Composition, form of production and packaging
The tablets covered with a cover of yellow color, round, biconcave.
ethinylestradiol 35 Ојg
cyproterone acetate 2 mg
Excipients: lactose monohydrate, corn starch, povidone K25, talc, magnesium stearate.
Sheath composition: sucrose, calcium carbonate, talc, titanium dioxide, povidone K90, macrogol 6000, glycerol 85%, iron dye oxide, mountain glycolic wax.
21 pcs. - blisters (1) - packs of cardboard.
21 pcs. - blisters (3) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2010.
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), 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 phenomenon of androgenization 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 pituitary gland by gonadotropic hormones 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.
Ciproterone acetate is fully absorbed after ingestion. After taking 1 tablet. Belloon 35 C max is 15 ng / ml and is reached after 1.6 hours. Bioavailability is 88% of the administered dose.
Virtually completely binds to albumin plasma. 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 first cycle and up to 24 ng / ml at the end of the third cycle of treatment.
AUC increases 2.2 times (the end of the first cycle) and 2.4 times (the end of the third cycle). C ss is created approximately 16 days after the start of treatment.
Metabolised in the liver through various reactions, including. hydroxylation and conjugation. The main metabolite is-15-hydroxy-cyproterone.
T 1/2 of plasma is biphase, T 1/2 of the first phase is 0.8 h, T 1/2 of the second phase is 2.3 days. The total clearance is 3.6 ml / min / kg. Part of the administered dose is excreted in the bile in unchanged form. It is mainly excreted by the kidneys, in the form of metabolites. T 1/2 with urine and bile is 1.9 days.
Ethinyl estradiol after oral administration is quickly and completely absorbed. After taking 1 tablet. Belloon 35 C max is 80 pg / ml and is reached after 1.7 h.
The apparent V d 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. C ss is created 3-4 days after the start of treatment.
T 1/2 of plasma is biphasic, T 1/2 of the first phase is 1-2 h, T 1/2 of the second phase is 20 h. It is excreted as metabolites through the intestine and kidneys (ratio 4: 6), T 1/2 is about 1 day.
- contraception in women with androgenization phenomena;
- treatment of androgen dependent diseases / conditions in women: acne papulopustulosa, acne nodulocystica, seborrhea, androgenic alopecia, hirsutism.
Belloon 35 is taken orally 1 tablet / day, without chewing and squeezed with a small amount of liquid. Reception should be done 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 a sequence along the direction of the foil applied to the foil until all the tablets are taken. After the end of taking all 21 tablets from the calendar package, a break is taken in taking the drug for 7 days, during which menstrual bleeding occurs.
After 28 days from the beginning of taking 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 combined oral contraceptive, taking Bellune 35 should begin the day after receiving the last tablet of the previous drug, but not in any case no later than the next day after an ordinary 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 used 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 was 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 had a sex life between childbirth or abortion and the start of taking Bellune 35, then first you should 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 is not reduced. 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 weeks of taking the drug , the woman should take the last missed tablet as soon as possible (even if it means taking two tablets simultaneously). The next tablet is taken at the usual time. In addition, the 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 last pill taking 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 she remembers (even if it means taking two 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, the 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 spots 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, you need to focus on recommendations when you skip 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 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. 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 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 completion of the course, Belloon 35 can be re-administered.
All women taking combined oral contraceptives are at increased risk of thrombosis and thromboembolism, some increase in the risk of developing and worsening the course of other diseases. When taking combined oral contraceptives, irregular (acyclic) bleeding from the vagina (spotting bleeding or breakthrough bleeding) can occur, especially during the first months of use.
The frequency of adverse reactions is presented according to the following gradation: often (> 1/100, <1/10), infrequently (> 1/1000, <1/100), rarely (> 1/10 000, <1/1000).
Often: nausea, abdominal pain, weight gain, headache, depression, mood swings, pain in the mammary glands, breast engorgement.
Infrequent: 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.
- Thrombosis (venous and arterial) and thromboembolism now or in the anamnesis (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 damage to the valvular heart apparatus (pulmonary hypertension, atrial fibrillation, subacute bacterial endocarditis in the anamnesis);
- uncontrolled arterial hypertension (systolic blood pressure above 160 mm Hg or diastolic blood pressure 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, incl. diseases of cerebral vessels or coronary arteries, arterial hypertension, elderly age;
- liver failure and severe liver disease (before the normalization of liver tests);
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 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 the previous pregnancy;
- herpes during pregnancy in anamnesis;
- the period of lactation (breastfeeding);
- Hypersensitivity to any of the components of the drug.
