Chloe pills, 28 pcs.

Composition

Yellow-orange film-coated tablets (21 pcs. in a blister).

1 tablet contains:

Active ingredients:

ethinyl estradiol 35 mcg,

ciproterone acetate 2 mg.

Auxiliary substances:

lactose monohydrate – 68.8 mg,

povidone-2 mg,

sodium carboxymethyl starch (type A) – 1.5 mg,

colloidal anhydrous silicon dioxide-0.188 mg,

colloidal aluminum oxide-0.04 mg,

magnesium stearate-0.375 mg.

Shell composition:

Opadry II Yellow OY-L-32901 dye (Opadry II Yellow OY-L-32901) – 3 mg (lactose monohydrate, hypromellose 2910, titanium dioxide, macrogol 4000, iron oxide yellow, iron oxide black, iron oxide red, purified water).

Tablets (placebo) of white color (7 pcs. in a blister).

Auxiliary substances:

lactose monohydrate,

povidone,

sodium carboxymethyl starch (type A),

colloidal anhydrous silicon dioxide,

colloidal aluminum oxide,

magnesium stearate.

The blister contains 28 tablets.

Film-coated tablets of yellow-orange color 21 pieces in a blister.

Tablets (placebo) of white color 7 pieces in a blister.

In a pack of cardboard 1 blister.

Pharmacological action

Pharmacodynamics

Combined low-dose monophasic oral contraceptive drug with antiandrogenic activity. The mechanism of action is due to the antiandrogenic drug of the steroid structure – ciproterone acetate and oral estrogen – ethinyl estradiol, which are part of it.

Ciproterone Acetate

It has the ability to competitively bind to the receptors of natural androgens (including testosterone, dihydroepiandrosterone, androstenedione), which are formed in small amounts in the body of women, mainly in the adrenal glands, ovaries and skin. By blocking androgen receptors in target organs, it reduces androgenization phenomena in women (due to disruption of processes mediated by hormone-receptor complexes at the level of basic intracellular mechanisms). Thus, it becomes possible to treat diseases caused by increased androgen production or specific sensitivity to these hormones.

Against the background of taking the drug, the increased activity of the sebaceous glands decreases, which plays an important role in the occurrence of acne and seborrhea. After 3-4 months of therapy, the existing rash usually disappears. Excessive greasiness of hair and skin disappears even earlier. It also reduces hair loss, which often accompanies seborrhea.

Treatment with Khloe ® 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 its antiandrogenic properties, ciproterone acetate has progestogenic activity that mimics the properties of the corpus luteum hormone. It inhibits the secretion of gonadotropic hormones by the pituitary gland and inhibits ovulation, which causes a contraceptive effect.

Ethinyl Estradiol

It enhances the central and peripheral effects of ciproterone acetate on ovulation, preserves the high viscosity of cervical mucus, making it difficult for spermatozoa to enter the uterine cavity and contributing to a reliable contraceptive effect.

While taking the drug, the cycle becomes more regular, painful menstruation is less frequent, the intensity of bleeding decreases, and the risk of iron deficiency anemia decreases.

Pharmacokinetics

of Ciproterone Acetate

Suction

After oral administration, ciproterone acetate is completely absorbed from the gastrointestinal tract. _cmax in blood plasma is reached in 1.6 hours and is 15 ng / ml. Bioavailability is 88%.

Distribution

Ciproterone acetate binds almost completely to plasma albumin, and is approximately 3.5-4% free. Since protein binding is non-specific, changes in the level of sex steroid binding globulin (SHBG) do not affect the pharmacokinetics of ciproterone acetate.

Metabolism

Biotransformed by hydroxylation and conjugation, the main metabolite is a 15b-hydroxyl derivative.

Elimination

The pharmacokinetics of ciproterone acetate are two-phase: T_1/2 is 0.8 hours and 2.3 days, respectively, for the first and second phases. The total plasma clearance is 3.6 ml / min / kg. It is mainly excreted in the form of metabolites by the kidneys and through the intestines in a ratio of 1: 2, a small part-unchanged through the intestines. Up to 0.2% of the ciproterone acetate dose is excreted in breast milk. T_1/2 for metabolites of ciproterone acetate is 1.8 days.

