Zoely, 84 pcs., 2.5 mg+1.5 mg, film-coated tablets

Compound

Zoely price, where to buy

The price of Zoely on the Russian pharmaceutical market ranges from 800 to 1100 rubles.

You can buy Zoely birth control pills in Moscow at an average cost of 850 rubles.

• Online pharmacies in RussiaRussia

ZdravCity

• Zoely tab.
  p.p.o. set 2.5mg+1.5mg/placebo 84 pcs. Delpharm Lille S.A.S./Merck Sharp and Dome B.V./N.V.Organon RUR 3,649 order
• Zoely tablets p.p.o. 2.5 mg + 1.5 mg placebo 28 pcs. Delpharm Lille S.A.S./Merck Sharp and Dome B.V./N.V.Organon

  RUB 1,171 order

Pharmacodynamics

Nomegestrol acetate is a highly selective progestogen that is a derivative of the natural steroid hormone progesterone. Nomegestrol acetate has a strong affinity for the human progesterone receptor, has antigonadotropic activity, progesterone receptor-mediated antiestrogenic activity, moderate antiandrogenic activity, and no estrogenic, androgenic, glucocorticoid or mineralocorticoid activity. Zoely® contains 17β-estradiol, a natural estrogen identical to endogenous human 17β-estradiol. Unlike ethinyl estradiol, which is included in other COCs, E2 does not have an ethynyl group at the 17α position. When using the drug Zoely®, the average concentrations of E2 are comparable to those in the initial follicular phase and the late phase of the corpus luteum of the menstrual cycle (see “Pharmacokinetics”). The contraceptive effect of Zoely® is due to a combination of various factors, the most important of which are suppression of ovulation and changes in the viscosity of cervical secretions.

In two randomized, open-label comparative studies of efficacy and safety, more than 3,200 women aged 18–50 years took Zoely® for 13 consecutive cycles and more than 1,000 women took the combination of drospirenone (3 mg)/ethinyl estradiol (30 mcg) in a dosing regimen of 21 /7. In the group taking Zoely®, weight gain was reported in 8.6% of women (in the comparison group - 5.7%), irregular withdrawal bleeding (mainly the absence of such) was reported in 10.5% of women (in the group comparison - 0.5%), acne was reported in 15.4% of women (in the comparison group - 7.9%) (see "Side effects"). An assessment of the development of acne while taking Zoely® showed that the majority of women (73.1%) did not experience a change in condition compared to the condition before treatment, 16.8% of women experienced an improvement in condition and 10.1% of women experienced appearance or worsening of acne. In a clinical study of the drug Zoely®, conducted in the EU, Asia and Australia, the following Pearl index indicators were calculated for the age group 18–35 years: ineffectiveness of the method - 0.4 (upper limit of the 95% confidence interval 1.03); ineffectiveness of the method and patient error - 0.38 (upper limit of 95% confidence interval 0.97).

In a clinical study of Zoely® conducted in the USA, Canada and Latin America, the following Pearl index values ​​were calculated for the age group 18–35 years: method ineffectiveness - 1.22 (upper limit of 95% confidence interval 2.18); method ineffectiveness and patient error - 1.16 (upper limit of 95% confidence interval 2.08).

In a randomized, open-label study, 32 women received Zoely® for 6 cycles. After stopping Zoely®, ovulation was restored on average 20.8 days after the last pill, with the earliest date of ovulation recorded on the 16th day.

Folic acid is an important vitamin in early pregnancy. While taking Zoely®, the concentration of folic acid in the blood plasma does not change and remains at the baseline level for 6 consecutive months of taking the drug. In a randomized, open-label comparative study of 2 years duration, Zoely® was administered to women aged 21–35 years and there was no clinically significant effect of Zoely® on bone mineral density.

