Silhouette, 2 mg+0.03 mg 21 pcs

Pharmaceutical group:

Contraceptive (estrogen+gestagen).

Pharmacological effects:

Siluet® is an oral combination medicine with antiandrogenic effect, containing ethinyl estradiol as estrogen and dienogestrogen as progestagen. The contraceptive effect of Siluet® is caused by various factors, the most important of which are inhibition of ovulation, increase in cervical mucus viscosity, change of tubal peristalsis and endometrial structure. The antiandrogenic effect of the combination of ethinylestradiol and dienogestrone is based on a decrease in the concentration of androgens in the plasma.

In repeated studies it has been shown that administration of a combination of ethinylestradiol and dienogest resulted in levelling the symptoms of mild to moderate acne and had positive results in patients with seborrhea.

Dienogest is a norethisterone derivative that 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 administered in isolation at a dose of 1 mg/day, dienogestr inhibits ovulation.

Pharmacokinetics:

Ethinylestradiol:

Intake
Ethinylestradiol is rapidly and completely absorbed in the small intestine after oral administration. Cmax in plasma (67 pg/ml) is reached after 1.5-4 hours. During primary passage through the liver, a significant portion of ethinylestradiol is metabolized. Absolute bioavailability is approximately 44%.

Distribution
Ethinylestradiol is almost completely (about 98%), although non-specific, bound to albumin. Ethinylestradiol increases the plasma concentration of sex hormone binding globulin (hSPH). The apparent Vd is 2.8-8.6 L/kg.
Css is reached during the second half of the treatment cycle, and the serum concentration of ethinylestradiol increases 2-fold.

Metabolism
Ethinylestradiol undergoes conjugation in the intestinal mucosa and in the liver. The main route of metabolism of ethinylestradiol is aromatic hydroxylation, but its metabolism also produces a large number of hydroxylated and methylated derivatives in free, glucuronated, and sulfated forms. Clearance is approximately 2.3-7 ml/min/kg.

Extraction
Reduction of plasma concentration of ethinylestradiol occurs in two stages: the first stage of elimination half-life is 1 hour, the second – 10-20 hours. Ethinylestradiol is not excreted unchanged. Ethinylestradiol metabolites are excreted by the kidneys and liver in a ratio of 4:6. The T1/2 of the metabolites is about 24 h.

Dienogest:

Intake
After oral administration, it is quickly and completely absorbed in the intestine. Cmax in plasma (51 pg/ml) is reached after 2.5 h. Absolute bioavailability when concomitantly administered with ethinylestradiol is 96%.

Distribution
Dienogest is bound to plasma albumin and does not bind to hGH and globulin binding corticosteroid hormones. The fraction of free dienogest in plasma is 10%, while 90% is nonspecifically bound to albumin. The apparent Vd is 37-45 L.
Plasma HSPH concentration has no effect on the pharmacokinetics of dienogest. The plasma concentration of dienogest is increased 1.5-fold and the Css is reached within 4 days.

Metabolism
Dienogest is mainly metabolized by hydroxylation, the alternative route being glucuronidation. Its metabolites are inactive and rapidly eliminated from plasma, so no significant amounts of metabolites can be detected in blood plasma, this does not apply to unchanged dienogest. Total clearance after a single dose is 3.6 l/h. T1/2 of dienogest is about 9 h. A small amount is excreted unchanged by the kidneys. After oral administration of 0.1 mg/kg excretion by the intestine and the kidneys has a ratio of about 3.2. When administered orally 86% is excreted within 6 days, of which 42% is excreted within the first 24 hours, mainly by the kidneys.

Indications

Active ingredient

Composition

1 tablet contains:

active ingredients:

ethinylestradiol 0.03 mg,

Dienogest 2 mg,

excipients:

lactose monohydrate, 47.66 mg;

p>corn starch – 10.46 mg;

Hypromellose 2910 – 0.65 mg;

talc, 1.6 mg;

polacryline potassium, 1.3 mg;

/p>

magnesium stearate – 1.3 mg

coat film:

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

How to take, the dosage

Overly, 1 tablet/day, daily, at approximately the same time, if necessary with a small amount of liquid, in the order indicated on the blister pack, for 21 days. The pills from the next package start 7 days after the last tablet from the previous package, during which time withdrawal bleeding usually occurs. It usually begins on the 2nd or 3rd day after taking the last pill and may not end by the time the pills from the next package start.

