Composition, form of production and packaging
Tablets covered with a film shell from white to almost white, round, biconvex, with engraving "ne" on both sides; color of the kernel on a section from white to almost white (24 pcs in a blister).
1 tab.
Estradiol hemihydrate 1.55 mg,
which corresponds to the content of estradiol 1.5 mg
Nomegastrol acetate 2.5 mg
Excipients: microcrystalline cellulose - 14 mg, crospovidone - 2.4 mg, talc - 0.7 mg, magnesium stearate - 0.7 mg, silicon dioxide colloid - 0.44 mg, lactose monohydrate - 57.71 mg.
The composition of the shell: opadrai II white - 1.6 mg (polyvinyl alcohol - 0.64 mg, titanium dioxide - 0.4 mg, macrogol 3350 - 0.32 mg, talc - 0.24 mg).
Tablets (placebo), coated with a film coating of yellow color, round, biconvex, with engraving "p" on both sides, color of the core on a section from white to almost white (4 pieces in a blister).
Excipients: microcrystalline cellulose - 14 mg, crospovidone - 2.4 mg, talc - 0.7 mg, magnesium stearate - 0.7 mg, silicon colloidal dioxide - 0.44 mg, lactose monohydrate - 61.76 mg.
The composition of the shell: opedrai II yellow - 2.4 mg (polyvinyl alcohol - 0.96 mg, titanium dioxide - 0.58 mg, macrogol 3350 - 0.48 mg, talc - 0.36 mg, iron oxide oxide yellow - 0.016 mg, iron oxide black oxide - 0.00024 mg).
28 pcs. - blisters made of PVC / aluminum foil (1) complete with a sticker with days of the week - packs cardboard.
28 pcs. - blisters made of PVC / aluminum foil (3) complete with a sticker with days of the week - packs cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2015.
PHARMACHOLOGIC EFFECT
Combined hormonal contraceptive preparation containing estrogen 17? -estradiol and progestagen nomegastrol acetate.
Estradiol (17? -estradiol) is a natural estrogen identical to endogenous human 17? -estradiol (E2). Unlike ethinyl estradiol, which is part of other combined oral contraceptives, E2 does not have an ethynyl group in the 17ОІ position. When using Zoeli В®, the average E2 concentrations are comparable to those in the initial follicular phase and the late phase of the yellow body of the menstrual cycle.
Nomegastrol acetate is a highly selective progestagen that is a derivative of the natural steroid hormone progesterone and structurally similar to it. Nomegastrol acetate has a pronounced affinity for the human receptor of progesterone, has a high antigonadotropic activity, moderate antiandrogenic activity and does not possess estrogenic, androgenic, glucocorticoid and mineralocorticoid activity.
The contraceptive effect of Zoeli В® is due to a combination of various factors, the most important of which are suppression of ovulation and a change in the secretion of cervical mucus. When taking Zoeli В® nomegastrol acetate mainly suppresses ovulation, and E2 enhances the effects of progestogen. After the abolition of Zoeli В®, in most women, ovulation is quickly restored.
At the time of administration, the serum folate concentration remains unchanged and remains at the baseline level for 6 consecutive months of Zoeli В® preparation.
In clinical studies, it was found that the Perl index for women aged 18 to 50 years was 0.66 (the upper limit is 95% confidence interval 1.07), and for women aged 18 to 35, the Perl index was 0.75 (the upper limit of 95% of the interval 1.23).
In clinical studies it was found that when Zoeli В® was administered, glucose tolerance and insulin sensitivity did not change, no clinically significant effects on lipid metabolism and hemostasis were found. Zoeli В® intake increased the protein content of the carriers of thyroxin-binding globulin and corticosteroid-binding globulin (COG), but to a lesser extent than the combination of levonorgestrel and ethinylestradiol. When taking Zoeli В® , the content of sex hormone binding globulin (SHBG) increased insignificantly, the content of androstenedione, dehydroepiandrosterone, total and free testosterone decreased significantly. After 13 cycles of taking the drug, no pathological changes were observed in the histological examination of the endometrium.
