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Active ingredients
Drospirenone + Ethinyl Estradiol
Release form
Pills
Composition
In 1 tablet: ethinyl estradiol 30 mcg; drospirenone 3 mg. Adjuvants: lactose monohydrate - 48.17 mg, corn starch - 14.4 mg, pregelatinized corn starch - 9.6 mg, povidone K25 - 4 mg, magnesium stearate - 800 μg.
Pharmacological effect
Low-dose monophasic oral combined estrogen-progestin contraceptive drug. Contraceptive effect of the drug Yarin; performed through complementary mechanisms, the most important of which include suppressing ovulation and increasing the viscosity of cervical mucus. Frequency of onset of venous thromboembolism (VTE) in women, with or without risk factors of VTE, using ethinyl estradiol / drospirenone-containing oral contraceptives in a dose of 0.03 mg / 3 mg, 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 that compared women using oral contraceptives at a dose of 0.03 mg ethinyl estradiol / 3 mg drospirenone with women using other combined oral contraceptives. Data analysis revealed the same risk of VTE among the sample. In women taking combined oral contraceptives, the menstrual cycle becomes more regular, painful menstrual-like bleeding is less common, and the bleeding rate decreases, resulting in a reduced risk of iron deficiency anemia. In addition, there is evidence that the risk of endometrial cancer and ovarian cancer is reduced. Drospirenone contained in the Yarin preparation has anti-mineralocorticoid action and can prevent weight gain and other symptoms (eg, edema) associated with hormone-induced retention. fluid. Drospirenone also has antiandrogenic activity and helps to reduce the symptoms of acne (acne), oily 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 (acne) and seborrhea. When correctly used, the Pearl index (an indicator reflecting the number of pregnancies in 100 women using a contraceptive during the year) is less than 1 If you skip pills or misuse, the Pearl Index may increase.
Pharmacokinetics
Drospirenone. Absorption: After oral administration, drospirenone is rapidly and almost completely absorbed from the gastrointestinal tract. After a single dose of the drug Cmax of drospirenone in plasma is achieved in 1-2 hours and is 37 ng / ml. Bioavailability ranges from 76% to 85%. Food intake does not affect bioavailability. Distribution: The concentration of drospirenone in plasma decreases in two phases. Drospirenone binds to plasma albumin (0.5-0.7%) and does not bind to sex hormone-binding globulin (GSPH) or corticosteroid-binding globulin (CRH). In the free form is only 3-5% of the total concentration in the serum. An ethinyl estradiol-induced increase in SHBG does not affect the binding of drospirenone to plasma proteins. During cycle treatment, Cssmax of drospirenone in plasma is reached in the second half of the cycle. A further increase in the concentration of drospirenone in plasma occurs after approximately 1-6 cycles of the drug, there is no subsequent increase in concentration. Metabolism : After oral administration, drospirenone is completely metabolized. Most plasma metabolites are represented by the acidic forms of drospirenone, which are formed without the participation of cytochrome P450 isoenzymes. Excretion: It is excreted as metabolites by the kidneys and through the intestine in a ratio of about 1.2-1.4. T1 / 2 metabolites is approximately 40 hours. Pharmacokinetics in special groups of patients. Women with moderate hepatic impairment (Child-Pugh class B) AUC is comparable to the corresponding indicator in healthy women with similar Cmax values in the absorption and distribution phases. T1 / 2 of drospirenone in patients with moderate liver dysfunction was 1.8 times higher than in healthy volunteers with intact liver function. In patients with moderately impaired liver function, there was a decrease in the clearance of drospirenone by 50% compared with women with intact liver function, and there were no differences in the concentration of potassium in the blood plasma in the studied groups.When diabetes mellitus is detected and the concomitant use of spironolactone (both states are regarded as factors predisposing to the development of hyperkalemia), an increase in the concentration of potassium in the blood plasma has not been