The potential risk and the expected benefit of using combined oral contraceptives in each individual case should be carefully weighed in the presence of the following diseases / conditions and risk factors:
- risk factors for thrombosis and thromboembolism: smoking, obesity, dyslipoproteinemia, arterial hypertension, migraine, heart valve defects, prolonged immobilization, serious surgical interventions, extensive trauma, hereditary predisposition to thrombosis (thrombosis, blood clotting disorders, myocardial infarction or cerebrovascular accident at a young age at any of the next of kin);
- diseases in which violations of peripheral circulation may occur: diabetes mellitus (or predisposition, for example, unexplained glucosuria), systemic lupus erythematosus, tetany, renal dysfunction, hemolytic uremic syndrome, Crohn's disease, ulcerative colitis, varicose veins, phlebitis of superficial veins;
- hypertriglyceridemia, liver disease, breast cancer in a family history or benign breast tumor in a personal history, diagnosed depression in a personal anamnesis, 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 (for example, jaundice and / or itching associated with cholestasis, cholelithiasis, porphyria, Sydenham's chorea, chloasma).
PREGNANCY AND LACTATION
The drug is contraindicated in pregnancy and lactation (breastfeeding).
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
The drug is contraindicated in case of liver failure.
If any of the conditions, diseases and risk factors identified below are present, careful consideration should be given to the potential risk and expected benefits of using combined oral contraceptives (CPCs) in each individual case and to discuss it with a 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:
- by 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 (for example, 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 a PDA;
- with obesity (body mass index more than 30 kg / m 2 );
- with dyslipoproteinemia;
- with arterial hypertension;
- with migraine;
- with diseases of the heart valves;
- with atrial fibrillation;
- with 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 four weeks before it) and not to resume reception within two weeks after immobilization is completed.
The question of the possible role of varicose veins and superficial thrombophlebitis in the development of venous thromboembolism remains controversial.
It should take into account the increased risk of thromboembolism during the postpartum period. Peripheral circulatory disorders as may 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 frequency and severity of migraine during use PDAs (which may be preceded by cerebrovascular disorders) can be grounds for immediate discontinuation of these drugs.
An important risk factor for cervical cancer is HPV persistence. The results of some epidemiological studies suggest a further increase this risk with prolonged use of the CPC, however, this remains controversial, as finally established, much research results take into account the related risk factors, such as screening for cervical status and sexual behaviors, including rarely used barrier methods of contraception.
The connection between breast unproven CCP receiving and cancer. There is a slightly increased relative risk of breast cancer diagnosed in women taking the CPC now. The increased risk disappears gradually within 10 years after discontinuation of these drugs. The observed increase in risk may be the result of careful observation and an earlier diagnosis of breast cancer in women who use PDAs cancer. Women who have ever used a PDA, revealed earlier stages of breast cancer and clinically it is less pronounced than in women, never let them apply.
In a few cases on the background of the PDA observed the development of benign and in extremely rare - malignant tumors of the liver, which in some cases lead to life-threatening intraabdominal bleeding. In the case of severe pain in the abdomen, or signs of liver enlargement intraabdominal bleeding in the differential diagnosis should take into account the possibility of liver tumors in patients receiving PDA.
Women with hypertriglyceridemia (or the presence of this condition have a family history) may increase the risk of developing pancreatitis while receiving handheld.
Despite the fact that a small increase in blood pressure have been reported in many women taking the CPC, clinically relevant increases were rare. However, if at the time of receiving the CPC developed a persistent, clinically significant increase in blood pressure, should be discontinued these drugs and begin treatment of hypertension. Receiving CCP can be continued, if using antihypertensive therapy achieved normal values вЂ‹вЂ‹of arterial pressure.
The following states have been reported to develop or worsen both during pregnancy and while taking combined oral contraceptives, but their connection with the reception of combined oral contraceptives has not been proven: jaundice and / or pruritus associated with cholestasis, the formation of gallstones, porphyria , systemic lupus erythematosus, hemolytic uremic syndrome, Sydenham's chorea, herpes gestationis, hearing loss associated with otosclerosis. Also described are cases of Crohn's disease and ulcerative colitis to treatment with CPC.
In women with hereditary forms of angioedema exogenous estrogens may induce or worsen symptoms of angioedema.
Acute or chronic disturbances of liver function may require the cancellation of the CCP as long as liver function tests have not returned to normal. Recurrent cholestatic jaundice that develops for the first time during pregnancy or previous use of sex hormones, requires discontinuation of the CPC.
Although the CCP may have an effect on insulin resistance and glucose tolerance, there is no need to change the therapeutic regimen in diabetics using low-dose PDAs (<0.05 mg ethinylestradiol). However, women with diabetes should be carefully monitored while receiving handheld.
