Composition, form of production and packaging
Tablets covered with a film shell of light yellow color, on the one hand, engraving in the form of letters "DO" in a hexagon.
ethinylestradiol 30 Ојg
drospirenone 3 mg
Excipients: lactose monohydrate - 48.17 mg, corn starch - 14.4 mg, corn pregelatinized corn starch - 9.6 mg, povidone K25 - 4 mg, magnesium stearate - 800 Ојg.
The composition of the membrane: hypromellose (hydroxypropylmethylcellulose) is 1.0112 mg, macrogol 6000 202.4 Ојg, talc (magnesium hydrosilicate) 202.4 Ојg, titanium dioxide (E171) 556.5 Ојg, iron (II) oxide (E172) 27.5 Ојg.
21 pcs. - blisters (1) - packs of cardboard.
21 pcs. - blisters (3) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2016.
Low-dose monophasic oral combined estrogen-gestagen contraceptive drug.
The contraceptive effect of the drug Yarin В® is carried out through complementary mechanisms, the most important of which are suppression of ovulation and increased viscosity of cervical mucus.
The incidence of venous thromboembolism (VTE) in women with or without VTE risk factors using ethinylestradiol / drospirenone-containing oral contraceptives at a dose of 0.03 mg / 3 mg is the same as in women,
using levonorgestrel-containing combined oral contraceptives or other combined oral contraceptives. This was confirmed in a prospective controlled database study comparing women who used oral contraceptives at 0.03 mg ethinylestradiol / 3 mg drospirenone with women using other combined oral contraceptives. Analysis of the data revealed the same risk of occurrence of VTE among the sample.
In women taking combined oral contraceptives, the menstrual cycle becomes more regular, less painful menstrual bleeding is observed, the intensity of bleeding decreases, and the risk of iron deficiency anemia is reduced. In addition, there is evidence that the risk of developing endometrial cancer and ovarian cancer is reduced.
Drospirenone, contained in the drug Yarin В® , has an antimineralocorticoid action and is able to prevent weight gain and other symptoms (eg, swelling) associated with the hormone-induced fluid retention. Drospirenone also has anti-androgenic activity and reduces the symptoms of acne (acne), oiliness of the skin and hair. This action of drospirenone is similar to the action of natural progesterone, produced by the female body. This should be taken into account when choosing a contraceptive, especially for women with hormone-dependent fluid retention, as well as for women with acne and seborrhea.
When used correctly, Perl's index (the indicator reflecting the number of pregnancies in 100 women who use the contraceptive during the year) is less than 1. When missing tablets or improperly used, the Pearl index may increase.
After intake drospirenone quickly and almost completely absorbed from the digestive tract. After a single dose of C max, drospirenone in plasma is achieved after 1-2 hours and is 37 ng / ml. Bioavailability ranges from 76% to 85%. Eating does not affect bioavailability.
The concentration of drospirenone in the blood plasma is reduced biphasic.
Drospirenone binds to plasma albumin (0.5-0.7%) and does not bind to sex hormone binding globulin (SHBG) or corticosteroid-binding globulin (CSG). In the free form is only 3-5% of the total concentration in the blood serum. The increase in SHBG induced by ethinyl estradiol does not affect the binding of drospirenone to plasma proteins.
During the cyclic treatment, C ss max, drospirenone in plasma is reached in the second half of the cycle.
A further increase in the concentration of drospirenone in the plasma is observed after approximately 1-6 cycles of the drug intake, subsequent increase in the concentration is not observed.
After ingestion, drospirenone is completely metabolized. Most metabolites in the plasma are acidic forms of drospirenone, which are formed without the participation of isoenzymes of the cytochrome P450 system.
It is excreted as metabolites by the kidneys and through the intestine in a ratio of approximately 1.2-1.4. T 1/2 of metabolites is approximately 40 h.
