Expiration date: 02/2025
Pharmachologic effect
Pharmacodynamics
Nomegestrola acetate - a highly selective progestogen, which is a derivative of the natural steroid hormone progesterone. Nomegestrola acetate has a pronounced affinity for the human progesterone receptor has antigonadotropnym activity, antiestrogenic activity mediated by progesterone receptors, and moderate activity antiandrogen has no estrogenic, androgenic, glucocorticoid and mineralocorticoid activity. The composition of the drug Zoely included 17?-estradiol - a natural estrogen identical to the endogenous human 17?-estradiol (E2). In contrast, ethinyl estradiol, which is included with other combined oral contraceptives (COCs), E2 has a methyl group in the 17? position. In applying the drug Zoely average concentrations of E2 are comparable to those in the initial follicular phase and late phase of the menstrual cycle, the corpus luteum (see. Subsection "Pharmacokinetics"). The contraceptive effect of the drug due to Zoely combination of various factors, the most important of which are inhibition of ovulation and changes in the viscosity of cervical secretion.
In two randomized, open comparative studies of the efficacy and safety of more than 3,200 women aged 18-50 years Zoely took the drug for 13 consecutive cycles, and more than 1,000 women received a combination of drospirenone (3 mg) / ethinyl estradiol (30 micrograms) in regimen 21 / 7. In the group treated with the drug Zoely, an increase in body weight has been reported in 8.6% of women (in the control group - 5.7%), of irregular bleeding "cancel" (mainly the absence of bleeding, "cancel") was reported in 10.5 % of women (in the control group - 0.5%), acne was reported in about 15.4% of women (in the control group - 7.9%) (see "Side effects" section.). Evaluation of acne development while taking the drug Zoely showed that the majority of women (73.1%) was not observed changes in the state, compared with the state before the start of treatment, 16.8% of women showed improvement in the state and 10.1% of women were noted the emergence or worsening of acne flow. In a clinical study of the drug Zoely conducted in the European Union, Asia and Australia, have been calculated following indicators Pearl Index for the age group 18-35 years: the ineffectiveness of the method - 0.40 (upper limit 95% confidence interval 1.03); the ineffectiveness of the method and the patient's mistake - 0.38 (upper limit 95% confidence interval 0.97).
In a clinical study of the drug Zoely conducted in the United States, Canada and Latin America, have been calculated following indicators Pearl Index for the age group 18-35 years: the ineffectiveness of the method - 1.22 (upper limit 95% confidence interval 2.18); the ineffectiveness of the method and the patient's mistake - 1.16 (upper limit 95% confidence interval 2.08).
In a randomized, open-label study of 32 women received Zoely drug for 6 cycles. After discontinuation Zoely ovulation was restored after an average of 20.8 days after the last administration of the tablet, with the earliest ovulation date was recorded on the 16th day.
Folic acid is an important vitamin in early pregnancy. During dosing Zoely folic acid in blood plasma concentration does not change and remains at a basic level for 6 consecutive months of treatment. In a randomized, open comparative study of 2 years while taking the drug Zoely women aged 21-35 years have seen no clinically significant effect Zoely drug on bone mineral density.
A randomized multicenter comparative open study to evaluate the effect of the drug on Zoely clotting parameters, lipid, carbohydrate metabolism, the functional status of thyroid gland and adrenal gland, as well as the concentration of androgens. Sixty women aged 18-50 years Zoely took the drug for six consecutive cycles. In clinical studies, it was found that while taking the drug Zoely insulin resistance and glucose tolerance remained unchanged and there was no evidence of clinically significant effects on lipid metabolism and homeostasis. Admission Zoely drug increases the concentration of carrier proteins thyroxine-binding globulin, and corticosteroid-binding globulin (CBG). When receiving the drug Zoely slightly increased concentration of globulin, sex hormone binding (SHBG), and significantly decreased the concentration of androstenedione, dehydroepiandrosterone, total and free testosterone. In a clinical study, a group of women (n = 32) after 13 cycles of dosing Zoely pathological changes were not observed in endometrial histology study.
Pharmacokinetics
Nomegestrola acetate
Suction
Nomegestrola acetate is rapidly absorbed after oral administration. After a single dose maximum plasma concentration of about 7 ng / ml and is achieved within 2 h. The absolute bioavailability after a single dose is 63%. The food has no clinically significant effect on the bioavailability of nomegestrola acetate.
