Instruction for use: Chloe

Active substance: Cyproterone + Ethinylestradiol

ATX code G03HB01 Cyproterone and estrogen

Pharmacological group

Contraceptive agents (estrogen + antiandrogen) [Androgens, antiandrogens in combinations]

Nosological classification (ICD-10)

E28.1 Excess androgen

Androgen-dependent diseases in women, Androgen-dependent conditions in women, Androgenation in women, Diseases androgen-dependent in women, Excess androgen in women

L21.8 Other seborrheic dermatitis

Seborrhea of the skin of the face, Seborrheic dermatitis due to Pityrosporum ovale

L64 Androgenic alopecia

Alopecia androgenic, Androgenetic alopecia, Androgenic alopecia of moderate severity, Severe Androgen-Dependent Alopecia, Male pattern hair loss

L68.0 Hirsutism

Pathological hair body and body

L70 Acne

Acne nodulocystica, Acne, Comedone acne, Acne Treatment, Papulous pustular acne, Papulopustulicular acne, Papulo-pustular acne, Acne, Acne Disease, Acne, Acne vulgaris, Nodular-cystic acne, Nodular-cystic acne

Z30 Monitoring contraceptive use

Local Contraception, Contraception oral, Local contraception, Episodic prevention of pregnancy, Hormonal Contraception, Contraception, Prevention of Pregnancy, Prevention of unwanted pregnancy, Contraceptive intrauterine, Contraception in women with androgenization phenomena, Installation and removal of the intrauterine device, Prevention of pregnancy (contraception)

Z30.0 General advice and advice on contraception

Safe sex, Intrauterine device contraception, Contraception, Contraceptive intrauterine, Oral contraception, Oral contraception during lactation and with estrogen contraindications, Postcoital contraception, Prevention of Pregnancy, Prevention of unwanted pregnancy, Emergency Contraception, Episodic prevention of pregnancy, Contraception in adolescents, Prevention of pregnancy (contraception)

Composition

Tablets, film-coated 1 set

1 tab. Yellow-orange color contains:

Active substances:

Cyproterone acetate 2 mg

Ethyl estradiol 0.035 mg

Excipients

Core: lactose monohydrate; Povidone; Sodium carboxymethyl starch (type A); Silicon dioxide colloidal anhydrous; Aluminum oxide colloid; Magnesium stearate

Film coating: dye Opadry II Yellow OY-L-32901 (lactose monohydrate, hypromellose 2910, titanium dioxide, macrogol 4000, iron oxide yellow, iron oxide black, iron oxide red, purified water)

1 tab. (Placebo) of white color contains:

Excipients: lactose monohydrate, povidone, sodium carboxymethyl starch (type A), silicon dioxide colloidal anhydrous, aluminum colloidal oxide, magnesium stearate

Description of dosage form

The tablets covered with a film cover: round, biconcave yellow-orange color.

Tablets (placebo): round, biconcave, white.

pharmachologic effect

Pharmacological action - contraceptive, contraceptive with antiandrogenic component.

Pharmacodynamics

Combined low-dose monophasic oral contraceptive with anti-androgenic activity. The mechanism of action is due to the anti-androgenic drug of the steroid structure - cyproterone acetate - and oral estrogen - ethinyl estradiol, which enter into its composition.

Cyproterone acetate has the ability to competitively bind to receptors of natural androgens (including testosterone, dihydroepiandrosterone, androstenedione), formed in small amounts in the body of women, mainly in the adrenal glands, ovaries and skin. By blocking the androgen receptors in target organs, it reduces the androgenization phenomena in women (due to disruption of the 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 taking ChloeŽ, the increased activity of the sebaceous glands decreases, which plays an important role in the appearance of acne and seborrhea. After 3-4 months of therapy, this usually leads to the disappearance of the existing rash. Excessive fatty hair and skin disappears even earlier. Also decreases hair loss, often accompanying seborrhea. Therapy CHLOEŽ in women of reproductive age reduces clinical manifestations of mild forms of hirsutism; However, the effect of treatment should be expected only after several months of use.

