Expiration date: 12/2025

Release form and composition:

Tablets, film-coated (active) light pink, round, biconvex, engraved with the letters DS in the correct hexagon on one side on a break - the core from white to almost white and light pink envelope (24 pcs in a blister pack. ).

1 tablet contains:

ethinylestradiol (betadeks clathrate form) 20 g

Drospirenone 3 mg

Excipients: lactose monohydrate, corn starch, magnesium stearate.

shell composition: hypromellose, talc, titanium dioxide, red iron oxide colorant.

Tablets, film-coated (inactive), white, round, biconvex, engraved with the letters in the right DP hexagon on one side on a break - the core from white to almost white and white shell (4 pieces in a blister pack.).

Excipients: lactose monohydrate, corn starch, povidone, magnesium stearate.

Cover structure: Valium, talc, titanium dioxide.

28 pcs. - Blisters (1) - book-cot (1) complete with a self-adhesive Calendar reception - film.

28 pcs. - Blisters (1) - Laptop-clamshell (3) complete with a self-adhesive Calendar reception - film.

Pharmachologic effect:

Monophasic oral contraceptive with antimineralocorticoid and anti-androgenic properties.

The contraceptive effect of combined oral contraceptives is based on the interaction of various factors, the most important of which include inhibition of ovulation and cervical secretions properties change, causing it to become tight sperm.

When used properly, Pearl Index (number of pregnancies per 100 women per year) is less than 1. When skipping pills or incorrect use Pearl Index may increase.

In women taking combined oral contraceptives, menstrual cycle becomes more regular, less often observed painful menstruation, it decreases the amount of bleeding, which reduces the risk of developing anemia. In addition, according to epidemiological studies with combined oral contraceptives reduce the risk of endometrial cancer and ovarian cancer.

Drospirenone contained in the product Yaz has antimineralokortikoidnym action. Prevents weight gain and the occurrence of edema associated with estrogen-induced water retention, which ensures a very good tolerability. Drospirenone has a positive effect on premenstrual syndrome (PMS). Yaz demonstrated clinical efficacy in alleviating the symptoms of a severe form of PMS, such as the expression of psycho-emotional disorders, breast tenderness, headache, muscle aches and joint pain, weight gain and other symptoms associated with the menstrual cycle.

Drospirenone is also possesses antiandrogenic activity and reduces acne, oily skin and hair. This action of drospirenone similar to the action of natural progesterone produced by the body.

Drospirenone has no androgenic, estrogenic, glucocorticoid and antiglucocorticoid activity. All this combined with antimineralokortikoidnym and antiandrogenic action drospirenone provides biochemical and pharmacological profile similar to natural progesterone.

In combination with ethinylestradiol Drospirenone exhibits a favorable effect on the lipid profile, characterized by an increase in HDL.

Pharmacokinetics:

Drospirenone

Absorption

When administered drospirenone is rapidly and almost completely absorbed. After a single oral administration of drospirenone in serum Cmax achieved after about 1-2 hours and is about 35 ng / ml. Bioavailability - 76-85%. As compared with the reception substance fasting food intake does not affect the bioavailability of drospirenone.

Distribution

Drospirenone is bound to serum albumin and does not bind to binding globulin sex steroids (SHBG) or corticosteroid-binding globulin (CBG). Only 5.3% of the total concentration in the serum is present as a free steroid. GTN ethinylestradiol induced increase does not affect the binding of serum proteins drospirenone. Average apparent Vd is 3.7 ± 1.2 L / kg.

During treatment cyclic Cssmax drospirenone in serum obtained between 7 and 14 day of treatment and is about 60 ng / ml. Drospirenone was an increase in serum concentration of about 2-3 times (due to accumulation), which causes the ratio T1 / 2 and in the terminal phase of the dosing interval. Further increase in the serum concentration of drospirenone observed between 1 and 6 cycles of reception, after which increasing the concentration is not observed.

Metabolism

After oral administration drospirenone is extensively metabolized. Most metabolites in plasma are presented acidic forms of drospirenone.

breeding

After ingestion observed biphasic decrease in serum levels of drospirenone from T1 / 2, respectively, h 1.6 ± 0.7 and 27 ± 7.5 hours. The metabolic clearance rate of drospirenone in serum is 1.5 ± 0.2 ml / min / kg. In unaltered drospirenone appears only in trace amounts. The metabolites of drospirenone are excreted in the feces and urine in a ratio of about 1.2: 1.4. T1 / 2 - 40 hours.

