Composition, form of production and packaging
The dragees are white, smooth.
ethinylestradiol 30 Ојg
dienogest 2 mg
Excipients: lactose monohydrate - 27.97 mg, potato starch - 15 mg, gelatin - 1.5 mg, talc - 1.5 mg, magnesium stearate - 0.5 mg.
The composition of the shell: sucrose - 23.6934 mg, dextrose - 1.65 mg, macrogol 35,000 - 1.35 mg, calcium carbonate - 2.4 mg, polyvidon K25 - 0.15 mg, titanium dioxide (E171) - 0.74244 mg, carnauba wax 0.01416 mg.
21 pcs. - blisters (1) - packs of cardboard.
21 pcs. - blisters (3) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2012.
Low-dose monophasic oral combined estrogen-gestagen contraceptive drug.
The contraceptive effect of Jeanine is carried out by means of complementary mechanisms, the most important of which are suppression of ovulation and a change in the viscosity of cervical mucus, as a result of which it becomes impenetrable for spermatozoa.
If used correctly, the Perl index (the indicator reflecting the number of pregnancies in 100 women taking the contraceptive during the year) is less than 1. When missing tablets or improperly used, the Pearl index may increase.
The gestagenic component of Jeanine - dienogest - has anti-androgenic activity, which is confirmed by the results of several clinical studies. In addition, dienogest improves the lipid profile of the blood (increases the number of high-density lipoproteins).
In women taking combined oral contraceptives, the menstrual cycle becomes more regular, less painful menstruation is observed, the intensity and duration of bleeding is reduced, resulting in a reduced risk of developing iron deficiency anemia. In addition, there is evidence of a reduced risk of developing endometrial cancer and ovarian cancer.
After ingestion, dienogest is quickly and completely absorbed from the digestive tract. C max is achieved in 2.5 hours and is 51 ng / ml. Bioavailability is approximately 96%.
Dienogest binds to blood serum albumin and does not bind to sex-steroids (GSHC) globulin and corticoid-binding globulin (CSG). In a free form is about 10% of the total concentration in the blood serum; about 90% - are nonspecifically associated with serum albumin. Induction with ethinyl estradiol synthesis of HSA does not affect the binding of dienogest to the whey protein.
The pharmacokinetics of the dienogest are not affected by the level of the GHS in the blood serum. As a result of daily administration of the drug, the serum dienogest level increases approximately 1.5-fold.
Dienogest is almost completely metabolized. The clearance from serum after taking a single dose is approximately 3.6 l / h.
T 1/2 is about 8.5-10.8 hours. An insignificant part of the dienogast is excreted by the kidneys in the unmodified state. Metabolites are excreted in urine and bile in a ratio of about 3: 1 with T 1/2 equal to 14.4 h.
After ingestion, ethinylestradiol is rapidly and completely absorbed. C max in the blood serum is achieved after 1.5-4 h and is 67 pg / ml. During absorption and "first passage" through the liver, ethinyl estradiol is metabolized, resulting in an average bioavailability of about 44%.
Ethinyl estradiol is almost completely (approximately 98%), although non-specific, binds to albumin. Ethinyl estradiol induces synthesis of SHBG. The apparent V d ofethinylestradiol is 2.8-8.6 l / kg.
C ss is achieved during the second half of the treatment cycle.
Ethinyl estradiol undergoes presystemic conjugation, both in the mucosa of the small intestine and in the liver. The main pathway of metabolism is aromatic hydroxylation. The clearance rate from the blood plasma is 2.3-7 ml / min / kg.
The decrease in the concentration of ethinyl estradiol in serum is biphasic; the first phase is characterized by T 1/2 of the first phase - about 1 h, T 1/2 of the second phase - 10-20 h. Unchanged from the body is not excreted. Metabolites of ethinyl estradiol are excreted in urine and bile in a ratio of 4: 6 with T 1/2 for about 24 hours.
Dragee should be taken orally in the order given on the package, every day at about the same time, with a small amount of water. Zhanin В® should be taken 1 tablet / day continuously for 21 days. The admission of each next package begins after a 7-day break, during which withdrawal bleeding (menstrual-like bleeding) is observed. It usually starts on the 2nd-3rd day after the last dragee has been taken and may not end before the start of the new package.