Distribution
Nomegestrola acetate avidly binds to albumin (97-98%), but does not bind to SHBG or DRG. The apparent volume of distribution nomegestrola acetate at steady state is 1,645 ± 576 l.
Metabolism
Nomegestrola acetate metabolized to several hydroxylated metabolites are inactive under the action of liver cytochrome P450 isoenzymes, mainly CYP3A4 and CYP3A5; also possible to participate in the metabolism isoenzymes CYP2C8 and CYP2C19.
Nomegestrola acetate and its hydroxylated derivatives undergo metabolism expressed 2nd phase to form the glucuronide and sulfate conjugates. The clearance at steady state is 26 L / h.
breeding
The half-life (t1 / 2) is 46 hours (from 28 to 83 hours) at steady state. The half-life of metabolites not installed. Nomegestrola acetate excreted by the kidneys and the bowel. Approximately 80% of the dose is excreted via the kidneys and intestines for 4 days. Nomegestrola acetate is almost completely eliminated within 10 days. Excretion through the intestinal tract exceeds excretion by the kidneys.
Linearity
Linearity in pharmacokinetics observed dose-dependent in the range of 0,625-5 mg (evaluated in women of reproductive age and postmenopausal).
equilibrium state
SHBG has no effect on the pharmacokinetics nomegestrola acetate. The equilibrium state is achieved after 5 days. The mean concentration at steady state is 4 ng / ml. Acetate nomegestrola maximum concentration in plasma is about 12 ng / ml achieved after 1.5 h after dosing.
interaction
In vitro nomegestrola acetate has no significant inducing or inhibitory effect on cytochrome P450 isoenzymes and does not interact with glycoprotein F.
Estradiol (E2)
Suction
Estradiol undergoes metabolism expressed at "first pass" through the liver after ingestion. The absolute bioavailability is about 1%. Food intake has no clinically significant impact on the bioavailability of estradiol.
Distribution
The distribution of exogenous and endogenous estradiol similar. Estrogens actively distributed throughout the body. Their concentration is generally higher in the target organs of hormones. The blood estradiol binds with SHBG (37%) and albumin (61%), and only 1-2% of circulating estradiol in the unbound form.
Metabolism
Exogenous estradiol actively biotransformed after ingestion. The metabolism of exogenous and endogenous estradiol is similar. Estradiol is rapidly converted into several metabolites in the intestine and liver (mainly estrone) that are conjugated and subsequently undergo enterohepatic recirculation. There is a dynamic equilibrium between estradiol, estrone, and estrone sulfate by the activity of various enzymes, including estradioldegidrogenazy, sulfotransferase and arylsulfatase. Oxidation of estrone and estradiol occurs by the action of cytochrome P450 isoenzymes, mainly CYP1A2, CYP1A2 (outside the liver), CYP3A4, CYP3A5, CYP1B1 and CYP2C9.
breeding
Estradiol is rapidly cleared from the blood. Due to metabolism and enterohepatic recirculation of a large circulating pool of estrogen sulfates and glucuronides. As a result, the half-life of estradiol-adjusted baseline varies within wide limits and is 3.6 ± 1.5 h after intravenous administration. The equilibrium state maximum concentration of estradiol in blood plasma is about 90 pg / ml and is attained at 6 hours after administration. The average plasma concentration - 50 pg / ml. These concentrations correspond to those of estradiol in the initial and late phases of the menstrual cycle.
Pharmacokinetics in special groups
Children
Pharmacokinetics nomegestrola acetate (primary objective) after single oral administration of the drug Zoely was comparable in healthy adolescent girls after menarche and adult women. estradiol concentration (secondary objective) in adolescents compared to adult women was comparable during the first 24 hours, and lower than that of adult women, after 24 hours. The clinical significance of this result is unknown.
Impaired Renal Function
Effect of renal disease on the pharmacokinetics of the drug has not been studied Zoely.
Abnormal liver function
The impact of liver disease on the pharmacokinetics of the drug has not been studied Zoely. However, in patients with impaired hepatic function may impair the metabolism of sex hormones.
Ethnic groups
The pharmacokinetics of the drug has not been studied specifically at ethnic groups.
Testimony
Contraception.
Contraindications
COCs should not be used if any of the following conditions / diseases. No epidemiological data on the use of COCs containing 17?-estradiol, but contraindications to the use of the drug correspond Zoely contraindications to the use of contraceptives containing ethinyl estradiol. In the event of any of these conditions / diseases during treatment Zoely should immediately stop taking the drug.