established. It should be concluded that the tolerability of drospirenone in women with mild and moderate liver dysfunction is good (class B on the Child-Pugh scale). The concentration of drospirenone in blood plasma when reaching an equilibrium state was comparable in women with mild renal impairment (CC 50-80 ml / min) and in women with intact kidney function (CC more than 80 ml / min). However, in women with moderate renal dysfunction (CC 30-50 ml / min), the average concentration of drospirenone in the blood plasma was 37% higher than in patients with preserved renal function. Drospirenone was well tolerated by all groups of patients. Changes in the concentration of potassium in the blood plasma are not observed when using drospirenone. Ethinyl estradiol Absorption: After taking the drug inside the ethinyl estradiol is quickly and completely absorbed from the gastrointestinal tract. Cmax in plasma is reached in 1-2 hours and is 54-100 pg / ml. Ethinyl estradiol undergoes a first-pass effect through the liver, resulting in an average of 45% of its bioavailability by ingestion. Distribution: Ethinyl estradiol is almost completely (approximately 98%), although not specifically, bound to albumin. Ethinyl estradiol induces HGHG synthesis. Decrease in ethinyl estradiol concentration blood plasma is biphasic. Css is established during the second half of the first cycle of the drug. Metabolism: Ethinyl estradiol undergoes systemic conjugation in mucous membrane of the small intestine and in the liver. The main metabolic pathway is aromatic hydroxylation. Excretion: Ethinyl estradiol is excreted in the form of metabolites by the kidneys and through the intestines in a ratio of about 4: 6. T1 / 2 of metabolites is about 24 hours.
Indications
Contraception.
Contraindications
Thrombosis (venous and arterial) at present or in history (including deep vein thrombosis, pulmonary artery thromboembolism, myocardial infarction, cerebrovascular disorders) - conditions preceding thrombosis (including transient cerebral circulation, angina pectoris ) at present or in history; - migraine with focal neurological symptoms at present or in history; - diabetes with vascular complications; - multiple or severe risk factors for venous or arterial thrombosis (includingcomplicated lesions of the valvular apparatus of the heart, atrial fibrillation, diseases of cerebral vessels or coronary arteries; uncontrolled arterial hypertension, serious surgical intervention with prolonged immobilization, smoking over the age of 35 years; - pancreatitis with severe hypertriglyceridemia now or in history; - liver failure and severe liver disease (before normalization of liver samples) - liver tumors (benign) or malignant) at present or in history; severe and / or acute renal failure; identified hormone-dependent malignant diseases (including genital organs or mammary glands) or suspicion of them; - bleeding from the vagina of unclear genesis; - pregnancy or suspicion of it; - lactation (breastfeeding); - hypersensitivity to the components of the drug. If any of the above diseases or conditions develop for the first time amid taking the drug, it should be immediately canceled.
Precautionary measures
The potential risk and expected benefit of using combined oral contraceptives in each individual case should be carefully weighed with the following diseases / conditions and risk factors: - risk factors for thrombosis and thromboembolism (smoking, obesity, dyslipoproteinemia, hypertension, migraine, valvular heart disease, long-term immobilization, serious surgical intervention, extensive trauma, hereditary predisposition to thrombosis / thrombosis, myocardial infarction or impaired m ozgovogo blood circulation at a young age in one of the closest relatives /); - other diseases in which there may be violations of the peripheral blood circulation (diabetes, SLE, hemolytic uremic syndrome, Crohn's disease, UC, sickle cell anemia, phlebitis of superficial veins) - hereditary angioedema; - hypertriglyceridemia; - liver disease; - diseases that first arose or worsened during pregnancy or against the background of previous intake of sex hormones (for example, jaundice, olestaz, gallbladder disease, otosclerosis with hearing impairment, porphyria, herpes gestationis, Sydenham chorea) - postpartum.
