Levonorgestrel, ingested, absorbed quickly and completely. 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). Value product fractions (free, albumin-linked and associated GSM) depends on the blood levels of SHBG. Following induction of protein binding, the fraction associated with SHBG increases, while the free and bound albumin fraction decreases. The sustanon 250 gains accumulation in the body when levonorgestrel daily intake occurs 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 20 Miniziston FEM concentration of SHBG increases by about 70% due to the fact that the preparation contains ethinylestradiol. The total concentration levonorgestrel serum increases linearly with its specific binding capacity. Levonorgestrel level in serum does not undergo further changes after one to three courses of regular reception because the induction of the activity of SHBG ends. Upon reaching equilibrium concentration of state level levonorgestrel in serum in three to four 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. Ethinylestradioladopted into ethinylestradiol It absorbed quickly and completely. Upon receiving the FEM 20 Miniziston maximum drug concentration in serum is approximately 60-70 pg / l is achieved in one to two hours.Then, the serum concentration of ethinyl estradiol is reduced, and the reduction is biphasic; the first phase is characterized by a half-life of the drug within 1-2 hours, The second one is within 10-20 hours. For technical reasons these parameters can only be calculated while taking the drug at high doses. It has been established 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 and the first passage through the liver, resulting in reduced individual variations and its bioavailability when administered orally. Ethinyl estradiol is not eliminated in a free form; its metabolites are eliminated, the half-life is equal to about one day. The ratio of the proportion of metabolites excreted in urine to the fraction released in the bile, corresponding to 40: 60. Due to the relatively large half-life of the drug in the terminal elimination phase, when the equilibrium concentration by 30-40% above the content of the drug in the plasma than after application for five or six days. The absolute bioavailability of ethinyl estradiol is subject to considerable individual variations. After receiving Miniziston 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. The reception 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.
Miniziston FEM 20 must 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.
- The presence of thrombosis (venous and arterial) present or in history (eg deep vein thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular accident).
- Available now or in the history of the state prior to thrombosis (eg, transient ischemic attack, angina pectoris)
- Diabetes mellitus with vascular complications.
- The presence of serious or multiple risk factors for venous or arterial thrombosis may also be regarded as a contraindication
- The presence of current or a history of severe liver disease (as long as liver function tests have not come back to normal).
- Available now or history of liver tumors (benign or malignant).
- Identified hormone malignant diseases (eg genital or mammary glands) or are suspected.
- Vaginal bleeding of unknown origin.
- Pregnancy or suspected it.
- Hypersensitivity to any component of Miniziston 20 FemDosing and Administration
Drops should be taken in the order indicated on the package, every day at 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 seven-day break, during which withdrawal bleeding usually occurs. It usually begins in the second or third day after the last pills, and can not end before you start taking a new package.
How to start admission Miniziston 20 Fem
- Without taking any hormonal contraceptive use in the preceding month.
Admission Miniziston 20 Fem begins on the first day of the menstrual cycle (ie the first day of menstrual bleeding). Shall start receiving 2-5 days 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 contraceptives. Preferably start taking Miniziston 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”, an injectable form, implant)
The woman may switch from the mini-pill to Miniziston 20 Fem any day (without a break), with the implant – the date of its removal from the injection mold – from the day sustanon 250 gains 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 an abortion in the first trimester
The woman may start taking immediately. Subject to this condition the woman does not need additional contraceptive protection.
- After delivery or abortion in the second trimester of pregnancy,
women should be advised to start taking the drug at 21-28 days after delivery or abortion in the second 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 Miniziston 20 Fem pregnancy should be excluded or must wait for the first menstrual period. Receiving 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, should be 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:
- The drug should never be interrupted for more than 7 days
- For an 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
should take the last missed pills as soon as possible, as soon as you remember (even if this means taking two pills at once). 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 to the period of the pass, do not provide for their admission, the higher the risk of pregnancy.
- The second week of
woman should take the last missed pills as soon as possible, as soon as you remember (even if this means taking two pills at once). 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 so, or woman misses more than 1 tablet, you should use extra precautions for 7 days.
- The 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 elections, there is no need to use extra contraceptive precautions, provided that in the 7 days preceding the first missed pills 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 two pills at once). Next take the pills at the usual time. Admission pills of the next pack should be started as soon as the end of the current package of pills, ie without the usual break. Withdrawal bleeding is unlikely, but may experience spotting or breakthrough bleeding during the tablet-taking.
2. A woman can also interrupt the reception of pills from the current package. Then sustanon 250 gains she should take a break from taking pills continuously for up to seven days, including the day of skipping pills, and then start receiving new packaging.
If the woman misses pills and then while taking pills she had no withdrawal bleeding, it is necessary to exclude pregnancy. Advice in case gastrointestinal disorders (vomiting) If she vomited within 3 to 4 hours after ingestion of pills, absorption may not be complete, 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 do I change the first day of the menstrual cycle or delay the onset of menstruation To delay the onset of menstruation, the woman should continue receiving new packaging Miniziston 20 Fem 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 her next break in taking pills for as many days, as much as she wants. The shorter the interval, the higher the risk that she will have spotting and breakthrough bleeding while taking second pack (just as when she wanted to delay the onset of menses).Side effects
The following undesirable effects have been reported in women taking Miniziston 20 Fem, and their relationship with the drug has neither been confirmed nor refuted: pain and tension of the mammary glands, breast enlargement, discharge from the breast; headache; migraine; changes in libido; reduction / mood changes; poor tolerance of contact lenses; nausea; vomiting; other gastrointestinal disorders; changes in vaginal secretion; various skin disorders); fluid retention; change in body weight; hypersensitivity reaction.
