Chloe
Active material: Cyproterone, Ethinylestradiol
When ATH: G03HB01
CCF: Monophasic oral contraceptive with anti-androgenic properties
ICD-10 codes (testimony): L64, L68.0, L70, Z30.0
When CSF: 15.11.04.02
Manufacturer: ZENTIVA a.s. (Czech Republic)
Pharmaceutical form, composition and packaging
Pills, Film-coated, two species.
Pills, film-coated yellow-orange, round, lenticular (21 PC. in blister).
1 tab. | |
cyproterone acetate | 2 mg |
ethinylestradiol | 35 g |
Excipients: lactose monohydrate, povidone, sodium carboxymethyl starch (Type A), Colloidal anhydrous silica, aluminium oxide colloid, magnesium stearate.
The composition of the shell: dye Opadry II Yellow OY-L-32901 (lactose monohydrate, gipromelloza 2910, Titanium dioxide, macrogol 4000, iron oxide yellow, iron oxide black, iron oxide red, Purified water).
Placebo pill white, round, lenticular (7 PC. in blister).
Excipients: lactose monohydrate, povidone, sodium carboxymethyl starch (Type A), Colloidal anhydrous silica, aluminium oxide colloid, magnesium stearate.
28 PC. – packings Valium planimetric (1) – packs cardboard.
28 PC. – packings Valium planimetric (3) – packs cardboard.
Pharmacological action
Combined low-dose monophasic oral contraceptive drug with antiandrogenna activity. The mechanism of action is due to its composition of antiandrogennym drug steroid structure – ciproteronom acetate and peroral estrogen – ethinylestradiol.
Cyproterone acetate
Has the ability to communicate with the natural receptor competitive androgen (incl. Testosterone, digidroèpiandrosteron, androstenedione), produced in small amounts in the body women, mainly in the adrenal glands, the ovaries and the skin. Blocking androgen receptors in organah-misheniah, reduces the phenomenon androgenization women (at the expense of processes, oposreduemyh hormone-receptor complexes at the level of basic intracellular mechanisms). Thus, It is possible to cure diseases, due to increased formation of androgens or specific sensitivity to these hormones.
Against the backdrop of the admission of drug reduces the enhanced activity of the sebaceous glands, plays an important role in causing acne and Seborrhea. Through 3-4 months of therapy available rash usually disappears. Excessive oiliness of the hair and skin disappears before. Also reduces hair loss, often accompanying Seborrhea.
Therapy Chloe® in women of reproductive age reduces clinical manifestations light forms of HIRSUTISM; However, the effect of treatment you should expect after only a few months of use.
Along with antiandrogennymi properties, cyproterone acetate has gestagennoj activity, simulating the corpus luteum hormone properties. Oppressing secretion gipofizom gonadotroponah hormones and inhibits ovulation, which makes contraceptive effect.
Ethinylestradiol
Strengthens the Central and peripheral effects ciproteron acetate at ovulation, keeps high viscosity mucus šeečnoj, impeding the penetration of sperm into the uterine cavity and helping to ensure reliable contraceptive effect.
Against the backdrop of the admission of the drug cycle becomes more regular, rarely observed painful menstruation, It decreases the amount of bleeding, reduces the risk of iron deficiency anaemia.
Pharmacokinetics
Cyproterone acetate
Absorption
After taking the drug inside cyproterone acetate completely absorbed from the digestive tract. Cmax plasma levels achieved after 1.6 h and is 15 ng / ml. Bioavailability is 88%.
Distribution
Cyproterone acetate is almost entirely associated with plasma albumin, in a free State is approximately 3.5-4%. Because the nonspecific protein binding, changes in the level of globulin, linking sex steroids (GTN), not affect the farmakokinetiku ciproteron acetate.
Metabolism
Biotransformiroetsa by gidrauxilirovania and conjugating, the major metabolite – 15b-hydroxyl derivative.
Deduction
Pharmacokinetics cyproterone acetate dvuhfazna: T1/2 is 0.8 and h 2.3 SUT respectively for the first and second phases. The total plasma clearance of 3.6 ml / min / kg. Report mostly in the form of metabolites in urine and feces in the ratio 1:2, a small part of the – unchanged in the feces. Breast milk is allocated to 0.2% doses of cyproterone acetate. T1/2 for metabolites ciproteron acetate is 1.8 d.
