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Active material: Drospirenone, ethinylestradiol
When ATH: G03AA12
CCF: Monophasic oral contraceptive with anti-androgenic properties
ICD-10 codes (testimony): Z30.0
When CSF: 15.11.04.01
Manufacturer: BAYER SCHERING PHARMA AG (Germany)

Pharmaceutical form, composition and packaging

Pills, Film-coated light yellow, on the one hand in the form of letters engraved “DO” a hexagon.

Excipients: lactose monohydrate, corn starch, pregelatinized corn starch, povidone K25, magnesium stearate, gipromelloza (hydroxypropyl), macrogol 6000, talc (magnesium hydrosilicate), Titanium dioxide (E171), gland (II) oxide (E172).

21 PC. – blisters (1) – packs cardboard.
21 PC. – blisters (3) – packs cardboard.

Pharmacological action

Low-dose monophasic oral combined estrogen-progestin contraceptive product.

The contraceptive effect of Yasmin^® carried out by means of complementary mechanisms, the most important of which are inhibition of ovulation and the increase in the viscosity of cervical mucus.

Women, taking combined oral contraceptives, the menstrual cycle becomes more regular, rarely observed painful menstruation, It decreases the amount of bleeding, thereby reducing the risk of iron deficiency anemia. Besides, there is evidence that, reducing the risk of endometrial cancer and ovarian cancer.

Drospirenone, contained in Jarinje^®, It has antimineralokortikoidnym action and is able to prevent weight gain and other symptoms (eg, edema), associated with fluid retention caused by hormones. Drospirenone also has antiandrogenic activity and helps to reduce the symptoms of acne (blackheads), oily skin and hair. This action is similar to that of drospirenone natural progesterone, produced by the female body. This should be considered when choosing a contraceptive, especially for women with hormone-dependent fluid retention, as well as women with acne (acne) and seborrhea.

When used properly, Pearl Index (index, reflecting the number of pregnancies 100 Women, applying a contraceptive for a year) is less than 1. When skipping pills or incorrect use Pearl Index may rise.

Pharmacokinetics

Drospirenone

Absorption

After oral administration drospirenone is rapidly and almost completely absorbed from the gastrointestinal tract. After a single dose of the drug C_max drospirenone plasma achieved through 1-2 h and is 37 ng / ml. Bioavailability ranges from 76% to 85%. Eating does not affect the bioavailability of.

Distribution

After ingestion observed biphasic decrease in serum concentration of drospirenone.

Drospirenone binds to serum albumin and globulin binds, binding sex steroids (SHBG) or corticosteroid-svyazыvayushtim globulinom (KSG). Estradiol-induced increase of SHBG not affect the binding to plasma proteins drospirenone.

During the cycle of treatment C_ss^max drospirenone is achieved during the second half cycle.

A further increase in the concentration observed in approximately 1-6 cycles of the drug, further increase in the concentration is not observed.

Metabolism

After oral administration drospirenone completely metabolized. Most metabolites in plasma are presented acid form of drospirenone, which are formed without the participation of cytochrome P450 isoenzymes.

Deduction

Displays in the form of metabolites in the faeces and urine at a ratio of about 1.2-1.4. T_1/2 metabolites is about 40 no.

Ethinylestradiol

Absorption

After taking the drug inside ethinylestradiol is rapidly and completely absorbed from the gastrointestinal tract.

C_max plasma achieved through 1-2 h and is 54-100 pg / ml. Ethinylestradiol undergoes effect “first pass” through the liver, as a result, its oral bioavailability averages 45%.

Distribution

The binding to plasma proteins (albumin) – about 98%.

Ethinyl estradiol induces the synthesis of SHBG.

Reducing the concentration of ethinyl estradiol in the blood serum is biphasic.

C_ss It is set in the second half of the first dosing cycle.

Metabolism

Ethinylestradiol presistemna undergoes conjugation in the mucosa of the small intestine and in the liver. The main pathway – aromatic hydroxylation.

