The instruction on medical primeneniyulekarstvenny средстваКЛОСТИЛБЕГИТ®Торговое the name Klostilbegit ®
the International unlicensed
name Clomifene Dosage Form of the Tablet of 50 mg
SostavOdna a tablet contains active agent – clomifene citrate of 50 mg, excipients: lactoses monohydrate, potato starch, E-553b talc, gelatin, magnesium E-572 stearate, acid stearin E-570.
OpisanieKruglyy, flat tablets with a facet, with an engraving in the form of CLO on one party, white, yellow-white, or grayish-white color, without or almost flavourless
Pharmacotherapeutic gruppapolovy hormones and modulators of a reproductive system. Gonadotrophins and other stimulators of an ovulation. Ovulation stimulators synthetic. KlomifenKod
Pharmacological to a svoystvaFarmakokinetikaPosla of intake is well soaked up by ATH G03G B02 from digestive tract. Clomifene is metabolized in a liver. Elimination half-life of 5-7 days. Within 5 days 50% of the dose accepted inside, mainly through intestines (42%) and urine (8%) are removed. Clomifene is found in Calais within 6 weeks. The average % of the removed dose for the 31st – after administration of drug marked isotope 14C averaged the 35th day 0.73%, and on the 42nd – the 45th day – 0.45%. Samples a calla and urine undertook at 6 examinees between 14 and 53 days of a research. Not removed initial substance / metabolite slowly is removed in the course of enterogepatichesky circulation. At prolonged use, clomifene can change cholesterol synthesis speed. At long-term treatment by clomifene at patients the cholesterol level in blood serum can increase. Clomifene citrate – racemic mix cis-(zuklomifen) and a trance – (enklomifen) isomers. Cis-isomer which content in drug is not less than 30-50% is more active. Elimination half-life of a zuklomifen longer, than at trans-isomer. Zuklomifen is found in healthy volunteers in a month after reception. This fact indicates enterohepatic recirculation of drug which has stereospecificity. Clomifene can be defined at the beginning of pregnancy at the women accepting it for induction of an ovulation. FarmakodinamikaKlostilbegit – anti-estrogenic drug of nonsteroid structure. The mechanism of action is explained by ability to contact specifically receptors of estrogen in a hypothalamus, oppressing linking of oestradiol with receptors. By the principle of positive feedback the development of a gonadotrophin increases and, thus, there is a simulation of an ovulation.
Indications – stimulation of an ovulation at women with an anovulatory cycle for the purpose of pregnancy approach. Patients can only apply tablets of Klostilbegit with the proved disturbance of an ovulatory cycle. Before prescribing of the drug Klostilbegit it is necessary to exclude or carry out adequate treatment of other causes of infringement of fertility.
The route of administration and doses use Drug strictly on doctor’s orders! the 1st course of treatment: the recommended dose makes 50 mg (1 tablet) a day within 5 days. In the absence of recent uterine bleeding the treatment can be begun in any day. If induction of bleeding by means of progestin is planned, or in the presence of spontaneous cyclic bleedings it is recommended to begin treatment from the 5th day of a cycle. If the ovulation comes at use of a dose of 50 mg, then further increase in a dose in the subsequent cycles has no advantages. the 2nd course of treatment: this scheme should be applied at inefficiency of the 1st course of treatment. If the ovulation did not come after the 1st course of treatment, it is necessary to appoint daily 100 mg of drug (two tablets of 50 mg as a single daily dose) within 5 days, since 5th day of the following cycle, that is in 30 days after the previous cycle. It is not necessary to exceed a dose or duration of treatment (more, than 100 mg/days within 5 days). Most of the patients capable to react to treatment reacts already to the first course of treatment, Three courses of treatment can usually be considered an adequate therapeutic measure. In the absence of ovulyatsionny bleeding it is necessary to specify the diagnosis. At patients without signs of an ovulation the further treatment is not reasonable. Long the lecheniyena recomenduyetsyaspetsialny groups a patsiyentova of patients with hypersensitivity to a hypophysial gonadotrophin (for example, at a syndrome of polycystic ovaries) should observe extra care and, whenever possible, to appoint drug in lower doses and during shorter span.
