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Active ingredients
Ziproterone + Ethinyl Estradiol
Release form
Pills
Composition
In 1 tablet: ethinyl estradiol 35 mcg; cyproterone acetate 2 mg. Adjuvants: lactose monohydrate - 68.8 mg, povidone - 2 mg, carboxymethyl starch sodium (type A) - 1.5 mg, colloidal anhydrous silicon dioxide - 0.188 mg, colloidal aluminum oxide - 0.04 mg, magnesium stearate - 0.375 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. women, mainly in the adrenal glands, ovaries and skin. By blocking androgen receptors in target organs, it 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, is reduced. 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 is also reduced. 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. Along with antiandrogenic properties, cyproterone acetate has a gestagenic activity that mimics the properties of the hormone of the corpus luteum. Inhibits the secretion of pituitary gonadotropic hormones and inhibits ovulation, which contributes to the contraceptive effect. Ethinyl estradiol: Strengthens the central and peripheral effects of cyproterone acetate on ovulation, retains a high viscosity of cervical mucus,complicating the penetration of sperm into the uterus and helping to ensure a reliable contraceptive effect. Against the background of the drug intake, the cycle becomes more regular, less frequent painful menstruation, decreases the intensity of bleeding, reduces the risk of iron deficiency anemia.
Pharmacokinetics
Tsiproterona acetate. Absorption: After taking the drug inside 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: Cyproterone acetate is almost completely bound to plasma albumin, approximately 3.5–4% is in a free state. Since protein binding is nonspecific, 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 15b-hydroxyl derivative. is 0.8 hours and 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. Absorption: After taking the drug, ethinyl estradiol is quickly 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: High plasma plasma protein binding (albumin): only 2% are in free plasma. Ethynyl estradiol increases hepatic synthesis of GSPS and corticosteroid-binding globulin (KSG) with continuous use. With Chloe treatment; The serum SHBG concentration rises from about 100 nmol / L to 300 nmol / L, and the serum concentration of CGG rises from about 50 mcg / ml to 95 mcg / ml. Metabolism: During the absorption and first pass through the liver, ethinyl estradiol is extensively metabolized. : The pharmacokinetics of ethinyl estradiol biphasic: 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;
Contraindications
Simultaneous use with other hormonal contraceptives; - thrombosis and thromboembolism, incl. history of (deep vein thrombosis, pulmonary thromboembolism, myocardial infarction, cerebrovascular disorders, for example, stroke) - conditions preceding thrombosis (including transient ischemic attacks, angina); - multiple or expressed risk factors for venous or arterial thrombus (including complicated valvular heart disease, atrial fibrillation, vascular diseases of the brain or coronary arteries; uncontrolled arterial hypertension, severe dyslipoproteinemia, subacute bacterial endocarditis, prolonged immobilization, surgery on the lower limbs, neurosurgical operations, extensive injuries, smoking over the age of 35 years, obesity with a BMI of more than 30 kg / m2) - revealed hereditary or acquired susceptibility to venous or arterial thrombosis, such as resistance to activated protein C (APS), antithrombin III deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinemia and the presence of antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulum nta); - diabetes mellitus with diabetic angiopathy; - severe liver disease now or in history or severe liver dysfunction not earlier than 6 months after the normalization of liver function indicators; - liver tumors (benign and malignant); - hormone-dependent malignant tumors or suspicion of them, incl. tumors of the mammary gland or genital organs (including history); - bleeding from the vagina of unknown etiology; - pancreatitis with severe hypertriglyceridemia (including history); - a history of migraine, which was accompanied by focal neurological symptoms; - pregnancy or suspicion of it; - breastfeeding period; - congenital hyperbilirubinemia (Gilbert's syndromes,Dubin-Johnson and Rotor); - age over 40 years; - hyperprolactinemia; - lactose intolerance, lactase deficiency, glucose / galactose malabsorption syndrome; - hypersensitivity to the components of the drug. If any of these conditions develop for the first time while taking Chloe; , the drug should be discontinued immediately. Chloe; not intended for use in men.
Precautionary measures
Chloe should be used with caution; with epilepsy, depression, ulcerative colitis, liver and gallbladder diseases, uterine myoma, mastopathy, chorea, tetany, porphyria, multiple sclerosis, varicose veins, tuberculosis, kidney diseases, during adolescence (without regular ovulatory cycles), dysliproteinemia, adrenal glands, dysfunctional diseases - cell anemia, idiopathic jaundice or itching during a previous pregnancy, otosclerosis with impairment of hearing during a previous pregnancy.
Use during pregnancy and lactation
The use of the drug is contraindicated in pregnancy, suspected pregnancy and during breastfeeding.