Ethinylestradiol
Absorption
After dose ethinyl estradiol rapidly and completely absorbed from the digestive tract. Cmax is approximately 80 PG/ml achieved through 1.7 no. Bioavailability is about 45%, has a significant individual variability.
Distribution
Protein binding (albumin) blood plasma high: only 2% are in the plasma in a free form.
Ethinyl estradiol increases the hepatic synthesis of GSPS and corticosteroid-binding globulin (KSG) during continuous use. Treatment with Chloe® the concentration of serum GSPS rises approximately 100 nmol/l to 300 nmoli /, and serum concentration of GLCS increases from approximately 50 ug / ml to 95 ug / ml.
Metabolism
In the process of absorption and “first pass” through the liver is exposed to ethinylestradiol intensive metabolism.
Deduction
Pharmacokinetics of ethinyl estradiol dvuhfazna: T1/2 1-2 h and approximately 20 h, respectively. Plasma clearance – about 5 ml / min / kg. Ethinyl estradiol is excreted as metabolites: about 40% – urine, 60% – with feces. Breast milk is allocated to 0.02% dose of ethinyl estradiol.
Testimony
Androgenzawisimae disease in women:
-Acne (especially their expressed form, accompanied by seborrhoea, inflammatory phenomena with the formation of nodes/delayed-Pustular acne, nodulo-cystic acne/);
-Androgenic alopecia;
light forms of HIRSUTISM;
is contraception in women with symptoms of androgenization.
Dosage regimen
The drug is taken orally by 1 tab. / day. Take a pill, without chewing, and the combination with a small amount of liquid. We recommend taking the drug at the same time, preferably after breakfast or dinner.
Welcome Chloe® begin in 1-St day cycle, using the pill of the corresponding day of the week from the calendar package. Daily intake of the drug is carried out, using the tablets from the calendar package consistently in the arrow printed on the foil, until you have taken all the tablets. After the end of the reception of all pill yellow-orange from the calendar package, must be in the following 7 days take the remaining pill white.
In the past 7 days of healing cycle (28 days), should be menstrualnopodobnoe bleeding (as a result of the treatment). Menstruation usually begins in 2-3 the day after the 21-day treatment cycle.
The following package to start the next day after a fully completed admission pill from a previous package, regardless of the fact the continuation/termination of bleeding.
At switching from combined oral contraceptives application of Chloe® to begin the next day after taking the last tablet with active components of previous product, but in any case not later than the day after the usual 7-day break in the reception (for products, containing 21 tablets). Continue as above.
If the patient has previous contraceptive every day during 28 days, application of Chloe® should start after taking the last inactive pills.
At switching from contraceptives, containing only progestin, (“minipill”) Chloe® You can start to apply without interruption.
At the use of injectable contraceptives Chloe® should apply from the date of, when it should be done next injection.
At the transition from the implant Chloe should be applied on the day of its removal.
In all cases, you must use an additional barrier method of contraception during the first 7 days of the drug.
After abortion in the I trimester of pregnancy a woman can start applying Chloe® immediately. In this case, there is no need for additional methods of contraception.
After childbirth or abortion in the II trimester of pregnancy the use of drugs should be started at 21-28 day. If the reception is started later, you must use an additional barrier method of contraception during the first 7 days of the drug.
If a woman lived sexuality between childbirth or abortion and the beginning of the use of the drug, should first rule out pregnancy or must wait for first menstruation.
The missed pill It should be taken as soon as possible, the next Tablet – in ordinary time. If you are late <12 h reliability contraception is not reduced. If the delay in accepting the pill amounted to >12 no, the reliability of contraception may be reduced.
If the delay in pill made >12 no (the interval from the moment of taking the last Tablet >36 no) during the 1-St and 2-nd week of reception of the drug, a woman should take the last missed pill as soon as possible: even if this means taking two tablets at the same time. Subsequent pill should be taken at the usual time. In addition, it is necessary to use a barrier method during the following 7 days.
