Expiration date: 01/2025

Dosage form

Tablets, film-coated (active) light pink color, round, lenticular, with marking "D2" on one side, caused by stamping; in cross section - from white to almost white (24 PCs. per blister).

Tablets, film-coated (placebo) white color, round, lenticular, with marking "PC" on one side, caused by stamping (4 PCs in a blister).

Composition

1 tablet contains: 

ethinyl estradiol 20 mcg 

drospirenone 3 mg 

Excipients: lactose monohydrate - 43.38* mg, corn starch - 12.8 mg, starch pregelatinization - 15.4 mg, povidone K25 - 3.4 mg, croscarmellose sodium 1.6 mg, magnesium stearate - 400 mcg.

The composition of the shell: Opadry yellow 03B34091 - 2 mg (hypromellose 6?? - 62.5%, titanium dioxide - 31.07%, macrogol 400 - 6.25%, colouring agent iron oxide red - 0.18%).

* the amount of lactose monohydrate may vary depending on the purity of the substances active substances.

Part of the "placebo": vspomogatelny substances: lactose monohydrate 60 mg, starch pregelatinization - 19.2 mg, magnesium stearate - 800 mcg.

The composition of the shell: white Opadry 03B28796 - 2 mg (hypromellose 6cP - 62.5%, titanium dioxide - 31.25%, macrogol 400 - 6.25%).

Pharmacological action

Low-dose monophasic combined oral hormonal contraceptive preparation containing ethinylestradiol and drospirenone.

The contraceptive effect of the drug Modell Trend is mainly due to the suppression of ovulation, increase viscosity of cervical mucus and changes the endometrial. In women, taking combined oral contraceptives (BCP), the menstrual cycle becomes more regular, less frequent are painful menstruation, decreases the intensity menstrualnopodobnoe bleeding, which reduces the risk of iron deficiency anemia. In addition, there is evidence that reduced risk of endometrial cancer and ovarian cancer.

The drospirenone contained in the drug Modell Trend, has antimineralokortikoidnym action. Prevents weight gain and peripheral edema associated with estrogen-induced hormone-dependent fluid retention, which ensures good tolerability. Drospirenone has a positive effect on premenstrual tension. Shown the clinical efficacy of the drug Modell Trend in alleviating the symptoms of a severe form of premenstrual tension, such as expressed psycho-emotional disorders, breast engorgement, headache, pain in muscles and joints, weight gain and other symptoms associated with the menstrual cycle.

Drospirenone is also possesses antiandrogenic activity and reduces acne (acne), oily skin and hair. This action of drospirenone is similar to the natural progesterone produced in the female body. This should be considered when choosing a contraceptive drug, especially for women with hormone-dependent fluid retention, as well as women with acne and seborrhea.

Drospirenone has no androgenic, estrogenic, glucocorticoid and antiglucocorticoid activity. All this combined with antimineralocorticoid and antiandrogenic action provides drospirenone pharmacological profile similar to the profile of natural progesterone.

In combination with ethinylestradiol drospirenone has a positive effect on the lipid profile, increasing the concentration of HDL.

With proper use of the drug, the Pearl index (indicator, reflecting the number of pregnancies in 100 women using a contraceptive during the year) is less than 1. When you miss a pill or incorrect application of the Pearl index may increase

Pharmacokinetics

Suction

After oral administration drospirenone is rapidly and almost completely absorbed from the gastrointestinal tract. After a single administration of the drug Cmax of drospirenone in serum is achieved through 1-2 h and is 35 ng/ml. Bioavailability of drospirenone is 76-85%. Ingestion not affect the bioavailability.

Distribution

Drospirenone binds to serum albumin and does not bind globulin, linking sex hormones (SHBG) or corticosteroid-binding globulin (glcs). Estradiol-induced increase in the concentration of SHBG in blood plasma does not affect the binding of drospirenone with blood plasma proteins.

During cyclic treatment Css drospirenone is achieved during the second half of the cycle. Further increase of concentration is observed in approximately 1-6 cycles of the drug, further increase in concentration is not observed.

