Диане®-35

General characteristics. Structure:

Active agents: 2 mg of a tsiproteron of acetate and 0,035 mg of ethinylestradiol.
Excipients: lactoses monohydrate - 31,115 mg, starch corn
- 18,000 mg, povidone - 2,100 mg, talc - 1,650 mg, magnesium stearate - 0,100 mg.
structure of a cover: sucrose - 19,371 mg, povidone of 700000 - 0,189 mg, polyethyleneglycol (a macrogoal 6000) - 2,148 mg, calcium a carbonate - 8,606 mg, talc
- 4,198 mg, глицерол - 0,137 mg, titanium dioxide - 0,274 mg, gland (II) oxide yellow - 0,027 mg, wax mountain glikoliyevy - 0,050 mg.

Description. Round biconvex dragees of light yellow color.

Pharmacological properties:

Pharmacodynamics. Diane-35 - the combined estrogen low-dosed monophase peroral - anti-androgenic contraceptive drug.
The contraceptive effect of Diane-35 is carried out by means of complementary mechanisms suppression of an ovulation and change of properties of a cervical secret therefore it becomes impenetrable for spermatozoa concern to the most important of which.
At the women accepting the combined oral contraceptives, the menstrual cycle becomes more regular, painful  periods are less often observed,    intensity  of bleeding  therefore the risk of an iron deficiency anemia decreases decreases. Besides, there are data that the risk of development of endometrial cancer and ovarian cancer decreases.
Against the background of reception of Diane-35 the strengthened activity of sebaceous glands which plays an important role in emergence of eels and seborrheas decreases. In 3-4 months of therapy it usually leads to disappearance of the available rash. Excessive fat content of hair and skin disappears even earlier. Also the hair loss which is often accompanying seborrhea decreases. Therapy of Diane-35 at women of reproductive age reduces clinical manifestations of easy forms of a hirsutism (in particular the increased growth of hair in the person); however the effect of treatment should be expected only after several months of use.
Along with the above described anti-androgenic action, a tsiproterona acetate possesses also pronounced gestagenny action.

Pharmacokinetics. • Tsiproterona acetate
Absorption. At intake of a tsiproteron acetate is completely absorbed with the broad range of doses. After intake of a dragee of Diane-35 the maximum concentration (Cmax) of a tsiproteron of acetate in serum, equal 15 ng/ml, are reached in 1,6 hours. Absolute bioavailability of a tsiproteron of acetate almost full (88% of a dose).
Distribution.
Tsiproterona acetate contacts only a seralbumin. In a free look there are only about 3,5-4% of the general concentration of blood serum. The increase in GSPS induced by ethinylestradiol does not influence binding of a tsiproteron of acetate proteins of serum. The average seeming volume of distribution makes 986±437 l

Metabolism. Tsiproterona acetate is metabolized in two ways, including a hydroxylation and a konjyugirovaniye. The main metabolite in plasma of the person - 15P-hydroxylic derivative.
Removal. Some part of a dose is removed in an invariable view with bile. The most part of a dose is excreted in the form of metabolites with urine or bile in the ratio 1:2. Metabolites from plasma eliminirutsya with an elimination half-life 1,8 days.
Equilibrium concentration. As linkng with proteins is not specific, changes of level of the globulin, connecting sexual steroids (G,CSS) do not influence pharmacokinetics of a tsiproteron of acetate. During cyclic treatment the maximum equilibrium concentration of a tsiproteron of acetate in serum is reached in the second half of a cycle.

