The instruction for medical use
of LINDINET 20 medicine
the Trade name
of Lindinet 20
International unlicensed name
Are not present
the Dosage form
of the Tablet, coated
One tablet contains
active agents: ethinylestradiol of 0.02 mg,
gestoden 0.075 mg,
excipients: calcium sodium edetat, magnesium stearate, silicon dioxide colloidal anhydrous, povidone, starch corn, lactoses monohydrate,
structure of a cover: quinolinic yellow (E 104), povidone, the titan dioxide
(E 171), a macrogoal 6000, talc, calcium a carbonate, sucrose
of the Tablet of round shape, with a biconvex surface, coated light yellow color (for Lindinet 20).
Sex hormones and modulators of a reproductive system. Hormonal contraceptives for system use. Progestogens and estrogen (the fixed combinations). Gestoden and estrogen
the ATX G03AA10 Code
Pharmacokinetics Gestoden properties Absorption Later of oral administration occurs fast and full absorption of a gestoden. Peak concentration in plasma after single dose is reached approximately in 1 hour and makes about 2-4 ng/ml. The bioavailability is about 99%.
Gestoden contacts seralbumin and the globulin, connecting sex hormones (G,CSH). Only 12% of the general concentration of substance in blood serum are in a type of free steroid, and 5075% are specific are connected with GSPG. The increase in the GSPG level induced by ethinylestradiol affects quantity of the gestoden connected with serum protein that causes increase in the fraction of a gestoden connected with GSPG and reduction of the fraction connected with albumine. The seeming volume of distribution of a gestoden is 0.7-1.4 l/kg.
Gestoden is completely metabolized by means of the known ways of metabolism of steroid hormones.
Average speed of metabolic clearance is 0.8-1.0 ml/min. of blood plasma.
the Level of a gestoden in serum is exposed to two-phase decrease. Elimination half-life in a terminal phase makes 12-20 hours. Gestoden is brought with urine and bile only in the form of metabolites in the ratio 6:4. Elimination half-life of metabolites makes about 1 day.
influences pharmacokinetics of a gestoden the GSPG level which increases approximately three times at a concomitant use of ethinylestradiol. After daily reception the level of a gestoden increases in blood serum approximately by three-four times, reaching equilibrium concentration in the second half of a course of administration of drug.
After oral administration occurs fast and full absorption of ethinylestradiol. Peak concentration in plasma is reached approximately in 1-2 hours and makes about 30-80 pg/ml. The absolute bioavailability as a result of presistemny conjugation and effect of the first passing through a liver is about 60%.
Ethinylestradiol strongly, but is not specific contacts seralbumin (about 98.5%) that leads to increase in concentration of GSPG in serum. The seeming volume of distribution of a gestoden is 5-18 l/kg.
Ethinylestradiol is metabolized mainly by aromatic hydroxylation, however, at the same time a large number of hydroxylated and metilirovanny metabolites among which both free metabolites, and conjugates with glucuronides and sulfates is formed. Speed of metabolic clearance is about 5-13 ml/min.
ethinylestradiol Level in serum is exposed to two-phase decrease, elimination half-life in a terminal phase makes about 16-24 hours. It is removed only in the form of metabolites, the ratio between urine and bile makes 2:3. Elimination half-life of metabolites makes about 1 day.
Equilibrium concentration is reached in 3-4 days, during this time the ethinylestradiol level in serum increases by 20% in comparison with level after reception of a single dose.
Action of the combined oral contraceptives (COC) is caused by suppression of production of gonadotropic hormones. Though the main mechanism of action is suppression of an ovulation, other mechanisms of action, including changes of a condition of cervical slime (that complicates penetration of spermatozoa into a uterus) and endometrium (that reduces implantation probability), also have contraceptive effect.
Besides contraceptive action, render some other positive impacts.
Influence on a menstrual cycle:
Regulate a menstrual cycle, losses of blood and gland reduce during periods, reduce the frequency of development of a dysmenorrhea.
The actions connected with braking of an ovulation:
Reduce quantity of cases of development of functional ovarian cysts and an extrauterine pregnancy.
Reduce the frequency of development of fibroadenomas and fibrocysts of mammary glands, infections of bodies of a small pelvis, endometrial cancer, improve a condition of skin in acne rash.