Deep vein thrombosis or pulmonary embolism, including the anamnesis.
Arterial thrombosis (myocardial infarction) or prodromal state (transient ischemic attack, angina), including the anamnesis.
Acute cerebral circulatory disorders, including history.
Migraine with focal neurological symptoms, including the anamnesis.
Severe or multiple risk factors for venous or arterial thrombosis (see "Special Instructions" section.), Such as: diabetes mellitus with vascular symptoms; uncontrolled hypertension; heavy dislipoproteinemia; obesity (body mass index greater than 30 kg / m2); prolonged immobilization; major surgery, any surgery to the lower limbs or serious injury; complicated heart defects; atrial fibrillation; smoking at the age of 35 years.
Hereditary or acquired predisposition to venous or arterial thrombosis, such as activated protein C resistance, antithrombin III deficiency, protein C deficiency and S, hyperhomocysteinemia and antiphospholipid antibodies (antibodies to cardiolipin, lupus anticoagulant).
Severe hypertriglyceridemia, pancreatitis, including the anamnesis.
Severe liver disease including a history prior to normalization of liver function.
Liver tumors (benign or malignant), including the anamnesis.
Known or suspected hormone-dependent malignant tumors (eg, genital or breast).
Known or suspected pregnancy, lactation.
Hypersensitivity to any current or auxiliaries.
Lactase deficiency, lactose intolerance, glucose-galactose malabsorption.
Vaginal bleeding of unknown etiology.
Postmenopausal women.
There are no data on the efficacy and safety of the drug in Zoely
teenage girls under the age of 18 years. The available information on the pharmacokinetics presented in "Pharmacokinetics" section.
Precautions: If any of the following conditions, diseases, risk factors should assess the benefits of the drug Zoely and the possible risks for each individual woman. This should be discussed with the woman before she starts receiving Zoely drug. Additional information can be found in the "Special Instructions". In case of deterioration, exacerbation or first appearance of any of these conditions, diseases, risk factors, the woman should contact your doctor to decide on possible further application Zoely drug. Diabetes mellitus without vascular lesions; severe depression or the presence of the disease history; systemic lupus erythematosus; Crohn's disease; ulcerative colitis; abnormal liver function; hypertriglyceridemia, including family history; risk factors for coronary heart disease (obesity, hypertension); the presence of a family history of venous thrombosis, arterial embolism in siblings or parents at a young age (see. "Special Instructions" section).
Pregnancy and breast-feeding
Pregnancy
Use of the drug Zoely contraindicated during pregnancy. In case of pregnancy when using Zoely drug should stop taking the drug.
Most epidemiological studies have found no increased risk of birth defects in children whose mothers before pregnancy taking COCs containing ethinylestradiol. If you accidentally received in early pregnancy COCs containing ethinylestradiol, no teratogenic effects were observed. There is limited experience with Zoely the drug in pregnant women, which indicates the absence of an undesirable effect of the drug on the fetus or newborn.
In combination studies nomegestrola acetate / estradiol on reproductive toxicity was recorded in laboratory animals.
Zoely The drug is designed to prevent unwanted pregnancies. If a woman wants to stop taking the drug Zoely to get pregnant, you should take into account that ovulation is restored after an average of 20.8 days after the last administration of the tablet formulation Zoely (see. "Pharmacological properties" section, "Pharmacodynamics" subsection).
Period breastfeeding
COCs may have an effect on lactation, because they cause changes in the amount and composition of breast milk. Therefore, the use of COCs is not recommended until the complete cessation of breastfeeding (should choose an alternative method of contraception). Small amounts of contraceptive hormones and / or their metabolites may be excreted in breast milk, but their adverse effect on the health of newborn unknown.
Special instructions
If any of the following conditions, diseases, risk factors should assess the benefits of the drug Zoely the possible risks for each individual woman. This should be discussed with the woman before she starts receiving Zoely® drug. In case of deterioration, exacerbation or first appearance of any of these conditions, diseases, risk factors, the woman should contact your doctor to decide on possible further application Zoely drug.
The following data were obtained during epidemiological studies in the application of COCs containing ethinylestradiol. The drug Zoely contains 17?-estradiol, however special instructions regarding the reception of the combined oral contraceptive containing ethinyl estradiol, and are considered to be applicable to the preparation Zoely.