Metabolism

After oral administration drospirenone is completely metabolized. Most of the metabolites in plasma is presented of the acid form of drospirenone, which are formed without the participation of isoenzymes of cytochrome P450.

Excretion

After ingestion observed a biphasic decrease in concentrations of drospirenone in serum. Excreted as metabolites through the intestines and kidney in the ratio of about 1.2:1.4. T1/2 metabolites is about 40 hours.

Pharmacokinetics in special patient groups

Css drospirenone in plasma in women with renal insufficiency, mild (QC 50-80 ml/min) comparable with those in women with normal renal function. In women with renal insufficiency medium severity (QC 30-50 ml/min), the concentration of drospirenone in serum on average 37% higher than in women with normal renal function.

In women with impaired liver moderate (class b on a scale child-Pugh) the AUC is comparable with the corresponding figure for healthy women with similar Cmax values in the phase of absorption and distribution. T1/2 of drospirenone in women with impaired liver moderate 1.8 times higher than in healthy volunteers with normal hepatic function.

In women with abnormal liver function moderate decrease in clearance of drospirenone by about 50% compared to women with normal hepatic function, while there was no difference in the concentration of potassium in the blood plasma in the studied groups. No marked changes in potassium concentration, even in the case of a combination of factors contributing to its increase (associated diabetes mellitus or treatment with spironolactone).

Ethinyl estradiol

Suction

After taking the drug inside ethinylestradiol is rapidly and completely absorbed from the gastrointestinal tract. Cmax in plasma is reached after 1-2 h and is 88-100 PG/ml. ethinyl estradiol is subjected to the effect of "first pass" through the liver, resulting in its oral bioavailability is on average 60%.

Distribution

Linking blood plasma proteins (albumin) is about 98%. Ethinyl estradiol induces an increase in the concentration of SHBG in plasma.

Css is set in the second half of the first cycle of the drug, the concentration of ethinyl estradiol is increased by approximately 1.4-2.1 times.

Metabolism

Ethinylestradiol undergoes presystemic conjugation in the mucosa of the small intestine and in the liver. The main pathway is aromatic hydroxylation.

Excretion

The decrease in the concentration of ethinyl estradiol in plasma is biphasic. Ethinyl estradiol is excreted as metabolites in the urine and feces in the ratio of about 4:6. T1/2 metabolites is about 24 hours.

Side effects

Reported on the following most common adverse reactions in women using a combination of drospirenone+ethinylestradiol on the testimony of "Contraception" and "Contraception and treatment of acne of moderate severity (acne vulgaris)": nausea, breast pain, irregular uterine bleeding, vaginal bleeding unspecified origin. These adverse reactions were encountered more than 3% of women. In women using drospirenone+ethinylestradiol on the indication "Contraception and treatment of severe forms of premenstrual tension" was reported the following most common adverse reactions (more than 10% of women): nausea, breast pain, irregular uterine bleeding. Serious adverse reactions are arterial and venous thromboembolism.

Frequency of adverse reactions identified in clinical trials, a combination of drospirenone+ethinyl estradiol, as follows: often (?1/100-<1 10="" 1="" 1000-="" 100="" 000-="" 1000="" br="">

Infectious and parasitic diseases: rarely - candidiasis mucous membranes of the oral cavity, vulvovaginal candidiasis.

With the hematopoietic system: rarely - anemia, thrombocytopenia.

The immune system: rarely - allergic reactions; frequency is unknown - hypersensitivity reactions.

From the metabolic and nutritional: rarely - increased appetite, anorexia, hyperkalemia, hyponatremia.

Mental disorders: often - emotional lability, depression/depressed mood; infrequent - decrease/loss libido, drowsiness; rare - anorgasmia, insomnia.

From the nervous system: often - headache; infrequently - dizziness, paresthesia; rare - vestibular dizziness, tremor.

From the body of the vision: rarely - conjunctivitis, dry eyes, blurred vision.

Of the cardiovascular system: infrequently - migraine, varicose veins, increased blood pressure, rarely - tachycardia, phlebitis, vascular disease, epistaxis, syncope, venous or arterial thromboembolism*.

