Modelle Pure (Ethinylestradiol + Cyproterone) tablets

Dosage form

Tablets, film-coated yellow color, round, lenticular.

Composition

1 tablet contains micronized ethinyl estradiol 35 µg 

cyproterone acetate 2 mg micronized 

Excipients: lactose monohydrate – 29.115 mg corn starch 20 mg, povidone K25 – 2.1 mg, talc – 1.65 mg, magnesium stearate – 100 mcg.

The shell: sucrose – 19.637 mg, calcium carbonate – 8.402 mg, talc – 4.095 mg, titanium dioxide – 278 µg of povidone К90 – 200 mg, macrogol 6000 – 2.178 mg, glycerol 85% – 139 ICG dye iron oxide – 27 mcg, wax mountain glycol – 44 µg.

Pharmacological action

A combined contraceptive product (estrogen+antiandrogen). 

Low-dose monophasic combined contraceptive drug with antiandrogenna activity. The mechanism of action is due to its antiandrogenic steroid by means of structure – cyproterone acetate and oral estrogen – ethinyl estradiol. Blocks the androgen receptors, inhibits the secretion of pituitary gonadotropins.

The cyproterone has the ability competitive to get in contact with the natural receptors of androgens (including testosterone, dehydroepiandrosterone, Androstenedione) produced in small amounts in women, mainly in the adrenal glands, ovaries and skin. Blocking androgen receptors in target organs, reduces the effect of androgenization in women (due to violations of the processes mediated hormone-receptor complexes at the level of the main intracellular mechanisms). Along with the anti-androgenic properties, has progestational activity, mimic the properties mimic the properties of hormone yellow phone Oppressing secretion gipofizom gonadotroponah hormones and inhibits ovulation, which accounts for its contraceptive effect.

Ethinylestradiol increases Central and peripheral effect of cyproterone on ovulation, retains a high viscosity of cervical mucus, inhibiting sperm entry into the uterus and helps to ensure a reliable contraceptive effect.

Pharmacokinetics

Cyproterone acetate

Suction

Completely absorbed after ingestion. Cmax in plasma is reached in 1.6 hours after taking 1 tab. drug Modelle Pure and is 15 ng/ml. Bioavailability of 88%.

Distribution

Almost completely binds to albumin in plasma. During the course of treatment is observed accumulation of the drug: serum concentration increased from 15 ng/ml in the 1st day of treatment up to 21 ng/ml at the end of 1 cycle and up to 24 ng/ml at the end of 3 cycles of treatment. AUC is increased by 2.2 times (end cycle 1) and 2.4 times (end of 3rd cycle). Css is created in approximately 16 days after the start of treatment.

Metabolism

Metabolized in the liver through various reactions, including hydroxylation and conjugation. The main metabolite is 15-hydroxycitrate.

Excretion

The elimination half-life (T1/2) from plasma is biphasic, with T1/2 of 0.8 hours and 2.3 days respectively for the first and second phase. The total plasma clearance is 3.6 ml/min/kg. the Main part of introduced dose is excreted by the kidneys as metabolites, with the remainder from jelchew in an unmodified form. T1/2 is 1.9 days.

Ethinyl estradiol

Suction

After intake of ethinylestradiol is rapidly and completely absorbed. Cmax in plasma is reached after 1.7 hours after taking 1 tab. drug Modelle Pure and is 80 PG/ml. Almost entirely associated with plasma proteins. During absorption and first pass through the liver is metabolized, leading to reduced bioavailability.

Distribution

Apparent Vd is 5 l/kg. Css is created in 3-4 days after the start of treatment.

Excretion

The elimination half-life (T1/2) from plasma is two-phase, T1/2 is 1-2 h and 20 h respectively for the first and second phase. Plasma clearance of 5 ml/min/kg. Excreted as metabolites through the intestines and kidney in the ratio 4:6, T1/2 is about 1 day.

Side effects

All women who have PDA are at increased risk of thrombosis and thromboembolism, the slight increase risk of worse other diseases. When you receive a PDA may include an irregular (acyclic) vaginal bleeding (spotting or breakthrough bleeding), especially during the first months of use.

Determination of the frequency of adverse reactions: often (>1/100 and <1 10=>1/1000 and <1 100=>1/10 000 and <1 1000= span=>

From the nervous system: often – headache, depression, mood swings; infrequently – migraine, decreased libido; rare – increase libido.

From the digestive system: often – nausea, abdominal pain; infrequently – vomiting, diarrhea.