If the delay in accepting the pill amounted to >12 no (the interval from the moment of taking the last Tablet >36 no) during the 3-week dose, a woman should take the last missed pill as soon as possible: even if this means taking two tablets at the same time. Subsequent pill should be taken at the usual time. Taking the pill of the new packaging should start, at the end of the current packaging – nonstop. Probably, withdrawal bleeding will not be until the end of the second package, but there may be spotting or breakthrough mazhushchie uterine bleeding in the days of tablet taking.
If a woman was vomiting in the range from 3 to 4 h after dosing, absorption of active substances may be incomplete. In this case, it is necessary to focus on the recommendations when skipping pills.
That postpone the date of the onset of menstruation, a woman should continue taking tablets from a new packaging of the drug immediately after, like all the previous pills, nonstop. Tablets of the new packaging can be so long, how a woman wants (until, until the package is over). Against the background of the drug from the second package, women may experience spotting or breakthrough uterine bleeding. You should begin taking tablets from the next Pack after completion of all admission 28 tablets.
That postpone the first day of menstruation to another day of the week, the woman should be shortened, the closest break in pill on so many days, how much she wants. The shorter the interval, the higher the risk, that it will not have withdrawal bleeding and, further, will mazhushchie spotting and breakthrough bleeding while taking the second packaging (in the same way as in the case of, when she wanted to delay the onset of menstruation).
At treatment of giperandrogennyh States duration of use of the drug is determined by the severity of the disease. After the disappearance of symptoms is recommended to take the drug, at least, during 3-4 Months. In case of relapse after a few weeks or months after the course you can re-test therapy Chloe®.
Side effect
On the part of the endocrine system: rarely – engorgement, soreness, Zoom in and allocating of mammary glands, weight gain.
On the part of the reproductive system: rarely – intermenstrual bleeding, changes in vaginal secretions, changes in libido.
CNS: rarely – headache, migraine, depressed mood.
From the digestive system: rarely – nausea, vomiting, gastralgia.
Other: rarely – poor tolerance of contact lenses, swelling of the eyelids, blurred vision, conjunctivitis, hearing loss, allergic reactions, tromboflebit, thromboembolism, generalized itching, jaundice, the appearance of age spots on the face (chloasma).
Listed side effects can develop in the first few months of use of the drug and usually decrease with time.
Contraindications
-thrombosis and thromboembolism, incl. history (deep vein thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular disorders);
- State, predshestvuyuschye thrombosis (incl. transient ischemic attacks, angina);
- Presence of severe or multiple risk factors for venous or arterial thrombosis;
- Arterial hypertension;
- Diabetes, complicated mikroangiopatiâmi;
-illness or expressed violations of the liver;
- Liver tumors (incl. history);
-congenital hyperbilirubinemia (Gilbert syndrome, Dubin-Johnson, Rotor);
- Pancreatitis (incl. history), If it was accompanied by severe hypertriglyceridemia;
-dependant malignant tumors, incl. tumors of the breast or sex organs (incl. history);
- Uterine bleeding of unknown etiology;
- Migraine, accompanied by focal neurological symptoms (incl. history);
- Sickle cell anemia;
-idiopathic jaundice or itching during last pregnancy;
— Otosclerosis with deterioration during pregnancy;
- Hyperprolactinemia;
- Breastfeeding;
- Pregnancy or suspected it;
-age over 40 years;
- Hypersensitivity to the drug.
FROM caution You should use the drug in epilepsy, depression, yazvennom cars, diseases of the liver and gallbladder, uterine myoma, mastitis, chorea, tetany, porfirii, rasseânnom sclerosis, varicose veins, tuberculosis, kidney disease, adolescence (without regular ovulatory cycles).
Pregnancy and lactation
The drug is contraindicated in pregnancy, suspicion of pregnancy and breastfeeding.
Cautions
Before the use of Chloe® There is a need to conduct a survey of obŝemedicinskoe (incl. breast cytology and cervical mucus), exclude pregnancy, a breach of the blood coagulation system. With long-term use the drug preventive monitoring surveys should be carried out every 6 Months.
If there are risk factors, you should carefully consider the potential risks and expected benefits from therapy and discuss it with a woman before applying the product.