PHARMACOKINETICS
Estradiol (E2)
Suction
17? -estradiol (E2) undergoes a pronounced metabolism at the "first passage" after ingestion. Absolute bioavailability is approximately 5%. Eating 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 organs-targets of sex hormones. In the blood, estradiol binds SHGG (37%) and albumin (61%) and only 1-2% of estradiol circulates unbound.
C max E2 in the serum is about 90 pg / ml and is achieved 6 hours after administration. The mean serum concentrations are 50 pg / ml. These concentrations of E2 correspond to those in the initial and late phases of the menstrual cycle.
Metabolism and excretion
Exogenous E2 is actively biotransformed after oral administration. Metabolism of exogenous and endogenous E2 is similar. E2 rapidly turns into several metabolites in the intestine and liver, mainly in estrone (E1), which are subsequently conjugated and subjected to intestinal-hepatic circulation. There is a dynamic equilibrium between E2, E1 and E1-sulphate (E1S) due to the activity of various enzymes, including E2-dehydrogenases, sulfotransferases and arylsulfatases. Oxidation of E1 and E2 occurs under the action of cytochrome P450 isoenzymes, mainly CYP1A2, CYP1A2 (outside the liver), CYP3A4, CYP3A5, CYP1B1 and CYP2C9.
E2 is quickly excreted from the blood. Due to metabolism and intestinal-hepatic circulation, there is a large pool of circulating sulfates and estrogen glucuronides. As a result, T 1/2 E2 varies over a wide range and is 8.4 В± 6.4 hours after intravenous administration.
Nomegestrol acetate
Suction
Nomegastrol acetate is rapidly absorbed after oral administration. After a single intake of C max 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.
The linearity of pharmacokinetics as a function of the dose was observed in the range of 0.625-5 mg (estimated in women of reproductive and postmenopausal age).
Distribution
Nomegastrol acetate actively binds to albumin (97-98%), but does not bind to GSH or CSG.
GSG does not affect the pharmacokinetics of nomegestrol acetate. The equilibrium state is reached after 5 days. The average C ss is 4 ng / ml. Cmax nmegestrol acetate in plasma is about 12 ng / ml and is achieved 1.5 hours after taking the drug in an equilibrium state.
Metabolism
Nomegastrol acetate is metabolized to several inactive hydroxylated metabolites under the action of cytochrome P450 isoenzymes of the liver, mainly CYP2C8, CYP2C19, CYP3A4 and CYP3A5. Nomegastrol acetate and its hydroxylated derivatives undergo a pronounced 2-phase metabolism with the formation of glucuronide and sulfate conjugates. The clearance in the equilibrium state is 26 l / h.
In vitro nomegastrol acetate does not have a significant inducing or inhibitory effect on cytochrome P450 isoenzymes and does not interact with the P-glycoprotein.
Excretion
T 1/2 in the equilibrium state is 46 h (from 28 to 83 h). T 1/2 of metabolites is not established.
Nomegastrol acetate is excreted by the kidneys and through the intestine. Approximately 80% of the dose is excreted by the kidneys and through the intestine for 4 days. Nomegastrol acetate is almost completely eliminated within 10 days. Excretion through the intestine exceeds excretion by the kidneys.
Pharmacokinetics in special clinical cases
Pharmacokinetic modeling did not reveal differences in the pharmacokinetics of nomegestrol acetate in girls aged 12-17 years after the onset of menarche and in adult women.
The effect of kidney disease on the pharmacokinetics of Zoeli В® was not studied.
The effect of liver disease on the pharmacokinetics of Zoeli В® has not been studied. However, in patients with impaired liver function, a deterioration in the metabolism of sex hormones is possible.
The pharmacokinetics of the drug in representatives of ethnic groups has not been specifically studied.
INDICATIONS
- Contraception.
DOSING MODE
The drug is intended for oral administration.
Recommendations for the reception of tablets are the same for all women.
Tablets are taken daily at the same time of the day, regardless of food intake in the order indicated on the package, if necessary, with a small amount of water. It should be taken 1 tablet / day for 28 consecutive days. Admission should begin with white tablets containing active ingredients for the first 24 days, and for the next 4 days - yellow tablets that do not contain active ingredients (placebo). The taking of tablets from each subsequent package should begin the day after the last tablet from the previous package, regardless of the presence or absence of bleeding cancellation. Bleeding cancellation usually begins 2-3 days after the last white pill and may not stop at the beginning of taking the tablets from the next package.
