ethinyl estradiol, dienogest | Dieziklen tablets coated.pl.ob. 2 mg + 0.03 mg 21 pcs.

Release form

Tablets.

Packing

21 tablets.

Pharmacological action

Pharmaceutical group: contraceptive (estrogen + progestogen).

Pharmaceutical Action: Dicyclylene is a low-dose monophasic oral hormonal contraceptive. The contraceptive effect is based on the interaction of various factors, the most important of which is the inhibition of ovulation and a change in the viscosity of cervical mucus, as a result of which it becomes impermeable to sperm, sperm penetration through the cervical canal is difficult. With proper use, the Pearl index (an indicator that reflects the number of pregnancies in 100 women who use contraceptives during the year) is less than 1. If the pill is missed or if it is used incorrectly, the Pearl index can increase.

In addition to the contraceptive effect, it also has other concomitant positive properties. In women taking combined oral contraceptives, the cycle becomes more regular, the pain, intensity and duration of menstrual bleeding decreases, resulting in a reduced risk of iron deficiency anemia. There is also evidence of a reduction in the risk of endometrial and ovarian cancer.

The progestogen component of the preparation, dienogest, is an active progestogen, It is a derivative of nortestosterone with antiandrogenic activity and has a positive effect on the lid profile, increasing the concentration of high density lipoproteins (HDL).

Pharmacokinetics: Ethinyl estradiol: When taken orally, it is rapidly and completely absorbed. The maximum concentration of estradaol in blood plasma (about 67 pg / ml) is achieved after 1.5-4 hours. After absorption and the effect of the "first passage" through the liver, ethinyl estradiol is metabolized, its absolute bioavailability when administered orally is about 44%.

Ethinyl estradiol significantly binds to serum albumin (approximately 98%) and induces the synthesis of sex hormone binding hormones (SHBG) in the blood plasma. The volume of distribution of ethinyl estradiol is about 2.8-8.6 l / kg.

Ethinylzstradiol undergoes presystemic conjugation both in the mucous membrane of the small intestine and in the liver. The main metabolic pathway is aromatic hydroxylation with the formation of many hydroxylated and methylated derivatives in the form of free metabolites, metabolites of glucuronides and sulfates. The clearance rate from blood plasma is approximately 2.3-7 ml / min / kg.

Up to 30-50% of ethinylzstradiol A metabolites are excreted by the kidneys, 30-40% through the intestines. The half-life of zstradiol (T1 / 2) does not exceed 10 hours after a single dose of 1 tablet and rises to 15 hours after 3 cycles of taking the drug.

The equilibrium concentration of ethinylzstradiol in blood plasma with regular admission is achieved in the second half of the cyclic administration of the drug.

Dienogest: When taken orally, it is rapidly and almost completely absorbed. The maximum concentration of dienogest in the blood serum (about 51 pg / ml) is achieved after 2.5 hours. The absolute bioavailability of the dienogest is 96%, the equilibrium concentration in the blood plasma with constant use is reached after 4 days.

90% of the total plasma concentration of dienogest binds to serum albumin, but does not bind to SHBG, or a corticosteroid-binding globulin. In unbound form is 10% of the total concentration of dienogest in blood plasma. The volume of distribution of dienogest is about 37-45 liters.

Metabolized mainly by hydroxylation, but also by hydrogenation, conjugation and aromatization with the formation of inactive metabolites. After taking a single dose, the total clearance of the dienogest is about 3.6 l / h.

After taking a dose of 0.1 mg / kg, the ratio of excretion of dienogest in the form of metabolites by the kidneys and through the intestines is 3: 1. Only a small amount of unchanged dienogest is excreted by the kidneys. The half-life (T1 / 2) of dienogest is approximately 8.5-10.8 hours. After oral administration, 86% of the accepted dose of dienogest is excreted within 6 days, a significant part of it is excreted in the first 24 hours after administration mainly by the kidneys.

