Description
Release form
film-coated tablets
Packing
21 pcs.
Pharmacological action
Strengthens – an oral combination drug with antiandrogenic effect, contains ethinyl estradiol as estrogen and dienogest as progestogen. The contraceptive effect of the drug is due to various factors, the most important among them are – inhibition of ovulation, increased viscosity of cervical mucus, changes in the peristalsis of the fallopian tubes and endometrial structure. The antiandrogenic effect of the combination of ethinyl estradiol and dienogest is based on a decrease in the concentration of androgens in plasma.
In repeated studies, it was shown that taking a combination of ethinyl estradiol and dienogest led to the alleviation of symptoms of mild to moderate acne and had a positive result in patients with seborrhea.
Dienogest is a derivative of norethisterone, which has 10-30 times lower affinity for progesterone receptors in vitro compared to other synthetic progesterones. Dienogest has no significant androgenic, mineralocorticoid, or glucocorticoid effects in vivo.
When isolated at a dose of 1 mg / day, dienogest inhibits ovulation.
Pharmacokinetics
EE
Absorption. EE after oral administration is rapidly and completely absorbed in the small intestine. Cmax in plasma – 67 pg / ml, Tmax – 1.5-4 hours. During the initial passage through the liver, a significant part of EE is metabolized. Absolute bioavailability is approximately 44%.
distribution. EE is almost completely (about 98%), although non-specific, binds to albumin. EE increases the plasma concentration of sex hormone binding globulin (SHBG). The apparent Vd is 2.8 8.6 l / kg.
Metabolism. EE is conjugated in the intestinal mucosa and in the liver. The main pathway of EE metabolism is aromatic hydroxylation, but its metabolism also leads to the formation of a large number of hydroxylated and methylated derivatives in free, glucuronated and sulfated form. The clearance is approximately 2.3 7 ml / min / kg.
Withdrawal. A decrease in the concentration of EE in plasma occurs in 2 stages: the 1st stage – T1 / 2 is 1 hour, the 2nd – 10 20 hours. EE is not excreted unchanged. EE metabolites are excreted by the kidneys and liver in a ratio of 4: 6. T1 / 2 metabolites – about 24 hours.
Equilibrium concentration. Css is achieved during the 2nd half of the treatment cycle, and the concentration of EE in serum increases by 2 times.
dng
suction. After oral administration, it is rapidly and completely absorbed in the intestine. Cmax in plasma is 51 pg / ml, Tmax is 2.5 hours. Absolute bioavailability while taking with EE is 96%.
distribution. DNG binds to blood plasma albumin and does not bind to SHBG and globulin, which binds corticosteroid hormones. The fraction of free DNG in plasma is 10%, while 90% are non-specifically bound to albumin. The apparent Vd is 37 45 liters.
Metabolism. DNG is mainly metabolized by hydroxylation, an alternative way is glucuronidation. Its metabolites are inactive and quickly eliminated from plasma, therefore, it is not possible to detect metabolites in blood plasma in significant quantities, this does not apply to unchanged DNG. The total clearance after a single dose is 3.6 l / h.
Withdrawal. T1 / 2 of DNG is about 9 hours. A small amount in unchanged form is excreted by the kidneys. When administered, 86% is excreted within 6 days, of which 42% is excreted during the first 24 hours, mainly by the kidneys.
Equilibrium concentration. Css is reached within 4 days.
Indications
oral contraception
treatment for mild to moderate acne (acne) with local treatment failure in women who need contraception.
Contraindications
Combined oral contraceptives (CPC) should not be used if any of the conditions / diseases listed below are present in a woman. The first occurrence of any of these conditions while taking a CPC, the drug should be stopped immediately:
hypersensitivity to the drug Siluet ® or any of its components
arterial and venous thromboembolic diseases at present or in history (for example, deep vein thrombosis, pulmonary thromboembolism arteries)
thrombosis (arterial and venous) and thromboembolism currently or in the anamnesis, incl. thrombosis, deep vein thrombophlebitis, pulmonary embolism, myocardial infarction, ischemic or hemorrhagic cerebrovascular disorders of the
state preceding thrombosis (including transient ischemic attacks, angina pectoris, complicated valvular heart disease, atrial fibrillation, atrial fibrillation, atrial fibrillation extended surgical intervention with prolonged immobilization, extensive trauma)
pancreatitis with currently expressed hypertriglyceridemia or a history of
porphyria
jaundice, congenital hyperbilirubinemia (Gilbert syndrome, Dubin-Johnson syndrome and Rotor cell-angiopenosis
or arterial thrombosis history of risk factors for arterial thrombosis: – diabetes mellitus with vascular complications (angiopathy, retinopathy)
– uncontrolled ar Terial hypertension (AH)
– severe dyslipoproteinemia.
