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Active ingredients
Drospirenone + Ethinyl Estradiol
Release form
Pills
Composition
Tablets, film coated pink, round, biconvex (24 pieces in a blister) .; 1 tab.; Ethinyl estradiol 20 mcg; drospirenone 3 mg; Auxiliary substances: lactose monohydrate - 68.18 mg, potassium polacrilin - 4 mg, povidone K30 - 4 mg, magnesium stearate - 0.8 mg.; Film coating composition: opadry II pink 85F34048 (macrogol 3350 - 0.404 mg, titanium dioxide - 0.496 mg, polyvinyl alcohol - 0.8 mg, talc - 0.296 mg, iron dye red oxide - 0.0036 mg, iron dye yellow oxide - 0.0004 mg) - 2 mg.; Tablets, film-coated (placebo), white, round , biconvex (4 pieces in a blister); Auxiliary substances: lactose monohydrate - 73.4 mg, potassium polacriline - 1.6 mg, povidone K30 - 4 mg, colloidal silicon dioxide - 0.2 mg, magnesium stearate - 0.8 mg; Film coating composition: Opadry II white 85F18422 (macrogol 3350 - 0.8 mg, titanium dioxide - 0.5 mg, polyvinyl alcohol - 0.404 mg, talc - 0.296 mg) - 2 mg.
Pharmacological effect
Monophasic combined oral contraceptive (COC), which includes ethinyl estradiol and progestogen drospirenone. The contraceptive effect of the drug Lea; It is based on the interaction of various factors, of which the most important are the suppression of ovulation and changes in the properties of the cervical secretion, as a result of which it becomes hardly permeable to spermatozoa. In therapeutic doses, drospirenone also has antiandrogenic and moderate anti-mineralocorticoid properties, which gives drospirenone a pharmacological profile similar to that of natural progesterone. Drospirenone helps to reduce the symptoms of acne (acne), oily skin and hair, prevents weight gain and the appearance of edema associated with estrogen-induced fluid retention, which ensures a very good tolerability of Leia ;. The positive effects and clinical efficacy of drospirenone in alleviating the symptoms of severe premenstrual syndrome (PMS), such as pronounced psycho-emotional disorders, engorgement of the mammary glands, headache, muscle and joint pain, weight gain, and other symptoms associated with the menstrual cycle. In combination with ethinyl estradiol, drospirenone demonstrates a beneficial effect on the lipid profile, characterized by an increase in HDL plasma levels. In women taking COCs, the menstrual cycle becomes more regular.less frequent painful periods, decreases the intensity of bleeding, which reduces the risk of anemia. In addition, according to epidemiological studies, the use of COC reduces the risk of developing endometrial cancer and ovarian cancer.
Pharmacokinetics
Drospirenone; Absorption; Oral administration of drospirenone is rapidly and almost completely absorbed. After a single ingestion of Cmax in the blood plasma, equal to about 38 ng / ml, is achieved in approximately 1-2 hours. Bioavailability is 76-85%. Eating does not affect the bioavailability of drospirenone.; Distribution; After oral administration, the concentration of drospirenone in the blood plasma decreases in two phases, with T1 / 2 in the second phase - 31 hours. ), or a corticosteroid-binding globulin (CSG). Only 3-5% of the total plasma concentration of the substance is present as a free steroid. An ethinyl estradiol-induced increase in SHBG does not affect the binding of drospirenone to plasma proteins. The average apparent Vd is 3.7 ± 1.2 l / kg.; Equilibrium concentration. During the cycle treatment, Cssmax of drospirenone in the blood plasma is reached after 8 days of taking the drug and is approximately 70 ng / ml. There was an increase in the concentration of drospirenone in plasma approximately 2-3 times (due to cumulation), which was caused by the T1 / 2 ratio in the terminal phase and the dosing interval. A further increase in the plasma