From the reproductive system and mammary gland: often – pain in the breast, engorgement; infrequently – hypertrophy of the mammary glands; rare – intermenstrual bleeding, oligomenorrhea.

Other: often – increased body mass index; infrequently – fluid retention in the body, rash, urticaria; rarely, allergic reaction, erythema nodosum, erythema multiforme, weight-loss, and deterioration tolerability of contact lenses, long-term use – chloasma.

Special conditions

Medical examinations

Before the start or resumption of the use of the drug Modelle Pure woman, you need to conduct a thorough General medical (including measurement of ADD, heart rate, determination of BMI) and gynecological examination, including examination of the mammary glands and cytological examination of scraping from the cervix (Papanicolaou test), to exclude pregnancy.

The amount of additional research and the frequency of inspections is determined individually. Typically, control examinations should be performed at least 2 times a year.

It should warn the woman that the drug Modelle Pure does not protect against HIV infection (AIDS) and other sexually transmitted diseases.

If any of the conditions, diseases and risk factors mentioned below are present, you should carefully weigh the potential risks and expected benefits of the use of CPC in each case and to discuss it with the woman before she decides to start taking the drug. In the case of weighting, gain, or first appearance of any of these conditions, diseases or risk factors, the woman should consult with her doctor, who may decide on the necessity of discontinuation of the drug.

Cardiovascular disease

There is evidence of the increase in the incidence of venous and arterial thrombosis and thromboembolism (such as deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke) in the application of the PDA. These diseases are rare. The risk of venous thromboembolism maximum in the first year of taking these drugs. The risk of thrombosis (venous and/or arterial) and thromboembolism is increased:

with age;

– smokers (with the increase in the number of cigarettes or increasing age the risk further increases, especially in women older than 35 years);

in the presence of:

– positive family history (eg, venous or arterial thromboembolism ever have close relatives or parents at a relatively young age). In the case of hereditary predisposition, the woman should be referred to the appropriate specialist to address the question about the possibility of using PDAs;

– obesity (BMI > 30 kg/m2);

– dyslipoproteinemia;

– arterial hypertension;

– migraine;

– diseases of valves of heart;

– atrial fibrillation;

– prolonged immobilization, major surgery, any surgery on the lower limbs, or extensive trauma. In these situations it is necessary to stop the use of PDA (in the case of the planned operation, at least 4 weeks in advance) and not to resume reception during 2 weeks after the immobilization.

The question of the possible role of varicose veins and superficial thrombophlebitis in venous thromboembolism remains controversial.

You should consider the increased risk of thromboembolism in the postpartum period.

Peripheral circulatory disorders also may occur with diabetes, lupus, tetany, hemolytic uremic syndrome, chronic inflammatory bowel diseases (Crohn’s disease or ulcerative colitis) and sickle cell anemia.

The increase in the frequency and severity of migraine during use of the CPC (which may precede cerebrovascular disorders) may be grounds for immediate discontinuation of these drugs.

Tumors

An important risk factor for development of cervical cancer is persistence of the HPV. The results of some epidemiological studies indicate a further increase this risk with prolonged use PDAs, however, this assertion remains controversial, as finally determined how the results of the studies take into account concomitant risk factors, such as the screening of the condition of the cervix and sexual behavior, including a rare use of barrier methods of contraception.

The relationship between use of PDAs and breast cancer has not been proven. There are several elevated relative risk of breast cancer diagnosed in women taking the BCP now. The increased risk gradually disappears during the 10 years after stopping use of these drugs. The observed increase in risk may be the result of careful observation and early diagnosis of breast cancer in women who use PDAs. In women, ever use PDAs, reveals more early stage breast cancer and

clinically, it is less pronounced than in women who never used the PDA.

In rare cases, application of the PDA was observed the development of benign, but in extremely rare cases, malignant liver tumours, which in some cases led to life threatening intra-abdominal hemorrhage. In case of severe pain in the abdomen, liver enlargement or signs of intra-abdominal hemorrhage in the differential diagnosis should take into account the possible presence of liver tumors in patients receiving PDA.

For more information, see the user manual

Overdose

Symptoms: nausea, vomiting, bleeding when the drug is removed. 

Treatment: symptomatic therapy; no specific antidote.

Testimony

— contraception in women with symptoms of androgenization.

— treatment of androgen-dependent diseases/conditions (vulgar acne (acne papulopustulosa, acne nodulocystica); seborrhea; androgenic alopecia; hirsutism).

