janine ® do not protect against HIV infection (AIDS) and other sexually transmitted diseases.
Janine dragee 0.03mg/2mg No. 21x1
Name
Janine tablets 0.03 mg 2 mg in blister pack. in pack No. 21x1
Description
White smooth dragees
Main active ingredient
Ethinyl estradiol + dienogest
Release form
dragee
Dosage
30 mcg+2 mg
Special instructions and precautions
Warnings If any of the following conditions or risk factors are present, it is necessary to discuss with the woman the advisability of using the drug Janine®. If any of the conditions or risk factors listed below worsen or occur for the first time, a woman should definitely consult a doctor. After this, the doctor decides on the need to discontinue the drug Zhanine®. In case of suspected or confirmed VTE or ATE, COC use should be discontinued. If anticoagulant therapy is started, adequate alternative contraception should be provided due to the teratogenic effects of anticoagulants (coumarins). Circulatory disorders Risk of developing venous thromboembolism (VTE) The use of any combined hormonal contraceptives (CHCs) increases the risk of developing venous thromboembolism (VTE) compared to the case of not using this group of drugs. Medicines containing levonorgestrel, norgestimate, or norethisterone are associated with a lower risk of VTE. It is currently unknown how the risk of using the drug Zhanine® compares with the risk of using drugs with a lower risk of VTE. The decision to use any CHC, including those with the lowest risk of VTE, should be made only after discussing with the woman her understanding of the risks of developing VTE associated with taking the drug Zhanine®; factors that increase the risk of developing VTE; and also that the risk of developing VTE is higher during the first year of CHC use. According to some data, the risk of developing VTE also increases after a break between doses of CHCs of 4 weeks or more. In women not taking CHCs and who are not pregnant, the risk of developing VTE is 2 per 10,000 women per year. However, this risk may increase significantly depending on each woman's individual risk factors (see below). Epidemiological studies have shown that the risk of developing VTE in patients taking low-dose combined hormonal contraceptives (
Pharmacological properties
Pharmacodynamics
All hormonal methods of contraception are characterized by low method error if the instructions for medical use are followed. The failure rate increases with improper use (for example, skipping tablets). In clinical studies of the drug Zhanine®, the following Pearl index was established: unadjusted Pearl index: 0.454 (upper 95% confidence interval: 0.701); adjusted Pearl index: 0.182 (upper 95% confidence interval: 0.358). Janine® is a combined oral contraceptive containing ethinyl estradiol and dienogest as a progestogen. The contraceptive effect of the drug Zhanine® is due to various factors, the most important of which are inhibition of ovulation and increased viscosity of cervical mucus. Dienogest is a nortestosterone derivative that has a 10-30 times lower affinity for progesterone receptors in vitro compared to other synthetic progestogens. In vivo animal studies have demonstrated the strong progestogenic and antiandrogenic effects of dienogest. Dienogest does not have significant androgenic, mineralocorticoid or glucocorticoid activity in vivo. The dose of dienogest that inhibits ovulation is 1 mg/day. The risk of developing endometrial and ovarian cancer is reduced when taking high-dose COCs (50 mcg ethinyl estradiol). For COCs with lower ethinyl estradiol content, there is no data to support this pharmacological effect.
