MINIZISTON 20 FEM
Active material: Ethinylestradiol, Levonorgestrel
When ATH: G03AA07
CCF: Monophasic oral contraceptive
ICD-10 codes (testimony): Z30.0
When CSF: 15.11.04.01
Manufacturer: JENAPHARM GmbH & Co.KG (Germany)
Pharmaceutical form, composition and packaging
Drop Pink colour.
| 1 drop | |
| ethinylestradiol | 20 g |
| levonorgestrel | 100 g |
Excipients: lactose monohydrate, corn starch, modified corn starch, polyvidone 25000, magnesium stearate.
The composition of the shell: sucrose, polyvidone 700000, polyethylene glycol 6000, calcium carbonate, talc, glycerol 85%, Titanium dioxide, iron oxide red, iron oxide yellow, Wax DAV.
21 PC. – blisters (1) – cardboard boxes.
21 PC. – blisters (3) – cardboard boxes.
Pharmacological action
Monophasic combined oral contraceptive product.
The contraceptive effect Minizistona® 20 FEM is based on the interaction of various factors, the most important of which are the inhibition of ovulation and changes in the viscosity of cervical mucus.
In addition to the contraceptive action, Combined oral contraceptives have a positive impact, which should be considered when choosing a method of family planning. The menstrual cycle becomes more regular, rarely observed painful menstruation, decreases the intensity of menstrual bleeding, thereby reducing the risk of iron deficiency anemia.
Pharmacokinetics
Levonorgestrel
Absorption
After oral levonorgestrel is absorbed rapidly and completely. Cmax serum is 2 ng / ml and is reached after about 1 no. The absolute bioavailability of levonorgestrel approaches 100%.
Distribution
Levonorgestrel binds to serum albumin and globulin, sex hormone binding (GTN). About 1.5% the total concentration levonorgestrel in serum are in the free form, 65% associated with SHBG. The ratio of the drug factions (free, bound to albumin and is associated with the GSM) It depends on the content in the blood SHBG. Ethinyl estradiol increases the content of GSM, therefore fraction, associated with increased SHBG, whereas the free and bound albumin fraction reduced.
The accumulation in the body of levonorgestrel with daily intake takes place almost entirely in the second phase launch. Css achieved at 3-4 day. Pharmacokinetics of levonorgestrel dependent upon the concentration of SHBG in plasma. When receiving Minizistona® 20 fems concentration of SHBG increases by about 70%, because, which preparation comprises ethinyl oestradiol.
The total concentration levonorgestrel serum increases linearly with its specific binding capacity. The level of levonorgestrel serum did not change after 1-3 Regular admission rates due to, The induction of GTN ends. Upon reaching Css levonorgestrel levels in serum 3-4 times higher, than after a single dose.
About 0.1% levonorgestrel dose is excreted in breast milk.
Metabolism
Biotransformation occurs on general metabolic pathways of steroids. Biologically active substances including metabolites were found.
Deduction
Levonorgestrel is not excreted unchanged form. Levonorgestrel metabolites are excreted in the urine and bile in the ratio of about 1:1. T1/2 – about 24 no. Reducing the concentration of drug in the blood serum of a biphasic. T1/2 in the first phase is 30 m, T1/2 in a second phase - 20 no. Rate of metabolic clearance of plasma is approximately 1.5 ml / min / kg.
Ethinylestradiol
Absorption
After oral ethinyl estradiol is absorbed rapidly and completely. Cmax is approximately 60-70 pg / L and is reached through 1-2 no. During the absorption and “first pass” ethinyl estradiol through the liver largely metabolized, resulting in reduced individual variations and its oral bioavailability.
The absolute bioavailability of ethinyl estradiol is approximately 40-60%.
Distribution
Established, that the apparent Vd ethinyl estradiol is approximately 5 l / kg, and its metabolic clearance rate from plasma is approximately 5 ml / min / kg. Ethinylestradiol highly (98%), hotya and nonspecific, It binds albumin.
About 0.02% daily dose of ethinyl estradiol is excreted in breast milk.
Metabolism and excretion
Ethinyl estradiol is metabolized during absorption and “first pass” through the liver.
