The contraceptive effect dianabol for sale , as well as other combined oral contraceptives (COCs), based on the interaction of various factors, the most important of which are inhibition of ovulation and changes in the cervical secretion. Progestogens drug (desogestrel) reduces the secretion of gonadotropin-releasing hormone, to a greater extent luteinizing hormone (LH), and thus prevents the maturation of the follicle (ovulation blocks). Ethinylestradiol, a synthetic analogue of the natural hormone estradiol, reduces the likelihood of acyclic bleeding when using COCs. In addition to these central and peripheral mechanisms, preventing the maturation able to fertilize an egg, a contraceptive effect is due to an increase in the viscosity of the mucus, located in the cervix, which makes it relatively impassable for sperm. In addition to the contraceptive properties of the drug Mersilon ® has a number of effects that can be taken into account when choosing a contraceptive method. Menstrualnopodobnoe reactions become more regular flow less painful and accompanied by less pronounced bleeding. The latter circumstance leads to a decrease in the frequency of concomitant iron deficiency anemia. When using COCs has been shown to reduce the risk of ovarian and endometrial cancer.
Pharmacokinetics Desogestrel Absorption Desogestrel passed orally, is rapidly and completely absorbed and then converted to etonogestrel. Its maximum concentration in serum is reached after 1.5 hours. Bioavailability is 62-81%. The distribution of etonogestrel is bound to albumin and serum globulin, sex hormone binding (SHBG). Only 2.4% of the total serum concentration of etonogestrel is present as free steroid, 40-70% specifically bind to SHBG. Increasing the concentration of SHBG induced by ethinylestradiol influences the distribution between the blood supply, leading to an increase in the SHBG-bound fraction and a decrease in the albumin-bound fraction. The apparent volume of distribution of desogestrel is 1.5 l / kg. Metabolism etonogestrel completely metabolized by the known pathways of steroid hormone metabolism; rate of metabolic clearance of serum was 2 ml / min / kg. There were no interactions with both etonogestrel received ethinylestradiol. Withdrawal concentration in serum etonogestrel reduced in 2 stages. The final stage is characterized by a half-life (T1 / 2) is about 30 hours. Desogestrel and its metabolites are excreted via the kidneys and intestines in a ratio of about 6: 4. Conditions of equilibrium on the pharmacokinetics of etonogestrel influences of SHBG, the concentration of which increases under the influence ethinylestradiol 3 times. When taken daily serum concentrations of etonogestrel is increased by 2-3 times, reaching a constant value in the second half of the cycle. Ethinylestradiol AbsorptionEthinylestradiol after oral administration is rapidly and completely absorbed. Its maximum plasma concentration is reached within 1-2 hours after ingestion. Absolute bioavailability (the result of first pass metabolism) is about 60%. The distribution of Ethinylestradiol nonspecifically binds serum albumin to substantially completely (98.5%), the concentration of SHBG increases. The apparent volume of distribution of ethinyl estradiol is 5 l / kg. Metabolism Ethinylestradiol undergoes first-pass metabolism in the intestinal mucosa and in the liver. Ethinyl estradiol is metabolized in the original aromatic hydroxylation to form various hydroxylated and methylated metabolites that are present in the free state and as conjugates with glucuronides and sulfates. Metabolic clearance rate of ethinylestradiol from plasma is about 5 ml / min / kg. Excretion concentration of ethinyl estradiol in the serum decreased in two stages. The final stage is characterized by T1 / 2 of about 24 hours. The drug does not appear unaltered, ethinyl estradiol metabolites are excreted via the kidneys and intestines in a ratio of 4: 6. T1 / 2 is about metabolites days. Terms equilibrium equilibrium concentration achieved after 3-4 days of treatment, when the serum concentration is 30-40% higher than the concentration after a single dose.
The drug Mersilon ® , as well as other combined oral contraceptives should not be taken if any of the conditions (states) listed below. If any of them occurs in patients receiving the drug should immediately stop taking it.
- Hypersensitivity to the active substances or to any excipient product Mersilon ® .
- Available at the moment, or a history of venous thrombosis (including deep vein thrombosis of the lower leg, pulmonary embolism).
- Available at the moment or in the history of arterial thrombosis (including myocardial infarction, stroke) or precursors of thrombosis (incl transient ischemic attack, angina pectoris).
- Detection of predisposition for venous or arterial thrombosis, including resistance to activated protein C, hyperhomocysteinemia, antithrombin III deficiency, protein C deficiency, protein deficiency of the S, antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant).
- Migraine with focal neurological symptoms history.