The switch from progesterone-only pills can be made any day.

If hormonal contraception has not been used previously (within a month)

The use of Siluet® must be started on day 1 of the menstrual cycle (i.e. day 1 of menstruation).

If you are switching from CRC

It is preferable to start Siluet® the day after your usual break or the day after the last pill in your current oral contraceptive package.

Injectable form, implants

The transition from using implants is the day the implant is removed; if switching from an injectable form, the day after the last injection.

After an abortion in the first trimester of pregnancy

The administration can be started immediately; in this case, no additional contraception is necessary.

After delivery or 2nd trimester abortion

It is recommended that the drug be started on day 21-28 after delivery or 2nd trimester abortion. If initiated later, women should be advised to use an additional barrier method (condom) for the first 7 days. However, if sexual intercourse has already occurred, pregnancy should be ruled out or the woman should wait until her first menstrual period before starting PDA.

Missed pills

If the delay in taking the medication is less than 12 hours, contraceptive protection is not reduced. The woman should take the medication as soon as possible, taking the next pill at the usual time. If the pill is taken more than 12 hours late, contraceptive protection may be reduced. The following two basic rules can guide you in this process:

– taking the drug should never be interrupted for more than 7 days;

– 7 days of continuous pill taking is required to achieve adequate suppression of hypothalamic-pituitary-ovarian regulation.

The following advice may be given accordingly if the delay in taking the pills is more than 12 h.

The 1st week. The woman should take the last missed pill as soon as possible, even if this means taking 2 pills at a time. The next pill is taken at the usual time. In addition, a barrier method of contraception (e.g. condom) should be used for the next 7 days. If you had intercourse during the week before skipping the pill, you should consider the possibility of pregnancy. The more pills you miss and the closer you miss to the 7-day pill interval, the greater the risk of pregnancy.

The 2nd week. The woman should take the last missed pill as soon as possible, even if this means taking 2 pills at the same time. The next pill is taken at the usual time. If the woman has taken the pills correctly in the 7 days before missing the pill, no additional contraception is necessary. However, if she missed taking more than the 1st pill, she should use additional methods of contraception (condom) for 7 days.

The 3rd week. The risk of decreased reliability is unavoidable because of the upcoming 7-day break in intake. However, adjusting your pill schedule can prevent a weakening of contraceptive protection. If one of the 2 suggested methods is followed, there is no need to use additional contraceptive methods if the woman was taking the pills correctly during the 7 days before the skip. Otherwise, she must follow 1 of these 2 methods and use additional methods of contraception for the next 7 days.

1. The woman should take the last missed pill as soon as possible, even if that means taking 2 pills at the same time. The next pill is taken at the usual time. The pills from the next blister pack should be taken immediately after the previous one, i.e. after the usual interval between doses. It is most likely that the woman will not have a bleeding discontinuation until the end of the 2nd package, but she may have a mucous bleeding or breakthrough uterine bleeding during the days of taking the pills.

2. It is possible to stop taking pills from the current blister pack. Then there should be a 7-day break from taking the pills, including the days of missed pills, and then the pills from the new package should be started. If the woman missed taking the pill and then has no bleeding cancellation in the 1st normal interval between the pills, pregnancy must be ruled out.

If a woman has vomited within 4 h of taking the pill

If a woman has vomited within 4 h of taking the pill, absorption may be incomplete and additional contraceptive measures should be taken. In these cases, a new (replacement) pill should be taken as soon as possible. The new pill should, if possible, be taken within 12 hours after the usual time of ingestion. If more than 12 hours have elapsed, the recommendations for skipping pills should be followed in the section Taking Missed Pills.

If a woman does not want to change her normal pill regimen, she should use an extra pill from a different blister pack.

How to delay bleeding withdrawal

In order to delay the onset of menstrual bleeding, a woman should continue taking Siluet® from a new pack immediately after taking all pills from the previous one, without interruption. While taking the drug from the 2nd package, a woman may have oozing or breakthrough uterine bleeding. Resume taking Siluet® from a new pack after the usual 7-day break.

In order to move the start date of menstrual bleeding to another day of the week, a woman may be advised to shorten her immediate break from taking the pill by as many days as she wants. The shorter the interval, the higher the risk that there will be no withdrawal bleeding and that later, while taking the next pack, there will be oozing and breakthrough bleeding (just like when she would like to delay the start of her menstrual-like bleeding).