Deduction

Ethinyl estradiol is excreted as metabolites in the urine and bile in the ratio of about 4:6. T_1/2 metabolites about 24 no.

Testimony

- Contraception.

Dosage regimen

The drug should be taken on 1 pi. / day continuously for 21 day.

Tablets should be taken in order, specified on the package, every day at about the same time, with a little water.

Receiving each next pack is started after a 7-day interval, during which withdrawal bleeding occurs (menstrualnopodobnoe bleeding), which usually begins on the 2-3rd day of taking the last tablet and may not end before the start of the drug from a new package.

At without taking any hormonal contraceptive use in the previous month reception Yarin^® start at day 1 of the menstrual cycle (ie. in the 1 st day of menstrual bleeding), while taking the pill, marked the relevant day of the week. Shall start receiving 2-5 th day of the menstrual cycle, but in this case it is recommended to use a barrier method of contraception during the first 7 days of receiving the tablets of the first package.

At switching from combined oral contraceptives (combined oral contraceptives, vaginal rings, transdermal patch) reception Yarin^® preferably started at the next day after the last tablet active ingredients preceding Preparation, but in any case not later than the day after the usual 7-day break in the reception (for products, containing 21 tab.) or after the last inactive tablet (for products, containing 28 tab. packaged. When switching from the vaginal ring, transdermal patch preferably start taking Yasmin^® day ring or patch removal, but not later than the day, must be entered when a new ring or pasted a new patch.

At switching from contraceptives, containing only progestin (“minipill”), Yarinu^® You can start using any day without a break. For the first 7 days of taking the pills necessary to use additional barrier method of contraception.

At the use of injectable contraceptives, Implant or intrauterine device with progestin Yarinu^® start taking the day, when the following statement shall be the day of injection or implant removal. In all cases, you must use an additional barrier method of contraception during the first 7 days of tablet.

After abortion in the I trimester of pregnancy a woman may start taking the drug immediately on the day of the abortion. In this case, the woman does not need any additional contraceptive methods.

To begin receiving the drug should be not earlier 21-28 day after childbirth (in the absence of breastfeeding) or abortion in the II trimester of pregnancy. If the reception is started later, you must use an additional barrier method of contraception during the first 7 days of tablet. However, if a woman has been sexually active, before you start taking Yasmin^® Pregnancy must be excluded or must wait for the first menstruation.

Admission missed tablets

If the delay in taking the pill less 12 no, reliable contraception is not reduced. Missed tablet the woman should take as soon as possible, take the next pill at the usual time.

If the delay in the pill was more than 12 no, the reliability of contraception may be reduced. The more missed tablets, and the closer to the pass-dnsvnomu 7 tablet-free interval, the greater the chance of pregnancy. It should be borne, that the pills should never be interrupted for more than 7 days and that 7 days of continuous administration of the drug needed to achieve adequate suppression of the hypothalamic-pituitary-ovarian system.

If the delay in the pill was more than 12 h the first week ingestion, A woman should take the missed pill as soon as possible, once remember (even if this means taking two tablets at the same time). Take the next pill at the usual time. Additionally, you should use a barrier method of contraception for the next 7 days. If intercourse took place in the week before the missed pills, you must consider the possibility of pregnancy.

If the delay in the pill was more than 12 hr during the second week ingestion, A woman should take the last missed tablet as soon as possible, once remember (even, if it needs to take two tablets at the same time). Take the next pill at the usual time. Given that, that women on the pill right for 7 days, preceding the first missed tablet, no need for additional contraceptive measures. Otherwise, as well as the passage of two or more pills must also use a barrier method of contraception (eg, condom) during 7 days.