concentration of drospirenone is observed between 1 and 6 cycles of administration, after which there is no increase in concentration.; Metabolism; After oral administration, drospirenone is extensively metabolized. Most plasma metabolites are represented by the acidic forms of drospirenone.; Elimination; The rate of metabolic clearance of drospirenone in the blood plasma is 1.5 ± 0.2 ml / min / kg. In unchanged form, drospirenone is excreted only in trace amounts. Metabolites of drospirenone are excreted through the intestine and the kidneys in a ratio of approximately 1.2: 1.4. T1 / 2 with excretion of metabolites is approximately 24 hours; Pharmacokinetics in special clinical situations; Patients with renal insufficiency. Css of drospirenone in plasma in women with mild renal insufficiency (CK 50-80 ml / min) were comparable to those in women with normal renal function (CK> 80 ml / min).In women with moderately severe renal failure (CK 30–50 ml / min), plasma concentration of drospirenone was on average 37% higher than in women with normal renal function. Drospirenone treatment was well tolerated in all groups. The intake of drospirenone did not have a clinically significant effect on the concentration of potassium in the blood plasma. The pharmacokinetics for severe renal failure has not been studied.; Patients with hepatic insufficiency; Drospirenone is well tolerated by patients with mild to moderate hepatic insufficiency (class B on the Child-Pugh scale). The pharmacokinetics for severe hepatic failure has not been studied.; Ethinyl estradiol; Absorption; After oral administration, ethinyl estradiol is rapidly and completely absorbed. The peak plasma concentration after a single oral administration is reached in 1-2 hours and is about 33 pg / ml. The absolute bioavailability as a result of presystemic conjugation and metabolism of the first passage is approximately 60%. Concomitant food intake reduces the bioavailability of ethinyl estradiol in about 25% of those examined, while no changes were observed in other patients. Distribution; The concentration of ethinyl estradiol in blood plasma decreases in two phases; T1 / 2 is approximately 24 hours. Ethinyl estradiol is largely and not specifically bound to plasma albumin (approximately 98.5%) and causes an increase in plasma SHG concentrations. The average apparent Vd is about 5 l / kg.; Metabolism; Ethinyl estradiol undergoes systemic conjugation in the mucosa of the small intestine and in the liver. Ethinyl estradiol is primarily metabolized by aromatic hydroxylation, with the formation of various hydroxylated and methylated metabolites, presented both as free metabolites and as conjugates with glucuronic and sulfuric acids. Ethinyl estradiol is fully metabolized; metabolic clearance rate is about 5 ml / min / kg; Elimination; Ethinylestradiol is practically not excreted unchanged. Ethinyl estradiol metabolites are excreted through the kidneys and intestines at a ratio of 4: 6; T1 / 2 is about 1 day.; Equilibrium concentration; The state of equilibrium concentration is reached during the second half of the drug intake cycle,moreover, the concentration of ethinyl estradiol in plasma increases by approximately 1.4-2.1 times.; Preclinical safety data; Preclinical data obtained in the course of standard studies to identify toxicity during repeated doses of the drug, as well as genotoxicity, carcinogenic potential and toxicity to the reproductive system, do not indicate the presence of particular risk to humans. Nevertheless, it should be remembered that sex hormones can promote the growth of certain hormone-dependent tissues and tumors.
Indications
- contraception ;; - contraception and treatment of acne of moderate severity (acne vulgaris) ;; - contraception and treatment of severe premenstrual syndrome (PMS).