Pharmacokinetics in specific patient groups
In women with moderate impaired hepatic function (class B on the Child-Pugh scale), the AUC is comparable to that in healthy women with similar C max values вЂ‹вЂ‹in the absorption and distribution phases. T 1/2 of drospirenone in patients with moderate impairment of liver function was 1.8 times higher than in healthy volunteers with preserved liver function. Patients with moderate impairment of liver function showed a decrease in clearance of drospirenone by 50% compared to women with preserved liver function, while there was no difference in the potassium concentration in the blood plasma in the studied groups. In the detection of diabetes mellitus and concomitant use of spironolactone (both conditions are regarded as factors predisposing to the development of hyperkalemia), an increase in the concentration of potassium in the blood plasma is not established. It should be concluded that tolerability of drospirenone in women with mild and moderate impairment of liver function is good (class B on the Child-Pugh scale).
The concentration of drospirenone in blood plasma upon reaching the equilibrium state was comparable in women with mild renal dysfunction (KK 50-80 ml / min) and in women with a preserved kidney function (KC more than 80 ml / min). Nevertheless, in women with moderate renal dysfunction (CK 30-50 ml / min), the average concentration of drospirenone in the blood plasma was 37% higher than in patients with preserved kidney function. Drospirenone was well tolerated by all groups of patients. There was no change in the concentration of potassium in blood plasma with drospirenone.
After taking the drug inside, ethinyl estradiol is quickly and completely absorbed from the digestive tract.
C max in plasma is achieved in 1-2 hours and is 54-100 pg / ml. Ethinyl estradiol undergoes the "first pass" effect through the liver, as a result of which its bioavailability when ingested is an average of 45%.
Ethinyl estradiol is almost completely (approximately 98%), although non-specific, binds to albumin.
Ethinyl estradiol induces synthesis of SHBG.
Reducing the concentration of ethinyl estradiol in blood plasma is biphasic.
C ss is established during the second half of the first cycle of drug administration.
Ethinyl estradiol undergoes presystemic conjugation in the mucosa of the small intestine and in the liver. The main pathway of metabolism is aromatic hydroxylation.
Ethinyl estradiol is excreted as metabolites by the kidneys and through the intestine in a ratio of approximately 4: 6. T 1/2 metabolites about 24 h.
Tablets should be taken orally in the order given on the package, every day at about the same time, with a small amount of water. Take 1 tablet / day continuously for 21 days. Receiving tablets from the next package begins after a 7-day break, during which menstrual-like bleeding usually develops (bleeding cancellation). As a rule, it begins on the 2-3 day after the last pill and may not end before taking the tablets from the new package.
The beginning of Yarin В®
In the absence of taking any hormonal contraceptives in the previous month , the drug Yarin В® begins on the 1st day of the menstrual cycle (ie, on the 1st day of menstrual bleeding). It is allowed to start taking the menstrual cycle on the 2nd-5th day, but in this case it is recommended to use the barrier method of contraception during the first 7 days of taking the tablets from the first package.
When switching from other combined oral contraceptives, vaginal rings or contraceptive patches, it is preferable to start taking YarinВ® on the day after taking the last active tablet from the previous package, but in no case later than the next day after the usual 7-day break , containing 21 tablets) or after taking the last inactive tablet (for preparations containing 28 tablets per package). The preparation of Yarin В® should be started on the day of removal of the vaginal ring or patch, but no later than the day when a new ring is to be inserted or a new patch is stuck.
When switching from contraceptives containing only gestagens ("mini-pili", injectable forms, implant), or with the progestogen-releasing progestogen (MirenaВ®). You can go from the "mini-drink" to the drug Yarin В® any day (without interruption), from the implant or intrauterine contraceptive with gestagen - on the day of its removal, from the injection form - from the day the next injection is to be made. In all cases, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the tablets.
After abortion in the first trimester of pregnancy. You can start taking the drug immediately - on the day of abortion. If this condition is met, the woman does not need additional contraception.
After childbirth or abortion in the second trimester of pregnancy. You should start taking the drug no earlier than 21-28 days after giving birth (if there is no breastfeeding) 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 tablets. However, if a woman already had a sex life, pregnancy should be excluded before starting the drug Yarin В® or it is necessary to wait for the first menstruation.
Acceptance of missed tablets
If the delay in taking the drug is less than 12 hours , the contraceptive protection is not reduced. A woman should take the pill as soon as possible, the next pill is taken at the usual time.