• Ethinylestradiol
Absorption. After intake ethinylestradiol is quickly and completely absorbed. The maximum concentration (Cmax) in blood serum, equal about 71 pg/ml, is reached for 1,6 h. During absorption and the first passing through a liver ethinylestradiol is metabolized therefore its bioavailability at intake averages about 45%.
Distribution. Ethinylestradiol almost completely (about 98%), though it is not specific, communicates albumine. Ethinylestradiol induces synthesis of GSPS. The seeming volume of distribution of ethinylestradiol is equal 2,8k8,6 to l/kg.
Metabolism. Ethinylestradiol is exposed to presistemny conjugation, both in mucous a small bowel, and in a liver. The main way of metabolism - an aromatic hydroxylation. Clearance speed makes 2,3-7 ml/min. of a blood plasma.
Removal. Reduction of concentration of ethinylestradiol in blood serum has two-phase character; the first phase is characterized by an elimination half-life about 1 hour, the second — 10-20 hours. In not changed view from an organism it is not removed. Metabolites of ethinylestradiol are removed with urine and bile in the ratio 4:6 with an elimination half-life about 24 h.
Equilibrium concentration. Equilibrium concentration is reached throughout the second half of a medical cycle.

Indications to use:

Contraception at women with the androgenization phenomena.
Treatment of androgenzavisimy diseases at women, such, as acne, especially common forms and forms which are followed by seborrhea, an inflammation or nodulation (papular and pustular eels, nodular and cystous eels); androgenetichesky alopecia and easy forms of a hirsutism.

Route of administration and doses:

For achievement of therapeutic effect and ensuring necessary contraception it is necessary to accept Diane-35 regularly. If prior to reception of Diane-35 any other drug of hormonal contraception was used, its reception has to be stopped. The mode of dosing Diane-35 matches the mode of dosing of the majority of oral contraceptives. Thus, Regulations of Admission of other oral contraceptives extend to reception of Diane-35. Irregular reception of Diane-35 can lead to intermenstrual bleedings, decrease in therapeutic effect and contraceptive efficiency. At the correct use Perl's index makes about 1.
The dragee of Diane-35 should be accepted inside on the order specified on packaging, every day approximately at the same time with a small amount of water. Accept on one dragee a day continuously within 21 days. Reception of the following packaging begins after a 7-day break in reception of a dragee during which cancellation bleeding usually takes place. Bleeding, as a rule, begins for 2-3 day after reception of the last dragee and can not end prior to reception of new packaging.
How to begin reception of Diane-35
• In the absence of reception of any hormonal contraceptives last month.
Reception of Diane-35 begins in the first day of a menstrual cycle (i.e. in the first day of menstrual bleeding).
The beginning of reception for 2-5 day of a menstrual cycle is allowed, but in this case it is recommended to use in addition a barrier method of contraception during the first 7 days of reception of a dragee from the first packaging.
• Upon transition from other combined oral contraceptives, a vaginal ring or a contraceptive plaster.
It is preferable to begin reception of Diane-35 next day after reception of the last hormonal dragee from the previous packaging, but by no means no later than the next day after a usual 7-day break (for the drugs containing 21 dragees) or after reception of the last inactive dragee (for the drugs containing 28 dragees in packaging).
Reception of Diane-35 should be begun in day of removal of a vaginal ring or plaster, but no later than day when the new ring has to be entered or the new plaster is pasted.
• Upon transition from the contraceptives containing only gestagena ("mini-drank", injection forms, an implant), or from the intrauterine therapeutic system (Mirren) releasing гестаген.
It is possible to pass with mini-saw on Diane-35 in any day (without interruption), from an implant or an intrauterine contraceptive with gestageny - in day of its removal, from an injection form - from the date of when the following injection has to be made. In all cases it is necessary to use in addition barrier method of contraception during the first 7 days of reception of a dragee.
• After abortion in the first trimester of pregnancy.
The woman can begin administration of drug immediately - in day of production of abortion. At observance of this condition the woman does not need additional contraceptive protection.
•  After the delivery or abortion in the second trimester of pregnancy.
It is necessary to begin administration of drug not earlier than 21-28 in the afternoon after the delivery in the absence of breastfeeding or after abortion in the second trimester of pregnancy. If to begin reception later, it is necessary to use in addition barrier method of contraception during the first 7 days of reception of a dragee. However, if the woman already led sex life, prior to reception of Diane-35 it is necessary to exclude pregnancy or to wait for the first periods.
Reception of the passed dragees
If delay in administration of drug made less than 12 hours, contraceptive protection does not decrease. The woman has to accept a dragee as soon as possible, following is accepted in usual time.
If delay in reception of a dragee made more than 12 hours, contraceptive protection can decrease. What more dragee is passed by, and than the admission is closer to a 7-day break in reception of a dragee, subjects a pregnancy high probability.
At the same time it is possible to be guided by the following two basic rules:
• Administration of drug never has to be interrupted more, than for 7 days.
• For    achievement    of adequate    suppression    гипоталамо - 7 days of continuous reception of a dragee are required for pituitary and ovarian regulation.
The following advice if delay in reception of a dragee made more than 12 hours (an interval can be respectively given from the moment of reception of the last dragee more than 36 hours):
• First week of administration of drug
The woman has to accept the last passed dragee as soon as possible as soon as remembers (even if it means reception of two dragees at the same time). The following dragee is accepted in usual time. The barrier method of contraception (for example, condom) during the next 7 days has to be in addition used. If the sexual intercourse took place within a week before the admission of a dragee, it is necessary to consider probability of approach of pregnancy.
• Second week of administration of drug
The woman has to accept the last passed dragee as soon as possible as soon as remembers (even if it means reception of two dragees at the same time). The following dragee is accepted in usual time.
Provided that the woman accepted a dragee correctly within 7 days preceding the first passed dragee there is no need for use of additional contraceptive measures. Otherwise, and also at the admission of two and more dragees it is necessary to use in addition barrier methods of contraception (for example, condom) within 7 days.
• Third week of administration of drug
The risk of pregnancy increases because of the forthcoming break in reception of a dragee, however, if within 7 days preceding the first passed dragee all dragees were accepted correctly, there is no need to use additional contraceptive methods.
1. The woman has to accept the last passed dragee as soon as possible as soon as remembers (even if it means reception of two dragees at the same time). The following dragees accept in usual time, dragees from the current packaging will not end yet. The following packaging should be begun at once. Bleeding of cancellation is improbable, the second packaging will not end yet, but the smearing allocations and breakthrough bleedings can be noted during reception of a dragee.
2. The woman can also interrupt reception of a dragee from the current packaging. Then it has to take a break for 7 days, including day of the admission of a dragee and then begin reception of new packaging.
If the woman missed reception of a dragee, and then during a break in reception she has no cancellation bleeding, it is necessary to exclude pregnancy.
Recommendations in case of vomiting and diarrhea
In case of vomiting or diarrhea during the period till 4 o'clock after reception of a dragee, absorption can be not full, additional measures of protection from unwanted pregnancy have to be respectively taken. In such cases it is necessary to be guided by the above recommendations at the admission of a dragee.
Change of day of the beginning of a menstrual cycle
To delay the beginning of periods, the woman has to continue reception of a dragee from new packaging of Diane-35 right after all dragees from previous, without interruption in reception are accepted. Dragees from this new packaging can be accepted as long as the woman wishes (until packaging does not end). Against the background of administration of drug from the second packaging at the woman the smearing bloody allocations or breakthrough uterine bleedings can be noted. It is necessary to resume reception of Diane-35 from a new pack after a usual 7-day break.
To transfer day began periods the next day of week, the woman needs to recommend to uskorotit the next break in reception of a dragee for so many days, on how many it wants. The interval is shorter, the risk is higher that it will have no cancellation bleeding, and further there will be smearing allocations and breakthrough bleedings during reception of the second packaging (also as in case she like to delay the beginning of periods.
Use duration
Duration of reception of a dragee depends on weight of symptoms of an androgenization and the response to treatment. Generally treatment is carried out within several months. The response to treatment of acne rash and seborrhea usually happens prompt reply to treatment of a hirsutism or an alopecia.
Not less than 3 - 4 courses after disappearance of symptoms of a disease are recommended to accept drug. In case of a disease recurrence in several weeks or months after the termination of reception of a dragee, treatment by the drug Diane-35 can be resumed. In case of resuming of administration of drug (after a four-week break and more) it is necessary to consider the increased risk of VTE (see also section "Special Instructions" and "With Care").
Additional information for some groups of patients
Children and teenagers.
The drug Diane-35 is shown only after approach of menarche. Patients of advanced age
It is not applicable. The drug Diane-35 is not shown after approach of a menopause. Patients with disturbances from a liver
The drug Diane-35 is contraindicated to women with a serious illness of a liver until indicators of function of a liver, do not return to normal. See also section "Contraindications".
Patients with disturbances from kidneys
The drug Diane-35 specially was not studied at patients with disturbances from kidneys. The available data do not assume change of treatment at such patients.