congenital or acquired predisposition to arterial thrombosis, e.g. resistance to activated protein C, antithrombin III deficiency, protein C, S deficiency, hyperhomocysteinemia and the presence of antibodies to phospholipids (antibodies to cardiolipin, lupus anticoagulant)
smoking over the age of 35 years old
severe liver disease (including history) before normalization of liver function tests
liver tumors (benign or malignant) including a history of
hormone-dependent malignant diseases of the genital organs or mammary glands, including history, or suspicion of
bleeding from the vagina of an unclear genesis of
migraine with local neurological symptoms, including a history of
epilepsy
lactase deficiency, lactose intolerance, glucose-galactose malabsorption
pregnancy
lactation period.
Precautions: presence of risk factors (varicose veins, heart disease, overweight, bleeding disorder) requires a more thorough study before taking CPC smoking under the age of 35 years (if a woman can not quit smoking, another method of contraception should be used, especially in the presence of other risk factors), the potential risk should be carefully weighed and the expected benefits of the use of oral contraceptives in each individual case with the following diseases, conditions or risk factors: dyslipoproteinemia, diabetes without complications of arthritis, controlled arterial hypertension, fibrocystic mastopathy, uterine fibroids, endometriosis, history of multiple sclerosis, severe depression, impaired renal function, contact lens intolerance, Crohn’s disease, ulcerative colitis, superficial vein phlebitis, thromboembolism, acute cerebrovascular accident, myocardial infarction at a young age, chronic heart failure, breast cancer in relatives of the 1st degree of kinship, visual impairment (risk of retinal thrombosis), tetany, hypercalcemia, hypokalemia, bronchial asthma, hereditary angioedema, liver disease, idiopathic jaundice during a previous pregnancy, herpes during pregnancy.
Use during pregnancy and lactation
Siluet ® is contraindicated during pregnancy.
If pregnancy occurs during the administration of the drug Siluet ®, then the use of the drug should be stopped immediately. The available information regarding the use of the drug Siluet ® during pregnancy is too limited to draw conclusions about the negative effects of the drug Siluet ® on pregnancy, fetal and newborn health.
Extensive epidemiological studies have not revealed an increased risk of developmental defects in children born to women who took sex hormones for contraception before pregnancy or, through carelessness, in early pregnancy.
The drug Siluet ® is contraindicated for use in breast-feeding women.
Special instructions
Before you start or resume taking Siluet ®, you need to take a medical history (including family history) and also exclude pregnancy. It is necessary to measure blood pressure and conduct a general examination taking into account contraindications and warnings. It is necessary to explain to the woman the need to carefully read the instructions for use of the drug Siluet ® and follow the recommendations contained in it. The nature of medical examinations, including general medical and gynecological examination, is determined by the attending gynecologist individually for each woman and is carried out with a different frequency, but at least 1 time in 6 months. A woman should be warned that oral contraceptives do not protect against contracting HIV infection (AIDS) or any other sexually transmitted disease.
Decreased efficacy of
Decreased efficacy of the combination of EE and DNG occurs in the case of, for example, missed administration, gastrointestinal upsets or concomitant therapy.
Change in the nature of bleeding
The use of the drug Siluet ®, especially in the first 3 cycles, may be accompanied by the appearance of acyclic bleeding / bleeding from the vagina, which can be considered as a period of adaptation.
If irregular bleeding is constantly present or appears after previous normal cycles, the non-hormonal causes of these phenomena should be considered and malignant neoplasms and pregnancy excluded. In this case, you must consult a gynecologist.
In some women, withdrawal bleeding may not occur in the interval between doses of the drug. If a woman has taken Siluet ® as directed, pregnancy is unlikely. However, if a woman had a violation of the drug before the 1st pass of withdrawal bleeding, or if there were 2 passes, pregnancy should be excluded before continuing with Siluet ®. Herbal-based medicines containing Hypericum perforatum perforatum should not be used concomitantly with Siluet ® (due to their ability to reduce the plasma level of the drug and reduce the effectiveness of the combination of DNG and EE).
