Expiration date: 04/2025

Pharmachologic effect:

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

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

In women taking combined oral contraceptives, menstrual cycle becomes more regular, less often observed painful menstruation, it decreases the amount of bleeding, thereby reducing the risk of iron deficiency anemia. Furthermore, there is evidence that reduces the risk of endometrial cancer and ovarian cancer.

Drospirenone contained in Yasmin has antimineralokortikoidnym action and can prevent weight gain and the occurrence of other symptoms (such as edema) associated with the fluid retention caused by hormones. Drospirenone is also possesses antiandrogenic activity, and reduces the symptoms of acne (acne) greasy skin and hair. This action of drospirenone similar to the action of 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 (an indicator of the number of pregnancies in 100 women using a contraceptive during the year) is less than 1. When skipping pills or incorrect use Pearl Index may increase.

Pharmacokinetics:

Drospirenone

Suction

After oral administration drospirenone is rapidly and almost completely absorbed from the gastrointestinal tract. After a single dose of the drug drospirenone Cmax in plasma achieved in 1-2 hours and is 37 ng / ml. Bioavailability ranged from 76% to 85%. Food does not affect the bioavailability.

Distribution

Once inside there is a two-phase reduction of drospirenone in serum.

Drospirenone is bound to serum albumin and does not bind to binding globulin sex steroids (SHBG) or corticosteroid-binding globulin (CBG). Estradiol-induced increase in SHBG does not affect the binding to plasma proteins drospirenone.

During treatment cyclic Cssmax drospirenone is achieved during the second half cycle.

Further increase of concentration is noted after about 1-6 cycles of administration of the drug, the subsequent increase in the concentration was observed.

Metabolism

After oral administration drospirenone is completely metabolized. Most metabolites in plasma are presented drospirenone acid forms, which are formed without the isozymes of cytochrome P450.

Breeding

Displays in the form of metabolites in the faeces and urine at a ratio of about 1.2-1.4. T1 / 2 of metabolites is about 40 hours.

Ethinylestradiol

Suction

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

Cmax in plasma achieved in 1-2 hours and is 54-100 pg / ml. Ethinylestradiol undergoes first-pass effect through the liver, resulting in its oral bioavailability is 45%.

Distribution

Binding to plasma proteins (albumin) - about 98%.

Ethinyl estradiol induces the synthesis of SHBG.

Decrease in serum concentration of ethinyl estradiol is biphasic.

Css is established during the second half of the first cycle of treatment.

Metabolism

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

Breeding

Ethinyl estradiol is excreted as metabolites in the urine and bile in a ratio of about 4: 6. T1 / 2 of about 24 h metabolites.

Testimony: Contraception.

Dosage and administration:

The drug should be taken on 1 tab. / Day continuously for 21 days.

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

Reception following each package is started after a 7-day break, during which withdrawal bleeding occurs (menstrualnopodobnoe bleeding), which usually begins at 2-3-th day of taking the last tablet and may not end before the start of the drug from a new package.

Without taking any hormonal contraceptive use in the preceding month of receiving Yarin begin in the 1 st day of the menstrual cycle (ie the 1st day of menstrual bleeding) while taking the pill, marked the relevant day of the week. Shall start receiving the 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 tablet-taking from the first package.

When changing from a combined oral contraceptive (COC, vaginal ring, transdermal patch) admission Yarina is preferable to start the next day after taking the last pill with the active components of the previous formulation, but in any case not later than the day after the usual 7-day break in reception (for products containing 21 tabs.) or after the last inactive tablet (for products containing 28 pi. in the package. in the transition from a vaginal ring, transdermal patch preferably start taking Yasmin on the day of removal of the ring or the patch, but not later than the day that should be introduced or a new ring pasted a new patch.

When switching from contraceptives containing only progestin (mini-pill), you can start to use Yasmin without a break any day. During the first 7 days of tablet-taking must use an additional barrier method of contraception.

When using injectables contraceptive implant or intrauterine device with progestin Yarin begin to take on the day when the next injection or daily removal of the implant must be made. In all cases, you must use an additional barrier method of contraception during the first 7 days of taking the pills.