Pharmacokinetics
Dienogest Absorption. When taken orally, dienogest is rapidly and completely absorbed, its maximum serum concentration of 51 ng/ml is achieved after approximately 2.5 hours. The absolute bioavailability in combination with ethinyl estradiol is approximately 96%. Distribution. Dienogest binds to serum albumin and does not bind to sex steroid binding globulin (SGBS) and corticoid binding globulin (CBG). About 10% of the total concentration in the blood serum is found in free form; about 90% are not specifically associated with plasma albumin. The induction of SHPS synthesis by ethinyl estradiol does not affect the binding of dienogest to plasma proteins. The volume of distribution of dienogest is about 37-45 liters. Metabolism. Dienogest is metabolized primarily by hydroxylation and conjugation to form predominantly endocrinologically inactive metabolites. These metabolites are rapidly eliminated from the blood plasma, thus the predominant fraction in the blood plasma is unchanged dienogest. Plasma clearance after a single dose is approximately 3.6 l/h. Excretion. The half-life is about 9 hours. A small amount of dienogest in unchanged form is excreted by the kidneys. After taking a dose of 0.1 mg/kg, the ratio of dienogest excretion in the form of metabolites by the kidneys and through the intestines is 3.2. When taken orally, 86% is excreted within 6 days, of which 42% is excreted within the first 24 hours, mainly by the kidneys. Equilibrium concentration. The pharmacokinetics of dienogest is not affected by the level of SHPS in the blood plasma. As a result of daily administration of the drug, the concentration of dienogest in the blood plasma increases by approximately 1.5 times, reaching an equilibrium state after approximately 4 days of administration. Ethinyl estradiol Absorption. After oral administration, ethinyl estradiol is rapidly and completely absorbed. The maximum serum concentration of approximately 67 pg/ml is achieved within 1.5-4 hours. During absorption and first passage through the liver, ethinyl estradiol is metabolized, resulting in its oral bioavailability averaging about 44%. Distribution. Ethinyl estradiol is almost completely (approximately 98%), although nonspecifically, bound by albumin. Ethinyl estradiol induces the synthesis of SHBG. The apparent volume of distribution of ethinyl estradiol is 2.8 - 8.6 l/kg. Metabolism. Ethinyl estradiol undergoes presystemic conjugation, both in the mucosa of the small intestine and in the liver. Ethinyl estradiol is metabolized mainly by aromatic hydroxylation, however, a large number of hydroxylated and methylated metabolites are additionally formed, including both free metabolites and conjugates with glucuronides and sulfates. The main route of metabolism is aromatic hydroxylation. The clearance rate from blood plasma is 2.3 - 7 ml/min/kg. Excretion. The decrease in the concentration of ethinyl estradiol in the blood serum is biphasic; the first phase is characterized by a half-life of about 1 hour, the second - 10-20 hours. It is not excreted from the body unchanged. Metabolites of ethinyl estradiol are excreted in urine and bile in a ratio of 4:6 with a half-life of about 24 hours. Equilibrium concentration. Steady-state concentrations are reached during the second half of the treatment cycle, when plasma concentrations increase approximately twofold compared to the concentration after taking a single dose.
Indications for use
Contraception. The decision to prescribe Janine® should be made taking into account the woman's current individual risk factors, including those associated with the risk of developing venous thromboembolism (VTE). You should also consider how the risk of developing VTE when taking the drug Zhanine® is comparable to the risk of developing VTE when taking other COCs.
Directions for use and doses
The pills should be taken orally in the order indicated on the package, every day at approximately the same time, with a small amount of water. Take one tablet per day continuously for 21 days. The next package begins after a 7-day break from taking the pills, during which withdrawal bleeding usually develops. Bleeding, as a rule, begins 2-3 days after taking the last pill and may not stop until you start taking the pill from a new package. How to start taking Janine® When no hormonal contraceptive has been used in the previous month Start taking Janine® on the first day of the menstrual cycle (ie, the first day of menstrual bleeding). When switching from other combined oral contraceptives (COCs), it is preferable to start taking Zhanine® the day after taking the last active tablet from the package of the previous COC, but in no case later than the next day after the usual break or after taking the last inactive tablet from the package previous COC. When switching from a vaginal ring or contraceptive patch When switching from a vaginal ring or contraceptive patch, it is preferable to start taking Janine® on the day the last ring or patch is removed, but no later than the day when a new ring is to be inserted or a new patch is applied. When switching from contraceptives containing only gestagens (“mini-pills”, injection forms, implant) or from an intrauterine therapeutic system with gestagen release, a woman can switch from a mini-pill to the drug Zhanine® on any day (without a break), from an implant or an intrauterine contraceptive with gestagen - on the day of their removal, from the injection form - on the day when the next injection is due. In all cases, during the first 7 days of use, it is necessary to additionally use a barrier method of contraception. After an abortion in the first trimester of pregnancy, a woman can start taking the medicine immediately. If this condition is met, additional contraceptive measures are not required. • After childbirth or abortion in the second trimester of pregnancy It is recommended to start taking the drug 21-28 days after childbirth or abortion in the second trimester of pregnancy. If use is started later, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the pill. If sexual contact took place before starting to take the drug Zhanine®, you must make sure that there is no pregnancy or you must wait until your first menstruation. Taking missed pills If the delay in taking the medicine is less than 12 hours, contraceptive protection is not reduced. You need to take the missed pill as soon as possible, the next one should be taken at the usual