More info
Active ingredients
Ziproterone + Ethinyl Estradiol
Release form
Pills
Composition
Active ingredient: Tsiproteron + Ethinylestradiol (Cyproterone + Ethinylestradiol) Active ingredient concentration (mg): Cyproterone acetate 2 mg, ethyl estradiol 0.035 mg
Pharmacological effect
Combined low-dose monophasic oral contraceptive drug with antiandrogenna activity. The mechanism of action is due to its antiandrogenic steroid preparation, cyproterone acetate and oral estrogen, ethinyl estradiol. mainly in the adrenal glands, ovaries and skin. blocking androgen receptors in target organs, reduces the effects of androgenization in women (due to the disruption of processes mediated by hormone-receptor complexes at the level of the main intracellular mechanisms). thus, it becomes possible to treat diseases caused by increased formation of androgens or specific sensitivity to these hormones. against the background of the drug intake, the enhanced activity of the sebaceous glands, which plays an important role in the occurrence of acne and seborrhea, decreases. after 3-4 months of therapy, the existing rash usually disappears. excessive oily hair and skin disappears even earlier. hair loss that often accompanies seborrhea also decreases. Chloe therapy in women of reproductive age reduces the clinical manifestations of mild forms of hirsutism; However, the effect of treatment should be expected only after several months of use. In addition to its antiandrogenic properties, cyproterone acetate has a gestagenic activity that mimics the properties of the corpus luteum hormone. inhibits the secretion of pituitary gonadotropic hormones and inhibits ovulation, which contributes to the contraceptive effect. Ethinyl estradiol enhances the central and peripheral effects of cyproterone acetate on ovulation, retains a high viscosity of the cervical mucus, making it difficult for spermatozoa to penetrate the uterine cavity and help ensure the reliability of the device. regular, less frequent painful menstruation, reduced intensity of bleeding, reduced risk of iron itsitnoy anemia.
Pharmacokinetics
Tsiproterona acetateAfter taking the drug into the interior of cyproterone acetate is completely absorbed from the gastrointestinal tract. Cmax in plasma is reached after 1.6 hours and is 15 ng / ml. Bioavailability is 88%. Distribution Ziproterone acetate is almost completely bound to plasma albumin, in the free state is approximately 3.5-4%. Since protein binding is not specific, changes in the level of the globulin that binds sex steroids (GSPS) do not affect the pharmacokinetics of cyproterone acetate. Metabolism Biotransformed by hydroxylation and conjugation, the main metabolite is a 15b-hydroxyl derivative. 2.3 days respectively for the first and second phases. Total plasma clearance is 3.6 ml / min / kg. It is derived mainly in the form of metabolites by the kidneys and through the intestine at a ratio of 1: 2, a small part - unchanged through the intestine. With breast milk, up to 0.2% of the dose of cyproterone acetate is excreted. T1 / 2 for metabolites of cyproterone acetate is 1.8 days. Ethinyl estradiol After taking the drug, ethinyl estradiol is rapidly and completely absorbed from the gastrointestinal tract. Cmax is about 80 pg / ml and is reached after 1.7 h. Bioavailability is about 45%, has significant individual variability. Distribution: Plasma protein binding (albumin) is high: only 2% is in plasma in free form. Ethynyl estradiol increases liver hepatic synthesis of GSM and corticosteroid -binding globulin (CSG) with continuous use. With Chloe treatment, serum SHS concentration increases from approximately 100 nmol / L to 300 nmol / L, and the serum concentration of CGC increases from approximately 50 mcg / ml to 95 mcg / ml. Metabolism In the process of absorption and the first passage through the liver, ethinyl estradiol is extensively metabolized. Introduction of the ethinyl estradiol biphasic pharmacokinetics: T1 / 2 for 1-2 h and approximately 20 h, respectively. Plasma clearance is about 5 ml / min / kg. Ethinyl estradiol is excreted in the form of metabolites: about 40% by the kidneys, 60% through the intestines. With breast milk, up to 0.02% of ethinyl estradiol is excreted.
Indications
Contraception in women with androgenization phenomena, androgen-dependent diseases in women: acne (especially their pronounced forms, accompanied by seborrhea, inflammatory phenomena with the formation of nodes, papular-pustular acne, nodular cystic acne), androgenic alopecia and mild forms of hirsutism.
