active substance: norethisterone acetate;
1 tablet contains 5 mg of norethisterone acetate
auxiliary substances: lactose, corn starch, povidone 25000, talc, magnesium stearate. Dosage form. Tablets.
Basic physical and chemical properties: tablets of white color with cross-shaped notch on one side and "AR" in a regular hexagon on the other.
Hormones of sexual glands and the preparations, used with the pathology of the sexual sphere. Gestagen.
Code ATX. G03D C02.
Norethisterone is a progestogen. In women who are sensitive to estrogen, with a course oral intake of 100-150 mg of norethisterone during one menstrual cycle, it is possible to achieve a continuous change in the endometrium, that is, from proliferative to secretive state.
The secretion of gonadotropins and anovulation, it inhibits with a daily intake of 0.5 mg of norethisterone acetate.
Norethisterone is a Pyrogenic substance and affects the base temperature of the body.
Norethisterone acetate (Aneta) during absorption and the first passage through the liver is hydrolyzed into norethisterone, the active ingredient of the drug, and acetic acid. The highest concentration of norethisterone in plasma is 18 ng/ml (after 5 mg Anet) and 25 ng/ml (after 10 mg Anet). These figures are achieved after 2:00 after ingestion of one tablet Primolut-holes. According to the study of relative bioavailability, the active substance is completely released from the tablet.
Norethisterone is associated with blood plasma proteins and globulin, linking sex hormones (SHBG). Only about 3-4% of the total concentration of the active substance in blood plasma is in the form of a free steroid, about 35% binds to gspg, and 61% binds to albumin. The volume of distribution of norethisterone is 4.4 ± 1.3 l/kg. After administration, the distribution of levels of active substance in blood plasma is biphasic. The half-life in plasma for the first and second phases is 1-3 hours and 5-13 hours, respectively.
Conditions for maintaining a stable state:
With multiple daily intake of norethisterone accumulation of this substance is unlikely due to a relatively short period of blood half-life. However, if the daily also accepted substances-inductors SHBG, such as ethinyl estradiol, can occur increasing the concentration of norethisterone in the blood plasma due to its binding to SHBG.
Norethisterone is metabolized mainly by saturating the double bond of ring a and reducing the 3-keto group to the hydroxyl group, followed by binding to the appropriate sulfates and glucoronides. Some of the metabolites are excreted from the blood plasma very slowly, their half-life in the blood plasma is about 67 hours. Therefore, during long-term treatment with daily oral administration of norethisterone, some of the metabolites accumulate in the blood plasma.
Norethisterone is metabolized in part into ethinyl estradiol, that is, with each mg of norethisterone that is taken orally, the amount of ethinyl estradiol is formed, equal to the oral dose for humans at about 4 µg.
Norethisterone is not excreted unchanged to a significant amount. Mainly metabolites with shortened ring a and hydroxylates, as well as their compounds (glucuronides and sulfates) are excreted in urine and feces in the proportion of 7: 3. A large part of the metabolites excreted by the kidneys is excreted in about 24 hours, the period of their half-life in plasma is approximately 19 hours.
Norethisterone passes into breast milk. The concentration of this substance in milk is about 10% of the plasma parameters of the mother regardless of the method of reception. Taking into account that on average the maximum level of active substance in the blood plasma of the mother is 16 ng/ml, and the daily feeding volume is about 600 ml of milk, the child can get a maximum of about 1 µg of this substance (0.02% of the mother's dose).
Secondary amenorrhea, and endometriosis.
You should not use the drug Primolut-nor under any of the conditions or illnesses listed below. If one of them will appear during treatment Primolut Nord, the drug should be discontinued immediately.
Pregnancy or suspicion on it.
Venous or arterial thrombotic/thromboembolic events (e.g. myocardial infarction, stroke, transient ischemic attack, deep vein thrombosis, pulmonary thromboembolism) in history.
