Norkolut tablets 5mg, No. 20

• Premenstrual syndrome;

• mammalgia;

• menstrual irregularities (including violations with a shortening of the secretory phase);

• dysfunctional uterine bleeding;

• glandular cystic hyperplasia of the endometrium;

• endometriosis;

• adenomyosis;

• cessation and prevention of lactation;

• dysfunctional uterine bleeding during menopause.

Inside. With premenstrual syndrome, mastalgia, dysmenorrhea: from 16 to 25 days of the menstrual cycle, 5-10 mg per day in combination with estrogens.

With dysfunctional uterine bleeding, cystic glandular hyperplasia of the endometrium: to stop bleeding - 5-10 mg per day for 6-12 days; to prevent bleeding - 5-10 mg per day from 16 to 25 days of the cycle for 6 months.

To stop lactation: the first 3 days - 20 mg per day, then 4 days - 15 mg each, then another 3 days - 10 mg each.

Contraception: 1.25Ц2.5 mg per day from 1Ц5 days of the menstrual cycle for 21 days (in combination with ethinyl estradiol), then a break for 7 days.

The tablets are white or off-white, round, flat, chamfered, marked 'NORCOLUT Х' on one side and '+' on the other.

1 tab.

norethisterone 5 mg

Excipients: potato starch, magnesium stearate, colloidal silicon dioxide, gelatin, talc, corn starch, lactose monohydrate.

• Puberty;

• pregnancy;

• mammary cancer;

• malignant tumors of the female genital organs;

• presence or risk of venous thromboembolism (VTE):

  • venous thromboembolism (VTE) - current or history of venous thromboembolism (while taking anticoagulants) (eg, deep vein thrombosis [DVT] or pulmonary embolism [PE]);

  • an established burdened heredity or an acquired predisposition to venous thromboembolism, for example, resistance to activated protein C (including Leiden V factor), antithrombin III deficiency, protein C or protein S deficiency;

  • extensive surgical interventions with prolonged immobilization (see the section 'Special instructions');

  • high risk of venous thromboembolism due to numerous risk factors (see section 'Special instructions').

• presence or risk of arterial thromboembolism (ATE):

  • arterial thromboembolism - present or a history of arterial thromboembolism (for example, myocardial infarction) or previous conditions (for example, angina pectoris);

  • violation of cerebral circulation - the presence of a stroke at the present time or in history, or previous conditions (for example, transient ischemic attack, TIA);

  • an established burdened heredity or an acquired predisposition to arterial thromboembolism, for example, hyperhomocysteinemia and antibodies to phospholipids (antibodies to cardiolipin, lupus anticoagulant);

  • a history of migraine with focal neurological symptoms;

  • high risk of developing arterial thromboembolism due to multiple risk factors (see section 'Special instructions') or the presence of one of the following serious risk factors

    • diabetes mellitus with vascular manifestations;

    • severe form of arterial hypertension;

    • severe form of dyslipoproteinemia.

• simultaneous use with medicinal products containing ombitasvir, paritaprevir, ritonavir and dasabuvir (see sections 'Drug interactions' and 'Special instructions');

• hereditary lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome;

• hypersensitivity to norethisterone or to any of the excipients of the drug.

With care: bronchial asthma; chronic heart failure, arterial hypertension; predisposition to thrombosis; renal failure; migraine; epilepsy, convulsive syndrome (including history); liver disease (including history); diabetes mellitus, obesity, dyslipoproteinemia; history of thrombophlebitis and / or thromboembolism; systemic lupus erythematosus; chronic inflammatory bowel disease (Crohn's disease, ulcerative colitis).

pharmachologic effect

Norethisterone is a progestogen. Promotes the transformation of the mucous membrane of the uterus from the proliferative to the secretory phase. Norethisterone inhibits the secretion of gonadotropic hormone by the pituitary gland, preventing the maturation of follicles and the onset of ovulation.

Pharmacokinetics

Suction

It is well absorbed from the gastrointestinal tract. As a result of intensive primary metabolism in the liver and in the intestinal wall, bioavailability is 50-77%. Norethisterone is characterized by a pronounced effect of the first passage through the liver.

Distribution

0.5-4 hours after taking norethisterone at a dose of 0.5 mg, 1 mg or 3 mg Cmax in blood plasma is 2-5 ng / ml, 5-10 ng / ml or 30 ng / ml, respectively. When used in combination with ethinyl estradiol, the concentration of norethisterone in the blood plasma may have higher values ??and, in the case of multiple doses, increase until an equilibrium state is reached. This is mainly due to the binding of norethisterone to SHBG and a slowdown in its metabolism.