Interaction

Microsomal enzyme activation interactions between oral contraceptives and other medications may result in breakthrough bleeding and/or decreased contraceptive efficacy. These effects have been shown for guidantoin, phenobarbital, primidone, carbamazepine and rifampicin.

Such effects are also possible for rifabutin, efavirenz, nevirapine, oxcarbazepine, topiramate, felbamate, ritonavir, griseofulvin and herbal medicines – Hypericum perforatum. The mechanism of these interactions is based on the ability of these drugs to activate microsomal liver enzymes.

According to clinical data, simultaneous use with some antibiotics (such as ampicillin and tetracycline) can 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 use barrier methods of contraception temporarily in addition to CPK, for example during the period of taking one of the above drugs and 7 days after.

Women taking rifampicin should use barrier methods during the time they are taking rifampicin and 28 days after they finish. If taking a concomitant medication falls at the end of the pills in the pack, the next pack should be started immediately, without the usual interval.

If a concomitant drug with the ability to activate liver enzymes is prescribed for a long time, the physician may consider increasing the dose of hormonal contraceptives. If this approach causes adverse events (such as irregular bleeding) or decreased efficacy, another contraceptive method should be used.

Based on in vitro studies, it has been shown that DNG does not inhibit cytochrome P450 at normal concentrations, so no interaction of this nature is expected.

Drug interactions that increase clearance of sex hormones can lead to breakthrough uterine bleeding and decreased contraceptive efficacy of the drug.

Special Instructions

Before starting or restarting Siluet® , a medical history (including family history) should be taken and pregnancy should be ruled out. Blood pressure should be measured and a general examination should be conducted, taking into account contraindications and precautions. Explain to the woman the need to carefully read the instructions for the use of Siluet® and follow the recommendations contained therein. The nature of medical examinations, which include general medical and gynecological examination, is determined by the attending gynecologist on an individual basis for each woman and is carried out with varying frequency, but not less than once every 6 months. Women should be warned that oral contraceptives do not protect against contracting HIV infection (AIDS) or any other sexually transmitted disease.

Decreased efficacy

Decreased efficacy of the combination of EE and DNG occurs if, for example, you miss a dose, have gastrointestinal distress, or take concomitant therapy.

Changing bleeding patterns

The use of Siluet®, especially in the first 3 cycles, may be accompanied by the appearance of acyclic bleeding/bleeding from the vagina, which may be considered as a period of adjustment.

If irregular bleeding is persistent or occurs after previous normal, regular cycles, non-hormonal causes should be considered, and malignancy or pregnancy should be excluded. In this case, it is necessary to see a gynecologist.

In some women, bleeding cancellations may not occur between doses of the drug. If a woman has taken Siluet® according to the instructions, pregnancy is unlikely. However, if a woman has had an irregularity in taking the drug before the 1st bleeding skip, or if there have been 2 skips, pregnancy should be ruled out before continuing to take Siluet®. Herbal medications containing Hypericum perforatum should not be used concomitantly with Siluet® (because of their ability to reduce plasma levels and decrease 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 highest in year 1 of PDA use. The risk of VTE associated with taking a combination of DNG with EE is less than the risk associated with pregnancy, at 60 per 100,000 pregnancies. VTE is fatal in 1-2% of cases.

The symptoms of arterial or venous thrombotic or thromboembolic complications may include the following conditions:

– unusual unilateral leg pain and/or swelling;

– sudden severe chest pain with possible irrigation to the left arm;

– sudden shortness of breath;

– sudden onset of coughing;

– any unusual, severe prolonged headache;

– sudden partial or complete loss of vision;

– diplopia;

– slurred speech or aphasia;

– dizziness;

– fainting, with or without a partial epileptic seizure;

– sudden weakness or significant numbness on one side or in one part of the body;

– motor disturbances;

– acute abdominal syndrome.

The risk of venous thromboembolic complications is increased:

– with age;

– if there is a family history (VTE ever occurring in close relatives and parents at a relatively young age); If there may be a congenital predisposition, the woman should be referred to a specialist for a decision on whether to prescribe Silhouette®;

– when there is prolonged immobilization, after major surgery, any leg surgery or after major trauma. In these cases, it is preferable to stop taking the pills (for elective surgery at least 4 weeks in advance) and not resume until 2 full weeks after remobilization. If the drug was not withdrawn in advance, antithrombotic therapy should be prescribed;

– in obesity (body mass index more than 30 kg/m2). There is no consensus about the role of varicose veins or superficial venous thrombophlebitis in the occurrence and development of venous thrombosis.