Vascular disorders
The use of any COC is accompanied by an increased risk of venous thrombosis and embolism is the highest during the first year after the start of COC use.
Epidemiological studies show that the incidence of venous thromboembolism (VTE) in patients without known risk factors, taking low-dose (<50 mcg ethinylestradiol) COCs is 20 to 40 cases per 10,000 person-years. For comparison, the same parameter in patients who are not taking COC is 5-10 cases per 10,000 person-years or 60 cases per 100,000 pregnancies. VTE is fatal in 1-2% of cases. There are no data on the effect of the drug Zoely on the risk of venous thrombosis and embolism compared with other COCs.
Epidemiological studies have established a link between the use of COCs and an increased risk of arterial thromboembolic events (myocardial infarction, transient ischemic attack).
Patients taking COCs, very rarely developed thrombosis of other vessels, including hepatic, mesenteric, renal, cerebral arteries and veins or the retinal vessels. Lack of sufficient information on the relationship between the occurrence of these complications and the use of COCs.
Symptoms of venous and arterial thrombosis or acute stroke may include the following conditions: sudden pain and / or swelling of the lower limbs, sudden intense pain in the chest, radiating or radiating to the left arm, sudden shortness of breath, sudden cough, unusual severe and prolonged headache, sudden partial or complete loss of vision, double vision, speech impairment, or aphasia, dizziness, collapse, accompanied or not by focal seizures, weakness or numbness expressed that suddenly appear on one side of the body, movement disorders, "acute abdomen".
Risk factors for venous thrombosis and embolism: age; the presence of diseases in the family history (venous thrombosis and embolism in siblings or parents at a young age). If you intend to genetic predisposition, that before taking any hormonal contraceptive use should be consulted with a specialist; prolonged immobilization, major surgery, any surgery to the lower limbs or serious injury. In these cases it is recommended to stop taking hormonal contraceptives (at least 4 weeks prior to elective surgery), and resume it only after 2 weeks after full restoration of motor activity. If the application has not been diverted COC advance should consider the need for antithrombotic agents; obesity (body mass index over 30 kg / m2).
Lack of sufficient information on the role of thrombophlebitis of superficial veins and varicose veins in the etiology of venous thrombosis.
Risk factors for arterial thrombosis or acute stroke: age; smoking (risk even further increases in heavy smoking, especially in women older than 35 years). Women older than 35 years should be strongly advised to stop smoking if they want to take the COC; dislipoproteinemia; obesity (body mass index greater than 30 kg / m2); arterial hypertension; migraine; valvular disease; atrial fibrillation; the presence of diseases in the family history (arterial thrombosis in siblings or parents at a young age). If you intend to genetic predisposition, that before taking any hormonal contraceptive use should be consulted with a specialist.
Other conditions that are accompanied by undesirable vascular disorders include diabetes mellitus, systemic lupus erythematosis, hemolytic uremic syndrome, inflammatory bowel disease (Crohn's disease and ulcerative colitis) and sickle cell anemia.
It is necessary to take into account the increased risk of thromboembolic complications in the postpartum period.
The increase in frequency or severity of migraine during use of COCs (which may precede the development of cerebrovascular complications) is grounds for immediate cancellation of admission Zoely drug.
Women taking COCs, seek medical advice when a possible thrombosis symptoms. In cases of suspected or confirmed thrombosis, COCs should be discontinued. It should start adequate contraception, given the teratogenicity of anticoagulant therapy (coumarins).
Tumors
The most important risk factor for cervical cancer - persistent infection with human papillomavirus (HPV). Epidemiological studies have shown that long-term use of combined oral contraceptive containing ethinyl estradiol, increases this risk, but it remains unclear to what extent this effect is related to other factors, such as more frequent study of the cervix or particular sexual behavior, including the use of barrier contraceptives or a combination of these factors. Causation with COC use is not proven.
In the application in COCs higher dose (50 micrograms ethinyl estradiol) the risk of endometrial cancer and ovarian reduced. It remains unclear whether this applies to COCs containing 17?-estradiol.
A meta-analysis of 54 epidemiological studies in women receiving COCs containing ethinyl estradiol, was found a slight increase in the relative risk (RR) of developing breast cancer (RR = 1.24). The increased risk disappears gradually within 10 years after discontinuation of the COC. Breast cancer rarely develops in women aged up to 40 years, so the number of additional cases of breast cancer in women who are taking or have taken COCs small compared to the overall risk of breast cancer. In women using COCs, revealed earlier stages of breast cancer than women who never let them apply. When using COCs the risk of developing breast cancer increases slightly, it is possible due to earlier diagnosis, the influence of a drug or a combination of these two factors.