Along with anti-androgenic properties, cyproterone acetate has gestagenic activity that mimics the properties of the hormone of the yellow body. He, like other drugs with gestagenic activity, inhibits the secretion of the pituitary gland by gonadotropic hormones and inhibits ovulation, which determines its contraceptive effect.

Ethinyl estradiol strengthens the central and peripheral effects of cyproterone acetate on ovulation, retains a high viscosity of the cervical mucus, which makes it difficult to penetrate the spermatozoon into the uterine cavity and helps to ensure a reliable contraceptive effect.

Against the background of taking the drug, the cycle becomes more regular, less painful menstruation is observed, the intensity of bleeding decreases, resulting in a reduced risk of iron deficiency anemia.

Pharmacokinetics

Cyproterone acetate

Suction. After taking ChloeŽ cyproterone, acetate is completely absorbed from the digestive tract. After oral administration of 1 table. ChloeŽ Cmax is 15 ng / ml and is achieved after 1.6 hours. Bioavailability is 88%.

Distribution. Cyproterone acetate almost completely binds to plasma albumin, approximately 3.5-4% is in a free state. Since protein binding is non-specific, changes in the level of globulin binding to sex steroids (GSHs) do not affect the pharmacokinetics of cyproterone acetate. Breast milk releases up to 0.2% of the dose of cyproterone acetate.

Metabolism and excretion. The pharmacokinetics of cyproterone acetate are two-phase, T1 / 2 is 0.8 h and 2.3 days, respectively, for the first and second phases.

The total plasma clearance is 3.6 ml / min / kg. Biotransformed by hydroxylation and conjugation, the main metabolite is the 15b-hydroxyl derivative. It is excreted primarily in the form of metabolites by the kidneys and through the intestine in a ratio of 1: 2, a small part - unchanged through the intestine.

T1 / 2 for metabolites of cyproterone acetate is 1.8 days.

Ethinylestradiol

Suction. After taking ChloeŽ, ethinyl estradiol is quickly and completely absorbed from the digestive tract. In the process of absorption and first passage through the liver, ethinyl estradiol undergoes intensive metabolism, which accounts for bioavailability of about 45% and its significant individual variability. After ingestion of 1 table, coated with a film coat of ChloroŽ Cmax is approximately 80 pg / ml and is achieved after 1.7 hours.

Distribution. The association with proteins (albumin) of blood plasma is high (2% are in the plasma in a free form).

With breast milk, up to 0.02% of the dose of ethinylestradiol is released. Ethinyl estradiol increases the hepatic synthesis of GSD and corticosteroid-binding globulin (CSF) during continuous administration. Against the backdrop of treatment with CHLOŽ, the serum concentration of HSCS increases from about 100 to 300 nmol / L, and the serum CSF concentration increases from about 50 to 95 μg / ml.

Metabolism and excretion. The pharmacokinetics of ethinylestradiol are two-phase, with T1 / 2 1-2 and approximately 20 hours, respectively. Plasma clearance is about 5 ml / min / kg. Ethinyl estradiol is excreted from the body in the form of metabolites; About 40% - kidneys, 60% - through the intestines.

Indications of ChloeŽ

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 knots, 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 at present or in the anamnesis (including deep vein thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular disorders, for example stroke);

Conditions preceding thrombosis (including angina pectoris, transient ischemic attacks);

Multiple or expressed risk factors for venous or arterial thrombosis (including complicated heart valve apparatus defects, atrial fibrillation, cerebrovascular or coronary artery disease, uncontrolled hypertension, severe dyslipoproteinemia, subacute bacterial endocarditis, prolonged immobilization, surgical interventions on the lower Extremities, neurosurgical operations, extensive injuries, smoking over the age of 35, obesity with a body mass index of more than 30 kg / m2);

Identified hereditary or acquired predisposition to venous or arterial thrombosis, for example resistance to activated protein C (APS), deficiency of antithrombin III, deficiency of protein C, deficiency of protein S, hyperhomocysteinemia and the presence of antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant);

Diabetes mellitus with diabetic angiopathy;