Metabolism

The most important metabolites of norethisterone are the individual isomers of 5-alpha-dihydronorethisterone and tetrahydronorethisterone, which are excreted primarily as glucuronic acid conjugates. The reactions of conjugation of norethisterone and some of its metabolites proceed at the position of the 17-beta-hydroxyl group.

Withdrawal

The decrease in the concentration of norethisterone in the blood plasma is carried out in two phases. T1 / 2 in the first phase lasts 2.5 hours, in the final phase - 8 hours. 80% of the metabolites formed in the liver are excreted by the kidneys.

Side effect

The incidence of reported adverse reactions is defined as 'unknown' because it cannot be estimated from the available data.

From the side of metabolism: fluid retention.

From the nervous system: headache, paresthesia.

From the side of the cardiovascular system: an increased risk of developing arterial and venous thrombotic and thromboembolic complications, including myocardial infarction, stroke, transient ischemic attacks, venous thrombosis and pulmonary embolism (see the section 'Special instructions').

From the digestive system: nausea, vomiting, complaints from the gastrointestinal tract.

On the part of the genitals and mammary gland: engorgement of the mammary glands, intermenstrual bleeding.

General disorders and disorders at the injection site: increased fatigue (usually goes away on its own during treatment).

Laboratory and instrumental data: change in body weight.

If there are adverse reactions indicated in the instructions, or they are aggravated, or any other adverse reactions that are not indicated in the instructions develop, the patient should be informed about this by the doctor.

Application during pregnancy and lactation

Pregnancy

The results of large epidemiological studies have not revealed an increased risk of congenital malformations of the fetus in women who took oral contraceptives containing norethisterone before pregnancy. According to recent studies, the drug NorkolutЃ (when taken unintentionally in early pregnancy) does not have a teratogenic effect, in particular, such as the development of heart defects or anomalies in the development of the extremities.

NorkolutЃ should not be used to induce withdrawal bleeding, as a pregnancy test. The drug NorkolutЃ should not be used during pregnancy for the treatment of threatened abortion or recurrent miscarriage.

When re-prescribing sex hormone drugs, one should take into account the high risk of developing VTE in the postpartum period.

Breastfeeding period

When norethisterone is used in the postpartum period, the drug may affect lactation, reducing the quantity and quality of breast milk.

Application for violations of liver function

Care should be taken to prescribe the drug for liver diseases (in history).

Application for impaired renal function

The drug should be prescribed with caution in case of renal failure.

Application in children

Contraindicated during puberty.

special instructions

Before starting treatment, it is necessary to exclude the presence of malignant neoplasms, to conduct a preliminary thorough gynecological, oncological examination and examination of the mammary glands.

Ethinyl estradiol is an active metabolite of norethisterone, therefore, when prescribing it, you should also take into account the general precautions that must be observed when using combined hormonal contraceptives (COCs) containing ethinyl estradiol. If any of the following conditions or risk factors appear, therapy with NorkolutЃ should be discontinued immediately.

WTE

The use of any COC increases the risk of developing VTE. COCs differ in the degree of risk of VTE depending on the type of progestogens that make up them. Available data indicate that COCs containing levonorgestrel, norethisterone or norgestimate have the lowest risk of VTE. Of 10,000 women who take COCs containing levonorgestrel, norethisterone, or norgestimate, about 5-7 may develop thrombosis during the year.

When prescribing COCs, risk factors for each individual patient (especially risk factors for VTE), as well as differences in the degree of risk of VTE between drugs, should be carefully evaluated. COCs are contraindicated if the patient has any serious risk factors that put her in a high-risk group for blood clots.

In the event of symptoms characteristic of thromboembolism, treatment should be stopped immediately. Before resuming therapy, it is necessary to re-evaluate the indications for prescribing the drug.

The risk of developing VTE with the use of sex hormone drugs can be significantly increased in women with additional risk factors, in particular, with multiple risk factors.

NorkolutЃ is contraindicated in women with multiple risk factors, which cause the patient to be at high risk of developing venous thrombosis. In women with a combination of several risk factors, consideration should be given to the possibility of their mutual reinforcement, when the degree of increased risk may be higher than with a simple sum of individual factors. In such cases, the overall risk of developing VTE should be considered. If the benefit / risk ratio in the assessment turns out to be unfavorable, the appointment of NorkolutЃ should be abandoned (see the section 'Contraindications').