From the digestive system: often - nausea; rare - abdominal pain, vomiting, dyspepsia, flatulence, gastritis, diarrhea; rare - abdominal distension, gastrointestinal disorder, feeling of fullness in the abdomen, hernia hiatal, constipation, dry mouth, biliary colic, cholecystitis.

The skin and subcutaneous tissue: often - acne, itching, rash; rare - chloasma, eczema, alopecia, prepodobnyi dermatitis, dry skin, erythema nodosum, hypertrichosis, striae, contact dermatitis, photodermatitis; frequency is unknown - erythema multiforme.

From the side of musculoskeletal system: infrequently - back pain, pain in extremities, muscle spasms.

From the reproductive system and mammary gland: often, breast tenderness, acyclic bleeding**, no menstrualnopodobne bleeding; infrequently - pain in the pelvic area, breast enlargement, fibropenobetona breast, discharge from the genital organs, congestion, vaginitis, painful menstrualnopodobnoe bleeding, poor menstrualnopodobnoe bleeding, dry vaginal mucosa, pathological changes in the smear by Papanicolaou; rarely is dyspareunia, vulvovaginitis, post-coital bleeding, breast cyst, hyperplasia of the mammary gland, tumors of the breast, polyps of the cervical canal, atrophy of the endometrium, ovarian cyst, uterine enlargement.

Laboratory and instrumental data: rarely, weight gain; rare - reducing body weight.

Other: often - asthenia, sweating, edema (generalized edema, peripheral edema, swelling of the face); rarely malaise.

* venous or arterial thrombosis includes occlusion of peripheral deep venous; thrombosis and embolism /pulmonary vascular occlusion; myocardial infarction, cerebral infarction and hemorrhagic stroke.

** in the process of continuous treatment irregular bleeding typically decreases. 

The following adverse reactions have been reported in women who use PDAs, with very rare frequency of occurrence or with delayed symptoms, which are believed can be associated with the receiving PDA:

• breast cancer;
  
• liver tumors (benign and malignant);
  
• erythema nodosum;
  
• increased blood pressure;
  
• pancreatitis in women with hypertriglyceridemia;
  
• occurrence or deterioration of conditions whose connection with the admission of the CCP is not completely established: porphyria, SLE, herpes pregnant, Sydenham chorea, haemolytic uremic syndrome, cholestatic jaundice and/or itchy, associated with cholestasis; cholelithiasis; otosclerosis with deterioration of hearing;
  
• abnormal liver function;
  
• change of glucose tolerance and development of insulin resistance;
  
• chloasma;
  
• Crohn's disease, ulcerative colitis;
  
• hypersensitivity reactions (including skin rash, urticaria).
  

In women with hereditary angioedema estrogens may induce or exacerbate its symptoms.

Special conditions

Medical examinations

Before the start or resumption of the use of the drug Modell the Trend should be familiar with the life history, family history of women, a thorough General medical (including measurement of blood pressure, heart rate, determination of BMI) and gynecological examination, including breast examination and cytological examination of scraping from the cervix (Papanicolaou test), to exclude pregnancy. The amount of additional research and the frequency of control examinations are set individually. Typically, control examinations should be conducted at least 1 time in 6 months.

A woman should be informed that the drug Modell Trend 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 application of the PDA in each individual case and to discuss it with the woman before she decides to start taking the drug. With weighting, strengthening or at the first sign of risk factors may require removal of the drug.

Cardiovascular disease

The results of epidemiological studies indicate a relationship between use of PDAs and increasing the incidence of venous and arterial thrombosis and thromboembolism such as deep vein thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular disease. These diseases are rare.

The risk of developing venous thromboembolism (VTE) is maximal in the first year of taking these drugs. Particularly high risk during the initial use of PDA or re-application of the same or different PC (after the break between doses of the drug in the 4 weeks or more). Data from a large prospective study involving 3 groups of patients show that the risk is highest mainly for the first 3 months.