If the delay in the pill was more than 12 h the third week ingestion, the risk of pregnancy increases because of the forthcoming tablet-free interval. A woman should strictly adhere to one of the two following options: (wherein, if during 7 days, preceding the first missed tablet, all the pills are taken correctly, there is no need to use additional contraceptive methods):

- Should take the last missed tablet as soon as possible, once remember (even, if it is, taking two tablets at the same time). Take the next pill at the usual time, until the end of the current tablet packaging. The next pack should be started immediately. Withdrawal bleeding is unlikely, until the end of the second pack, but may experience spotting and breakthrough bleeding while taking the pill.

- You can stop taking the tablets from the current package, starting, thus, break 7 days, including the day of skipping pills and then begin receiving a new package. If a woman misses pills, and then during a break from the pill she had no withdrawal bleeding, Pregnancy must be excluded.

Recommendations in case of vomiting and diarrhea

At rvote or diarrhea a period of from 3 h to 4 h after administration Yarin^®, absorption of active substances may be incomplete. In this case, you must rely on recommendations by skipping pills.

Recommendations to change the date of the onset of menstruation

For, that delay the onset of menstruation, women should continue taking pills from a new package Yarin^® 7 days without interruption. Tablets of this new packaging can take so long, as needed (until, until the package is over). Against the background of the drug from the second package, women may experience spotting or breakthrough uterine bleeding. Resume reception Yarin^® of the next new package follows the conventional 7-day break.

For, that postpone the first day of menstruation to another day of the week, the woman should be reduced next break in taking the drug for as many days, how much she wants. The shorter the interval, the more likely, that will not have withdrawal bleeding will continue to be observed spotting and breakthrough bleeding while taking the second package (as in the case, when it required to delay the onset of menstruation).

Side effect

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

While taking combined oral contraceptive in women were observed, and other undesirable effects, are classified as follows:: often (≥1/100), sometimes (≥1/1000, but <1/100), rarely (<1/1000).

From the digestive system: often – nausea, abdominal pain; sometimes – vomiting, diarrhea.

On the part of the reproductive system: often – engorgement, breast tenderness; sometimes – hypertrophy breast; rarely – vaginal discharge, discharge from the breast.

CNS: often – headache, depressed mood, mood swings; sometimes – decreased libido, migraine; rarely – increased libido.

On the part of the organ of vision: rarely – intolerance to contact lenses (discomfort when wearing).

Metabolism: often – weight gain; sometimes – fluid retention; rarely – weight loss.

Dermatological reactions: sometimes – rash, hives; rarely – uzlovataya эritema, erythema multiforme.

Other: allergic reactions.

How and when taking other combined oral contraceptives, in rare cases may develop thrombosis and thromboembolism.

Contraindications

- Thrombosis (venous and arterial) in the present or past (incl. deep vein thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular disorders);

- State, predshestvuyuschye thrombosis (incl. transient ischemic attacks, angina) in the present or past;

- Migraine with focal neurological symptoms in the present or in history;

- Diabetes with vascular complications;

- Multiple or severe risk factors for venous or arterial thrombosis (incl. complicated valvular lesions, Atrial fibrillation, cerebrovascular disease, or coronary artery; uncontrolled hypertension, major surgery with prolonged immobilization, smoking at the age of 35 years);

- Pancreatitis with severe hypertriglyceridemia now or in history;

- Hepatic failure and severe liver disease (to normalize the liver samples);

- Liver tumors (benign or malignant) in the present or past;

- Severe and / or acute renal failure;

- Identification of hormone-dependent cancers (incl. genital or breast) or suspicion of them;

- Vaginal bleeding of unknown origin;

- Pregnancy or suspected it;

- Lactation (breast-feeding);

- Hypersensitivity to the drug.

If any of the above diseases or conditions develop for the first time while taking the drug, it should be lifted immediately.