Sometimes it can develop chloasma, especially in women with a history of chloasma during pregnancy.
See. Warnings also. Overdose
No serious side effects have been reported in overdose. Symptoms that may occur with overdose include nausea, vomiting and, in young girls, slight vaginal bleeding. There is no specific antidote; should be symptomatic treatment.
Cautions and Warnings
If any of the conditions / risk factors mentioned below are currently available, you should carefully weigh the potential risks and expected benefits of treatment Miniziston 20 of themes in each individual case and discussed with the woman before she decides 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 the combined oral contraceptive.
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 low estrogen dose (less than 50 micrograms ethinylestradiol) is up to 4 to 10 women a year in the company compared to 0.5-3 per 10 women LLC a year to women not use of oral contraceptives. However, the incidence of venous thromboembolism while taking combined oral contraceptives, is less than the rate associated with pregnancy (6 to 10 OOO pregnant women per year).
In women taking combined oral contraceptives are described in extremely rare cases, thrombosis in other blood vessels, eg, hepatic, mesenteric, renal arteries and veins, central retinal vein and its branches.Contact receiving combined oral contraceptive has not been proved.
Symptoms of venous and arterial thrombosis include pain in one leg, its swelling or a combination thereof; sudden onset of severe pain in the chest (regardless of whether it radiates to the left arm); sudden shortness of breath; suddenly starts teasing cough; severe prolonged dull headache; sudden partial or complete loss of vision; diplopia; violation of articulation or aphasia; collapse, sometimes accompanied by local spasms; weakness or very severe paresthesia, suddenly appearing on one side or in one part of the body; motor disturbances; . “acute” abdomen
risk of thrombosis (venous and / or arterial) and thromboembolism is increased:
y smoking (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 (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;
-ozhireniya (body mass index over 30 kg / m2);
-zabolevany heart valves;
-Duration immobilization, major surgery, any surgery to the legs, or major trauma. In these situations it is desirable to discontinue the use of combined oral contraceptives (in the case of the planned operation, at least four weeks prior to her) and not to renew the appointment within two weeks after the immobilization.
It is necessary to take into account the increased risk of thromboembolism during the postpartum period.
Circulatory disorders may also celebrated in diabetes mellitus, systemic lupus erythematosus, hemolytic uremic syndrome, chronic inflammatory bowel disease (Crohn’s disease or ulcerative colitis) and sickle cell disease.
The increase in the frequency and severity of migraine during use of combined oral contraceptives (which may be preceded by cerebrovascular disorders) may be grounds 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 antibody (cardiolipin antibodies, lupus anticoagulant). it should be borne in mind that the risk of thrombosis during pregnancy is higher than when taking combined oral contraceptives.
of the 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. Saved controversy as to the extent to which these findings relate to the characteristics of sexual behavior and other factors such as human papilloma virus.
Meta-analysis of epidemiological studies have demonstrated that there is a slightly increased relative risk (RR = 1.24) of developing breast cancer diagnosed in women who 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 during treatment with combined oral contraceptives was observed the development of liver tumors. 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. Acceptance of 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 It has not been proven: jaundice and / or pruritus related to cholestasis; the formation of gallstones; porphyria; systemic lupus erythematosus; hemolytic uremic syndrome; chorea; herpes gestationis; hearing loss associated with otosclerosis. Cases of Crohn’s disease and ulcerative colitis during treatment with combined oral contraceptives have also been described.
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 combined oral contraceptives.
Although combined oral contraceptives may have an effect on insulin resistance and glucose tolerance, there is no need to change the therapeutic regimen in diabetics using low-dose COCs (<0.05 mg ethinylestradiol). However, women with diabetes should be carefully observed while taking combined oral contraceptives.
Women with a tendency to chloasma while taking combined oral contraceptives should avoid prolonged exposure to sunlight and ultraviolet radiation.
- Laboratory tests
using combined oral contraceptives can affect the results of certain lab tests, including liver function, 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.Interaction with other drugs
Drug interactions that result in increased clearance of sex hormones can lead to breakthrough bleeding and / or reduce the contraceptive reliability.
This has been established with respect to phenytoin, barbiturates, primidone, carbamazepine and rifampicin; also have assumptions about oxcarbamazapine, topiramate, felbamate and griseofulvin. The mechanism of this interaction sustanon 250 gains is based on the change in the work of liver enzymes.
The contraceptive protection is reduced when taking 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 Miniziston 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 Miniziston of themes to be used a barrier method of contraception (eg, condoms). If the use of the following drugs launched in the end of the reception package Miniziston 20 Fem, the next pack should be started without the usual break at the reception.
The women receiving these drugs long course, should be encouraged to other (non-hormonal) method of contraception (eg, condoms).
While taking combined oral contraceptives may experience irregular bleeding (spotting or breakthrough bleeding), especially during the first months of use. Therefore, the evaluation of any irregular bleeding should be performed only after a period of adaptation of approximately three cycles.
If the 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.These may include 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 menstrualopodobnyh bleeding, to continue receiving the drug should be excluded pregnancy.
Pregnancy and lactation
Miniziston 20 Fem is not appointed during pregnancy. If pregnancy is detected during the reception Miniziston 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.
Receiving combined oral contraceptives can reduce the amount of breast milk and change its composition, therefore, 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.
Before you start the application Miniziston 20 Fem she will need to undergo a thorough general medical and gynecological examination (including breast examination and cytological examination of cervical mucus), exclude unusual, severe or prolonged headache or migraine attack; partial or complete loss of vision or double vision; slurred speech; sudden changes in hearing, smell or taste; dizziness or fainting;weakness or numbness in any part of the body; severe abdominal pain; severe pain in the leg, or sudden swelling caused any of the legs.