If the delay in taking the drug is more than 12 hours , contraceptive protection is reduced. The more pills are missed, and the closer the pass to the 7-day break in taking pills, the greater the likelihood of pregnancy.
In this case, you can follow the following two basic rules:
1. The drug should never be interrupted for more than 7 days.
2. 7 days of continuous intake of tablets are required to achieve adequate suppression of hypothalamic-pituitary-ovarian regulation.
Accordingly, the following tips can be given if the delay in taking the tablets is greater than 12 hours (the interval from the time the last tablet is taken is more than 36 hours).
The first week of taking the drug
It is necessary to take the last missed pill as soon as possible, as soon as a woman remembers it (even if you need to take two tablets at the same time). The next tablet is taken at the usual time. In addition, a barrier method of contraception (for example, a condom) should be used for the next 7 days. If sexual intercourse took place within a week before passing the pill, it is necessary to consider the likelihood of pregnancy.
The second week of taking the drug
It is necessary to take the last missed pill as soon as possible, as soon as a woman remembers it (even if you need to take two tablets at the same time). The next tablet is taken at the usual time. Provided that the woman took the pill correctly for 7 days preceding the first missed pill, there is no need to use additional contraceptive measures. Otherwise, as well as when two or more tablets are missed, barrier methods of contraception (for example, a condom) should be used additionally within 7 days.
The third week of taking the drug
The risk of pregnancy is increased because of the upcoming pause in taking pills. A woman should strictly adhere to one of the following two options. If, during the 7 days preceding the first missed tablet, all the pills were taken correctly, there is no need to use additional contraceptive methods.
1. It is necessary to take the last missed pill as soon as possible, as soon as a woman remembers it (even if you need to take two tablets at the same time). The following tablets are taken at the usual time, until the tablets from the current package run out. The next package should be started immediately without interruption.Bleeding cancellation is unlikely until the second package is finished, but there may be spotting and breakthrough bleeding during taking the tablets.
2. You can interrupt the reception of tablets from the current package, thus starting a 7-day break (including the day of skipping the tablets), and then start taking the tablets from the new package.
If the woman missed taking the pills, and then during a break in admission she does not have a withdrawal bleeding, it is necessary to exclude pregnancy.
Recommendations in case of vomiting and diarrhea
In the case of vomiting or diarrhea for up to 4 hours after taking the pill, absorption may not be complete and additional measures to protect against unwanted pregnancy should be taken. In such cases, you should focus on the above recommendations when skipping tablets.
Changing the day of the beginning of the menstrual cycle
In order to postpone the onset of menstrual bleeding, it is necessary to continue taking the tablets from a new package of Yarin В® without a 7-day break. Tablets from a new package can be taken for as long as necessary, including until the tablets from the package is finished. Against the background of taking the drug from the second package, it is possible to smear bloody discharge from the vagina or breakthrough uterine bleeding. Resume the reception of the drug Yarin В® from the next package follows the usual 7-day break. In order to transfer the day of the onset of menstrual bleeding to another day of the week, the woman should shorten the nearest break in taking the pills for as many days as she wants. The shorter the interval, the higher the risk that it will not have withdrawal bleeding, and later there will be spotting and breakthrough bleeding at the time of taking the second package (as well as in case she would like to delay the onset of menstrual bleeding).
Additional information for specific patient categories
Children and adolescents drug Yarina В® is shown only after the onset of menarche. The available data do not suggest correction of the dose in this group of patients.
After the onset of menopause , YarinВ® is not shown.
The drug Yarin В® is contraindicated in women with severe liver disease until the liver function is normalized.
The drug Yarin В® is contraindicated in women with severe renal insufficiency or with acute renal failure.
The most frequent adverse reactions to Yarin В® include nausea and pain in the mammary glands. They were found in more than 6% of women who use this drug.
Severe adverse reactions are arterial and venous thromboembolism.