Use during pregnancy and lactation
The drug is not prescribed during pregnancy and lactation. If pregnancy is detected during the use of the drug Yarin ;, the drug should be immediately canceled. However, extensive epidemiological studies have not revealed an increased risk of developmental defects in children born to women who received sex hormones before pregnancy, or teratogenic effects, when sex hormones were taken by negligence in the early stages of pregnancy. At the same time, the results of taking Yarin; during pregnancy are limited, which does not allow to draw any conclusions about the negative impact of the drug on pregnancy, the health of the newborn and the fetus. Currently, there are no significant epidemiological data. Receiving combined oral contraceptives can reduce the amount of breast milk and change its composition, therefore, their use is not recommended until breastfeeding stops. A small amount of sex steroids and / or their metabolites can be excreted in milk.
Dosage and administration
Tablets should be taken orally in the order indicated on the packaging, every day at about the same time, with a small amount of water. Take 1 tab. / Day continuously for 21 days. Taking the pills from the next pack begins after a 7-day break, during which menstrual-like bleeding usually develops (withdrawal bleeding). As a rule, it starts 2-3 days after taking the last pill and may not end before taking the pills from the new package. Start taking Yarin ;: In the absence of taking any hormonal contraceptives in the previous month, take Yarin; starts on the 1st day of the menstrual cycle (i.e., on the 1st day of menstrual bleeding). It is allowed to start taking on the 2-5th 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 taking the pills from the first package. When switching from other combined oral contraceptives, vaginal ring or contraceptive patch, it is preferable to start taking drug Yarin; the next 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 (for drugs containing 21 pills) or after taking the last inactive tablet (for drugs containing 28 pills in packaging).Taking the drug Yarin; should begin on the day of removal of the vaginal ring or patch, but not later than the day when a new ring needs to be inserted or a new patch is pasted. When switching from contraceptives containing only gestagens (mini-pili, injectable forms, implant), or intrauterine discharger contraceptive (Mirena;). You can go with a mini-drank drug Yarin; on any day (without a break), from the implant or intrauterine contraceptive with the progestogen - on the day of its removal, from the injection form - from the day when the next injection should be made. In all cases, you must use an additional barrier method of contraception during the first 7 days of taking pills. After abortion in the first trimester of pregnancy. You can start taking the drug immediately - on the day of the abortion. If this condition is observed, the woman does not need additional contraception. After childbirth or abortion in the second trimester of pregnancy. To start taking the drug should be no earlier than 21-28 days after birth (in the absence of breastfeeding) or abortion in the second trimester of pregnancy. If reception is started later, you must use an additional barrier method of contraception during the first 7 days of taking the pills. However, if a woman has already lived sexually, before taking the drug Yarin; pregnancy should be excluded or it is necessary to wait for the first menstruation. Acceptance of missed pills: If the delay in taking the drug was less than 12 hours, contraceptive protection is not reduced. A woman should take a 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, the contraceptive protection is reduced. The more pills are missed, and the closer the pass to a 7-day break in taking pills, the greater the likelihood of pregnancy. At the same time, you can be guided by the following two basic rules: 1. The drug should never be interrupted for more than 7 days.2 . 7 days of continuous taking pills are required to achieve adequate suppression of the hypothalamic-pituitary-ovarian regulation. Accordingly, the following tips can be given if a delay in taking the pills is more than 12 hours (the interval since the last pill is more than 36 hours). : You need to take the last missed pill as soon as possible, as soon as the woman remembers this (even if you need to take two pills at the same time). The next pill is taken at the usual time.Additionally, a barrier method of contraception (for example, a condom) should be used within the next 7 days. If sexual intercourse took place within a week before the pill is missed, the likelihood of pregnancy must be considered. Second week of taking the drug: You need to take the last missed pill as soon as possible when the woman remembers it (even if you need to take two pills at the same time) . The next pill is taken at the usual time. Provided that the woman took the pills correctly within 7 days preceding