The concentration of ethinyl estradiol in the serum is reduced, and the reduction is biphasic. T1/2 in the first phase – about 1 no, T1/2 in a second phase - 10-20 no. Ethinylestradiol is not output in the free form. Ethinyl estradiol metabolites excreted by the kidneys and the liver in the ratio 40:60. T1/2 – about 24 no.
Due to the relatively large T1/2 drug in the terminal phase elimination, drug content in the plasma when the Css on 30-40% higher, than after application for 5-6 Nights.
Pharmacokinetics in special clinical situations
Acceptance of other drugs may influence the systemic bioavailability of ethinyl estradiol. However, interaction with high doses of ascorbic acid was identified. Chronic administration of ethinyl estradiol induces an increase in the synthesis of corticosteroid-binding globulin (KSG) and SHBG, with the degree of synthesis of SHBG induction depends on the type and dose of progestogen received simultaneously.
Testimony
- Contraception.
Dosage regimen
Drops should be taken in order, indicated on the packaging, every day at about the same time, with a little water. The drug should be taken on 1 pellets / day continuously for 21 day. Admission to each successive package begins after the 7-day break, during which withdrawal bleeding occurs (menstrualnopodobnoe bleeding). It usually begins at 2-3 day from the receipt of the last of the pellet and may not end before you start taking a new package.
At without taking any hormonal contraceptive use in the previous month the drug begin in the 1 st day of the menstrual cycle (ie. in the 1 st day of menstrual bleeding). Shall start receiving 2-5 th day of the menstrual cycle, but in this case it is recommended to use a barrier method of contraception during the first 7 days of the first package of pills. If you do not receive any hormonal contraceptive use in the previous month.
At switching from combined oral contraceptives the drug should be started on the next day after taking the last pills with active components of the previous formulation, but in any case not later than the day after the usual 7-day break in the reception (for products, containing 21 drop) or after the last inactive dragee (for products, containing 28 Bean in a package).
At switching from contraceptives, containing only progestin (“minipill”, injectable form, Implant), You can start using the drug without a break. At the transition from “minipill” – any day without a break. At the use of injectable contraceptives start taking the drug the day, when it should be done next injection. At the transition from the implant – on the day of its removal. In all cases, you must use an additional barrier method of contraception during the first 7 days of pills.
After abortion in the I trimester of pregnancy a woman may start taking the drug immediately. In this case, the woman does not need any additional contraceptive methods.
After childbirth 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 during the first 7 days of pills. However, if the woman lived a sexual life between birth or abortion and the beginning of the drug, you must first eliminate the need to wait for the pregnancy or the first menstruation.
Missing pills woman should take as soon as possible, next pills taken at the usual time.
If the delay in taking pills less 12 no, reliable contraception is not reduced.
If the delay in taking pills made more than 12 no, the reliability of contraception may be reduced. It should be borne, that taking pills should never be interrupted for more than 7 days and that 7 days continuous administration dragees are required to achieve adequate suppression of the hypothalamic-pituitary-ovarian system.
If the delay in taking pills made more than 12 no in the first week ingestion, A woman should take the last missed pills as soon as possible, once remember (even if it means taking two pills at once). Next pills taken at the usual time. Additionally, you should use a barrier method of contraception for the next 7 days. If a woman has been sexually active for a week before skipping pills, must take into account the risk of pregnancy. The more pills missed and the closer this pass to the 7-day break in taking pills, the higher the risk of pregnancy.
If the delay in taking pills made more than 12 no during the second week ingestion, A woman should take the last missed pills as soon as possible, once remember (even, if it needs to take two pills at once). Next take the pills at the usual time. Given that, that women take pills correctly for 7 days, preceding the first missed pills, no need for additional contraceptive measures. Otherwise, as well as the passage of two or more pills must also use a barrier method of contraception (eg, condom) during 7 days.