The frequency of adverse reactions reported in the course of clinical trials of Yarin В® (n = 4897) is given in the table below. Within the limits of each group, isolated depending on the incidence, undesirable reactions are presented in order of decreasing severity. In frequency, they are divided as follows: often (? 1/100 and <1/10), infrequently (? 1/1000 and <1/100), rarely (? 1/10 000 and <1/1000). For additional unwanted reactions, revealed only in the postmarketing research process, and for which it was not possible to estimate the frequency of occurrence, "frequency is unknown" is indicated.
Mental disorders: often - mood swings, depression / depressed mood, decreased or loss of libido.
From the nervous system: often - a migraine.
From the cardiovascular system: rarely - venous or arterial thromboembolism *.
From the side of the digestive system: often - nausea.
From the skin and subcutaneous tissues: the frequency is unknown - erythema multiforme.
From the reproductive system and breast: often - pain in the mammary glands, irregular uterine bleeding, bleeding from the genital tract, unspecified genesis.
Adverse events in clinical trials have been codified using the MedDRA dictionary (Medical Dictionary of Regulatory Activity, version 12.1). The various MedDRA terms reflecting the same symptom were grouped together and presented as the only side reaction, in order to avoid weakening or blurring the true effect.
* - Estimated frequency based on the results of epidemiological studies covering the group of combined oral contraceptives. The frequency bordered on very rare."Venous or arterial thromboembolism" includes the following nosological units: peripheral deep vein occlusion, thrombosis and pulmonary embolism / occlusion, thrombosis, embolism and myocardial infarction / cerebral infarction and stroke not defined as hemorrhagic.
Listed below are the side reactions with very rare incidence or delayed symptoms, which are believed to be associated with drug administration group of combined oral contraceptives.
- frequency of diagnosis of breast cancer in women taking combined oral contraceptives slightly increased. Due to the fact that breast cancer is rare in women under the age of 40 years, an increase in the number of breast cancer diagnoses in women taking combined oral contraceptives it is insignificant in relation to the total risk of the disease;
- liver tumors (benign and malignant).
- erythema nodosum;
- Women with hypertriglyceridemia (increased risk of pancreatitis when using combined oral contraceptives);
- increase in blood pressure;
- condition developing or worsening while taking combined oral contraceptives, but their connection with the administration of the drug is not proven (jaundice and / or itching associated with cholestasis, formation of gallstones; porphyria; SLE; hemolytic-uremic syndrome, chorea Sydenham; herpes gestationis; hearing loss associated with otosclerosis);
- in women with hereditary angioedema estrogen may cause or exacerbate symptoms;
- violations of the liver function;
- impaired glucose tolerance or effect on insulin resistance;
- Crohn's disease, ulcerative colitis;
- hypersensitivity (including symptoms such as rash, urticaria).
Interaction oral contraceptives with other drugs (microsomal liver enzyme inducers, some antibiotics) may lead to breakthrough bleeding and / or reducing contraceptive efficacy.
- thrombosis (venous and arterial) currently or history (including deep vein thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular disorders);
- state prior thrombosis (including transient cerebral circulatory disorders, angina) currently or history;
- Migraine with focal neurological symptoms in the present or in history;
- diabetes mellitus with vascular complications;
- multiple or severe venous or arterial thrombosis risk factors (including complicated lesions valvular atrial fibrillation, cerebrovascular disease or coronary arteries, uncontrolled hypertension, major surgery with prolonged immobilization, smoking at the age of 35 years );
- pancreatitis with severe hypertriglyceridemia at present or in history;
- hepatic failure, and severe liver diseases (liver samples before normalization);
- liver tumors (benign or malignant) now or in the anamnesis;
- severe and / or acute renal failure;
- identified hormone malignant diseases (including genital or mammary glands) or suspicion of them;
- vaginal bleeding of unknown origin;
- pregnancy or suspected it;
- lactation (breastfeeding);
- Hypersensitivity to the components of the drug.
If any of the above diseases or conditions develop for the first time while taking the drug, it should be lifted immediately.
