Index of drugs

Oral contraception. Treatment of severe menstrual bleeding without pathological changes of an organic nature in women intending to use oral contraception.

Each blister contains 28 tables. powl. arranged in the following order: 2 tables dark yellow, each containing 3 mg estradiol valerate; 5 tables red, each containing 2 mg estradiol valerate and 2 mg dienogest; 17 tables light yellow, each containing 2 mg estradiol valerate and 3 mg dienogest; 2 tables dark red, each containing 1 mg estradiol valerate; 2 tables white, which do not contain active substances. The preparation contains lactose.

Sequential preparation containing progestin (dienogest) and estrogen (estradiol valerate). The contraceptive effect is the result of the interaction of several factors, of which the most important are: inhibition of ovulation, changes in the secretion of the uterine cervix and changes in the endometrium. Dienogest is absorbed quickly and almost completely after oral administration. The maximum concentration in plasma reaches about 1 hour after oral intake. Bioavailability is about 91%. Food intake does not affect the frequency and prolonged absorption of dienogest. The 10% fraction is present in the plasma in unbound form, and about 90% are associated non-specifically with albumin. Dienogest does not bind to sex hormone binding globulin (SHBG) or corticosteroid binding globulin (CBG). It is almost completely metabolised in the steroid metabolism pathways (hydroxylation, conjugation), mainly by CYP3A4. T_0,5 in plasma is about 11 hours. It is excreted in the form of metabolites, and only 1% in unchanged form, mainly in the urine. Estradiol valerate is completely absorbed after oral administration. Its breakdown into estradiol and valeric acid occurs during absorption in the intestinal mucosa or during the first pass through the liver. This creates estradiol and its metabolites - estrone and estriol. The maximum serum concentration is obtained after 1.5 to 12 h. Estradiol is subject to a clear first-pass effect and a significant part of the administered dose is metabolized already in the mucous membrane of the gastrointestinal tract. The main metabolites are estrone, estrone sulfate and estrone glucuronide. In plasma, 38% of estradiol is associated with SHBG, 60% with albumin, and only 2-3% circulate in unbound form. T_0,5 in plasma is about 13-20 h. Estradiol and its metabolites are excreted mainly in the urine, and only about 10% in the faeces.

Hypersensitivity to the active substances or to any of the excipients. Current or past venous thrombosis (deep vein thrombosis, pulmonary embolism). Current or past arterial thrombosis (e.g., myocardial infarction) or conditions conducive to the occurrence of thrombosis (e.g., angina pectoris and transient cerebral ischemia). Current or past cerebrovascular incident. The presence of severe or multiple risk factors for venous or arterial thrombosis: diabetes with vascular lesions, severe hypertension, severe dyslipoproteinaemia. Inherited or acquired predisposition to arterial or venous thrombosis, eg resistance to activated C protein (APC), antithrombin III deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinemia and the presence of anti-phospholipid antibodies (anti-cardiolipin antibodies, lupus anticoagulant). Current or previous pancreatitis associated with significant hypertriglyceridemia. Current or past severe liver disease (until liver function tests return to normal). Current or past history of benign or malignant liver tumors. Occurrence or suspicion of cancers dependent on steroidal sex hormones (eg, genital or breast cancer). Bleeding from the genital tract of undetermined etiology. Presence of migraine headaches with focal neurological symptoms in the past.