Initiation of Zoeli В®
In the absence of prior application of hormonal contraceptives
Tablets should be taken on the first day of the menstrual cycle (the first day of menstrual bleeding). In this case, the use of additional contraceptives is not required.You can begin taking pills and from the 2-5th day of the cycle, but then during the first 7 days of taking the tablets it is recommended to use the barrier method of contraception in addition.
Transition from a combined hormonal contraceptive (combined oral contraceptive, vaginal ring or transdermal patch)
Taking Zoeli В® is recommended starting the day after taking the last pill containing the active ingredients, but no later than the day after the end of the usual interval between cycles or taking placebo tablets. If a woman used a vaginal ring or a transdermal patch, it is advisable to start taking Zoeli В® on the day they are removed, but no later than on the day when a new ring should be inserted or another patch applied.
If a woman regularly and correctly used the previous method of contraception, and there is no doubt that she is not pregnant, then you can switch to taking Zoeli В® in any day. In no case should the recommended non-hormonal interval of the previous method be exceeded.
Transition from preparations containing only progestogen (tablets, implants, injectable forms or hormone-containing intrauterine systems - IUDs)
A woman can stop taking pills containing only progestogen on any day and start taking Zoeli В® the next day. Implant or IUD can be removed on any day, taking ZoeliВ® should be started on the day of their removal.
If a woman received injections, then Zoeli В® is started on the day of the next injection. In all these cases, the woman is recommended to use the barrier method of contraception in the first 7 days of taking the tablets containing the active substances.
After the abortion, made in the first trimester of pregnancy
A woman can start taking the drug right away; in this case there is no need for an additional method of contraception.
After childbirth or abortion in the second trimester of pregnancy
A woman should start taking the drug between the 21st and 28th day after childbirth or abortion in the second trimester. At a later start of the drug, an additional barrier method of contraception is recommended during the first 7 days of taking the tablets. However, if you have had sexual intercourse after childbirth or abortion, you must exclude pregnancy or wait for the first menstrual period before starting Zoeli В® .
In case of missing tablets
The recommendations below concern only the admission of white tablets containing active ingredients.
If a woman takes another pill with a delay of less than 12 hours , then the contraceptive effect does not decrease. A woman should take a pill as soon as possible, as soon as she remembers it. Follow-up tablets should be taken at the usual time.
If a woman takes an active tablet with a delay of more than 12 hours , the contraceptive effect may decrease. If you miss taking pills, it is advisable to follow two rules:
- to achieve adequate suppression of the hypothalamic-pituitary-ovarian system, white tablets containing active ingredients must be taken for at least 7 consecutive days;
- the more white white tablets containing active ingredients are missed, and the closer the time of taking 4 yellow tablets, the higher the risk of pregnancy.
If a single white tablet containing active ingredients is missed
The contraceptive effect is not reduced. A woman should take the last missed white pill as soon as she remembers it, even if she has to take two tablets at the same time. Then the tablets should be taken as usual. No additional contraceptive measures are required.
If you missed taking two white tablets or more
If after missing two or more white tablets containing active ingredients, there was no withdrawal bleeding during taking yellow tablets, then pregnancy should be excluded.
Days 1-7
A woman should take the last missed white pill as soon as she remembers it, even if she has to take two tablets at the same time. Then the tablets should be taken as usual. Thus during the first week of continuous reception of white tablets it is necessary to use a barrier method of contraception. If during the previous 7 days there was a sexual intercourse, then the possibility of pregnancy should be taken into account.
Days 8-17
A woman should take the last missed white pill as soon as she remembers it, even if she has to take two tablets at the same time. Then the tablets should be taken as usual. In this case, during the next 7 days of taking white tablets, a barrier method of contraception should be used.