After an abortion in the I trimester of pregnancy, a woman can begin 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 than 21-28 days after birth (no 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 taking the pills. However, if a woman has been sexually active, before you start taking Yasmin should be excluded pregnant or you must wait for the first menstrual period.

Admission missed tablets

If the delay in receiving the tablets at least 12 hours, contraceptive reliability is not reduced. woman should take as soon as possible missed pills, take the next pill at the usual time.

If the delay in receiving the tablets was more than 12 hours, contraceptive reliability 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 in mind that pills should never be interrupted for more than 7 days, and that 7 days of continuous administration of the drug are needed to achieve adequate suppression of the hypothalamic-pituitary-ovarian system.

If the delay in receiving the tablets accounted for more than 12 hours during the first week of taking the drug, the woman should take the missed pill as soon as possible, as soon as you remember (even if this means taking two tablets at the same time). The next tablet is taken at the usual time. Additionally, you should use a barrier method of contraception for the next 7 days. If intercourse took place during the week before a pass taking the pill, you need to consider the possibility of pregnancy.

If the delay in receiving the tablets accounted for more than 12 hours during the second week of taking the drug, the woman should take the last missed tablet as soon as possible, as soon as you remember (even if it needs to take two tablets at the same time). The next tablet is taken at the usual time. Provided that the woman is on the pill correctly within 7 days preceding the first missed tablet, there is no need to use additional contraceptive measures. Otherwise, as well as skipping of two or more tablets must also use barrier contraception (such as a condom) for 7 days.

If the delay in receiving the tablets was more than 12 hours during the third week of administration of the drug, increases risk of pregnancy due to the forthcoming tablet-free interval. A woman should strictly stick to one of the following options (in this case, if during the 7 days preceding the first missed tablet, taken all the tablets correctly, there is no need to use additional contraceptive methods):

• Should take the last missed tablet as soon as possible, as soon as you remember (even if this means taking two tablets at the same time). The next tablet at the usual time taken until the end tablets from the current package. 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 pills.
  
• You can stop taking the tablets from the current package, starting, so a break of 7 days, including the day of skipping pills and then start taking a new package. If a woman misses pills, and then during the tablet-free interval it does not have withdrawal bleeding, pregnancy must be excluded.
  

Recommendations in case of vomiting and diarrhea

Vomiting and diarrhea during the period of from 3 hours to 4 hours after administration of Yasmin, the absorption of active substances may be incomplete. In this case, you need to focus on the recommendations by skipping pills.

Recommendations for changing the date of the onset of menstruation

In order to delay the onset of menstruation, the woman should continue taking pills from a new package Yarin without 7-day break. Tablets of this new packaging can take as long as necessary (as long as the packing is completed). Against the background of the drug from the second package, women may experience spotting or breakthrough uterine bleeding. Resume Yarin reception from the following new package follows the usual 7-day break.

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

Side effects:

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

While taking combined oral contraceptives in women were observed and other undesirable effects, which were classified as follows: often (ge1 / 100), sometimes (ge1 / 1000 but t1 / 100), rare (t1 / 1000).

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

On the part of the reproductive system: often - bloating, breast tenderness sometimes - hypertrophy of the breast is rare - vaginal discharge, discharge from the breast.

CNS: often - headache, depressed mood, mood swings sometimes - decreased libido, headache, rarely - increased libido.

From a sight organ: rare - contact lens intolerance (discomfort when wearing them).

On the part of metabolism: often - weight gain sometimes - fluid retention in the body rarely - weight loss.

Dermatological reactions: sometimes - rash, urticaria, rarely - erythema nodosum, erythema multiforme.

Other: allergic reactions.

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

Contraindications:

• Thrombosis (venous and arterial) present or in history (including deep vein thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular accident)
  
• State prior thrombosis (including transient ischemic attacks, angina pectoris) at present or in history
  
• Migraine with focal neurological symptoms in the present or in history
  
• Diabetes with vascular complications
  
• Multiple or severe venous or arterial thrombosis risk factors (including complicated lesions valvular atrial fibrillation, cerebrovascular disease, or coronary artery uncontrolled hypertension, major surgery with prolonged immobilization, smoking at the age of 35 years)
  
• Pancreatitis with severe hypertriglyceridemia now or in history
  
• Hepatic failure and severe liver disease (liver function tests before normalization)
  
• Liver tumors (benign or malignant) at present or in history
  
• Severe and / or acute renal failure
  
• Hormone identified malignant diseases (including genital or mammary glands) or are suspected
  
• Vaginal bleeding of unknown origin
  
• Pregnancy or suspected it
  
• Lactation (breastfeeding)
  
• Hypersensitivity to the drug.
  