Equilibrium concentration. Induction of ethinyl estradiol ol globulin synthesis does not affect the pharmacokinetics of dienogest. With daily use of the drug, the concentration of dienogest in serum increases by 1.5 times.

Indications

- oral contraception

- treatment of mild to moderate acne and seborrhea.

Contraindications

- hypersensitivity to any of the components of the drug Dicyclin

- thrombosis (venous and arterial) and thromboembolism at present or in the anamnesis (including deep vein thrombosis, pulmonary artery thromboembolism, pulmonary heart disease, - conditions preceding thrombosis (including transient ischemic attacks, angina pectoris) at present or in the history of

- multiple or pronounced risk factors for venous or arterial thrombosis, m including complicated lesions of the valvular apparatus of the heart, atrial fibrillation, diseases of the vessels of the brain or coronary arteries uncontrolled arterial hypertension, volumetric surgery with prolonged immobilization, smoking over the age of 35 years, obesity with a body mass index> 30 kg / m2

- diabetes mellitus with diabetic angiopathy

- detected predisposition venous or arterial thrombosis, including resistance to activated protein C, antithrombin III deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinemia, anti la to phospholipids, lupus antigen

- severe liver disease (before reduction and normalization of liver function laboratory parameters)

- benign or malignant liver tumors, including a history of

- severe forms of arterial hypertension with blood pressure> 160/100 mm Hg. Art.

- identified or suspected hormone-dependent malignant diseases of the genitals or mammary glands, including in the history of

- vaginal bleeding of unknown origin

- migraine with focal neurological symptoms at present or in the history of

- pancreatitis, accompanied by severe hypertriglyceridemia at present or in the history of

- severe or severe her

- lactation period

- hereditary lactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome or hypersensitivity to peanuts or soy (due to the presence of Leave the drug Dicyclylene lactose and soya lecithin).

Precautions: Risk factors for thrombosis and thromboembolism: obesity, smoking, dyslipoproteinemia, arterial hypertension, migraine without focal neurological symptoms, heart valve defects, prolonged immobilization, serious surgical intervention, extensive trauma, a hereditary predisposition to thrombosis (thrombosis, myocardial infarction or impaired cerebral circulation in young people of close relatives).

Other diseases in which peripheral circulation disorders can occur: diabetes mellitus without diabetic angiopathy, superficial vein phlebitis, systemic lupus erythematosus (SLE), hemolytic-uremic syndrome, Crohn's disease, ulcerative colitis, sickle cell anemia.

Diseases that arose for the first time or worsened during pregnancy or against the background of previous use of sex hormones, for example, jaundice and / or itching with cholestasis, gallbladder disease, porphyria, Sydenham chorea, a history of herpes during pregnancy, hearing loss (associated with otosclerosis).

Endogenous depression, epilepsy, hereditary angioedema, hypertriglyceridemia, liver disease of the postpartum period.

Use during pregnancy and lactation

Dicyclylene is contraindicated during pregnancy. If pregnancy is detected, oral contraceptives should be discontinued immediately.

If it is necessary to use the drug during lactation, it is necessary to decide on the termination of breastfeeding.

Special instructions

Irregular use can lead to acyclic bleeding and reduce the contraceptive effectiveness of the drug.

Before starting or resuming the use of the drug, it is recommended to conduct a thorough general medical and gynecological examination (including examination of the mammary glands and cytological examination of scraping from the cervix), to exclude pregnancy. In addition, violations of the blood coagulation system should be excluded. When using the drug, it is necessary to conduct preventive control examinations at least 1 time in 6 months.

The drug Dicyclin does not protect against HIV infection (AIDS) and other sexually transmitted diseases.

Diseases of the cardiovascular system: Venous thromboembolism (VTE) may occur in the form of deep vein thrombosis and / or pulmonary embolism with the use of hormonal contraceptives. The approximate incidence of VTE in women taking oral contraceptives with a low dose of estrogen (less than 50 micrograms of ethinyl estradiol) is up to 4 per 10 thousand women per year, compared with 0.5-3 per 10 thousand women not using oral contraceptives. However, the frequency of VTE developing when taking combined oral contraceptives is less than the frequency of VTE associated with pregnancy (6 per 10 thousand. pregnant women per year).