Days 18-24
The risk of a decrease in the contraceptive effect increases with the approach of taking yellow tablets to a placebo. However, changing the regimen of taking tablets helps to avoid a decrease in contraceptive activity. A woman should take the last missed white pill as soon as she remembers it, even if she has to take two tablets at the same time. You can not simultaneously take more than two white tablets containing active ingredients. During the next 7 days of taking white tablets, a barrier method of contraception should be used, and the next package should begin immediately after the end of the white tablets from the previous package, i.e. a woman should not take a yellow placebo pill. In this case, bleeding cancellation usually occurs during the reception of yellow tablets from the following package, however, during the reception of white tablets, breakthrough bleeding or spotting can occur.
If a woman is not sure of the number of missed tablets or their color and, accordingly, does not know what recommendations she should follow, then a barrier method of contraception should be used until the woman takes white tablets for 7 consecutive days.
If the yellow tablets of placebo are missed
The contraceptive effect is not reduced. A woman can not take yellow tablets from the last (fourth) row of blisters. However, the missed tablets should be discarded to avoid an unintended increase in the duration of the placebo phase.
Recommendations in case of gastrointestinal disorders
In the case of gastrointestinal disorders (eg, vomiting or diarrhea), the absorption of the drug may be incomplete, therefore additional contraceptive measures should be taken.
If vomiting occurs within 3-4 hours after taking the pill, then its reception should be considered missed. If you missed taking one white pill, then the contraceptive effect is not reduced. If the next day or days again develops vomiting, then it is necessary to follow the recommendations for missing two or more tablets. If a woman does not want to change the usual scheme for taking tablets, she should take an additional white tablet or tablets from another package.
How to move or delay the onset of menstrual bleeding
To delay the onset of menstrual bleeding, a woman should continue taking white tablets from another package without taking yellow tablets. White tablets from the second package can be taken until they run out. After the completion of the reception of yellow tablets from the second package, it is necessary to resume the reception of Zoeli В® according to the usual scheme. With an extended admission scheme, breakthrough bleeding or spotting can occur.
In order to shift the day of onset of menstrual bleeding the next day, you can reduce the phase of taking placebo tablets (maximum 4 days). The shorter the interval, the higher the risk of lack menstrualnopodobnoe withdrawal bleeding and occurrence of breakthrough bleeding or spotting while taking the pills from the second pack.
SIDE EFFECT
Tolerability Zoeli В® is good, and the safety profile is similar to that of other combined oral contraceptives. The table lists the possible adverse effects that have been reported when using the drug.
Determining the frequency of adverse reactions: common (1/100?), Rare (<1/100, 1/1000?), Rare (<1/1000).
Often Infrequent Seldom
From a metabolism
increase body weight increased appetite, decreased appetite, fluid retention
From the psyche
reduced libido, depression, mood swings increase libido
From the nervous system
migraine, headache, impaired attention
From the side of the organ of vision
intolerance to contact lenses, dry eyes
From the vessels
tides
From the digestive system
nausea, bloating, increased liver enzymes dry mouth
From the skin and subcutaneous tissues
acne hyperhydrosis, alopecia, pruritus, dry skin, seborrhea chloasma, hypertrichosis
From the musculoskeletal system
a feeling of heaviness
of the reproductive organs and mammary glands
irregular withdrawal bleeding, metrorrhagia, menorrhagia, breast tenderness, pain in the pelvic area gipomenoreya, breast engorgement, galactorrhea, spasm of the uterus, premenstrual syndrome, sealing in the mammary glands, dyspareunia, dryness of the vulva and vaginal foul odor from the vagina, discomfort in the vaginal area
General reactions
Irritability, edema hunger
Side effects that arise when receiving combined oral contraceptives containing ethinylestradiol: venous and arterial thromboembolism, increased blood pressure, hormone dependent tumors (e.g., liver tumors, breast cancer), chloasma.
The incidence of breast cancer slightly higher in women receiving combined oral contraceptives. Breast cancer is rare in women under 40 years of age and the number of additional cases while taking combined oral contraceptives is small compared to the overall risk of breast cancer. Communication with the reception of combined oral contraceptives has not been established.
In patients with impaired renal or hepatic functionstudies have been conducted of the drug. In women with impaired liver function may result in poor metabolism of steroid hormones.
