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Active ingredients
Chlormadinone + Ethinyl Estradiol
Release form
Pills
Composition
ethinyl estradiol 30 mcg, chlormadinone acetate 2 mg. Adjuvants: povidone K30 - 4.5 mg, corn starch - 9 mg, lactose monohydrate - 68.97 mg, magnesium stearate - 0.5 mg. Composition of film coating: hypromellose 6 mPa · s - 1.115 mg, lactose monohydrate - 0.575 mg, macrogol 6000 - 0.279 mg, propylene glycol - 0.093 mg, talc - 0.371 mg, titanium dioxide - 0.557 mg, iron dye red oxide - 0.01 mg.
Pharmacological effect
Combined contraceptive drug for oral administration. Prolonged use of the drug Belara leads to a decrease in the secretion of FSH and LH and, consequently, to suppress ovulation. At the same time, endometrial proliferation and secretory transformation occur, preventing implantation of a fertilized egg, increases the viscosity of the mucous secretion of the cervix, which is accompanied by difficulty in passing spermatozoa through the cervical canal and impaired mobility. Its action is based on the ability to replace androgens on specific receptors, eliminating and weakening the effect of endogenous and exogenous androgens. The Pearl Index is 0.291-0.698, depending on how carefully the woman follows the drug intake regimen. To completely suppress ovulation, 1.7 mg of chlormadinone acetate is required daily. The required dose per cycle is 25 mg.
Pharmacokinetics
Chlormadinone acetate Absorption After ingestion of chlormadinone acetate is quickly and completely absorbed. C max is achieved in 1-2 hours. Distribution Over 95% of chlormadinone acetate binds to human plasma proteins, mainly albumin. Metabolism Different processes of reduction, oxidation and binding to glucuronides and sulfates lead to the formation of many metabolites. The main metabolites in plasma are 3-alpha- and 3-beta-hydroxy-chlormadinone acetate with T1 / 2, not significantly different from unmetabolized chlormadinone acetate. 3-hydroxy-metabolites have antiandrogenic activity, similar to the activity of chlormadinone acetate itself. In the urine, the metabolites are contained mainly in the form of conjugates.After enzymatic cleavage, 2-alpha-hydroxy-chlormadinone acetate becomes the main metabolite, 3-hydroxy-metabolites and dihydroxymetabolites are also formed. Withdrawal The average T1 / 2 of chlormadinone acetate from the blood plasma is about 34 hours (after a single dose) and about 36-39 hours (with repeated use). When used orally, chlormadinone acetate and its metabolites are excreted in approximately equal amounts by the kidneys and through the intestines. Ethynyl estradiol Absorption Ethinyl estradiol is rapidly and almost completely absorbed after oral administration, reaching C max in blood plasma after 1.5 hours. Due to presystemic binding and metabolism in the liver, the absolute bioavailability is about 40% and is subject to strong individual variability (20-65%). DistributionIn-literature data on the concentration of ethinyl estradiol in the blood plasma strengths to vary. About 98% of ethinyl estradiol binds to plasma proteins, almost exclusively with albumin. Metabolism Like natural estrogens, ethinyl estradiol is biotransformed through hydroxylation of an aromatic ring (mediator is cytochrome P450). The main metabolite is 2-hydroxy-ethinylestradiol, which is transformed to other metabolites and conjugates. Ethinyl estradiol is subjected to presystemic binding, both in the mucous membrane of the small intestine and in the liver. In the urine, glucuronides are mainly found, and sulfates are found in the bile and blood plasma. Excretion The average T1 / 2 of ethinyl estradiol from the blood plasma is approximately 12-14 hours. Ethinyl estradiol is excreted by the kidneys and through the intestine in a 2: 3 ratio. Ethinyl estradiol sulfate, excreted in the bile after hydrolysis by intestinal bacteria, is subject to enterohepatic recirculation.
Indications
- oral contraception.