If any of the above mentioned 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 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, prolonged immobilization, major surgery, major trauma, genetic predisposition to thrombosis / thrombosis, myocardial infarction or cerebrovascular accident at a young age, someone from the next of kin /)
  
• Other diseases, which may occur when peripheral circulatory disorders (diabetes, lupus, hemolytic uremic syndrome, Crohn's disease, ulcerative colitis, sickle cell anemia, phlebitis of superficial veins)
  
• Hereditary angioedema
  
• hypertriglyceridemia
  
• Liver disease
  
• Diseases caused or aggravated 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:

Use in pregnancy and lactation (breastfeeding) is contraindicated.

If pregnancy is detected during the reception of Yasmin, the preparation should be immediately abolished. However, extensive epidemiological studies have revealed no increased risk of defects in children born to women treated with hormones before pregnancy, or teratogenic effects when sex hormones were taken inadvertently in early pregnancy. Currently, data on the results Yarina® receiving the drug 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.

Admission combined oral contraceptives can reduce the amount of breast milk and change its composition, so their use is not recommended until weaning. Small amounts of sex steroids and / or their metabolites may be excreted in breast milk, but there is no confirmation of their negative impact on the health of newborn

Special instructions:

Before the start or resumption of use of the drug Yarina® should be familiar with the history of life, a family history of the women, to conduct a thorough general medical (including blood pressure measurement, heart rate, body mass index) and gynecological examination, including a study of mammary glands and cytological examination of scrapings from the cervix (the test Pap), exclude pregnancy. The amount of additional research and the frequency of check-ups is determined individually. Typically, control examinations should be carried out not less than 1 time per year.

Women should be informed that Yarina® 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 combined oral contraceptives in each individual case and discussed with the woman before she decides to start taking drug. When weighting, gain or at the first sign of risk factors may require removal of the drug.

Diseases of the cardiovascular system

There is epidemiological evidence of increased frequency of venous and arterial thrombosis and thromboembolism (such as deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke) when taking combined oral contraceptives. These diseases are rare.

The risk of developing venous thromboembolism (VTE) is greatest in the first year of receiving such drugs. The approximate incidence of VTE in women taking low-dose oral contraceptives (t 0.05 mg ethinyl estradiol), up to 4 cases per 10 000 person-years compared to 0.5-3 per 10 000 person-years among women who did not use oral contraceptives. The incidence of VTE in the background of pregnancy is 6 cases per 10 000 person-years.

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

Keep in mind that the risk of venous or arterial thrombosis and / or thromboembolic events increases with age in smokers (with the number of cigarettes or increasing age the risk further increases, especially in women older than 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 the appropriate specialist to resolve the question of the possibility of using combined oral contraceptives), obesity (body mass index over 30 kg / m2) dislipoproteinemia hypertension disorders migraine the valves of the heart atrial fibrillation prolonged immobilization major surgery of any operation on the legs or major trauma. In these situations, it is recommended to stop the application of Yasmin (in case the intended operation of at least 4 weeks prior to it) and not to resume reception at 2 weeks after the immobilization.

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

It is necessary to take into account the increased risk of thromboembolism during the postpartum period.

Peripheral circulatory disorders also may occur in diabetes mellitus, 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 combined oral contraceptives (which may be preceded by a cerebrovascular accident) may be a reason for immediate discontinuation of these drugs.

In assessing the risks and benefits should be taken into account that adequate treatment of the respective disease may reduce the associated risk.

Tumors

The most important risk factor for cervical cancer is persistent papilloma virus 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 intake of combined oral contraceptives has not been proved. Contradictions persist as to the extent to which the data associated with screening for cervical abnormalities or with features of sexual behavior (a rare use of barrier methods of contraception).

