Instruction for use: MODEL PIUR

Active substance: Cyproterone + Ethinylestradiol

ATX code G03HB01 Cyproterone and estrogen

Pharmacological group

Androgens, antiandrogens in combinations

Nosological classification (ICD-10)

L21 Seborrheic dermatitis

Dermatitis seborrheic, Increased sebum separation, Seborrheic Eczema, Seborrheic dermatitis of the scalp, Seborrheic pyodermatitis, Seborrhea, Eczema seborrheic

L64 Androgenic alopecia

Alopecia androgenic, Androgenetic alopecia, Androgenic alopecia of moderate severity, Severe Androgen-Dependent Alopecia, Male pattern hair loss

L68.0 Hirsutism

Pathological hair body and body

L70 Acne

Acne nodulocystica, Acne, Comedone acne, Acne Treatment, Papulous pustular acne, Papulopustulicular acne, Papulo-pustular acne, Acne, Acne Disease, Acne, Acne vulgaris, Nodular-cystic acne, Nodular-cystic acne

Z30 Monitoring contraceptive use

Local Contraception, Contraception oral, Local contraception, Episodic prevention of pregnancy, Hormonal Contraception, Contraception, Prevention of Pregnancy, Prevention of unwanted pregnancy, Contraceptive intrauterine, Contraception in women with androgenization phenomena, Installation and removal of the intrauterine device, Prevention of pregnancy (contraception)

Z30.0 General advice and advice on contraception

Safe sex, Intrauterine device contraception, Contraception, Contraceptive intrauterine, Oral contraception, Oral contraception during lactation and with estrogen contraindications, Postcoital contraception, Prevention of Pregnancy, Prevention of unwanted pregnancy, Emergency Contraception, Episodic prevention of pregnancy, Contraception in adolescents, Prevention of pregnancy (contraception)

Composition

Tablets, coated with a film membrane 1 tab.

Active substances:

Ethinyl estradiol micronized 35 μg

Cyproterone acetate micronized 2 mg

Auxiliary substances: lactose monohydrate - 29,115 mg; Corn starch - 20 mg; Povidone K25 - 2,1 mg; Talc - 1.65 mg; Magnesium stearate - 100 μg

Membrane film: sucrose - 19.637 mg; Calcium carbonate - 8,402 mg; Talc - 4.095 mg; Titanium dioxide - 278 μg; Povidone K90 - 200 mcg; Macrogol 6000 - 2,178 mg; Glycerol 85% - 139 μg; Dye iron oxide - 27 mcg; Wax glycolic mountain - 44 mcg

Description of dosage form

The tablets covered with a film cover: yellow color, round, biconcave.

pharmachologic effect

Pharmacological action - contraceptive, antiandrogenic, estrogenic.

Pharmacodynamics

Combined low-dose monophasic oral contraceptive with anti-androgenic activity. The mechanism of action is due to its anti-androgenic steroid compound - cyproterone acetate - and oral estrogen - ethinyl estradiol. It blocks the androgen receptors, inhibits the pituitary secretion of gonadotropic hormones.

Cyproterone has the ability to competitively bind to receptors of natural androgens (including testosterone, dihydroepiandrosterone, androstenedione), formed in small amounts in the body of women, mainly in the adrenal glands, ovaries and skin. Blocking the androgen receptors in target organs, reduces the phenomenon of androgenization in women (due to disruption of processes mediated by hormone-receptor complexes at the level of the main intracellular mechanisms). Along with anti-androgenic properties, it possesses gestagenic activity that mimics the properties of the hormone of the yellow body. Oppresses the secretion of the pituitary gland by gonadotropic hormones and inhibits ovulation, which determines its contraceptive effect.

Ethinyl estradiol strengthens the central and peripheral effects of cyproterone on ovulation, retains a high viscosity of the cervical mucus, which makes it difficult to penetrate the spermatozoon into the uterine cavity and helps to ensure a reliable contraceptive effect.

Pharmacokinetics

Cyproterone acetate

Suction. Completely absorbed after ingestion. Cmax in the blood serum is achieved 1.6 hours after taking 1 table. Of the preparation Modell Pure and is 15 ng / ml. Bioavailability - 88%.