Collateral deystviyaochen often (1/10) – vasomotorial inflows – increase yaichnikachasto (1/100 – & lt, 1/10) – a headache – nausea, vomiting, a meteorism – a disorder of vision (indistinct spots or flashes in the form of spots, feeling of the vibrating light in eyes – so-called scintillating scotomas, the residual image) – sensation of discomfort and morbidity of mammary glands – acyclic uterine bleeding, menorragiyanechasto (1/1000 –<, 1/100) – a depression – dizziness – vertigo (feeling of rotation) – nervous tension, utomlyaemostredko (1/10,000 –<, 1/1000) – the cataract, an optic neuritis – convulsive the pristupychastot is unknown (it is impossible to define on the basis of the available data) – hormone – the dependent or connected with hormones new growths/tumours allergic reactions – gipertriglitseridemiya-paranoid psychosis – syncopal conditions, acute disorders of cerebral circulation, thrombosis of vessels of a brain – dysfunction of nervous system, a disorientation, disturbances of the speech – pancreatitis – an abnormal liver function (change of results of bromsulfaleinovy test, jaundice) – urticaria, rash, a hair loss (alopecia) – a mnogoformny erythema, ecchymomas, a Quincke’s disease – polycarpous pregnancy – a combination of extrauterine and uterine pregnancy – an extrauterine pregnancy – endometriosis, deterioration in a course of endometriosis, reduction of thickness of endometrium, significant increase yaichnikovprovedenny researches specify that side reactions develop more often at prolonged use of drug and when using higher dosed At use of drug in the recommended doses side reactions are insignificant and only in rare instances become a hindrance for treatment. Increase in a yaichnikovpra use of drug in the recommended doses seldom is observed increase in ovaries up to the pathological sizes, though in comparison with usual cyclic changes of its sizes, increase can be more expressed. Similarly, the cyclic morbidity of ovaries can be more significant. At use of higher doses or extension of term of treatment the increase in ovaries and forming of cysts is observed more often, besides, the lyuteinovy phase of an ovulatory cycle can be extended. It was in rare instances reported about the significant increase in ovaries. Such case was described at the patient with a syndrome of polycystic ovaries accepting Klostilbegit in a dose of 100 mg/days within 14 days. Not normal increase in ovaries usually takes place spontaneously. At most of patients with such state it is possible to carry out conservative treatment. Disturbances from bodies zreniyas increase in the general dose the frequency of development of the symptoms known as blurring of sight and also emergence of spots or flashes increases (ophthalmic migraine). Also it was reported about emergence of an ocular spectrum (after-image). It is characteristic that the first emergence or strengthening of these symptoms from an organ of sight, is generally observed at bright lighting. There are messages about ophthalmologic the confirmed scotomas, phosphene and deterioration in sharpness of visual perception. It was in rare instances reported about a cataract and an optic neuritis. These visual disturbances usually have reversible character though there were messages about long disorders of vision after the end of treatment by clomifene. In certain cases the disorder of vision can have also irreversible character, especially at use of clomifene in high doses or at its appointment during the long span.Disturbances from a liver and bile-excreting putace the quantity brought out of BSF blood after intravenous administration of the known quantity of BSF is defined by the help of the bromsulfaleinovy test (BSF). In 45 minutes after intravenous administration of 5 mg/kg of BSF in blood there are only 5% of a dose. This test is an effective method of detection of the diseases which are followed by defeat of cells of a liver and detoksitsiruyushchy function of a liver, however, this method is not applicable for diagnosis of extrahepatic diseases or for detection of intra hepatic obstructive jaundice. At 32 of 141 patients who carried out BSF test the delay of BSF exceeded 5%. From 43 patients of 5 people entering into this group accepted clomifene in the dose of 50 mg recommended now. Retention of BSF usually was minimum, except for the patients who were constantly accepting clomifene throughout a long time or in cases of the diseases of a liver which are not connected with administration of drug. Results of other hepatic tests usually were normal. In a research in which patients received either placebo, or clomifene in tablets on 50 mg (for 3 days a month in a dose of 50 mg or 100 mg/days) during a 6-month course of treatment of BSF the test was carried out at 94 patients. The results indicating more than 5% BSF delay were received at 11 patients, 6 of which accepted clomifene, and 5 – placebo. In other research it was reported that at one patient accepting tablet clomifene in a dose of 50 mg/days for the 19th day of treatment the jaundice developed. The biopsy of a liver revealed a cholestasia without symptoms of hepatitis. Disturbances from exchange the veshchestvgipertriglitseridemiya (in certain cases with pancreatitis) was observed at the patients who were suffering or having a gipertriglitseridemiya in the family anamnesis, and/or accepting clomifene throughout a span or in the doses exceeding recommended.
Contraindications – hypersensitivity to active or to excipient of drug – abnormal liver functions or their existence in the anamnesis – an oothecoma (except for a syndrome of a polycystosis of ovaries) – a metrorrhagia of not clear etiology – hormone – dependent tumors – endometriosis – disgenez ovaries, a menopause or any state at which the response to treatment – pregnancy is not expected – children’s and teenage age up to 18 years
Medicinal interactions Data on medicinal interaction of the drug Klostilbegit are absent.