The use of combined oral contraceptives leads to an increased risk of venous thromboembolism (VTE). The risk of VTE is the highest in the 1st year of application of the CCP. The risk of VTE associated with taking a combination of DNG with EE is less than the risk associated with pregnancy, it accounts for 60 cases per 100,000 pregnancies. VTE is fatal in 1 ² 2% of cases.
Symptoms of arterial or venous thrombotic or thromboembolic complications may include the following conditions:
– unusual unilateral leg pain and / or edema
– sudden severe chest pain with possible radiation to the left arm
– sudden shortness of breath
any – unusual, severe prolonged headache
– sudden partial or complete loss of vision
– diplopia
– slurred speech or aphasia
– dizziness
– fainting, accompanied by a partial epileptic seizure or without it
– sudden weakness or significant numbness on one side or in one part of the body
– motor disorders
– acute abdominal syndrome.
The risk of venous thromboembolic complications increases:
– with age
– in the presence of a family history (VTE, which ever occurred in close relatives and parents at a relatively young age) if a congenital predisposition is possible, a woman should be referred to a specialist for decision-making about the appointment Siluet ®
– for prolonged immobilization, after serious surgery, any surgery on the legs, or after a serious injury. In these cases, it is preferable to stop taking the tablets (during planned operations for at least 4 weeks) and not to resume until 2 full weeks after remobilization. If the drug has not been canceled in advance,
antithrombotic therapy should be prescribed – for obesity (body mass index more than 30 kg / m2). There is no consensus on the role of varicose veins or thrombophlebitis of superficial veins in the occurrence and development of venous thrombosis.
The risk of arterial thromboembolic complications or the risk of stroke in women using a combination of DNG with EE increases:
– with age
– with dyslipoproteinemia
– presence of hypertension
– heart valve disease
– atrial fibrillation
– smoking – smokers are at increased risk of severe cardiovascular complications (such as myocardial infarction, stroke and age) smoked cigarettes.
The presence of one severe or several risk factors for the development of venous or arterial diseases, respectively, may also be a contraindication. The possibility of using anticoagulant therapy should also be taken into consideration. You should pay attention to women receiving the drug Siluet ®, the need to contact your doctor if you suspect the presence of symptoms of thrombosis. In case of suspected or proven thrombosis, the drug should be discontinued. In this case, women need to use other suitable methods of contraception due to the teratogenic effects of anticoagulant drugs (coumarins).
The increased risk of postpartum thromboembolism must be taken into account.
Diseases such as diabetes mellitus, SLE, hemolytic uremic syndrome, Crohn’s disease, ulcerative colitis, sickle cell anemia, increase the risk of venous thromboembolic diseases.
An increase in the frequency and severity of migraine when taking a combination of DNG and EE (which may be a harbinger of cerebrovascular accident) may be an indication for immediate withdrawal of the drug.
Tumors
Some epidemiological studies have reported an increased risk of developing cervical cancer with prolonged use of a combination of DNG and EE (more than 5 years). However, contradictions remain regarding the extent to which these cases are associated with sexual behavior and other factors, such as the human papillomavirus.
Studies have shown a slight increase in the relative risk (RR – relative risk – 1.24) of developing breast cancer in women who use CPC. The increased risk gradually decreases within 10 years after the withdrawal of these drugs.
In rare cases, against the background of the use of a combination of DNG and EE, benign liver tumors developed, in even more rare cases, malignant ones. In some cases, these tumors led to life-threatening intra-abdominal bleeding. With the appearance of severe pain in the upper abdominal region, an enlarged liver and signs of intraperitoneal bleeding in women taking combinations of DNG and EE, liver tumors should be excluded.
Other conditions
Women with hypertriglyceridemia, currently or in history, have an increased risk of developing pancreatitis when using a combination of DNG and EE. Although a slight increase in blood pressure has been described in many women taking a combination of DNG and EE, clinically significant increases were rare.
Nevertheless, if during the administration of CPC by women with AH there is a steady increase in blood pressure or sharp increases in blood pressure do not respond to antihypertensive therapy, the drug should be discontinued. If possible, the reception can be continued, if antihypertensive therapy achieved normal blood pressure values.
Acute or chronic liver disease may require you to stop taking Siluet ® until your liver function returns to normal.
Recurrent cholestatic jaundice, which developed for the first time during pregnancy or the previous intake of sex hormones, requires stopping the combination of DNG and EE.