Distribution. Almost completely binds to blood plasma proteins (albumin). During the course of treatment, cumulation of the drug is observed: serum concentration increases from 15 ng / ml on the 1st day of treatment to 21 ng / ml at the end of the 1st cycle and up to 24 ng / ml at the end of the third cycle of treatment. The AUC increases 2.2 times (the end of the 1st cycle) and 2.4 times (the end of the third cycle). Css is created approximately 16 days after the start of treatment.

Metabolised in the liver through various reactions, including. Hydroxylation and conjugation.

The main metabolite is 15-hydroxyciproterone.

Excretion. The pharmacokinetics of cyproterone acetate are two-phase, T1 / 2 is 0.8 h and 2.3 days, respectively, for the first and second phases. The total plasma clearance is 3.6 ml / min / kg. The main part of the administered dose is excreted in the urine in the form of metabolites, the remaining part - with bile in unchanged form. T1 / 2 is 1.9 days.

Ethinylestradiol

Suction. After ingestion, ethinylestradiol is rapidly and completely absorbed. Cmax in the blood serum is achieved 1.7 hours after taking 1 table. Of the Modell-Puri preparation is 80 pg / ml. It is affected by the effect of the first passage through the liver, which leads to a decrease in bioavailability.

Distribution. The apparent Vd is 5 l / kg. Virtually completely binds to plasma proteins. Css is created 3-4 days after the start of treatment.

Excretion. The pharmacokinetics of ethinyl estradiol is two-phase, T1 / 2 is 1-2 hours and 20 hours for the first and second phases, respectively. Plasma clearance - 5 ml / min / kg. It is excreted as metabolites through the intestine and kidneys in a ratio of 4: 6, T1 / 2 is about 24 hours.

Indications

Contraception in women with androgenization phenomena;

Treatment of androgen-dependent diseases / conditions in women:

- vulgar acne (papular-pustular acne, nodular-cystic acne);

- seborrhea;

- Androgenic alopecia;

- Hirsutism.

Contraindications

Hypersensitivity to any of the components of the drug;

Thrombosis (venous and arterial) and thromboembolism now or in history (including deep vein thrombosis, pulmonary embolism, pulmonary embolism), coronary heart disease, stroke;

Conditions preceding thrombosis (including transient ischemic attacks, angina pectoris) at present or in the anamnesis;

Complicated heart valve apparatus lesions (pulmonary hypertension, atrial fibrillation, subacute bacterial endocarditis in the anamnesis);

Uncontrolled arterial hypertension (SAD above 160 mmHg or DAD above 100 mmHg);

Serious surgical intervention with prolonged immobilization;

Diabetes mellitus with vascular complications;

multiple or severe venous or arterial thrombosis risk factors, including Diseases of the vessels of the brain or coronary arteries, arterial hypertension, not middle-aged;

Hepatic insufficiency and severe liver disease (before normalization of liver samples);

Active viral hepatitis, cirrhosis of the liver in the stage of decompensation;

idiopathic jaundice or pruritus during pregnancy in history;

Congenital hyperbilirubinemia (syndromes Gilbert, Dubin-Johnson and Rotor);

Liver tumors (benign or malignant) at present or in the anamnesis;

Migraine with focal neurologic symptoms at present or in the anamnesis;

Pancreatitis with severe hypertriglyceridemia at present or in the anamnesis;

Identified hormone-dependent malignant diseases (including breast and endometrial cancer) or suspected of them;

Bleeding from the vagina of unknown origin;

Sickle-cell anemia;

otosclerosis with deterioration during pregnancy;

Herpes of pregnant women in the anamnesis;