Special instructions It is recommended to control function of a liver regularly. Prior to treatment the careful gynecologic inspection of the patient is necessary. Use of drug has to be under constant control of the gynecologist. The necessary level of endogenous estrogen (determined on the basis of vaginal smears, a biopsy of endometrium, determination of level of estrogen in urine or endometrial bleeding in response to progesterone) is necessary for an ovulation in response to the Klostilbegit drug treatment. The lowered estrogen level – though from the clinical point of view less favorable – does not exclude efficiency of treatment. The Klostilbegit drug treatment is not effective at primary insufficiency of a hypophysis or ovaries. The Klostilbegit drug treatment does not substitute special treatment of insufficiency of the function of ovaries caused by other reasons, for example, in diseases of a thyroid gland or adrenal glands. Giperprolaktinemiya can also be treated by other methods. In the infertility connected with low body weight, Klostilbegit is not drug of the first choice, besides, this drug does not influence the increased FSG level observed at an early menopause. The Syndrome of Hyper Stimulation of Ovaries (SHSO) there Are messages about development of SGYa when prescribing clomifene for the purpose of induction of an ovulation. At cyclic use of clomifene in certain cases SGYa developed when clomifene was combined with a gonadotrophin. Symptoms of this syndrome observed at clomifene use are: a pericardiac exudate, an anasarca, a hydrothorax, an acute abdomen, a renal failure, a fluid lungs, hemorrhage in ovary tissue, a deep vein thrombosis, twisting of an ovary and acute respiratory insufficiency. At conception the fast progressing of a severe form of a syndrome can begin. For the purpose of prevention of danger of possible increase in ovaries at the Klostilbegit drug treatment, it is necessary to apply the lowest doses sufficient for achievement of good treatment outcome. Patients should be warned that in case of development of pain in a stomach or in the field of bodies of a small pelvis, at increase in body weight, feeling sick or a meteorism after reception of tablets Klostilbegit, it is necessary to tell the doctor. In several days after Klostilbegit’s cancellation, further increase in ovaries does not happen. Patients with polycystic ovaries with hypersensitivity on a gonadotrophin, can have also the increased reaction to usually recommended Klostilbegit’s doses. Patients with complaints to pains in a stomach or in the field of bodies of a small pelvis, on increase in body weight, feeling sick or a meteorism after reception of tablets Klostilbegit, it is necessary to examine concerning a possible oothecoma or other pathological changes. Owing to the increased vulnerability patholologically of the increased ovaries, inspection of area of a stomach and a basin should be carried out with exclusive care. At pathological increase in ovaries of Klostilbegit it is impossible to appoint until the sizes of ovaries do not reach initial (those prior to treatment). Increase and cysts of ovaries against the background of treatment by clomifene are usually spontaneously normalized in several days or weeks after drug withdrawal. Most of patients can carry out conservative therapy. In the following cycle of treatment the dose or duration of a cycle should be reduced. Change from body a zreniyapatsiyentok should be prevented about possible development of blurring of sight or a disorder of vision like a dot or ophthalmic migraine. These disturbances can develop in time or soon after the end of Klostilbegit drug treatment. Usually, these changes have reversible character though there were messages about long disorders of vision after the end of treatment by clomifene. The disorder of vision can have also irreversible character, especially at use of clomifene in high doses or at its appointment during the long span. The mechanism of such disorders of vision is not known. At complaints to any disorder of vision treatment it is necessary to cancel and consult immediately with the ophthalmologist. Patsiyentov it is necessary to warn that owing to possible disorders of vision there can be a danger at control of vehicles and work with mechanisms, especially under unequal light working conditions. Gipertriglitseridemiyav the post-registration period it was reported about gipertriglitseridemiya cases at the patients accepting clomifene. Risk of development of a gipertriglitseridemiya increases at the patients who were suffering or having a gipertriglitseridemiya in the family anamnesis, and/or accepting clomifene throughout longer span or in the doses exceeding recommended. At such patients it is regularly recommended to determine the level of triglycerides in blood plasma. Polycarpous beremennostpr conception against the background of treatment by clomifene the probability of polycarpous pregnancy increases. Patients should be warned about the possible complications and risks connected with polycarpous pregnancy. Ectopic beremennostpr conception against the background of treatment by clomifene in some cases the extrauterine pregnancy developed (in ovaries or pipe). There are messages about cases of polycarpous pregnancy at which was inside – and an extrauterine pregnancy. Myoma the matkiobsledovaniye of the patients with a hysteromyoma receiving Klostilbegit should be carried out with care in connection with the possible further growth of myoma.Loss of pregnancy and inborn defektypo to literary data, the average frequency of emergence of