time. If the delay in taking the medicine is more than 12 hours, contraceptive protection may be reduced. In this case, you can be guided by the following two basic rules: Taking the drug should never be interrupted for more than 7 days. 7 days of continuous use of the pills are required to achieve adequate suppression of the hypothalamic-pituitary-ovarian regulation. Accordingly, the following advice can be given if there is a delay in taking the pills was more than 12 hours: First week of taking the medicine It is necessary to take the last missed tablet as soon as possible, as soon as the woman remembers it (even if this means taking two tablets at the same time). The next pill should be taken at the usual time. Over the next 7 days, an additional barrier method of contraception (for example, a condom) must be used. If sexual intercourse took place during the week before missing the pills, the possibility of pregnancy must be taken into account. The more tablets missed, and the closer they are to a break in taking the tablets, the higher the likelihood of pregnancy. Second week of taking the medicine It is necessary to take the last missed pill as soon as possible, as soon as the woman remembers (even if this means taking two pills at the same time). The next pill should be taken at the usual time. Provided that the woman took the pill correctly during the 7 days preceding the first missed pill, there is no need to use additional contraceptive measures. Otherwise, or if you miss two or more pills, you must additionally use barrier methods of contraception (for example, a condom) for the next 7 days. Third week of taking the drug The risk of a decrease in contraceptive reliability is inevitable due to the upcoming break in taking the pill. But by adjusting the dosage regimen, a decrease in contraceptive protection can be avoided. If you adhere to one of the two options below, there will be no need to use additional methods of contraception, provided that during the 7 days preceding the first missed tablet, all tablets were taken correctly. If during the 7 days preceding the first missed pill, pills were taken incorrectly, you must follow the first of the rules described below and additionally use a barrier method of contraception. It is necessary to take the missed pill as soon as possible, as soon as the woman remembers, even if this means taking two pills at the same time. The next pill is taken at the usual time. You should start taking pills from the next package immediately after finishing the current one, i.e. without a break between packs. Withdrawal bleeding is unlikely until the pills from the second package are finished, but spotting and breakthrough bleeding may occur on the days of taking the pills. You can also stop taking the pill from the current package, take a break for 7 days or less, including the day you skipped the pill, and then start taking the pill from a new package. If a woman misses taking a pill and then does not experience withdrawal bleeding during the break in taking it, it is necessary to make sure that there is no pregnancy. Recommendations for gastrointestinal disorders In severe gastrointestinal disorders, absorption may be incomplete, so additional methods of contraception should be used. If vomiting or diarrhea occurs within 3-4 hours after taking the pill, you should take additional pills as soon as possible. If the delay in taking the medicine is more than 12 hours, then you should follow the recommendations for skipping pills (see section “Method of administration and dosage”, subsection “Taking missed pills”). If a woman does not want to change her usual dosing regimen, additional tablets should be taken from a different package. Changing the day of the start of the menstrual cycle In order to delay the onset of menstrual-like bleeding, it is necessary to continue taking the pills from the new package of the drug Zhanine® immediately after all the pills from the previous package have been taken, without interruption in use. Dragees from a new package can be taken for as long as a woman wishes (until the package runs out). While taking the medicine from the second package, a woman may experience spotting or breakthrough uterine bleeding. You should resume taking the drug Zhanine® after the usual 7-day break. In order to move the day of the onset of menstrual-like bleeding to another day of the week, a woman should shorten the next break in taking the pills by as many days as she wants. The shorter the interval, the higher the likelihood that she will not have withdrawal bleeding, and in the future, she will experience spotting and breakthrough bleeding while taking the second package (just as if she would like to delay the onset of menstruation). Use in certain groups of patients Children and adolescents The drug Zhanine® is indicated only after the onset of menarche. Elderly patients Not applicable. The drug Zhanine® is not indicated after menopause. Patients with impaired liver function Zhanine® is contraindicated in women with severe liver disease until liver function tests return to normal (see 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 changes in treatment in these patients.
Use during pregnancy and lactation
Pregnancy The drug Zhanine® is not prescribed during pregnancy. If pregnancy is detected while taking the drug Zhanine®, the drug should be discontinued immediately. However, extensive epidemiological studies have not found an increased risk of developmental defects in children born to women who received COCs before pregnancy, or teratogenicity when COCs were taken inadvertently in early pregnancy. Animal studies have shown undesirable effects of the drug during pregnancy and lactation. The results of animal studies indicate that undesirable effects associated with the hormonal effects of the active compounds cannot be excluded. However, general experience with the use of COCs during pregnancy does not indicate a negative effect on people. When resuming taking the drug Zhanine®, the increased risk of developing VTE in the postpartum period should be taken into account. Breastfeeding Period Taking COCs can reduce the amount of breast milk and change its composition, therefore, their use is contraindicated during lactation. Small amounts of sex steroids and/or their metabolites may be excreted in milk. These amounts may affect the child's health. Therefore, the drug Zhanine® should not be used until breastfeeding is stopped.