Although a combination of DNG and EE can influence tissue resistance to insulin and glucose tolerance, there is usually no need to adjust the treatment regimen for patients with diabetes. However, women with diabetes should be closely monitored by a doctor while taking Siluet ®.
Against the background of the use of a combination of DNG and EE, the course of Crohn’s disease and ulcerative colitis may be aggravated.
Chloasma may appear periodically, especially in women with a history of pregnant chloasma. Women with a tendency to chloasma should avoid prolonged exposure to the sun and exposure to UV radiation while taking Siluet ®.
Laboratory tests
Contraceptive steroid use may affect the results of several laboratory tests, including biochemical parameters of liver, thyroid, adrenal and kidney function, as well as plasma levels of transport proteins, such as globulin that binds corticosteroid hormones, and lipid / lipoprotein fractions, on the parameters of carbohydrate metabolism, coagulation and fibrinolysis. Changes usually remain within the normal range.
Influence on the ability to drive vehicles and work with mechanisms. Siluet ® does not affect the ability to drive a car and use sophisticated equipment. When using the drug, the possibility of visual impairment or dizziness should be considered.
Composition of
1 tablet contains:
active ingredients:
ethinyl estradiol 0.03 mg,
dienogest 2 mg,
excipients:
lactose monohydrate – 47.66 mg
starch girosellum 10 mg, 10 mg – 10.4 – 10.4 65 mg
talc – 1.6 mg
potassium polacryline – 1.3 mg
magnesium stearate – 1.3 mg
film sheath:
Opadry II white 85F18422 (polyvinyl alcohol – 1.2 mg, titanium dioxide – 0.750 mg, macrogol 3350 – 0.606 mg, talc – 0.444 mg) – 3 mg
Dosage and administration
Inside, 1 tablet / day, every day, at about the same time, if necessary with a small amount of liquid, in the order indicated on the blister pack, for the 21st day. Reception of tablets from the next package begins 7 days after taking the last tablet from the previous package, during which withdrawal bleeding usually occurs. It usually begins on the 2nd 3rd day after taking the last pill and may not end at the beginning of taking the pill from the next package.
Switching from taking progesterone-only tablets can be done any day.
If hormonal contraception has not been used before (for a month)
Taking Siluet ® should be started on the 1st day of the menstrual cycle (i.e. on the 1st day of menstruation).
In the event of a switch from PDA
It is preferable to start taking Siluet ® the next day after the usual break in intake or the day after the last dose of the last tablet from the current package of oral contraceptives.
Injection form, implants
Transition from the use of implants is carried out on the day of removal of the implant during the transition from the injection form – the day after the last injection.
After an abortion in the first trimester of pregnancy
You can start taking it immediately, in this case there is no need to use additional contraception.
After childbirth or abortion in the second trimester
It is recommended to start taking the drug on the 21 28th day after childbirth or abortion in the second trimester of pregnancy. If you start taking the drug later, should warn a woman about the need to use additional barrier methods (condom) during the first 7 days. However, if sexual intercourse has already occurred, before starting CPC, it is necessary to exclude pregnancy or wait for the 1st menstruation.
Taking missed
tablets If the delay in taking the drug was less than 12 hours, contraceptive protection does not decrease. A woman should take the drug as soon as possible, taking the next pill at the usual time. If the delay in taking the pill was more than 12 hours, contraceptive protection may be reduced. In this case, one can be guided by the following two basic rules:
– the drug should never be interrupted for more than 7 days
– it takes 7 days to take the pill continuously to achieve adequate suppression of hypothalamic-pituitary-ovarian regulation.
Accordingly, the following tips can be given if the delay in taking the pills was more than 12 hours.
1st week. A woman should take the last missed pill as soon as possible, even if this means taking 2 tablets. at the same time. The next tablet is taken at the usual time. Additionally, a barrier method of contraception (such as a condom) should be used over the next 7 days. If there was sexual intercourse within a week before skipping a pill, the probability of pregnancy should be taken into account. The more pills missed and the closer this pass to the 7-day break in taking pills, the higher the risk of pregnancy.
2nd week A woman should take the last missed pill as soon as possible, even if this means taking 2 tablets. at the same time. The next tablet is taken at the usual time. In the event that within 7 days before the pass the woman took the pills correctly, there is no need for additional contraception. However, if she missed taking more than the 1st tablet, she should use additional methods of contraception (condom) for 7 days.
