Instruction for use: Bellune 35

Active substance: Cyproterone + Ethinylestradiol

ATX code G03HB01 Cyproterone and estrogen

Pharmacological group

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

Nosological classification (ICD-10)

L21 Seborrheic dermatitis

Dermatitis seborrheic, Increased sebum separation, Seborrheic Eczema, Seborrheic dermatitis of the scalp, Seborrheic pyodermatitis, Seborrhea, Eczema seborrheic

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, coated with a coating.

Cyproterone acetate micronized 2 mg

Ethinylestradiol micronized 0.035 mg

Auxiliary substances: lactose monohydrate; corn starch; Povidone K25; talc; Magnesium stearate

Shell: sucrose; Calcium carbonate; talc; Titanium dioxide; Povidone K90; Macrogol 6000; Glycerol 85%; Iron oxide dye; Wax mountain glycolic

In a blister of 21 pcs .; In a pack of cardboard 1 or 3 blisters.

Description of dosage form

Round biconvex tablets, coated with a yellow coating.

pharmachologic effect

Pharmacological action - contraceptive, antiandrogenic.

Pharmacodynamics

Monophasic combined contraceptive drug with antiandrogenic activity. It blocks the androgen receptors, inhibits the pituitary secretion of gonadotropic hormones. The mechanism of action is due to its constituent antiandrogen steroid structure - cyproterone acetate and oral estrogen - ethinyl estradiol.

Ciproterone has the ability to compete with the receptors of natural male sex hormones - androgens (testosterone, dihydroepiandrosterone, androstenedione, etc.), 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). Along with anti-androgenic properties, it possesses gestagenic activity that mimics the properties of the hormone of the yellow body. Cyproterone, possessing gestagenic activity, inhibits the secretion of the gonadotrophic hormones by the pituitary gland and inhibits ovulation, which determines its contraceptive effect.

Ethinyl estradiol strengthens the central and peripheral effects of cyproterone 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.

Pharmacokinetics

Cyproterone acetate. Completely absorbed after ingestion. After taking 1 table. Belloon 35 Cmax in serum is 15 ng / ml and is produced after 1.6 hours. It is almost completely bound to plasma albumins. During the course of treatment, cumulation of the drug is observed: its serum concentration increases from 15 ng / ml - on the 1st day of treatment to 21 ng / ml - at the end of the 1st cycle and up to 24 ng / ml - at the end of the third cycle of treatment .

The area under the concentration-time curve increases 2.2 times (the end of the 1st cycle) and 2.4 times (the end of the third cycle). The equilibrium concentration is created approximately 16 days after the start of treatment.

Bioavailability is 88% of the administered dose.

T1 / 2 from the plasma - two-phase, the first phase - 0.8 hours, the second - 2.3 days. The total clearance is 3.6 ml / min / kg. Metabolised in the liver through various reactions, including. Hydroxylation and conjugation. The main metabolite is 15-hydroxyciproterone.

Part of the administered dose is excreted in the bile in unchanged form; The main way of excretion is by the kidneys, in the form of metabolites. T1 / 2 kidney and with bile is 1.9 days.

Ethinylestradiol. After oral administration, it is quickly and completely absorbed.

After receiving 1 table of Belloon, 35 Cmax in serum is 80 pg / ml and is created through 1.7 parts of T1 / 2 from plasma - two-phase, the first phase - 1-2 hours, the second - 20 hours.

The apparent volume of distribution is 5 l / kg, the plasma clearance is 5 ml / min / kg.

Virtually completely binds to plasma proteins. During the absorption and the first passage through the liver is metabolized, which leads to a decrease in bioavailability.

The equilibrium concentration is created 3-4 days after the start of treatment.

It is excreted as metabolites through the intestine and kidneys (ratio 4: 6), T1 / 2 is about 1 day.

Indications

Contraception in women with androgenization phenomena;

Treatment of androgen dependent diseases / conditions in women ("vulgar" acne - acne papulopustulosa, acne nodulocystica, seborrhea, androgenetic alopecia, hirsutism).