Approximate frequency of venous thromboembolism (VTЭ) When you apply oral contraceptives with low dose estrogen (< 50 mcg ethinyl estradiol) up to 4/10 000 women per year in comparison with 0.5-3/10 000 Women, not taking oral contraceptives. The frequency of VTE while taking combined oral contraceptives less, than the frequency of VTE, associated with pregnancy (6/10 000 pregnant women per year).
The patient should notify, that when developing symptoms of venous or arterial thrombosis, you should immediately consult your doctor. These symptoms include unilateral leg pain and / or swelling, sudden severe chest pain radiating to the left arm or without irradiation, sudden shortness of breath, sudden onset of coughing, any unusual, strong, prolonged headache, increased frequency and severity of migraine, sudden partial or complete loss of vision, diplopia, slurred speech or aphasia, dizziness, collapse with / without partial seizures, weakness or very marked numbness, suddenly appear on one side or in one part of the body, movement disorders, simptomokompleks “sharp” life.
The relationship between the use of combined oral contraceptives and hypertension is not installed. If you experience persistent hypertension drug should be lifted and assign appropriate antihypertensive therapy. Receiving contraceptive can be continued when the normalization of HELL.
If you encounter violations of the liver may require suspension of the drug to the normalization of the laboratory parameters.
Recurrent cholestatic jaundice, developing for the first time during pregnancy, or during previous admission of sexual hormones, It requires discontinuation of combined oral contraceptives.
Despite, that combined oral contraceptives affect tissue resistance to insulin and glucose tolerance, usually there is no need to correct dose gipoglikemicakih drugs in patients with diabetes mellitus. Nonetheless, for this category of patients should be careful medical supervision.
Women, prone to the appearance of Chloasma, While taking combined oral contraceptives should avoid prolonged exposure to sunlight and ultraviolet light.
If women with girsutizmom symptoms or increased substantially recently, When performing a differential diagnosis should take into account other possible causes, such as the androgenproduciruûŝaâ tumor, congenital dysfunction napochechnikov crust.
When applying Chloe® bleeding may occur (mazhushchie selection or breakthrough bleeding), especially during the first months of therapy. Therefore, evaluation of any irregular bleeding should be done only after a period of adaptation, approximately 3 cycle.
If irregular bleeding or develop after repeated previous regular cycles, consider non-hormonal causes and implement adequate diagnostic measures (incl. curettage) to exclude malignant neoplasms or pregnancy.
In some cases, bleeding may not cancel evolve during a break in the application of the drug. The irregular pill or two menstrual′nopodobnyh bleeding in a row should be deleted pregnancy before continuing use of the drug.
It is possible to change the results of skin allergic samples, reducing the concentration of LH and FSH on the background of the use of the drug.
Because, that the contraceptive action fully manifest to 7 day from the beginning of the reception of the drug, in the first week of the recommended additional non-hormonal methods of contraception.
Use of the drug after childbirth, it is recommended that you not previously, what will be the first normal menstrual cycle.
Treatment should be immediately discontinued 3 months before the planned pregnancy and for roughly 6 weeks before the planned surgery, during prolonged immobilization.
If you have diarrhea and vomiting contraceptive effect is reduced (not stopping taking the drug, You should use an additional non-hormonal methods of contraception).
Smokers, receiving hormonal contraceptive drugs, have an increased risk of cardiovascular disease with serious consequences (myocardial infarction, stroke). The risk increases with age and, depending on the number of cigarettes smoked (especially in older women 30 years).
Overdose
Symptoms: nausea, vomiting, a slight vaginal bleeding.
Treatment: symptomatic therapy. No specific antidote.
Drug Interactions
If you are Chloe® with inducers of liver microsomal enzymes (gidantoinami, ʙarʙituratami, primidone, carbamazepine and rifampicin; and, perhaps, with oxcarbazepine, topiramatom, felbamatom and grizeoful′vinom) increased clearance of ethinyl estradiol and cyproterone, that can lead to breakthrough bleeding or uterine unreliable contraception.
Together with the use of ampicillin, rifampicin and tetracyclines contraceptive reliability of Chloe® decreases.
Conditions of supply of pharmacies
The drug is released under the prescription.
Conditions and terms
The drug should be stored out of reach of children at or above 25 ° C. Shelf life – 3 year.