Contraindications
Hypersensitivity to the components of the drug, simultaneous use with another hormonal contraceptive, thrombosis (venous and arterial) or thromboembolism currently or in history (including deep venous thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular disorders, for example insulin ; conditions preceding thrombosis (including angina pectoris, transient ischemic attacks); multiple or severe risk factors for venous or arterial thrombosis (including complicated valvular valve defects) heart disease, atrial fibrillation, cerebral vascular disease or coronary arteries, uncontrolled arterial hypertension, severe dyslipoproteinemia, subacute bacterial endocarditis, prolonged immobilization, surgery on the lower extremities, neurosurgical operations, extensive traumas, age-aged surgery, age-related smoking, age, age, age-related surgery, age-related surgery, age-related smoking, age-related smoking, age, age-related surgery, age-related smoking, age, age-related surgery, age-related surgery, adult age body mass more than 30 kg / m2); revealed hereditary or acquired susceptibility to venous or arterial thrombosis, for example, resistance to protein C (APS), antithrombin III deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinemia and the presence of antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant), diabetes mellitus with diabetic angiopathy; liver function - no earlier than 6 months after normalization of liver function indicators, liver tumors (benign and malignant), hormone-dependent malignant tumors or suspicion n them, including tumors of the mammary gland or genital organs (including a history), vaginal bleeding of unknown etiology, pancreatitis with severe hypertriglyceridemia (including history), a history of migraine, which was accompanied by focal neurological symptoms, the period of chest cancer, the period of the chest in the body, the history of migraine, which was accompanied by focal neurological symptomatology; ; congenital hyperbilirubinemia (Gilbert, Dubin-Johnson and Rotor syndromes); age over 40 years; hyperprolactinemia; lactose intolerance, lactase deficiency, glucose-galactose malabsorption; pregnancy or suspicion of it. If any these states are developing for the first time while taking Chloe the drug, the drug should be immediately otmenen.Preparat Chloe is not intended for use in men.
Precautionary measures
The drug should be stored out of the reach of children at a temperature not higher than 25 ° C.
Use during pregnancy and lactation
The use of the drug is contraindicated in pregnancy, suspected pregnancy and during breastfeeding.
Dosage and administration
Inside, on 1 tab. / Day. The pill is taken without chewing, and washed down with a small amount of liquid. While taking the drug does not matter, however, the subsequent reception should be made at the same selected hour, preferably after breakfast or dinner.
Side effects
From the nervous system: often - headache; infrequently - migraine: frequency is unknown - worsening of the course of epilepsy. On the part of the organ of vision: rarely - intolerance of contact lenses. On the side of the gastrointestinal tract: often - nausea, abdominal pain; infrequently - vomiting, diarrhea. On the side of the skin and subcutaneous tissues: rarely - rash, urticaria; frequency is unknown - erythema nodosum, erythema multiforme. On the side of metabolism and nutrition: often - an increase in body weight; infrequently - fluid retention; rarely - weight loss. From the immune system: rarely - hypersensitivity reactions. From the genitals and mammary gland: often - pain / tenderness in the mammary glands, engorgement of the mammary glands; infrequently - an increase in the mammary glands; rarely, vaginal discharge, breast discharge *; frequency is unknown - acyclic bleeding / bleeding (metrorrhagia). Psychiatric disorders: often - decrease in mood, mood swings; infrequently - decreased libido; rarely - increased libido; unknown frequency - worsening of the course of endogenous depression. From the vessels: rarely - thromboembolism. * During postmarketing studies, painful menstrual-like bleeding and the absence of menstrual-like bleeding were reported, the frequency of which was not estimated. The following serious adverse events in COC women were reported ( which include the drug Chloe): - venous thromboembolic disorders; - arterial thromboembolic disorders; - stroke; - increased blood pressure; - hypertriglyceridemia; - impaired glucose tolerance or effects on peripheral insulin resistance; liver tumors (benign and malignant); impaired liver function; chloasma; - in women with hereditary angioedema, exogenous estrogens can cause or exacerbate the symptoms of angioedema; for which the association with the use of COCs (to which the Chloe drug belongs) is not indisputable: jaundice and / or pruritus,associated with cholestasis; the formation of gallstones; porphyria; systemic lupus erythematosus; hemolytic uremic syndrome; chorea; herpes during a previous pregnancy; hearing loss associated with otosclerosis; Crohn's disease; ulcerative colitis; cervical cancer; - blurred vision; - dizziness; - pancreatitis; - cholecystitis; - the frequency of breast cancer diagnostics in women who use COCs (which includes the drug CHLOE) is very slightly increased. Breast cancer is rarely observed in women under 40 years, the frequency excess is negligible relative to the overall risk of developing breast cancer. The causal relationship of breast cancer with the use of COC is not installed.
Overdose
Symptoms: nausea, vomiting, slight vaginal bleeding. Treatment: symptomatic therapy is carried out. There is no specific antidote.
