Expiration date: 11/2026

Structure and Composition:

Dragee. 1 dragee contains:

0.02 mg ethinylestradiol

levonorgestrel 0.1 mg

Excipients: lactose monohydrate, corn starch, corn starch modified, polyvidone 25000, sucrose, magnesium stearate, polyvidone 700000, polyethylene glycol 6000, calcium carbonate, talc, glycerol 85% iron pigment oxide yellow, iron pigment oxide red, titanium dioxide, wax

in blister 21 pcs. In the paper cartons 1 or 3 blisters.

Characteristic:

Monophasic combined oral contraceptive.

Pharmacokinetics:

levonorgestrel

Levonorgestrel, ingested, absorbed quickly and completely. Cmax of the drug in the blood serum, equal to approximately 2 ng / ml achieved after about 1 hour after ingestion Minizistone 20 Fem. Reduced serum levels of the drug has a biphasic exemplary T1 / 2 in the first phase was 0.5 hours in the second - 20 hours. The metabolic clearance rate from plasma is approximately 1.5 ml / min / kg.

Levonorgestrel is not excreted in unchanged form: it is eliminated as metabolites with T1 / 2 duration of about 1 day, and almost the same part of the kidney and biliary system. Biotransformation occurs on common pathways of metabolism of steroids. Biologically active substances are not found among the metabolites.

Levonorgestrel binds to serum albumin and globulin, sex hormone binding (SHBG). Only about 1.5% relative the total concentration of the drug found in the serum in free form, while about 65% is bound to SHBG. Value product fractions (free, albumin-linked and associated GSM) depends on the blood levels of SHBG. Following induction binding protein fraction associated with SHBG increases, while the free and bound albumin fraction decreases.

The accumulation in the body of levonorgestrel in its daily intake is almost entirely in the second elimination phase. State of the equilibrium concentration is reached on the 3-4th day. Pharmacokinetics of levonorgestrel dependent on the concentration of SHBG in plasma. When receiving Minizistone 20 Fem SHBG concentration increases by approximately 70%, due to the fact that this drug contains ethinyl estradiol.

The total concentration levonorgestrel serum increases linearly with its specific binding capacity. The level of levonorgestrel in serum does not undergo further changes after the 1-3 regular courses reception because the induction of the activity ends. Upon reaching equilibrium concentration of state level levonorgestrel in serum is 3-4 times higher than after a single dose.

The absolute bioavailability of levonorgestrel is close to 100%.

Approximately 0.1% of the dose of levonorgestrel obtained mother passed the child with milk.

Ethinylestradiol

Taken internally ethinylestradiol is absorbed rapidly and completely. Upon receiving the Minizistone 20 Fem drug Cmax serum equal to about 60-70 pg / l is achieved in 1-2 hours. Then, the serum concentration of ethinyl estradiol is decreased, and the decrease is the first phase of the biphasic characterized T1 / 2 within 1 preparation -2 hours, the second -. within 10-20 h For technical reasons, these figures can only be calculated while taking the drug in high doses.

It is found that the apparent volume of distribution of ethinyl estradiol is about 5 liters / kg, and its metabolic clearance rate from plasma is about 5 ml / min / kg. Ethinylestradiol highly (98%), albeit nonspecifically binds albumin.

Ethinyl estradiol is metabolized in the suction phase of the first passage through the liver, resulting in reduced individual variations and its bioavailability when administered orally. Ethinyl estradiol is not eliminated in the free form are eliminated its metabolites, T1 / 2 is equal to about 1 day. The ratio of the proportion of metabolites excreted in the urine, to the share allocated to the bile, corresponds to 40:60.

Due to the relatively large T1 / 2 of the drug in the terminal phase elimination of the drug content in the plasma when the equilibrium concentration is 30-40% higher than after application for 5-6 days.

The absolute bioavailability of ethinyl estradiol is subject to considerable individual variations. After receiving Minizistone 20 Fem inside it is about 40-60% of the dose.

In nursing mothers about 0.02% of the daily dose of ethinyl estradiol can enter the body of the child with breast milk.

Acceptance of other drugs may affect the systemic bioavailability of ethinyl estradiol. However, interaction with high doses of vitamin C have been identified. Chronic administration of ethinyl estradiol induces an increase in the synthesis of corticosteroid-binding globulin (CBG) and GSM, and the degree of induction of SHBG synthesis depends on the type and dose of progestogen is used at the same time.