Contraindications

Hypersensitivity to any of the components of the drug;

Pregnancy and lactation;

Thromboses (venous and arterial) and thromboembolism now or in history (including deep vein thrombosis, pulmonary embolism, pulmonary embolism), ischemic heart disease, stroke;

Conditions preceding thrombosis (including transient ischemic attacks, angina pectoris) at present or in the anamnesis;

Complicated heart valve apparatus lesions (pulmonary hypertension, atrial fibrillation, subacute bacterial endocarditis in the anamnesis);

Uncontrolled arterial hypertension (SAD above 160 mm Hg or DAD above 100 mm Hg);

Serious surgical intervention with prolonged immobilization;

Diabetes mellitus with vascular complications;

Multiple or expressed risk factors for venous or arterial thrombosis, including: cerebrovascular or coronary artery disease, arterial hypertension, old age;

Hepatic insufficiency and severe liver disease (before normalization of liver samples); Active viral hepatitis, cirrhosis of the liver in the stage of decompensation; Idiopathic jaundice or itching during a previous pregnancy; Congenital hyperbilirubinemia (syndromes Gilbert, Dubin-Johnson and Rotor); Liver tumors (benign or malignant) at present or in the anamnesis;

Migraine with focal neurologic symptoms at present or in the anamnesis;

Smoking over the age of 35;

Pancreatitis with severe hypertriglyceridemia at present or in the anamnesis;

Identified hormone-dependent malignant diseases (including breast and endometrial cancer) or suspected of them;

Bleeding from the vagina of unknown origin;

Sickle-cell anemia, otosclerosis with worsening during pregnancy, herpes during pregnancy in the anamnesis.

With caution: the potential risk and the expected benefit of using combined oral contraceptives (CPC) in each individual case should be carefully weighed in the presence of such diseases / conditions and risk factors as:

- risk factors for thrombosis and thromboembolism: smoking; obesity; Dyslipoproteinemia, arterial hypertension; migraine; Heart valve flaws; Prolonged immobilization, serious surgical interventions, extensive trauma; Hereditary predisposition to thrombosis (thrombosis, blood clotting disorders, myocardial infarction or cerebral circulation impairment at a young age at any of the next of kin);

- diseases in which there may be violations of peripheral circulation: diabetes mellitus or predisposition (for example, unexplained glucosuria); Systemic lupus erythematosus; Tetany, renal dysfunction, hemolytic uremic syndrome; Crohn's disease and ulcerative colitis; Varicose veins, phlebitis of superficial veins;

- hypertriglyceridemia, liver disease, breast cancer in a family history or a benign breast tumor in a personal history, diagnosed depression in a personal history, uterine fibroids, cholelithiasis, intolerance to contact lenses;

- diseases that first appeared or worsened during pregnancy or against the background of previous reception of sex hormones (eg jaundice and / or itching associated with cholestasis, cholelithiasis, porphyria, Sydenham's chorea, chloasma).

pregnancy and lactation

The drug is contraindicated during pregnancy and lactation.

Side effects

All women taking combined oral contraceptives are at increased risk of thrombosis and thromboembolism, a slight increase in the risk of developing and worsening the course of other diseases (see "With caution"). When receiving PDC, irregular (acyclic) bleeding from the vagina (spotting bleeding or breakthrough bleeding) can occur, especially during the first months of use.

Often -> 1/100 and <1/10, sometimes -> 1/1000 and <1/100, rarely -> 1/10000 and <1/1000.

Often: nausea, abdominal pain, weight gain, headache, depression, mood swings, pain in the mammary glands, breast engorgement

Sometimes: vomiting, diarrhea, fluid retention in the body, migraine, decreased libido, skin rash, urticaria, mammary hypertrophy.

Rarely: intermenstrual bleeding, oligomenorrhea, increased libido, weight loss, worsening of the tolerance of contact lenses, allergic reactions, erythema nodosum, erythema multiforme; With prolonged use - chloasma.

Interaction

Influence on hepatic metabolism: the use of drugs inducing microsomal enzymes of the liver can lead to an increase in the clearance of sex hormones, which in turn can lead to breakthrough bleeding or a decrease in the reliability of contraception. These drugs include: phenytoin, barbiturates, primidone, carbamazepine, rifampicin, rifabutin, possibly also - oxcarbazepine, topiramate, felbamate, griseofulvin and preparations containing St. John's Wort.

HIV proteases (eg ritonavir) and non-nucleoside reverse transcriptase inhibitors (eg, nevirapine) and their combinations also have the potential to affect hepatic metabolism.