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:
- thrombosis risk factors for thromboembolism (smoking, obesity, dislipoproteinemia, hypertension, migraine, valvular disease, long-term immobilization, major surgery, major trauma, genetic predisposition to thrombosis / thrombosis, myocardial infarction, or violation of mo zgovogo circulation at a young age, someone from the next of kin /);
- other diseases, which may occur when the peripheral circulatory disorders (diabetes, SLE, hemolytic uremic syndrome, Crohn's disease, ulcerative colitis, sickle cell anemia, phlebitis superficial veins);
- hereditary angioedema;
- liver disease;
- diseases caused or aggravated by the first time during pregnancy, or on the background of the previous use of sex hormones (eg, jaundice, cholestasis, gallbladder disease, otosclerosis with hearing impairment, porphyria, herpes gestationis, Sydenham's chorea);
- postpartum period.
PREGNANCY AND LACTATION
The drug is not appointed during pregnancy and lactation.
If a pregnancy is detected during use of the drug Yaryna В® , the drug should be immediately canceled. 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.
At the same time, data on the results of receiving the drug Yasmin В® during pregnancy are limited, that does not allow any conclusions about the negative effects of the drug on pregnancy, health of the newborn and the fetus. Currently, any significant epidemiological data are not available.
Admission combined oral contraceptives can reduce the amount of breast milk and change its composition, so their use is not recommended until weaning. A small amount of sex steroids and / or their metabolites may be derived from milk.
APPLICATION FOR FUNCTIONS OF THE LIVER
Contraindicated in acute renal failure and severe renal insufficiency.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Not use this drug in the presence of a current or history of severe liver disease (as long as the indicators are not normalized liver samples), available currently or a history of benign or malignant liver tumors.
With caution should prescribe the drug for liver disease.
APPLICATION FOR CHILDREN
Children and adolescents preparation Yaryna В® shown only after menarche. Available data do not require dose adjustment in these patients.
APPLICATION IN ELDERLY PATIENTS
After menopause drug Yaryna В® not shown.
or before the resumption of the drug Yasmin В® should be familiar with the history of life, a family history of a woman, a thorough general medical and gynecological examination to exclude pregnancy. The volume of research and the frequency of control examinations should be based on existing standards of medical practice when the need to consider the individual characteristics of each patient. Typically, the measured blood pressure, heart rate, BMI determined, checked the condition of breast, abdomen and pelvic organs, including cytology cervical epithelium (Papanicolaou test). Typically, control studies should be carried out at least 1 time in 6 months.
Woman should notify that hormonal contraceptives do not protect against HIV infection (AIDS) and other diseases, sexually transmitted diseases.
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 Yasmin drug В® in each individual case and discuss it with the woman before she decides to start receiving the drug. With weighting, amplification or at the first sign of risk factors may require removal of the drug.
Diseases of the cardiovascular system
Epidemiological studies indicate a relationship between the use of combined oral contraceptives and increased incidence of venous and arterial thrombosis and thromboembolic events such as deep vein thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular disease) when receiving combined oral contraceptives. These diseases are rare.
The risk of developing venous thromboembolism (VTE) is greatest in the first year of taking these drugs. The increased risk is present after initial use of combined oral contraceptives or resume use of the same or different combined oral contraceptives (after the interval between doses of the drug in 4 weeks or more). Data from a large prospective study involving 3 groups of patients suggest that this increased risk is present mainly in the first 3 months.
The overall risk of VTE in patients receiving low-dose combined oral contraceptives (<50 micrograms ethinyl estradiol) are 2-3 times higher than in non-pregnant patients who are not taking combined oral contraceptives, however, the risk is lower than the risk of VTE during pregnancy and childbirth.
VTE may be life threatening or fatal (in 1-2% of cases).
VTE, manifested as deep vein thrombosis or pulmonary embolism may occur when using any combined oral contraceptives.
Very rarely the application of combined oral contraceptives thrombosis occurs in other blood vessels, for example, hepatic, mesenteric, renal, and cerebral arteries veins or the retinal vessels. 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 lower extremity edema unilateral or along veins in the leg, pain or discomfort in the foot only in a vertical position or during walking, the local temperature rise in the affected leg, redness or discoloration of the skin on the foot.