Dosage and administration
The drug should be taken orally on 1 tab. / Day. The pill is taken without chewing, and washed down with a small amount of liquid. Taking the drug is recommended at the same time, preferably after breakfast or dinner. In the absence of taking any hormonal contraceptive drugs in the previous month, take Chloe; begin on the 1st day of the cycle (i.e., on the first day of the menstrual bleeding) using a pill of the corresponding day of the week from the calendar package. It is allowed to start taking on the 2-5 day of the menstrual cycle, but in this case it is recommended to additionally use a barrier method of contraception during the first 7 days of taking pills from the first package. The daily administration of the drug is carried out using pills from the calendar package in the direction of the arrow printed on the foil, until all pills are taken. After all 21 pills of yellow-orange color are taken from the calendar package, it is necessary to take the remaining white pills for the next 7 days. During the last 7 days of the treatment cycle (28 days), menstrual bleeding should occur (as a result of treatment withdrawal).Menstrual bleeding usually begins 2-3 days after the 21st day of the drug treatment cycle. The next package must be started the next day after the complete completion of the pill from the previous package, regardless of whether the bleeding continues or not. When switching from combined contraceptive drugs (oral contraceptives (OCCs), vaginal ring or contraceptive patch) Chloe preparation; should begin the day after taking the last active tablet of the previous drug, but in no case later than the next day after the usual 7-day break in reception (for drugs containing 21 pills). Further, according to the scheme described above. If the patient has taken the previous contraceptive daily for 28 days, take the Chloe drug; should start after taking the last inactive pill. Chloe drug; should begin on the day of removal of the vaginal ring or contraceptive patch, but no later than the day when a new patch is to be introduced or a new patch is pasted. In the transition from a mini-drinking the drug Chloe; You can begin to use without interruption. When using injectable forms of contraceptives, taking the drug Chloe should be applied from the day when the next injection should be done. When switching from Chloe's implant; should be applied on the day of its removal. In all cases, an additional barrier method of contraception must be used during the first 7 days of taking the drug. After an abortion in the first trimester of pregnancy, a woman can start using Chloe; immediately. In this case, there is no need for additional methods of contraception. After delivery, in the absence of breastfeeding or abortion in the second trimester of pregnancy, the drug should be started on days 21-28. If reception is started later, it is necessary to use an additional barrier method of contraception during the first 7 days of use of the drug. If a woman has sex life during the period between birth or abortion, then before you start taking the drug Chloe; missed pills: The missed pill should be taken as soon as possible, the next pill at the usual time. With a delay of less than 12 hours, the reliability of contraception is not reduced.If the delay in taking the pill was more than 12 hours, the reliability of contraception can be reduced. The more pills are missed and the closer the pass to the 7-day break in taking pills, the greater the likelihood of pregnancy. The following two basic rules can be followed: - taking the drug should never be interrupted for more than 7 days; in taking the pills was more than 12 hours (the interval from the moment of taking the last pill is more than 36 hours). The first week of taking the drug: A woman should take the last missed pill as soon as possible. just remember (even if this means taking two pills at the same time). The next pill should be taken at the usual time. Additionally, you should use a barrier method of contraception for the next 7 days. If sexual intercourse took place within a week before the pill is missed, the likelihood of pregnancy must be considered. The following pill should be taken at the usual time. Provided that the woman took the pills correctly within 7 days preceding the first missed pill, there is no need to use additional contraceptive measures. Otherwise, as well as skipping two or more pills, it is necessary to additionally use barrier methods of contraception (for example, a condom) for 7 days. 7 days preceding the first missed pill, all pills were taken correctly, there is no need to use additional contraceptive methods. A woman should take the last missed pill as soon as she remembers (even if it means taking two pills at the same time). The following pills are taken at the usual time, until the pills from the current packaging run out.The next package should start immediately. Withdrawal bleeding is unlikely until the pills from the second package run out, but there may be spotting and breakthrough bleeding while taking the pills. A woman can also stop taking pills from the current pack. She should then take a break for 7 days, including the day she misses the pill, and then start taking the pills from the new pack. If a woman misses a pill, and then there is no withdrawal bleeding during a break, pregnancy should be excluded. Recommendations for gastrointestinal disorders: If a woman has vomiting within 3 to 4 hours after taking the drug, the absorption of active substances can to be incomplete. In this case, it is necessary to be guided by the recommendations when skipping the pill. Changing the day of menstrual-like bleeding: In order to delay the onset of menstrual-like bleeding, a woman should continue taking the pills from the new package immediately after taking all the pills from the previous package, without interruption. Tablets from this new package can be taken as long as the woman wants (until the package is finished). While taking the drug from the second package, a woman may have spotting or breakthrough uterine bleeding. Resume taking the drug Chloe; from a new pack follows the usual 7-day break. In order to postpone the day of the start of menstrual bleeding to another day of the week, a woman should shorten the nearest break in taking the pills for as many days as she wants. The shorter the interval, the higher the risk that she will not have withdrawal bleeding and will continue to have spotting and breakthrough bleeding while taking the second package (just as if she would like to delay the onset of menstrual bleeding). When treating hyperandrogenic States: Duration of treatment is determined by the severity of the disease. After the symptoms disappear, it is recommended to take the drug for at least another 3-4 months. In the event of a relapse within a few weeks or months after completion of the course, you can repeat the treatment with Chloe ;.In the case of resuming the drug (after a 4-week break or more), the increased risk of VTE should be considered.
