After oral administration of levonorgestrel is rapidly and completely absorbed, its maximum concentration in plasma is about 2 ng / ml, is reached in about 1 hour. After a single oral administration of 0.125 mg of levonorgestrel, together with 0.03 mg of ethinyl estradiol (which corresponds to the highest content of levonorgestrel in a three phase formulation), the highest concentration in the serum component of 4.3 ng / ml, was determined in about 1 hour.
Levonorgestrel binds to serum albumin and globulin, sex hormone binding . The free form is only 1.4% of the total serum concentrations, whereas 55% of the specifically bound to metandienone and about 40% – to albumin. As a result of the induction of the synthesis of ethynyl estradiol binding protein fraction associated increases, while the fraction bound to albumin is reduced. The apparent volume of distribution of levonorgestrel – about 128 l after a single oral tablet Trigestrela containing a higher dose of levonorgestrel.
The equilibrium concentration.
On the pharmacokinetics of levonorgestrel affects concentration in the serum, which is for a 21-day course of Trigestrela increased approximately 2-fold. As a result, the daily ingestion of levonorgestrel serum concentration increases to about 2 times, and the equilibrium concentration is reached in the second half of the course. The volume of distribution at steady state clearance and reduced to 52 l and 0.5 ml / min / kg.
Levonorgestrel is completely metabolized characteristic of sex hormones by metabolizing. After a single oral dose of levonorgestrel high plasma clearance .
Concentration levonorgestrel serum undergoes biphasic decrease. The half-life in the terminal phase is about 22 hours as unchanged Levonorgestrel is not displayed, but only as metabolites via the kidneys and intestines with the half-life of about 24 hours at a ratio of approximately 1: 1..
After oral administration, ethinylestradiol is absorbed rapidly and completely. Maximum serum concentration equal to about 115 pg / ml, is reached in about 1.3 hours. Ethinylestradiol metabolized due to the effect of “primary” passing through the liver, resulting in its oral bioavailability averages about 45%, and there is considerable interindividual differences within 20-65%.
The equilibrium concentration.
The equilibrium concentration is reached after 1 week,
Ethinyl estradiol is almost completely (98%) binds to albumin. Ethinyl estradiol induces the synthesis of SHBG. The apparent volume of distribution of ethinylestradiol – about 3-8 l / kg.
Ethinylestradiol undergoes conjugation presistemna metandienone as in the mucosa of the small intestine and in the liver. The main pathway – aromatic hydroxylation. Clearance from plasma is 2.3-7 ml / min / kg.
of ethinyl estradiol concentration in the serum is reduced bi-phase; The first phase is characterized by a half-life of about 1 hour, and the second -. 10-20 h in an unmodified form of the organism is not displayed. Ethinyl estradiol metabolites are excreted by the liver and kidneys in the ratio 4: 6, with a half-life of about 24 hours.
drug Trigestrel should not be applied if any of the conditions listed below. If any of these conditions develop for the first time in patients receiving the drug should be immediately repealed:
- Hypersensitivity to any component .
- Thrombosis (venous and arterial) and thromboembolism present or in history (including deep vein thrombosis, pulmonary embolism, myocardial infarction), cerebrovascular disorders.
- Conditions prior thrombosis (including transient ischemic attack, angina pectoris) now or in history.
- Multiple or severe venous or arterial thrombosis risk factors, including valvular lesions, cardiac arrhythmias, deep vein thrombophlebitis, cerebrovascular disease, or coronary artery; uncontrolled hypertension (see. “Special instructions”).
- Prolonged immobilization, advanced surgery, surgery on the lower extremities, extensive trauma.
- Migraine with focal neurological symptoms in the present or in history.
- Diabetes mellitus with vascular complications.
- Pancreatitis with severe hypertriglyceridemia now or in history.
- Liver failure and severe liver disease (as long as liver function tests have not returned to normal).
- Liver tumors (benign or malignant) now or in history.
- Identified malignant hormone-dependent diseases (including genital or mammary glands) or are suspected.
- Bleeding from the genital tract of unknown origin.
- Pregnancy or suspected it.
- The period of lactation.
- Lactase deficiency, deficiency of sucrase / isomaltase, fructose intolerance, lactose intolerance, glucose-galactose malabsorption.
Application with caution
if any of the conditions / risk factors mentioned below are currently available, it is necessary to correlate the potential risks and expected benefits of the use of combined oral contraceptives in each case:
- Risk factors for thrombosis and thromboembolism: smoking; thrombosis, myocardial infarction or cerebrovascular accident at a young age in any of the next of kin; obesity (BMI over 30 kg / m2);dislipoproteinemia, hypertension, migraine without focal neurological symptoms;
- Other diseases in which may occur peripheral metandienone circulatory disorders: diabetes mellitus without vascular lesions; systemic lupus erythematosus; hemolytic-uremic syndrome; Crohn’s disease and ulcerative colitis; sickle cell anemia; and phlebitis of superficial veins;
- liver disease;
- Diseases caused or aggravated first time during pregnancy, or on the background of the previous use of sex hormones (eg, jaundice, cholestasis, gallbladder disease, otosclerosis with hearing impairment, porphyria, herpes gestationis, Sydenham’s chorea).
Pregnancy and lactation
Trigestrel not appointed during pregnancy and lactation. If pregnancy is detected during the reception Trigestrel drug, the drug should be immediately abolished. Extensive epidemiological studies have revealed no increased risk of defects in children born to women treated with hormones prior to pregnancy or teratogenic effects when sex hormones were taken inadvertently in early pregnancy.