Severe liver diseases at present or in the history or expressed violations of liver function - no earlier than 6 months after the normalization of liver function;

Liver tumors (benign and malignant);

Hormone-dependent malignant tumors or suspicion of them, incl. Tumors of the mammary gland or genitals (including in the anamnesis);

Bleeding from the vagina of an unclear etiology;

Pancreatitis with severe hypertriglyceridemia (including in the anamnesis);

The presence in the anamnesis of migraine, which was accompanied by focal neurological symptoms;

The period of breastfeeding;

Congenital hyperbilirubinemia (syndromes Gilbert, Dubin-Johnson and Rotor);

Age over 40 years;

Hyperprolactinemia;

Lactose intolerance, lactase deficiency, glucose-galactose malabsorption;

Pregnancy or suspicion of it.

If any of these conditions develop for the first time against the background of taking the drug Chloe, the drug should be immediately withdrawn.

The drug CHLOEŽ is not intended for use in men.

With caution: epilepsy, depression, ulcerative colitis, liver and gallbladder disease, uterine fibroids, mastopathy, chorea, tetany, porphyria, multiple sclerosis, varicose veins, tuberculosis, kidney disease, adolescence (without regular ovulatory cycles), dyslipoproteinemia, Sickle-cell anemia, idiopathic jaundice or pruritus during a previous pregnancy, otosclerosis with deterioration of hearing during anterior pregnancy.

Side effects

The following side effects are presented in accordance with the following gradations of their frequency: very often (≥1 / 10); Often (≥1 / 100 to <1/10); Infrequently (≥1 / 1000 to <1/100); Rarely (≥1 / 10000 to <1/1000); Very rarely (<1/10000); The frequency is unknown (the frequency can not be estimated from the available data).

From the nervous system: often - headache; Infrequently - migraine: frequency unknown - worsening of epilepsy.

From the side of the organ of vision: rarely - intolerance of contact lenses.

From the digestive tract: often - nausea, pain in the abdomen; Infrequently - vomiting, diarrhea.

From the skin and subcutaneous tissues: infrequently - rash, hives; Frequency is unknown - erythema nodosum, erythema multiforme.

From 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 breast: often - pain / soreness in the mammary glands, engorgement of the mammary glands; Infrequently - enlargement of mammary glands; Rarely - discharge from the vagina, discharge from the mammary glands *; Frequency unknown - acyclic bleeding / bleeding (metrorrhagia).

Mental disorders: often - reduced mood, mood swings; Infrequently - decreased libido; Rarely - increased libido; Frequency unknown - worsening of the course of endogenous depression.

From the side of the vessels: rarely - thromboembolism.

* Postmarketing studies reported painful menstrual bleeding and the absence of menstrual bleeding, the frequency of which was not assessed.

The following serious adverse events have been reported in women using COCs (which include the ChloeŽ preparation):

Venous thromboembolic disorders;

- arterial thromboembolic disorders;

- stroke;

- Increased blood pressure;

- hypertriglyceridemia;

- impaired glucose tolerance or influence on peripheral insulin resistance;

- Liver tumors (benign and malignant);

- impaired liver function;

- Chloasma;

- in women with hereditary angioedema, exogenous estrogens can cause or exacerbate symptoms of angioedema;

- the onset or worsening of conditions for which communication with the use of COCs (which include the drug Chloe) is not undeniable: jaundice and / or pruritus associated with cholestasis; Formation of stones in the gallbladder; Porphyria; Systemic lupus erythematosus; Hemolytic-uremic syndrome; chorea; Herpes during an earlier pregnancy; Hearing loss associated with otosclerosis; Crohn's disease; ulcerative colitis; cervical cancer;

- impaired vision;

- dizziness;

- pancreatitis;

- cholecystitis;

- the incidence of breast cancer diagnosis in women using COCs (which include the drug ChloeŽ) is increased very slightly. Breast cancer is rarely seen in women under 40 years of age, exceeding the frequency is insignificant in relation to the overall risk of breast cancer. The causal relationship of the occurrence of breast cancer with the use of COC is not established. For more information, see "Contraindications" and "Special instructions".