Commonly recognized risk factors for VTE include:

• age over 35;

• obesity (BMI over 30 kg / m2);

• a family history of venous thrombosis or thromboembolism in brothers, sisters or parents under the age of 50 (in case of a hereditary predisposition, consult a specialist before taking the drug);

• prolonged immobilization, serious surgical interventions; surgical interventions on the lower extremities, in the pelvic area; neurosurgical surgical interventions; extensive trauma. In these situations, you should stop taking COCs (in the case of a planned surgical intervention, at least 4 weeks before it) and not resume it within 2 weeks after full recovery of mobility. In the event that the administration of the drug NorkolutЃ was not discontinued in advance, the possibility of antithrombotic therapy is considered. Temporary immobilization (eg, air travel longer than 4 hours) can also be a risk factor for VTE, especially when other risk factors are present.

• any diseases associated with VTE: cancer, systemic lupus erythematosus, hemolytic uremic syndrome, chronic inflammatory bowel disease (Crohn's disease or ulcerative colitis) and sickle cell anemia.

The question of the possible role of varicose veins and superficial thrombophlebitis in the development or progression of venous thrombosis remains controversial.

Consideration should be given to the increased risk of thromboembolism during pregnancy and especially in the first 6 weeks of the postpartum period.

VTE symptoms (DVT and PE). Women should be informed that in the event of symptoms, they should seek emergency medical help and inform a healthcare professional about the use of NorkolutЃ.

DVT symptoms: unilateral swelling of the lower extremities or along a vein; pain or discomfort in the leg only when upright or when walking; local increase in temperature, redness or discoloration of the skin of the affected lower limb.

Pulmonary embolism symptoms: sudden onset of causeless shortness of breath or rapid breathing; sudden cough, incl. with hemoptysis; sharp chest pain; lightheadedness or dizziness; fast or irregular heartbeat.

Some of the symptoms listed (eg, shortness of breath, cough) are nonspecific and can be mistaken for more common or less severe illnesses (eg, respiratory tract infections).

Other signs of vascular occlusion: sudden pain, swelling and mild cyanosis of the limb.

In the case of occlusion of the eye vessels, symptoms can range from blurred vision (no pain) to vision loss (with progression of occlusion). In some cases, complete loss of vision can develop almost immediately.

ATE

Epidemiological studies show that there is a relationship between taking sex hormone drugs and an increased risk of arterial thromboembolism (myocardial infarction) or cerebrovascular accident (eg, transient cerebrovascular accident, stroke). ATE can be fatal.

Risk factors for the development of ATE. The risk of developing arterial thromboembolism or cerebrovascular accident with the use of sex hormone drugs increases in women with risk factors. The drug NorkolutЃ is contraindicated in women with one serious risk factor or multiple risk factors for the development of ATE, which cause the patient to be at high risk of developing arterial thrombosis. In women with a combination of several risk factors, the possibility of their mutual reinforcement should be considered when the degree of increased risk may be higher than with a simple sum of individual factors. In such cases, the overall risk of developing ATE should be considered. If the benefit / risk ratio in the assessment turns out to be unfavorable, the appointment of NorkolutЃ should be abandoned (see the section 'Contraindications').

The generally recognized risk factors for the development of ATE include:

• age over 35;

• smoking (women over 35 who have not quit smoking are strongly advised to choose other methods of contraception);

• arterial hypertension;

• obesity (BMI over 30 kg / m2);

• a family history of arterial thrombosis or thromboembolism in brothers, sisters or parents under the age of 50 (in case of a hereditary predisposition, consult a specialist before taking the drug);

• migraine;

• other diseases / conditions associated with adverse vascular events: diabetes mellitus, hyperhomocysteinemia, heart valve disease, atrial fibrillation, dyslipoproteinemia, systemic lupus erythematosus.

An increase in the frequency or severity of migraine during the use of sex hormone drugs (which may precede cerebrovascular disorders) is the basis for immediate discontinuation of these drugs.

ATE symptoms. A woman should be informed that in case of symptoms she should seek emergency medical help and inform a healthcare professional about the use of NorkolutЃ.

—имптомы инсульта: внезапна¤ слабость или онемение лица, руки или ноги, особенно с одной стороны тела; нарушение походки, головокружение, потер¤ равновеси¤ или координации движений; внезапна¤ спутанность сознани¤, проблемы с речью или пониманием; одно- или двухсторонн¤¤ потер¤ зрени¤; сильна¤ или продолжительна¤ головна¤ боль без видимой причины; потер¤ сознани¤ или обморок с судорожным приступом или без него. ¬ременный характер симптомов позвол¤ет предположить транзиторную ишемическую атаку (“»ј).