Receiving combined oral contraceptives can reduce the amount of breast milk and change its composition, therefore, as a rule, their use is not recommended during lactation.
small amounts of sex hormones and / or their metabolites may be excreted in breast milk, but there is no confirmation of their negative impact on infant health.
Dosing and Administration
The tablets should be taken orally in the order indicated on the package, every day at about the same time, with a little water. Take 1 tablet a day continuously for 21 days. Reception begins after the next pack 7dnevnogo tablet-free interval during which bleeding is usually the case “cancellation”.
The bleeding usually starts on day 2-3 after the last tablet and may not end before you start taking a new package.
How to start taking Trigestrela
- Without taking any hormonal contraceptive use in the preceding month.
Trigestrela Admission starts at the 1st day of the menstrual cycle (ie the 1st day of menstrual bleeding). Shall start receiving 2-5 days of the menstrual cycle, but in this case it is recommended to additionally use a barrier method of contraception during the first 7 days of tablet-taking from the first package.
- When switching from other combined oral contraceptive vaginal ring or contraceptive patch.
Preferably start taking Trigestrela the next day after taking the last active tablet of the previous package, but in any case not later than the day after the usual 7-day break (for products containing tablet 21), or after the last inactive tablets (for formulations containing 28 tablets per pack). Admission Trigestrela should start on the day of removal of the vaginal ring or the patch, but not later than the day when it should be inserted a new ring or pasted a new patch.
- When switching from contraceptives containing only progestin ( “mini-pill”, an injectable form, implant) or releasing progestogen .
A woman can go to the mini-pill to Trigestrel any day (without a break), with the implant or intrauterine device with progestogen – the date of its removal from the injection mold – from the day when the next injection should be done. In all cases, you must use an additional barrier method of contraception during the first 7 days of taking the pills.
- After the abortion I trimester of pregnancy.
A woman may start taking the drug immediately. Subject to this condition the woman does not need additional contraceptive protection.
- After delivery or abortion in the II trimester of pregnancy.
It is recommended to start taking the drug at 21-28 days after delivery 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 Trigestrel pregnancy should be excluded or must wait for the first menstrual period.
Receiving Missed tablets
If the delay in receiving the drug was less than 12 hours, contraceptive protection is not reduced. The woman should take the tablet as soon as possible, as soon as remembered; It should be taken at the usual times. If the delay in the pill was more than 12 hours, contraceptive protection may be reduced. The more missed tablets and the closer to the pass 7-day tablet-free interval, the greater the likelihood of pregnancy. It is possible to be guided by the following two basic rules:
- The drug should never be interrupted for more than 7 days.
- 7 days continuous administration of pills required to achieve adequate suppression of the hypothalamic-pituitary-ovarian regulation. Accordingly the following advice can be given:
- The first week of taking the drug 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 metandienone tablet is taken at the usual time. Additionally, it should be used a barrier method of contraception (such as a condom) for the next 7 days. If intercourse took place during the week before skipping pills, you need to take into account the chance of pregnancy.
- The second week of taking the drug 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. Provided that the woman is on the pill correctly within 7 days preceding the first missed tablet, there is no need to use additional contraceptive measures. Otherwise, as well as skipping of two or more tablets must also use barrier contraception (such as a condom) for 7 days.
- The third week of ingestion risk of reduced reliability is imminent because of the forthcoming tablet-free interval. A woman should strictly adhere to one of the two following options. Moreover, if during the 7 days preceding the first missed tablet, taken all the tablets correctly, there is no need to use additional contraceptive methods. 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 at the usual time taken until the end tablets from the current package. Acceptance of the drug from the next pack should be started immediately. Bleeding “cancel” is unlikely until the end of the second pack, but may experience varying degrees of intensity of bleeding (spotting on to breakthrough bleeding) while taking the pills.
A woman can also interrupt taking the tablets from the current package. Then she should take a break for 7 days, including the day of skipping pills and start taking a new package.
If the woman misses pills, and then during a break in taking the drug she has no bleeding, “cancellation”, it is necessary to exclude pregnancy.
Recommendations in case of vomiting and diarrhea
If a woman has had vomiting or diarrhea within 4 hours after taking the pill, the absorption may be incomplete and should be additional contraceptive measures are taken. In these cases, you should be guided by the recommendations by skipping pills.
Changing the date of commencement menstrualnopodobnoe bleeding
To delay the onset menstrualnopodobnoe bleeding, the woman should continue taking the drug, using the last 10 tablets from other packaging Trigestrel drug, without making a break in the reception. Thus, the cycle may be extended for up to 10 days until the end of the second pack. Against the background of the drug from the second package, women may experience spotting or breakthrough uterine bleeding.Regular intake of the drug Trigestrel then resumed after the usual 7-day tablet-free interval. In order to move the first day of bleeding menstrualnopodobnoe on another day of the week, the woman should be reduced the next tablet-free interval to the desired number of days. The shorter the interval, the higher the risk that she will not be bleeding, “cancel” and, in the future, will be spotting or breakthrough bleeding while taking second pack (just as when she wanted to delay the onset of menstrualnopodobnoe bleeding).
Children and adolescents
Trigestrel indicated for use only after menarche.
When receiving combined oral contraceptives metandienone may experience irregular bleeding (spotting or breakthrough bleeding), especially during the first months of use. While taking combined oral contraceptives in women were observed and other undesirable effects, whose connection with the drug intake was not confirmed, but not refuted.
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