The presence of currently or in the history of precursors of thrombosis (eg transient ischemic attack, angina pectoris).
The presence of high-risk factors of arterial thrombosis (see Section "Peculiarities of use").
Diabetes mellitus with vascular complications.
Severe liver disease now or in the past until liver function indicators are normalized.
Dubin-Johnson syndrome, Rotor syndrome, and jaundice or cases of severe itching during previous pregnancies.
Previous cases of pemphigoid pregnant (herpes pregnant).
Benign or malignant liver tumors at present or in the past.
Malignant tumors, dependent on the influence of sex hormones, or suspicion of their presence.
Hypersensitivity to norethisterone or to any of the auxiliary components of the drug.
Migraine with focal neurological symptoms in history.
History of idiopathic jaundice or severe itching during pregnancy.
Vaginal bleeding of unknown etiology.
Untreated endometrial hyperplasia.
Interaction with other medicinal products and other forms of interaction
Interaction with other drugs that lead to an increase in the clearance of sex hormones can lead to a decrease in the therapeutic efficacy of the drug. This effect is observed in many drugs-inducers of liver enzymes (such as phenytoin, barbiturates, primidone, carbamazepine, rifampicin, oxcarbazepine, St. John's wort and rifabutin). There is a suspicion of such an effect and griseofulvin.
The progestogen may affect the metabolism of other drugs. As a result, the concentration of these drugs (eg, cyclosporine) in blood plasma and tissues may vary.
Note: you should read the instructions for the use of drugs taken at the same time to identify possible interactions.
Data were obtained on the effect of combined oral contraceptives (CPC) on laboratory test results, including biochemical parameters of liver function, thyroid gland, coagulation.
To prevent pregnancy, it is necessary to use non-hormonal methods of contraception (barrier).
Before you start or continue treatment with Primolut-nor, should conduct an individual assessment of risk/benefit, or worse if there are any abnormalities/risk factors that will be described below.
Based on epidemiological studies, it was found that oral administration of ovulation inhibitors containing estrogens/progestagens leads to an increase in cases of thromboembolic disorders. Therefore, it is necessary to consider the possibility of increasing the risk of thromboembolism, primarily in the presence of such diseases in the history.
Generally recognized risk factors for venous thromboembolism (VTE) are: personal or family history of the disease (VTE in a brother/sister or one of the parents at a relatively early age), age, obesity, prolonged immobilization, extensive surgery, severe injuries.
You should consider the increased risk of thromboembolism in the postpartum period.
You should immediately stop the treatment if you have symptoms of arterial or venous thrombosis or suspected him.
Patients with a history of VTE or known thromboembolic condition, have an increased risk of developing VTE. Treatment with steroid hormones can increase this risk. Patients with personal or family history of thromboembolism or recurrent spontaneous abortions should be investigated to rule out the tendency to thromboembolism. Patients who used anticoagulant therapy should be carefully evaluated for tromboembolica risks before starting treatment with a progestogen. With prolonged immobilization, routine surgery, especially in the abdominal area, orthopedic surgery on the lower extremities, it is necessary to stop therapy with progestins 4-6 weeks before the operation. Continuation of treatment with a progestogen is possible only after full recovery of motor mode.
Described isolated cases benign liver tumours and even more rarely - malignant tumors in patients receiving such hormonal substances that are included Primolut-holes. In some cases, these tumours led to life-threatening intra-abdominal bleeding.
In women taking COC, in rare cases, benign liver tumors and very rarely malignant liver tumors have been reported. In rare cases, these tumors lead to intra-abdominal bleeding that was life threatening. If women attribuut PDA, there is severe pain in the upper abdomen are signs of liver enlargement or signs of intraabdominal bleeding, it is necessary to differentiate a tumor of the liver.
Patients with diabetes should be under a doctor's supervision.
In rare cases, chloasma may occur, especially in women with a history of chloasma during pregnancy. Women prone to the appearance chloasma, should avoid staying in the sun or under ultraviolet rays while taking Primolut-holes.