Smoking over the age of 35;

pregnancy;

lactation /

With caution, the potential risk and the expected benefit of using COCs in each case should be carefully weighed in the presence of the following diseases / conditions and risk factors: risk factors for thrombosis (smoking, obesity, dyslipoproteinemia, arterial hypertension, migraine, valvular heart defects, prolonged immobilization, Serious surgical interventions, extensive trauma, hereditary predisposition to thrombosis - thrombosis, blood clotting disorders, myocardial infarction or cerebral infarction rashchenija at a young age, someone from the next of kin); Diseases in which there may be violations of peripheral circulation - diabetes mellitus (or predisposition to diabetes mellitus, for example unexplained glucosuria), systemic lupus erythematosus, renal dysfunction, hemolytic uremic syndrome, Crohn's disease and ulcerative colitis (NNC), varicose veins , Phlebitis of superficial veins; Hypertriglyceridemia; Liver disease; Breast cancer in a family history, or a benign breast tumor in a personal anamnesis; Diagnosed depression in anamnesis; Uterine myoma; cholelithiasis; Intolerance to contact lenses; Diseases that first appeared or worsened during pregnancy or on the background of previous reception of sex hormones (eg jaundice and / or itching associated with cholestasis, cholelithiasis, Sydenham's chorea, chloasma).

pregnancy and lactation

The use of the drug is contraindicated in pregnancy and lactation.

Side effects

All women taking COC are at increased risk of thrombosis and thromboembolism, some increased risk of developing and worsening the course of other diseases.

When taking COC, irregular (acyclic) bleeding from the vagina (spotting bleeding or breakthrough bleeding) can occur, especially during the first months of use. Determination of the frequency of undesired reactions: often (> 1/100 and <1/10); Infrequently (> 1/1000 and <1/100); Rarely (> 1/10000 and <1/1000).

From the nervous system: often - headache, depression, mood swings; Infrequently - migraine, decreased libido; Rarely - increased libido.

From the digestive system: often - nausea, abdominal pain; Infrequently - vomiting, diarrhea.

On the part of the reproductive system and breast: often - soreness of the mammary glands, engorgement of the mammary glands; Infrequently, mammary gland hypertrophy; Rarely - intermenstrual bleeding, oligomenorrhoea.

Other: often - weight gain; Infrequently - fluid retention in the body, rash, hives; Rarely - allergic reactions, erythema nodosum, erythema multiforme, weight loss, deterioration in the tolerability of contact lenses, with prolonged use - of chloasma.

Interaction

The use of drugs that induce microsomal liver enzymes can lead to an increase in the sex hormone clearance, which in turn can lead to breakthrough bleeding or a decrease in the reliability of contraception. These drugs include: phenytoin, barbiturates, primidone, carbamazepine, rifampicin, rifabutin, possibly also - oxcarbazepine, topiramate, felbamate, griseofulvin and preparations containing St. John's Wort. HIV protease inhibitors (eg ritonavir) and NNRTI (eg, nevirapine) and their combinations also have a potential effect on hepatic metabolism.

During the application of drugs that affect microsomal enzymes, and within 28 days after their withdrawal, the barrier method of contraception should be used additionally. Some antibiotics (eg penicillins and tetracyclines) can reduce the intestinal hepatic circulation of estrogens, thereby lowering the concentration of ethinylestradiol. During the application of antibiotics (such as penicillins and tetracyclines) and within 7 days after their withdrawal, the barrier method of contraception should additionally be used. If the period of use of the barrier method of prevention ends later than the tablets in the package, you need to move on to the next pack of the Modell Pure drug without an ordinary break in taking the tablets.

COCs can affect the metabolism of other drugs, leading to an increase (eg, cyclosporine) or a decrease (eg, lamotrigine) in their concentrations in plasma and tissues. You may need to adjust the dosage regimen.

Dosing and Administration

Inside, 1 tablet / day, every day at the same time, preferably after breakfast or dinner. The tablet should be swallowed whole, without chewing and washing down with a small amount of liquid. Reception of the drug Modell Pure begins on the 1st day of the menstrual cycle (ie on the 1st day of menstrual bleeding), using a tablet of the corresponding day of the week from the calendar package.

Daily administration of the drug is carried out using tablets from the calendar pack in sequence along the direction of the foil-applied arrow until all the tablets are taken. After the termination of reception 21 tab. From the calendar packing a break is taken in taking the drug for 7 days, during which menstrual bleeding occurs.

After 28 days from the start of the drug (21 days of admission and 7 days of interruption), i.e. On the same day of the week as at the beginning of the course, continue taking the drug from the next package.

