JANÏN
Active material: Dienogest, Ethinylestradiol
When ATH: G03AA
CCF: Monophasic oral contraceptive with anti-androgenic properties
ICD-10 codes (testimony): Z30.0
When CSF: 15.11.04.01
Manufacturer: JENAPHARM GmbH & Co.KG (Germany)
Pharmaceutical form, composition and packaging
Drop white, smooth.
| 1 drop | |
| ethinylestradiol | 30 g |
| dienogest | 2 mg |
Excipients: lactose monohydrate, potato starch, gelatin, talc, magnesium stearate.
The composition of the shell: sucrose, dextrose, macrogol 35 000, calcium carbonate, polyvidone K25, Titanium dioxide (E171), carnauba wax.
21 PC. – blisters (1) – packs cardboard.
21 PC. – blisters (3) – packs cardboard.
Pharmacological action
Low-dose monophasic oral combined estrogen-progestin contraceptive product.
The contraceptive effect is achieved by Jeanine complementary mechanisms, the most important of which are inhibition of ovulation and changes in the viscosity of cervical mucus, whereby it becomes impenetrable to sperm.
When used properly, Pearl Index (index, reflecting the number of pregnancies 100 Women, taking contraceptive during the year) is less than 1. When skipping pills or incorrect use Pearl Index may rise.
Progestogens component Janine – dienogest – It has anti-androgen activity, which is confirmed by the results of several clinical studies. Besides, dienogest improves blood lipid profile (increases the amount of high density lipoprotein).
Women, taking combined oral contraceptives, the menstrual cycle becomes more regular, rarely observed painful menstruation, decreasing the intensity and duration of bleeding, thereby reducing the risk of iron deficiency anemia. Besides, there is evidence of reducing the risk of endometrial cancer and ovarian cancer.
Pharmacokinetics
Dienogest
Absorption
After oral dienogest is rapidly and completely absorbed from the gastrointestinal tract. Cmax achieved through 2.5 h and is 51 ng / ml. Bioavailability is approximately 96%.
Distribution
Dienogest binds to serum albumin and globulin binds, binding sex steroids (GTN) and corticoid-binding globulin (KSG). The free form is about 10% total serum concentrations; about 90% – nonspecifically bound to serum albumin. Induction of synthesis of SHBG ethinylestradiol not affect the binding of serum protein dienogest.
Pharmacokinetics dienogest not affect the level of SHBG serum. As a result, the daily ingestion dienogest serum level increased about 1.5 times.
Metabolism
Dienogest almost completely metabolized. Clearance of serum after a single dose of approximately 3.6 l /.
Deduction
T1/2 is about 8.5-10.8 no. A small part of the dienogest excreted by the kidneys in an unaltered state. The metabolites are excreted in the urine and bile at a ratio of about 3:1 with T1/2 equal 14.4 no.
Ethinylestradiol
Absorption
After oral ethinyl estradiol rapidly and completely absorbed. Cmax of serum is reached after 1.5-4 h and is 67 pg / ml. During the suction and “first pass” ethinyl estradiol is metabolized through the liver, whereby its oral bioavailability averages about 44%.
Distribution
Ethinyl estradiol is almost completely (about 98%), hotya and nonspecific, It binds to albumin. Ethinyl estradiol induces the synthesis of SHBG. In Кажущийсяd ethinyl estradiol is 2.8-8.6 l / kg.
Css It achieved during the second half of the treatment cycle.
Metabolism
Ethinylestradiol undergoes conjugation presistemna, in the mucosa of the small intestine, and liver. The main pathway – aromatic hydroxylation. Clearance rate from plasma is 2.3-7 ml / min / kg.
Deduction
Reducing the concentration of ethinyl estradiol in the blood serum is biphasic; The first phase is characterized by T1/2 Phase – about 1 no, T1/2 Phase II – 10-20 no. In unaltered from the body will not be displayed. Ethinylestradiol metabolites are excreted in the urine and bile in the ratio 4:6 with T1/2 about 24 no.
Testimony
- Contraception.
Dosage regimen
Jeanine Drops should be taken in order, indicated on the packaging, every day at about the same time, with a little water. Jeanine should take 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 Jeanine reception 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.
At switching from combined oral contraceptives, vaginal rings, transdermal patch Jeanine reception should begin the day after the last drops with the 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). When switching from the vaginal ring, transdermal patch preferably start taking Jeanine day remove the ring or patch, but not later than the day, must be entered when a new ring or pasted a new patch.
At switching from contraceptives, containing only progestin (“minipill”, injectable form, Implant) or a progestogen-releasing intrauterine device Janine can begin to apply without interruption. At the transition from “minipill” – any day without a break. At the use of injectable contraceptives Jeanine start taking the day, when it should be done next injection. At the transition from the implant or intrauterine device with progestin – 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 start taking Jeanine, 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, So what 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 (the interval from the receipt of the last pills More 36 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 (the interval from the receipt of the last pills More 36 no) in 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 (the interval from the receipt of the last pills More 36 no) in 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).