Contraindications

— thrombosis (venous and arterial) and thromboembolism in the present or in history (e.g. deep venous thrombosis, pulmonary embolism), ischemic heart disease, stroke;

— state prior thrombosis (including transient ischemic attack, angina pectoris) now or in history;

— complicated valvular lesions of the heart (pulmonary hypertension, atrial fibrillation, subacute bacterial endocarditis history);

— uncontrolled hypertension (systolic blood pressure above 160 mm Hg.St. or diastolic blood pressure above 100 mm Hg.St.);

— major surgery with prolonged immobilization;

— diabetes with vascular complications;

multiple or severe risk factors for venous or arterial thrombosis, including vascular disease of the brain or coronary arteries, arterial hypertension, elderly age;

— hepatic failure and severe liver disease (up to normalization of liver samples);

— active viral hepatitis, liver cirrhosis in the decompensation stage;

— idiopathic jaundice or itching during former pregnancy;

— congenital hyperbilirubinemia (Gilbert syndrome, Dubin-Johnson and Rotor);

— liver tumors (benign or malignant) currently or in history;

— migraine with focal neurological symptoms in the present or in history;

— pancreatitis with severe hypertriglyceridemia in the present or in history;

— identification of hormone-dependent cancers (including breast cancer and endometrial) or suspicion on them;

— vaginal bleeding ambiguous Genesis;

— sickle cell anemia;

— otosclerosis with deterioration during pregnancy;

herpes during pregnancy in history;

— Smoking age 35 years;

— pregnancy;

— lactation;

— hypersensitivity to any component of the drug.

With caution

You should carefully weigh the potential risks and expected benefits of the use PDAs in each case in the presence of the following diseases/conditions and risk factors.

— risk factors for thrombosis: Smoking, obesity, dislipoproteinemia, hypertension, migraine, valvular disease, prolonged immobilization, major surgery, extensive trauma, hereditary predisposition to thrombosis (thrombosis, blood coagulation disorders, myocardial infarction or cerebrovascular accident at a young age any of the next of kin);

— diseases in which can be observed violations of the peripheral circulation: diabetes (or a predisposition, e.g. unexplained glycosuria), SLE, impaired renal function, hemolytic uremic syndrome, Crohn’s disease and ulcerative colitis, varicose veins, phlebitis of the superficial veins;

hypertriglyceridemia;

— liver disease;

breast cancer a family history or benign breast tumor in the personal history;

— diagnosed depression in history;

— uterine fibroids;

— cholelithiasis;

— intolerance to contact lenses;

the disease was first incurred or aggravated by the pregnancy or on the background of the previous reception of sex hormones (e.g., jaundice and/or itchy, associated with cholestasis, cholelithiasis, porphyria, chorea Sydenham, chloasma).

Application of pregnancy and breastfeeding

The drug is contraindicated during pregnancy and lactation

Drug interactions

Influence on the hepatic metabolism of drugs, inducing microsomal liver enzymes may lead to increased clearance of sex hormones, which in turn may lead to breakthrough bleeding or reduce the reliability of contraception. Such medicines include: phenytoin, barbiturates, primidon, carbamazepine, rifampicin, rifabutin, and possibly also oxcarbazepine, topiramate, felbamate, griseofulvin and products containing St. John’s wort.

The HIV protease inhibitors (eg, ritonavir) and non-nucleoside reverse transcriptase inhibitors (e.g. nevirapine) and combinations thereof may also potentially affect hepatic metabolism.

During the application of drugs affecting microsomal enzymes, and for 28 days after their cancellation should additionally use a barrier method of contraception.

Some antibiotics (e.g. penicillins and tetracyclines) may reduce enterohepatic circulation of estrogens, thereby lowering the concentration of ethinyl estradiol. During the use of antibiotics (such as penicillins and tetracycline) and for 7 days after their cancellation should additionally use a barrier method of contraception. If the period of use of barrier method of protection ends later than the tablets in a package, you need to go to the next package of the drug Modelle Pure without the usual break from the pill.

PDA can affect the metabolism of other drugs, which leads to an increase (e.g. ciclosporin) or decrease (e.g. lamotrigine) their concentration in plasma and tissues. May require correction dosing regimen of drugs.