In women taking combined oral contraceptives, extremely rare cases of thrombosis of other blood vessels, such as the hepatic, mesenteric, renal arteries and veins, or retinal veins and arteries, are described. The relationship of these cases with the use of combined oral contraceptives has not been proven. A woman needs to stop taking the drug and consult a doctor if symptoms of venous or arterial thrombosis develop, which may include one-sided pain in the lower limb and / or edema, sudden severe chest pain with or without radiation in the left arm, sudden shortness of breath, sudden coughing attacks, any unusual, severe , prolonged headache, increased frequency and severity of migraine, sudden partial or complete loss of vision, diplopia, inarticulate speech, or aphasia, dizziness, collapse with or without a partial seizure, weakness or very significant loss of sensitivity, which suddenly appeared on one side or in one part of the body, motor disturbances of an acute abdomen.

The risk of thrombosis (venous and / or arterial) and thromboembolism increases: with age, in smokers (with an increase in the number of cigarettes smoked or an increase in age, the risk further increases, especially in women over 35), with a family history (i.e. venous or arterial thromboembolism ever in close relatives or parents at a relatively young age), obesity dyslipoproteinemia, arterial hypertension, heart valve disease, prolonged immobilization, extensive surgery, any surgery on the lower extremities or extensive trauma, atrial fibrillation.

In case of prolonged immobilization, in case of serious surgical intervention, any leg surgery or extensive injury, it is advisable to stop using the drug (in case of a planned operation, at least 4 weeks before it) and not to resume taking it within 2 weeks after the end of the immobilization.

The question of the possible role of varicose veins and superficial thrombophlebitis in the development of venous thromboembolism remains controversial. The increased risk of postpartum thromboembolism should be considered.

Microcirculatory disorders can also occur in diabetes mellitus, SLE, hemolytic uremic syndrome, Crohn's disease, ulcerative colitis and sickle cell anemia.

Tumors: The most significant risk factor for cervical cancer is persistent human papillomavirus infection. There are reports of a slight increase in the risk of developing cervical cancer with prolonged use of combined oral contraceptives. However, the connection with the use of combined oral contraceptives has not been proven. The possibility of the relationship of these data with the screening of diseases of the cervix uteri and with the features of sexual behavior (a more rare use of barrier methods of contraception) is discussed.

A meta-analysis of 54 epidemiological studies showed that there is a slightly increased relative risk of developing breast cancer diagnosed in women currently taking combined oral contraceptives (relative risk 1.24). The increased risk gradually disappears within 10 years after stopping these drugs. Due to the fact that breast cancer is rare in women under 40 years of age, an increase in the number of breast cancer diagnoses in women who are currently taking combined oral contraceptives or who have recently taken is insignificant in relation to the overall risk of this disease. The relationship between the development of breast cancer and the use of combined oral contraceptives has not been proven. The observed increased risk may also be the result of careful observation and earlier diagnosis of breast cancer in women using combined oral contraceptives. Women who have ever used combined oral contraceptives have earlier stages of breast cancer than women never used them.

In rare cases, with the use of combined oral contraceptives, the development of benign, and in extremely rare, malignant liver tumors was observed, which in some cases led to life-threatening intraperitoneal bleeding. In the case of severe pain in the abdomen, liver enlargement, or signs of intra-abdominal bleeding, this should be considered when making a differential diagnosis.

Other conditions: Women with hypertriglyceridemia or a family history of it may have an increased risk of developing pancreatitis when taking combined oral contraceptives.

Although a slight increase in blood pressure (BP) has been described in many women taking combined oral contraceptives, clinically significant increases were rare. The relationship between the use of combined oral contraceptives and an increase in blood pressure has not been established. However, if persistent, clinically significant arterial hypertension develops during their administration, it is advisable to cancel combined oral contraceptives and treat hypertension. Taking combined oral contraceptives can be continued if normal blood pressure values ​​are achieved with antihypertensive therapy.