Description of the pharmacological actions:

The contraceptive effect Minizistone 20 Fem based on the interaction of various factors, the most important of which are inhibition of ovulation and changes in cervical mucus viscosity.

In addition to the contraceptive action of combined oral contraceptives have a positive impact, which should be considered when choosing a method of family planning. The cycle is more regular and less painful periods are observed, reduced the amount of bleeding, thereby reducing the risk of iron deficiency anemia.

Indications:

Contraception.

Contraindications:

Minizistone 20 Fem should not be used if 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:

• Hypersensitivity to any component of Minizistone 20 Fem
  
• the presence of thrombosis (venous and arterial) present or in history (eg deep vein thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular accident)
  
• the existence at the present time or in the state history of previous thrombosis (eg transient ischemic attack, angina pectoris)
  
• diabetes with vascular complications
  
• the presence of serious or multiple risk factors for venous or arterial thrombosis
  
• the presence of current or a history of severe liver disease (as long as liver function tests have not come back to normal)
  
• the presence of current or a history of liver tumors (benign or malignant)
  
• hormone-dependent cancers identified (eg genital or mammary glands) or are suspected
  
• vaginal bleeding of unknown origin
  
• pregnancy or suspected it.
  

Application of pregnancy and breastfeeding:

Minizistone 20 Fem is not appointed during pregnancy. If pregnancy is detected during the reception Minizistone 20 Fem, the drug immediately canceled. However, extensive epidemiological studies have revealed no increased risk of defects in children born to women treated with hormones prior to pregnancy or teratogenic effects when sex hormones were taken inadvertently in early pregnancy.

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

Side effect:

The following undesirable effects have been reported in women taking Minizistone 20 Fem, but their relationship to the drug has been neither confirmed nor refuted: hypersensitivity reactions, pain and tension of the mammary glands, breast enlargement, discharge from the breast headache migraine libido change reduction / mood changes poor tolerance of contact lenses nausea, vomiting, other gastrointestinal disorder changes the vaginal secretion of a variety of skin disorders fluid retention weight change.

Sometimes it can develop chloasma, especially in women with a history of chloasma during pregnancy.

Drug Interactions:

Drug interactions that result in increased clearance of sex hormones can lead to breakthrough bleeding and / or reduce the contraceptive reliability.

It was established in respect of phenytoin, barbiturates, primidone, carbamazepine and rifampicin also have assumptions about oxcarbamazapine, topiramate, felbamate and griseofulvin. The mechanism of this interaction is based on the change in the work of liver enzymes.

The contraceptive protection is reduced with antibiotics (such as ampicillin and tetracycline). This mechanism of action has not been elucidated.

Women treated with any of the above classes of drugs, short-course, in addition to the 20 Minizistone Fem should temporarily use a barrier method of contraception at the time of concomitant drug administration and for 7 days after their cancellation. While receiving rifampicin and for 28 days after its cancellation in addition to 20 Minizistone of themes to be used a barrier method of contraception (eg condom). If the use of the following drugs launched in the end of the reception package Minizistone 20 Fem, the next pack should be started without the usual break at the reception.

Women receiving these drugs long course, should be encouraged to other (non-hormonal) method of contraception (eg condom).

Dosage and administration:

Inside, on a daily basis, in the order indicated on the package, about the same time, if necessary with a small amount of liquid. Take one tablet a day continuously for 21 days. Drops of each subsequent packaging are beginning to take after a 7-day break, during which withdrawal bleeding usually occurs. It usually begins 2-3 days after receiving the last pills, and can not end before you start taking a new package.

How to start taking Minizistone 20 Fem

Without taking any hormonal contraceptive use in the previous month

Admission Minizistone 20 Fem begins on the first day of the menstrual cycle (ie the first 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

Preferably start taking Minizistone 20 Fem next day after taking the last active pills from the previous package, but in any case not later than the day after the usual 7-day break in the reception (for products containing 21 pills) or after the last inactive pills ( for preparations containing 28 pills in the package).

When switching from contraceptives containing only progestin (mini-pill, injectable form, implant)

A woman can go to the mini-pill to Minizistone 20 Fem any day (without a break), with the implant - the date of its removal from the injection mold - the day when the next injection should have to be made. In all cases, you must use an additional barrier method of contraception during the first 7 days of tablet-taking.