During the administration of drugs affecting microsomal enzymes, and within 28 days after their withdrawal, the barrier method of contraception should additionally be used.

Influence on intestinal-hepatic circulation: Some antibiotics (eg, penicillins and tetracyclines) can reduce the intestinal hepatic circulation of estrogens, thereby lowering the concentration of ethinylestradiol.

During the reception of antibiotics (such as penicillins and tetracyclines) and within 7 days after their withdrawal, the barrier method of contraception should be used additionally. If the period of use of the barrier method of protection ends later than the tablet in the package, you need to move on to the next Bellun 35 package without the usual pause in taking the tablets.

PDA can influence the metabolism of other drugs, which leads to an increase (for example, cyclosporine) or a decrease (eg lamotrigine) in their concentration in plasma and tissues.

You may need to adjust the dosage regimen for hypoglycemic drugs.

Dosing and Administration

Inside, 1 tab. Per day, without chewing and washing down with a small amount of liquid. Reception should be made daily at the same selected hour, preferably after breakfast or dinner.

The reception of Bellune 35 begins on the 1st day of the menstrual cycle (ie on the first day of menstrual bleeding), using a tablet of the corresponding day of the week from the calendar package.

The daily intake of the drug is carried out using a tablet from the calendar pack in sequence along the direction of the foil-applied arrow until all the tablets are taken. After completing the intake of all 21 table. From the calendar packing a break is taken in taking the drug for 7 days, during which menstrual bleeding occurs.

After 28 days from the start of the drug (21 days of admission and 7 days of interruption), i.e. On the same day of the week as at the beginning of the course, continue taking the drug from the next package.

When switching from a 21-day PDA, the reception of Bellune 35 should be started the day after the last tablet of the previous drug was taken, but in no case later than the next day after the usual 7-day break in admission. Further - according to the scheme described above. The use of additional contraceptives is not required.

When switching from a 28-day combined oral contraceptive, taking Bellune 35 should begin the day after taking the last active tablet. Further - according to the scheme described above. The use of additional contraceptives is not required.

When switching from contraceptives containing only gestagens ("mini-drank") Bellune 35 should be started without interruption. Further - according to the scheme described above. The use of additional contraceptives is not required.

When injecting forms of contraceptives are used, Bellune 35 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 (condom) during the first 7 days of taking the tablets.

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 childbirth 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 (condom) during the first 7 days of taking the tablets.

If a woman has a sex life between childbirth or abortion and the start of taking Bellune 35, then first you must exclude pregnancy or you must wait for the first menstrual period.

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 tablet is more than 12 hours, the reliability of contraception can be reduced.

It should be borne in mind that the pill should never be interrupted for more than 7 days, and that 7 days of continuous tablet intake is required to achieve adequate suppression of the hypothalamic-pituitary-ovarian system.

Therefore, if the delay in taking the tablet is more than 12 hours (the interval from the time of taking the last tablet is more than 36 hours) during the first and second week of taking the drug, the woman should take the last missed tablet as soon as possible (even if it means taking 2 tables simultaneously).

The next tablet is taken at the usual time. In addition, a barrier method of contraception (condom) should be used for the next 7 days.

If the delay in taking the tablet is more than 12 hours (the interval from the time of taking the last tablet is more than 36 hours) during the third week of taking the drug, the woman should take the missed tablet as soon as possible, as soon as remembered (even if it means taking 2 tablets simultaneously ). The next tablet is taken at the usual time. In addition, taking a pill from a new package should be started as soon as the current package is finished, i. E. Without a 7-day break. In addition, a barrier method of contraception (condom) should be used for the next 7 days. Most likely, the woman will not have withdrawal bleeding until the end of the second package, but she may have spotting spotting or breakthrough uterine bleeding on the days of taking the tablets.

If you miss a dose of 3 or more tablets, you should consult your doctor. If a woman has vomiting or diarrhea within 3 to 4 hours after taking Bellune 35, the absorption of the active substances may be incomplete. In this case, it is necessary to focus on the recommendations when skipping the tablet. If a woman does not want to change the normal mode of taking the drug, she should take an additional tablet (or several tablets) from another package if necessary. In order to delay the onset of menstruation, a woman should continue taking the tablets from a new package to Bellune 35 immediately after taking all the pills from the previous one, without interruption in the reception. 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. To resume reception of Bellune 35 from a new package follows after usual 7-day break.