The beginning of reception of Zhanin
In the absence of taking any hormonal contraceptives in the previous month, the intake of Janine begins on the 1st day of the menstrual cycle (ie, on the 1st day of menstrual bleeding). It is allowed to start taking the menstrual cycle on the 2nd-5th day, but in this case it is recommended to use the barrier method of contraception during the first 7 days of taking the pills from the first package.
When switching from combined oral contraceptives, vaginal rings, transdermal patches, the administration of Jeanine should be started the day after the last active pills were taken from the previous package, but, in no case, no later than the next day after the usual 7-day break in admission (for preparations , containing 21 dragees) or after taking the last inactive dragee (for preparations containing 28 dragees in a package). When moving from the vaginal ring, the transdermal patch, it is preferable to start taking Jeanine on the day of removal of the ring or patch, but no later than the day when a new ring is to be inserted or a new patch is stuck.
When switching from contraceptives containing only gestagens ("mini-pili", injection forms, implant) or with the progestogen-releasing progestogen (Mirena), awoman can switch from "mini-saw" reception to Janine В® any day (without interruption), with implant or intrauterine contraceptive with gestagen - on the day of its removal, with an injection contraceptive - on the day the next injection is to be made. In all cases, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the pills.
After abortion in the first trimester of pregnancy, a woman can start taking the drug immediately. In this case, the woman does not need additional methods of contraception.
After childbirth or abortion in the second trimester of pregnancy, it is recommended to start taking the drug on the 21-28th day after childbirth or abortion in the second trimester of pregnancy. If the reception is started later, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the pills. However, if a woman already had a sex life, pregnancy should be excluded before taking Jeanine or it is necessary to wait for the first menstruation.
Acceptance of missed pills
If the delay in taking the dragee is less than 12 hours , the contraceptive protection does not decrease. Missed pills woman should take as soon as possible, the next dragee is taken at the usual time.
If the delay in taking the dragee is more than 12 hours , the contraceptive protection can be reduced.
In this case, you can follow the following two basic rules:
- taking the drug should never be interrupted for more than 7 days;
- to achieve adequate suppression of the hypothalamic-pituitary-ovarian system, 7 days of continuous reception of the dragees are required.
Accordingly, if the delay in the intake of active dragees was more than 12 hours (the interval from the moment of reception of the last active dragee is more than 36 hours), one can recommend the following:
The first week of taking the drug
It is necessary to take the last missed pills as soon as possible, as soon as a woman remembers this (even if you need to take two pills at the same time). The next dragee is taken at the usual time. In addition, a barrier method of contraception (for example, a condom) should be used for the next 7 days. If sexual intercourse took place within a week before skipping the dragees, the probability of pregnancy should be taken into account. The more pills are missed, and the closer they are to the break in the intake of active substances, the greater the probability of pregnancy.
The second week of taking the drug
It is necessary to take the last missed pills as soon as possible, as soon as a woman remembers this (even if you need to take two pills at the same time). The next dragee is taken at the usual time. Provided that the woman took the dragee correctly for 7 days preceding the first missed pellet, there is no need to use additional contraceptive measures. Otherwise, as well as when two or more pills are missed, barrier methods of contraception (for example, a condom) should be used additionally within 7 days.
The third week of taking the drug
The risk of pregnancy is increased because of the upcoming interruption in taking pills. A woman should strictly adhere to one of the following two options. If, during the 7 days preceding the first missed pellet, all pills were taken correctly, there is no need to use additional contraceptive methods.
1. It is necessary to take the last missed pills as soon as possible, as soon as a woman remembers this (even if you need to take two pills at the same time). The next dragee is taken at the usual time, until the dragee runs out of the current packaging. The next package should be started immediately without interruption. Bleeding cancellation is unlikely until the second package is finished, but there may be spotting and breakthrough bleeding when taking the pills.
2. A woman can also interrupt the reception of pills from the current package. She then needs to take a break for 7 days, including the day of skipping the dragees and then start taking a new package.
If a woman missed taking the pills, and then during a break in admission she does not have a withdrawal bleeding, it is necessary to exclude pregnancy.
Recommendations in case of vomiting and diarrhea
If a woman has vomiting or diarrhea within up to 4 hours after taking active dragees, absorption may not be complete and additional contraceptive measures should be taken. In these cases, you should focus on recommendations when skipping the dragee.