The use of combined oral contraceptives is associated with a higher risk of venous thromboembolism (VTE). The risk is the highest in 1.one year of use in women who start taking a combined oral contraceptive for the first time or when they start using it for at least a month. The use of ethinylestradiol-containing combined oral contraceptives is associated with an increased risk of arterial thromboembolic events (myocardial infarction, transient ischemic attacks). The occurrence of thrombosis of other blood vessels, such as hepatic, mesenteric, renal, cerebral or retinal vessels, is uncommon - it is uncertain whether these events are associated with the use of hormonal contraceptives. Factors that increase the risk of venous thromboembolism: age; positive family history (ie occurrence of venous or arterial thromboembolism in siblings or parents at a relatively young age) - if genetic predisposition is suspected, a woman should be referred to a specialist before consultation with a combined oral contraceptive; immobilization for a longer period, extensive surgery, any surgery in the lower limbs or a serious injury - in these situations, it is recommended to discontinue the preparation (at least 4 weeks before the planned surgery) and resume admission after 2 weeks from the time of return the woman's full mobility; consideration should be given to the introduction of anticoagulant therapy if tablets are not discontinued; obesity (index above 30 kg / m)²). The presence of varicose veins and thrombophlebitis of superficial veins in the early stages and progression of venous thrombosis is not established. The following factors increase the risk of arterial thromboembolic events or cerebrovascular events: age; smoking (women over 35 who intend to use combined oral contraceptives, smoking should be strongly advised); positive family history (ie the occurrence of arterial thromboembolism in siblings or parents at a relatively young age) - if genetic predisposition is suspected, before a decision to apply a woman should be referred to a specialist for consultation; obesity (index above 30 kg / m)²); dyslipoproteinaemia; hypertension; migraine; heart valve defects; atrial fibrillation. The presence of one serious or several risk factors for venous or arterial disease may be a contraindication to use. In such cases, the possibility of anticoagulation should also be considered. In case of suspected or diagnosed thrombosis, the preparation should be put on. Due to the teratogenic effect of anticoagulants (coumarin), another appropriate method of contraception should be used. Increasing the risk of thromboembolic complications during the postpartum period should be considered. Other disorders conducive to the occurrence of cardiovascular side effects include: diabetes mellitus, systemic lupus erythematosus, haemolytic-uremic syndrome, chronic enteritis (Crohn's disease or ulcerative colitis) and sickle cell anemia. Increasing the frequency and severity of migraine headaches while taking the preparation may be a prodromal sign of ischemic stroke and, in this case, the preparation should be discontinued immediately. Long-term use of combined oral contraceptives (over 5 years) may increase the risk of cervical cancer. Nevertheless, disputes over the importance of additional factors, such as sexual behavior and others such as human papillomavirus (HPV) infections continue. In women taking combined oral contraceptives there is a slightly increased risk of relative diagnosis of breast cancer. The increased risk gradually disappears within 10 years of the end of the preparation. In women taking combined oral contraceptives in the event of severe epigastric pain, enlargement of the liver or symptoms of abdominal haemorrhage, differential diagnosis should include liver cancer. In women with hypertriglyceridemia or a positive family history of hypertriglyceridaemia, there may be an increased risk of pancreatitis when taking combined oral contraceptives.If persistent hypertension develops during treatment, the physician should consider discontinuation and initiation of antihypertensive therapy. In justified cases, it is possible to return to the use of combined oral contraceptives in patients who have normalized their blood pressure under the effect of antihypertensive therapy. The following conditions have been reported or worsening both during pregnancy and when taking combined oral contraceptives: jaundice and / or pruritus associated with cholestasis, cholelithiasis, porphyria, systemic lupus erythematosus, haemolytic-uremic syndrome, Sydenhama chorea. herpes of pregnant women, hearing loss associated with otosclerosis. In women with congenital angioneurotic edema, exogenous oestrogens may cause or worsen symptoms of angioedema. acute or chronic liver dysfunction sometimes requires discontinuation of the preparation until the liver parameters return to normal. If the cholestatic jaundice recurs during pregnancy or prior sex hormone replacement, the preparation should be discontinued. Combined oral contraceptives may affect peripheral resistance to insulin and Glucose tolerance - however, there is no need to change the treatment regimen of diabetes; the condition of diabetic patients should be carefully monitored, especially in the initial period of use of combined oral contraceptives. There have been reports of worsening of the course of endogenous depression, epilepsy, Crohn's disease and ulcerative colitis in women taking combined oral contraceptives. Women predisposed to chloasma should avoid exposure to solar and ultraviolet light during treatment. Estrogens can cause fluid retention, so patients with impaired cardiac or renal function should stay under constant medical supervision. Patients with terminal renal failure should be closely monitored. The preparation contains lactose - in patients with rare hereditary galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption using a lactose-free diet, the lactose content of the preparation should be taken into account. The efficacy of combined oral contraceptives can be reduced, inter alia, in the following cases: skipping the active substance, gastrointestinal disorders when tablets containing active substances are used, or other medicines. Irregular bleeding (spotting or intracycular bleeding) may occur during use, especially in the first months of use - the assessment of irregular bleeding may only be meaningful after the adaptation period, which lasts about 3 cycles. If cyclical bleeding persists or occurs in a woman who has had regular menstrual cycles, non-hormonal etiology should be considered and appropriate diagnostics should be performed to rule out malignant tumors or pregnancy. This diagnosis may include curettage of the uterine cavity.