the first missed pill, there is no need to use additional contraceptive measures. Otherwise, as well as skipping two or more pills, you must additionally use barrier methods of contraception (for example, a condom) for 7 days. The third week of taking the drug: The risk of pregnancy increases due to the upcoming break in taking the pills. A woman should strictly adhere to one of the following two options. Moreover, if within the 7 days preceding the first missed pill, all the pills were taken correctly, there is no need to use additional contraceptive methods. You must take the last missed pill as soon as possible as soon as the woman remembers this (even if you need to take two pills at the same time). The following pills are taken at the usual time, until the pills from the current packaging run out. The next package should start immediately without a break. Withdrawal bleeding is unlikely until the second package ends, but there may be spotting and breakthrough bleeding while taking the pills. You can stop taking the pills from the current package, thus starting the 7-day break (including the day you skip the pills), and then start taking the pills from the new package. If a woman misses taking the pills and then does not have withdrawal bleeding, pregnancy should be excluded. Recommendations for vomiting and diarrhea: In case of vomiting or diarrhea up to 4 hours after taking the pills, absorption may not be complete and additional measures should be taken to prevent unwanted pregnancy.In such cases, you should be guided by the above recommendations when you skip the pills. Changing the day of the beginning of the menstrual cycle: In order to postpone the onset of menstrual bleeding, you must continue taking the pills from the new Yarin package; without a 7-day break. Tablets from a new package can be taken as long as necessary, including until the pills from the package have run out. While taking the drug from the second package, spotting blood from the vagina or breakthrough uterine bleeding is possible. Resume taking the drug Yarin; from the next package should be after the usual 7-day break. In order to postpone the day of the onset of menstrual bleeding to another day of the week, a woman should reduce the next break in taking the pill for as many days as she wants. The shorter the interval, the higher the risk that she will not have withdrawal bleeding, and later there will be spotting and breakthrough bleeding while taking the second package (just as if she would like to delay the onset of menstrual bleeding). Additional information for special categories of patients: For children and adolescents, the drug Yarina; shown only after the onset of menarche. The available data do not suggest dose adjustment in this group of patients. After the onset of menopause, the drug Yarina; not shown. The drug Yarin; contraindicated in women with severe liver disease, as long as the indicators of liver function do not normalize. The drug Yarin; contraindicated in women with severe renal insufficiency or acute renal failure.
Side effects
To the most frequent adverse reactions to the drug Yarin; include nausea and pain in the mammary glands. They occurred in more than 6% of women using this drug. Serious adverse reactions are arterial and venous thromboembolism. The table below shows the incidence of adverse reactions that were reported during clinical studies of the drug Yarin; (n = 4897). Within each group, selected depending on the frequency of occurrence, unwanted reactions are presented in order of decreasing severity.By 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 adverse reactions identified only in the process of post-marketing research, and for which it was not possible to assess the frequency of occurrence, the frequency is unknown. Psychiatric disorders: often - mood swings, depression / depressed mood, decrease or loss of libido. From the nervous system: often - migraine. From the cardiovascular system: rarely - venous or arterial thromboembolism *. On the part of the digestive system: often - nausea. From the side of the skin and subcutaneous Tissues: frequency unknown - erythema multiforme. From the reproductive system and the mammary gland: often - pain in the mammary glands, irregular uterine bleeding, bleeding from the genital tract of unspecified origin. The adverse events in clinical studies were codified using the MedDRA dictionary (Medical Regulatory Dictionary Activities, version 12.1). Different MedDRA terms reflecting the same symptom were grouped together and presented as the only adverse reaction in order to avoid weakening or blurring the true effect. * - The approximate frequency of epidemiological studies covering the group of combined oral contraceptives. Frequency bordered on very rare. Venous or arterial thromboembolism includes the following nosological units: peripheral deep vein occlusion, thrombosis and pulmonary vascular embolism / occlusion, thrombosis, embolism and myocardial / myocardial / cerebral infarction