Contraindications
Taking Belara is contraindicated in the following diseases / conditions: - Thrombosis (venous and arterial) and thromboembolism at present or in history (for example, deep vein thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular disorders); - presence of the first signs of thrombosis, myocardial infarction, cerebrovascular disorders); or symptoms of embolism (for example, transient ischemic attacks, angina pectoris) - planned surgery (at least 4 weeks before it) and the period of immobilization, for example, after an injury (includingafter applying gypsum dressings); - diabetes mellitus with vascular complications; - diabetes mellitus that is not amenable to adequate control; - uncontrolled arterial hypertension or a significant increase in blood pressure (over 140/90 mm Hg); - hereditary or acquired susceptibility to development venous or arterial thrombosis: increased resistance of the body to activated protein C (APC-resistance); antithrombin III deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinemia and antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant); - acute or chronic severe liver disease (before normalization of liver function indicators); - generalized itching, cholestasis, especially in the previous period pregnancy or taking hormones in history; - Dubin-Johnson syndrome, Rotor syndrome, a violation of bile outflow; - the presence of liver tumors now or in ana Veronese - expressed epigastric pain, enlargement of the liver or symptoms intraabdominal bleeding; - initially identified porphyria or relapse (all three forms, especially acquired porphyria); - the presence of hormone-dependent malignancies, including history of (for example, breast or uterus), or suspicion of them; pronounced impairment of lipid metabolism; pancreatitis currently or in history, in combination with severe forms of hypertriglyceridemia; first occurrence of migraine pain or frequent severe headaches; - migraine in combination with local neurological symptoms (associated migraine); - acute sensory disturbances, such as visual or hearing impairment; - motor disturbances (in particular, paresis); - an increase in the number of epilepsy episodes; - tons severe depression; - deterioration of otosclerosis during previous pregnancies; - amenorrhea of unclear etiology; - endometrial hyperplasia; - vaginal bleeding of unknown etiology; - pregnancy or suspicion of it; - lactation (breastfeeding); - smoking over 35 years old - lactose intolerance, lactase deficiency, glucose-galactose malabsorption; - presence of pronounced or multiple factors of arterial or venous thrombosis (age increase, smoking,especially over the age of 35, obesity> 30 kg / m2; dyslipoproteinemia; the presence of a family history of venous or arterial insufficiency in relatives of the 1st lineage; valvular disease; atrial fibrillation; bacterial endocarditis; any operations on the lower limbs; extensive injury); - hypersensitivity to the components of the drug. With caution (only after assessing the potential risk and expected benefits, as well as with careful medical monitoring), Belara should be prescribed in the presence of the following conditions / diseases / risk factors at present or in anamnesis : epilepsy, multiple sclerosis; convulsive syndrome (tetany); migraine without focal neurological symptoms; bronchial asthma; heart or kidney failure; chorea; diabetes with uncomplicated course; acute and chronic liver diseases of mild and moderate severity (with normal indicators of functional liver samples); violation of lipid metabolism, dyslipoproteinemia; autoimmune diseases (including SLE); obesity (BMI less than 30 kg / m2); controlled arterial hypertension; endometriosis; varicose veins, phlebitis of the superficial veins of the lower extremities; violation of the blood coagulation system; mastopathy; uterine fibroids; herpes pregnant; depression; chronic inflammatory bowel diseases (Crohn's disease, ulcerative colitis).
Precautionary measures
Do not exceed the recommended daily dose.
Use during pregnancy and lactation
The use of the drug Belar during pregnancy is contraindicated. Before you start using the drug Belar, it is necessary to exclude the presence of pregnancy. When pregnancy occurs during the period of use of Belara, the drug should be stopped immediately. Existing epidemiological data do not contain information on the development of teratogenic or embryotoxic effects in women who accidentally took during pregnancy drugs containing estrogen and gestagens in the same combination as in Belara. The use of Belar during breastfeeding is contraindicated because the drug reduces produced milk and changes its composition.Small quantities of hormones that are part of the contraceptive and / or their metabolites are excreted in breast milk and can affect the baby.