Changing the day of the beginning of the menstrual cycle
To delay the onset of menstruation , a woman should continue taking the pills from a new package of Jeanine immediately after all the pills are taken from the previous one, without taking a break. Dragee from this new package can be taken for as long as the woman wishes (until the packaging is finished). Against the background of taking the drug from the second package, a woman may have spotting or breakthrough uterine bleeding. Renew the reception of Jeanine from the new package follows the usual 7-day break.
To postpone the day of the onset of menstruation on the next day of the week , the woman should shorten the nearest break in taking the dragees for as many days as she wants. The shorter the interval, the higher the risk that it will not have withdrawal bleeding, and thereafter will be spotting spot bleeding and breakthrough bleeding during the second package (just like when it wants to delay the onset of menstruation).
Additional information for specific patient categories
For children and adolescents, the preparation Jeanine В® is shown only after the onset of menarche.
After the onset of menopause, the preparation Jeanine В® is not shown.
The drug Jeanine В® is contraindicated in women with severe liver disease , until the liver function is normalized.
The preparation Jeanine В® has not been specifically studied in patients with impaired renal function . The available data do not imply a change in treatment in such patients.
When taking combined oral contraceptives, there may be irregular bleeding (spotting spotting or breakthrough bleeding), especially during the first months of use.Against the background of taking the drug Jeanine В® in women, there were other undesirable effects, indicated in the table below. Within each group, isolated depending on the frequency of the undesirable effect, the undesirable effects are presented in order of decreasing severity.
Determination of the frequency of adverse reactions: often (? 1/100 and <1/10), infrequently (? 1/1000 and <1/100), rarely (? 1/10 000 and <1/1000). For additional side reactions, revealed only in the process of postmarketing observations and for which it is not possible to estimate the frequency, the frequency is unknown.
Frequently (? 1/100 and <1/10) Not infrequently (? 1/1000 and <1/100) Rarely (? 1/10 000 and <1/1000) Frequency is unknown
Infection and infection
Vaginitis / vulvovaginitis Vaginal candidiasis or other vulvovaginal infections Salpingoophoritis (adnexitis) Urinary tract infections Cystitis Mastitis Cervicitis Fungal infections Candidiasis Herpetic oral lesions Influenza Bronchitis Sinusitis Upper respiratory tract infections Viral infections
Benign, malignant and unspecified tumors (including cysts and polyps)
Myoma of the uterus Lymphoma of the breast
Blood and lymphatic system
Increased appetite Anorexia
Decreased mood Depression Mental disturbances Insomnia Sleep disorders Aggression Mood changes Decreased libido Increased libido
Headache Dizziness Migraine Ischemic stroke Cerebrovascular disorders Dystonia
Dryness of the eye mucosa Irritation of the eye mucosa Oscilloscopy Sudden hearing loss Noice in the ears Dizziness Hearing impairment Intolerance to contact lenses (discomfort when wearing)
The cardiovascular system
Arterial hypertension Arterial hypotension Cardiovascular disorders Tachycardia including increased heart rate Thrombosis / pulmonary thromboembolism Thrombophlebitis Diastolic hypertension Orthostatic circulatory dystonia Tides Varicose veins Pathology of veins Pain in the region of veins
Bronchial asthma Hyperventilation
Abdominal pain, including pain in the upper and lower abdomen, discomfort / bloating Nausea Vomiting Diarrhea Gastritis Enteritis Indigestion
Acne Alopecia Rash, including macular rash Itching, including generalized itching Atopic dermatitis / neurodermatitis Eczema Psoriasis Hyperhidrosis Chloasma Disorders of pigmentation / hyperpigmentation Seborrhea Dandruff Hirsutism Pathological skin changes Orange peel Vascular asterisks Erythema multiforme
Manifestations of allergic reactions, including allergic dermatitis Urticaria Nodal erythema
Back pain Musculoskeletal pain Myalgia Pain in the extremities
Reproductive system and mammary glands
Pain in the mammary glands, a feeling of discomfort, breast engorgement Abnormal withdrawal bleeds, including menorrhagia, hypomenorrhoea, oligomenorrhoea and amenorrhea Intermenstrual bleeding, including vaginal bleeding and metrorrhagia Breast enlargement, swelling and feeling of swelling of the mammary glands Mammary edema Dysmenorrhea Discharge from the genital tract / discharge from the vagina Ovarian cysts Pelvic pain Cervical dysplasia Cysts of the uterine appendages Pain in the appendages of the uterus Cysts of milk les fibrocystic breasts Dipareuniya galactorrhea Violations menstrual discharge from the breast
Fatigability Asthenia Malnutrition Chest pain Peripheral edema Flu-like symptoms Inflammation Temperature rise Irritability Liquid retention
Changes in body weight (increase, decrease and fluctuations in body weight) Increased level of TG in the blood Hypercholesterolemia
Congenital and genetic disorders
Detection of additional mammary gland / polymastia
In women receiving combined oral contraceptives , the following adverse events have been reported: venous thromboembolic complications, arterial thromboembolic complications, cerebrovascular complications, arterial hypertension, hypertriglyceridemia, changes in glucose tolerance, or effects on insulin resistance of peripheral tissues, liver tumors (benign or malignant), disorders functions of the liver, chloasma.