If the delay in taking pills made more than 12 no during the third week ingestion, the risk of reduced reliability is imminent because of the forthcoming free interval dragees. A woman should strictly adhere to one of the two following options: (wherein, if during 7 days, preceding the first missed pills, all the pills are taken correctly, there is no need to use additional contraceptive methods):
- The woman should take the last missed pills as soon as possible, once remember (even, if it is, taking two pills at once). Next take the pills at the usual time, until the end of the current package of pills. The next pack should be started immediately. Withdrawal bleeding is unlikely, until the end of the second pack, but may experience spotting and breakthrough bleeding while taking pills.
- A woman can also interrupt the reception of pills from the current package. Then she should take a break for 7 days, including the day of skipping pills, then start taking the new packaging. If a woman misses pills, and then during a break in taking pills she had no withdrawal bleeding, Pregnancy must be excluded.
If a woman has vomiting between 3 to 4 h after administration dragee, absorption may not be complete and should be taken additional measures contraceptives. In these cases, it should be guided by the recommendations by skipping pills. If a woman does not want to change the normal dosing, it should take if necessary additional dragee (or more dragee) from other packaging.
In order to delay the onset of menstruation, women should continue taking the new packaging without interruption. Dragee of this new packaging can take as long, until they run out. Against the background of the drug from the second package, women may experience spotting or breakthrough vaginal uterine bleeding. Then make the 7-day break, and then resume the regular intake of medication.
In order to postpone the first day of menstruation to another day of the week, women should shorten its nearest break in reception pills on many days, how much she wants. The shorter the interval, the higher the risk, that she will be spotting and breakthrough bleeding while taking the second package (same, as in the case, when she wanted to delay the onset of menstruation).
Side effect
In rare cases, may experience the following side effects.
From the digestive system: nausea, vomiting.
On the part of the reproductive system: changes in vaginal secretion.
On the part of the endocrine system: tension and breast tenderness, breast enlargement, the allocation of these secret; weight change, changes in libido.
CNS: reduction / mood changes, headache, migraine.
Other: poor tolerance of contact lenses, fluid retention, allergic reactions.
Sometimes it can develop chloasma, especially in women with a history of chloasma pregnant.
Contraindications
The drug should not be applied if any of the conditions / diseases, listed below. If any of these conditions develop for the first time against the backdrop of its reception, the drug should be immediately abolished:
- The presence of thrombosis (venous and arterial) in the present or past (eg, deep vein thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular disorders);
- The presence of current or a history of states, predshestvuyuschyh thrombosis (eg, transient ischemic cerebrovascular accident, angina);
- Diabetes with vascular complications;
- Presence of severe or multiple risk factors for venous or arterial thrombosis;
- The presence of current or a history of severe liver disease (until, while the figures are not normalized liver function tests);
- The presence of current or a history of benign or malignant liver tumors;
- Identification of hormone-dependent cancers of genitals or mammary gland or suspicion on them;
- Vaginal bleeding of unknown origin;
- Pregnancy or suspected it;
- Lactation (breast-feeding);
- Hypersensitivity to the drug.
Pregnancy and lactation
The drug is not prescribed during pregnancy. If pregnancy is detected during reception Minizistona® 20 FEM, drug immediately canceled. However, extensive epidemiological studies have revealed no increased risk of developmental defects in children, born to women, treated with hormones prior to pregnancy or teratogenicity, when sex hormones were taken inadvertently in early pregnancy.
Acceptance of combined oral contraceptives may decrease the amount of breast milk and change its composition, so, their use is not recommended during lactation. Small amounts of sex steroids and / or their metabolites may be excreted with breast milk, but there is no confirmation of their negative impact on the health of newborn.
Cautions
Before you start the application Miniziston® 20 FEM neobhodimo hold obschemedytsynskoe Surveying (incl. breast cytology and cervical mucus), exclude pregnancy, disorders of the blood coagulation system. With long-term use of the drug control testing should be performed at least 1 per year.
Women should be informed that, that Miniziston® 20 fems do not protect against HIV infection (AIDS) and other diseases, sexually transmitted.
In the presence of risk factors should carefully evaluate the potential risks and expected benefits of the therapy and to discuss this with a woman before, she decides to start taking the drug. When weighting, strengthening or at the first sign of risk factors may require removal of the drug.