When switching from 21-day COCs, taking Modell Pure should be started the day after the last tablet of the previous preparation, but in no case later than the day after the usual 7-day break in admission. Further - according to the scheme described above. The use of additional contraceptives is not required.

When switching from a 28-day COC, taking Modell Pure should be started the day after the last active tablet. Further - according to the scheme described above. The use of additional contraceptives is not required.

When switching from contraceptives containing only gestagens (mini-pili), the Modell Pure drug should be used without interruption. Further - according to the scheme described above. The use of additional contraceptives is not required.

When using injectable forms of contraceptives, Modell Pure is taken from the day the next injection is to be taken.

When moving from the implant - the day it is removed. In all cases, it is necessary to use an additional barrier method of contraception (condom) during the first 7 days of taking the tablets.

After abortion in the first trimester of pregnancy, a woman can start taking the drug immediately. In this case, the woman does not need additional methods of contraception.

After childbirth or abortion in the second trimester of pregnancy, the drug should be taken on the 21-28th day. If the reception is started later, it is necessary to use an additional barrier method of contraception (condom) during the first 7 days of taking the tablets. If a woman has had a sex life between childbirth or abortion and the beginning of taking Modèle Pure, first you must exclude pregnancy or wait for the first menstrual period.

The missed tablet should be taken as soon as possible, the next tablet is taken at the usual time.

At a delay of less than 12 hours, the reliability of contraception does not decrease. If the delay in taking the tablet is more than 12 hours, the reliability of contraception can be reduced. It should be borne in mind that the pill should never be interrupted for more than 7 days, and that 7 days of continuous tablet intake is required to achieve adequate suppression of the hypothalamic-pituitary-ovarian system.

If the delay in taking the tablet is more than 12 hours (the interval from the time of taking the last tablet is more than 36 hours) during the 1 st and 2 nd weeks of taking the drug, the woman should take the last missed tablet as soon as possible, as soon as she remembers (even if This means taking two tablets simultaneously). The next tablet is taken at the usual time. In addition, a barrier method of contraception (condom) should be used for the next 7 days.

If the delay in taking the tablet is more than 12 hours (the interval from the last pill taken more than 36 hours) during the 3rd week of taking the drug, the woman should take the missed tablet as soon as possible, as soon as it remembers (even if it means taking two tablets At the same time). The next tablet is taken at the usual time. In addition, taking a pill from a new package should be started as soon as the current package is finished, i. E. Without a 7-day break. In addition, a barrier method of contraception (condom) should be used for the next 7 days. Most likely, a woman will not have a withdrawal bleeding to the end of the second package, but there may be spotting spotting or breakthrough uterine bleeding on the days of taking the tablets. If you miss a dose of 3 or more tablets, you should consult your doctor.

If a woman has vomiting or diarrhea within 3 to 4 hours after receiving Modell Pure, the absorption of the active substances may be incomplete. In this case, it is necessary to focus on the recommendations when skipping the tablet. If a woman does not want to change the usual mode of taking the drug, an additional tablet (or several tablets) from another package should be taken if necessary.

In order to delay the onset of menstruation, a woman should continue taking pills from a new package of the Modell Pure drug immediately after taking all the pills from the previous one, without interruption in admission. Tablets from this new package can be taken for as long as the woman wishes (until the package is finished). Against the background of taking the drug from the second package, a woman may have spotting or breakthrough uterine bleeding. To resume taking the drug Modell Pure from the new package follows the usual 7-day break.

In order to postpone the day of the onset of menstruation on the next day of the week, the woman should shorten the nearest break in taking the pills for as many days as she wants. The shorter the interval, the higher the risk that withdrawal bleeding will not occur, and later spotting spotting and breakthrough bleeding will be noted during the second package (just like when she wants to delay the onset of menstruation).

In the treatment of hyperandrogenic conditions, the duration of admission is determined by the severity of the disease. After the disappearance of symptoms it is recommended to take the drug Modell Pure, at least another 3-4 months. In the case of relapse after a few weeks or months after the completion of the course, you can re-use the drug Modell Pure.