After the abortion I trimester of pregnancy

The woman may start taking immediately. Subject to this condition the woman does not need additional contraceptive protection.

After delivery or abortion in the II trimester of pregnancy

Women should be advised 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 tablet-taking. However, if a woman has been sexually active, before you start taking Minizistone 20 Fem pregnancy should be excluded or must wait for the first menstrual period.

Admission missed pills

If the delay in taking pills is less than 12 hours, contraceptive protection is not reduced. The woman should take pills as soon as possible, the following - taken at the usual time.

If the delay in taking pills made more than 12 hours, contraceptive protection may be reduced. It is possible to be guided by the following two basic rules:

- Receiving the drug should never be interrupted for more than 7 days

- For adequate suppression of the hypothalamic-pituitary-ovarian system requires several days of continuous tablet-taking.

Accordingly, we can give the following practical tips.

The first week of taking the drug

The woman should take the last missed pills as soon as possible as soon as you remember (even if this means taking 2 tablets at the same time). Next take the pills at the usual time. In addition to be used a barrier method (condom) for the next 7 days. If intercourse took place during the week before skipping pills, you need to take into account the chance of pregnancy. The more pills missed and the closer this pass to the period unintended health taking them, the higher the risk of pregnancy.

second week

The woman should take the last missed pills as soon as possible as soon as you remember (even if this means taking 2 tablets at the same time). Next take the pills at the usual time.

Provided that the woman has taken pills correctly in the 7 days preceding the first missed pills, there is no need to use additional contraceptive measures. However, if this is not the way or the woman misses more than 1 tablet, you should use extra precautions for 7 days.

third week

The risk of reduced reliability is imminent because of the approaching scheduled break in receiving pills.

However, by adjusting the tablet-taking mode, you can still prevent a decrease contraceptive protection. If you adhere to any of the following two rules, there is no need to use extra contraceptive precautions, provided that in the 7 days preceding the first missed pills, the woman took all the pills correctly.

1. The woman should take the last missed pills as soon as possible, as soon as you remember (even if this means taking 2 tablets at the same time). Next take the pills at the usual time. Acceptance of the next pack should be started as soon as the end pellets in the current package, ie without the usual break. Withdrawal bleeding is unlikely, but may experience spotting or breakthrough bleeding during the tablet-taking.

2. The woman may also interrupt the reception of pills from the current package. Then she should take a break in the reception of up to 7 days, including the day of skipping pills and start taking a new package.

If a woman misses, and then while taking pills she had no withdrawal bleeding, pregnancy must be excluded.

Tips in case of gastro-intestinal disorders (vomiting)

If the woman was vomiting within 3 to 4 hours after ingestion, absorption may be incomplete, it is necessary to focus on advice on the pellets pass. If a woman does not want to change the normal dose, it must take, if necessary, additional pills (or more pellets) from a new package.

How to change the day of the menstrual cycle or delay the onset of menstruation

In order to delay the onset of menstruation, the woman should continue to receive a new package of themes Minizistone 20 without interruption. Drops of this new packaging can be accepted as long as they do not run out. Against the background of the drug from the second package, women may experience spotting from the vagina or breakthrough uterine bleeding. Then make the seven-day break, and then resume the regular intake of medication.

In order to move the first day of menstruation to another day of the week, a woman should shorten the next break in taking pills for as many days, as much as she wants. The shorter the interval, the higher the risk that the bore will be spotting and breakthrough bleeding while taking second pack (just as when she wanted to delay the onset of menses).

Overdose:

No serious side effects have been reported in overdose.

Symptoms: nausea, vomiting and, in young girls, slight vaginal bleeding.

Treatment: symptomatic. No specific antidote.

Precautionary measures:

If any of the conditions / risk factors mentioned below are currently available, you should carefully weigh the potential risks and expected benefits of treatment Minizistone 20 Fem 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. A number of epidemiological studies have revealed a slight increase in the incidence of venous and arterial thrombosis and thromboembolism while taking combined oral contraceptives.