Dosage and administration
The drug should be taken orally. The pill, marked with the appropriate day of the week, should be removed from the blister pack and swallowed whole, squeezed with a small amount of water if necessary. One pill should be taken every day at the same time (preferably in the evening) for 21 consecutive days, then you should take a 7-day break in taking the pills; two to four days after taking the last pill, there will be withdrawal bleeding, similar to menstrual bleeding. After the 7-day break, you should start taking Belar from the following package, regardless of whether the bleeding has stopped or not. If hormonal contraceptives have not been used previously (during the last menstrual cycle), the first pill should be taken on the 1st day of the woman’s natural cycle i.e. on the 1st day of the next menstrual bleeding. If the first pill is taken on the 1st day of menstrual bleeding, the contraceptive effect of the drug begins on the first day of use and lasts for a 7-day break in taking the pills. The first pill can also be taken on the 2-5 day of menstrual bleeding, regardless of bleeding stopped or not. In this case, you should use additional barrier methods of contraception during the first 7 days. If menstrual bleeding began more than 5 days ago, a woman should be advised to wait until the next menstrual bleeding begins, to start receiving Belara. When switching from another hormonal contraceptive containing 21 or 22 active pills should finish taking all the pills of the old package. The first pill of the drug Belar must be taken the next day. There should not be a break in taking the pills, and the patient should not wait until the next menstrual cycle. Additional contraceptive measures are not required. When switching from contraceptives containing only gestagen (mini-pili), the first pill of Belar should be taken the next day after taking the last pill containing only gestagen.During the first 7 days, you must use additional barrier methods of contraception. When switching from hormonal injectable contraceptives or a contraceptive implant, you can start taking Belar on the day of the removal of the implant or on the day of the originally scheduled injection. During the first 7 days it is necessary to use additional barrier methods of contraception. After a spontaneous or medical abortion in the first trimester of pregnancy, you can start taking Belar immediately after the abortion. In this case, there is no need to apply additional contraceptive measures. After delivery, spontaneous or medical abortion in the second trimester of pregnancy, it is recommended to start taking Belar on days 21-28 after giving birth if the woman does not breastfeed or after an abortion in the second trimester of pregnancy. In this case, there is no need to use additional barrier methods of contraception. If the drug was started more than 28 days after delivery or abortion, then additional barrier methods of contraception should be used within the first 7 days. If the woman already had sexual intercourse, then exclude the presence of pregnancy or wait for the start of the next menstrual cycle before taking the drug. After stopping the Belar drug, the current cycle may be extended by about one week. Irregular pr pills If the patient forgot to take the pill at the scheduled time, but took it within the next 12 hours, no additional contraceptive measures are required. The patient should continue taking the drug as usual. If the patient forgot to take the pill at the scheduled time, but took it after 12 hours, the contraceptive protection can be reduced. If you miss a pill, you should act according to the following two basic rules: 1) you should never interrupt pill for more than 7 days; 2) 7 days of continuous pill taking is necessary to achieve adequate suppression of the regulation of the hypothalamic-pituitary-ovarian system. Take immediately, even if it means that you need to take 2 pills at the same time. The following pills should be taken as usual.Over the next 7 days, you must additionally use barrier methods of contraception, such as condoms. If the pill was missed during the 1st week of the cycle, and during the 7 days before the missed pill there was sexual intercourse (including a seven-day break in the pill), consider the likelihood of pregnancy. The greater the number of pills was missed, and the closer they were to the usual break in taking the pills, the higher the chance of pregnancy. When you skip the pills on the 2nd and 3rd week of taking the drug, you should immediately take the missed pill, even if means taking two pills at the same time. The following pill is taken as usual. For the next 7 days, you need to use additional methods of contraception, for example, condoms. If less than 7 pills are left in the used pack, immediately after you finish taking the pills from the used pack, you should start taking the pills from the new package of Belar, ie There should be no break between two packages. It is likely that normal withdrawal bleeding will not occur until the pills from the second package run out; however, breakthrough bleeding or spotting bleeding from the vagina may occur while taking pills from a new package. If withdrawal bleeding does not occur after taking the pills from the second package, a pregnancy test should be done. If vomiting or severe diarrhea occurs within 4 hours after taking the tablet, absorption of the drug may be incomplete and contraceptive reliability cannot be guaranteed. In this case, you should act in accordance with the recommendations given in the section Irregular pills. You should continue taking Belara. In order to delay the bleeding, a woman should continue taking the pills from the next package of Belar, without taking a break. You can continue taking pills as desired until the pills from the second pack run out. Minor bleeding or breakthrough bleeding may occur while taking pills from the second pack. After the usual 7-day break in taking the pills, you should resume regular use of the drug Belar.To shift the onset of bleeding on another day of the week, different from the day of onset of bleeding under the current scheme, a woman can be recommended to reduce the next 7-day break for the desired number of days. The shorter the break in taking the pills, the higher the likelihood of no withdrawal bleeding and breakthrough bleeding or minor bleeding while taking the pills from the next package (as well as delaying bleeding).