Overdose

Symptoms: nausea, vomiting, bleeding when drug is withdrawn.

Treatment: symptomatic therapy; There is no specific antidote.

special instructions

Medical check-ups

Before starting or resuming the use of Modell Pure, a woman needs to undergo a thorough general medical examination (including measurement of blood pressure, heart rate, BMI definition) and gynecological examination, including breast examination and cervical scraping (Papanicolaou test), and to exclude pregnancy.

The volume of additional studies and the frequency of follow-up visits are determined individually. Usually, follow-up examinations should be conducted at least 2 times a year. A woman should be warned that the Modell Pure drug does not protect against HIV infection (AIDS) and other sexually transmitted diseases.

If any of the conditions, diseases and risk factors outlined below are present, careful consideration should be given to the potential risk and expected benefits of using the COC in each case and to discuss it with the woman before she decides to start taking the drug.

In case of weighting, strengthening or the first manifestation of any of these conditions, diseases or risk factors, a woman should consult a doctor who can decide whether to cancel the drug.

CCC diseases. There is evidence of an increase in the incidence of venous and arterial thrombosis and thromboembolism (such as deep vein thrombosis, PE, myocardial infarction, stroke) with COCs. These diseases are rare. The risk of developing venous thromboembolism is maximal in the first year of taking such drugs. The risk of developing thrombosis (venous and / or arterial) and thromboembolism increases:

- with age;

- for smokers (with an increase in the number of cigarettes or an increase in age, the risk further increases, especially in women over 35 years of age);

in the presence of:

- a burdened family history (for example, venous or arterial thromboembolism ever at close relatives or parents at a relatively young age). In the case of hereditary predisposition, a woman should be referred to the appropriate specialist to decide on the possible use of COCs;

- obesity (BMI more than 30 kg / m2);

- dyslipoproteinemia;

- arterial hypertension;

- migraine;

- heart valve diseases;

- Atrial fibrillation;

- prolonged immobilization, serious surgical intervention, any operation on the lower extremities or extensive trauma. In these situations, it is necessary to stop the use of COCs (in the case of a planned operation, at least 4 weeks before it) and not resume reception for 2 weeks after the end of immobilization.

The question of the possible role of varicose veins and superficial thrombophlebitis in the development of venous thromboembolism remains controversial. An increased risk of thromboembolism in the postpartum period should be considered. Violations of peripheral circulation can also occur in diabetes mellitus, systemic lupus erythematosus, tetany, hemolytic uremic syndrome, chronic inflammatory bowel disease (Crohn's disease or NNC), and sickle cell anemia.

An increase in the frequency and severity of migraine during the use of COCs (which may precede cerebrovascular disorders) may be the reason for the immediate discontinuation of these medications.

Tumors

An important risk factor for cervical cancer is the persistence of papillomavirus. The results of some epidemiological studies indicate an additional increase in this risk with prolonged use of COC, however, this statement remains controversial, since it has not been fully established whether the results of studies take into account co-occurring risk factors, for example screening of the cervix and sexual behavior, Barrier methods of contraception.

The relationship between the use of COCs and breast cancer has not been proven. There is a slightly increased relative risk of developing breast cancer diagnosed in women currently taking COCs. Increased risk gradually disappears within 10 years after discontinuation of the use of these drugs. The observed increase in risk may be the result of careful monitoring and earlier diagnosis of breast cancer in women using COCs. In women who have ever used COC, earlier stages of breast cancer are detected, and it is clinically less pronounced than in women who never used COCs. In isolated cases, against the background of the use of COC, the development of benign, and in very rare cases, malignant liver tumors, which in some cases led to life-threatening intraperitoneal bleeding. In the event of severe pain in the abdominal region, liver enlargement, or signs of intraperitoneal bleeding in differential diagnosis, the possibility of a liver tumor in patients taking COC should be considered.

Other states

Women with hypertriglyceridemia (or having this condition in a family history) may have an increased risk of developing pancreatitis during COC use.

Despite the fact that a small increase in blood pressure was described in many women taking COC, a clinically significant increase in blood pressure was noted rarely. However, if a persistent, clinically significant increase in blood pressure develops during the application of COC, these drugs should be discontinued and treatment of hypertension should begin. Reception of COCs can be continued if normal blood pressure values are achieved with the help of antihypertensive therapy.