In rare cases, women taking COCs, there was the development of liver benign tumors and even more rarely - malignant. In some cases, these tumors have led to life-threatening intra-abdominal bleeding. In case of intense pain in the upper abdomen, liver enlargement or signs of intra-abdominal haemorrhage in women taking COCs, should be excluded liver tumor.
Other conditions
Women with hypertriglyceridemia, or a family history of the corresponding increased risk of pancreatitis when taking COCs.
Many women receiving COC noted a slight increase in blood pressure, although clinically significant increase in blood pressure was observed rarely. The relationship between COC use and hypertension has not been established. However, if the intake of COCs develops resistant hypertension, it is advisable to cancel the COCs and assign antihypertensive therapy. With adequate blood pressure control using antihypertensive drugs possible resumption of COCs. In clinical trials lasting up to two years, no clinically relevant changes in blood pressure was observed when using Zoely drug.
Against the background of pregnancy and during use of COCs, it was noted the development or worsening of these conditions, although their connection with the reception of contraceptives not been finally established: jaundice and / or pruritus related to cholestasis, the formation of gallstones, porphyria, systemic lupus erythematosus, gemolitiko- uremic syndrome, Sydenham's chorea (chorea), herpes during pregnancy, hearing loss associated with otosclerosis.
In women with hereditary forms of angioedema exogenous estrogens may induce or worsen symptoms of angioedema.
In acute and chronic disturbances of liver function may need to cancel COCs until until normalized liver function. When relapse cholestatic jaundice, first observed during pregnancy or previous use of sex hormones, you need to stop taking COCs.
Despite the fact that HEC can influence insulin resistance and glucose tolerance, necessary to change the dosing regimen hypoglycemic agents in patients with diabetes mellitus, host COCs contain less than 0.05 mg ethinylestradiol absent. However, you must carefully carry out periodic examinations of women with diabetes taking COCs, especially during the first months. Zoely The drug has no effect on peripheral tissue insulin resistance and glucose tolerance in healthy women (see. The section "Pharmacological properties" "Pharmacodynamics" subsection).
Worsening of depression, Crohn's disease and ulcerative colitis associated with COC use.
Sometimes it developed chloasma, especially in women with the disease history. Women are predisposed to develop chloasma should avoid sun exposure or exposure to ultraviolet light during the use of COCs.
Medical examination / consultation
Before the appointment Zoely drug should be thoroughly familiar with the medical history (including family) exclude women and pregnancy.
It is necessary to measure blood pressure and the presence of evidence to conduct a physical examination, taking into account contraindications and warnings. The interval between the medical check is determined in each case, but not less than 1 time in 6 months.
Women should be advised that COCs do not protect against HIV infection (AIDS) and other diseases, sexually transmitted diseases.
decline in efficiency
The efficacy of COCs may be reduced in the case of missing tablets (see. "Dosage and Administration" section), gastrointestinal disorders while taking active tablets (see. Section "Dosing and administration") or in case of concomitant therapy (see. Section " The interaction with other drugs ").
Changes in the nature of menstruation
Upon receipt of any COCs may experience "breakthrough" bleeding or "spotting" spin-off, especially in the first few months. Consequently, the survey while irregular bleeding is justified only after a period of adjustment (approximately 3 cycles). In 15-20% of women in the application of the drug Zoely observed acyclic bleeding after this adaptation period. If bleeding irregularities persist or occur after previous regular cycles, we must assume non-hormonal causes and conduct diagnostic tests to exclude malignancy or pregnancy. You may need diagnostic curettage.
Women who took the drug Zoely duration "cancel" bleeding amounted to an average of 3-4 days.
Some of the women who took the drug Zoely, noted the absence of bleeding, "cancel" while taking the yellow placebo tablets, although they were not pregnant. In clinical studies no bleeding "cancel" was noted in 18-32% of cases (for 1 to 12 cycles). In such cases, the absence of bleeding, "cancellation" has not been associated with a higher incidence of "breakthrough" bleeding / "smearing" discharge in the subsequent cycles. At 4.6% of women observed no bleeding "cancel" in each of the first three cycles of the drug. This subgroup had a high percentage of women with no bleeding "cancel" in the subsequent cycles (76-87%). Of the 28% of women who bleed "cancel" was absent in at least one cycle (during cycles 2, 3 or 4) in 51-62% of patients also showed no bleeding "cancellation" in subsequent cycles.