Interaction

With the simultaneous use of HLOEŽ with inducers of microsomal hepatic enzymes (hydantoins, barbiturates, primidone, carbamazepine and rifampicin, and also possibly oxcarbazepine, topiramate, felbamate and griseofulvin), the clearance of ethinyl estradiol and cyproterone increases, which can lead to breakthrough uterine bleeding or impaired reliability Contraception.

With simultaneous use with ampicillin, rifampicin and tetracyclines, the contraceptive reliability of CHLOŽ is reduced.

Dosing and Administration

Inside, 1 table / day. The tablet is taken without chewing, and washed down with a small amount of liquid. The time of taking the drug does not play a role, but the subsequent reception should be done at the same selected hour, preferably after breakfast or dinner.

In the absence of taking any hormonal contraceptive drugs in the previous month. Reception of the drug ChloeŽ begins on the 1st day of the menstrual cycle (ie, on the 1st day of menstrual bleeding), using a tablet of the corresponding day of the week from the calendar package. It is allowed to start taking the menstrual cycle on the 2nd-5th day, but in this case it is recommended to additionally use the barrier method of contraception during the first 7 days of taking the pills from the first package.

Daily administration of the drug is carried out using tablets from the calendar pack in sequence along the direction of the foil-applied arrow until all the tablets are taken. After the termination of reception 21 tab. Yellow-orange color from the calendar package, it is necessary in the next 7 days to take the remaining white tablets. During the last 7 days of the treatment cycle (28 days), menstrual bleeding (bleeding due to cancellation of treatment) should occur. Menstruation-like bleeding usually begins 2-3 days after the 21st day of the cycle of treatment with the drug CHLOEŽ. The next package must be started the day after the completely completed taking of the tablets from the previous package, whether bleeding continues or not.

When switching from combined contraceptive drugs (COC, vaginal ring or contraceptive patch). The administration of the drug CHLOEŽ should be started the day after the last active tablet of the previous preparation, but in no case later than the next day after an ordinary 7-day break in admission (for preparations containing 21 tablets). Further - according to the scheme described above. If the patient took the previous contraceptive on a daily basis for 28 days, the drug HLOEŽ should be taken after the last inactive tablet was taken. Reception of the drug CHLOEŽ should begin on the day of removal of the vaginal ring or contraceptive patch, but no later than the day when a new ring is to be inserted or a new patch is stuck.

When switching from contraceptives containing only gestagens (mini-pili, injection forms, implants, gestagen releasing intrauterine contraceptive). When switching from a mini-drink, you can start taking ChloeŽ without interruption.

When using injectable forms of contraceptives, the drug ChloeŽ is taken from the day the next injection is to be taken. When moving from the implant - the day it is removed. In all cases, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the drug.

After abortion in the first trimester of pregnancy, a woman can start taking the drug immediately. In this case, the woman does not need additional methods of contraception.

After delivery in the absence of breastfeeding or abortion in the second trimester of pregnancy, the drug should be taken on the 21-28th day. If the reception is started later, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the drug.

If a woman has had a sex life between childbirth or abortion and the beginning of taking ChloeŽ, first you should exclude pregnancy or you must wait for the first menstrual period.

Acceptance of missed tablets

The woman should take the missed tablet as soon as possible, the next tablet is taken at the usual time. At a delay of less than 12 hours, the reliability of contraception does not decrease. If the delay in taking the tablets is more than 12 hours, the reliability of contraception can be reduced. The more pills are missed and the closer the pass to a 7-day break in taking pills, the greater the probability of pregnancy. In this case, you can follow the following two basic rules:

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

- to achieve adequate suppression of hypothalamic-pituitary-ovarian regulation, 7 days of continuous administration are required.

Accordingly, the following recommendations can be given, if the delay in taking the tablets was more than 12 hours (the interval from the time the last tablet was taken was more than 36 hours).