In order to postpone the day of the onset of menstruation on the next day of the week, the 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 it will not have withdrawal bleeding and thereafter there will be spotting spot bleeding and breakthrough bleeding during the second package (just like when it wants to delay the onset of menstruation).

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 Bellune 35 for at least another 3-4 months. In the event of a relapse within a few weeks or months after the completion of the course, Belluna 35 can be re-administered.

Overdose

Symptoms: nausea, vomiting, bleeding when drug is withdrawn.

Treatment: symptomatic. There is no specific antidote.

special instructions

If any of the conditions, diseases and risk factors outlined below are present, careful consideration should be given to the potential risk and expected benefits of using CPC in each individual case and to discuss it with the woman before she decides to start taking the drug. In case of weighting, strengthening or the first manifestation of any of these conditions, diseases or risk factors, a woman should consult with her doctor who can decide whether to cancel the drug.

Diseases of the cardiovascular system

There is evidence of an increase in the incidence of venous and arterial thrombosis and thromboembolism (such as deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke) with CCPs. These diseases are rare.

The risk of developing venous thromboembolism is maximal in the first year of taking such drugs. The risk of developing thrombosis (venous and / or arterial) and thromboembolism increases:

- with age;

- for smokers (with an increase in the number of cigarettes or an increase in age, the risk further increases, especially in women over 35 years of age);

- in the presence of a burdened family history (eg venous or arterial thromboembolism ever at close relatives or parents at a relatively young age). In the case of hereditary predisposition, a woman should be examined by an appropriate specialist to decide on the possibility of taking combined oral contraceptives;

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

- dyslipoproteinemia;

- arterial hypertension; migraine; Heart valve diseases; Atrial fibrillation;

- prolonged immobilization, serious surgical intervention, any foot surgery or extensive trauma. In these situations, it is desirable to stop using the PDA (in the case of a planned operation - at least 4 weeks before it) and not resume reception for 2 weeks after the end of immobilization.

The question of the possible role of varicose veins and superficial thrombophlebitis in the development of venous thromboembolism remains controversial.

An increased risk of thromboembolism in the postpartum period should be considered.

Violations of peripheral circulation can also occur in diabetes mellitus, systemic lupus erythematosus, tetany, hemolytic uremic syndrome, chronic inflammatory bowel diseases (Crohn's disease or ulcerative colitis) and sickle cell anemia.

The increase in the frequency and severity of migraine during the use of CPC (which may precede cerebrovascular disorders) may be the reason for the immediate discontinuation of these drugs.

Tumors

An important risk factor for cervical cancer is the persistence of papillomavirus. The results of some epidemiological studies indicate an additional increase in this risk with prolonged use of CPC, however, this statement remains controversial, since it has not been fully established whether the results of studies take into account co-occurring risk factors, for example screening of the cervix and sexual behavior, including a more rare application Barrier methods of contraception.

The relationship between CPC and breast cancer has not been proven. There is a slightly increased relative risk of advanced breast cancer diagnosed in women taking CPC at this time. Increased risk gradually disappears within 10 years after discontinuation of these medications. The established increase in risk may be the result of careful observation and earlier diagnosis of breast cancer in women using CPC. Women who have ever used CPC have earlier stages of breast cancer and are less clinically active than women who have never used them.

In isolated cases, against the backdrop of the use of CPC, there was a development of benign, and extremely rarely malignant liver tumors, which in some cases led to life-threatening intraabdominal hemorrhage. In the case of severe pain in the abdominal region, liver enlargement, or signs of intra-abdominal bleeding, differential diagnosis should consider the possibility of a liver tumor in patients taking CPC.

Other states

Women with hypertriglyceridemia (or the presence of this condition in a family history) may increase the risk of developing pancreatitis while taking CPC.

Despite the fact that a small increase in blood pressure was described in many women taking CPC, clinically significant increases were rarely noted. Nevertheless, if a persistent, clinically significant increase in blood pressure develops during the administration of the PDA, it is necessary to cancel these drugs and begin treatment of arterial hypertension. Reception of PDA can be continued if normal blood pressure values are achieved with the help of antihypertensive therapy.