Interaction with other drugs
Information on medications used concomitantly should be reviewed to identify potential interactions. The influence of other drugs on the drug Zhanine® Possible interaction with drugs that induce microsomal enzymes, as a result of which the clearance of sex hormones may increase, which, in turn, can lead to breakthrough uterine bleeding and/or a decrease in the contraceptive effect. Enzyme induction is observed within a few days after the start of administration. Maximum enzyme induction is usually observed within a few weeks. After stopping the drug, it can be maintained for at least another 4 weeks. Women who are treated with such drugs in addition to Janine® are advised to use a barrier method of contraception or choose another non-hormonal method of contraception. A barrier method of contraception should be used during the entire period of taking concomitant medications, as well as for 28 days after their discontinuation. If the period of use of the barrier method of contraception ends later than the pills in the package of the drug Zhanine®, you should start taking the pills from the new package of the medicine Zhanine® without interruption in taking the pills. If long-term use of drugs that induce microsomal enzymes is necessary, it is recommended to use another reliable non-hormonal method of contraception. Substances that increase the clearance of COCs (weakening the effectiveness of COCs by enzyme induction): Barbiturates, carbamazepine, finytoin, primidone, rifampicin and possibly also oxcarbazepine, topiramate, felbamate, griseofulvin, as well as medicines containing St. John's wort. Substances with varying effects on the clearance of COCs When used concomitantly with COCs, many HIV or hepatitis C virus protease inhibitors and non-nucleoside reverse transcriptase inhibitors can either increase or decrease plasma concentrations of estrogens or progestins. In some cases, this effect may be clinically significant. Therefore, before using HIV or hepatitis C virus protease inhibitors and non-nucleoside reverse transcriptase inhibitors, the nature of their possible interaction with the drug Zhanine® should first be studied, and in case of any doubt, the woman should be advised to additionally use barrier methods of contraception. Substances that reduce the clearance of COCs (enzyme inhibitors) The clinical significance of potential interactions with enzyme inhibitors is unknown. Concomitant use of strong and moderate CYP3A4 inhibitors may result in increased plasma concentrations of estrogen or progestin, or both. Etoricoxib at doses of 60 and 120 mg/day, when coadministered with COCs containing 0.035 mg ethinyl estradiol, has been shown to increase plasma ethinyl estradiol concentrations by 1.4 and 1.6 times, respectively. Effect of the drug Zhanine® on other drugs COCs can affect the metabolism of other drugs, leading to an increase (for example, cyclosporine) or a decrease (for example, lamotrigine) in their concentrations in blood plasma and tissues. Based on data from in vitro studies, inhibition of SUR enzymes by dienogest at a therapeutic dose is unlikely. In clinical studies, administration of a hormonal contraceptive containing ethinyl estradiol resulted in mild (eg, theophylline) to moderate (eg, tizanidine) increases in concentrations of CYP1A2 substrates. Pharmacodynamic Interactions Coadministration of ethinyl estradiol-containing medicinal products with direct-acting antiviral medicinal products containing ombitasvir, paritaprevir or dasabuvir, as well as their combinations, is associated with a more than 20-fold increase in ALT levels compared with the upper limit of normal in healthy female subjects and in female subjects. infected with the hepatitis C virus (see section “Contraindications”). Other types of interactions Laboratory tests Taking COCs may affect the results of some laboratory tests, including liver, kidney, thyroid, adrenal function, plasma transport protein concentrations, carbohydrate metabolism, blood coagulation and fibrinolysis parameters. Changes usually do not go beyond normal values.
Contraindications
Combined hormonal contraceptives (CHCs) should not be used if any of the conditions listed below are present. If any of these conditions develop for the first time while taking a CHC, the drug should be discontinued immediately. Presence or risk of developing venous thromboembolism (VTE) Venous thromboembolism - current VTE (taking anticoagulants) or a history (including deep vein thrombosis (DVT) or pulmonary embolism (PE) Identified hereditary or acquired predisposition to venous thromboembolism, such as activated protein C resistance (including factor V Leiden), antithrombin III deficiency, protein C deficiency, protein S deficiency Major surgery with prolonged immobilization (see section "Special Instructions and Precautions") High risk of venous thromboembolism due to the presence of multiple risk factors (see section “Special