The first week of taking the drug. A woman should take the last missed pill as soon as possible, as soon as she remembers (even if it means taking two tablets at the same time). The next tablet is taken at the usual time. Additionally, a barrier method of contraception should be used for the next 7 days. If sexual intercourse took place within a week before passing the pill, it is necessary to consider the likelihood of pregnancy.

The second week of taking the drug. A woman should take the last missed pill as soon as possible, as soon as she remembers (even if it means taking two tablets at the same time). The next tablet is taken at the usual time.

Provided that the woman took the pill correctly for 7 days preceding the first missed pill, there is no need to use additional contraceptive measures. Otherwise, as well as when skipping 2 or more tablets, barrier methods of contraception (for example, a condom) should be used additionally within 7 days.

The third week of taking the drug. The risk of pregnancy is increased due to the upcoming interruption in taking the tablets, but if within 7 days preceding the first missed tablet, all the pills were taken correctly, there is no need to use additional contraceptive methods.

1. A woman should take the last missed tablet as soon as possible, as soon as she remembers (even if it means taking two tablets at the same time). The following tablets are taken at the usual time, until the tablets run out of the current package. The next package should be started immediately. Bleeding cancellation is unlikely until the tablets from the second package run out, but there may be spotting and breakthrough bleeding during taking the tablets.

2. A woman can also interrupt the taking of tablets from the current package. She then needs to take a break for 7 days, including the day the tablet is missed, and then start taking the tablets out of the new package.

If the woman missed taking the pill and then during a break in admission she does not have a withdrawal bleeding, it is necessary to exclude pregnancy.

Recommendations for gastrointestinal disorders. If a woman had vomiting within 3 to 4 hours after taking the drug, the absorption of the active substances may be incomplete. In this case, it is necessary to focus on the recommendations when skipping the tablet.

Change in the menstrual bleeding day. In order to delay the onset of menstrual bleeding, a woman should continue taking the tablets from a new package of the drug immediately after taking all the pills from the previous package, without interruption in admission. Tablets from this new package can be taken for as long as the woman wishes (until the package is finished). Against the background of taking the drug from the second package, a woman may have spotting or breakthrough uterine bleeding. Resume the use of the drug ChloeŽ from the new pack after a normal 7-day break.

In order to transfer the day of the onset of menstrual bleeding to another day of the week, a woman should shorten the nearest break in taking pills for as many days as she wants. The shorter the interval, the higher the risk that it will not have withdrawal bleeding and thereafter there will be spotting bleeding and breakthrough bleeding during the second package (just like when she would like to delay the onset of menstrual bleeding).

In the treatment of hyperandrogenic conditions, the duration of admission is determined by the severity of the disease. After the disappearance of the symptoms, it is recommended to take the drug for at least another 3-4 months. In the case of relapse after a few weeks or months after the completion of the course, you can re-use the drug ChloeŽ. If the drug is resumed (after a 4-week break or more), an increased risk of VTE should be considered (see also "Special instructions" and Precautions).

Children and teenagers. The drug CHLOEŽ is shown only after the onset of menarche.

Patients in postmenopausal women. Not applicable. The drug HLOEŽ is not indicated after the onset of menopause.

Patients with impaired liver function. The drug CHLOEŽ is contraindicated in women with severe liver disease until the liver function is normal (see also "Contraindications").

Patients with impaired renal function. The drug ChloeŽ has not been specifically studied in patients with impaired renal function. The available data do not imply a change in treatment in such patients.

Overdose

Symptoms: nausea, vomiting, slight vaginal bleeding.

Treatment: conduct symptomatic therapy. There is no specific antidote.

special instructions

Before starting the use of the drug, it is necessary to conduct a general medical examination (including mammary glands and cytological examination of the cervical epithelium), to exclude pregnancy, violations by the blood coagulation system. With prolonged use of the drug, preventive check-ups should be performed every 6 months.

In the presence of risk factors, the potential risk and the expected benefits of therapy should be carefully evaluated and discussed with the woman before she decides to start taking the drug.

With weighting, strengthening, or the first manifestation of any of these conditions or risk factors, it may be necessary to cancel the drug.