Contraindications
Taking the drug Lea; contraindicated in the presence of any of the conditions listed below; if any of these conditions arise for the first time during the treatment of COCs, they should be immediately discontinued. - Thrombosis (venous and arterial) and thromboembolism at present or in history (including deep vein thrombosis, pulmonary thromboembolism, myocardial infarction), cerebrovascular disorders (including history) ;; - conditions that precede thrombosis (including transient ischemic attacks, angina) are currently or in history ;; - hereditary or acquired susceptibility to the development of venous or arterial thrombosis, such as resistance to activated protein C, antithrombin III deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinemia and antiphospholipid antibodies (antibodies to cardiolipin, lupus anticoagulant) ;; - in the current mode, a headache with a neurologic symptom, lupus anticoagulant); - the headaches with the neurological symptoms that are present in the current vein, lupus anticoagulant) ;; - multiple or pronounced risk factors of venous or arterial thrombosis, including complicated lesions of the valvular apparatus of the heart, atrial fibrillation; diseases of cerebral vessels or coronary arteries; uncontrolled arterial hypertension; severe dyslipoproteinemia, diabetes mellitus with vascular complications, serious surgical intervention with prolonged immobilization; smoking over the age of 35; obesity with a BMI of more than 30 kg / m2; extensive trauma ;; - liver failure, severe liver disease (until normalization of liver function indicators) ;; - liver tumors (benign or malignant), incl. history ;; - severe renal failure, acute renal failure ;; - adrenal insufficiency ;; - pancreatitis, incl.in history if it is associated with the presence of severe triglyceridemia ;; - identified hormone-dependent malignant diseases (including the genitals or mammary glands) or suspicion of them ;; - bleeding from the vagina of unspecified etiology ;; - pregnancy or suspicion of it ;;; - breastfeeding period ;; - lactose intolerance, lactase deficiency, glucose-galactose malabsorption (lactose monohydrate is included) ;; - hypersensitivity to any component of the Ley preparation;; With caution; If the patient has Kaki - Of the conditions / risk factors listed below, the potential risk and the expected benefits of using COCs, including Ley, should be carefully weighed in. - Risk factors for thrombosis and thromboembolism: smoking, thrombosis (including history), myocardial infarction or impaired cerebral circulation at a young age in one of the closest relatives; obesity with a BMI less than 30 kg / m2; dyslipoproteinemia; controlled arterial hypertension; migraine without focal neurological symptoms; valvular disease without complications; heart rhythm disorder; - other diseases in which disorders of the peripheral circulation can occur: diabetes mellitus; systemic lupus erythematosus; hemolytic uremic syndrome; Crohn's disease and ulcerative colitis; sickle cell anemia; and phlebitis of the superficial veins ;; - hereditary angioedema ;; - hypertriglyceridemia ;; - liver disease ;; - diseases first arisen or aggravated during pregnancy or against the background of previous intake of sex hormones impairment of hearing, porphyria, herpes of pregnant women, Sydengam's chorea) ;; - postpartum period.
Dosage and administration
Leia's drug; intended for oral administration daily for 28 days without interruption, approximately at the same time, with a small amount of water, in the order indicated on the blister package. Taking the pills from the new package begins the next day after taking the last pill from the previous package. How to take the drug Leia ;; If you have not taken any hormonal contraceptives in the previous month; Taking the drug Lea; starts on the first day of the menstrual cycle (i.e., on the first day of the menstrual bleeding).It is allowed to start taking on the 2-5 day of the menstrual cycle, but in this case it is recommended to additionally use a barrier method of contraception during the first 7 days of taking the pills from the new package; start taking inactive pills and may not end before taking the pills from the new package.; When switching from other combined oral contraceptives (COC, vaginal ring or transdermal patch); It is preferable to start taking Le I; the next day after taking the last active tablet from the previous package, but in no case later than the next day after the usual 7-day break (for drugs containing 21 active pills) or after taking the last inactive tablet (for drugs containing 28 pills in packaging). Taking the drug Lea; should begin on the day the vaginal ring or the contraceptive patch is removed, but not later than the day when a new patch is to be inserted or a new patch is stuck. ;) A woman can switch from a mini-drank to a drug Leia; on any day (without a break), from the implant or the intrauterine therapeutic system, releasing the progestogen - on the day of its removal, from the injection contraceptive - on the day when the next injection should be made. In all cases, you must use an additional barrier method of contraception during the first 7 days of taking the pills. After an abortion in the first trimester of pregnancy; A woman can start taking Leia; from the first day after the abortion. If this condition is observed, the woman does not need additional contraceptive measures. After childbirth or abortion in the second trimester of pregnancy; It is recommended to start taking Leia; at 21-28 days after birth, in the absence of breastfeeding, or abortion in the second trimester of pregnancy. If reception is started later, you must use an additional barrier method of contraception during the first 7 days of taking the pills. However, if a woman has already lived sexually, before Leia starts taking; pregnancy should be excluded.; Acceptance of missed pills; Skip inactive pills can be ignored. However, they should be thrown away in order not to