Features of use:

If any of the states/risk factors provided below are available now, then it is necessary to weigh carefully potential risk and the expected advantage of treatment of Diane-35 in each individual case and to discuss it with the woman before she decides to begin administration of drug. In case of weighting, strengthening or the first manifestation of any of these states or risk factors, the woman has to consult with the doctor who can make the decision on need of drug withdrawal.
•  Diseases of cardiovascular system
There are frequencies of development of venous and arterial thromboses and thromboembolisms given about increase (such as deep vein thrombosis, thromboembolism of a pulmonary artery, myocardial infarction, stroke) at reception of the combined oral contraceptives.
The risk of development of a venous thromboembolism (VTE) is maximum in the first year of reception of such drugs. The increased risk is present after initial use of the combined oral contraceptives or resuming of use same or the different combined oral contraceptives (after a break between administrations of drug in 4 weeks and more). Data of a large prospective research with participation of 3 groups of patients show that this increased risk is present, generally within the first 3 months.
The general risk of a venous thromboembolism (VTE) at the patients accepting the low-dosed combined oral contraceptives (<50 mkg of ethinylestradiol) is two-three times higher, than at patients who do not accept the combined oral contraceptives, are not pregnant, and it remains to lower in comparison with risk of pregnancy and childbirth.
Very seldom VTE can result in incapacity or by a lethal outcome.
The venous thromboembolism (VTE) which is shown as a deep vein thrombosis, or an embolism of a pulmonary artery can occur when using of any combined oral contraceptives.
Extremely seldom when using of the combined oral contraceptives there is thrombosis of other blood vessels, for example, of veins or arteries of a liver, mesenteric, renal, a brain or a retina. The general opinion concerning communication between emergence of these events and use of the combined oral contraceptives is absent.
Symptoms of the deep vein thrombosis (DVT) include the following: unilateral hypostasis of a leg or on the vein course on a leg, pain or morbidity in a leg only during the standing or circulation, a caumesthesia in a leg, reddening or change of coloring of integuments on a leg.
Symptoms of the embolism of a pulmonary artery (EPA) consist in the following: sudden inexplicable asthma or hurried breathing; sudden cough, including with blood; an acute pain in a breast which can amplify at a deep breath; feeling of alarm; severe dizziness; the speeded-up or irregular heartbeat. Some of these symptoms (for example, "short wind", "cough") are nonspecific and can be interpreted incorrectly as signs of more or less heavy events (for example, respiratory infection).
The arterial thromboembolism can lead to a stroke, occlusion of vessels or a myocardial infarction. Symptoms of a stroke are as follows: sudden weakness or anesthesia of the person, hand or leg, especially on the one hand bodies, sudden confusion of consciousness, problem with the speech and understanding; sudden loss of sight of one or two eyes; sudden disturbance of gait, dizziness, loss of balance or coordination of movements; sudden, heavy or long headache for no apparent reason; a loss of consciousness or a syncope with an epileptic seizure or without it. Other signs of occlusion of vessels: sudden pain, hypostasis and weak posineniye of extremities, acute abdomen.
Symptoms of a myocardial infarction include: pain, discomfort, pressure, weight, feeling of compression or a raspiraniye of a breast, hand or under a breast; discomfort with irradiation in a back, a cheekbone, a throat, a hand, a stomach; cold sweat, nausea, vomiting or dizziness, strong weakness, alarm or asthma; the speeded-up or irregular heartbeat.
The arterial thromboembolism can lead to a lethal outcome.
The risk of thrombosis (venous and/or arterial) and thromboembolisms increases:
• with age
• at smokers (with increase in quantity of cigarettes or increase in age the risk increases further, especially at women 35 years are more senior);
in the presence:
• the family anamnesis (i.e. a venous or arterial thromboembolism ever at close relatives or parents at rather young age); in case of genetic predisposition, the woman has to be examined by the corresponding specialist for the solution of a question of a possibility of reception of the combined oral contraceptives;
• obesity (index of body weight of more than 30 kg/sq.m);
• dislipoproteinemiya;
• arterial hypertension;
• migraines;
• diseases of valves of heart;
• fibrillations of auricles;
• long immobilization, serious surgical intervention, any operation standing or extensive injury. In these situations it is desirable to stop use of the combined oral contraceptives (in case of the planned operation, at least, in four weeks prior to it) and not to resume reception within two weeks after the termination of an immobilization.
The question of a possible role of a varicosity and superficial thrombophlebitis in development of a venous thromboembolism remains disputable.
It is necessary to consider the increased risk of thromboembolisms in a puerperal period.