Effect on the menstrual cycle: Irregular (acyclic) bleeding (“spotting” spotting or “breakthrough” bleeding) may occur with combined oral contraceptives, especially during the first months of use. Therefore, any irregular bleeding should be evaluated only after an adaptation period of approximately 3 cycles.

If irregular bleeding recurs or develops after previous regular cycles, a thorough examination should be performed to rule out malignant neoplasms or pregnancy.

Some women may not develop “withdrawal” bleeding during a break in taking pills. If combined oral contraceptives were taken in accordance with the instructions, then pregnancy is unlikely. However, if before that combined oral contraceptives were taken irregularly, or if there are two consecutive “withdrawal” bleeding, then pregnancy should be excluded before continuing with the drug.

Effect on laboratory test results: The use of oral combination contraceptives may affect the results of some laboratory tests, including a biochemical blood test (indicators of liver, thyroid, kidney, and adrenal function, plasma transport protein concentrations (such as SHBG), carbohydrate metabolism, lipid / lipoprotein fractions), and coagulation and fibrinolysis. However, changes in these indicators remain within the normal range.

Influence on the ability to drive vehicles and mechanisms: There is no evidence of a negative effect of the drug Dicyclin on the ability to drive vehicles and engage in potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

Composition

1 tab.: - ethinyl estradiol 0.03 mg

- dienogest 2 mg

Dosage and administration

Inside, daily, preferably at the same time, in the order indicated on the package, with a small amount of water. Take 1 tablet per day continuously for 21 days. Taking pills from each next pack begins after a 7-day break, during which withdrawal bleeding (menstrual bleeding) is observed. It usually begins 2–3 days after the last tablet is taken and can continue until the tablet is started on a new package.

In the absence of any hormonal contraceptives in the previous month, the drug begins on the first day of the menstrual cycle (on the first day of menstrual bleeding). It is allowed to start taking on the 2nd-5th day of the menstrual cycle, but in this case it is recommended to additionally use the barrier method of contraception during the first 7 days of taking the tablets from the first package.

If you switch from the previous intake of other combined oral contraceptives, it is preferable to start taking the drug the day after taking the last active pill from the previous package, but later the next day after the usual 7-day break in taking (for drugs containing 21 tablets) or after taking last inactive tablet (for preparations containing 28 tablets per pack).

When switching from the vaginal ring of the transdermal patch, it is preferable to start taking Dicyclin on the day the ring or patch is removed, but no later than the day when a new ring is to be inserted or a new patch is glued.

When switching from contraceptives containing only progestogens ("mini-drank", injection forms, implant), the drug is taken: with "mini-drank" - on any day (without a break), from the implant - on the day of its removal, from the injection form - from the day when the next injection should have been made. In all cases, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the tablets.

After an abortion in the first trimester of pregnancy, you can start taking it immediately. If this condition is met, there is no need for additional contraceptive protection.

After childbirth or abortion in the second trimester of pregnancy, it is recommended to start taking Dicyclinum on the 21-28th day after childbirth or abortion. If you start it later, you must use the additional barrier method of contraception during the first 7 days of taking the pill. However, if a woman has already lived sexually, pregnancy should be ruled out before the start of taking the drugs or it is necessary to wait for the first menstruation.

Recommendations in case of irregular administration of the drug Dicyclin: If you miss the drug if the delay in taking the pill was less than 12 hours, the contraceptive protection does not decrease. You must take the pill as soon as possible, the next pill is taken at the usual time. If the delay in taking the pill was more than 12 hours, contraceptive protection may be reduced.

In the first 2 weeks of taking the drug, if the interval since taking the last pill is more than 36 hours: you need to 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. Additionally, a barrier method of contraception (condom) should be used over the next 7 days. If there was sexual intercourse for 1 week before skipping a pill, it is necessary to consider the likelihood of pregnancy. The more tablets missed and the closer this pass to the 7-day break in taking the drug, the higher the risk of pregnancy.