—имптомы инфаркта миокарда: боль, дискомфорт, давление, т¤жесть, чувство сжати¤ или распирани¤ в груди или за грудиной с иррадиацией в спину, челюсть, верхнюю конечность, область эпигастри¤; холодный пот, тошнота, рвота или головокружение; сильна¤ слабость, тревога или одышка; учащенное или нерегул¤рное сердцебиение.

ѕовышение активности јЋ“

ѕри проведении клинических исследований с участием пациенток, получающих курс терапии вирусного гепатита — (комбинацию лекарственных препаратов, содержащих омбитасвир, паритапревир, ритонавир, дасабувир в сочетании с рибавирином или без) повышение активности јЋ“ более чем в 5 раз выше ¬vЌ было зарегистрировано чаще у женщин, примен¤ющих этинилэстрадиолсодержащие препараты.

Ћабораторные исследовани¤

ѕрием половых гормонов может вли¤ть на результаты некоторых лабораторных тестов, включа¤ биохимические показатели функции печени, щитовидной железы, надпочечников и почек, концентрацию транспортных протеинов в плазме (например, транскортина, фракции липидов/липопротеидов, параметры углеводного метаболизма, коагул¤ции и фибринолиза). Ёти изменени¤, как правило, остаютс¤ в пределах нормальных физиологических значений.

¬спомогательные вещества

ѕрепарат содержит лактозы моногидрат, поэтому пациенты с редкой наследственной непереносимостью галактозы, дефицитом лактазы или нарушенным всасыванием глюкозы/галактозы не должны принимать данный препарат.

¬ли¤ние на способность к управлению транспортными средствами и механизмами

Ќорэтистерон не оказывает вли¤ни¤ на способность управл¤ть транспортными средствами и работать с механизмами.

ѕередозировка

ѕосле приема детьми младшего возраста высоких доз пероральных контрацептивов, содержащих норэтистерон, серьезные побочные эффекты не зарегистрированы.

—имптомы: при передозировке могут наблюдатьс¤ тошнота и кровотечение 'отмены' у женщин.

Ћечение: провод¤т симптоматическую терапию.

Ћекарственное взаимодействие

—пособность других лекарственных средств оказывать вли¤ние на норэтистерон

¬озможно взаимодействие с лекарственными средствами, индуцирующими микросомальные ферменты печени, в результате чего может увеличиватьс¤ клиренс половых гормонов.

»ндукци¤ ферментов может наблюдатьс¤ уже через несколько дней приема препарата. ћаксимальна¤ индукци¤ ферментов обычно наблюдаетс¤ в течение нескольких недель. ѕосле отмены препарата индукци¤ ферментов может сохран¤тьс¤ до 4 недель.

¬ещества, повышающие клиренс половых гормонов: барбитураты, бозентан, карбамазепин, фенитоин, примидон, рифампицин, препараты дл¤ лечени¤ ¬»„-инфекции (ритонавир, невирапин и эфавиренз), фелбамат, гризеофульвин, окскарбазепин, топирамат и препараты, содержащие зверобой продыр¤вленный (Hypericum perforatum).

¬ещества с различным вли¤нием на клиренс половых гормонов

ѕри совместном применении с препаратом многие ингибиторы протеазы ¬»„ и ненуклеозидных ингибиторов обратной транскриптазы, включа¤ ингибиторы протеазы вируса гепатита C, могут увеличивать или уменьшать концентрацию эстрогенов или прогестагенов в плазме крови. ќбщий эффект таких изменений может быть в некоторых случа¤х клинически значимым.

?л¤ вы¤влени¤ возможного лекарственного взаимодействи¤ и св¤занных с этим рекомендаций следует проводить анализ информации, представленной в инструкци¤х по медицинскому применению сопутствующих препаратов, предназначенных дл¤ лечени¤ ¬»„-инфекции/гепатита —, при их одновременном применении с препаратами половых гормонов.

—пособность норэтистерона оказывать вли¤ние на другие лекарственные средства

Sex hormones can affect the metabolism of some other drugs, which leads to an increase (for example, cyclosporine) or a decrease (for example, lamotrigine) their concentration in blood plasma and tissues.

Pharmacodynamic interaction

The concomitant use of norethisterone and medicines containing ombitasvir / paritaprevir / ritonavir and dasabuvir, in combination with or without ribavirin, is associated with an increase in ALT activity (see sections 'Contraindications' and 'Special instructions').