Disturbances of peripheric circulation can be also noted at a diabetes mellitus, a system lupus erythematosus, a hemolitic uraemic syndrome, chronic inflammatory diseases of intestines (a disease Krone or nonspecific ulcer colitis) and a sickemia.
Increase in frequency and weight of migraine during use of the combined oral contraceptives (that can precede cerebrovascular disturbances) can be the basis for the immediate termination of reception of these drugs.
The following belongs to the biochemical indicators indicating the hereditary or acquired predisposition to venous or arterial thrombosis: resistance to the activated protein With, a gipergomotsisteinemiya, insufficiency антитромбинаШ, недостаточноть a protein With, insufficiency of a protein of S, anti-phospholipidic antibodies (anti-cardiolipin antibodies, lupoid anticoagulant).
At ratio assessment advantage/risk, the doctor has to consider that adequate treatment of a disease can reduce the related risk of thrombosis and that the risk connected with pregnancy, above the risk connected with reception of the low-dosed combined oral contraceptives (<0,05 mg of ethinylestradiol).
• Tumors
There are messages on some increase in risk of development of cancer of neck of uterus at prolonged use of the combined oral contraceptives. Communication with reception of the combined oral contraceptives is not proved. There is disputable a question in what degree these finds are connected with pathology of a neck of uterus or with features of a sexual behavior (more rare use of barrier methods of contraception). The most essential risk factor of development of cancer of neck of uterus is the persistent human papillomavirus infection.
Meta-analysis of 54 epidemiological researches showed that there is a little increased relative risk of development of the breast cancer diagnosed for the women accepting the combined oral contraceptives now (relative risk 1,24). The increased risk gradually disappears within 10 years after the termination of reception of these drugs.
Because the breast cancer is noted seldom at women to 40 years, increase in number of diagnoses of a breast cancer at the women accepting the combined oral contraceptives now or accepting recently is insignificant in relation to the general risk of this disease. Its communication with reception of the combined oral contraceptives is not proved. Observed increase in risk can be also a consequence of earlier diagnosis of a breast cancer at the women applying the combined oral contraceptives. At the women ever using the combined oral contraceptives earlier stages of a breast cancer, than at women, never their applying come to light.
In rare instances against the background of use of the combined oral contraceptives development of tumors of a liver which in some cases led to life-threatening intra belly bleeding was observed. It should be considered when carrying out the differential diagnosis in case of severe pains in a stomach, increase in a liver or symptoms of intra belly bleeding.
•  Other states
At women with a gipertriglitseridemiya during reception of the combined oral contraceptives (in the presence of this state in the family anamnesis) increase in risk of development of pancreatitis is possible.
Though small increase in arterial pressure was described at many women accepting the combined oral contraceptives, clinically significant increase was noted seldom. Nevertheless, if during reception of the combined oral contraceptives permanent, clinically significant increase in arterial pressure develops, it is necessary to cancel these drugs and to begin treatment of arterial hypertension. Reception of the combined oral contraceptives can be continued if by means of hypotensive therapy normal values of arterial pressure are reached.
The following states as it was reported, develop or worsen both during pregnancy, and at reception of the combined oral contraceptives, but their communication with reception the COOK is not proved: jaundice and/or the itch connected with a cholestasia; formation of stones in a gall bladder; porphyria; system lupus erythematosus; hemolitic uraemic syndrome; Sydenham's chorea; herpes of pregnant women; the hearing loss connected with an otosclerosis. Disease cases Krone and nonspecific ulcer colitis against the background of use of the combined oral contraceptives are also described.
The hloazma can sometimes develop, especially women with existence in the anamnesis have hloazma of pregnant women. Women with tendency to a hloazma during reception the COOK have to avoid long stay to the sun and influences of ultraviolet radiation.
Acute or chronic abnormal liver functions can demand cancellation the COOK until indicators of function of a liver do not return to norm. Рецидивив cholestatic jaundice which developed for the first time in time of pregnancy or previous reception of sex hormones the COOK demands the reception termination.
Though the combined oral contraceptives can exert impact on resistance to insulin and tolerance to glucose, the patients with a diabetes mellitus using low-dosed the COOK (<0,05 mg of ethinylestradiol) have no need of change of the therapeutic mode. Nevertheless, women with a diabetes mellitus during reception the COOK have to be observed carefully.
If at the woman suffering from a hirsutism, symptoms arose recently or are expressed substantially, the differential diagnosis for the purpose of identification of a possible cause of illness (an androgenprodutsiruyushchy tumor, deficit of enzymes of adrenal glands) has to be carried out.