3rd week The risk of a decrease in reliability is inevitable due to the upcoming 7-day break in admission. However, by adjusting the schedule for taking the pills, weakening of contraceptive protection can be prevented. Subject to one of the 2 proposed methods, there is no need to use additional methods of contraception in case if within 7 days before the pass the woman took the pills correctly. Otherwise, she must follow 1 of these 2 methods, and also use additional methods of contraception for the next 7 days.
1. A woman should take the last missed pill as soon as possible, even if it means taking 2 tablets. at the same time. The next tablet is taken at the usual time. Reception of tablets from the next blister pack should be started immediately after the reception of the previous one, i.e. there should not be a usual break between receptions. Most likely, the woman will not have withdrawal bleeding until the end of the 2nd package, but she may have spotting spotting or breakthrough uterine bleeding on the days of taking the tablets.
2. It is possible to stop taking tablets from the current blister pack. Then there should be a 7-day break in taking the tablets, including the days of the missed tablets, and then you need to start taking the tablets from the new package. If a woman missed taking the pill and then in the 1st normal interval between doses of the drug she does not have withdrawal bleeding, pregnancy must be excluded.
If a woman has vomited within 4 hours after taking the
tablet, absorption may not be complete and additional contraceptive measures should be taken. In these cases, take a new (replacement) tablet as soon as possible. If possible, a new tablet should be taken within 12 hours after the usual time of administration. If more than 12 hours have passed, you should be guided by the recommendations for skipping tablets in the section for taking missed tablets.
If a woman does not want to change the normal regimen of taking pills, she should use an extra tablet from another blister pack.
How to delay withdrawal bleeding
In order to delay the onset of menstrual bleeding, a woman should continue taking Siluet ® from a new package immediately after taking all the pills from the previous one, without interruption in intake. Against the background of taking the drug from the 2nd package, a woman may have spotting or breakthrough uterine bleeding. Resume taking Siluet ® from a new pack should be after a normal 7-day break.
In order to transfer the day the menstrual bleeding begins to another day of the week, a woman can be recommended to shorten the next break in taking the pill for as many days as she wants. The shorter the interval, the higher the risk, that there will be no withdrawal bleeding and in the future, during the reception of the next package, spotting and breakthrough bleeding will appear (as well as in the case when she would like to delay the onset of menstrual bleeding).
Drug Interactions
Interactions associated with the activation of microsomal enzymes between oral contraceptives and other drugs can lead to breakthrough bleeding and / or decrease the effectiveness of contraception. These effects have been shown for hydantoin, phenobarbital, primidone, carbamazepine and rifampicin. Such effects are also possible for rifabutin, efavirenz, nevirapine, oxcarbazepine, topiramate, felbamate, ritonavir, griseofulvin and herbal drugs – drugs of St. John’s wort (Hypericum perforatum). The mechanism of these interactions is based on the ability of these drugs to activate microsomal liver enzymes.
According to clinical observations, the simultaneous administration of certain antibiotics (such as ampicillin and tetracycline) may lead to a decrease in the effectiveness of contraception, the cause of this phenomenon is unknown.
Women taking the above drugs for a short period of time (up to a week) should in addition to CPC temporarily use barrier methods of contraception, for example, during the period of taking one of the listed drugs and 7 days after.
Women taking rifampicin should use barrier methods during the time they take rifampicin and 28 days after graduation. If the concomitant drug is taken at the end of the pill from the package, the next package should be started immediately, without the usual gap.
With a long-term prescription of a concomitant drug with the ability to activate liver enzymes, the doctor may consider the need to increase doses of hormonal contraceptives. If this approach leads to adverse events (for example, irregular bleeding) or a decrease in effectiveness, another method of contraception must be used.
Based on in vitro studies, it has been shown that DNG does not inhibit cytochrome P450 using conventional concentrations, so this kind of interaction is not expected.
Drug interactions that enhance the clearance of sex hormones can lead to breakthrough uterine bleeding and a decrease in the contraceptive effectiveness of the drug.
overdose
Acute toxicity with oral administration of a combined preparation of EE and DNG with an overdose is low.
Symptoms: nausea, vomiting and bleeding / bleeding from the vagina may occur.
Treatment: symptomatic, no need for special therapy.
Storage Conditions
In a dark place at a temperature not exceeding 25 ° C.
Shelf life
2 years.
Deystvuyushtee substance
tinilÑstradiol, Dienogest
Dosage form
tablets
Prescribing
Prescribing
For women of childbearing age, Adults prescribed by a doctor
Gedeon Richter Vengriya