Symptoms of pulmonary embolism (PE) are as follows: difficulty or tachypnea; sudden cough, including hemoptysis; sharp chest pain, which may be aggravated by deep inspiration; sense of anxiety; severe dizziness; fast or irregular heartbeat. Some of these symptoms (eg, dyspnea, coughing) are nonspecific and may be incorrectly interpreted as signs of other more or less severe events (e.g., respiratory infection).
Arterial thrombosis may lead to stroke, vascular occlusion or myocardial infarction. The symptoms of a stroke: sudden weakness or loss of sensitivity of the face, arm or leg, especially on one side of the body, sudden confusion, trouble speaking and understanding; single- or double-sided sudden vision loss; sudden gait disturbance, dizziness, loss of balance or coordination; sudden, severe or prolonged headache with no apparent cause; loss of consciousness or fainting with or without epileptic seizure him. Other signs of vascular occlusion: sudden pain, swelling and slight bluish limbs symptom "acute abdomen".
Symptoms of heart attack include: pain, discomfort, pressure, heaviness, or constriction of fullness in the chest, arm or behind the breastbone; discomfort radiating to the back, cheeks, throat, arm, stomach; cold sweat, nausea, vomiting or dizziness, severe weakness, anxiety or shortness of breath; fast or irregular heartbeat.
Arterial thrombosis can be life-threatening or fatal.
The risk of thrombosis (venous and / or arterial) and thromboembolism is increased:
- smokers (with an increase in the number of cigarettes and increasing age the risk increases, especially in women over 35 years old);
- obesity (BMI over 30 kg / m 2 );
- if there is a family history of instructions (eg, venous or arterial thromboembolism ever in close relatives or parents at a relatively young age). In the case of hereditary or acquired predisposition, the woman should be assessed and the appropriate specialist to address the issue of the possibility of using combined oral contraceptives;
- with prolonged immobilization, major surgery, any surgery to the legs, or major trauma. In these situations, it is desirable to terminate the application of the drug (in the case of planned operation, at least 4 weeks prior to it) and not to resume reception within 2 weeks after immobilization;
- when dislipoproteinemia;
- arterial hypertension;
- in diseases of the heart valves;
- atrial fibrillation.
The possible role of varicose veins and superficial thrombophlebitis in venous thromboembolism is controversial.
It should take into account the increased risk of thromboembolism during the postpartum period.
Peripheral circulatory disorders as may occur in diabetes mellitus, systemic lupus erythematosus, hemolytic-uremic syndrome, chronic inflammatory bowel diseases (Crohn's disease or ulcerative colitis) and sickle cell anemia.
The increase in frequency and severity of migraine during use of combined oral contraceptives (which may be preceded by cerebrovascular disorders) can be grounds for immediate discontinuation of these drugs.
By biochemical parameters indicating the inherited or acquired predisposition to venous or arterial thrombosis include: resistance to activated protein C, hyperhomocysteinemia, lack of antithrombin III, protein C deficiency, protein deficit S, antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant).
In assessing the risks and benefits should be taken into account that adequate treatment of the relevant condition may reduce the associated risk of thrombosis. It should also be borne in mind that the risk of thrombosis and thromboembolism in pregnancy is higher than when taking low-dose oral contraceptives (<50 micrograms ethinyl estradiol).
The most significant risk factor for cervical cancer is persistent HPV infection. There are reports of some increase in the risk of cervical cancer in long-term use of combined oral contraceptives. However, communication with the reception of combined oral contraceptives has not been proved. The possibility of the relationship of these data with screening cervical disease or features of sexual behavior (less frequent use of barrier methods of contraception).
A meta-analysis of 54 epidemiological studies showed that there is a slightly increased relative risk of breast cancer diagnosed in women taking combined oral contraceptives currently (relative risk 1.24). The increased risk disappears gradually within 10 years after discontinuation of these drugs. Due to the fact that breast cancer is rare in women under 40 years, an increase in the number of breast cancer diagnoses in women taking combined oral contraceptives are currently taking or have recently, it is insignificant in relation to the total risk of the disease. The relationship between the development of breast and receiving combined oral contraceptives cancer has not been proved. obs