Ethinyl Estradiol

Suction

After taking the drug, ethinyl estradiol is rapidly and completely absorbed from the gastrointestinal tract. _cmax is approximately 80 pg / ml and is reached in 1.7 hours. Bioavailability is about 45%, and has significant individual variability.

Distribution

Binding to plasma proteins (albumin) is high: only 2% is found in plasma in free form.

Ethinyl Estradiol increases hepatic synthesis of SHBPS and corticosteroid-binding globulin (CSG) with continuous use. During treatment with Chloe®, the serum SHBP concentration increases from approximately 100 nmol / L to 300 nmol/L, and the serum CSG concentration increases from approximately 50 mcg / ml to 95 mcg/ml.

Metabolism

In the process of absorption and “first passage” through the liver, ethinyl estradiol undergoes intensive metabolism.

Elimination

The pharmacokinetics of ethinyl estradiol are biphasic: T_1/2 1-2 h and approximately 20 h, respectively. Plasma clearance is about 5 ml/min/kg. Ethinyl Estradiol is excreted from the body in the form of metabolites: about 40% – by the kidneys,60% – through the intestines. Up to 0.02% of the ethinyl estradiol dose is excreted in breast milk.

Indications

• Contraception in women with androgenization symptoms.

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;
• mild forms of hirsutism.

Use during pregnancy and lactation

It is contraindicated to use the drug during pregnancy, suspected pregnancy and during breastfeeding.

Contraindications

• Thrombosis and thromboembolism, including history (deep venous thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular disorders);
• state prior thrombosis (including transient ischemic attack, angina);
• arterial hypertension;
• diabetes mellitus complicated by microvascular complications;
• the presence of a severe or multiple risk factors for venous or arterial thrombosis;
• disease or severe violations of liver function;
• liver tumors (including in the anamnesis);
• hormone-dependent malignant tumors including tumors of the breast or genital organs (including in the anamnesis);
• congenital hyperbilirubinemia (Gilbert syndrome, Dubin-Johnson, Rotor); — pancreatitis (including in history), if it was accompanied by severe hypertriglyceridemia; — uterine bleeding of unknown etiology;
• migraine, accompanied by focal neurological symptoms (including in the anamnesis);
• sickle cell anemia;
• idiopathic jaundice or itching during the last pregnancy;
• otosclerosis with deterioration during pregnancy;
• hyperprolactinemia;
• lactation;
• pregnancy or suspicion of it;
• the age of 40 years;
• hypersensitivity to the components of the drug.

If any of these conditions develop for the first time while taking Khloe®, the drug should be discontinued immediately.

With caution: the drug should be used for epilepsy, depression, ulcerative colitis, liver and gallbladder diseases, uterine fibroids, mastopathy, chorea, tetany, porphyria, multiple sclerosis, varicose veins, tuberculosis, kidney disease, in adolescence (without regular ovulatory cycles).

Side effects

From the endocrine system: rarely-engorgement, soreness, enlargement and discharge from the mammary glands, weight gain.

From the genital system: rarely-intermenstrual bleeding, changes in vaginal secretions, changes in libido.

From the central nervous system: rarely-headache, migraine, decreased mood.

From the digestive system: rarely-nausea, vomiting, gastralgia.

Other: very rarely – poor contact lens tolerance, eyelid edema, visual impairment, conjunctivitis, hearing loss, allergic reactions, thrombophlebitis, thromboembolism, generalized itching, jaundice, the appearance of pigmented spots on the face (chloasma).

These side effects can develop in the first few months of using the drug and usually decrease with time.

Interaction

Concomitant administration of Chlo® with inducers of microsomal liver enzymes (hydantoins, barbiturates, primidone, carbamazepine and rifampicin; and possibly with oxcarbazepine, topiramate, felbamate and griseofulvin) increases the clearance of ethinyl estradiol and ciproterone, which may lead to breakthrough uterine bleeding or reduce the reliability of contraception.