Carefully

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

- Risk factors for thrombosis and embolism (smoking, obesity, dyslipoproteinemia, arterial hypertension, migraine, valvular heart, prolonged immobilization, major surgery, extensive trauma, a genetic predisposition to thrombosis / thrombosis, myocardial infarction or cerebrovascular accident at a young age in any of the next of kin /);

- Other diseases, which may occur when peripheral circulatory disorders (diabetes, SLE, hemolytic uremic syndrome, Crohn's disease, NYAK, drepanocytemia, phlebitis of superficial veins);

- Hereditary angioedema;

- Hypertriglyceridemia;

- Liver disease;

- Diseases, for the first time created or aggravated during pregnancy or previous use of the background of sex hormones (eg, jaundice, cholestasis, gallbladder disease, otosclerosis with hearing impairment, porphyria, Herpes pregnant, Huntington Sidengama);

- Postpartum.

Pregnancy and lactation

Pregnancy and lactation (breast-feeding) contraindicated.

If pregnancy is detected during reception Yarin^®, the drug should be immediately canceled. However, extensive epidemiological studies have revealed no increased risk of developmental defects in children, born to women, treated with hormones before pregnancy, or teratogenicity, when sex hormones were taken inadvertently in early pregnancy. Currently, data on the results of the drug Yasmin^® during pregnancy is limited, that does not allow any conclusions about the negative impact of the drug on pregnancy, the health of the fetus and newborn.

Acceptance of combined oral contraceptives may decrease 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 human milk, but there is no confirmation of their negative impact on the health of newborn

Cautions

Before the start or resumption of the drug Yasmin^® You should be familiar with the history of life, family history of women, conduct a thorough general medical (including measurement of blood pressure, Heart Rate, body mass index) and gynecological examination, including the study of mammary glands and cytological examination of scrapings from the cervix (Test by Papanikolaou), exclude pregnancy. The amount of additional research and the frequency of control examinations determined individually. Typically, control examinations should be carried out not less 1 per year.

Women should be informed that, that Yasmin^® do not protect against HIV infection (AIDS) and other diseases, sexually transmitted.

If any of the conditions, diseases and risk factors, the following, currently available, you should carefully weigh the potential risks and expected benefits of the use of combined oral contraceptive in each individual case and discuss it with the woman before, she decides to start taking the drug. When weighting, strengthening or at the first sign of risk factors may require removal of the drug.

Diseases of the cardiovascular system

Available epidemiological data on the increase in the incidence of venous and arterial thrombosis and thromboembolism (such as deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke) while taking combined oral contraceptive. These diseases are rare.

The risk of venous thromboembolism (VTЭ) is maximum in the first year of use of these drugs. The approximate incidence of VTE in women, taking low-dose oral contraceptives (< 0.05 mg of ethinyl estradiol), up to 4 accidents 10 000 person-years as compared with 0.5-3 on 10 000 person-years among women, do not use oral contraceptives. The incidence of VTE in the background of pregnancy 6 accidents 10 000 person-years.

The risk of developing deep vein thrombosis in women, taking combined oral contraceptives above, than in women, do not take them, but not so high, as in pregnancy.

It should be taken into account, that the risk of venous or arterial thrombosis and / or thromboembolic events increases with age; Smokers (with the number of cigarettes or increasing age the risk further increases, especially in older women 35 years); in the presence of family history (eg, venous or arterial thromboembolism ever in close relatives or parents at a relatively young age; in the case of hereditary predisposition woman should be assessed and appropriate specialists to address the issue of the possibility of using combined oral contraceptives); obesity (body mass index 30 kg / m²); dyslipoproteinemia; hypertension; migraine; valvular heart disease; Atrial Fibrillation; prolonged immobilization; major surgery; any surgery on the legs or major trauma. In these situations, it is recommended to stop the use of Yasmin^® (in the case of the planned operation, at least, for 4 weeks earlier) and not to renew the appointment within 2 weeks after immobilization.

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

It should take into account the increased risk of thromboembolism during the postpartum period.

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

Increased frequency and severity of migraine during use of COCs (that may precede cerebrovascular disorders) It may be grounds for the immediate cessation of these drugs.