A meta-analysis of 54 epidemiological studies showed that there is a slightly increased relative risk of developing 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, increasing number of diagnoses of breast cancer in women receiving combined oral contraceptives currently or recently taking is insignificant relative to the total risk of the disease. The relationship between the development of breast cancer and taking combined oral contraceptives cancer has not been proven. The observed increase in risk may be the result of careful observation and an earlier diagnosis of breast cancer in women using combined oral contraceptives. In women, ever use a combined oral contraceptives, revealed earlier stages of breast cancer than women who never let them apply.

In rare cases, against the background of the use of combined oral contraceptives was observed 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 potassium concentration 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 content of potassium at ULN or in patients receiving medicinal products that lead to potassium retention.

Women with hypertriglyceridemia (or the presence of the state in family history) may increase the risk of developing pancreatitis while taking combined oral contraceptives.

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

The following conditions have been reported to develop or worsen both during pregnancy and while taking combined oral contraceptives, but their relationship with the intake of combined oral contraceptives has not been proven: jaundice and / or pruritus associated with cholestasis formation of stones in the gallbladder porphyria SLE hemolytic uremic Sydenham chorea syndrome herpes pregnant hearing loss associated with otosclerosis. cases of Crohn's disease and ulcerative colitis are also described 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 as long as 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, requires discontinuation of COCs.

Although COCs may have an effect on insulin resistance and glucose tolerance, there is no need to change the therapeutic regimen in patients with diabetes who use low-dose combined oral contraceptives (t0.05 mg ethinyl estradiol). However, women with diabetes should be carefully monitored during treatment.

In applying the drug may develop chloasma, especially in women with a history of chloasma during pregnancy. 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 and 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 performed only after a period of adaptation of approximately three cycles.

If irregular bleeding recur or develop after previous regular cycles, you 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 combined oral contraceptives was conducted in accordance with the instructions, then pregnancy is unlikely. However, if before receiving combined oral contraceptives are irregular or if there are no two consecutive withdrawal bleeding, it is necessary to exclude pregnancy before continuing the treatment.

Effect on laboratory tests performance

Admission combined oral contraceptives can affect the results of certain lab tests, including liver function tests, kidney, thyroid, adrenal, levels of transport proteins in the plasma, carbohydrate metabolism, coagulation and fibrinolysis parameters. Changes do not usually go beyond the normal range. Drospirenone increases plasma renin activity and aldosterone, which is due to 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 that require high concentration and speed of psychomotor reactions.

The results of experimental studies

Preclinical data obtained in the course of standard research on the toxicity after repeated taking the drug and hepatotoxicity, carcinogenic potential and toxicity to the reproductive system, do not indicate a particular risk to humans. However, it should be borne in mind that sex steroids can promote the growth of certain hormone-dependent tissues and tumors.

Overdose:

• Serious violations were reported in overdose.
  
• Symptoms include 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.

The use of drugs that induce hepatic microsomal enzymes which may lead to increased clearance of sex hormones, which in turn can lead to breakthrough bleeding or decreased contraceptive reliability. Such drugs include phenytoin, barbiturates, primidone, carbamazepine, rifampicin, rifabutin, also possible - oxcarbazepine, topiramate, felbamate, and griseofulvin preparations containing St. John's wort.

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

According to separate studies, some antibiotics (e.g., penicillin and tetracycline) may reduce the enterohepatic circulation of estrogen, thereby decreasing the concentration of ethinyl estradiol.

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

While antibiotics (except rifampicin and griseofulvin) and for 7 days after their removal should additionally use a barrier method of contraception. If the period of use of a barrier method of contraception ends later than tablets in a package, 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 isoenzymes of cytochrome P450. Therefore, it is unlikely the effect of inhibitors of this enzyme system in the metabolism of drospirenone.

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

Based on interaction studies in vitr, as well as research in viv volunteers women taking omeprazole, simvastatin and midazolam as a marker, it can be concluded that the effect of drospirenone 3 mg on the metabolism of other drugs is unlikely.

There is a theoretical possibility of increasing serum potassium in women receiving Yarin concurrently with other drugs that may increase potassium levels (eg, angiotensin II receptor antagonists, some NSAIDs, potassium-sparing diuretics and aldosterone antagonists). However, studies evaluating the interaction with drospirenone or ACE inhibitors and