When used concomitantly with ampicillin, rifampicin and tetracyclines, the contraceptive reliability of Chloe ® decreases.

How to take it, course of administration and dosage

The drug should be taken orally for 1 tab. /day. The tablet is taken without chewing, and washed down with a small amount of liquid. It is recommended to take the drug at the same time, preferably after breakfast or dinner.

Start taking Khloe® on the 1st day of the cycle, using a tablet of the corresponding day of the week from the calendar package. Daily intake of the drug is carried out using tablets from the calendar package sequentially in the direction of the arrow applied to the foil, until all tablets are taken. After the end of taking all the yellow-orange tablets from the calendar package, it is necessary to take the remaining white tablets in the next 7 days.

During the last 7 days of the treatment cycle (28 days), menstrual-like bleeding should occur (as a result of discontinuation of treatment). Menstruation usually begins 2-3 days after the 21st day of the drug treatment cycle.

The next package should be started on the day after the tablets from the previous package are completely finished, regardless of the fact that the bleeding continues/stops.

When switching from combined oral contraceptives, the use of Chloe® should be started on the next day after taking the last tablet with the active components of the previous drug, but in no case later than the next day after the usual 7-day break in taking (for drugs containing 21 tablets). Then follow the scheme described above.

If the patient has taken a previous contraceptive daily for 28 days, the use of Chloe® should begin after taking the last inactive tablet.

When switching from progestogen-only contraceptives (“mini-pills”) Khloe® can be applied without interruption.

When using injectable forms of contraceptives, Khloe® should be used from the day when the next injection should be made.

When switching from the implant, Khloe® should be used as early as the day of its removal.

In all cases, it is necessary to use an additional barrier method of contraception during the first 7 days of using 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 childbirth or abortion in the second trimester of pregnancy, the drug should be started on 21-28 days. If reception is started later, it is necessary to use an additional barrier method of contraception during the first 7 days of using the drug.

If a woman has had sexual activity in the period between childbirth or abortion and the start of using the drug, pregnancy should be excluded first or it is necessary to wait for the first menstruation.

The missed pill should be taken as soon as possible, and the next pill should be taken at the usual time. If you are late If the delay in taking the pill is > 12 hours, the reliability of contraception may be reduced.

If the delay in taking pills is > 12 hours (the interval from the last pill >> 36 hours) during the 1st and 2nd weeks of taking the drug, the woman should take the last missed pill as soon as possible: even if this means taking two tablets at the same time. The next tablet should be taken at the usual time. Additionally, you must use a barrier method of contraception for the next 7 days.

If the delay in taking a pill is > 12 hours (the interval from the last pill >> 36 hours) during the 3rd week of taking the drug, the woman should take the last missed pill as soon as possible: even if this means taking two tablets at the same time. The next tablet should be taken at the usual time. You should start taking the tablet from the new package, and at the end of the current package – without a break. Probably, withdrawal bleeding will not occur until the end of the second package, but there may be spotting or breakthrough uterine bleeding on the days of taking the pills.

If a woman has had vomiting within 3 to 4 hours after taking the drug, the absorption of active substances may be incomplete. In this case, you need to follow the recommendations when skipping a pill.

To delay the start date of menstruation, a woman should continue taking pills from the new package of the drug immediately after taking all the pills from the previous one, without interruption. Tablets from the new package can be taken for as long as the woman wants (until the package runs out). Against the background of taking the drug from the second package, a woman may experience spotting or breakthrough uterine bleeding. You should start taking tablets from the next package after you have finished taking all 28 tablets.

To move the day of the beginning of menstruation to another day of the week, a woman should shorten the next break in taking pills for as many days as she wants. The shorter the interval, the higher the risk that she will not have withdrawal bleeding and, in the future, will have spotting and breakthrough bleeding while taking the second package (as well as in the case when she would like to delay the onset of menstruation).

In the treatment of hyperandrogenic conditions, the duration of use of the drug is determined by the severity of the disease. After the symptoms disappear, it is recommended to take the drug for at least 3-4 months. If a relapse occurs a few weeks or months after the end of the course, you can repeat therapy with Khloe®.