In women with hereditary angioedema, exogenous estrogens can cause an exacerbation of symptoms.
The emergence or aggravation of conditions for which the relationship with the use of combined oral contraceptives has not been unequivocally proven: jaundice and / or pruritus associated with cholestasis, gallstones, porphyria, systemic lupus erythematosus; hemolytic-uremic syndrome, Sydenham's chorea, pregnant herpes, otosclerosis with hearing impairment, Crohn's disease, ulcerative colitis, cervical cancer.
In women using combined oral contraceptives, there is a very slight increase in the incidence of breast cancer. Because Breast cancer rarely occurs in women under 40 years, subject to the overall risk of breast cancer, the additional number of cases is very small. The relationship with the use of combined oral contraceptives is not known.
Janine В® should not be used in the presence of any of the conditions / diseases listed below. If any of these conditions develop for the first time on his patients receiving the drug should be immediately repealed.
- presence of thrombosis (venous and arterial) currently or history (e.g., deep vein thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular disorders);
- presence of a current or a history of states preceding thrombosis (e.g., transient ischemic attack, angina pectoris);
- diabetes mellitus with vascular complications;
- the presence of current or a history of migraine with focal neurological symptoms;
- the presence of serious or multiple risk factors for venous or arterial thrombosis (including complicated lesions valvular atrial fibrillation, cerebrovascular disease or coronary heart arteries, uncontrolled hypertension, major surgery with prolonged immobilization, smoking age 35 years);
- hepatic failure, and severe liver diseases (liver samples before normalization);
- the presence of current or a history of pancreatitis with severe hypertriglyceridemia;
- presence in the moment or a history of benign or malignant liver tumors;
- hormone-dependent cancers identified genital or breast or a suspicion of them;
- vaginal bleeding of unknown origin;
- pregnancy or suspected it;
- the period of breastfeeding;
- Hypersensitivity to the components of the drug.
You should carefully weigh the potential risks and expected benefits of the use of combined oral contraceptives in each individual case in the presence of the following diseases / conditions and risk factors:
- thrombosis risk factors for thromboembolism (smoking, obesity, dislipoproteinemia, hypertension, migraine, valvular disease, long-term immobilization, major surgery, major trauma, genetic predisposition to thrombosis / thrombosis, myocardial infarction, or violation of mo zgovogo circulation at a young age, someone from the next of kin /);
- other diseases, which may occur when the peripheral circulatory disorders (diabetes, systemic lupus erythematosis, hemolytic uremic syndrome, Crohn's disease, ulcerative colitis, sickle cell anemia, phlebitis superficial veins);
- hereditary angioedema;
- liver disease;
- diseases caused or aggravated by the first time during pregnancy, or on the background of the previous use of sex hormones (eg, jaundice, cholestasis, gallbladder disease, otosclerosis with hearing impairment, porphyria, herpes gestationis, Sydenham's chorea);
- postpartum period.
PREGNANCY AND LACTATION
Jeanine В® is not indicated for pregnancy and breastfeeding.
If a pregnancy is detected during reception Janine, the drug should be immediately canceled. However, extensive epidemiological studies have revealed no increased risk of defects in children born to women treated with hormones before pregnancy, or teratogenic effects when sex hormones were taken inadvertently in early pregnancy.