The overall risk of VTE in women taking low-dose MMR (containing less than 50 µg ethinyl estradiol), 2-3 times higher than in nonpregnant women who do not take your PDA, however, this risk remains lower than the risk of VTE during pregnancy and childbirth. VTE can lead to death (1-2% of cases).

VTE, manifested as deep vein thrombosis or pulmonary embolism (PE) can develop in the application of any PDA.

Extremely rare in the application of the CCP occurs thrombosis other blood vessels, e.g. hepatic, mesenteric, renal, cerebral veins and arteries or vessels of the retina. A unified view on the relationship between the occurrence of these events and the use of PDA is missing. Symptoms of deep vein thrombosis (DVT) include: unilateral swelling of the lower limbs along the veins on the lower limbs, pain or discomfort in the lower limbs in an upright position or during walking, the local temperature increase in the affected lower limbs, redness, or discoloration of the skin on the lower limbs.

Symptoms of pulmonary embolism the following: difficulty or rapid breathing; sudden cough, including coughing up blood; sharp chest pain which may increase with deep breathing; sense of anxiety; severe dizziness; fast or irregular heartbeat. Some of these symptoms (e.g., dyspnea, cough) are nonspecific and may be misinterpreted as symptoms of other more or less severe events (e.g. respiratory infection).

Arterial thromboembolism may lead to stroke, vascular occlusion or myocardial infarction. Symptoms of a stroke: sudden weakness or loss of sensation of the face, limbs, especially on one side of the body sudden confusion, trouble speaking and understanding; sudden uni - or bilateral loss of vision; sudden gait disturbance, dizziness, loss of balance or coordination; sudden, severe or prolonged headache with no apparent cause; loss of consciousness or fainting with seizure. Other signs of vascular occlusion: sudden pain, swelling and mild bruising of the extremities, the syndrome of "acute abdomen."

For more information, see the user manual

Testimony

• contraception;
  
• contraception and treatment of acne of moderate severity (acne vulgaris);
  
• contraception and treatment of severe forms of premenstrual tension
  

Contraindications

• thrombosis (venous and arterial) now or in history (e.g. deep venous thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular disorders);
  
• state prior thrombosis (including transient ischemic attack, atrial fibrillation, angina pectoris) now or in history;
  
• identified predisposition to venous or arterial thrombosis, including resistance to activated protein C, antithrombin III deficiency, protein deficiency, protein S deficiency, hyperhomocysteinemia, antibodies to phospholipids (antibodies to cardiolipin, lupus anticoagulant);
  
• migraine with focal neurological symptoms in the present or in history;
  
• diabetes with vascular complications;
  
•  multiple or severe risk factors for venous or arterial thrombosis (including complicated lesions valvular apparatus of the heart, atrial fibrillation, vascular diseases of the brain or coronary arteries; uncontrolled hypertension, prolonged immobilization, extensive surgery, surgery on the lower extremities, extensive trauma, Smoking age 35 years, obesity with BMI > 30 kg/m2);
  
• pancreatitis with severe hypertriglyceridemia in the present or in history;
  
• hepatic failure and severe liver disease (up to normalization in liver function tests and within 3 months after the return of these indicators to normal);
  
• liver tumors (benign or malignant) currently or in history;
  
• acute renal failure or renal failure severe;
  
• identification of hormone-dependent malignant diseases (including genital or mammary glands) or suspicion on them;
  
• vaginal bleeding ambiguous Genesis;
  
• pregnancy or suspicion on it;
  
• lactation (breastfeeding);
  
• hereditary lactose intolerance, lactase deficiency or malabsorption syndrome glucose-galactose;
  
• hypersensitivity to the drug.
  

If any of the above diseases or conditions develop for the first time while taking the drug, it should be discontinued immediately.

