Monophasic low-dose combined oral contraceptive preparation with antiandrogenic activity. The mechanism of action is due to its constituent anti-androgenic steroid drug structure – cyproterone acetate and oral estrogen – ethinyl estradiol.
It has the ability to competitively bind to the natural receptors of androgens (including testosterone, dehydroepiandrosterone, androstenedione) formed in small amounts in the body of women, mostly in the adrenal glands, skin and ovaries. By blocking the androgen receptors in target organs, reduces androgenization phenomena in women (by disrupting processes mediated by the hormone-receptor complexes on the basic mechanisms of intracellular level). Thus, it becomes possible to treat diseases caused by increased formation of androgens or a particular sensitivity to these hormones.
On the background of the drug decreases increased activity of the sebaceous glands, which plays an important role in the occurrence of acne and seborrhea. After 3-4 months of therapy available rash usually disappears. Excessive oiliness of hair and skin disappears earlier. It also reduces hair loss, often accompanied by seborrhea.
Hloe® therapy in women of reproductive age reduces the clinical manifestations of mild forms of hirsutism; however, the effect of treatment can be expected only after a few months of use.
Along with antiandrogenic properties, cyproterone acetate possesses progestational activity simulating properties luteum hormone. Inhibits secretion of pituitary gonadotropins and inhibits ovulation, resulting in contraceptive effect.
Enhances the central and peripheral effect of cyproterone acetate ovulation, retains a high viscosity of the cervical mucus, making it difficult for sperm entry into the uterus and helping ensure a reliable contraceptive effect.
On the background of the drug cycle becomes more regular and less painful periods are observed, decreasing the amount of bleeding, the risk of iron deficiency anemia.
After taking the drug inside cyproterone acetate is completely absorbed from the gastrointestinal tract. Cmax plasma levels achieved after 1.6 hours and of 15 ng / ml. Bioavailability is 88%.
Cyproterone acetate is almost completely bound to albumin of blood plasma is approximately 3.5-4% in a free state. Since nonspecifically binding proteins, changes in the level of globulin binding sex steroids (GSM), did not affect the pharmacokinetics of cyproterone acetate.
Biotransformed by hydroxylation and conjugation, the major metabolite – 15b-hydroxyl derivative.
Pharmacokinetics biphasic cyproterone acetate: T1 / 2 was 0.8 hours and 2.3 days, respectively for the first and second phases. Total plasma clearance was 3.6 mL / min / kg. Excreted mainly as metabolites through the kidneys and the intestine in the ratio 1: 2, a small proportion – unchanged through the gut. Since breast milk is allocated to 0.2% of the dose of cyproterone acetate. T1 / 2 for metabolites cyproterone acetate is 1.8 days.
After receiving medication ethinyl estradiol is rapidly and completely absorbed from the gastrointestinal tract. Cmax amounts to approximately 80 pg / ml, achieved after 1.7 hours. The bioavailability of approximately 45%, has a significant individual variability.
Binding proteins (albumin) plasma high: only 2% in the plasma are in free form.
Ethinylestradiol increases hepatic synthesis of SHBG and corticosteroid binding globulin (CBG) during continuous use. The treatment Hloe® SHBG serum concentration rises to about 100 nmol / l 300 nmol / l and the serum concentration of DRG increases from approximately 50 mg / ml to 95 ug / ml.
During the suction and the “first pass” through the liver ethinylestradiol undergoes extensive metabolism.
Pharmacokinetics ethinylestradiol biphasic: T1 / 2 1-2 h and about 20 hours respectively. Plasma clearance – about 5 ml / min / kg. Ethinylestradiol excreted from the body as metabolites: about 40% – the kidneys, 60% – through the intestine. Since breast milk is allocated to 0.02% of the dose of ethinyl estradiol.
Zentiva KS, Czech Republic
Adults are prescribed by a doctor for women of childbearing age
tablets, film-coated orange-yellow (21 pcs. In blister).
1 tablet contains:
ethinyl estradiol 35 mcg,
2 mg cyproterone acetate.
lactose monohydrate – 68.8 mg,
povidone – 2 mg,
sodium carboxymethylstarch (type A) – 1.5 mg,
Anhydrous colloidal silica – 0.188 mg,
colloidal aluminum oxide – 0.04 mg,
magnesium stearate – 0.375 mg.
dye Opadry Yellow II OY-L-32901 (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) .
The tablets (placebo), white (7 pcs. In blister).
sodium carboxymethylstarch (type A),
colloidal silica anhydrous,
colloidal aluminum oxide,
The blister pack of 28 tablets.
Tablets, film-coated orange-yellow pieces 21 in the blister.
The tablets (placebo), white pieces 7 in the blister.
The blister cardboard pack 3.
Acne, hirsutism From, seborrhea, for contraception
- Contraception in women with symptoms of androgenization.
Androgen-dependent diseases in women:
- acnes, especially their expressed forms accompanied by seborrhea, inflammatory phenomena to form nodes (papulopustular acne, nodulocystic acne);
- androgenic alopecia;
- mild forms of hirsutism.