– oral contraception
the Route of administration and doses
Should be accepted on one tablet a day (preferably at the same time day) within 21 days. Reception of tablets from the following packing should be begun after a 7-day break during which cancellation bleeding has to begin. Usually bleeding begins for 2 or 3 day after reception of the last tablet and can not end prior to reception of tablets from the following packing.
Lindinet’s reception 20 for the first time
it is necessary to take the First pill Lindineta 20 in the first day of a menstrual cycle.
Reception of tablets can also be begun from 2 to 5 day of periods, however in this case it is necessary to use additional non-hormonal measures of contraception during the first seven days of reception of tablets during the first cycle.
Transition from reception of other combined oral contraceptive
it is necessary to take the First pill Lindineta 20 next day after reception of the last active (gormonsoderzhashchy) tablet from the previous packing of an oral contraceptive, but no later than the next day after reception of usual tablets (or reception of tablets of placebo) from the previous packing of oral contraceptives.
Transition from the progestagen-containing drugs (mini-drank, injections, an implant, Naval Forces)
Transition from reception mini-was drunk to Lindinet’s reception 20 it is possible to make in any day of a menstrual cycle (from an implant and an intrauterine spiral – in day of their removal, from injections – in day when it is necessary to make the following injection). In these cases during the first 7 days of reception of tablets it is necessary to use additional measures of contraception.
After abortion in the 1st trimester
the Reception of oral contraceptives can be begun at once after abortion in the first trimester. Additional measures of contraception are not required.
After the delivery or abortion in the 2nd trimester
of the Woman, not nursing, can begin reception of oral contraceptives for 21-28 day after natural childbirth or after abortion in the 2nd trimester. At later beginning of reception of oral contraceptives during the first 7 days as additional measures it is necessary to apply barrier methods of contraception.
If the sexual contact already took place, prior to reception of tablets it is necessary to exclude pregnancy existence, or it is necessary to postpone administration of drug prior to the beginning of the first menstrual bleeding.
The passed tablets
If the pill was not taken in time, it should be accepted as soon as possible. If the passed pill was taken within 12 hours after usual time of its reception, the contraceptive effect of drug does not decrease, and additional measures of contraception are not required. The subsequent pill should be taken in usual time.
If the delay in reception of a tablet exceeds 12 hours, the contraceptive effect can decrease. The woman has to take the passed pill as soon as she remembers it even if it is necessary to take 2 pill at the same time. From this point the woman has to take a pill in usual time. Additional measures of contraception are necessary during the next 7 days of reception of tablets. If in the current packing there were less than 7 tablets, the woman has to begin reception of tablets from the following packing at once after reception of the last tablet from the current packing: it means that between reception of tablets from two packs there will be no break. In this case it is not necessary to expect cancellation bleeding until as tablets from the second packing will end, however the smearing or breakthrough bleedings can develop.
If after the end of reception of tablets from the second packing the bleeding of cancellation does not develop, then prior to reception of tablets it is necessary to exclude pregnancy existence from the following packing.
The measures taken in case of vomiting
If vomiting arises within 3-4 hours after reception of a tablet, absorption of a tablet can be incomplete. In such cases it is necessary to take the precautionary measures described above concerning the passed tablets. If the woman does not want to change the usual mode of reception of tablets, she has to take a necessary additional pill from other packing.
Acceleration of terms of approach of periods or a delay of periods
That menstrual bleeding began earlier, than usually at reception of tablets, it is recommended to reduce a break between reception of tablets by the desirable number of days. The break is shorter, the risk of breakthrough bleedings or the smearing discharges at reception of tablets from the second packing will be higher (as well as in case of a delay of menstrual bleeding).
To delay approach of menstrual bleeding, it is necessary to begin reception of tablets from new packing at once after tablets from the current packing end, without leaving between them a break. Periods it is possible to detain as long as it is required, all tablets from the second packing will not come to an end yet. At reception of tablets from the second packing there can be breakthrough bleedings or the smearing discharges. Regular reception of Lindinet 20 can be resumed after a usual 7-day break.