The risk of arterial thromboembolic complications or risk of stroke is increased in women using the combination of DNG with EE:

– with age;

– in the presence of dyslipoproteinemia;

– the presence of AH;

– heart valve disease;

– atrial fibrillation;

– Smoking – smokers have an increased risk of serious cardiovascular complications (such as myocardial infarction, stroke); the risk increases with age and the number of cigarettes smoked.

The presence of one severe or more risk factors for venous or arterial disease, respectively, may also be a contraindication. The use of anticoagulant therapy should also be taken into consideration. Women receiving Siluet® should be advised to contact their physician if symptoms of thrombosis are suspected. In case of suspected or proven thrombosis, the drug should be discontinued. At the same time, women should use other suitable methods of contraception due to the teratogenic effect of anticoagulant drugs (coumarins).

The increased risk of thromboembolism in the postpartum period should be taken into account.

Diseases such as diabetes mellitus, SLE, hemolytic-uremic syndrome, Crohn’s disease, nonspecific ulcerative colitis, and sickle cell anemia increase the risk of venous thromboembolic disease.

An increase in the frequency and severity of migraines when taking the combination of DNG and EE (which may be a precursor to cerebral circulation disorders) may be an indication for immediate withdrawal of the drug.

Tumors

Some epidemiological studies have reported an increased risk of cervical cancer with long-term use of the combination of DNG and EE (more than 5 years). However, controversy persists about the extent to which these cases are related to sexual behaviors and other factors, such as human papillomavirus.

The studies show some increase in the relative risk (RR – relative risk – 1.24) of developing breast cancer in women who have used PDA. The increased risk gradually declines over a 10-year period after withdrawal of these drugs.

In rare cases, development of benign liver tumors has been observed with the combination of DNG and EE, and in even rarer cases, malignant tumors. In some cases, these tumors have led to life-threatening intra-abdominal bleeding. If severe upper abdominal pain, liver enlargement, and signs of intra-abdominal bleeding occur in women taking combinations of DNG and EE, liver tumors should be ruled out.

Other conditions

Women with current or history of hypertriglyceridemia have an increased risk of pancreatitis when using the combination of DNG and EE. Although small increases in BP have been described in many women taking combinations of DNG and EE, clinically significant increases have been rare.

Nonetheless, if stable BP increases are noted while taking PDA in women with AH or if BP spikes do not respond to hypotensive therapy, the drug should be discontinued. If possible, administration may be continued if normal BP values are achieved with hypotensive therapy.

Acute or chronic liver disease may require discontinuation of Siluet® until liver function returns to normal.

Recurrent cholestatic jaundice developing for the first time during pregnancy or previous use of sex hormones requires discontinuation of the DNH and EE combination.

While the combination of DNG and EE may affect tissue insulin resistance and glucose tolerance, there is usually no need to adjust the regimen in diabetic patients. However, women with diabetes should be closely monitored by a physician while taking Siluet®.

The course of Crohn’s disease and ulcerative colitis may worsen with the combination of DNH and EE.

Chloasma may occasionally appear, especially in women with a history of pregnancy chloasma. Women with a history of chloasma should avoid prolonged sun exposure and exposure to UV radiation while taking Siluet®.

Laboratory studies

. Contraceptive steroid use may affect several laboratory findings, including biochemical measures of liver, thyroid, adrenal, and renal function and plasma levels of transport proteins such as corticosteroid hormone-binding globulin and lipid/lipoprotein fractions, carbohydrate metabolism, coagulation, and fibrinolysis parameters. Changes usually remain within normal values.

Impact on the ability to drive vehicles and operate machinery. Siluet® has no effect on the ability to drive vehicles and operate complex machinery. When using the drug the possibility of visual impairment or dizziness should be considered.

Contraindications

Combination oral contraceptives (CICs) should not be used if any of the conditions/diseases listed below are present in a woman at this time. The first time any of these conditions occur while taking a CPC, the drug should be stopped immediately:

Side effects

Blood and lymphatic system disorders: rare – anemia.

The heart: rare – tachycardia; very rare – myocardial infarction.

Nervous system disorders: frequent – headache; infrequent – migraine, irritability, dizziness; rare – cerebral circulatory disorders.

As for the eyes: rare – visual impairment, conjunctivitis, dry mucous membranes, intolerance to contact lenses.