accidentally extend the intake of inactive pills.The following recommendations apply only to skipping active pills:; - if the delay in taking the drug was less than 24 hours, contraceptive protection is not reduced. A woman should take the missed pill as soon as possible, and take the next pill at the usual time. - If the delay in taking the pills is more than 24 hours, the contraceptive protection can be reduced. The more pills are missed, and the closer the pill passes to the inactive pill intake phase, the higher the probability of pregnancy. At the same time, the following basic rules can be followed: - the drug should never be interrupted for more than 7 days (the recommended inactive pills is 4 days) ;; - to achieve adequate suppression of the hypothalamic-pituitary-ovarian system requires 7 days of continuous administration of pills. Thus, if a delay in taking active pills was more than 24 hours, We can recommend the following: From the 1st to the 7th day; A woman should take the last missed pill as soon as she remembers it, even if it means taking two pills at the same time. She continues to take the following pills at the usual time. In addition, over the next 7 days, you must additionally use a barrier method of contraception (for example, a condom). If sexual intercourse took place within 7 days before the tablet was missed, consider the possibility of pregnancy. From the 8th to the 14th day; A woman should take the last missed pill as soon as she remembers, even if it means taking two pills at the same time. The following pills should be taken at the usual time. Provided that the woman took the pill correctly for the 7 days preceding the first missed pill, there is no need to use additional contraceptive measures. Otherwise, as well as skipping two or more pills, it is necessary to additionally use barrier methods of contraception (for example, a condom) for 7 days. From the 15th to the 24th day; pills. A woman should strictly adhere to one of the following two options. However, if in the 7 days preceding the first missed pill, all the pills were taken correctly, there is no need to use additional contraceptive methods.Otherwise, she needs to use the first of the following schemes and additionally use a barrier method of contraception (for example, a condom) for 7 days.; 1 option: a woman should take the last missed pill as soon as she can (even if it means taking two pills at the same time). The following pills are taken at the usual time until the active pills in the package run out. Four inactive pills should be thrown away and immediately start taking the pills from the next package. Bleeding "cancellation" is unlikely until the active pills in the second pack run out, but there may be a "spotting" discharge and "breakthrough" bleeding while taking the pills. Option 2: A woman may also interrupt taking the pills from the current package. Then she should take a break of no more than 4 days, including the days of skipping the pills, and then start taking pills from a new pack. If a woman missed active pills, and while taking inactive pills, "cancellation" bleeding did not occur, pregnancy should be excluded. Recommendations for gastrointestinal disorders; In severe gastrointestinal disorders, absorption of the drug may be incomplete, therefore additional contraceptive measures should be taken. ; If vomiting occurs within 4 hours after taking the active pill, refer to the recommendations for skipping pills. If a woman does not want to change her usual regimen and transfer the onset of menstruation to another day of the week, an additional active pill should be taken from another package; Change the day of the onset of menstrual bleeding; In order to delay the onset of menstrual bleeding, the woman should continue taking the pills from the next package by skipping the inactive pills from the current packaging. Thus, the cycle can be extended, if desired, for any period until the active pills from the second package run out. While taking the pills from the second package, a woman may experience "spotting" discharge or "breakthrough" uterine bleeding. Regular use of the drug Lea; resumes after the end of the inactive pill phase. In order to transfer the day of the onset of menstrual bleeding to another day of the week, the woman should reduce the next phase of the inactive pill for the desired number of days.The shorter the interval, the higher the risk that she will not have “withdrawal” bleeding and in the future there will be “spotting” spotting and “breakthrough” bleeding while taking the second package (just as in the case when she would like to delay the onset of a menstrual bleeding); How to delay bleeding "cancellation"; To delay the onset of menstruation, a woman should switch to taking pills from a new package of Leia; skipping taking placebo pills. Such a prolongation of the cycle can be continued until the active pills of the second package run out. During this extension, a woman may experience "breakthrough" bleeding or spotting. In the future, you should resume regular use of the drug Leia; after the usual interval without taking the pill, which is 7 days.; To postpone the menstruation to another day, more suitable for a woman's usual schedule, you can reduce the second phase of taking the placebo pills for as many days as you need. The shorter this phase, the higher the risk that the "withdrawal" bleeding will not develop, and that there will be "breakthrough" bleeding or bleeding during the taking of pills from the second package (as well as deferred menstruation) .; Special categories of patients; Children and adolescents: drug Lea; shown only after the onset of menarche. The available data do not imply dose adjustment in this group of patients.; Elderly patients: not applicable. Leia's drug; not shown after menopause.; Ley's drug; contraindicated in women with severe liver disease, until liver function indicators return to normal.; Leia; contraindicated in women with severe renal insufficiency or acute renal failure.