If you are taking the drug Zoely in accordance with the recommendations described in the section "Dosage and administration", there is no bleeding, "cancel", the probability of pregnancy is low. However, if a woman does not take the drug as recommended or if there are no two bleeding "cancel" in a row, it is necessary to exclude pregnancy.
Effects on ability to drive vehicles and other machines that require high concentration of attention
Zoely The drug has no effect on ability to drive and use machines.
Composition
For tablets containing active substances
1 tablet contains:
Active ingredients: nomegestrola acetate 2.50 mg estradiol hemihydrate 1.55 mg (equivalent to 1.50 mg estradiol).
Excipients: microcrystalline cellulose 14.00 mg Crospovidone 2.40 mg, 0.70 mg of talc, magnesium stearate 0.70 mg colloidal silicon dioxide 0.44 mg, 57.71 mg lactose monohydrate;
Tablet Coating: Opadry II white (1.6 mg) contains 0.64 mg of polyvinyl alcohol, titanium dioxide 0.40 mg macrogol 3350 0.32 mg talc 0.24 mg.
For tablets containing no active agents (placebo)
1 tablet contains:
Excipients: microcrystalline cellulose 14.00 mg Crospovidone 2.40 mg, 0.70 mg of talc, magnesium stearate 0.70 mg colloidal silicon dioxide 0.44 mg, 61.76 mg lactose monohydrate;
Tablet Coating: Opadry II yellow (2.4 mg) contains 0.96 mg of polyvinyl alcohol, titanium dioxide 0.58 mg macrogol 3350 0.48 mg, 0.36 mg talc, iron oxide yellow colorant 0.016 mg iron colorant black oxide 0.00024 mg.
Dosing and Administration
The drug is intended for oral administration.
How should I take the medication Zoely
Tablets are taken daily at the same time of the day regardless of the meal in the order indicated on the package, if necessary with a little water. It should take one tablet a day for 28 consecutive days. Admission should start with the white tablets containing the active ingredients. White tablets containing active substances taken in the first 24 days. The yellow taking tablets not containing active substance (placebo) for the next 4 days. Receiving tablets of each subsequent package should start on the next day after taking the last tablet of the previous package, regardless of the presence or absence of bleeding "cancel." Bleeding "cancellation" usually begins 2-3 days after the last white pill and can not stop taking the pills to the top of the next pack. Additional information is provided in the "Special Instructions" subsection "Changes in the nature of menstruation."
Special patient groups
Impaired Renal Function
Data on the use in patients with renal insufficiency are not available, but the effect of renal impairment on the excretion nomegestrola acetate and estradiol is unlikely.
Abnormal liver function
The impact of liver disease on the pharmacokinetics of the drug has not been studied Zoely.
For breastfeeding women see. "Pregnancy and lactation" section.
Women should start taking the drug between the 21 th and 28 th day after second-trimester abortion or childbirth. At a later start of dosing it is recommended to use an additional barrier method of contraception during the first 7 days of taking the pills. However, if after childbirth or abortion already had sexual intercourse, before taking the drug Zoely necessary to exclude pregnancy or wait until the first menstrual period.
What to do in case of tablets admission
The following recommendations apply only to pass reception white tablets containing the active ingredients.
If a woman takes another tablet with a delay of less than 12 hours, the contraceptive effect is not reduced. The woman should take the tablet as soon as possible, as soon as she remembers it. Subsequent tablets should be taken at the usual time.
If a woman takes an active tablet delayed more than 12 hours, the contraceptive effect may be reduced. At the admission of reception of tablets it is expedient to carry out two rules:
to achieve an adequate suppression of the hypothalamic-pituitary-ovarian system, white tablets containing the active ingredients must be taken for at least 7 consecutive days;
more missing white tablets containing active substances and nearer the reception 4 yellow placebo tablets, the higher the risk of pregnancy.
Recommendations for missed tablets
If you miss a single white tablet containing the active substances
The contraceptive effect is not reduced. The woman should take the last missed white tablet as soon as she remembers this, even if she had to take two tablets at the same time. Then, the tablets should be taken as usual. Additional contraceptive measures are not needed.