In case of acute visual impairment, exophthalmos, diplopia or migraine, edema of the optic nerve disc or retinal lesions should be excluded.
The progestogen can cause fluid retention. Used with caution in patients with epilepsy, migraine, asthma, cardiac dysfunction.
When using CPC in women with hypertriglyceridemia or with its presence in the family history, an increased risk of pancreatitis is possible.
Patients with a history of depression should be closely monitored by doctors. It is necessary to stop taking the drug if the depression progresses.
Medical examination, physical examination and doctor's consultation
Before the start or resumption of treatment Primolut-nor the woman ought to undergo a full medical examination, including a pelvic exam: please note contraindications and application features of the drug. Research must be repeated periodically during treatment drug Primolut-holes. The frequency and type of these studies depend on the individual characteristics of each woman, but they must necessarily include measurement of blood pressure, study of mammary glands, abdominal and pelvic organs, as well as cytological examination of the cervix.
The reasons for the immediate cessation of treatment.
The primary onset of severe headache and migraine or increased frequency of unusually severe headaches, sudden perceptual disorders, first signs of thrombophlebitis or thromboembolic symptoms, feeling of pain and compression in the chest, a planned surgical intervention (6 weeks before surgery), immobilization, appearance of jaundice, development of hepatitis (nectarinia), generalized itching, significant increase in blood pressure, pregnancy.
Influence on the results of laboratory research methods.
Receiving a progestogen can affect the results of certain laboratory methods doslidzhennya.
Additional reservations based on the partial conversion of norethisterone to ethinyl estradiol.
Epidemiological studies have shown that the incidence of VTE in patients taking oral contraceptives with a low content of estrogen (
The risk of VTE is the highest during the 1st year of use. This increased risk is observed after the first time or repeatedly (after 4 weeks or more of a break in admission) began receiving CPC. VTE can be life-threatening and can be fatal (in 1-2% of cases).
VTE, which is manifested by deep vein thrombosis and/or pulmonary embolism, may occur when taking any of the CCP.
Thrombosis of other blood vessels, such as arteries and veins of the liver, kidneys, mesenteric vessels, veins and arteries of the brain or retina in women using CPC, has rarely been reported.
Common signs/symptoms of VTE include:
severe pain in the Shin area of one leg swelling in lower leg
sudden shortness of breath;
pain in the chest.
In General, CPC is associated with an increased risk of acute myocardial infarction (AMR) or stroke, such risk is largely associated with the presence of other risk factors (see Below).
Common signs/symptoms associated with arterial thromboembolism include:
sudden severe chest pain with possible radiating to the left arm;
a sudden fit of coughing;
any unusual, severe and prolonged headache, especially if it occurs for the first time or worsens, or is associated with sudden partial or total loss of vision/bifurcation in the eyes, aphasia, dizziness, collapse with or without focal epilepsy
weakness, sudden numbness of one side or part of the body;
Risk factors for thromboembolic complications:
obesity (body mass index over 30 kg/m2 );
relevant family history (i.e., the presence of brothers, sisters or parents of venous or arterial thromboembolism at a relatively early age). If there is a suspicion of hereditary predisposition, the woman should be referred to the appropriate specialist for consultation before deciding on the application of CPC.
prolonged immobilization, large surgery, any surgery on the lower extremities or extensive trauma. In these situations, it is advisable to stop using CPC (with planned surgery at least 4 weeks before the intervention) and do not resume taking the drug before remobilization;
Smoking (with intensive Smoking and with age, the risk increases, especially in women over 35 years);
migraine (an increase in the frequency and severity of migraine during the use of the CPC may be prolonged by the phenomena of cerebral circulation disorders and, therefore, is the basis for the immediate cessation of CPC administration).
pathology of heart valves
Other conditions associated with unwanted effects from the circulatory system include diabetes mellitus, systemic lupus erythematosus, hemolytic uremic syndrome, chronic inflammatory bowel disease (Crohn's disease and ulcerative colitis) and sickle cell anemia.