A number of epidemiological studies have revealed a slight increase in the incidence of venous and arterial thrombosis and thromboembolism while taking combined oral contraceptives.
When you receive a combined contraceptive drugs may develop venous thromboembolism (VTЭ), manifested as deep vein thrombosis and / or pulmonary embolism. The approximate incidence of VTE with oral contraceptives with a low dose of estrogen (less 50 mcg ethinyl estradiol) up to 4 accidents 10 000 women per year in comparison with 0.5-3 accidents 10 000 women per year among women, not taking contraceptives. The frequency of VTE while taking combined oral contraceptives less, than the frequency of VTE, associated with pregnancy (6 accidents 10 000 pregnant women per year).
Women, taking the combined contraceptive drugs, It describes very rare cases of thrombosis of other blood vessels (Hepatic, mesenteric, renal arteries and veins, arteries and veins of the retina). The relationship of these cases, the reception of the combined oral contraceptives has not been proven.
The patient should be informed, that the development of symptoms of venous or arterial thrombosis should seek medical advice immediately. These symptoms include unilateral leg pain and / or swelling, sudden severe chest pain radiating to the left arm or without irradiation, sudden shortness of breath, sudden onset of coughing, any unusual, strong, prolonged headache, increased frequency and severity of migraine, sudden partial or complete loss of vision, diplopia, slurred speech or aphasia, dizziness, collapse with / without partial seizures, weakness or very marked numbness, suddenly appear on one side or in one part of the body, movement disorders, simptomokompleks “sharp” life.
It should be taken into account, that the risk of venous or arterial thrombosis and / or thromboembolic events increases with age; Smokers (with the number of cigarettes or increasing age the risk further increases, especially in older women 35 years); in the presence of family history (ie. venous or arterial thromboembolism ever in close relatives or parents at a relatively young age); when, If you intend to genetic predisposition, a woman should be assessed appropriately skilled to address the issue of the possibility of using combined oral contraceptives; obesity (BMI than 30 kg / m2); dyslipoproteinemia; hypertension; valvular heart disease; Atrial Fibrillation; prolonged immobilization; major surgery; any surgery on the legs or major trauma (In these situations it is desirable to discontinue the use of the drug / in the case of the planned operation, at least, for 4 weeks before she /) and not to renew the appointment within 2 weeks after immobilization.
It should take into account the increased risk of thromboembolism during the postpartum period.
It should be taken into account, the risk of thrombosis during pregnancy higher, than when taking combined oral contraceptives.
Circulatory disorders can be observed also in patients with diabetes mellitus, systemic lupus erythematosus, hemolytic uremic syndrome, Crohn's disease, NYAK, sickle cell disease.
Increased frequency and severity of migraine during use of combined oral contraceptives (that may precede cerebrovascular disorders) It may be grounds for the immediate cessation of these drugs.
It should also consider the biochemical parameters, which may indicate a predisposition to thrombosis: resistance to activated protein C., hyperhomocysteinemia, antithrombin III deficiency, Protein C, протеина S, the presence of antiphospholipid antibodies (antibodies to cardiolipin, volchanochnyi anticoagulant).
There are reports of some increase in the risk of cervical cancer in long-term use of combined oral contraceptives. However, the connection with the reception of the combined oral contraceptives has not been proven. Reserved controversy regarding, the extent to which the data associated with screening for cervical pathology, or with the sexual behavior (less frequent use of barrier methods of contraception).
A meta-analysis of epidemiological studies have shown, that there is a slightly increased relative risk of developing breast cancer, diagnosed in women, who used combined oral contraceptives. His connection with the reception of the combined oral contraceptives has not been proven. The observed increase in risk may also be due to an earlier diagnosis of breast cancer in women, applying the combined oral contraceptives. Women, ever use combined oral contraceptives, revealed earlier stages of breast cancer, than in women, never let them to apply.
In rare cases, against the background of the use of combined oral contraceptives to observe the development of liver tumors, which in some cases led to life-threatening intra-abdominal haemorrhage. In case of severe pain in the abdomen, liver enlargement or signs of intra-abdominal bleeding it should be considered in the differential diagnosis.