- A 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, or diarrhea to within 4 hours after administration of active pellets, 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.
That delay the onset of menstruation, women should continue taking pills from a new package Jeanine soon, taken as a whole pellet from the previous, without interruption in reception. Dragee of the new package may be made so long, how a woman wants (until, until the package is over). Against the background of the drug from the second package, women may experience spotting or breakthrough uterine bleeding. Resume Jeanine reception of the new packaging should be after the usual 7-day break.
That postpone the first day of menstruation to another day of the week, women should shorten the next tablet-taking break in on so many days, how much she wants. The shorter the interval, the higher the risk, that it will not have withdrawal bleeding will continue to 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
When receiving combined oral contraceptives may experience irregular bleeding (spotting or breakthrough bleeding), especially during the first months of use.
While taking combined oral contraceptive in women were observed, and other undesirable effects, are classified as follows:: often (≥1/100), infrequently (≥1 / 1000 <1/100), rarely (<1/1000).
From the digestive system: often – nausea, abdominal pain; infrequently – vomiting, diarrhea.
On the part of the reproductive system: often – engorgement, breast tenderness; infrequently – hypertrophy breast; rarely – vaginal discharge, discharge from the breast.
CNS: often – headache, depressed mood, mood swings; infrequently – decreased libido, migraine; rarely – increase libido.
On the part of the organ of vision: rarely – intolerance to contact lenses (discomfort when wearing).
Dermatological reactions: infrequently – rash, hives; rarely – uzlovataya эritema, erythema multiforme.
Other: often – weight gain; infrequently – fluid retention; rarely – weight loss, allergic reactions.
How and when taking other combined oral contraceptives, in rare cases may develop thrombosis and thromboembolism.
Contraindications
Janine should not be used in the presence of 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 attacks, angina);
- Diabetes with vascular complications;
- The presence of current or a history of migraine with focal neurological symptoms;
- Presence of severe or multiple risk factors for venous or arterial thrombosis (incl. complicated valvular lesions, Atrial fibrillation, cerebrovascular disease, or coronary artery of the heart, uncontrolled hypertension, major surgery with prolonged immobilization, smoking at the age of 35 years);
- Hepatic failure and severe liver disease (to normalize the liver samples);
- The presence of current or a history of pancreatitis with severe hypertriglyceridemia;
- 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;
- Breastfeeding;
- Hypersensitivity to the drug.
Carefully
You should carefully weigh the potential risks and expected benefits of the use of combined oral contraceptive in each individual case in the presence of the following diseases / conditions and risk factors:
- Risk factors for thrombosis and embolism (smoking, obesity, dyslipoproteinemia, arterial hypertension, migraine, valvular heart, prolonged immobilization, major surgery, extensive trauma, a genetic predisposition to thrombosis / thrombosis, myocardial infarction or cerebrovascular accident at a young age in any of the next of kin /);
- Other diseases, which may occur when peripheral circulatory disorders (diabetes, systemic lupus erythematosus, hemolytic uremic syndrome, Crohn's disease, NYAK, drepanocytemia, phlebitis of superficial veins);
- Hereditary angioedema;
- Hypertriglyceridemia;
- Liver disease;
- Diseases, for the first time created or aggravated during pregnancy or previous use of the background of sex hormones (eg, jaundice, cholestasis, gallbladder disease, otosclerosis with hearing impairment, porphyria, Herpes pregnant, Huntington Sidengama);
- Postpartum.
Pregnancy and lactation
Janine is not appointed during pregnancy and lactation.
If pregnancy is detected during reception of Janine, the drug should be immediately canceled. However, extensive epidemiological studies have revealed no increased risk of developmental defects in children, born to women, treated with hormones before 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 contraindicated during lactation. A small amount of sex steroids and / or their metabolites may be derived from milk, but there is no confirmation of their negative impact on the health of newborn.
Cautions
Before the start or resumption of the drug Jeanine should be familiar with the life history, family history of women, conduct a thorough general medical (including measurement of blood pressure, Heart Rate, body mass index) and gynecological examination, including the study of mammary glands and cytological examination of scrapings from the cervix (Test by Papanikolaou), exclude pregnancy. The amount of additional research and the frequency of control examinations determined individually. Typically, control examinations should be carried out not less 1 per year.
Women should be informed that, Jeanine that do not protect against HIV infection (AIDS) and other diseases, sexually transmitted.
If any of the conditions, diseases and risk factors, the following, currently available, you should carefully weigh the potential risks and expected benefits of the use of combined oral contraceptive in each individual case and discuss it with the 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.