- Thrombosis and thromboembolism, including in history (deep venous thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular accident);
- state prior thrombosis (including transient ischemic attack, angina);
- diabetes complicated by micro-angiopathies;
- the presence of serious or multiple risk factors for venous or arterial thrombosis;
- disease or severe liver dysfunction;
- liver tumors (including history);
- hormone-dependent cancers, including breast tumors or genital organs (including history);
- congenital hyperbilirubinemia (Gilbert syndrome, Dubin-Johnson syndrome, Rotor); – pancreatitis (including history), if it is accompanied by severe hypertriglyceridemia; – Uterine bleeding of unknown etiology;
- migraine, accompanied by focal neurological symptoms (including history);
- sickle-cell anemia;
- idiopathic jaundice or pruritus during late pregnancy;
- otosclerosis with deterioration during pregnancy;
- during breastfeeding;
- Pregnancy or suspicion of it;
- 40 years of age;
- increased sensitivity to the drug.
If any of these conditions develop for the first time while taking Hloe®, the drug should be discontinued immediately.
Precautions: use in patients with epilepsy, depression, ulcerative colitis, diseases of the liver and gall bladder, uterine myoma, mastopathy, chorea, tetany, porphyria, multiple sclerosis, varicose veins, tuberculosis, renal disease in adolescence (without regular ovulatory cycles).
From endocrine system: rarely – bloating, pain, and increase the allocation from mammary glands, increase in body weight.
On the part of the reproductive system: rarely – intermenstrual bleeding, change in vaginal secretions, change in libido.
CNS: rarely – headache, migraine, mood decline.
From the digestive system: rarely – nausea, vomiting, gastralgia.
Other: very rarely – poor tolerance of contact lenses, swelling of the eyelids, blurred vision, conjunctivitis, hearing loss, allergic reactions, thrombosis, embolism, generalized pruritus, jaundice, the appearance of age spots on the face (chloasma).
These side effects may develop in the first few months of using the drug, and usually diminish over time.
How to accept, acceptance rate and dosage
The drug should be taken orally on 1 tab. / Day. The tablets are not liquid, and washed down with a small amount of liquid. The drug is recommended in one and the same time, preferably after breakfast or dinner.
Admission Hloe® begin in the 1st day of the cycle, using a tablet corresponding day of the week from a calendar packaging. Daily intake of the drug was carried out using tablets of the calendar packaging sequentially in the direction of arrows printed on the foil until you have taken all the tablets. After receiving all tablets yellow-orange color of the calendar packaging, it is necessary to take the next 7 days remaining white tablets.
During the last 7 days of the treatment cycle (28 days), menstrualnopodobnoe bleeding should occur (as a result of withdrawal of treatment). Menstruation usually begins 2-3 days after the 21-day cycle of drug treatment.
Next pack should be started the day after the full completion of receiving the tablets of the previous packaging, regardless of whether the continuation / stop bleeding.
When changing from the use of combined oral contraceptives Hloe® should begin the day after the last tablet with the active components of the previous formulation, but in any case no later than the next day after the usual 7-day free interval (for formulations containing 21 tablet). Further, according to the above scheme.
If a patient has taken previous contraceptive daily for 28 days, the application Hloe® should start after the last inactive tablet.
When switching from contraceptives containing only progestogens ( “mini-pill”) Hloe® can begin to apply without interruption.
When using injectables Hloe® contraceptives should be applied from the day when the next injection should be done.
When changing from an implant Hloe® should be applied on 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 the drug.
After the abortion I trimester of pregnancy, a woman can begin use immediately Hloe®. In this case, there is no need for additional methods of contraception.
After delivery or abortion in the II trimester of pregnancy, the use of the drug should be started on day 21-28. If reception is started later, it is necessary to use an additional barrier method of contraception during the first 7 days of the drug.
If a woman has been sexually active in the period between the birth or abortion and the beginning of the drug, it should first rule out pregnancy or the need to wait for the first menstruation.
Missed tablet should be taken as soon as possible, the next pill – the usual time. At delay < 12 hours of contraceptive reliability is not reduced. If the delay in reception of tablets was > 12 hours, contraceptive reliability may be reduced.
If the delay in reception of tablets was > 12 h (the interval from the receipt of the last tablet > 36 h) during the 1st and 2nd week of dosing, the woman should take the last missed tablet as soon as possible even if this means taking two tablets at the same time. Subsequent pill to be taken at the usual time. Additionally, you must use a barrier method of contraception for the next 7 days.
If the delay in reception of tablets was > 12 h (the interval from the receipt of the last tablet > 36 h) during the third week of dosing, the woman should take the last missed tablet as soon as possible even if this means taking two tablets at the same time. Subsequent pill to be taken at the usual time. A pill from a new pack should be started at the end of the current package – without interruption. Possibly, withdrawal bleeding was not until the end of the second package, but may spotting or breakthrough uterine bleeding during the tablet-taking.
If the woman was vomiting in the range from 3 to 4 hours after ingestion, absorption of the active substances may be incomplete. In this case, you need to focus on the recommendations by skipping pills.