CONTRAINDICATIONS
There are no epidemiological data on the use of combined oral contraceptives containing 17? -estradiol, however contraindications Zoeli preparation В® correspond contraindications to the use of contraceptives, containing ethinyl estradiol. In case of any of these states in the application period Zoeli В® should immediately discontinue taking the drug:
- deep vein thrombosis or pulmonary thromboembolism, including in history;
- arterial thrombosis (myocardial infarction, stroke) or prodromal state (transient ischemic attack, angina), including: in history;
- Migraine with focal neurological symptoms, including in history;
- expressed or multiple risk factors for venous or arterial thrombosis, such as: diabetes mellitus with vascular symptoms, severe arterial hypertension, severe dislipoproteinemia;
- 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 antibody (antibodies to cardiolipin, lupus anticoagulant);
- pancreatitis with severe hypertriglyceridemia, including in history;
- severe liver disease, including a history before normalization of liver function;
- liver tumors (benign or malignant), including: in history;
- known or suspected hormone-dependent cancers (e.g. breast or genital gland);
- vaginal bleeding of unknown etiology;
- postmenopause;
- established or suspected pregnancy;
- the period of lactation (breastfeeding);
- Lactase deficiency, lactose intolerance, glucose-galactose malabsorption;
- Hypersensitivity to the components of the drug.
Carefully
If any of the following conditions / diseases should assess the benefits of applying Zoeli В® and the potential risk for each woman. This should be discussed with the woman before she starts receiving the drug Zoeli В® . In case of deterioration, exacerbation or occurrence of any of these states for the first time a woman should see a doctor to decide on possible further application Zoeli В® :
- diabetes mellitus with no vascular lesions;
- severe depression or having a history of the disease;
- systemic lupus erythematosus;
- Crohn's disease;
- ulcerative colitis;
- violations of the liver function;
- hypertriglyceridemia, including family history;
- coronary heart disease risk factors (obesity, smoking at age 35 or older, hypertension);
- long-term immobilization or extensive surgery;
- the presence of a family history of venous thrombosis, arterial embolism in siblings or parents at a relatively young age.
PREGNANCY AND LACTATION
Application Zoeli preparation В® pregnancy contraindicated. In case of pregnancy when using Zoeli В® should stop taking the drug.
Most epidemiological studies have found no increased risk of birth defects in children of women treated with ethinyl estradiol-containing combined oral contraceptives prior to pregnancy. If you have accidentally received in early pregnancy combined oral contraceptives containing ethinyl estradiol, no teratogenic effects were observed.
Limited experience with Zoeli В® in pregnant women have demonstrated the absence of undue influence of the drug on the fetus or newborn.
Combined oral contraceptives may have an effect on lactation, because they cause changes in the amount and composition of breast milk. Consequently, the use of combined oral contraceptives is not recommended until the complete cessation of breastfeeding. Small amounts of contraceptive steroids and / or their metabolites may be excreted in breast milk, but their adverse effect on the health of newborn unknown.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Contraindications severe liver disease, including a history before normalization of liver function; liver tumors (benign or malignant), including: history.
APPLICATION FOR CHILDREN
Data on the efficacy and safety of the drug in children under the age of 18 years are not available.
SPECIAL INSTRUCTIONS
The following data were obtained in epidemiological studies with combined oral contraceptives containing ethinylestradiol. Zoeli В® contains 17? -estradiol, however, special instructions relating to receiving a combined oral contraceptive containing estradiol, are considered to be applicable for Zoeli В® .
Vascular disorders
Epidemiological studies have established a link between the use of combined oral contraceptives containing ethinyl estradiol, and an increased risk of arterial and venous thrombosis and thromboembolic events such as myocardial infarction, stroke, deep vein thrombosis and pulmonary embolism. These complications are rare.
The use of any combined oral contraceptives containing ethinylestradiol, accompanied by an increased risk of venous thrombosis and embolism, is the highest during the first year after the start of a combined oral contraceptive. This increased risk is less risk of venous thrombosis and embolism associated with pregnancy (60 per 100 000 person-years). In women not taking oral contraceptives, the risk of venous thrombosis and embolism is 5-10 per 100 000 person-years. Venous thrombosis and embolisms end in death in 1-2% of cases.