Pharmacokinetics in special clinical situations

Css drospirenone in serum of women with mild renal impairment (creatinine clearance of 50-80 ml / min) were comparable to those of women with normal renal function (creatinine clearance gt 80 ml / min). In women with moderate renal impairment (creatinine clearance of 30-50 ml / min) drospirenone serum was on average 37% higher than in women with normal nochek. drospirenone treatment was well tolerated in all groups. Receiving drospirenone no clinically significant effect on the potassium concentration in the serum. Pharmacokinetics in renal failure severe has not been studied.

Drospirenone is well tolerated by patients with mild or moderate hepatic insufficiency (class B on a scale Child-Pugh). Pharmacokinetics in severe hepatic impairment has not been studied.

Ethinylestradiol

Absorption

After oral ethinyl estradiol is rapidly and completely absorbed. Cmax after a single oral administration is achieved in 1-2 hours and is about 88-100 pg / ml. Absolute bioavailability as a result of first pass conjugation and first-pass metabolism through the liver is about 60%. Concomitant intake of food reduces the bioavailability of ethinylestradiol in about 25% of the patients, while other subjects such changes were noted.

Distribution

Ethinylestradiol largely, but not specifically associated with a serum albumin (about 98.5%) and causes an increase in the serum concentrations of SHBG. Apparent Vd is about 5 l / kg. Css achieved during the second half of the treatment cycle and serum levels of ethinyl estradiol increased about 1.4-2.1 times.

Metabolism

Ethinyl estradiol is subject to first-pass kongirovaniyu in the mucous membrane of the small intestine and in the liver. Ethinyl estradiol is metabolized primarily by aromatic hydroxylation formed with various hydroxylated and methylated metabolites are presented in the form of free metabolites and as conjugates with glucuronic acid and sulfuric acid. Ethinyl estradiol is metabolised completely. The metabolic clearance rate of ethinyl estradiol is about 5 ml / min / kg.

breeding

Concentration of ethinyl estradiol decreased serum bi-phase, T1 / 2 terminal phase - 24 hours. Ethinylestradiol hardly excreted unchanged. Ethinylestradiol metabolites are excreted in urine and bile in a ratio of 4: 6. T1 / 2 metabolites - 24 hours.

Testimony:

• contraception
  
• Treatment of moderate forms of acne (acne vugaris)
  
• Treatment of a severe form of PMS.
  

Dosage and administration:

Tablets should be taken in the order indicated on the package, every day at about the same time, with a little water. The tablets are without a break in reception. It is necessary to take 1 tab. / Day consecutively for 28 days. Each subsequent pack should be started the following day after the last tablet of the previous package.

Withdrawal bleeding usually starts 2-3 days after you start taking the inactive pills and may not yet be completed before the next pack.

Without taking any hormonal contraceptive use in the previous month

Acceptance of the drug begin in the 1 st day of the menstrual cycle (ie the 1st day of menstrual bleeding). Shall start receiving the 2-5 th 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 tablet-taking from the first package.

When switching from other combined oral contraceptive vaginal ring or contraceptive patch

Preferably taking this medication on the day after the last active tablet from the previous package, but in any case no later than one day after the usual 7 day interval (for formulations containing 21 tablet) or after the last inactive tablets (for drugs, containing 28 tablets per pack). Admission Yaz drug should be started on the day of removal of the vaginal ring or patch, but not later than the day when it should be inserted a new ring or pasted a new patch.

When switching from contraceptives containing only progestin (mini-pill, injectable form, implant) or from a progestogen-releasing intrauterine device (Mirena)

A woman can go to receive mini-pill on any day of Yaz (without interruption), since the implant or intrauterine device with progestin - the day of its removal, from the injectable contraceptive - the day when the next injection should be done. In all cases, you must use an additional barrier method of contraception during the first 7 days of taking the pills.

After the abortion I trimester of pregnancy

The woman may start taking the drug immediately. Subject to this condition, the woman does not need additional measures of contraception.

After delivery or abortion in the II trimester of pregnancy

It is recommended to start taking the drug at 21-28 days after delivery 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 Yaz pregnancy should be excluded or must wait for the first menstrual period.

Admission missed tablets

Skipping inactive pills can be ignored. Nevertheless, they should be discarded to make sure we do not extend the period of receiving the inactive tablets. The following recommendations apply only to pass the active pills.

If the delay in receiving the drug was less than 12 hours, contraceptive protection is not reduced. The woman should take the missed pill as soon as possible, and should be taken at the usual time.