Interaction with other drugs
With simultaneous use of Chloe with inducers of microsomal liver enzymes (hydantoins, barbiturates, primidone, carbamazepine and rifampicin; as well as, possibly, with oxcarbazepine, topiramate, felbamate and cipromatol,), I will use Ipidiol and I need to use ip = 20% and I need to use Ip-4 and I-20, I will use I-20 and I should be using Ipidone, I-20, I will use I-20 and I will use I-20 and I-20, I will use I-20 and I will use Ipcd, I-203, I will use Iptoxidi, I will give me I will need to use it to increase the clearance. contraception. When used simultaneously with ampicillin, rifampicin and tetracyclines, Chloe contraceptive reliability is reduced.
special instructions
Before using Chloe, it is necessary to conduct a general medical examination (including the mammary glands and cytological examination of cervical mucus), to exclude pregnancy, disorders of the blood coagulation system. With prolonged use of the drug, prophylactic follow-up examinations should be carried out every 6 months. If there are risk factors, the potential risk and the expected benefits of the therapy should be carefully evaluated and discussed with the woman before the drug is started. When the severity increases, increases or at the first manifestation of any of the following below conditions or risk factors may require the abolition of the drug. The use of the drug Chloe increases the risk of venous thromboembolism (VTE), compared to with risk in women not taking the drug.The additional risk of VTE is highest during the first year of Chloe drug use or when resuming use after a break of 4 weeks or more. VTE in 1-2% of cases can be fatal. The approximate frequency of VTE when taking oral contraceptives with a low dose of estrogen (less than 50 μg of ethinyl estradiol) is up to 4 per 10,000 women per year compared to 0.5–1 per 10,000 women not taking COCs. At the same time, the frequency of VTE when taking COCs is less than the frequency of VTE associated with pregnancy (6 per 10,000 pregnant women per year). Epidemiological studies have shown that the frequency of VTE is 1.5 to 2 times higher in women taking Chloe compared to KOC containing levonorgestrel is similar to KOC containing desogestrel / gestoden / drospirenone. Patients with polycystic ovarian syndrome have an increased risk of developing cardiovascular diseases. Epidemiological studies have also shown a connection with the use of hormonal contraceptives with an increased risk of arterial thromboembolism (myocardial infarction, transient ischemic attacks). Thrombosis of other vessels, namely, veins and arteries of the liver, mesentery, kidneys, brain or retina, has been rarely reported in individuals taking hormonal contraceptives. The patient should be warned that if symptoms of venous or arterial thrombosis develop, one should immediately consult a doctor. These symptoms include unilateral pain in the lower limb and / or swelling; sudden severe chest pain radiating to the left hand or without irradiation; sudden shortness of breath; sudden coughing up 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 partial seizure; weakness or significant loss of sensitivity, suddenly appearing on one side or in one part of the body; movement disorders; acute abdomen symptom complex. The risk of VTE increases: - with increasing age; - when smoking (with intensive smoking and with increasing age, the risk increases further, especially in women over 35. Women over 35 should be urged to stop smoking if they want to take Chloe drug); - with aggravated family history (i.e., with a history of cases of venous thromboembolism at a relatively young age among parents or close relatives).If a hereditary predisposition is suspected, a woman should consult with a specialist before making a decision on any hormonal contraception; - during prolonged immobilization, surgery on the lower limbs, neurosurgical operations or extensive trauma. In these situations, it is necessary to discontinue use (in the case of a planned operation at least 4 weeks), and not to resume it until 2 weeks after the full recovery of motor activity. If the use of the Chloe drug was not stopped in advance, the issue of antithrombotic therapy should be considered; - for obesity (BMI over 30 kg / m2). The risk of arterial thromboembolic complications or cerebrovascular accident increases: - with increasing age; - when smoking (with intensive smoking and with increasing age, the risk increases further, especially in women over 35. Women over 35 should be strongly advised to stop smoking if they want to take Chloe) - with dyslipoprotein ii - in hypertension; - migraine - in diseases of the heart valves - atrial fibrillation - with a family history (ie, with a history of arterial thrombosis cases in the relatively young age of the parents or close relatives). If a hereditary predisposition is suspected, a woman should consult a specialist before making a decision on any hormonal contraception. Disorders of the peripheral circulation can also be noted in diabetes mellitus, systemic lupus erythematosus, hemolytic-uremic syndrome, chronic inflammatory bowel disease (namely, Crohn's disease or ulcerative colitis) and sickle cell anemia. It is necessary to take into account the increased risk of thromboembolism in the postpartum period. Increased tea Toty or severity of migraine attacks during use Chloë drug (which can be a precursor of cerebral circulation) is the