congenital defects at mothers receiving clomifene (to or after conception) does not differ from that, observed in average population of comparison. It is specified in the cases published in literature (spontaneous messages) that at induction of an ovulation clomifene among congenital defects of development defects of development of a neurotubule meet more often, however, researches at the population level do not confirm these observations. To doctors it is necessary to inform in a form, available to patients, them on the possible danger and risks connected both with natural pregnancy and at its induction by means of clomifene. Patients should be informed that some factors and states can become risk factors for their pregnancy. Treat such factors: age of the woman and man, the previous spontaneous abortions, a genotype of Rh, disturbance of a menstrual cycle and disturbance of reproductive function (irrespective of the reason) in the anamnesis, organic heart diseases, diabetes, causative agents of infections (for example, a rubella), presence of congenital defects in family and other risk factors. On the basis of results of inspection of patients, genetic inspection can be shown them. Results of population researches about possible increase in risk of developing a Down syndrome at induction of an ovulation and about increase in frequency of a trisomy among spontaneous abortions of the women with the lowered fertility receiving medicines for induction of an ovulation were published (any patient did not receive monotherapy by clomifene without the additional inducing drugs). However the number of messages still are not enough to confirm or disprove the increased risk. This issue can be resolved by means of amniocentesis which is carried out according to usual indications (age, the family anamnesis). In clinical trials of monocarpic or polycarpous pregnancy at the patients receiving clomifene it was established: loss of a fruit – 21.4% (frequency of abortions of 19%), ectopic pregnancy – 1.18%, molar pregnancy – 0.17%, a fruit paper (fetus papyraceous) – 0.04%, pregnancies with one or several still births – 1.01%. In clinical trials clomifene was applied after conception in 158 cases from 2369 pregnancies which ended with childbirth. From these 158 pregnancies 8 newborns (from 7 pregnancies) had congenital defects. Differences in the frequency of congenital defects at patients to whom clomifene was appointed till 19 in the afternoon after conception or between the 20th and 35th days after conception were not revealed. This frequency corresponds to the expected frequency interval at the general population level. Cancer rare messages about development of cancer of ovary at use of the drugs improving fertility yaichnikaimetsya. Primary risk factor is disturbance of fertility. Epidemiological data specify that prolonged use of Klostilbegit can increase this risk. Thus, it is not necessary to exceed the recommended treatment duration. The LaktozaKazhdyy tablet Klostilbegit contains 100 mg of lactose. It should be considered when prescribing drug to patients with a lactose intolerance. In rare hereditary diseases, including persons with intolerance of fructose, deficiency of Lapp-lactases enzyme and malabsorption of glucose galactose cannot use drug. Pregnancy and the period of a laktatsiipra pregnancy confirmation administration of drug of Klostilbegit should be cancelled. Klostilbegit it is allocated with breast milk therefore its use in the period of a lactation demands careful risk analysis and advantage. In avoidance of inadvertent appointment of Klostilbegit at early stages of pregnancy, during each cycle of treatment the existence of an ovulation should be defined by the corresponding tests. Before each new course of treatment the drug Klostilbegit it is necessary to carry out the test for pregnancy.Features of influence of medicine on ability to run the vehicle and potentially dangerous mekhanizmamiv bonds with passing disorders of vision in an initiation of treatment drug, driving and other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions, in particular, at the changing intensity of lighting is not recommended.
PeredozirovkaSimptoma: nausea, vomiting, vasomotorial inflows, a disorder of vision (decrease in visual acuity, light flash, scotoma), increase in ovaries and pain in pelvic or belly bodies. Treatment: after drug withdrawal the symptomatic treatment is recommended. There are no data on possible removal of drug by means of dialysis.
A form of release and upakovkapo 10 tablets in a bottle from brown glass the corked PE FG7 cover with control of the first opening and supplied with the shock-absorber accordion. On a bottle paste the label self-adhesive. On 1 bottle together with the instruction for medical use in the state and Russian languages place in a cardboard pack.
Conditions to hraneniyakhranit at a temperature from 15 °C up to 25 °S.Hranit out of children’s reach!
hraneniya5 to the leena to use term after an expiration date.
Prescription status from aptekpo
to ProizvoditelZAO’s prescription EGIS PHARMACEUTICAL PLANT 1106 BUDAPEST, Keresturi St., 30-38 VengriyaTelefon: (36-1) 803-5555, fax: (36-1) 803-5529
Owner registration udostovereniyazao EGIS pharmaceutical plant, Hungary
the Address of the organization accepting in the territory of the Republic of Kazakhstan claims from consumers on quality of products (goods) Representation in RK CJSC EGIS Pharmaceutical Plant 050060, Almaty, Zharokov St. of 286 G ph. + 7 (727) 247 63 34, + 7 (727) 247 63 33, fax: + 7 (727) 247 61 41, e-mail:
To Develop firstname.lastname@example.org