A randomized, open-label, comparative multicenter study was conducted to evaluate the effect of Zoely® on blood coagulation parameters, lipid profile, carbohydrate metabolism, the functional state of the adrenal glands and thyroid gland, as well as androgen concentrations. 60 women aged 18–50 years took Zoely® for 6 consecutive cycles. In clinical studies, it was found that when taking Zoely®, insulin resistance and glucose tolerance did not change, and clinically significant effects on lipid metabolism and hemostasis were not detected. Taking Zoely® increased the concentrations of the transport proteins thyroxine-binding globulin and corticosteroid-binding globulin (CBG). When taking Zoely®, the concentration of sex hormone binding globulin (SHBG) slightly increased and the concentrations of androstenedione, dehydroepiandrosterone, total and free testosterone significantly decreased. In a clinical study in a group of women (n=32), after 13 cycles of taking Zoely®, no pathological changes were observed in histological examination of the endometrium.

Zoely's analogs

Level 4 ATC code matches:
Ovidon

Rigevidon

Non-Ovlon

Mercilon

Yarina Plus

Yarina

Miniziston 20 fem

Novinet

Microgynon

Janine

Lindineth

Cyclo-Proginova

Regulon

Logest

Midiana

Belara

Femoden

Jess Plus

Jess

Analogues of Zoely are represented by the following contraceptive drugs:

• Claira;
• Trisiston;
• Trigestrel;
• Tri-regol;
• Triquilar.

Zoely or Klaira - which is better?

Despite some differences in the composition of the active ingredients, nomegestrol + estradiol in Zoely and dienogest + estradiol valerate in Qlaira , the mechanism of action of both drugs is almost the same. Both drugs are microdosed, however, Klaira , in each group of tablets (different in color), contains a different mass fraction of active substances, while in Zoely the dosage in each active tablet is the same. These contraceptives practically repeat each other, both in contraindications and side effects. In this regard, it is not possible to give a definite answer which of these drugs is better.

Oral contraceptives of hormonal action are selected individually and the best suitable drug can be prescribed only after undergoing many tests and undergoing some research. We should not forget about chronic diseases, a history of painful conditions (both personal and family) and many other factors that can also affect the choice of contraceptive.

Whenever you choose between Zoely and Claira , you should remember that these drugs, if you strictly follow the recommendations for their use, are highly effective and cause fewer side effects compared to other contraceptives. But the choice of COCs should be purely individual.

Pharmacokinetics

Nomegestrol acetate

Suction. Nomegestrol acetate is rapidly absorbed after oral administration. After a single dose, Cmax in plasma is about 7 ng/ml and is achieved after 2 hours. Absolute bioavailability after a single dose is 63%. Food does not have a clinically significant effect on the bioavailability of nomegestrol acetate.

Distribution. Nomegestrol acetate binds actively to albumin (97–98%), but does not bind to SHBG or DSG. The apparent Vss of nomegestrol acetate is (1645±576) l.

Metabolism. Nomegestrol acetate is metabolized to several inactive hydroxylated metabolites under the influence of liver cytochrome P450 isoenzymes, mainly CYP2C8, CYP2C19, CYP3A4 and CYP3A5, with possible participation in the metabolism of CYP2C8 and CYP2C19 isoenzymes. Nomegestrol acetate and its hydroxylated derivatives undergo pronounced phase 2 metabolism with the formation of glucuronide and sulfate conjugates. Clearance at steady state is 26 l/h.

Excretion. T1/2 at steady state is 46 hours (from 28 to 83 hours). T1/2 of metabolites has not been established. Nomegestrol acetate is excreted by the kidneys and intestines (approximately 80% of the dose is excreted within 4 days). Nomegestrol acetate is almost completely eliminated within 10 days. Excretion through the intestines exceeds excretion by the kidneys.

Linearity. Linearity of pharmacokinetics depending on the dose was observed in the range of 0.625–5 mg (assessed in women of reproductive and postmenopausal age).

Equilibrium state. SHBG does not affect the pharmacokinetics of nomegestrol acetate. The equilibrium state is achieved after 5 days. The average Css is 4 ng/ml. Cmax of nomegestrol acetate in plasma is about 12 ng/ml and is achieved 1.5 hours after taking the drug.

Interactions. In vitro, nomegestrol acetate does not have a significant inducing or inhibitory effect on cytochrome P450 isoenzymes and does not interact with glycoprotein P.