With caution

Should evaluate the potential risk and expected benefit of the drug Modell Trend in each individual case if the following diseases/conditions and risk factors:

• risk factors for thrombosis and thromboembolism: Smoking, obesity (BMI <30 2="" -="" 35="" br="">
  
• other diseases which may include peripheral circulatory disorders: diabetes mellitus without diabetic angiopathy, systemic lupus erythematosus (SLE), hemolytic-uremic syndrome, Crohn's disease or ulcerative colitis, sickle cell anemia, flebit superficial veins;
  
• hereditary angioedema;
  
• hypertriglyceridemia;
  
• liver disease not related to contraindications;
  
•  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, otosclerosis with deterioration of hearing, porphyria, herpes pregnant, chorea Sydenham);
  
• postpartum period.
  

Application of pregnancy and breastfeeding

Pregnancy

The use of the drug Modell Trend is contraindicated in pregnancy. If pregnancy is detected during the application of the drug Modell Trend, the drug should immediately cancel. Extensive epidemiological studies have not identified an increased risk of developmental defects in children born to women treated with sex hormones before pregnancy, or teratogenic effects in cases when sex hormones were taken inadvertently in early pregnancy.

In animal studies, the effects of drospirenone and ethinyl estradiol were associated with their pharmacological effects. In particular, in reproductive toxicity studies in animals revealed embryotoxic and fetotoksi?eskoe effect, but these effects were considered as associated with specific animal species. At levels of exposure in animals greater than the corresponding levels in patients taking drospirenone and ethinyl estradiol, was observed the influence on the sex differentiation of rat embryos, which was absent from the small monkeys. According to the data obtained in animal studies cannot exclude the possibility of development of undesirable effects caused by the hormonal activity of active substances, the person. However, the cumulative experience of using a PDA during pregnancy did not provide evidence of adverse effects in humans. Data on the results of the drug Modell Trend in pregnancy is limited, which does not allow to draw any conclusions about the negative impact of the drug on pregnancy, health of the fetus and newborn. Currently, any significant epidemiological data are not available.

Lactation

The use of the drug Modell Trend is contraindicated during breastfeeding. PDAs can decrease the amount of breast milk and change its composition, so their use is not recommended until the cessation of breastfeeding. A small amount of sex hormones and/or their metabolites may be excreted with the milk.

Drug interactions

The interaction of oral contraceptives with other drugs may lead to breakthrough bleeding and/or reduce the contraceptive reliability. Women taking these drugs should temporarily use a barrier method of contraception in addition to the drug Modell Trend or choose another method of contraception.

Drugs that reduce the effectiveness of the drug Modell Trend

The use 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 drugs 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.

While taking drugs that affect hepatic 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. While antibiotics (such as penicillins and tetracycline) and for 7 days after their cancellation should additionally use a barrier method of contraception. If during these 7 days of use of barrier methods of contraception more active pills, skip taking the inactive pills from the current package and start taking active pills from the next package of the drug Modell Trend.

Other interactions

The main metabolites of drospirenone are generated in the plasma without the participation of cytochrome P450. Therefore, it is unlikely the effect of inhibitors of cytochrome P450 on the metabolism of drospirenone.

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.

Based on the studies of interactions in vitro and studies in female volunteers taking omeprazole, simvastatin and midazolam revealed that the effect of drospirenone in a dose of 3 mg on the metabolism of other drugs is unlikely.

There is a theoretical possibility of increasing the concentration of potassium in the blood plasma in women receiving the drug Modell Trend in combination with other drugs, which can increase the concentration of potassium in the blood plasma. These drugs include ACE inhibitors, antagonists of angiotensin II receptor some anti-inflammatory drugs, potassium-sparing diuretics and aldosterone antagonists. However, in studies investigating the interaction of drospirenone with ACE inhibitors or indomethacin, there were no significant differences between the concentration of potassium in the blood plasma compared to placebo.