The use of the drug CHLOE leads to an increased risk of developing VTE compared with the risk in women who do not take the drug.

The additional risk of VTE is the highest during the first year of the use of the drug CHLOE, or with the resumption of admission after an interval of 4 weeks or more. VTE in 1-2% of cases can be fatal. The approximate frequency of VTE when taking COC with a low dose of estrogens (less than 50 μg ethinyl estradiol) is up to 4 cases per 10,000 women per year, compared to 0.5-1 per 10,000 women who do not take COCs. In this case, the frequency of VTE when taking COC is lower than the frequency of VTE associated with pregnancy (6 cases 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 the drug CLEEŽ, compared to COCs containing levonorgestrel, and is similar for COCs containing desogestrel / gestodene / drospirenone.

Patients with polycystic ovary syndrome have an increased risk of developing cardiovascular disease.

Epidemiological studies have also shown the connection of the use of hormonal contraceptives with an increased risk of developing arterial thromboembolism (myocardial infarction, transient ischemic attacks).

Very rarely reported on thrombosis of other vessels, namely veins and arteries of the liver, mesentery, kidneys, brain or retina, in persons taking hormonal contraceptives.

The patient should be warned that with the development of symptoms of venous or arterial thrombosis should immediately consult a doctor. These symptoms include unilateral pain in the lower limb and / or swelling; Sudden severe pain in the chest with irradiation in the left arm or without irradiation; Sudden shortness of breath; Sudden attack of cough; Any unusual, strong, prolonged headache; Increased frequency and severity of migraine; Sudden partial or complete loss of vision; Diplomacy; Slurred speech or aphasia; dizziness; Collapse with or without partial seizure; Weakness or significant loss of sensitivity, suddenly appeared on one side or in one part of the body; Motor disorders; An acute abdomen.

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. Women over 35 should be strongly advised to quit smoking if they want to take the drug ChloeŽ);

- with a family history (family history of cases of VTE at a relatively young age with parents or close relatives). In case of suspected hereditary predisposition, a woman should consult a specialist before deciding on any hormonal contraception;

- with prolonged immobilization, surgical interventions on the lower extremities, neurosurgical operations or extensive trauma. In these situations, it is necessary to stop using (in the case of a scheduled operation for at least 4 weeks), and not to resume it until the end of 2 weeks after complete recovery of motor activity. If the use of the ChloeŽ preparation has not been discontinued in advance, consideration should be given to antithrombotic therapy;

- with obesity (body mass index more than 30 kg / m2).

The risk of arterial thromboembolic complications or cerebrovascular accidents increases:

- with increasing age;

- when smoking (with intensive smoking and with increasing age, the risk is further increased, especially in women over 35. Women over 35 should be strongly advised to quit smoking if they want to take the drug ChloeŽ);

- with dyslipoproteinemia;

- with arterial hypertension;

- with migraine;

- with diseases of the heart valves;

- with atrial fibrillation;

- with a family history (family history of cases of arterial thrombosis at a relatively young age in the parents or close relatives). In case of suspected hereditary predisposition, a woman should consult a specialist before deciding on any hormonal contraception.

Violations of peripheral circulation can also occur in diabetes mellitus, systemic lupus erythematosus, hemolytic uremic syndrome, chronic inflammatory bowel diseases (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.

An increase in the frequency or severity of migraine attacks during the use of the ChloeŽ preparation (which may be a harbinger of cerebral circulatory disorders) is the basis for the immediate discontinuation of the drug.

There is no consensus on the potential role of varicose veins and superficial thrombophlebitis in the development of VTE.

Biochemical factors that may indicate hereditary or acquired predisposition to venous or arterial thrombosis include resistance to APS, hyperhomocysteinemia, antithrombin III deficiency, protein C deficiency, protein deficiency S, antiphospholipid 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 the drug HLOEŽ should explain the need for timely communication to the doctor in case of a possible development of possible symptoms of thrombosis. In the case of thrombosis or suspected of its occurrence, treatment with the drug HLOEŽ should be discontinued. Given the teratogenicity of anticoagulants (coumarins), the use of adequate contraceptive methods should begin.