Very often (& ge,/10)
– the breakthrough bleedings smearing discharges between periods
Often (& ge, 1/100 to & lt, 1/10)
– a headache, dizziness, migraine
– change of mood, a depression, nervousness, irritability, decrease or increase in a libido
– a liquid delay
– vulvaginalny candidiasis
– nausea, vomiting, an abdominal pain
– an acne
– morbidity and a nagrubaniye of mammary glands
– decrease/increase in body weight
Infrequently (& ge, 1/1000 to & lt, 1/100)
– decrease/increase in appetite
– a breast cancer
– arterial hypertension
– hloazma, a melazma
Seldom (& ge, 1/10000 to & lt, 1/1000)
– anaphylactic reactions
– disturbance of a toleratnost to glucose, a lipidemia, a gipertriglitseridemiya
– intolerance of contact lenses
– an otosclerosis
– thrombosis, an embolism
Very seldom & lt, 1/10000)
– diseases of a gall bladder, cholelithiasis, pancreatitis, a hepatocellular carcinoma, liver adenoma
– aggravations of a system lupus erythematosus
– aggravation of a chorea, an optic neuritis
– a stroke, a myocardial infarction
– an eye retina artherothrombosis
– a gemolitiko-uraemic syndrome
Use of oral contraceptives is connected with the increased risk of development of the following states:
– arterial and venous trombotichesky and tromboembolic episodes, including a myocardial infarction, a stroke, a vein thrombosis and an embolism of a pulmonary artery.
– the intraepithelial neoplasia of a neck of the uterus and cervical cancer
– a breast cancer
can lead the Optic neuritis to partial or full loss of sight. Use the COOK can aggravate a course of the existing disease of a gall bladder and accelerate a course of a disease at the women who earlier did not have disease symptoms.
– hypersensitivity to drug components
– pregnancy or suspicion on it
– vaginal bleeding of an unknown etiology
– arterial or venous thrombosis now or in the anamnesis
– presence of serious risk factors of developing thrombosis or embolism (disturbances of blood clotting, valvular heart disease and fibrillation of auricles)
– existence of prodromal symptoms of thrombosis in the anamnesis (for example, the tranzitorny cerebral ischemic attack, stenocardia)
– cardiovascular disturbances (pathology of the valve (valves) of heart, arrhythmia)
– heavy arterial hypertension
– liver tumors in the anamnesis (benign or malignant)
– serious diseases of a liver, before normalization of parameters of functional trials of a liver
– the diagnosed or suspected malignant tumors of mammary glands
– the diagnosed or suspected malignant tumors of endometrium or other estrogenzavisimy new growths
– a vascular ophthalmopathy
– herpes of pregnant women in the anamnesis
– drepanocytic anemia
– a lipidemia
– the diabetes complicated by an angiopatiya
– migraine with focal neurologic symptomatology
– children’s and teenage age up to 18 years
– the hereditary intolerance of fructose, deficiency of Lapp-lactases enzyme, galactose glucose malabsorption
can lead Interaction between ethinylestradiol and at the same time used drugs to increase or decrease in level of ethinylestradiol in plasma.
Decrease in level of ethinylestradiol in plasma can lead to increase in quantity of breakthrough bleedings and disturbances of a menstrual cycle, sometimes decrease in contraceptive effect of Lindinet 20 is also observed. Therefore, in case of the simultaneous use of ethinylestradiol and drugs reducing ethinylestradiol level in plasma in addition to Lindinet’s reception 20 it is recommended to use non-hormonal methods of contraception (for example, condoms, spermitsida). If prolonged use of the drugs containing such active agents is necessary it is necessary to consider the possibility of refusal of use of hormonal contraceptives as the main method of contraception.
After the termination of intake of the medicines reducing concentration of ethinylestradiol in blood it is recommended to use additional non-hormonal methods of contraception at least within 7 days. After the termination of intake of the medicines capable to cause induction of microsomal enzymes of a liver and to lead to decrease in concentration of ethinylestradiol in blood serum, it is recommended to use additional non-hormonal methods of contraception during longer period. Sometimes, depending on a dose, duration of treatment and clearance rate of the drug causing induction of enzymes there can pass weeks before induction of enzymes of a liver completely stops.
Active agents which can reduce concentration of ethinylestradiol in blood serum:
– any active agent which reduces transit time on digestive tract and is reduced, therefore, by absorption,
– substances which induce microsomal enzymes of a liver, for example, rifampicin, rifabutin, barbiturates, Primidonum, phenylbutazone, Phenytoinum, dexamethasone, griseofulvin, topiramat, some inhibitors of protease also were modafinit,
– Hypericum perforatum (St. John’s wort) and ritonavir (thanks to ability to induce microsomal enzymes of a liver),
– some antibiotics (for example, ampicillin and other penicillin, tetracyclines) as they reduce hepatoenteric recirculation of estrogen.