At 3 weeks of taking the drug, if the interval since taking the last pill is more than 36 hours: you must 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 (condom) should be used over the next 7 days. In addition, taking a pill from a new package should be started as soon as the current package is over i.e. nonstop. Most likely, there will be no withdrawal bleeding until the end of taking the tablets from the second package, but spotting or uterine breakthrough bleeding may occur on breakthrough days.

If a woman missed taking the pill and then during the break in taking the drug she does not have withdrawal bleeding, pregnancy must be excluded.

In case of gastrointestinal upsets: If a woman has vomiting or diarrhea within 3 to 4 hours after taking Dicyclylene, absorption may not be complete. In this case, it is necessary to focus on recommendations regarding skipping pills. If a woman does not want to change the normal regimen of taking the drug, she must take, if necessary, an additional tablet from a spare package.

Change in the day onset of menstrual bleeding: To delay the onset of menstrual bleeding, it is necessary to continue taking tablets from a new package immediately after all tablets from the previous one have been taken, without interruption in intake. Tablets from new packaging may be taken until the packaging is complete. Against the background of taking the drug from the second package, a woman may experience spotting or uterine breakthrough bleeding. Resume taking the drug from a new pack should be after the usual 7-day break.

In order to postpone the day of the onset of menstrual bleeding to another day of the week, it is necessary to shorten the immediate interval in taking Dicyclin tablets by as many days as you need to postpone the day of the onset of menstrual bleeding. The shorter the interval the higher the risk of the absence of withdrawal bleeding and the appearance of spotting and breakthrough bleeding in the future while taking tablets from the second package (as well as in case of delaying the onset of menstrual bleeding).

Drug interactions

Some drugs can increase the metabolic clearance rate of sex hormones and lead to severe bleeding or a decrease in the contraceptive effect of the drug. Similar effects are characteristic of drugs that induce microsomal liver enzymes: hydantoin, barbiturates, primidone, carbamazepine and rifampicin. There are also suggestions regarding rifabutin, efavirenza, nevirapine, oxcarbazenin, topiramate, felbamate, ritonavir, nelvinafir, fizeofulvin, as well as drugs containing St. John's wort perforated (Hypericum perforatum).

Some antibiotics that reduce the enterohepatic circulation of estrogens (such as ampicillin or tetracycline) decrease the effectiveness of combined oral contraceptives.

Women taking short courses (maximum 1 week) of the above medications should resort to additional contraceptive measures (for example, the barrier method) during the period of simultaneous use of the drug and for the next 7 days.

If you are using oral contraceptives with rifampicin, you should take additional contraceptive measures (e.g. barrier method) during the simultaneous use of drugs and in the next 4 weeks after discontinuation of treatment. If the packaging of oral contraceptives ends before the completion of the course of other drugs, the tablets from the next package of the drug should be taken without interruption.

Increase the dose of contraceptives with a long-term course of treatment with drugs that induce microsomal liver enzymes. In case of side effects (for example, irregular menstruation) or drug inefficiency, other non-hormonal contraceptives should be additionally used. Oral contraceptives may affect the metabolism of some other drugs. Accordingly, this can lead to an increase (cyclosporine) or a decrease (lamotrigine) of their concentration in plasma or tissues.

Dienogest is a substrate of cytochrome P450 (CYP3A4). Known CYP3A4 inhibitors, such as antifungal drugs (e.g. ketoconazole), cimetidine, verapamil, macrolides (e.g. erythromycin), diltiazem, antidepressants and grapefruit juice, can increase the concentration of dienogest in the blood plasma.

Overdose

Possible symptoms of an overdose of Dicyclin: nausea, vomiting, irregular spotting, lack of menstrual bleeding.

If necessary, symptomatic therapy is performed.

drugstore conditions

drugstore

dosage form

tablets

Appointment

Adults, by appointment women of childbearing age

Indications

seborrhea, for kontratseptsyy, Uhrevaya s p

Laboratory of Leon Pharma S.A, Spain