Side effects
Determination of the frequency of adverse reactions: very often (≥1 / 10); often (≥1 / 100 to less than 1/10); infrequently (≥1 / 1000 to less than 1/100); rarely (≥ 1/10 000 to less than 1/1000); very rarely (less than 1/10 000); the frequency is unknown (the frequency cannot be estimated on the basis of the available data) .Co the side of 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 to contact lenses. On the part of the digestive system: 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 endogenous depression. Cardiovascular system: rarely - thromboembolism. * During post-marketing studies, painful menstrual-like bleeding and lack of menstrual-like bleeding were reported, the frequency of which was not estimated. Serious adverse events reported in women using COCs (to which the Chloe preparation belongs;) From the side of the cardiovascular system: venous thromboembolic disorders, arterial thromboembolic disorders disruption, stroke, increased blood pressurecholecystitis. From the skin and subcutaneous tissues: chloasma. Allergic reactions: in women with hereditary angioedema, exogenous estrogens can cause or exacerbate the symptoms of angioedema. From the nervous system and sensory organs: blurred vision, dizziness. with the use of COCs (to which the Chloe preparation belongs;) is not indisputable: jaundice and / or itching associated with cholestasis; the formation of gallstones; porphyria; systemic lupus erythematosus; hemolytic uremic syndrome; Chorea Sydenham; herpes during a previous pregnancy; hearing loss associated with otosclerosis; Crohn's disease; ulcerative colitis; cervical cancer. The frequency of diagnosing breast cancer in women who use COCs (which includes the Chloe drug;) is very slightly elevated. 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 the simultaneous use of Chloe; with inducers of liver microsomal enzymes (hydantoins, barbiturates, primidone, carbamazepine, and ct; c), and, possibly, with oxcarbazepine, topiramate, felbamate, and griseofulvin, the clearance of ethinyl estradiol and ciproterone increases, and the program can be applied; use of ampicillin, rifampicin, and tetracycline contraceptive reliability of Chloe; going down.
special instructions
Before starting the application of chloe; it is necessary to conduct a general medical examination (including mammary glands and cytological examination of cervical mucus), to exclude pregnancy, disorders of the blood coagulation system. With long-term 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 using the drug. When the severity increases,augmentation or at the first manifestation of any of the conditions or risk factors listed below, may require withdrawal of the drug. Use of the Chloe drug; leads to increased risk of venous thromboembolism (VTE), compared with the risk of women not taking the drug. The additional risk of VTE is highest during the first year of Chloe; or when resuming reception after a break lasting 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 COC 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; in comparison with KOC containing levonorgestrel, and similar to KOC containing deogestrel / 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 is further increased, especially in women over 35 years of age.Women over 35 should be strongly advised to quit smoking if they want to take the Chloe drug;); - with a family history (i.e. if there is 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 drug Chloe; has not been terminated in advance, the issue of antithrombotic therapy should be considered; - in obesity (BMI over 30 kg / m2). The risk of arterial thromboembolic complications or cerebral circulation rises: - with increasing age; - with smoking (with intensive smoking and with increasing age the risk is further increased, especially in women over the age of 35. Women over the age of 35 should be strongly advised to stop smoking if they want to take the drug Chloe;); - for dyslipoproteinemia; - for hypertension with arterial hypertension AI - 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; (what could be the harbingercerebral circulatory disorders) is a reason for immediate discontinuation of the drug. There is no consensus on the potential role of varicose veins and superficial thrombophlebitis in the development of venous thromboembolism. Biochemical factors that 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, antiphospholipid e antibodies (anticardiolipin antibodies, lupus anticoagulant). When assessing the risk / benefit ratio, the physician should consider that appropriate treatment of the underlying pathology can reduce the risk of thrombosis. Women taking Chloe ;, should clarify the need for timely notification to your doctor about the development of possible symptoms of thrombosis. In the case of thrombosis or suspicion of its occurrence, treatment with Chloe; should stop. Given the teratogenicity of coagulants (coumarins), you should start using adequate methods of contraception. Other conditions: Women with hypertriglyceridemia during COC (with this condition in the family history) may increase the risk of pancreatitis. The relationship between COC and arterial hypertension is not established. In the event of persistent arterial hypertension Chloe; it is necessary to cancel and prescribe appropriate antihypertensive therapy. 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 withdraw Chloe; to normalize 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 should be considered, such as androgen-producing tumor,congenital dysfunction of the adrenal cortex. Against the background of the drug Chloe; occasionally irregular bleeding (spotting or breakthrough bleeding) may occur, 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) .Opuholi: There are reports of 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.