In assessing the risks and benefits, should be considered, that adequate treatment of the disease may reduce the associated risk.

Tumors

The most important risk factor for cervical cancer, It is persistent human papilloma virus infection. There are reports of some increase in the risk of cervical cancer in long-term use of combined oral contraceptives. However, the connection with the reception of the combined oral contraceptives has not been proven. Reserved controversy regarding, the extent to which the data associated with screening for cervical pathology, or with the sexual behavior (less frequent use of barrier methods of contraception).

Meta-analysis 54 Epidemiological studies have shown, that there is a slightly increased relative risk of developing breast cancer, diagnosed in women, receiving combined oral contraceptives currently (relative risk 1.24). The increased risk gradually disappears during the 10 years after stopping these drugs. Because, that breast cancer is rare in women under 40 years, increase in the number of breast cancer diagnoses in women, taking combined oral contraceptives are currently taking or have recently, is small relative to the total risk of the disease. The relationship between the development of breast cancer and receiving combined oral contraceptives has not been proven. The observed increase in risk can also be the result of careful observation and an earlier diagnosis of breast cancer in women, applying the combined oral contraceptives. Women, ever use combined oral contraceptives, revealed earlier stages of breast cancer, than in women, never let them to apply.

In rare cases, against the background of the use of combined oral contraceptives to observe the development of liver tumors, which in some cases led to life-threatening intra-abdominal haemorrhage. In case of severe pain in the abdomen, liver enlargement or signs of intra-abdominal bleeding it should be considered in the differential diagnosis.

Other conditions

Clinical studies have shown no effect of drospirenone concentration of potassium in the serum of patients with mild to moderate renal insufficiency. There is a theoretical risk of hyperkalemia in patients with impaired renal function, and the original potassium level ULN or in patients receiving drugs, resulting in a delay of potassium in the body.

In women with hypertriglyceridaemia (or the presence of this condition in the family history) may increase the risk of developing pancreatitis while taking combined oral contraceptives.

Despite, that a small increase in blood pressure have been reported in many women, taking combined oral contraceptives, clinically significant hypertension is rare. Nonetheless, If while taking combined oral contraceptives develops persistent, a clinically significant increase in blood pressure, these drugs should be discontinued and treat hypertension. Acceptance of combined oral contraceptives may be continued, if using antihypertensive treatment achieved normal blood pressure values.

The following states, as reported, develop or worsen both during pregnancy, and when receiving combined oral contraceptives, but their relationship with the intake of combined oral contraceptives has not been proven: Jaundice and / or itching, associated with cholestasis; the formation of gallstones; porphyria; SLE; hemolytic uremic syndrome; Huntington Sidenhema; Herpes pregnant; hearing loss, otosclerosis-related. Also described cases of Crohn's disease and ulcerative colitis in the background of the use of combined oral contraceptives.

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

When acute or chronic disturbances of liver function may require removal of the drug until, until liver function tests have not returned to normal. Recurrent cholestatic jaundice, which develops for the first time during pregnancy or previous use of sex hormones, It requires discontinuation of combined oral contraceptives.

Although combined oral contraceptives may influence insulin resistance and glucose tolerance, no need to change the therapeutic regimen in patients with diabetes, applying low-dose combined oral contraceptives (<0.05 mg of ethinyl estradiol). Nonetheless, Women with diabetes should be carefully monitored during treatment.

In applying the drug may develop chloasma, especially in women with a history of chloasma pregnant. Women with a tendency to chloasma while taking combined oral contraceptives should avoid prolonged exposure to sunlight and ultraviolet radiation.

The effectiveness of combined oral contraceptive pills can be reduced by skipping pills, vomiting or diarrhea or as a result of drug interactions.

The effect on the menstrual cycle

While taking combined oral contraceptives may experience irregular bleeding (spotting or breakthrough bleeding), especially during the first months of use. Therefore, evaluation of any irregular bleeding should be done only after a period of adaptation, of approximately three cycles.