Biochemical factors that may indicate hereditary or acquired predisposition for venous or arterial thrombosis include resistance to activated protein C (APC), hyperhomocysteinemia, deficiency of antithrombin III, deficiency of protein C, deficiency protein S, antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant ).
The most important risk factor for development of cervical cancer is persistence of human papillomavirus infection (HPV). Some epidemiological studies have shown that prolonged use of PDAs may increase the risk.
A meta-analysis of 54 epidemiological studies indicate a slight increase in the relative risk (RR = 1,24) of developing breast cancer in women who use PDAs. This increased risk gradually disappears during the 10 years after stopping use of PDAs. Because breast cancer in women is younger
40 years is rare, the increase in the incidence of breast cancer in women currently applying or recently applied CPC is negligible compared to the overall risk of breast cancer. The results of these studies do not provide evidence of the existence of a causal relationship. The revealed increased risk may be due to earlier diagnosis of breast cancer in women who use PDAs, and biological effects of a PDA or a combination of both factors. Observed that breast cancer detected in women ever had to a PDA, as a rule, clinically less pronounced, than those who have never used a PDA.
Although it was reported a slight increase in blood pressure in many women, taking a PDA clinically significant improvement are rare. However, if during reception of a PDA develops persistent clinically significant arterial hypertension, the physician should cancel the CCP and begin the treatment of hypertension. If normal blood pressure is reached after antihypertensive therapy, the administration of CPC can be restored if it is considered appropriate.
There have been reports of the occurrence or exacerbation of the following diseases during pregnancy and in the application of CPC, but their relationship with CPC has not been fully proven::
jaundice and/or itching associated with cholestasis;
formation of gallstones;
systemic lupus erythematosus,
hearing loss associated with otosclerosis.
In women with hereditary angioedema exogenous estrogens may induce or exacerbate symptoms of the disease.
Acute or chronic disturbances of liver function may require the suspension of admission of the CCP to the normalization of indicators of liver function. Relapse of cholestatic jaundice, first manifested during pregnancy or previous administration of sex steroids, requires cessation of CPC. Crohn's disease and ulcerative colitis are associated with intake of PDA.
Warnings about auxiliary substance.
This medicinal product contains lactose. Patients with hereditary forms of galactose intolerance, Lapp lactase deficiency (insufficiency observed in some settlements of Lapland) or poor absorption of glucose or galactose should not use this drug.
Application during pregnancy and lactation
Studies of reproductive toxicity have shown the risk of virilization of female embryos when taking high doses in the development of external genitals. In addition, epidemiological studies have shown that when taking high doses, this risk is quite significant in humans. Primolut-nor can cause virilization of female fetuses if taken during the period of somatic sexual differentiation, characterized by a sensitivity to hormones (starting from the 45th day of pregnancy). In addition to the above, no other signs of teratogenic influence were obtained as a result of studies.
Primolut-nor cannot be taken by women during pregnancy and lactation (see "Contraindications" ).
The ability to influence the reaction rate when driving motor transport or operating other mechanisms
There has been no effect of the drug on the ability to drive or operate machinery.
Method of application and doses
To prevent pregnancy, it is necessary to use non-hormonal methods of contraception (barrier).
· Secondary amenorrhea.
Hormonal treatment of secondary amenorrhea can be carried out only after the exclusion of pregnancy.
Before starting the treatment of secondary amenorrhea, the presence of a tumor of the pituitary gland that releases prolactin should be excluded. It is impossible to exclude that macroadenomas increase in size under the influence of high doses of estrogens for a long period of time.
Prior to use of the drug Primolut-nor it is necessary to prepare the endometrium with estrogen (for example within 14 days). Then take 1-2 tablets Primolut-nor within 10 days. Withdrawal bleeding begins a few days after taking the last pill.