Receiving COCs can reduce the amount of breast milk and change its composition, however, their use is contraindicated in lactation. A small amount of sex steroids and / or their metabolites may be derived from milk.
APPLICATION FOR FUNCTIONS OF THE LIVER
Admission Jeanine may have an impact on biochemical indicators of renal function.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
In the event of liver dysfunction may require temporary cancellation Janine to normalization of laboratory parameters. With the development of cholestatic jaundice or cholestatic pruritus (first occurred during pregnancy or previous use of sex hormones) Jeanine В® should be discontinued.
APPLICATION IN ELDERLY PATIENTS
Before the start or resumption of use of the drug Jeanine В® should be familiar with the history of life, a family history of a woman, a thorough general medical (including blood pressure measurement, heart rate, body mass index) and gynecological examination, including the study of mammary glands and cytological examination of scrapings from the cervix (the test Papanicolaou) to exclude pregnancy. The volume of additional research and frequency inspection tests determined individually. Typically, control examinations should be carried out not less than 1 time per year.
The woman must be informed that Janine В® does not protect against HIV infection (AIDS) and other diseases, sexually transmitted diseases.
If any of the conditions, diseases, and the risk factors listed below are currently available, you should carefully weigh the potential risks and expected benefits of the use of combined oral contraceptives in each individual case and discuss it with the woman before she decides to start receiving the drug. With weighting, amplification or at the first sign of risk factors may require removal of the drug.
Diseases of the cardiovascular system
Epidemiological studies indicate a relationship between the use of combined oral contraceptives and increased incidence of venous and arterial thrombosis and thromboembolism such as deep vein thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular disease) when receiving combined oral contraceptives. These diseases are rare.
The risk of developing venous thromboembolism (VTE) is greatest in the first year of taking these drugs. The increased risk is present after initial use of oral contraceptives or resume use of the same or different combined oral contraceptives (after the interval between doses of the drug in 4 weeks or more). Data from a large prospective study involving 3 groups of patients suggest that this increased risk is present mainly in the first 3 months.
The overall risk of VTE in patients receiving low-dose combined oral contraceptives (<50 micrograms ethinyl estradiol) are 2-3 times higher than in non-pregnant patients who are not taking combined oral contraceptives, however, the risk is lower than the risk of VTE during pregnancy and childbirth. VTE may be fatal (in 1-2% of cases).
Venous thromboembolism (VTE), manifesting as deep vein thrombosis or pulmonary embolism may occur when using any combined oral contraceptives.
Very rarely using COCs thrombosis occurs in other blood vessels, for example, hepatic, mesenteric, renal, and cerebral arteries veins or the retinal vessels. Consensus about the connection between the occurrence of these events and the use of combined oral contraceptives available. Symptoms of deep vein thrombosis (DVT) include lower extremity edema unilateral or along veins in the leg, pain or discomfort in the foot only in a vertical position or during walking, the local temperature rise in the affected leg, redness or discoloration of the skin on the foot.
Symptoms of pulmonary embolism (PE) are as follows: difficulty or tachypnea; sudden cough, including hemoptysis; sharp chest pain, which may be aggravated by deep inspiration; sense of anxiety; severe dizziness; fast or irregular heartbeat. Some of these symptoms (eg, dyspnea, cough) are nonspecific and may be misinterpreted as the symptoms of other more or less severe events (eg, respiratory tract infection).
Arterial thrombosis may lead to stroke, vascular occlusion or myocardial infarction. The symptoms of a stroke: sudden weakness or loss of sensitivity of the face, arm or leg, especially on one side of the body, sudden confusion, trouble speaking and understanding; single- or double-sided sudden vision loss; sudden gait disturbance, dizziness, loss of balance or coordination; sudden, severe or prolonged headache with no apparent cause; loss of consciousness or fainting with or without epileptic seizure him. Other signs of vascular occlusion: sudden pain, swelling and slight bluish limbs, acute abdomen.
Symptoms of heart attack include: pain, discomfort, pressure, heaviness, or constriction of fullness in the chest, arm or behind the breastbone; discomfort radiating to the back, cheeks, throat, arm, stomach; cold sweat, nausea, vomiting or dizziness, severe weakness, anxiety or shortness of breath; fast or irregular heartbeat.