Venous thromboembolism, manifested in the form of deep vein thrombosis and / or pulmonary embolism, may occur during the use of combined oral contraceptives. Approximate frequency of venous thrombosis and thromboembolism in women taking oral contraceptives, with a low dose of estrogen (ethinyl estradiol content - less than 50 mcg) is up to 4 per 10,000 women per year compared to 0.5-3 per 10,000 women per year - in patients Not used oral contraceptives. However, the incidence of venous thromboembolism while taking combined oral contraceptives less than the rate associated with pregnancy (6 per 10,000 pregnant women per year).

In women taking combined oral contraceptives are described in very rare cases of thrombosis, other blood vessels, eg hepatic, mesenteric, renal arteries and veins, central retinal vein and its branches. Communication with the reception of combined oral contraceptives has not been proved.

Symptoms of venous and arterial thrombosis include pain in one leg, her swelling or a combination of sudden onset of severe chest pain (regardless of whether or not it radiates to the left arm) sudden shortness of breath sudden starts racking cough severe prolonged dull headache sudden partial or complete loss of vision or double vision violation articulation aphasia collapse, sometimes accompanied by local spasms weakness or very severe paresthesia, suddenly appearing on one side or in one part of the body movement disorders acute abdomen.

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

a) age

b) smokers (with the number of cigarettes or increasing age the risk further increases, especially in women over 35 years old)

c) in the presence of:

- Family history (ie venous or arterial thromboembolism ever in close relatives or parents at a relatively young age) if the supposed hereditary 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 -> 30 kg / m2)

- dislipoproteinemia

- Hypertension

- Diseases of the heart valves

- Atrial fibrillation

- 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 4 weeks before it), resuming the reception and for 2 weeks after the immobilization.

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

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.

Biochemical parameters which can be indicative of hereditary or acquired predisposition to venous or arterial thrombosis include resistance to activated protein C, hyperhomocysteinemia, deficiency of antithrombin-III, deficiency of protein C, protein deficit S, antiphospholipid antibodies (antibodies to cardiolipin, lupus anticoagulant).

Keep in mind that the risk of thrombosis during pregnancy is higher than when taking combined oral contraceptives.

Tumors. An increased risk of cervical cancer in long-term use of combined oral contraceptives has been reported in some epidemiological studies. His connection with the intake of combined oral contraceptives has not been proved. Contradictions persist as to the extent to which these findings relate to the characteristics of sexual behavior and other factors such as human papilloma virus.

A meta-analysis of epidemiological studies showed that there is a slightly increased relative risk (RR = 1,24) of breast cancer diagnosed in women who are at the time of the study were used combined oral contraceptives. His connection with the intake of combined oral contraceptives has not been proved. The observed increase in risk may be due to an earlier diagnosis of breast cancer in women using combined oral contraceptives. Breast cancers in women who had ever used combined oral contraceptives were clinically less severe than in women, never did not use them.

In rare cases, against the background of the use of combined oral contraceptives was observed liver tumor development. 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. Women with hypertriglyceridemia, or a family history of it, we can not exclude an increased 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 hypertension, a doctor is prudent for the cancellation of these drugs and the treatment of hypertension. Receiving COCs can be continued, if using antihypertensive therapy 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.

Acute or chronic disturbances of liver function may require the elimination of the use 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 (ethinyl estradiol content - <0.05 mg). However, women with diabetes should be carefully monitored during the reception of combined oral contraceptives.

Women with a tendency to chloasma to the reception of 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.

Special instructions:

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, it should be considered non-hormonal causes and implemented adequate diagnostic measures to exclude malignancy or pregnancy (vkyuchaya diagnostic curettage).

In some women withdrawal bleeding may not develop during a break in taking pills. If the drug is taken according to directions, it is unlikely that the woman is pregnant. However, if before the pills are taken regularly or if there are no two consecutive menstrualnopodobnoe bleeding, to continue receiving the drug should be excluded pregnancy.

On the application of the drug during pregnancy and lactation, see. In the field "Application of pregnancy and lactation."

Medical examinations. Before starting the application Minizistone® 20 Fem she will need to undergo a thorough general medical and gynecological examination (including breast examination and cytological examination of cervical mucus), exclude pregnancy. In addition, to exclude blood coagulation disorders.

In the case of long-term use of the drug must be at least 1 once a year check-up.

It should warn the woman that drugs such Minizistone 20 Fem do not protect against HIV infection (AIDS) and other sexually transmitted diseases through!

Effects on ability to drive machinery. There were no effects.