Laboratory tests
Reception of the combined oral contraceptives can influence results of some laboratory tests, including indicators of function of a liver, kidneys, a thyroid gland, adrenal glands, level of transport proteins in plasma, indicators of carbohydrate metabolism, parameters of coagulation and a fibrinolysis. Changes usually do not overstep the bounds of normal values.

Influence on a menstrual cycle
Against the background of reception of the combined oral contraceptives the irregular bleedings (smearing bloody allocations or breakthrough bleedings), especially within the first months of use can be noted. Therefore, assessment of any irregular bleedings has to be carried out only after the period of adaptation making about three cycles.
If irregular bleedings repeat or develop after the previous regular cycles, it is necessary to conduct careful examination for an exception of malignant new growths or pregnancy.
At some women during a break in reception of a dragee cancellation bleeding can not develop. If the combined oral contraceptives were accepted as directed, it is improbable that the woman is pregnant. Nevertheless, if before the combined oral contraceptives were accepted irregularly or if there are no in a row two bleedings of cancellation, before continuation of administration of drug pregnancy has to be excluded.

Medical examinations
Before use of the drug Diane-35 the woman is recommended to undergo careful all-medical and gynecologic examination (including a research of mammary glands and a cytologic research of cervical slime), to exclude pregnancy. Besides, it is necessary to exclude disturbances of system of a blood coagulation.
In case of prolonged use of drug it is necessary regularly (approximately each 6 months) to conduct control examinations.
It is necessary to warn the woman that Diane-35 drugs do not protect from HIV infection (AIDS) and other diseases, sexually transmitted!