When sufficient production of estrogen by the body can try to stop the estrogen treatment and to induce cyclical bleeding by the application of 1 tablet Primolut-nor 2 times a day with 16 for 25 day of a cycle.
The treatment begins between the 1st and 5th day of the cycle for the drug Primolut Nord is 1 tablet 2 times a day. In the case of bleeding, it is necessary to increase the dose and take 2 times daily 2 tablets of the drug Primolut-holes. After the bleeding has stopped you can reduce the dose to the initial one. The duration of treatment is at least 4-6 months. With continuous daily use of the drug ovulation and menstruation are absent.
Method of application.
Tablets are taken by drinking a small amount of liquid without chewing.
Do not use this medicine in children.
Studies of acute toxicity showed the risk of acute adverse reactions if you accidentally taking the drug in doses several times higher than daily therapeutic dose.
Adverse reactions often occur in the first months of taking the drug Primolut-holes. Over time, their number decreases. The following describes adverse reactions in patients taking Primolut-holes. However, a causal relationship could not always be confirmed.
The following table lists adverse reactions according to the classification of System Organ Class (MedDRA SOCs). Adverse reactions are presented in the order of reducing the severity within each indicator. Data on the frequency of adverse reactions is based on post-marketing studies and scientific literature.
System Organ Grader often (?1/10)often (?1/100, <1/10) Infrequently (?1/1000, <1/100)single
The immune system Reaction Hyper-sensitivity
From the nervous system Headache
From the organs of vision visual impairment
The respiratory system, organs of the mediastinum and chest shortness of breath
The gastro-intestinal tract nausea
From the skin and subcutaneous tissue urticaria,
Reproductive system and mammary glands/
vaginal bleeding, including spotting *.
Moderate menstruation (hypomenorrhea *)amenorrhea *
Violation of the General condition and condition at the place of injection of edema
* When endometriosis
To describe a certain reaction and its symptoms and related disorders was used the corresponding MedDRA terms.
The frequency is unknown (cannot be determined from the available data) (See details in the "application Details" section»):
liver tumors that lead to intra-abdominal bleeding,
severe headache and migraine or an increase in the frequency of unusually severe migraine sudden perception disorders; first signs of thrombophlebitis or symptoms of thromboembolism pain and compression in the chest appearance of jaundice, the development of hepatitis, itching of the skin, a significant increase in blood pressure.
Dizziness, increased depression, abdominal pain, and cholestasis were also observed.
Very high doses Primolut-nor can in some cases lead to cholestatic disorders of the liver.
Store at a temperature not exceeding 30 ° C out of reach of children.
10 tablets per blister, 6 blisters in a carton box.
Category home away from home
Bayer Weimar GmbH & Co. KG, Germany/Bayer Weimar GmbH & Ko. KG, Germany.
Manufacturer's location and address of the place of business
Dobrinishte 20 99427 Weimar, Germany/Dobereinerstasse 20 99427 Weimar, Germany
PRIMOLUT-NOR TABLETS 5 MG
The drug is used in pathological diseases of the sexual system in women.
Indications for the use of the drug
Primolut-nor effective in:
Cyclically recurring symptoms of premenstrual syndrome, which is characterized by mental instability and disappears after the onset of menstruation.
Formation of the risk of miscarriage.
Established infertility when for 2 years the woman has no approach of pregnancy.
Pain (algomenorrhea), accompanying the rejection of the endometrium during menstruation.
The absence of menstruation for 6 months or more.
Abnormal growths of the endometrium (endometriosis).
Changes in the structure of the breast (mastopathy).
It is necessary to stop or prevent lactation.
The pathologic course of the process of restructuring the female body into menopause (menopause).
Features of the use of the drug
Primolut Nord is prescribed by a doctor gynecologist after laboratory and clinical studies of the patient.
When missing the next dose should be taken as soon as possible. The drug can be used as a contraception medication.