Data on the effect of the drug Zoeli В® on the risk of venous thrombosis and embolism when compared with other combined oral contraceptives available.
Patients who were taking combined oral contraceptives, only rarely developed thrombosis of other vessels, including hepatic, mesenteric, renal, cerebral arteries and veins or the retinal vessels. There is insufficient information on the relationship between the occurrence of these complications and the use of combined oral contraceptives.
Symptoms of venous and arterial thrombosis can include the following conditions: pain and / or leg swelling, sudden severe 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 e disorder syndrome "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 relatively early 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 to resume it only after 2 weeks after the full restoration of motor activity;
- obesity (BMI over 30 kg / m 2 );
- perhaps superficial vein thrombophlebitis and varicose veins.
There is insufficient information about the role of these conditions in the etiology of venous thrombosis.
Risk factors for arterial thrombosis :
- age;
- smoking (risk even more increased by intensive smoking, especially in women over 35 years old);
- dislipoproteinemia;
- obesity (BMI over 30 kg / m 2 );
- arterial hypertension;
- Migraine;
- defect of the heart valves;
- atrial fibrillation;
- the presence of diseases in the family history (arterial thrombosis in siblings or parents at a relatively early 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: diabetes, 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.
Increasing the frequency or severity of migraine (which may precede the development of cerebrovascular complications) is the basis for immediate lifting of the drug receiving Zoeli В® .
Women taking combined oral contraceptives, you should seek medical advice when a possible thrombosis symptoms. In cases of suspected or confirmed thrombosis, receiving combined oral contraceptives 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 contraceptives containing ethinyl estradiol, increases this risk, but it remains unclear to what extent this effect is due 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.
In the application of combined oral contraceptives in higher doses (50 .mu.g of ethinylestradiol) the risk of endometrial cancer and ovarian reduced. It remains unclear whether this applies to combined oral contraceptives containing 17? -estradiol.
A meta-analysis of 54 epidemiological studies in women treated with ethinyl estradiol-containing combined oral contraceptives, revealed a small increase in the relative risk of developing breast cancer (relative risk = 1.24). The increased risk disappears gradually within 10 years after discontinuation of combined oral contraceptives. Breast cancer rarely occurs in women under the age of 40 years, so the number of additional cases of breast cancer in women who are taking or have taken combined oral contraceptives, small compared to the overall risk of breast cancer. Breast cancer is diagnosed in women using combined oral contraceptives, clinically less pronounced than identified cancer in women who never use these drugs.During application of combined oral contraceptives breast cancer risk is increased slightly, which is possible due to an earlier diagnosis, the action of the drug or a combination of these two factors.
In rare cases, women taking combined oral contraceptives, observed the development of liver benign tumors and even more rarely - malignant. In some cases, these tumors have led to life-threatening intra-abdominal bleeding. When intense pain in the upper abdomen, liver enlargement or symptoms intraabdominal bleeding in women receiving combined oral contraceptives, liver tumor should be excluded.
Other conditions
Women with hypertriglyceridemia, or a family history of the corresponding increased risk of pancreatitis when taking COCs.
Many women receiving combined oral contraceptives has been a slight increase in blood pressure, although a clinically significant increase in blood pressure are rare. Association between combined oral contraceptives and the development of hypertension has not been established. However, if while taking combined oral contraceptives develops resistant hypertension, it is advisable to cancel the combined oral contraceptives and assign antihypertensive therapy. With adequate control of blood pressure via antihypertensives possible to resume receiving combined oral contraceptive. In clinical studies of up to 1 year showed no clinically relevant changes in blood pressure when used Zoeli В® .
Against the background of pregnancy and during the use of combined oral contraceptives was observed the development or worsening of these conditions, although their relationship with oral contraceptives not been definitively established: jaundice and / or pruritus related to cholestasis, the formation of gallstones, porphyria, systemic lupus erythematosus, hemolytic uremic syndrome, Sydenham chorea, gestational herpes, etc.