Estradiol (E2)

Suction. 17β-estradiol undergoes extensive first-pass metabolism after oral administration. Absolute bioavailability is approximately 1%. Food intake does not have a clinically significant effect on the bioavailability of E2.

Distribution. The distribution of exogenous and endogenous E2 is similar. Estrogens are actively distributed throughout the body. Their concentrations are usually higher in the target organs of sex hormones. In the blood, estradiol binds to SHBG (37%) and albumin (61%), and only 1–2% of estradiol circulates in unbound form.

Metabolism. Exogenous E2 is actively biotransformed after oral administration. The metabolism of exogenous and endogenous E2 is similar. E2 is rapidly converted to several metabolites in the intestine and liver (mainly estrone), which are subsequently conjugated and undergo enterohepatic circulation. There is a dynamic equilibrium between E2, estrone and estrone sulfate due to the activity of various enzymes, including estradiol dehydrogenases, sulfotransferases and arylsulfatases. Oxidation of estrone and E2 occurs under the influence of cytochrome P450 isoenzymes, mainly CYP1A2, CYP1A2 (outside the liver), CYP3A4, CYP3A5, CYP1B1 and CYP2C9.

Excretion. E2 is quickly eliminated from the blood. Due to metabolism and enterohepatic circulation, there is a large pool of circulating estrogen sulfates and glucuronides. As a result, T1/2 E2, adjusted to the initial value, varies widely and amounts to (3.6 ± 1.5) hours after i.v. administration.

Equilibrium state. Cmax E2 in serum is about 90 pg/ml and is achieved 6 hours after administration. The average serum concentration is 50 pg/ml. This E2 concentration corresponds to that in the initial and late phases of the menstrual cycle.

Special patient groups

Children. The pharmacokinetics of nomegestrol acetate (primary target) following a single oral dose of Zoely® were comparable in healthy postmenarchean adolescent girls and adult women. Concentrations of E2 (secondary target) in adolescent girls compared with adult women were comparable during the first 24 hours and lower than in adult women after 24 hours. The clinical significance of this finding is unknown.

Renal dysfunction. The effect of renal disease on the pharmacokinetics of Zoely® has not been studied.

Liver dysfunction. The effect of liver disease on the pharmacokinetics of Zoely® has not been studied. However, in patients with impaired liver function, the metabolism of sex hormones may deteriorate.

Ethnic groups. The pharmacokinetics of the drug in representatives of ethnic groups has not been specifically studied.

Contraindications

COCs should not be used if any of the following conditions/diseases are present. There are no epidemiological data on the use of COCs containing 17β-estradiol, however, the contraindications to the use of Zoely® correspond to the contraindications to the use of contraceptives containing ethinyl estradiol. If any of these conditions occur while using Zoely®, you should immediately stop taking the drug:

hypersensitivity to any active or auxiliary substances;

deep vein thrombosis or pulmonary embolism, incl. in the anamnesis;

arterial thrombosis (myocardial infarction) or prodromal conditions (transient ischemic attack, angina), incl. in the anamnesis;

acute cerebrovascular accidents, incl. in the anamnesis;

migraine with focal neurological symptoms, incl. in the anamnesis;

severe or multiple risk factors for venous or arterial thrombosis (such as diabetes mellitus with vascular symptoms; uncontrolled arterial hypertension; severe dyslipoproteinemia; obesity (body mass index more than 30 kg/m2); prolonged immobilization; major surgery, any surgery on the lower extremities or serious injury; complicated heart defects; atrial fibrillation; smoking over the age of 35 years - see “Special Instructions”);

hereditary or acquired predisposition to the development of venous or arterial thrombosis, for example, activated protein C resistance, antithrombin III deficiency, protein C and S deficiency, hyperhomocysteinemia and the presence of antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant);

pancreatitis with severe hypertriglyceridemia, incl. in the anamnesis;

severe liver diseases, incl. in the anamnesis, until normalization of liver function indicators;

liver tumors (malignant or benign), incl. in the anamnesis;

known or suspected hormone-dependent malignant tumors (for example, tumors of the genital organs or breast);

lactase deficiency, lactose intolerance, glucose-galactose malabsorption;

bleeding from the vagina of unknown etiology;

postmenopause;

established or suspected pregnancy;

breastfeeding period.