If the delay in receiving the tablets accounted for more than 12 hours, contraceptive protection may be reduced. The more missed tablets and the closer to the phase of the tablets pass reception inactive pills, the higher the probability of pregnancy.

It is possible to be guided by the following two basic rules:

• Receiving the drug should never be interrupted for more than 4 days
  
• To achieve adequate suppression of the hypothalamic-pituitary-ovarian system requires 7 days of uninterrupted tablet-taking.
  

Accordingly, if the delay in taking the active tablets accounted for more than 12 hours (interval from the receipt of the last active pill more than 36 hours), we can recommend the following:

From the 1st to the 7th day

The woman should take the last missed tablet as soon as you remember about it, even if this means taking two tablets at the same time. Next she continues to take tablets at the usual time. In addition, during the next 7 days is necessary to use an additional barrier method of birth control (such as a condom). If intercourse took place during the 7 days before skipping pills, you should consider the possibility of pregnancy.

From 8th to 14th day

The woman should take the last missed tablet as soon as you remember about it, even if this means taking two tablets at the same time. Next she continues to take tablets 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.

From 15 th to 24 th day

The risk of reduced reliability is imminent because of the approaching phase of receiving the inactive tablets. A woman should strictly adhere to one of the two following options. Thus, if during the 7 days preceding the first missed tablet, taken all the tablets correctly, there is no need to use additional contraceptive methods. Otherwise it is necessary to use the first of the following schemes and additionally use a barrier method of birth control (such as a condom) for 7 days.

1. The woman 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 following tablets taken at the usual time, there are no more active pills in a pack. Four inactive tablets should be discarded and immediately start taking pills of the next pack. Withdrawal bleeding is unlikely until the end active tablets in the second pack, but may experience spotting and breakthrough bleeding while taking the pills.

2. The woman may also interrupt taking the tablets from the current package. Then she should take a break of not more than 4 days, including the days of skipping pills, and then start taking the drug from a new package.

If the woman missed active tablets, and while taking inactive pills bleeding cancellation does not come, it is necessary to exclude pregnancy.

Recommendations in the gastro-intestinal disorders

In severe gastrointestinal disorders, absorption may not be complete, therefore it is necessary to take additional contraceptive measures.

If within 4 hours after taking active pill vomiting occurs, it should be guided by the recommendations by skipping pills. If a woman does not want to change their usual dosage regimen and move the start of menstruation to another day of the week, more active pill should be taken from a different package.

How to change the menstrual cycles or delay the onset of menstruation

To delay the onset of menstruation, the woman should continue taking the tablets from the next package Yaz , skipping inactive tablets from the current package. Thus, the cycle can be extended at will, at any time, there are no more active tablets in the second package. Against the background of the drug from the second package, women may experience spotting or breakthrough uterine bleeding. Regular intake of Yaz then resumed after the end of the reception phase of inactive pills.

To move the start of menstruation to another day of the week, the woman should be reduced the next phase of receiving the inactive tablets to the desired number of days. The shorter the interval, the higher the risk that she will not have withdrawal bleeding, and will continue to spotting and breakthrough bleeding while taking the second package.

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, whose connection with the drug intake is not confirmed, but not refuted.

The incidence of adverse events was classified as follows: often (ge 1/100), rarely (ge1 / 1000, t1 / 100), rare (t1 / 1000).

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

CNS: often - asthenic syndrome, headache, depressed mood, mood swings, nervousness rarely - headache, decreased libido, rarely - increase libido.

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

On the part of the reproductive system: often - breast pain, breast tenderness, menstrual disorders, vaginal candidiasis, uterine bleeding infrequently - hypertrophy of the breast is rare - vaginal discharge, discharge from the breast.

On the part of the skin and its appendages: often - rarely acne - rash, urticaria, rarely - erythema nodosum, erythema multiforme.

Other: often - increased body mass infrequently - fluid retention rarely - weight loss, hypersensitivity reactions.

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

In women with hereditary angioedema estrogen may cause or worsen its symptoms.

Contraindications:

Yaz drug should not be used in the presence of any of the conditions listed below. If any of these conditions develop for the first time in patients receiving the drug should be immediately repealed.