Active agents which can increase concentration of ethinylestradiol in blood serum:
– drugs which are also exposed to sulphation in a digestive tract wall, for example, ascorbic acid (vitamin C) and paracetamol,
– substances which inhibit isoenzymes of P 450 3A4 cytochrome, for example, indinavir, flukonazol, troleandomitsin.
Troleandomitsin at combined use with oral contraceptives can increase risk of an intra hepatic cholestasia.
Ethinylestradiol can affect metabolism of other drugs, inhibiting microsomal enzymes of a liver or causing conjugation of drugs in a liver, in particular, a glyukuronidation. Thus, concentration of other drugs in plasma and fabrics can increase (for example, concentration of cyclosporine, theophylline, corticosteroids) or to decrease. Registering any drugs, it is necessary to take into account information on their combined use, for the purpose of establishment of possible reactions of interaction.
Changes in results of the laboratory
researches Use of Oral Contraceptives can affect results of some laboratory researches among which there are tests of function of a liver, thyroid gland, adrenal glands, kidneys, levels of lipoproteins and proteins carriers and also parameters of carbohydrate metabolism, coagulation and fibrinolysis.
Usually changes are not beyond referensny values and remain within norm.
of Disturbance of blood circulation
Use of contraceptives is connected with the increased risk of developing a myocardial infarction. The risk is higher at the smoking women having accessory factors of risk of developing diseases of coronary vessels, such as arterial hypertension, the increased cholesterol level, pathological obesity and diabetes.
Smoking increases risk of the serious cardiovascular complications connected with reception of oral contraceptives. The risk increases with age and also in case of smoking of a large number of cigarettes, this risk is quite essential at women 35 years are more senior. The women accepting oral contraceptives should recommend to refuse smoking.
Women, with risk factors of developing cardiovascular diseases, need to appoint oral contraceptives with care.
It was proved that reception of oral contraceptives increases risk of developing cerebrovascular diseases (ischemic and hemorrhagic stroke).
Also it was reported about increase in the arterial blood pressure (ABP) at the women accepting oral contraceptives. Increase in the ABP is usually observed at women of advanced age and at those who accept oral contraceptives for a long time.
The obtained data show that the frequency of development of arterial hypertension increases depending on amount of estrogen.
Women who suffered from the arterial hypertension or diseases connected with arterial hypertension or a renal failure earlier should recommend to use other method of contraception. It is necessary to watch a condition of these women if they decided to accept oral contraceptives carefully. In case of substantial increase of arterial blood pressure it is necessary to stop reception of oral contraceptives.
At most of women raised by the ABP it is normalized after cancellation of oral contraceptives, differences in the frequency of development of arterial hypertension between the women who were earlier using and not using oral contraceptives no.
Venous and arterial thrombosis and a thrombembolia
Use of the combined oral contraceptives is connected with the increased risk of venous and arterial trombotichesky and tromboembolic episodes. For each specific combination it is oestrogenic / progestagen it is necessary to register that mode of dosing which contains the minimum quantity of estrogen and progestogen, and at the same time provides low interest of failures and corresponds to needs of the patient.
Venous thrombosis and thrombembolia
Use of any combined oral contraceptives involves the increased risk of a venous thrombembolia (VTE) in comparison with that without use the COOK. The additional risk of a venous thrombembolia is highest within the very first year of use of the combined oral contraceptives. This risk is less than risk of VTE connected with pregnancy which is 60 cases on 100,000 pregnancies, VTE leads to a lethal outcome in 1-2% of cases.
Frequency of development of VTE for the combined oral contraceptives containing levonorgestrel and less than 50 mkg of ethinylestradiol is about 20 cases on 100,000 women for a year of use. Frequency of development of VTE for the combined oral contraceptives containing gestoden, about 30-40 cases on 100,000 women for a year of use. Influence of relative risk on quantity of additional cases is higher at women within the very first year of use of the combined oral contraceptives.