With caution (if any of the following conditions/diseases are present), the benefits of using Zoely® and the possible risks for each individual woman should be assessed. This should be discussed with the woman before she starts taking Zoely® (for more information, see " Special instructions") In cases of deterioration, exacerbation of the disease or the occurrence of any of these conditions, diseases, risk factors for the first time, a woman should consult a doctor to decide on the possibility of further use of Zoely®: diabetes mellitus without vascular damage; severe depression or the presence of this disease history; systemic lupus erythematosus; Crohn's disease; ulcerative colitis; liver dysfunction; hypertriglyceridemia, including a family history; risk factors for coronary heart disease (obesity, arterial hypertension); family history of venous thrombosis, arterial embolism in siblings or parents at a young age (see “Special Instructions”).

special instructions

The data below were obtained during epidemiological studies of COCs containing ethinyl estradiol . The drug Zoely includes 17β-estradiol , however, the special instructions described apply to it as well.

Vascular disorders

An association has been observed between taking COCs and the risk of thromboembolism , as well as venous and arterial thrombosis ( myocardial infarction, deep vein thrombosis, stroke, pulmonary embolism). Against the general background, these conditions rarely develop, but during the first year of taking COCs, the risk of developing these complications is highest. You should know that 1-2% of cases of embolism and venous thrombosis .

With the development of thrombosis, the following may occur:

• pain and/or swelling of the legs;
• sudden shortness of breath ;
• sharp pain in the chest, with or without rebound, in the left arm;
• unexpected cough ;
• sudden loss of vision (partial or complete), uncharacteristic severe prolonged headaches;
• diplopia;
• dizziness;
• speech disorder;
• collapse (possibly with convulsions);
• weakness;
• movement disorders;
• sudden severe numbness on one side of the body;
• acute abdomen syndrome.

Risk factors for embolism and venous thrombosis :

• advanced age;
• hereditary predisposition (family history of these diseases);
• obesity;
• thrombophlebitis;
• phlebeurysm;
• serious injury;
• major surgery;
• long-term immobilization.

Risk factors for arterial thrombosis :

• smoking;
• advanced age;
• dyslipoproteinemia;
• arterial hypertension;
• obesity;
• migraine;
• atrial fibrillation;
• heart valve disease;
• hereditary predisposition.

It is worth remembering the increased risk of thromboembolic exacerbations in the postpartum period.

For any of these disorders, you should consult your doctor before taking Zoely tablets. In cases of suspected thrombosis or its diagnosis, while using COCs, the tablets should be discontinued. For conditions requiring hospitalization (serious trauma, major surgery, prolonged immobilization), it is better to stop using COCs (one month before a planned operation), with resumption of use 14 days after normal resumption of motor functions.

Also, consultation with a doctor will be required for such diseases as:

• diabetes;
• uremic hemolytic syndrome;
• systemic lupus erythematosus;
• ulcerative colitis;
• Crohn's disease;
• sickle cell anemia.

Increased migraine is an indication for immediate discontinuation of Zoely.

Tumors

Long-term use of ethinyl estradiol-containing COCs , according to research results, increases the risk of developing cervical cancer , however, the question of other exposure factors remains open. It is not fully understood whether COC use, more frequent cervical testing, sexual intercourse (including barrier contraception), or a combination of these leads to an increased risk.

reliable information about the effect of Zoely on the development of ovarian and endometrial .

A slight increase in the relative risk (RR) of breast cancer (RR = 1.24). This risk decreases over 10 years after discontinuation of COCs. This increase is possibly due to earlier detection, the effects of COCs, or a combination of both.

Sometimes, when taking COCs, the development of liver tumors (benign) was detected, and even less often - malignant. In rare cases, these tumors, due to intra-abdominal bleeding, became a threat to the patient’s life. If an enlarged liver, intense abdominal pain, or symptoms of intra-abdominal bleeding are detected, a possible liver tumor should be excluded.