- Diabetes mellitus with vascular disease.
- The presence of serious or multiple risk factors for venous or arterial thrombosis (including hypertension with BP 160/100 mm Hg or higher).
- Pancreatitis (including history), accompanied by severe hypertriglyceridemia
- Severe liver disease (up to normalization of liver function), including: history.
- Liver tumors (benign or malignant), including: history.
- Hormone-dependent malignant tumors of genitals or mammary gland (including suspects).
- Bleeding from the vagina of unknown etiology.
- Smoke over the age of 35 years (more than 15 cigarettes per day).
- Pregnancy (including estimated).
- Lactose intolerance, lactase deficiency, glucose-galactose malabsorption.Precautions
If any of the conditions / risk factors mentioned below are currently available, you should carefully weigh the potential risks and expected benefits of the drug application dianabol for sale in each individual case:
- age over 35 years;
- in the presence of a family history of thromboembolic disease (venous or arterial thrombosis / thromboembolism in siblings or parents at a relatively early age);
- obesity (body mass index> 30 kg / m);
- arterial hypertension;
- valvular heart disease;
- atrial fibrillation;
- prolonged immobilization, major surgery, surgery on the lower extremities, severe injury (during prolonged immobilization and above surgery it is recommended to stop using the drug, with elective surgery no later than 4 weeks before the operation, and not to renew the appointment within 2 weeks after complete remobilization);
- varicose veins, superficial thrombophlebitis (currently there is no single opinion on the possible role of these conditions in the etiology of venous thromboembolism);
- postpartum period;
- changes in biochemical indicators that may be markers of congenital or acquired predisposition for venous or arterial thrombosis, including resistance to activated protein C, hyperhomocysteinemia, antithrombin III deficiency, protein C deficiency, protein deficiency of the S, antiphospholipid antibodies (antibodies to cardiolipin, lupus anticoagulant);
- systemic lupus erythematosus;
- hemolytic-uremic syndrome;
- chronic inflammatory bowel disease (Crohn’s disease or ulcerative colitis);
- sickle cell anemia;
- hypertriglyceridemia (including family history);
- acute and chronic liver disease, includingcongenital hyperbilirubinemia (Gilbert’s syndrome, Dubin-Johnson syndrome, Rotor),.Pregnancy and lactation
Use of the drug Mersilon ® during pregnancy is contraindicated. In case of pregnancy during use of the drug Mersilon ® should stop taking the drug. It should be noted that extensive epidemiological studies have revealed no increased risk of having children with birth defects in women taking COCs before pregnancy, or teratogenic effect of Accidental COC at the beginning of pregnancy.
Small amounts of contraceptive steroids and / or their metabolic products may be excreted in milk.
Dosing and Administration
The tablets should be taken orally in the order directed on the package every day at about the same time, with a little water, if necessary. Take 1 tablet per day for 21 days. Taking the pills from the next pack should be started 7 days after the end of the previous one. During these 7 days menstrualnopodobnoe bleeding occurs. It usually starts on day 2-3 after the last tablet and may not end before you start taking the next pack. As start taking the drug dianabol for sale – If not used hormonal contraceptives during the last month Receiving tablets should begin on day 1 of the menstrual cycle (ie. e. the first day of menstrual bleeding). You can start taking the drug for 2-5 day cycle, but in this case it is recommended to use an additional (non-hormonal) method of contraception during the first 7 days of tablet-taking in the first cycle. – The transition from a combined hormonal contraceptive (combined oral contraceptive vaginal ring or transdermal patch ) It is advisable to start taking the drug the next day after taking the last active tablet previously used the drug (the last tablet containing the active substances), but not later than the next day after the usual tablet-free interval or the next day after taking the last pill containing no hormones. In the case of a vaginal ring or transdermal patch, it is advisable to start taking the drug on the day of removal, but not later than the day that should have been introduced a new ring or make the following application of the patch. If a woman has applied previous contraceptive method consistently and correctly and if certain that she is not pregnant, in this case, a woman can go to the reception on any day of the cycle. it should be borne in mind that the normal range in the application of the previous method of contraception, must not exceed the recommended duration. – transition from products containing only progestogen ( “mini-pill”, injection, implant) or from a progestogen-releasing intrauterine system (IUS) The woman receiving the “mini-pill” can go to the reception of the drug Mersilon ® on any given day; using an implant or an IUD – the day of their removal; used drugs by injection – the day when the next injection should be, in all cases within the first 7 days of taking the drug Mersilon ® is recommended to use additional methods of contraception. – After the abortion done in the first trimester The woman may start taking the drug immediately. No need to use any additional methods of contraception. – After childbirth or abortion done in the second trimester For breastfeeding women, see section “Pregnancy and breast-feeding period.”