and stroke, not defined as hemorrhagic. with a very rare occurrence or delayed symptoms, which are believed to be associated with the administration of drugs from the oral combination contraceptive group. whether; the frequency of breast cancer diagnosis in women taking combined oral contraceptives is somewhat increased. Due to the fact that breast cancer is rarely observed in women under the age of 40 years, an increase in the number of breast cancer diagnoses in women,taking combined oral contraceptives is insignificant relative to the overall risk of the disease; liver tumors (benign and malignant). Other conditions; erythema nodosum; women with hypertriglyceridemia (increased risk of pancreatitis while taking combined oral contraceptives); increased blood pressure; conditions developing or worsening while taking combined oral contraceptives, but their relationship with the use of the drug has not been proven (jaundice and / or pruritus associated with cholestasis; formation of gallstones; porphyria; SLE; hemolytic-uremic syndrome; Sydenhem chorea; herpes pregnant women; hearing loss associated with otosclerosis); in women with hereditary angioedema, estrogen administration may cause or aggravate symptoms; abnormal liver function; impaired glucose tolerance or the effect on insulin resistance; Crohn's disease, ulcerative colitis; - Chloasma; hypersensitivity (including symptoms such as rash, urticaria). Interaction: The interaction of oral contraceptives with other drugs (inducers of liver microsomal enzymes, some antibiotics) can lead to breakthrough bleeding and / or reduced contraceptive efficacy.
Overdose
No serious violations in overdose were reported. Based on the cumulative experience with combined oral contraceptives, symptoms that can occur during an overdose: nausea, vomiting, bloody vaginal bleeding, or metrorrhagia. Treatment: symptomatic therapy is carried out. There is no specific antidote.
Interaction with other drugs
The interaction of oral contraceptives with other drugs can lead to breakthrough bleeding and / or a decrease in contraceptive reliability. Women taking these drugs should temporarily use barrier methods of contraception in addition to Yarin; or choose another method of contraception. The following types of interaction have been reported in the literature. Effects on hepatic metabolism: The use of drugs that induce liver microsomal enzymes can lead to an increase in clearance sex hormones, which in turn can lead to breakthrough bleeding or a decrease in contraceptive reliability.Such drugs include phenytoin, barbiturates, primidone, carbamazepine, rifampicin, rifabutin, possibly also oxcarbazepine, topiramate, felbamate, griseofulvin, and drugs containing St. John's wort. HIV inhibitor inhibitors (for example, ritonavir) and non-nucleosidic, and other forms that have been applied to them, have been added to all of them. ) and their combinations can also potentially affect hepatic metabolism. Effects on the enterohepatic circulation: According to separate studies, some antibiotics (for example, penicillins and tetracycline) m Gut reduce enterohepatic circulation of estrogen, thereby decreasing the concentration of ethinyl estradiol. During the taking of drugs that affect microsomal enzymes, and within 28 days after their cancellation, you should additionally use a barrier method of contraception. While taking antibiotics (such as penicillins and tetracyclines) and within 7 days after their cancellation, you should additionally use a barrier method of contraception . If during these 7 days of the barrier method of contraception the pills in the current package run out, then you should start taking the pills from the next package of Yarin; without the usual interruption in taking pills. The main metabolites of drospirenone are formed in plasma without the participation of the cytochrome P450 system. Therefore, the effect of cytochrome P450 inhibitors on the metabolism of drospirenone is unlikely. Oral combination contraceptives can affect the metabolism of other drugs, which leads to an increase (for example, cyclosporine) or a decrease (for example, lamotrigine) in plasma and tissue concentrations. On the basis of in vitro interaction studies , as well as an in vivo study on female volunteers taking omeprazole, simvastatin, and midazolam as markers, it can be concluded that the effect of drospirenone at a dose of 3 mg on the metabolism of other l drug substances are unlikely. There is a theoretical possibility of increasing the serum potassium concentration in women receiving the drug Yarin; simultaneously with other drugs that can increase the content of potassium in the serum. These drugs include angiotensin II receptor antagonists, some anti-inflammatory drugs, potassium-sparing diuretics, and aldosterone antagonists.However, in studies evaluating the interaction of drospirenone with ACE inhibitors or indomethacin, there was no significant difference between the serum potassium concentration compared to placebo.