If you skipped intake of two or more white tablets
If, after passing the reception of two or more white tablets containing the active ingredients, there was no bleeding "cancel" while taking the yellow placebo tablets, it is necessary to exclude pregnancy (see. Also "Special Instructions" section, subsection "Changes in the nature of menstruation ').
Days 1-7
The woman should take the last missed white tablet as soon as she remembers this, even if she had to take two tablets at the same time. Then, the tablets should be taken as usual. Thus during the first week of continuous reception white tablets necessary to use a barrier method of contraception. If during the previous 7 days, there was a sexual act, it is necessary to consider the possibility of pregnancy.
Days 8-17
The woman should take the last missed white tablet as soon as she remembers this, even if she had to take two tablets at the same time. Then, the tablets should be taken as usual. In the next 7 days of white tablets should use a barrier method of contraception.
Days 18-24
Risk reduction contraceptive effect is increased with the approaching start taking the yellow placebo tablets. However, changing the dosage regimen of pills to avoid reducing the contraceptive effect. The woman should take the last missed white tablet as soon as she remembers this, even if she had to take two tablets at the same time. It is impossible to simultaneously take more than two white tablets that contain the active ingredients. For the next 7 days of white tablets should use a barrier method of contraception, and the next package to start immediately after the end of white tablets from the previous packaging, t. E. A woman should not take the yellow placebo tablets. In this case, the "cancel" bleeding usually occurs while taking the yellow pills of the next pack, but while taking the white pills may experience "breakthrough" bleeding or "spotting" selection.
If a woman is not sure of the number of missed pills or color and, accordingly, does not know what recommendations it should be done, it is necessary to use a barrier method of contraception until a woman will take for 7 consecutive days white tablets.
If you skipped intake of yellow placebo tablets
The contraceptive effect is not reduced. A woman can not take yellow tablets from the last (fourth) number of blisters. However, the missed tablets should be discarded to avoid unintentionally increase the duration of the placebo phase.
References in the case of gastrointestinal disorders
In the case of gastrointestinal disorders (such as vomiting or diarrhea) absorption of the drug may not be complete, so must resort to additional measures of contraception.
If vomiting occurs within 3-4 hours after ingestion of the tablets, it should be considered missed reception. If you miss a single white pill, the contraceptive effect is not reduced. If the next day or days of the newly developed vomiting, it is necessary to implement the recommendations on the missing two or more pills (see. "Recommendations for missed tablets"). If a woman does not want to change the usual scheme of taking the pills, she should take extra white tablet or pill from a new package.
How to move or delay the onset of bleeding menstrualnopodobnoe
To delay the onset menstrualnopodobnoe bleeding, the woman should continue taking the white tablets from another package without receiving the yellow pills. White pills from the second package can continue to take as long as they do not run out. After the reception of yellow tablets of the second package is necessary to resume the reception Zoely preparation in the usual way. When the extended regimen may experience "breakthrough" bleeding or "spotting" selection.
In order to move the first day of bleeding menstrualnopodobnoe the next day, it is possible to reduce the phase receiving the yellow placebo tablets (the maximum duration of receiving the yellow placebo tablets - 4 days). The shorter the interval, the higher the risk of lack of menstrualnopodobnoe bleeding "cancel" and the emergence of "breakthrough" bleeding or "spotting" bleeding while taking tablets from the second package (as in the case of delayed onset menstrualnopodobnoe bleeding).
Side effects
The safety of the drug Zoely evaluated during seven multicenter clinical studies of up to two years. In these studies included 3490 women aged 18-50 years (a total of 35028 cycles).
Tolerability Zoely good safety profile similar to that of other COCs. The following table lists the possible adverse effects that have been reported with the use of the drug.
The frequency of adverse events listed in the following terms:
"Very often» (? 1/10),
«Often» (<1/10, ? 1/100),
"Infrequently» (<1/100, ? 1/1000),
"Rarely" (<1/1000)
according to MedDRA (synonymous or related condition is not listed, but should also be considered).
Violations of the Metabolic and nutritional: Infrequent - increased appetite, fluid retention; rarely - decreased appetite.
Mental disorders: often - reduced libido, depression, mood swings; rarely - increased libido.
Disorders of the nervous system: often - headache, headache; rarely - a violation of attention.