The preparation should not be used in pregnant women. If a woman becomes pregnant while using the preparation, her use should be discontinued immediately. In extensive epidemiological studies, there was no increased risk of congenital malformations in the children of women who used combined oral contraceptives prior to pregnancy or teratogenic due to unintentional use during pregnancy. Complex oral contraceptives may affect lactation, reducing the amount and changing the composition of the food. They are not recommended until breastfeeding is completed. Small amounts of contraceptive steroids and / or their metabolites may be secreted with milk - such amounts may affect the child.

Common: headache, abdominal pain (including flatulence), nausea, acne (including acne pustular), amenorrhea, breast pain, painful menstruation, intracerebral bleeding (uterine haemorrhage), weight gain.Uncommon: fungal infections, vaginal candidiasis, vaginal infection, increased appetite, depression, mood depression, mood disorders (including the tendency to cry and emotional instability), insomnia, decreased libido, mental disorders, mood swings, dizziness, migraine, shock heat, hypertension, diarrhea, vomiting, increased levels of liver enzymes, alopecia, hyperhidrosis, pruritus, rash, muscle spasms, breast enlargement (including breast swelling), breast bumps, cervical dysplasia, uterine bleeding, painful sexual intercourse , fibrocystic cystic dysplasia Keywords: dysmenorrhoea, dysmenorrhoea, menstrual disorders, ovarian cyst, pelvic pain, premenstrual syndrome, uterine fibroids, uterine contractions, uterine bleeding, including spotting, vaginal discharge, dry vulva and vagina, fatigue, irritability, edema (including edema) peripheral), weight loss, changes in blood pressure. Rare: candidosis, herpes simplex, putative ocular histoplasmosis, dandruff, urinary tract infection, vaginitis, fluid retention, hypetriglyceridaemia, aggression, anxiety, dysphoric disorder, increased libido, nervousness, psychomotor agitation, sleep disorders, tension, attention deficit , paresthesia, dizziness, contact lens intolerance, dry eye syndrome, eye edema, myocardial infarction, palpitations, bleeding from varicose veins, hypotension, phlebitis, venous pain, constipation, dry tongue, indigestion, gastrointestinal reflux, focal hyperplasia in the liver, cholecystitis, allergic dermatitis, chloasma, dermatitis, hirsutism, hypertrichosis, pruritus, pigmentation disorders, seborrhea, skin changes (including skin sensation), backache, jaw pain, feeling of heaviness, urinary tract pain unnatural bleeds from the ods petrifaction, benign breast cancer, breast cysts, breast cancerin situ, breast discharge, cervical polyps, erythema of the cervix, bleeding during sexual intercourse, galactorrhea, genital secretions, minor menstruation, delayed menstruation, ovarian cyst rupture, burning sensation in the vagina, unpleasant odor from the vagina, discomfort of the vulva and vagina , lymphadenopathy, asthma, shortness of breath, nosebleed, chest pain, malaise, fever, unnatural cervical smear. In women taking combined oral contraceptives, the following serious side effects have been reported: venous thromboembolic events; arterial thromboembolic disorders; hypertension; liver cancer; lack of unambiguous data on the relationship between the use of these preparations and the induction or deterioration: Crohn's disease, ulcerative colitis, epilepsy, migraine, uterine fibroids, porphyria, systemic lupus erythematosus, herpes simplex, Sydenhama chorea, hemolytic-uremic syndrome, cholestatic jaundice ; chloasma; acute or chronic liver dysfunction, sometimes requiring discontinuation of the preparation until liver parameters return to normal; in women with congenital angioedema, exogenous estrogens may cause or worsen the symptoms of this disease. In the group of women using oral contraceptives, breast cancer is more often diagnosed. In addition, erythema erythema, erythema multiforme, breast secretions and hypersensitivity reactions were observed with ethinyloestradiol oral contraceptives.