Epidemiological researches did not confirm that the women accepting the combined oral contraceptives containing dezogestret or gestoden and 0.02 mg of ethinylestradiol, have smaller risk of development of VTE, than the women accepting the combined oral contraceptives containing dezogestret or gestoden and 0.03 mg of ethinylestradiol.
Risk factors of an arterial and/or venous thrombembolia
– smoking (at malicious smokers with age the risk increases more and more, especially at women 35 years)
– genetic predisposition are more senior (for example, an arterial or venous thrombembolia at brothers and sisters or parents at relatively young age). With genetic predisposition, before making decision on reception of oral contraceptives the woman should be directed to reception to the expert
– obesity (body mass index more than 30 kg/sq.m)
– a dislipoproteinemiya
– arterial hypertension
– valvular heart disease
– fibrillation of auricles
– a long immobilization (as risk of developing a thrombembolia is increased during the postoperative period, it is recommended to stop reception of oral contraceptives at least in four weeks prior to planned operation and to return to their reception not earlier than in two weeks after return to normal physical activity).
As the period directly after the delivery is associated with the increased risk of a thrombembolia, 20 it is necessary to begin Lindinet’s reception not earlier, than for 28 day after the delivery or abortion in the second trimester of pregnancy.
Arterial thrombosis and
Lindinet’s thrombembolia 20 increases risk of development of arterial trombotichesky and tromboembolic episodes. The described complications include a myocardial infarction and cerebrovascular disturbances (ischemic and hemorrhagic stroke, the tranzitorny ischemic attack). Risk of development of arterial trombotichesky and tromboembolic episodes is higher at the women having accessory factors of risk.
It is necessary to appoint with care Lindinet to 20 women having risk factors of development of trombotichesky and tromboembolic episodes.
Examples of the risk factors contributing to the development of trombotichesky and tromboembolic episodes:
– certain hereditary and acquired thrombophilias
– arterial hypertension
– a lipidemia
of the Woman, having migraine and accepting the COOK, have the increased risk of developing a stroke.
Administration of drug should be stopped immediately at emergence of the symptoms indicating development of thrombosis: severe pain in a breast which can give to the left hand an unusual scelalgia, swelled legs, an acute pain during breath or cough, emergence of a phlegm with blood.
The biochemical parameters indicating presence of the hereditary or acquired predisposition to venous or arterial thrombosis include the following: resistance to the activated protein With (AP), a gipergomotsisteinemiya, deficiency of antithrombin III, deficit of a protein With, deficit of a protein of S, anti-phospholipidic antibodies (anti-cardiolipin antibodies, lupoid anticoagulant).
To a tumor
In some researches it was reported about the increased risk of developing cancer of gang of a uterus at the women accepting the combined oral contraceptives for a long time however this information is disputable. The sexual behavior and other risk factors, such as human papillomavirus (HP), can also influence development of cervical cancer.
Meta-analysis 54 pharmako-epidemiological researches showed that relative risk of developing a breast cancer is slightly higher at the women accepting the combined oral contraceptives (the SHOUTING = 1.24). This increased risk gradually decreases within 10 years after the termination of reception of the combined oral contraceptives. However these researches did not confirm existence of relationship of cause and effect between a disease and administration of drug.
At the women accepting oral contraceptives, the breast cancer is diagnosed at earlier stage, than for those who do not apply them.
Connection between formation of benign tumors of a liver and reception of oral contraceptives is established though such benign tumors meet seldom. At a rupture of these tumors the intraperitoneal bleeding which can lead to a lethal outcome is observed.
It was in rare instances reported about development of malignant tumors of a liver in women, it is long accepting oral contraceptives.
At the patients having in the anamnesis cholestatic jaundice or an itching during pregnancy and also at the patients who were earlier accepting the combined oral contraceptives, risk of developing the diseases described above is higher. In case such patients accept Lindinet 20, careful monitoring of their state is necessary, and at return of morbid condition the use of drug needs to be stopped.
it was In rare instances reported about eye retina fibrinferment at reception of oral contraceptives. In case of inexplicable partial or total loss of sight, emergence of an exophthalmos or diplopia, a papilledema or damage of vessels of a retina, it is necessary to stop reception of oral contraceptives and to undergo additional medical examination.