The following conditions have been reported to develop or worsen, both during pregnancy and when taking COC, but their relationship with COCs has not been proven: jaundice and / or pruritus associated with cholestasis; Formation of stones in the gallbladder; Porphyria; Systemic lupus erythematosus; Hemolytic-uremic syndrome; chorea; Herpes of pregnant women; Hearing loss associated with otosclerosis. Cases of Crohn's disease and NNC are also described in the background of the use of COCs.

In women with hereditary forms of angioedema, exogenous estrogens can cause or worsen symptoms of angioedema.

Acute or chronic liver dysfunction may require cancellation of COC until liver function returns to normal.

Recurrent cholestatic jaundice, which develops for the first time in pregnancy or the previous use of sex hormones, requires the cessation of COCs. Although COCs can affect insulin resistance and glucose tolerance, there is no need to change the therapeutic regimen in diabetic patients using low-dose COCs (<0.05 mg ethinyl estradiol). Nevertheless, women with diabetes should be carefully monitored during the use of COCs.

Sometimes chloasma can develop, especially in women with a history of pregnancy chloasma. Women with a tendency to chloasma during the use of COC should avoid prolonged exposure to sunlight and exposure to UV radiation.

Treatment (contraception) should be stopped immediately after pregnancy, the development of migraine headaches (if they were not previously), the appearance of early signs of phlebitis or phlebothrombosis (unusual pain or bloating of the veins on the lower extremities), jaundice, visual impairment, cerebrovascular disorders, stitching Pain of unclear etiology during breathing or coughing, pain and tightness in the chest, increased blood pressure. Admission is also terminated 3 months before the planned pregnancy, for 6 weeks before the planned surgical intervention and with prolonged immobilization.

With diarrhea and vomiting contraceptive effect is reduced, therefore, without stopping the use of Modell Pure, it is necessary to use additional non-hormonal methods of contraception.

Laboratory Tests

Admission COC can affect the results of some laboratory tests, including indicators of liver function, kidney function, thyroid gland, adrenal gland, transport protein content in plasma, carbohydrate metabolism, coagulation and fibrinolysis parameters. Laboratory staff should be warned about taking oral contraceptives. It is possible to change the results of skin allergic tests, decrease the concentration of LH and FSH. In connection with the fact that the contraceptive effect is fully manifested by the 14th day from the beginning of admission, in the first 2 weeks it is recommended to additionally use non-hormonal (barrier) methods of contraception.

The drug Modell Pure does not affect the course of puberty during the formation of a normal menstrual cycle. The appointment after childbirth is recommended not earlier than the first normal after the birth of menstruation. In cases of acyclic bleeding in the first 3 weeks of hormonal contraception, it is possible to continue taking the drug, as a rule, bloody discharge stops on their own. If there is no bleeding during the 7-day interval between taking the drug, taking the pills should be stopped until pregnancy is excluded.

Effects on the menstrual cycle

Against the background of the use of COC, irregular (acyclic) bloody discharge / bleeding from the vagina (spotting bleeding or breakthrough bleeding) can occur, especially during the first months of use. Therefore, any irregular bleeding should be assessed after an adaptation period of approximately three cycles. If irregular bleeding recurs or develops after previous regular cycles, a thorough examination should be performed to exclude malignant neoplasms or pregnancy. Some women may not develop withdrawal bleeding during a break in taking pills. If COCs were taken according to recommendations, it is unlikely that a woman is pregnant. However, with the occasional use of COCs and the absence of two consecutive bleeding abortions, taking the drug can not be continued until pregnancy is excluded.

Influence on the ability to drive vehicles and control mechanisms. Not found.

Form of issue

The tablets covered with a cover. In the blister is 21 pcs. By 1 or 3 bl. Put in a pack of cardboard.

Terms of leave from pharmacies

On prescription.

storage Conditions

At a temperature not exceeding 30 ° C.

Keep out of the reach of children.

Shelf life

3 years.

Do not use after the expiry date printed on the package.