Overdose

Symptoms: nausea, vomiting, slight vaginal bleeding.

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

Special instructions

Before starting the use of Chloe®, it is necessary to conduct a general medical examination (including mammary glands and cytological examination of cervical mucus), exclude pregnancy, disorders of the blood coagulation system. With prolonged use of the drug, preventive control examinations should be carried out every 6 months.

If there are risk factors, the potential risk and expected benefit of therapy should be carefully evaluated and discussed with the woman before starting the drug.

Estimated incidence of venous thromboembolism ( VTE) with low-dose oral contraceptives ( At the same time, the frequency of VTE when taking combined oral contraceptives is less than the frequency of VTE associated with pregnancy (6/10,000 pregnant women per year).

The patient should be warned that if symptoms of venous or arterial thrombosis develop, it is necessary to immediately consult a doctor. These symptoms include unilateral leg pain and/or swelling, sudden severe chest pain with or without radiating to the left arm, sudden shortness of breath, sudden coughing, any unusual, severe, prolonged headache, increased frequency and severity of migraines, sudden partial or complete loss of vision, diplopia, slurred speech or aphasia, dizziness, collapse with or without a partial seizure, weakness, or very significant loss of sensation that suddenly appears on one side of the head. sideways or in one part of the body, motor disorders, acute stomach symptom complex.

The relationship between the use of combined oral contraceptives and arterial hypertension has not been established. If persistent arterial hypertension occurs, the drug should be discontinued and appropriate antihypertensive therapy should be prescribed. Taking a contraceptive can be continued if blood pressure is normalized.

If liver function disorders occur, it may be necessary to temporarily discontinue the drug until laboratory parameters normalize.

Recurrent cholestatic jaundice, which develops for the first time during pregnancy or during a previous intake of sex hormones, requires discontinuation of combined oral contraceptives.

Despite the fact that combined oral contraceptives have an effect on tissue insulin resistance and glucose tolerance, it is usually not necessary to adjust the dose of hypoglycemic drugs in patients with diabetes mellitus. However, this category of patients should be closely monitored.

Women who are prone to chloasma should avoid prolonged exposure to the sun and exposure to ultraviolet radiation while taking combined oral contraceptives.

If women with hirsutism have recently developed symptoms or have significantly worsened, other causes should be considered when making a differential diagnosis, such as an androgen-producing tumor or a congenital dysfunction of the adrenal cortex.

Irregular bleeding (spotting or breakthrough bleeding) may occur during the first months of treatment, especially during the first months of treatment. Therefore, any irregular bleeding should only be evaluated after an adjustment period of approximately 3 cycles.

If irregular bleeding recurs or develops after previous regular cycles, then non-hormonal causes should be considered and adequate diagnostic measures (including diagnostic curettage) should be carried out to exclude malignancies or pregnancy.

In some cases, withdrawal bleeding may not develop during a break in the use of the drug. If the pills are taken irregularly or if there are no two menstrual-like bleeding events in a row, pregnancy should be excluded until the drug is continued.

It is possible to change the results of skin allergic tests, reduce the concentration of LH and FSH against the background of the drug.

Due to the fact that the contraceptive effect is fully manifested by the 7th day from the start of taking the drug, additional non-hormonal methods of contraception are recommended in the first week.

The use of the drug after childbirth is recommended not earlier than the first normal menstrual cycle has passed.

Treatment should be stopped immediately 3 months before the planned pregnancy and approximately 6 weeks before the planned surgical intervention, with prolonged immobilization.

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

Women who smoke and take hormonal contraceptive medications have an increased risk of developing vascular diseases with serious consequences (myocardial infarction, stroke). The risk increases with age and depending on the number of cigarettes smoked (especially in women over 30 years of age).

Form of production

There are two types of film-coated tablets.

Storage conditions

Keep out of reach of children at a temperature not exceeding 25°C.

Shelf

life is 3 years.

Active ingredient

Ciproterone, Ethinyl Estradiol

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as prescribed by a doctor, For women of childbearing age

Indications

Acne, Seborrhea, Hirsutism, Contraception

Weight

Weight: 17 gr.