Dosage

The drug is taken orally, 1 tab./day, every day at the same time, preferably after Breakfast or dinner. The tablet should be swallowed whole, with liquid squeezed small amount of liquid. The drug Modelle Pure start in 1 day menstrual cycle (i.e. the 1st day of menstrual bleeding), using the tablet of the corresponding day of the week from the calendar package. Daily carry out the drug using the pills from the calendar package consistently in the direction marked on the foil arrows, until you have taken all the pills. After taking 21 tablets of the calendar package is a break in taking the drug duration of 7 days, during which bleeding occurs menstrualnopodobnoe. After 28 days from start of treatment (21 days of admission and 7 days break), i.e., on the same day of the week, and the beginning of the course, continue the drug of the next package. When switching from 21-day combined oral contraceptives (PDA), a drug Modelle Pure should start the day after taking the last tablet of the previous formulation, but in any case not later than the next day after the usual 7-day break in the reception. Further, according to the scheme described above. The use of additional contraception is not required. When switching from a 28-day PDA the drug Modelle Pure should start the next day after taking the last active pill. Further, according to the scheme described above. The use of additional contraception is not required. In the transition from contraceptives containing only progestin (minipill), the drug Modelle Pure should begin to apply without interruption. Further, according to the scheme described above. The use of additional contraception is not required. When using the injectable forms of contraceptives drug Modelle Pure start taking from the day should be made following injection. During the transition from the implant to the day of his removal. In all cases, you must use an additional barrier method of contraception (condom) during the first 7 days of taking the pills. After abortion in the first trimester of pregnancy the woman may start taking the drug immediately. In this case, the woman does not need any additional contraceptive methods. After delivery or abortion in the II trimester of pregnancy the drug should be started at 21-28 day. If the reception is started later, you must use an additional barrier method of contraception (condom) during the first 7 days of taking the pills. If a woman has been sexually active in the period between births or abortions and start taking the drug Modelle Pure, the first should be deleted pregnancy or must wait for first menstruation. The missed pill should be taken as soon as possible, the next pill is taken at the usual time. If you are late less than 12 h, reliability of contraception is not reduced. If the delay in taking the pill was more than 12 h, reliability of contraception may be reduced. Note that the pills should never be interrupted for more than 7 days and that 7 days of continuous reception of pills required to achieve adequate suppression function of the hypothalamic-pituitary-ovarian system. If the delay in taking the pill was more than 12 h (the interval since the last tablet, more 36 h) during 1st and 2nd weeks of taking the drug, the woman should take the last missed tablet as soon as possible, as soon as you remember (even if this means taking two tablets at the same time). The next tablet is taken at the usual time. Additionally, you should use a barrier method of contraception (condom) for following 7 days. If the delay in taking the pill was more than 12 h (the interval since the last tablet, more 36 h) during the 3rd week of the treatment, the woman should take the missed pill as soon as possible, as soon as you remember (even if this means taking two tablets at the same time). The next tablet is taken at the usual time. In addition, taking the pill from the new package should be started as soon as the current pack, i.e. without a 7 day break. Additionally, you should use a barrier method of contraception (condom) for following 7 days. It is likely that the woman will not have withdrawal bleeding before the end of the second package, but may experience spotting or breakthrough uterine bleeding during the days of taking the pills. If you miss 3 or more pills, you should consult your doctor. If the woman has vomiting or diarrhoea within 3 to 4 h after administration of the drug Modelle Pure, absorption of active substances may be incomplete. In this case, you must rely on recommendations when skipping pills. If a woman does not want to change conventional mode of drug intake should be taken, if necessary, additional tablet (or several tablets) from a different package. In order to delay the onset of menstruation, women should continue taking tablets from a new packaging of the drug Modelle Pure immediately after taken all tablets of the previous one, without interruption in reception. Pills from this new packaging can be made as long as a woman wants (as long as the package is over). On the background of the drug from the second package, women may experience spotting or breakthrough uterine bleeding. To resume taking the drug Modelle Pure from a new package follows the usual 7-day break.STI the day of the beginning of menstruation to another day of the week, the woman should shorten the nearest break in the pill for as many days as she wants. The shorter the interval, the higher the risk that you will not have withdrawal bleeding, and in the future will be marked with spotting and breakthrough bleeding while taking the second packaging (the same as in the case when she would like to delay the onset of menstruation). In the treatment hyperandrogenic States the duration of reception is determined by the severity of the disease. After the disappearance of symptoms is recommended to take the drug Modelle Pure, at least another 3-4 months. In case of a relapse a few weeks or months after completion of the course can be repeated the treatment with the drug Modelle Pure.