. It is recommended to start taking the drug no earlier than 21-28 days after birth or abortion done in the second trimester of pregnancy. At the beginning of the drug at a later date recommended for the first 7 days of taking the drug Mersilon ®use barrier methods of contraception. In any case, if a woman after childbirth or abortion before you start taking the drug Mersilon ® has been sexual intercourse, pregnancy should be ruled prior to ingestion, or wait until the first menstrual period. What to do in case of missing the next dose if receiving regular tablets detained less than to 12 hours of contraceptive reliability is not reduced. The woman should take the tablet as soon as she thought about it, and the next tablet at the usual time taken. If the reception is another tablet detained more than 12 hours, contraceptive reliability may be reduced. In this case, should be guided by the following two rules: 1. pills should never be interrupted for more than 7 days. 2. for adequate suppression of the hypothalamic-pituitary-ovarian system is necessary to take the tablets for 7 consecutive days. Cyclical dosing means 3 weeks of use. Accordingly, we can give the following recommendations:
- Week 1
The woman should take the missed pill as soon as she thought about it, even if this means taking two tablets at the same time. Then, should continue to receive the usual way. Additionally, you should use barrier methods of contraception for the next 7 days. If a woman has had sexual intercourse within the preceding 7 days, the possibility of pregnancy should be considered. The more missed tablets and the closer a break in taking the drug at the time of sexual intercourse, the greater the risk of pregnancy.
- Week 2
The woman should take the missed pill as soon as she thought about it, even if this means taking two tablets at the same time. Then, should continue to receive the usual way. Provided that the woman took pills on time for 7 days preceding the first missed dose is not necessary to use additional (non-hormonal) contraceptive methods. Otherwise, or if the woman missed more than one tablet, it is recommended to use additional methods of contraception for the next 7 days.
- Week 3
The reliability of contraception may be reduced due to the subsequent break in taking the drug. This can be avoided by adapting the scheme of the drug. If you use either of the two following schemes, there is no need to use additional contraceptive measures, provided that the woman is on the pill in time for the 7 days preceding the first missed dose. Otherwise, it is recommended to use one of the two following schemes and also use additional contraceptive measures during the next 7 days.
1. The woman should take the missed pill as soon as she thought about it even if it means taking two tablets at the same time. Then, should continue to receive the usual way. New packaging should be started as soon as the current package ends, ie, should not make a break between packs. Probability of “withdrawal bleeding” before the end of the second package is small, but some may experience spotting or profuse bleeding even during treatment.
2. Women can be advised to discontinue the drug from the current package. Women should take a break from taking the drug Mersilon ® no longer than 7 days, including the days she forgot to take the pill, and then start a new pack.
If you forget to taking the drug and the subsequent absence of “withdrawal bleeding” in the near tablet-free interval should be consider the possibility of pregnancy. Advice in case of gastro-intestinal disorders, the presence of severe gastro-intestinal disorders absorption may be incomplete and should take additional contraceptive measures. If vomiting occurs within 3-4 hours after taking the drug, you should use the recommendations for skipping the next dose. If a woman does not want to change their usual dosage regimen, it is necessary to take additional (s) tablet (s) from another package (number of additional tablets is determined by the specialist obstetrician-gynecologist at the internal consultation). How to change the term offensive menstrualnopodobnoe bleeding To delay menstrualnopodobnoe bleeding should continue taking pills from another drug packaging Mersilon ® without the usual break at the reception. Postpone menstrualnopodobnoe bleeding can be for any period up to the end of the tablets of the second pack. During this period, the woman may experience spotting or heavy bleeding. The drug in the usual way should be resumed after the 7-day interval in taking. In order to bias the first day of bleeding menstrualnopodobnoe the next day, it is possible to reduce the usual tablet-free interval for as many days as necessary. The shorter the interval, the higher the risk of lack of menstrualnopodobnoe bleeding during the break and the occurrence of abundant or spotting while taking tablets from the second pack.
- Thrombosis or thromboembolism (including myocardial infarction, stroke, deep vein thrombosis, dianabol for sale pulmonary embolism), thrombosis of hepatic, mesenteric, renal arteries and veins, retinal arteries.
- Increased blood pressure.
- Hormone-dependent tumors (liver tumors, breast cancer).
- Chloasma (especially if there is a history of chloasma during pregnancy).
- Acyclic spotting more often in the first months of administration.
- Allergic reactions.
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