The following conditions have been reported to develop or worsen, both during pregnancy and when taking CPC, but their relationship with the use of CPC has not been proven: jaundice and / or pruritus associated with cholestasis; Formation of stones in the gallbladder; Porphyria; Systemic lupus erythematosus; Hemolytic uremic syndrome; chorea; Herpes of pregnant women; Hearing loss associated with otosclerosis. Also, cases of Crohn's disease and ulcerative colitis are described in the background of the use of CPC.

In women with hereditary forms of angioedema, exogenous estrogens can cause or worsen symptoms of angioedema.

Acute or chronic liver dysfunction may require the withdrawal of CPC until the liver function returns to normal. Recurrent cholestatic jaundice, which develops for the first time during pregnancy or previous reception of sex hormones, requires discontinuation of the PDA.

Although PDAs can influence insulin resistance and glucose tolerance, there is no need to change the therapeutic regimen in diabetic patients using low-dose PDA (<0.05 mg ethinyl estradiol). Nevertheless, women with diabetes should be carefully observed during the reception of the PDA

Sometimes chloasma can develop, especially in women with a history of pregnancy chloasma. Women with a tendency to chloasma during the reception of the PDA should avoid prolonged exposure to the sun and exposure to UV radiation.

Treatment (contraception) should be stopped immediately upon pregnancy, the development of migraine headaches (if they were not previously), the appearance of early signs of phlebitis or phlebotrombosis (unusual pain or bloating of the veins on the legs), jaundice, visual impairment, cerebrovascular disorders, stitching Pain of unclear etiology during breathing or coughing, pain and feeling of tightness in the chest, with increasing blood pressure.

Admission is also terminated 3 months before the planned pregnancy, for 6 weeks before the planned surgical intervention and with prolonged immobilization. With diarrhea and vomiting contraceptive effect is reduced, therefore, without stopping the drug, it is necessary to use additional non-hormonal methods of contraception.

Laboratory Tests

Reception of PDA can influence the results of some laboratory tests, including indicators of liver function, kidney function, thyroid gland, adrenal gland, transport protein level in plasma, carbohydrate metabolism, coagulation and fibrinolysis parameters.

Laboratory staff should be warned about taking oral contraceptives.

It is possible to change the results of skin allergic tests, decrease the concentration of LH and FSH.

In connection with the fact that the contraceptive effect is fully manifested by the 14th day from the beginning of admission, in the first 2 weeks it is recommended to additionally use non-hormonal (barrier) methods of contraception. The drug has no effect on the course of puberty in the period of formation of the normal menstrual cycle.

The appointment after childbirth is recommended not earlier than the onset of the first normal menstruation. In cases of acyclic bleeding, during the first 3 weeks of hormonal contraception, it is possible to continue taking the drug (as a rule, bloody discharge stops on its own). If there is no bleeding during the 7-day interval between taking the drug, taking the pills should be stopped until pregnancy is excluded.

Effects on the menstrual cycle

On the background of taking CPC, irregular (acyclic) bloody discharge / bleeding from the vagina (spotting bleeding or breakthrough bleeding) can occur, especially during the first months of use. Therefore, any irregular bleeding should be assessed after an adaptation period of approximately 3 cycles.

If irregular bleeding recurs or develops after previous regular cycles, a thorough examination should be performed to exclude malignant neoplasms or pregnancy.

Some women may not develop withdrawal bleeding during a break in taking pills. If the CCP were taken according to recommendations, it is unlikely that a woman is pregnant. Nevertheless, with the occasional use of CPC and the absence of two consecutive bleeding cancellations, taking the drug can not be continued until the pregnancy is excluded.

Medical check-ups

Before starting or resuming the use of the preparation, 35 women need to undergo a thorough general medical examination, including measurement of blood pressure, heart rate, body mass index, and gynecological examination, including breast examination and cervical scraping (Papanicolaou test), and to exclude pregnancy. The volume of additional studies and the frequency of follow-up visits are determined individually. Usually, control examinations should be conducted at least twice a year.

A woman should be warned that preparations such as Bellune 35 do not protect against HIV infection (AIDS) and other sexually transmitted diseases.

Influence on the ability to drive and technique. Not found.

storage Conditions

At a temperature not exceeding 30 ° C.

Keep out of the reach of children.

Shelf life

3 years.

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