Available epidemiological data on the increase in the incidence of venous and arterial thrombosis and thromboembolism (such as deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke) while taking combined oral contraceptive. These diseases are rare.
The risk of venous thromboembolism (VTЭ) is maximum in the first year of use of these drugs. 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 cases on 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).
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 (eg, venous or arterial thromboembolism ever in close relatives or parents at a relatively young age; in the case of hereditary predisposition woman should be assessed and appropriate specialists to address the issue of the possibility of using combined oral contraceptives); obesity (BMI than 30 kg / m2); dyslipoproteinemia; hypertension; migraine; valvular heart disease; Atrial Fibrillation; prolonged immobilization; major surgery; any surgery on the legs or major trauma. In these situations it is desirable to stop using Jeanine (in the case of the planned operation, at least, for 4 weeks earlier) and not to renew the appointment within 2 weeks after immobilization.
The question of the possible role of varicose veins and superficial thrombophlebitis in venous thromboembolism remains controversial.
It should take into account the increased risk of thromboembolism during the postpartum period.
Peripheral circulatory disorders also may occur in diabetes, systemic lupus erythematosus, hemolytic uremic syndrome, Crohn's disease, NYAK, sickle cell disease.
Increased frequency and severity of migraine during use of COCs (that may precede cerebrovascular disorders) It may be grounds for the immediate cessation of these drugs.
In assessing the risks and benefits, should be considered, that adequate treatment of the disease may reduce the associated risk. Also note, the risk of thrombosis and thromboembolism in pregnancy higher, than when low-dose oral contraceptives (less 50 mcg ethinyl estradiol).
The most important risk factor for cervical cancer, It is persistent human papilloma virus infection. 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).
Meta-analysis 54 Epidemiological studies have shown, that there is a slightly increased relative risk of developing breast cancer, diagnosed in women, who used combined oral contraceptives. The increased risk gradually disappears during the 10 years after stopping these drugs. Because, that breast cancer is rare in women under 40 years, increase in the number of breast cancer diagnoses in women, taking combined oral contraceptives are currently taking or have recently, is small relative to the total risk of the disease. 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 therapy achieved normal values of arterial pressure.
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.
In women with hereditary forms of angioedema exogenous estrogens may induce or worsen symptoms of angioedema.
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.
The effectiveness of combined oral contraceptive pills can be reduced by skipping pills, with vomiting and diarrhea, or resulting from drug interactions.
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.
Some women during the tablet-free interval 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.
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.
Preclinical data, obtained in the standard tests to identify multiple dose toxicity at doses, Jeanine and genotoxicity, carcinogenic potential and toxicity to the reproductive system, It does not indicate a special risk for humans. Nonetheless, it should be remembered, that sex steroids can promote the growth of certain hormone-dependent tissues and tumors.
Effects on ability to drive vehicles and management mechanisms
Not found.
Overdose
Serious violations of an overdose have not been reported Jeanine.
Symptoms: nausea, vomiting, spotting or metrorrhagia.
Treatment: symptomatic therapy. No specific antidote.
Drug Interactions
The interaction of oral contraceptives with other drugs may lead to breakthrough bleeding and / or reduce the contraceptive reliability. The literature reports the following types of interaction.
Use of drugs, inducing hepatic microsomal enzymes, can lead to increased clearance of sex hormones. These drugs include phenytoin, barbiturates, prymydon, Carbamazepine, rifampicin; also have assumptions about oxcarbazepine, topiramate, felbamate, griseofulvin and preparations, containing St. John's wort.
HIV protease inhibitors (eg, ritonavir) and non-nucleoside reverse transcriptase inhibitors (eg, Nevirapine) and combinations thereof may also potentially affect hepatic metabolism.
According to separate studies, certain antibiotics (eg, penitsillinы and tetracycline) may reduce the enterohepatic circulation of estrogens, thereby, lowering the concentration of ethinyl estradiol.
During the reception of any of these drugs, women should additionally applying a barrier method of contraception (eg, condom).
During supplementation, influencing microsomal enzymes, and for 28 days after their cancellation should additionally use a barrier method of contraception.
While antibiotics (except rifampicin and griseofulvin) and for 7 days after their cancellation should additionally use a barrier method of contraception. If the period of use of barrier methods ends later, than Bean in a package, you need to go to the next Janine package without the usual free interval dragees.
Combination oral contraceptives may affect the metabolism of other drugs, which leads to increased (eg, cyclosporine) or reduction (eg, lamotrigine) their concentration in the plasma and tissues.
Conditions of supply of pharmacies
Jeanine drug by prescription.
Conditions and terms
Jeanine drug should be stored out of reach of children at temperature not exceeding 25 ° C. Shelf life – 3 year.