Violations of the organ of vision: rarely - intolerance to contact lenses, dryness of the eyes
Violations of the vessels: Infrequent - "hot flashes."
Disorders of the gastrointestinal tract: often - nausea; infrequently - bloating; rarely - dry mouth.
Disorders of the skin and subcutaneous tissue disorders: very often - akne1; rare - rash, alopecia, pruritus, dry skin, seborrhea; rarely - chloasma, hypertrichosis.
Violations of the musculoskeletal system and connective tissue disorders: rarely - a feeling of heaviness.
Violations of the genital organs and the breast: very often - irregular bleeding "cancel"; often - abundant acyclic bleeding, abundant menstrualnopodobnye bleeding, breast tenderness, pain in the pelvic area; infrequently - menstrualnopodobnye scanty bleeding, breast tenderness, galactorrhoea, uterine spasm of muscles, predmenstrualnopodobny syndrome, sealing in the mammary glands, dyspareunia, dryness of the vulva and vagina; rarely - an unpleasant odor from the vagina, discomfort in the vaginal area.
General disorders and administration site at: Infrequent - irritability, swelling; rarely - a feeling of hunger.
Laboratory and instrumental data: often - increase in body weight; rare - increase in liver enzymes.
1 - Acne is not spontaneously reported, but the phenomenon is requested, since the evaluation was performed at each visit during the study.
Besides the above undesirable phenomena when applying Zoely reported drug hypersensitivity reactions (frequency of occurrence is not installed).
Side effects that occurred while taking COCs containing ethinyl estradiol, are described in detail in the section "Special instructions": venous and arterial thromboembolism, blood pressure, hormone-dependent tumors (eg liver tumors, breast cancer), chloasma.
Drug interactions
To eliminate possible interactions should be familiar with the instructions for use of concomitant medications.
The influence of other drugs on the drug Zoely
The interaction of oral contraceptives with other drugs that induce enzymes can lead to a "breakthrough" bleeding and / or reduce the effectiveness of contraception.
For drugs inducing liver enzymes (and thus increasing the clearance of hormones) include preparations containing phenytoin, phenobarbital, primidone, bosentan, carbamazepine, rifampicin, medicines or herbal preparations containing St. John's wort (Hypericum perforatum), and to a lesser degree drugs containing oxcarbazepine, topiramate, felbamate and griseofulvin. HIV protease inhibitors having inducing activity (for example, ritonavir and nelfinavir) and non-nucleoside reverse transcriptase inhibitors (eg nevirapine and efavirenz) can also affect the liver metabolism.
During concomitant drugs that induce microsomal enzymes, and within 28 days after their cancellation should use a barrier method of contraception. If necessary, long-term treatment drugs that induce microsomal enzymes, consideration should be given to use another method of contraception.
For preparation Zoely no studies of drug interactions, but using a combination of two studies nomegestrola acetate and estradiol were conducted at higher doses (3.75 mg nomegestrola acetate estradiol + 1.5 mg) in combination with rifampicin and in combination with ketoconazole in the population postmenopausal women. Concomitant rifampicin reduces AUC0-? nomegestrola acetate 95% and increases the AUC0-t (last) 25% estradiol. Concomitant ketoconazole (200 mg single dose) did not affect the metabolism of estradiol, but increases the maximal concentration (85%) and AUC0-? (115%) nomegestrola acetate, but these changes are not clinically significant. It is assumed that similar changes can occur in case of application of these drugs in women of reproductive age.
Effect of the drug on Zoely other drugs
The oral contraceptives may affect the metabolism of other drugs.
Precautions should be prescribed the drug Zoely in combination with lamotrigine.
Zoely Effect of the drug on laboratory tests
COCs may affect the results of certain laboratory tests, including biochemical parameters of liver, thyroid, adrenal and kidney concentrations of (transport) proteins in plasma (eg, GLCs and the fractions
lipids / lipoproteins), carbohydrate metabolism, indicators of blood coagulation and fibrinolysis. These figures do not usually go beyond the normal range.
Overdose
Reapply Zoely drug in doses that are 5 times higher than recommended, and single dose nomegestrola acetate in doses that are 40 times higher than recommended, adverse events were not accompanied.
Symptoms that may occur with overdose include nausea, vomiting, bloody discharge from the vagina.
Treatment: antidotes exist. Further treatment should be symptomatic.
Storage conditions
Store at 2 to 30 ° C.
Keep out of the reach of children.
Shelf life
3 years.