Side effects
On the part of the digestive system: dyspepsia, nausea, abdominal pain, constipation, reversible increase in liver enzymes, cholestatic jaundice, hepatitis; very rarely - severe toxic liver damage (including cases of acute liver failure with a fatal outcome). From the CNS and peripheral nervous system: anorexia, headache, fatigue, dizziness, peripheral neuropathy. From the reproductive system: menstrual disorders . On the urinary system: hypercreatininemia, dyeing of urine in a dark color. On the side of metabolism: edema, hypokalemia. On the side of the cardiovascular system: possible congestive heart failure, edema, pulmonary edema. Allergic reactions: itching, rash, urticaria, angioedema, Stevens-Johnson syndrome. Others: alopecia.
Overdose
With an overdose of the drug is not observed any serious toxic reactions. Symptoms: if you accidentally take a large number of pills, nausea, vomiting, bleeding from the vagina are possible. Treatment: if necessary, carry out symptomatic therapy. There is no specific antidote. In rare cases, it is necessary to monitor indicators of water and electrolyte metabolism and liver function.
Interaction with other drugs
The interaction of ethinyl estradiol, an estrogenic component of the Belar drug, with other drugs may cause an increase or decrease in serum ethinyl estradiol concentration. If you need long-term treatment with these drugs, you should switch to non-hormonal contraception. A decrease in the concentration of ethinyl estradiol in the blood serum can lead to an increase in episodes of breakthrough bleeding, disruption of the cycle and a decrease in the contraceptive efficacy of the drug Belar.Increasing serum ethinylestradiol may increase the frequency and severity of side effects. The following drugs / active substances may decrease serum ethinyl estradiol concentration: - all drugs that increase GI motility (eg, metoclopramide) or impair absorption (for example, activated charcoal) - active substances that induce microsomal liver enzymes, such as rifampicin, rifabutin, barbiturates, anticonvulsants (for example, carbamazepine, phenytoxy , topiramate), griseofulvin, barbecaclon, primidone, modafinil, some protease inhibitors (for example, ritonavir) and Hypericum perforatum preparations (Hypericum perforatum); - some antibiotics (for example, ampicillin, tetracycline) - due to the reduction of the interfer en route circulation for the elapsed generation of the normal circulation of the elapsed source for the elapsed generation of the elapsed process for the elapsed generation of the normal circulation of the adrenaline for the treatment of heart failure the use of such drugs / active substances with Belar's drug requires the use of additional barrier methods of contraception, both during treatment and within 7 days after it. When taking active substances that reduce the concentration of ethinyl estradiol in the blood serum due to the induction of hepatic microsomal enzymes, additional barrier methods should be used within 28 days after the end of treatment. The following drugs / active substances can increase the concentration of ethinyl estradiol in the blood serum: - active substances that suppress sulphation of ethinyl estradiol in the intestinal wall, for example, ascorbic acid or paracetamol; - atorvastatin (increases AUC of ethinyl estradiol by 20%); - substances that inhibit the activity of hepatic microsomal enzymes, such as antifungal imidazoles (for example, fluconazole), indinavir or troleandomycin. Ethinyl estradiol can affect the metabolism of other substances: - suppress the activity of hepatic microsomal enzymes and, accordingly, increase the concentration in the serum of such active substances, as diazepam (and other benzodiazepines, which are metabolized through hydroxylation), cyclosporine, theophylline and prednisolone; - to induce glucuronization in the liver and, accordingly, reduce the serum concentration of drugs such as clofibrate, paracetamol, morphine and lorazepam. When taking Belar, the need for insulin and oral hypoglycemic drugs may change asthe drug has an effect on glucose tolerance. Before prescribing any drug, its brief characteristic should be studied to identify possible interactions with the Belar drug.