In women with hypertriglyceridaemia (condition or presence of a family history) may increase the risk of developing pancreatitis while taking combined oral contraceptives.
Although a slight increase in blood pressure have been reported in many women, taking combined oral contraceptives, clinically significant increase occurred rarely. Nonetheless, If while taking combined oral contraceptives develops persistent, a clinically significant increase in blood pressure, these drugs should be discontinued and treat hypertension. Acceptance of combined oral contraceptives may be continued, if using antihypertensive treatment achieved normal blood pressure values.
The following states, as reported, develop or worsen both during pregnancy, and when receiving combined oral contraceptives, but their relationship with the intake of combined oral contraceptives has not been proven: Jaundice and / or itching, associated with cholestasis; the formation of gallstones; porphyria; systemic lupus erythematosus; hemolytic uremic syndrome; Huntington Sidengama; Herpes pregnant; hearing loss, otosclerosis-related. Also described cases of Crohn's disease and ulcerative colitis in the background of the use of combined oral contraceptives.
Acute or chronic disturbances of liver function may require the cancellation of combined oral contraceptives until, until liver function tests have not returned to normal. Recurrent cholestatic jaundice, which develops for the first time during pregnancy or previous use of sex hormones, It requires discontinuation of combined oral contraceptives.
Although combined oral contraceptives may influence insulin resistance and glucose tolerance, no need to change the therapeutic regimen in patients with diabetes, using low-dose combined oral contraceptives (less 50 mcg ethinyl estradiol). Nonetheless, Women with diabetes should be carefully observed while taking combined oral contraceptives.
Sometimes it can develop chloasma, especially in women with a history of chloasma pregnant. Women with a tendency to chloasma while taking combined oral contraceptives should avoid prolonged exposure to sunlight and ultraviolet radiation.
Acceptance of combined oral contraceptives can affect the results of certain lab tests, including liver function tests, kidney, Thyroid, adrenal, level in the plasma transport proteins, carbohydrate metabolism, parameters of coagulation and fibrinolysis. Changes do not usually go beyond the normal range.
While taking combined oral contraceptives may experience irregular bleeding (spotting or breakthrough bleeding), especially during the first months of use. Therefore, evaluation of any irregular bleeding should be done only after a period of adaptation, of approximately three cycles. If irregular bleeding or develop after repeated previous regular cycles, should conduct a thorough examination to exclude malignancy or pregnancy.
In some women, during a break in receiving pills may not develop withdrawal bleeding. If combined oral contraceptives are taken according to the directions, unlikely, that a woman is pregnant. Nonetheless, Before that combined oral contraceptives taken regularly or, if there are no two consecutive withdrawal bleeding, to continue taking the drug should be excluded pregnancy.
Effects on ability to drive vehicles and management mechanisms
Not found.
Overdose
No serious side effects have been reported in overdose.
Symptoms: nausea, vomiting, spotting (girls).
Treatment: symptomatic therapy. No specific antidote.
Drug Interactions
In an application Minizistona® 20 FEM with drugs, inducing hepatic microsomal enzymes (phenytoin, ʙarʙituratami, primidone, carbamazepine and rifampicin, and, perhaps, with oxcarbazepine, topiramatom, felʙamatom, griseofulvin), increased clearance of ethinyl estradiol and levonorgestrel, that could reduce the reliability of contraception and development of breakthrough bleeding.
In an application Minizistona® 20 fems with ampicillin and tetracycline marked reduction in ethinyl estradiol and therefore decrease contraceptive effect and development of breakthrough bleeding.
It should be taken into account, women, take any of the above medications, short-course, In addition to Minizistonu® 20 fems should use a barrier method of contraception during the concomitant drug administration and for 7 days after their cancellation.
While receiving rifampicin and for 28 days after its cancellation, in addition to Minizistonu® 20 fems should use a barrier method of contraception. If concomitant use of the drug began in the late admission package Minizistona® 20 FEM, The following pack should be started without the usual break at the reception.
Conditions of supply of pharmacies
The drug is released under the prescription.
Conditions and terms
The drug should be stored out of reach of children. Shelf life – 3 year.