Influence on ability to drive the car and the equipment.
It is not revealed.

Side effects:

By-effects about which it was reported at reception the COOK, but communication of which with administration of drug it is not confirmed and not disproved.

System of bodies       Often (> 1/100)   Infrequently (> 1/1000 and <1/100)    it is rare (<1/1000)
Organ of sight                                                                                     intolerance 
                                                                                                          contact lenses
Gastrointestinal     nausea, pain       vomiting, diarrhea 
 path                                    in a stomach
Immune system                                                                                 of reaction 
                                                                                                          hypersensitivity
General symptoms     increase in body weight                                       Decrease in body weight
Metabolism                                                 liquid delay 
Nervous system       headache                  migraine 
Psychiatric   decrease in mood,    decrease in a libido              increase in a libido
 frustration       differences of mood
Reproductive system  mammary gland pain, a hypertrophy milk Allocations from a vagina
and mammary glands        nagrubany mammary glands of glands                of allocation from mammary glands
Skin and
hypodermic fabrics                                               rash, urticaria          knotty erythema, 
                                                                                                            multiformny erythema

It was reported about the following serious undesirable phenomena at the women using the combined oral contraceptives. These undesirable phenomena are discussed in the section "Special Instructions":
• Venous thromboembolic disturbances
• Arterial thromboembolic disturbances
• Stroke
• Hypertensia
• Gipertriglitseridemiya
• Changes in portability of glucose or influence on peripheral insulin resistance
• Liver tumors (high-quality and malignant)
• Disturbance of functional indicators of a liver
• Hloazma
• At women with a hereditary Quincke's disease exogenous estrogen can cause or strengthen symptoms of a Quincke's disease.
• Approach or deterioration in states for which communication with use of the combined oral contraceptives is not indisputable: the jaundice and/or an itch connected with a cholestasia; formation of stones of a gall bladder; porphyria; system lupus erythematosus; gemolitiko-uraemic syndrome; Sydenham's chorea; herpes of pregnant women; the hearing loss connected with an otosclerosis; disease Krone; ulcer colitis; cancer of a neck of uterus.
Frequency of diagnosing of a breast cancer at the women using oral contraceptives is increased very slightly. The breast cancer is seldom observed at women up to 40 years, exceeding of frequency is insignificant in relation to the general risk of developing of a breast cancer. Relationship of cause and effect of developing of a breast cancer the COOK is not established with use. You watch additional information in the section "Contraindications" and "Special Instructions".

Interaction with other medicines:

Interaction of oral contraceptives with other medicines can lead to breakthrough bleedings and/or decrease in contraceptive efficiency. The women accepting these drugs have to use temporarily barrier methods of contraception in addition to the drug Diane-35, or choose other method of contraception. In literature it was reported about the following types of interaction.
Influence on hepatic metabolism: use of the drugs inducing microsomal enzymes of a liver can lead to increase of clearance of sex hormones. Treat such medicines: Phenytoinum, barbiturates, Primidonum, carbamazepine, rifampicin; also there are assumptions concerning an okskarbazepin, a topiramata, a felbamata, the griseofulvin and drugs containing a St. John's Wort. HIV protease inhibitors (for example, ритонавир) and nenukleozidny inhibitors of the return transcriptase (for example, not Virapinum) and their combinations also potentially can influence hepatic metabolism.
Influence on enterogepatichesky circulation: according to separate researches, some antibiotics (for example penicillin and tetracycline) can reduce enterogepatichesky circulation of estrogen, thereby lowering concentration of ethinylestradiol.
During administration of drugs, influencing microsomal enzymes, and within 28 days after their cancellation it is necessary to use a barrier method of contraception in addition.
During reception of antibiotics (excepting rifampicin and griseofulvin) and within 7 days after their cancellation it is necessary to use a barrier method of contraception in addition. If the period of use of a barrier method of protection comes to an end later, than a dragee in packaging, it is necessary to pass to the following packaging of Diane-35 without usual break in reception of a dragee. The oral combined contraceptives can influence metabolism of other drugs that leads to increase (for example, cyclosporine) or to decrease (for example, ламотриджин) their concentration in plasma and fabrics.