special instructions
Medical examinations: Before starting or resuming the use of the drug Yarin; It is necessary to get acquainted with the history of life, family history of women, to conduct a thorough general medical and gynecological examination, to exclude pregnancy. The scope of research and the frequency of control examinations should be based on existing norms of medical practice, taking into account the individual characteristics of each patient. As a rule, blood pressure, heart rate are measured, BMI is determined, the condition of the mammary glands, abdominal cavity and pelvic organs is checked, including cytological examination of the cervical epithelium (Pap test). Usually, control studies should be carried out at least 1 time in 6 months. It is necessary to warn a woman that hormonal contraceptives do not protect against HIV infection (AIDS) and other sexually transmitted diseases. If any of the conditions, diseases and risk factors indicated below, currently available, the potential risk and the expected benefit of using Yarin should be carefully weighed; in each individual case and discuss it with a woman before she decides to start taking the drug. When weighting, amplification, or at the first manifestation of risk factors may require the abolition of the drug. Cardiovascular diseases: The results of epidemiological studies indicate a relationship between the use of combined oral contraceptives and an increased incidence of venous and arterial thrombosis and thromboembolism, such as deep vein thrombosis, pulmonary artery thromboembolism, myocardial infarction, cerebrovascular disease) while taking combined oral contraceptives. These diseases are rare. The risk of venous thromboembolism (VTE) is maximum in the first year of taking such drugs. Increased risk is present after the initial use of combined oral contraceptives or the resumption of the use of the same or different combined oral contraceptives (after a break between taking the drug in 4 weeks or more).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 (<50 μg of ethinyl estradiol) is 2-3 times higher than in non-pregnant patients who do not take combined oral contraceptives, however, this risk remains lower compared to the risk of VTE during pregnancy and childbirth. HE may be life threatening or lead to major outcome (1-2% of cases). VTE, manifested as deep vein thrombosis, or pulmonary embolism, can occur when using any combined oral contraceptives. Thrombosis of other blood vessels, such as liver, occurs very rarely when using combined oral contraceptives. mesenteric, renal, cerebral veins and retinal arteries or vessels. There is no consensus on the relationship between the occurrence of these events and the use of combined oral contraceptives. Symptoms of deep vein thrombosis (DVT) include: unilateral edema of the lower limb or along the leg vein, pain or discomfort in the leg only in an upright position or when walking, local temperature rise in the affected leg, redness or discoloration of the skin on the leg. The symptoms of pulmonary thromboembolism (PE) are as follows: shortness of breath or rapid breathing; sudden cough, incl. with hemoptysis; acute pain in the chest, which may increase with a deep breath; sense of anxiety; severe dizziness; rapid or irregular heartbeat. Some of these symptoms (eg, shortness of breath, cough) are nonspecific and can be interpreted incorrectly 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: sudden weakness or loss of sensitivity of the face, arm or leg, especially on one side of the body, sudden confusion, problems with speech and understanding; sudden one or two-sided vision loss; 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 epileptic seizures.Other signs of vascular occlusion are: sudden pain, swelling and weak blue limbs, acute abdomen symptom complex. Symptoms of myocardial infarction include: pain, discomfort, pressure, heaviness, a feeling of constriction or distension in the chest, arm or behind the sternum; discomfort radiating to the back, cheekbone, larynx, arm, stomach; cold sweat, nausea, vomiting, or dizziness, severe weakness, anxiety, or shortness of breath; rapid or irregular heartbeat. Arterial thromboembolism can be life-threatening or fatal. The risk of thrombosis (venous and / or arterial) and thromboembolism increases: - with age; - in smokers (with increasing number of cigarettes or increasing age, the risk increases, especially senior women