special instructions
Smoking increases the risk of developing severe adverse reactions from the cardiovascular system when using PDAs. The risk increases with age and depends on the number of cigarettes smoked. The risk is more pronounced in women over the age of 35 years. Smoking women over the age of 35 should use other methods of contraception. When using CPC, the risk of developing serious diseases increases: myocardial infarction, thromboembolism, stroke and liver tumors. Other risk factors such as hypertension, hyperlipidemia, obesity and diabetes mellitus clearly increase the risk of morbidity and mortality. If you have one of the above diseases / risk factors, you should weigh the possible benefits of taking Belar against the risks, and this should be discussed with the woman before starting taking her drug. If these diseases or risk factors begin to manifest or progress while taking the drug, you should consult a doctor. The doctor must decide whether to stop taking this drug. Thromboembolism and other vascular diseases Epidemiological studies have shown that there is a relationship between taking CPC and an increased risk of developing diseases caused by venous or arterial thromboembolism, for example, myocardial infarction, brain stroke, deep vein thrombosis or pulmonary embolism. These complications are rare. Accepting CPC leads to an increased risk of venous thromboembolism (VTE). The risk of VTE is greatest during the first year of administration. The degree of this risk is less than during pregnancy, when the incidence of VTE is 60 cases per 100,000 pregnancies. VTE is fatal in 1-2% of cases. There is no data on the assessment of the development of the risk of VTE when taking the drug Belar in comparison with other PDAs. The risk of venous thromboembolic complications when taking PDA increases: - with age; relatively young age).If a hereditary predisposition is assumed, it is recommended to send a woman for a consultation to a specialist before prescribing the drug Belar; - for prolonged immobilization; - for obesity (BMI> 30 kg / m2). in smokers; - with dyslipoproteinemia; - with obesity (BMI> 30 kg / m2); - with arterial hypertension; - with heart defects; - with atrial fibrillation; - with thromboembolism in relatives (arterial thromboembolism siblings, sisters or parents at a relatively young age). If a hereditary predisposition is assumed, it is recommended to refer a woman to a specialist for a consultation before prescribing Belara. Other diseases affecting the blood circulation are: diabetes, SLE, hemolytic-uremic syndrome, chronic intestinal inflammation (Crohn's disease and ulcerative colitis), sickle cell anemia. When assessing the risk / benefit, it should be remembered that adequate treatment of the above diseases can reduce the risk of thrombosis. It is necessary to take into account the increased risk of developing thromboembolic complications in the postpartum period. There is no consensus about whether there is a relationship between surface vein thrombophlebitis and / or varicose veins and the etiology of venous thromboembolism. With the development of venous or arterial thrombosis, the following symptoms may occur: - pain in the lower limbs and / or swelling; - sudden severe pain in the chest, with or without irradiation to the left arm; - sudden shortness of breath, cough for no apparent reason; - unexpected strong prolonged headache; - partial or complete loss of vision; - diplopia / speech disorders or aphasia; - dizziness, fainting, in some cases accompanied by a focal epileptic seizure; - sudden weakness or dysesthesia (a violation of and void) on one side or in one part of the body - motor disturbances - acute pain in zhivote.Zhenschiny taking the drug Belarus, should be informed of the fact that the appearance of symptoms that resemble the symptoms of thrombosis, you should consult your doctor.The drug Belara should be canceled if you suspect or confirm the diagnosis of thrombosis. The occurrence or increase in the severity of migraine attacks while taking the drug Belar (which may indicate the prodromal phase of the cerebral blood supply) is an indication for the immediate cancellation of the drug Belara. Tumors Some epidemiological studies indicate that long-term use of KPC is a risk factor for cervical cancer in women infected with the human papillomavirus (HPV). However, the question of the extent to which other related factors (for example, the number of sexual partners or the use of barrier methods of contraception) influence the results of this observation remains controversial. The relative risk (RR = 1.24) of breast cancer in women who take PDA is slightly higher. Over the course of 10 years after the discontinuation of PDA, the level of risk gradually decreases and returns to the age