Other forms of interaction
Use of such drugs as Diane-35 can influence results of some laboratory tests, including biochemical parameters of a liver, concentration of proteins in plasma (for example, the globulin connecting corticosteroids, fractions of lipids / lipoproteids, parameters of a hemostasis and fibrinolysis, karbogidratny metabolism). These changes, as a rule, remain within normal physiological values.

Contraindications:

Diane-35 it should not be applied in the presence of any of the states which are listed below. If any of these states develop for the first time against the background of reception, drug has to be immediately cancelled.
• Fibrinferments (venous and arterial) and thromboembolisms now or in the anamnesis (including, a deep vein thrombosis, a thromboembolism of a pulmonary artery, a myocardial infarction, cerebrovascular disturbances).
• The states preceding thrombosis (including, the tranzitorny ischemic attacks, stenocardia) now or in the anamnesis.
• Migraine with focal neurologic symptoms in the anamnesis.
• A diabetes mellitus with vascular complications.
• The multiple or expressed risk factors of venous or arterial thrombosis, including defeat of the valve device of heart, disturbance of a cordial rhythm, a disease of vessels of a brain or coronary arteries of heart; uncontrollable arterial hypertension.
• Pancreatitis with the expressed gipertriglitseridemiya now or in
anamnesis.
• A serious illness of a liver (until indicators of function of a liver do not return to normal).
• Liver tumors (high-quality or malignant) now or in the anamnesis.
• The revealed hormonedependent malignant diseases (including generative organs or mammary glands) or suspicion of them.
• Vaginal bleeding of not clear genesis.
• Pregnancy or suspicion on it.
• Feeding period breast.
• Hypersensitivity to any of components of the drug Diane-35.
• With care
If any of the states/risk factors provided below are available now, then it is necessary to weigh carefully potential risk and the expected advantage of use of the combined oral contraceptives in each individual case:
• Risk factors of development of thrombosis and thromboembolisms: smoking; thromboses, a myocardial infarction or disturbance of cerebral circulation at young age at any of the immediate family; obesity; dislipoproteinemiya (for example, arterial hypertension; migraine; diseases of valves of heart; disturbances of a cordial rhythm, long immobilization, serious surgical interventions, extensive injury)
• Other diseases at which disturbances of peripheric circulation can be noted: diabetes mellitus; system lupus erythematosus; hemolitic uraemic syndrome; disease Krone and nonspecific ulcer colitis; sickemia; and also phlebitis of superficial veins
• Gipertriglitseridemiya
• Liver diseases
• The diseases which for the first time arose or aggravated during pregnancy or against the background of the previous reception of sex hormones (for example, jaundice, a cholestasia, diseases of a gall bladder, an otosclerosis with deterioration in hearing, a porphyria, herpes of pregnant women, Sydenham's trochee)

Pregnancy and lactation
Diane-35 it is not appointed during pregnancy and during feeding a breast.
If pregnancy comes to light during administration of drug of Diane-35, drug should be cancelled at once. Tsiproterona acetate is brought with milk therefore use of Diane-35 is contraindicated during a lactation.

Overdose:

About serious violations at overdose it was not reported. Symptoms which can be noted at overdose: nausea, vomiting, the smearing bloody allocations or a metrorrhagia.
There is no specific antidote, it is necessary to carry out a symptomatic treatment.

Storage conditions:

At a temperature not above 30 °C. To store in the place, unavailable to children. Period of validity of 5 years. Not to use after a period of validity!

Issue conditions:

According to the recipe

Packaging:

Dragee. On 21 dragees in the blister from PVC and aluminum foil. The blister together with the application instruction is placed in a cardboard pack.