Hearing and labyrinth organ: rarely – hypoacusis, tinnitus, sudden hearing loss, hearing disorders.

Respiratory organs, chest and mediastinum: rarely – sinusitis, bronchial asthma, bronchitis.

Gastrointestinal system disorders: frequently – nausea, vomiting; infrequently – abdominal pain; rarely – diarrhea, dyspepsia, gastritis, enteritis; very rarely – cholecystitis, cholelithiasis.

With the kidneys and urinary tract: infrequent – infection of the urinary system.

Skin and subcutaneous tissue disorders: infrequent – acne, acneiform dermatitis, exanthema, skin allergic reactions, chloasma, alopecia, erythema multiforme, skin itching, including generalized itching, erythema nodosa, vascular purpura; rarely – hypertrichosis, virilism, hyperhidrosis, seborrhea, hyperpigmentation, eczema, dandruff, angioedema, telangiectasia (spider veins).

Metabolism and nutrition: frequently – weight gain; infrequently – increase of appetite, weight loss; rarely – decreased appetite.

Infectious and parasitic diseases: infrequent – vaginitis, vaginal candidiasis; rare – fungal infections, herpetic lesions of the oral cavity.

Vascular system disorders: infrequent – AH, arterial hypotension, varicose veins, superficial vein thrombophlebitis; rare – deep vein thrombophlebitis, thrombosis, pulmonary embolism, hematoma, stroke, hot flashes, pain along the veins.

General disorders and disorders at the site of administration: infrequent – feeling of fatigue/malaise, edema; rarely – flu-like symptoms.

The immune system: rarely – allergic reactions.

Perior genital system disorders: frequent – pain and soreness of the mammary glands, enlarged mammary glands; infrequent – acyclic bloody discharge or bleeding, painful menstrual-like bleeding, ovarian cysts, dyspareunia, increased discharge from the vagina, endometrial hyperplasia, vaginitis/vulvovaginitis, salpingitis, endometritis; rarely – scanty menstrual bleeding, mastitis, cystic fibrosis of the mammary glands, breast secretions, leiomyoma, endometritis, salpingitis, cervicitis, vulvovaginal pruritus, breast lipoma; very rare – endometrial cancer.

Psychiatric disorders: often – decreased mood; rarely – insomnia, sleep disturbances, depression, anorexia, changes in libido, aggressiveness, apathy.

Skeletal, muscular and connective tissue disorders: often – back pain, cramps in the calf muscles; rarely – arthralgia, myalgia.

The following serious adverse events have been reported in women using Siluet®:

– venous thromboembolic disorders;

– arterial thromboembolic disorders;

– AH;

– liver tumors;

– the occurrence or exacerbation of conditions for which there is no proven association with PDA intake – Crohn’s disease, ulcerative colitis, porphyria, systemic lupus erythematosus, herpes of pregnancy, Sydingham chorea, hemolytic-uremic syndrome, cholestatic jaundice;

– chloasma.

The incidence of breast cancer in women taking PDA increases very slightly. Because breast cancer rarely occurs in women under the age of 40, this excess is very small relative to the overall risk of developing breast cancer. Breast cancer is a hormone dependent tumor. Known risk factors for breast cancer, such as early menarche, late menopause (later than age 52), no childbirth, having anovulatory cycles, etc., indicate a role for hormones in the development of the disease. Receptors to hormones play a key role in the cell biology of breast cancer, and estrogens can increase the effects of growth factors (e.g., TGF-alpha).

Epidemiological studies have shown a possible causal link between long-term use of CRPS starting at a young age and the development of breast cancer in middle age. However, PDA use is only one of many risk factors.

Overdose

Acute oral toxicity of the combined drug EE and DNG in overdose is low.

Symptoms: possible nausea, vomiting and bloody discharge/bleeding from the vagina.

Treatment: symptomatic, no special therapy is necessary.

Pregnancy use

Siluet® is contraindicated during pregnancy.

If pregnancy occurs while taking Siluet® , the drug should be stopped immediately. The information available regarding the use of Siluet® during pregnancy is too limited to draw conclusions about the adverse effects of Siluet® on pregnancy, fetal and neonatal health.

Extensive epidemiologic studies have found no increased risk of birth defects in children born to women who took sex hormones for contraception before pregnancy or, inadvertently, in early pregnancy.

The drug Siluet® is contraindicated in breastfeeding women.

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