The previous researches demonstrated the relative risk of diseases of a gall bladder increasing during all life at the women accepting the oral contraceptives and drugs containing estrogen. However the last researches showed that the women accepting low-dose oral contraceptives can have the minimum relative risk of developing diseases of a gall bladder.
Appearance of migraine, or strengthening of attacks of migraine and also appearance of the headache of new type repeating constant or very strong, demands the termination of reception of oral contraceptives.
It is necessary to stop immediately Lindinet’s reception 20 in case of appearance of an itching on all body or epileptic seizures.
Influence on metabolism of carbohydrates and lipids
the women accepting oral contraceptives Have messages about disturbance of tolerance of glucose. Therefore it is necessary to watch a condition of the women having diabetes and using oral contraceptives carefully.
At a small amount of women during reception of oral contraceptives the resistant gipertriglitseridemiya is observed. At use of some progestagensoderzhashchy drugs it was reported about decrease in level of the lipoproteins of high density (LHD). As estrogen increases LVP cholesterol level, cumulative impact of oral contraceptives on metabolism of lipids depends on a ratio between doses of estrogen and progestogen, like progestogen and also absolute amount of the progestogen used in an oral contraceptive.
It is necessary to watch carefully a condition of the women suffering from a lipidemia if they decided to accept oral contraceptives.
There are messages that at the women suffering from a hereditary lipidemia and accepting the oral contraceptives containing estrogen the substantial increase of level of triglycerides in plasma is observed that can lead to pancreatitis.
Disturbances of a menstrual cycle
At reception of tablets, especially within the first three months, can be observed the irregular periods (smearing or breakthrough bleedings).
If irregular periods remain a long time or develop after the regular cycle was established, it is necessary to consider that this phenomenon can have the non-hormonal reason. In this case, to exclude a possibility of development of a malignant new growth or pregnancy, it is necessary to perform gynecologic examination. If morbid condition is excluded, it is possible to recommend use of oral contraceptives of other type.
In some cases the 7-day break in contraception is not followed by bleeding. In cases when reception of a contraceptive was carried out not according to the instruction or when upon termination of reception of all tablets from the current packing there is no bleeding before continuing reception of a contraceptive from the following packing, it is necessary to exclude pregnancy existence.
Medical examination and the subsequent observation
Prior to use of oral contraceptives should be collected the family and personal anamnesis of the patient, to perform the general medical and gynecologic examination, including measurement of arterial blood pressure, laboratory analyses, inspection of mammary glands and bodies of a small pelvis and also to take a smear from a vagina on cytology, further these procedures should be repeated periodically.
It is necessary to tell patients that this drug does not protect from HIV infection (AIDS) and other diseases, sexually transmitted.
Function of a liver
in case of an acute or chronic abnormal liver function it is necessary to stop administration of drug until functional trials of a liver are not normalized. Patients from the liver broken by function can have an insufficient metabolism of steroid hormones.
of the Woman at which during use of oral contraceptives the heavy depression develops have to stop taking a pill. Such women need to recommend to use an alternative method of contraception, it is also necessary to try to define whether there are these symptoms as a result of use of drugs for oral contraception. It is necessary to watch carefully a condition of women who had a depression earlier if attacks of a depression renew, it is necessary to stop taking the drug for oral contraception.
Level of folates
the Level of folates in blood serum can decrease owing to use of oral contraceptives. It can have clinical value if soon after the termination of reception of oral contraceptives the woman becomes pregnant.
Poyavleniye of a hloazma is especially often observed at the women having a hloazma of pregnant women in the anamnesis. The women predisposed to a hloazma should avoid stay in the sun and also ultraviolet radiation during reception the COOK.
Krom of the listed above states, it is necessary to take the raised precautionary measures in case of an otosclerosis, multiple sclerosis, epilepsy, a chorea, the alternating porphyria, spasms, a renal failure, obesity, a system lupus erythematosus and a hysteromyoma.
To patients with such rare hereditary pathology, such as intolerance of fructose, malabsorption of glucose galactose or insufficiency of sucrose-isomaltase, it is not necessary to use this drug.
Pregnancy and the period of a lactation
Prior to Lindinet’s reception 20 it is necessary to exclude pregnancy. If pregnancy occurred during drug use, it is necessary to stop reception of oral contraceptives immediately.
Extensive epidemiological researches did not find the increased risk of developing congenital malformations in newborns, rodivsh