To postpone the date of the onset of menstruation, the woman should continue taking pills from a new package of the drug immediately after taking all the tablets from the previous one without interruption. Tablets of new packaging may be taken for as long as she wants (as long as the packaging is not finished). On the background of the drug from the second package, women may experience spotting or breakthrough uterine bleeding. Should start taking the pill from the next pack after the reception of 28 tablets.
To move the first day of menstruation to another day of the week, a woman should shorten the next tablet-free interval for as many days, as much as she wants. The shorter the interval, the higher the risk that it will have no withdrawal bleeding and, hereinafter, will be spotting and breakthrough bleeding while receiving a second package (as in the case where it wishes to delay the onset of menses).
In the treatment of hyperandrogenic conditions the duration of the drug is determined by the severity of the disease. After the disappearance of the symptoms it is recommended to take the drug for at least 3-4 months. In case of relapse after a few weeks or months after the completion of the course can be carried out re-therapy with Hloe®.
Keep out of reach of children at a temperature not higher than 25 ° C.
When applied simultaneously with Hloe® inducers of microsomal liver enzymes (hydantoins, barbiturates, primidone, carbamazepine and rifampicin, as well as possibly with oxcarbazepine, topiramate, felbamate and griseofulvin) increases clearance of ethinyl estradiol and cyproterone acetate, which may lead to breakthrough uterine bleeding or reduction contraceptive reliability.
When applied simultaneously with ampicillin, rifampicin and tetracycline Hloe® contraceptive reliability is reduced.
Before starting the application Hloe® necessary to carry out general medical examination (including the breasts and a cytological examination of cervical mucus), exclude pregnancy, disorders of the blood coagulation system. With long-term use of the drug prevention control examinations should be carried out every 6 months.
In the presence of risk factors should carefully evaluate the potential risks and expected benefits of the therapy and to discuss it with the woman before the start of the drug.
Approximate incidence of venous thromboembolism (VTE) in the use of oral contraceptives with a low dose of estrogen (< 50 .mu.g of ethinylestradiol) is up to 4/10 000 women per year compared to 0.5-3 / 10, 000 women who were not taking oral contraceptives. In this case, the incidence of VTE when taking COC less than the frequency of VTE associated with pregnancy (6/10 000 pregnant women per year).
The patient should be warned that in the development of venous or arterial thrombosis symptoms should seek immediate medical attention. 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 cough, any unusual, severe, prolonged headache, increased frequency and severity of migraine headaches, 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 violations symptom “acute abdomen”.
The relationship between the use of combined oral contraceptives and hypertension has not been established. In the event of drug-resistant hypertension must be withdrawn and the corresponding antihypertensive therapy. Oral contraceptives can be continued in the normalization of blood pressure.
In the event of liver dysfunction may require temporary removal of the drug to normalize laboratory parameters.
Recurrent cholestatic jaundice that develops for the first time during pregnancy or during previous use of sex hormones, requires discontinuation of COCs.
Despite the fact that the combined oral contraceptives have an impact on the resistance of the tissues to insulin and glucose tolerance, there is usually no need to correct the dose of hypoglycemic drugs in patients with diabetes mellitus. However, for this category of patients should maintain close medical supervision.
Women who are prone to the appearance of chloasma, while taking combined oral contraceptives should avoid prolonged exposure to sunlight and ultraviolet radiation.
If hirsutism symptoms in women newly developed or significantly strengthened, in the differential diagnosis should take into account other factors, such as androgen tumor, congenital adrenal hyperplasia.
In applying Hloe® may experience irregular bleeding (spotting or breakthrough bleeding), especially during the first few months of therapy. Therefore, assessment of any irregular bleeding should be performed only after a period of adaptation of approximately 3 cycles.
If irregular bleeding or develop after repeated previous regular cycles, hormonal reasons should consider and implement appropriate diagnostic procedures (including diagnostic scraping) to prevent pregnancy or malignancies.
In some cases, withdrawal bleeding may not develop during a break in the use of the drug. When irregular pill or in the absence of two consecutive bleedings menstrualnopodobnoe should exclude pregnancy to continue using the drug.
To change the results of skin allergy tests, reducing the concentration of LH and FSH during treatment with the drug.
Due to the fact that the contraceptive effect is fully manifested day 7 from the start of the drug during the first week recommended additional hormonal contraceptive methods.
Use of the drug after birth is recommended not earlier than will be the first normal menstrual cycle.
Treatment must be stopped immediately for 3 months before a planned pregnancy and approximately 6 weeks before the planned surgery, after prolonged immobilization.
Diarrhea and vomiting contraceptive effect is reduced (not stopping the drug should be used additional methods of hormonal contraception).
Smoking women taking hormonal contraceptive drugs have an increased risk of developing cardiovascular disease with serious consequences (myocardial infarction, stroke). The risk increases with age and, depending on the number of cigarettes you smoke (especially in women older than 30 years).
Pregnancy and lactation
Do not use this drug during pregnancy, suspected pregnancy and during breastfeeding.
Symptoms include nausea, vomiting, slight vaginal bleeding.
Treatment: symptomatic therapy. No specific antidote.