• Thrombosis (venous and arterial) and thromboembolism present or in history (including deep vein thrombosis, pulmonary embolism, myocardial infarction), cerebrovascular disorders
  
• State prior thrombosis (including transient ischemic attack, 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 valve lesions complicated by atrial fibrillation of the heart device cerebral vascular disease or coronary artery uncontrolled hypertension serious surgery with prolonged immobilization smoking over the age of 35 years)
  
• Pancreatitis with severe hypertriglyceridemia now or in history
  
• Hepatic failure, and severe liver disease (as long as liver tests are not normalized)
  
• Liver tumors (benign or malignant) at present or in history
  
• Severe renal insufficiency, acute renal failure
  
• Adrenal insufficiency
  
• Hormone identified malignant diseases (including genital or mammary glands) or are suspected
  
• Vaginal bleeding of unknown origin
  
• Pregnancy or suspected it
  
• Lactation
  
• Hypersensitivity to any component of the drug Yaz.
  

The use with caution

If any of the conditions / risk factors mentioned 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:

• Risk factors for thrombosis and thromboembolism (smoking thrombosis, myocardial infarction or cerebrovascular accident at a young age in any of the next of kin dislipoproteinemia obesity hypertension migraine valvular heart disease irregular heartbeat prolonged immobilization serious surgical interventions extensive trauma)
  
• Other diseases, which may occur when peripheral circulatory disorders (diabetes mellitus, systemic lupus erythematosus, hemolytic uremic syndrome, Crohn's disease and 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, cholelithiasis, otosclerosis with hearing impairment, porphyria, herpes gestationis, Sydenham's chorea)
  
• Postpartum period.
  

Pregnancy and lactation:

Yaz is not indicated during pregnancy and lactation.

If pregnancy is detected during the reception Yaz drug, the drug should be immediately abolished. However, extensive epidemiological studies have revealed no increased risk of defects in children born to women who received sex steroids (including combined oral contraceptives) before pregnancy, or teratogenic effects when sex steroids were taken inadvertently in early pregnancy.

Existing data on the results of Yaz receiving the drug during pregnancy are limited, that does not allow any conclusions on the effect of the drug on pregnancy, health of the newborn and the fetus. Any relevant epidemiological data on drug Yaz currently available.

Admission combined oral contraceptives can reduce the amount of breast milk and change its composition, therefore, 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 the newborn.

Special instructions:

If any of the conditions / risk factors mentioned 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 the drug. In the case of aggravation, or amplification of the first manifestations of any of these conditions or risk factors, the woman should consult with your doctor, who can decide whether to cancel 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 50 mcg ethinyl estradiol), up to 4 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 per 10 000 person-years.

The risk of thrombosis (venous and / or arterial) and thromboembolism is increased:

• with age
  
• Smokers (with the number of cigarettes or increasing age the risk further increases, especially in women older than 35 years). Women taking combined oral contraceptives are strongly encouraged to quit smoking
  
• The presence of family history (ie 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 resolve the question of the possibility of using combined oral contraceptives
  
• Obesity (body mass index greater than 30 kg / m2)
  
• When dislipoproteinemia
  
• Arterial hypertension
  
• Migraine
  
• For diseases of the heart valves
  
• Atrial fibrillation
  
• With prolonged immobilization, major surgery, any surgery to the legs, or major trauma. In these situations, it is desirable to discontinue the use of combined oral contraceptive (in case the intended operation of at least four weeks prior to it) and not to resume reception within two 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. 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 (t 50 mcg ethinyl estradiol).

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. Communication with the reception of combined oral contraceptives has not been proved. Contradictions persist as to the extent to which these findings are 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 observed increase in risk may be due to an earlier diagnosis of breast cancer in women who use combined oral contraceptives, the biological effects of oral contraceptives or a combination of both factors. In women who used combined oral contraceptives, clinically revealed less pronounced 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 benign and extremely rare - malignant 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 at the initial concentration of potassium in the ULN while receiving drugs that lead to potassium retention. However, in women with an increased risk of hyperkalemia it is recommended to determine the concentration of potassium in the plasma during the first cycle Yaz receiving the drug.

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

Although a slight increase in blood pressure have been reported in many women taking COCs, clinically relevant increases were 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 systemic lupus erythematosus, hemolytic uremic syndrome, Sydenham's chorea herpes pregnant hearing loss associated with otosclerosis. cases of Crohn's disease are also described and ulcerative colitis background on the use of combined oral contraceptives.

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

Acute or chronic disturbances of liver function may require the cancellation of combined oral contraceptives 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 diabetics using low-dose combined oral contraceptives (t50 mcg ethinyl estradiol). However, women with diabetes should be carefully monitored during the reception of combined oral contraceptives. Sometimes it can 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.

Laboratory tests

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.