Sometimes it can develop chloasma, especially in women with a history of chloasma during pregnancy. Women with a tendency to chloasma while receiving CCP should avoid prolonged exposure to sunlight and ultraviolet radiation.
Treatment (contraception) should be immediately discontinued if pregnancy occurs, the development of migraine headaches (if they were not before), the appearance of early signs of phlebitis or phlebothrombosis (unusual pain or swelling of veins), with the appearance of jaundice, visual disturbances, cerebrovascular disorders, stabbing pain of unknown etiology when breathing or coughing, pain and tightness in the chest, with an increase in blood pressure.
The reception also stopped 3 months before a planned pregnancy, 6 weeks before the planned surgery and during prolonged immobilization. Diarrhea and vomiting contraceptive effect is reduced, however, without interrupting the reception of a preparation, it is necessary to use additional non-hormonal contraception.
CCP Admission may affect the results of certain lab tests, including liver function, kidney, thyroid, adrenal glands, the level of transport proteins in the plasma, carbohydrate metabolism, coagulation and fibrinolysis parameters.
It is necessary to warn the laboratory personnel on oral contraceptives. To change the results of skin allergy tests, reducing the concentration of LH and FSH.
Due to the fact that the contraceptive effect is fully manifested to the 14th day from the start of reception, the first 2 weeks is recommended to additionally apply hormonal (barrier) methods of contraception. The drug has no effect on the course of puberty during the formation of the normal menstrual cycle.
Appointment recommended after childbirth or after the first normal menstruation after childbirth. In cases of acyclic bleeding during the first 3 weeks of hormonal contraception - perhaps continued administration of the drug - usually spotting terminated independently. In the absence of bleeding during the 7-day interval between administration of the drug, should stop the pills to exclude pregnancy.
Effects on the menstrual cycle
While receiving CCP may experience irregular (acyclic) spotting / vaginal bleeding (spotting or breakthrough bleeding), especially during the first few months of use. Therefore, evaluation of any irregular bleeding should be performed after an adaptation period of approximately three cycles.
If irregular bleeding recur or develop after previous regular cycles, you should conduct a thorough examination to exclude malignancy or pregnancy.
Some women during the tablet-free interval may not develop withdrawal bleeding. If the CCP were made according to the recommendations, it is unlikely that the woman is pregnant. However, the irregular application of the CPC and the absence of two consecutive cancellation of bleeding, the drug can not be extended to the exclusion of pregnancy.
Before the start or resumption of the drug Bellona 35 women need a thorough medical, including the measurement of blood pressure, heart rate, body mass index, and gynecological examination, including the examination of mammary glands and cytology scraping from the cervix (Pap test) exclude pregnancy. The volume of additional research and frequency inspection tests determined individually. Typically, control examinations should not be performed at least 2 times a year.
Woman should notify that preparations such Bellona 35 do not protect against HIV infection (AIDS) and other diseases, sexually transmitted diseases.
Impact on the ability to drive vehicles and manage mechanisms
Symptoms: nausea, vomiting, bleeding, to remove the drug.
Treatment: symptomatic therapy. No specific antidote.
The use of drugs that induce hepatic microsomal enzymes which may lead to increased clearance of sex hormones, which in turn may lead to breakthrough bleeding or reduction in contraceptive reliability. Such drugs include phenytoin, barbiturates, primidone, carbamazepine, rifampicin, rifabutin, it is also possible - oxcarbazepine, topiramate, felbamate, griseofulvin and products containing St. John's wort.
HIV protease (e.g., ritonavir) and non-nucleoside reverse transcriptase inhibitors (e.g. nevirapine) and combinations thereof may also potentially affect hepatic metabolism.
During reception of drugs affecting the microsomal enzymes, and for 28 days after their withdrawal should additionally use a barrier method of contraception.
Some antibiotics (e.g., penicillin and tetracycline) may reduce the enterohepatic circulation of estrogen, thereby decreasing the concentration of ethinyl estradiol.
During antibiotics (such as penicillins and tetracyclines) and for 7 days after their withdrawal should additionally use a barrier method of contraception. If the period of use of barrier methods ends later than pills in a package, you need to go to the next package Bellona 35 without the usual tablet-free interval.
Combination oral contraceptives may affect the metabolism of other drugs, which leads to an increase (e.g., cyclosporin) or decrease (e.g., lamotrigine) concentrations in plasma and tissues.
May require correction dosing regimen hypoglycemic drugs.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be kept out of reach of children at a temperature not higher than 30 В° C. Shelf life - 3 years.