basis for immediate lifting preparata.V the potential role of varicose veins and superficial thrombophlebitis in the development of venous thromboembolism consensus net.Biohimicheskie factorswhich may indicate hereditary or acquired susceptibility to venous or arterial thrombosis, include resistance to activated protein C (APS), hyperhomocysteinemia, antithrombin III deficiency, protein C deficiency, protein S deficiency, anti-phospholipid antibodies (anti-phosphorylipid antibodies, lucidant complex, anti-phosphorylipid antibodies, anti-thrombin III, anti-thrombin III, anti-thrombin III antibodies risk / benefit relationship, the doctor should consider that appropriate treatment of the underlying pathology can reduce the risk of thrombosis. Women taking Chloe should be made aware of the need to inform the attending physician in a timely manner of any possible symptoms of thrombosis. In the case of thrombosis or suspicion of its occurrence, treatment with Chloe should be stopped. Given the teratogenicity of coagulants (coumarins), you should start using adequate methods of contraception. Other conditions The women with hypertriglyceridemia while taking COCs (with this condition in the family history) may increase the risk of developing pancreatitis. The relationship between taking COCs and hypertension is not established. If persistent arterial hypertension occurs, Chloe must be canceled and appropriate antihypertensive therapy prescribed. Intake of contraceptive can be continued with the normalization of blood pressure. In the event of an abnormal liver function, it may be necessary to temporarily discontinue Chloe before normalization of laboratory parameters. Recurrent cholestatic jaundice, which develops for the first time during pregnancy or previous intake of sex hormones, requires discontinuation of COC. Although COCs affect insulin resistance and glucose tolerance, it is usually not necessary to correct the dose of hypoglycemic drugs in patients with diabetes mellitus. However, this category of patients should be under close medical supervision. Women with a tendency to chloasma while taking COC should avoid prolonged exposure to the sun and exposure to ultraviolet radiation. If women with hirsutism have recently developed symptoms or have significantly increased, during the differential diagnosis Other causes, such as androgen-producing tumor, congenital dysfunction of the adrenal cortex, should be considered. regular bleeding (spotting or breakthrough bleeding), especially during the first months of therapy.Therefore, any irregular bleeding should be assessed only after an adaptation period of approximately 3 cycles. If irregular bleeding recurs or develops after previous regular cycles, non-hormonal causes should be considered and adequate diagnostic measures should be taken to exclude malignant tumors (including diagnostic curettage of the uterus) or pregnancy. In some cases, withdrawal bleeding may not develop during a break in the pill. If you take pills irregularly or in the absence of two menstrual-like bleeding in a row, pregnancy should be avoided before the drug is continued. Allergy skin tests can be changed, and the concentration of LH and FSH can decrease. Due to the fact that the contraceptive effect is fully manifested by the 7th day from the beginning of the drug, additional non-hormonal methods of contraception are recommended in the first week. 3 months before the planned pregnancy. In diarrhea and vomiting, the contraceptive effect is reduced (without discontinuing the drug, it is necessary to use additional non-hormones flax methods of contraception) .OpuholiImeyutsya reports some increase in the risk of cervical cancer in long-term use of COCs. Connection with taking COC is not proven. It remains a controversial question to what extent these findings are associated with pathology of the cervix or with the characteristics of sexual behavior (more rare use of barrier methods of contraception). The most important risk factor for cervical cancer is persistent HPV infection. A meta-analysis of 54 epidemiological studies has shown that there is a slightly increased relative risk of developing breast cancer diagnosed in women taking COCs at the present time (relative risk 1.24). The increased risk gradually disappears within 10 years after discontinuation of these drugs. Due to the fact that breast cancer is rarely observed in women under 40 years old, an increase in the number of breast cancer diagnoses in women who are taking COCs now or have recently taken is not significant in relation to the overall risk of this disease. His association with KOC is not proven.The observed increase in risk may also be due to an earlier diagnosis of breast cancer in women using COCs. Women who have ever used COCs detect earlier stages of breast cancer than women who have never used them. In rare cases, the development of liver tumors were observed with COCs, which in some cases led to life-threatening intra-abdominal bleeding. This should be taken into account when carrying out a differential diagnosis in the event of severe abdominal pain, enlarged liver or signs of intra-abdominal bleeding. blood plasma proteins, for example, corticosteroid-binding globulin, as well as lipid / lipoprotein composition of the blood, carbohydrate indicators metabolism and blood coagulation parameters. However, usually the deviations remain within the range of normal laboratory values.