Dosage

The tablets are taken orally in order specified on the package every day at about the same time, squeezed small amounts of water. It should take 1 tab./day continuously for 28 days. Taking pills from the next pack should be started the day after taking the last pill from the previous package. Withdrawal bleeding usually starts 2-3 days after you start taking the inactive pills and may not end before you start taking pills from a new package. The beginning of the drug in the absence of any hormonal contraceptive use in previous month use of the drug start in 1 day menstrual cycle (i.e., in the 1-St day menstrual bleeding). Allowed to start at the 2-5 day menstrual cycle, but in this case it is recommended to additionally use a barrier method of contraception during the first 7 days of taking the pills from the first package. The transition from other combined hormonal contraceptives (PDA, vaginal ring or contraceptive patch), it is Preferable to start taking the drug Modell Trend the next day after taking the last active tablet from the previous packaging, but in any case not later than the next day after taking the last inactive tablet (for drugs, containing 28 tablets per pack). The drug Modell Trend should begin on the day of removal of the vaginal ring or patch, but not later than the day when it should be introduced a new ring or apply a new patch. The transition from contraceptives containing only progestogen ("mini-pili", injectable form, implant or intrauterine system (IUD) controlled release of progestogen) you Can go to the reception "mini-pill" for the drug Modell Trend any day (without a break), with implants or IUD with progestogen - the day of its removal, from an injectable contraceptive - on the day when should be made following injection. In all cases, you must use an additional barrier method of contraception during the first 7 days of taking the pills. After abortion in the first trimester of pregnancy. You can start taking the drug immediately - on the day of the abortion. Under this condition the woman needs no additional contraceptive methods. After delivery or abortion in the II trimester of pregnancy is Recommended to start taking the drug for 21-28 days after birth (with no breastfeeding) or abortion in the II trimester of pregnancy. If the reception is started later, you must use an additional barrier method of contraception during the first 7 days of taking the pills. However, if a woman has been sexually active, before you start taking the drug Modell Trend should be deleted pregnancy or must wait for first menstruation. Receiving missed pills, Skipping the inactive tablets can be ignored. However, they should be discarded in order not to prolong the period of taking the inactive pills. The following recommendations apply only to the missing active pills. If the delay in receiving the drug was less than 24 hours, contraceptive protection is not reduced. You should take the missed pill as soon as possible, and should be taken at the usual time. If the delay in the pill was more than 24 hours, contraceptive protection may be reduced. The more missed tablets and the closer the skipping pills to the phase of taking the inactive pills, the greater the chance of pregnancy. This can be guided by the following two basic rules: - the drug should never be interrupted for more than 4 days; - to achieve adequate suppression of the hypothalamic-pituitary-ovarian system required 7 days of continuous pill-taking. Accordingly, if the delay in taking active pills was more than 24 hours, we can recommend the following. The first week of use of the drug Should take the last missed tablet as soon as possible, as soon as the woman remembers this (even if you just need to take two pills at the same time). Take the next pill at the usual time. Must additionally be used a barrier method of contraception (e.g. condom) for the next 7 days. If intercourse took place 7 days before skipping pills, you must take into account the probability of pregnancy. Second week use of the drug Should take the last missed tablet as soon as possible, as soon as the woman remembers this (even if you just need to take two pills at the same time). Take the next pill at the usual time. Provided that the woman took the pills correctly during the 7 days preceding the first missed tablet, there is no need to use additional contraceptive measures. Otherwise, as well as the passage of two or more pills should also use a barrier method of contraception (e.g. condom) for 7 days. Third week of the drug, the Risk of pregnancy increases due to the upcoming of taking the inactive pills. Should strictly adhere to one of the following two options. If during the 7 days preceding the first missed pill, all the pills are taken correctly, there is no need to use additional contraceptive methods. Otherwise, you must use the first of the following schemes and additionally use a barrier method of contraception (e.g. condom) for 7 days. 1. You should take the last missed tablet as soon as possible, as soon as the woman about this recall (even if this means taking two tablets at the same time). Next take the pills at the usual time until the active tablets in the package. Four inactive tablets should be discarded and immediately start taking pills from the next pack. Withdrawal bleeding is unlikely until the end of the active tablets in the second pack, but may experience spotting and breakthrough bleeding while taking the pills. 2. You can also stop taking tablets from the current package. Then the woman should take a break of not more than 4 days, including the days of missing the pills, and then start the drug of the new packaging. If the woman missed active tablets, and while taking the inactive pills withdrawal bleeding does not occur, pregnancy must be excluded.