Other states

In women with hypertriglyceridemia, while taking COC (if this condition exists in a family history), an increased risk of developing pancreatitis is possible. The relationship between the administration of COC and hypertension is not established. In the event of persistent arterial hypertension, the drug HLOEŽ should be discontinued and appropriate antihypertensive therapy should be prescribed. Reception of a contraceptive can be continued at normalization of a BP.

If there is a violation of liver function, it may be necessary to temporarily stop the drug HLOEŽ before normalizing the laboratory parameters.

Recurrent cholestatic jaundice, which develops for the first time during pregnancy or previous reception of sex hormones, requires discontinuation of COCs.

Although COCs have an effect on insulin resistance and glucose tolerance, there is usually no need to correct the dose of hypoglycemic drugs in patients with diabetes mellitus. Nevertheless, this category of patients should be under careful medical supervision.

Women with a tendency to chloasma while taking COC should avoid prolonged exposure to sunlight and exposure to UV radiation.

If women with hirsutism have recently developed symptoms or have significantly increased, other causes, such as androgen-producing tumors, congenital adrenal cortex dysfunction, should be taken into account when making a differential diagnosis.

On the background of taking the drug, sometimes bleeding irregularities (spotting or breakthrough bleeding) can 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 taken to exclude malignant neoplasms (including both diagnostic curettage of the uterine cavity) or pregnancy.

In some cases, bleeding cancellations may not develop during a break in taking the tablets. If the tablets are taken irregularly or if there are no two menstrual bleeding in a row, you should exclude pregnancy before continuing with the drug.

It is possible to change the results of skin allergic tests, decrease the concentration of LH and FSH. Due to the fact that the contraceptive effect is fully manifested by the 7th day from the beginning of the drug intake, in the first week additional non-hormonal methods of contraception are recommended.

Prescribe the drug after delivery in the absence of breastfeeding is recommended only after the completion of the first normal menstrual cycle.

Treatment should be stopped 3 months before the planned pregnancy.

With diarrhea and vomiting, the contraceptive effect is reduced (without stopping the drug, additional non-hormonal methods of contraception should be used).

Tumors

There are reports of a slight increase in the risk of developing cervical cancer with prolonged use of COCs. Communication with the reception of the COC has not been proved. The question remains to what extent these findings are related to the pathology of the cervix or the features of sexual behavior (the more rare use of barrier methods of contraception).

The most significant risk factor for developing cervical cancer is persistent papillomavirus infection. 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 COC (relative risk 1.24). Increased risk gradually disappears within 10 years after discontinuation of these medications. Due to the fact that breast cancer is rarely seen in women under 40 years of age, the increase in the number of breast cancer diagnoses in women who are currently taking COCs or who have recently taken COC is insignificant in relation to the overall risk of this disease. His connection with the use of COC is not proven. The observed increase in risk may also be a consequence of an earlier diagnosis of breast cancer in women using COCs. Women who have ever used COC have earlier stages of breast cancer than women who have never used them.

In rare cases, with the use of COCs, development of liver tumors was observed, which in some cases led to life-threatening intraabdominal bleeding. This should be taken into account when making a differential diagnosis in the event of severe pain in the abdomen, increased liver, or signs of intra-abdominal bleeding.

Laboratory Tests

The use of COCs can influence the results of laboratory tests, including biochemical indices of liver, thyroid, adrenal and kidney efficiency, the concentration of plasma proteins, such as CSF, as well as the lipid / lipoprotein composition of the blood, the parameters of carbohydrate metabolism and the blood coagulation system. However, deviations usually remain within the range of normal laboratory values.

Form of issue

The tablets covered with a film cover. According to 21 tables. Yellow-orange color, covered with a film membrane, together with 7 tablets. White (placebo) in a PVC / aluminum blister. By 1 or 3 bl. Are placed in a cardboard box.

Terms of leave from pharmacies

On prescription.

Storage conditions for ChloeŽ

At a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life of ChloeŽ

3 years.

Do not use after the expiry date printed on the package.