If irregular bleeding or develop after repeated previous regular cycles, should conduct a thorough examination to exclude malignancy or pregnancy.

Some women during the tablet-free interval may not develop withdrawal bleeding. If the reception of the combined oral contraceptives was conducted in accordance with the instructions, the pregnancy is unlikely. Nonetheless, if before receiving COCs held irregularly or, if there are no two consecutive withdrawal bleeding, then to continue receiving the drug should exclude pregnancy.

Effect on laboratory tests

Acceptance of combined oral contraceptives can affect the results of certain lab tests, including liver function tests, kidney, Thyroid, adrenal, level in the plasma transport proteins, carbohydrate metabolism, parameters of coagulation and fibrinolysis. Changes do not usually go beyond the normal range. Drospirenone increases plasma renin activity and aldosterone, because of its effect antimineralokortikoidnym.

Effects on ability to drive vehicles and management mechanisms

There was no effect of the drug on the ability to drive vehicles and other activities, require high concentration and speed of psychomotor reactions.

The results of experimental studies

Preclinical data, obtained in standard tests in order to study the toxicity by repeated drug taking, and hepatotoxicity, carcinogenic potential and toxicity to the reproductive system, It does not indicate a special risk for humans. Nonetheless, should be considered , that sex steroids can promote the growth of certain hormone-dependent tissues and tumors.

Overdose

Serious violations have been reported in overdose.

Symptoms: nausea, vomiting, spotting or metrorrhagia.

Treatment: symptomatic therapy. No specific antidote.

Drug Interactions

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

Use of drugs, inducing hepatic microsomal enzymes, can lead to increased clearance of sex hormones, which in turn can lead to breakthrough bleeding and decrease the reliability of contraception. These drugs include phenytoin, barbiturates, prymydon, Carbamazepine, rifampicin, rifabutin, may also – okskarʙazepin, topiramate, felʙamat, griseofulvin and preparations, containing St. John's wort.

HIV protease inhibitors (eg, ritonavir) and non-nucleoside reverse transcriptase inhibitors (eg, Nevirapine) and combinations thereof may also potentially affect hepatic metabolism.

According to separate studies, certain antibiotics (eg, penitsillinы and tetracycline) may reduce the enterohepatic circulation of estrogens, thereby, lowering the concentration of ethinyl estradiol.

During supplementation, influencing microsomal enzymes, and for 28 days after their cancellation should additionally use a barrier method of contraception.

While antibiotics (except rifampicin and griseofulvin) and for 7 days after their cancellation should additionally use a barrier method of contraception. If the period of use of barrier methods of contraception ends later, than tablets per pack, you need to go to the next package Yarin^® without the usual tablet-free interval.

The main metabolites of drospirenone are formed in the plasma without the participation of cytochrome P450 isoenzyme system. Therefore, it is unlikely the effect of inhibitors of the enzyme system on the metabolism of drospirenone.

Combination oral contraceptives may affect the metabolism of other drugs, which leads to increased (eg, cyclosporine) or reduction (eg, lamotrigine) their concentration in the plasma and tissues.

Based on in vitro studies of the interaction , as well as in vivo study in women volunteers, prinimayushtih omeprazole, simvastatin and midazolam as markers, we can conclude, that the effect of drospirenone in a dose of 3 mg of the metabolism of other drugs is unlikely.

There is a theoretical possibility of increasing serum potassium levels in women, receiving Yarin^® simultaneously with other preparations, that may increase potassium levels (eg, angiotensin II receptor antagonists, Some NSAIDs, potassium-sparing diuretics and aldosterone antagonists). However, studies, evaluating the interaction of drospirenone with ACE inhibitors or indomethacin, There were no significant differences between the serum potassium concentration compared to placebo.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored out of reach of children at temperature not exceeding 25 ° C. Shelf life – 3 year.