Arterial thromboembolism can be fatal.
The risk of thrombosis (venous and / or arterial) and thromboembolism is increased:
- smokers (with an increase in the number of cigarettes and increasing age the risk increases, especially in women over 35 years old);
- obesity (BMI over 30 kg / m 2 );
- if there is a family history (eg venous or arterial thromboembolism ever in close relatives or parents at a relatively young age). In the case of hereditary or acquired predisposition woman should be assessed and the appropriate specialist to address the issue of the possibility of using combined oral contraceptives;
- with prolonged immobilization, major surgery, any surgery to the legs, or major trauma. In these situations, it is desirable to discontinue the use of combined oral contraceptives (in case the intended operation of at least four weeks prior to it) and not to resume reception within two weeks after immobilization;
- when dislipoproteinemia;
- arterial hypertension;
- in diseases of the heart valves;
- atrial fibrillation.
The possible role of varicose veins and superficial thrombophlebitis in venous thromboembolism is controversial. It should take into account the increased risk of thromboembolism during the postpartum period.
Peripheral circulatory disorders as may occur in diabetes mellitus, systemic lupus erythematosus, hemolytic uremic syndrome, chronic inflammatory bowel diseases (Crohn's disease or ulcerative colitis) and sickle cell anemia.
The increase in frequency and severity of migraine during use of combined oral contraceptives (which may be preceded by cerebrovascular disorders) can be grounds for immediate discontinuation of these drugs.
By biochemical parameters indicating the inherited or acquired predisposition to venous or arterial thrombosis include: resistance to activated protein C, hyperhomocysteinemia, lack of antithrombin III, protein C deficiency, protein deficit S, antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant).
In assessing the risks and benefits should be taken into account that adequate treatment of the relevant condition may reduce the associated risk of thrombosis. It should also be borne in mind that the risk of thrombosis and thromboembolism in pregnancy is higher than when taking low-dose oral contraceptives (<50 micrograms ethinyl estradiol).
The most significant risk factor for cervical cancer is persistent papilloma virus infection. There are reports of some increase in the risk of cervical cancer in long-term use of combined oral contraceptives. However, communication with the reception of combined oral contraceptives has not been proved. Reserved controversy as to the extent to which these data are associated with screening for cervical abnormalities or features with sexual behavior (less frequent use of barrier methods of contraception).
A meta-analysis of 54 epidemiological studies showed that there is a slightly increased relative risk of breast cancer diagnosed in women who used combined oral contraceptives. The increased risk disappears gradually within 10 years after discontinuation of these drugs. Due to the fact that breast cancer is rare in women under 40 years, an increase in the number of breast cancer diagnoses in women taking combined oral contraceptives are currently taking or have recently, it is insignificant in relation to the total risk of the disease. His connection with the reception of combined oral contraceptives has not been proved. The observed increase in risk may be due to an earlier diagnosis of breast cancer in women,applying the combined oral contraceptives. In women, ever use a combined oral contraceptives, revealed earlier stages of breast cancer than women who never let them apply.
In rare cases on the background of the use of combined oral contraceptives observed the development of liver tumors, which in some cases lead to life-threatening intraabdominal bleeding. In case of severe pain in the abdomen, liver enlargement or signs of intra-abdominal bleeding it should be considered in the differential diagnosis.
Women with hypertriglyceridemia (or the presence of this condition have a family history) may increase the risk of developing pancreatitis while taking combined oral contraceptives.
Although a slight increase in blood pressure have been reported in many women taking COCs, clinically relevant increases were rare. However, if while taking combined oral contraceptives develops persistent, clinically significant increase in blood pressure, should be discontinued these drugs and begin treatment of hypertension. Receiving COCs can be continued, if using antihypertensive therapy achieved normal blood pressure values.
The following states have been reported to develop or worsen both during pregnancy and when taking combined oral contraceptives, but their connection with the reception of combined oral contraceptives has not been proven: jaundice and / or pruritus related to cholestasis; the formation of gallstones; porphyria; systemic lupus erythematosus; hemolytic uremic syndrome; Sydenham's chorea; herpes gestationis; hearing loss associated with otosclerosis. cases of Crohn's disease are also described and ulcerative colitis against application to combined oral