Orally. The tablets should be taken in the order indicated on the pack, every day, at about the same time of the day, with a small amount of liquid if necessary. The tablets are taken without a break. Take 1 tabl. daily for 28 consecutive days. Each subsequent package should be started the day after the last tablet from the previous pack. The withdrawal bleed usually begins when taking the last tablets from the pack and may not end until the Next packet begins. In some women, the bleeding begins after taking the first tablets from the new pack.Beginning of the preparation. No hormonal contraception last month: taking tablets should start on day 1 of the woman's natural cycle (ie on day 1 of menstrual bleeding).A change from another combined hormonal contraceptive (combined oral contraceptive, vaginal therapeutic system or transdermal patch): should be started the day after the last tablet containing the active ingredients of the previous combined oral contraceptive. If a vaginal or transdermal system is used, the preparation should start on the day the system is removed.Change from a preparation containing only progestagen (Progestin tablet, injection, implant) or the IOP (progestogen releasing system): you can stop the progestogen tablet on any day and start taking the product (in the case of an implant or IUS on the day of removal, in the case of an injection) when the next injection should be made). In each of these cases, it is recommended to use additional mechanical contraception for the first 9 days of taking the tablets of the preparation.After a miscarriage in the first trimester of pregnancy: the preparation can be started immediately. There is no need for additional contraceptive methods.After delivery or miscarriage in the second trimester of pregnancy: tablets should be started between the 21st and 28th days after delivery or miscarriage in the second trimester of pregnancy. If the use of tablets starts later, an additional method of mechanical contraception should be used for the first 9 days of taking tablets. Before starting taking a combined oral contraceptive, pregnancy should be ruled out or the first menstrual bleeding should be allowed if there is an intercourse.Proceeding in case of skipping tablets. The omission of placebo tablets (white) can be ignored. However, they should be discarded so that the period between tablets containing active substances is not unnecessarily prolonged. In the case of omitting the table containing active substances, the following recommendations should be used. If the tablet has elapsed less than 12 hours since the established time, the effectiveness of contraceptive protection is not reduced, you should take the missed tablet as soon as possible and then the next tablet at the set time. If more than 12 hours have elapsed since the established time of taking the tablet, the contraceptive protection may be reduced, take the missed tablet as soon as possible, even if it is equivalent to taking two tablets at the same time. The next tablets should be taken at the set time. Depending on the day of the cycle in which the tablet was missed, additional contraceptive precautions should be used (eg a mechanical method, such as a condom), according to the following rules: if tablets are omitted between day 1 and day 17 of the cycle, the missed tablet should be taken immediately and the next tablet at the set time (even if it is equivalent to taking 2 tablets on the same day); take the next tablets as usual, use additional contraception for 9 consecutive days; if you miss the tablets between the 18th and 24th day of the cycle, you should stop taking the tablets from the current package and immediately take the first tablet from the new packet, take the next tablet as usual, use additional contraception for 9 consecutive days; if you miss the tablets between the 25th and 26th day of the cycle, you should take the missed tablet immediately and the next tablet at the set time (even if it means taking 2 tablets on the same day), there is no need for additional contraception; if you miss the tablets between 27 and 28 days of the cycle, you should throw away the missed tablet, and then take the next tablet as usual, no need for additional contraception. If you do not take your tablets from a new pack, or if you have missed one or more tablets from days 3 to 9, you may be pregnant (if there has been a ratio within 7 days before the missed dose). The more tablets (among those containing two active substances on days 3 to 24) were missed and, if this was closer to the placebo tablet phase, the greater the risk of getting pregnant. If you miss a tablet while using the tablets from the end of the current packaging / the beginning of a new package, there is no withdrawal bleeding, you should consider the possibility of pregnancy.Recommendations in case of stomach or intestinal disorders. In case of severe stomach or intestinal disorders (eg vomiting, diarrhea), absorption may not be complete and additional contraceptive preparations should be used. If vomiting occurred within 3 to 4 hours after taking the tablet containing the active substance, take the next tablet as soon as possible. This additional tablet should be taken as soon as possible within 12 hours of the time of application. If more than 12 hours have elapsed, recommendations for omitted tablets should be taken into account. If a woman does not want to change her current tablet schedule, she should take the right tablet (s) from another pack.