Other states

Taking COCs with hypertriglyceridemia or a family history of it slightly increases the risk of pancreatitis .

increase in blood pressure was often observed , which was rarely clinically significant. The connection between COC use and the formation of arterial hypertension . However, if it develops, it is worth stopping the use of COCs and considering prescribing adequate antihypertensive therapy. When blood pressure is stabilized with the use of antihypertensive drugs, it is possible to resume the use of COCs. According to the results of clinical studies, taking Zoely for up to 12 months did not lead to clinically significant blood pressure disorders.

During the use of COCs and during pregnancy, complications or development were noted: itching and/or jaundice , cholelithiasis, gestational herpes, porphyria, hemolytic uremic syndrome, systemic lupus erythematosus, Sydenham's chorea, angioedema , as well as hearing loss.

Liver pathologies may require discontinuation of COCs until the liver condition is completely normalized.

In case of recurrence of cholestatic jaundice, which was first diagnosed during pregnancy or previous steroids

glucose tolerance and insulin resistance . However, while taking them, it is necessary to conduct careful periodic examinations, especially for women with diabetes .

ulcerative colitis, Crohn's disease and was observed .

chloasma developed , especially when this disease was mentioned in the anamnesis. In this case, it is better to avoid prolonged exposure to the sun, solarium and other exposure to ultraviolet radiation.

Conducting consultations and examinations

Before prescribing a COC, it is necessary to obtain an understanding of the woman’s personal and family history, and also to exclude possible pregnancy. Measure blood pressure and, if indicated, prescribe a physical examination , taking into account all contraindications. The frequency of control examinations in each case is determined separately, but at least twice a year.

Women should receive full information about the action and side effects of COCs, and also be informed that this method of contraception does not prevent HIV infection and other sexually transmitted diseases.

Reduced efficiency

The effectiveness of COCs may be reduced if active tablets are missed, as well as gastrointestinal disorders.

Menses

The use of COCs, especially in the first months, may be accompanied by spotting or breakthrough bleeding . In this regard, it is advisable to conduct a study of these manifestations after the adaptation period (3 months). If these symptoms persist after three cycles of taking COCs, their non-hormonal nature should be assumed and diagnostics should be prescribed to exclude possible tumors or pregnancy . may be performed .

When studying the drug Zoely, bleeding developed rarely and was short-lived, mild and slightly painful. In some cases, the absence of proper withdrawal bleeding was observed when taking placebo, without diagnosing pregnancy, which indicates its low probability even in the absence of withdrawal bleeding. If two bleedings are missed, when taking the drug in accordance with the instructions, a possible pregnancy must be excluded.

Use during pregnancy and breastfeeding

The use of Zoely® is contraindicated during pregnancy. If pregnancy occurs while using Zoely®, you should stop taking the drug.

Most epidemiological studies have not found an increased risk of birth defects in children whose mothers took COCs containing ethinyl estradiol before pregnancy. No teratogenic effects were observed with the occasional use of COCs containing ethinyl estradiol at the beginning of pregnancy.

There is limited experience with the use of Zoely® in pregnant women, which indicates the absence of undesirable effects of the drug on the condition of the fetus or newborn.

Reproductive toxicity has been reported in laboratory animal studies of the nomegestrol acetate/estradiol combination.

Zoely® is intended to prevent unwanted pregnancy. If a woman wants to stop taking Zoely® in order to become pregnant, it should be taken into account that ovulation is restored on average 20.8 days after the last dose of Zoely® tablet (see Pharmacodynamics).

COCs may affect lactation because they cause changes in the quantity and composition of breast milk. Therefore, the use of COCs is not recommended until breastfeeding has completely stopped (an alternative method of contraception should be selected). Small amounts of contraceptive sex hormones and/or their metabolites can be excreted in breast milk, but there is no data on their undesirable effects on the health of the newborn.