level. However, a causal relationship between the disease and the drug intake has not been established. The observed increased risk may be explained by the fact that women taking CPC have breast cancer diagnosed at an earlier stage than those who do not use them, as well as the biological effects of CPC or a combination of both factors. In rare cases, after taking CPC the occurrence of benign tumors of the liver, even more rarely recorded malignant tumors. In some cases, these tumors are the causes of the development of life-threatening intra-abdominal bleeding. In the event of severe abdominal pain that does not go away on its own, hepatomegaly or signs of intra-abdominal bleeding, it is necessary to take into account the possibility of a liver tumor, and to stop Belara. Other diseases Many women taking oral contraceptives have a slight increase in blood pressure; however, a clinically significant increase is rare. The relationship between the appointment of oral contraceptives and the clinical manifestation of hypertension has not yet been confirmed. If while taking the drug Belara appears clinically significant increase in blood pressure, the drug should be canceled and the treatment of hypertension.As soon as the blood pressure indicators return to normal on the background of antihypertensive therapy, the use of the drug Belar can be continued. Women with a herpes history of pregnant women with CPC may have a relapse of the disease. In women with a history of hypertriglyceridemia or in such a family history, the risk of pancreatitis increases while taking the drug Belar. Acute or chronic liver dysfunction may require discontinuation of Belar’s drug before normalization of liver function indicators. Relapse of cholestatic jaundice, which first appeared during pregnancy or a previous intake of sex hormones, requires discontinuation of the drug Belara. CPK may have an effect on the resistance of peripheral insulin tissues or glucose tolerance. Therefore, patients with diabetes mellitus while taking the drug Belar should be under constant observation. In rare cases, chloasma can develop, especially in women who have undergone chloasma of pregnant women. Women at risk of developing chloasma should avoid exposure to the sun and ultraviolet radiation while taking the drug Belara. Patients with rare congenital abnormalities - galactose intolerance, lactase deficiency lapp (lactase deficiency in some northern nations) or glucose-galactose malabsorption syndrome - use of the drug Belara contraindications Medical examination Before prescribing Belar, it is necessary to conduct a medical examination and collect complete data on the health of the woman and her p individuals to identify contraindications and risk factors. Medical examination should be carried out 1 time in 6 months while taking the drug Belar. Regular medical examinations are also necessary due to the fact that diseases that are contraindications (for example, transient ischemic attacks) or risk factors (for example, vein or artery thrombosis in personal or family history) may occur for the first time while taking the drug Belara.Medical examination should include measurement of blood pressure, examination of the mammary glands, abdominal organs and small pelvis, including cytological examination of the cervical epithelium and the conduct of appropriate laboratory tests. Women should be warned that the use of oral contraceptives, includingand Belara’s drug does not protect it from HIV infection (AIDS) or other sexually transmitted diseases. Laboratory indicators While taking the Belar drug, some laboratory parameters may change, including functional activity of the liver, thyroid gland, adrenal glands, concentration of bound proteins in plasma (for example, globulin that binds sex hormones, lipoproteins), indicators of carbohydrate metabolism, coagulation and fibrinolysis. The nature and extent of the changes are partly determined by the nature and dose of the hormones taken. Insufficient efficacy. Skipping the pill, vomiting and diarrhea, long-term simultaneous use of certain medications or, in very rare cases, metabolic disturbances can reduce the effectiveness of contraception. oral contraceptives can cause irregular vaginal bleeding (breakthrough bleeding or acyclic spotting s), especially during the first few cycles in patients receiving the drug. Therefore, a medical examination for irregular cycles should be carried out only after a period of adaptation, which usually lasts for 3 cycles. If during the course of taking Belara, the appearance of extraordinary bleeding continues or appears for the first time in a woman with a regular cycle, it is necessary to conduct an examination to rule out pregnancy or organic pathology. After exclusion of pregnancy and organic pathology drug intake B