Reviews about Zoely

The pharmaceutical industry produces many hormonal contraceptives for oral use. Considering Zoely's birth control pills, reviews from gynecologists, subject to all the rules for taking the pills, are mostly positive. Naturally, any doctor in his practice has encountered many side effects of medications, and Zoely cannot do without them. Although, compared to many other COCs, Zoely tablets exhibit fewer side effects, and those that are detected are less pronounced.

Reviews of Zoely among women using this drug are purely positive, and this suggests that the active and auxiliary composition of the tablets is completely suitable for their body. Negative reviews are found among women who tried this contraceptive and eventually abandoned its use due to various side effects.

Each organism is individual and has its own set of characteristics, therefore, when choosing a contraceptive, you need to rely on the experience of a gynecologist, as well as undergo all the tests recommended by him. In this case, you have a much better chance of choosing exactly “your” contraceptive, which will not only protect you from unwanted pregnancy, discomfort into your life .

Side effects

The safety of Zoely® was assessed in seven multicenter clinical studies lasting up to 2 years. These studies included 3,490 women aged 18–50 years (a total of 35,028 cycles). Zoely® is well tolerated and the safety profile is similar to that of other COCs. The table lists possible undesirable effects that have been reported with the use of the drug.

The frequency of adverse events is indicated in terms of - very often (≥1/10); often (<1/10, ≥1/100); uncommon (<1/100, ≥1/1000); rare (<1/1000) according to MedDRA (synonyms or associated conditions are not listed but should also be considered).

Table

1Acne is not a spontaneously reported event, but a solicited one, as assessments were completed at every study visit.

In addition to the above-mentioned adverse events, hypersensitivity reactions have been reported when using Zoely® (the frequency of occurrence has not been established). Side effects that occurred when taking COCs containing ethinyl estradiol are described in detail in the “Special Instructions” section: venous and arterial thromboembolism, increased blood pressure, hormone-dependent tumors (for example, liver tumors, breast cancer), chloasma.

Interaction

To exclude possible interactions, you should read the instructions for use of concomitant medications.

Effect of other drugs on Zoely®

Interaction of oral contraceptives with other enzyme-inducing drugs may lead to breakthrough bleeding and/or decreased contraceptive effectiveness.

Drugs that induce liver enzymes (and therefore increase the clearance of sex hormones) include drugs containing phenytoin, phenobarbital, primidone, bosentan, carbamazepine, rifampicin, drugs or herbal preparations containing St. John's wort (Hypericum perforatum), and to a lesser extent medicines containing oxcarbazepine, topiramate, felbamate and griseofulvin.

HIV protease inhibitors with inducing activity (eg ritonavir and nelfinavir) and non-nucleoside reverse transcriptase inhibitors (eg nevirapine and efavirenz) may also affect hepatic metabolism. During concomitant use of drugs that induce microsomal enzymes, and for 28 days after their discontinuation, a barrier method of contraception should be used. If long-term treatment with drugs that induce microsomal enzymes is necessary, the use of another method of contraception should be considered.

No drug interaction studies have been conducted for Zoely®, but two studies have been conducted using a combination of nomegestrol acetate and E2 at higher doses (nomegestrol acetate 3.75 mg + estradiol 1.5 mg) in combination with rifampicin and in combination with ketoconazole in the population postmenopausal women.

Concomitant use of rifampicin reduces the AUC0–∞ of nomegestrol acetate by 95% and increases the AUC0–t (last) E2 by 25%. Concomitant administration of ketoconazole (single dose 200 mg) does not affect E2 metabolism, but increases Cmax (85%) and AUC0–∞ (115%) of nomegestrol acetate, but these changes are not clinically significant. It is assumed that similar changes may occur if these drugs are used in women of reproductive age.

Effect of Zoely® on other drugs

Oral contraceptives may affect the metabolism of other drugs. Zoely® should be administered with caution in combination with lamotrigine.

Effect of Zoely® on laboratory tests

Taking COCs may affect the results of some laboratory tests, including biochemical indicators of liver, thyroid, adrenal and kidney function, plasma concentrations of transport proteins (for example, DRGs and lipid/lipoprotein fractions), indicators of carbohydrate metabolism, blood coagulation and fibrinolysis. These indicators usually do not go beyond normal values.