Expiration date: 04/2025

Structure and Composition: 

Dragee. 1 dragee contains: 

2 mg cyproterone acetate

ethinyl estradiol 0.035 mg

Excipients: lactose monohydrate - 31.115 mg maize starch - 18 mg Povidone - 2.1 mg magnesium silicate (talc) - 1.65 mg magnesium stearate - 0.1 mg

shell: sucrose - 19.371 mg Povidone 700000 - 0.189 mg Macrogol 6,000 - 2,148 mg of calcium carbonate - 8.606 mg of magnesium silicate (talc) - 4,198 mg of titanium dioxide - 0.274 mg glycerol - 0.137 mg glycol wax mountain - 0.05 mg iron (II) oxide - 0.027 mg

in a blister pack with a calendar scale of 21 pcs. in one blister box.

Characteristic:

Low-dose monophasic oral contraceptive with antiandrogenic effect.

Pharmacokinetics:

Cyproterone acetate. If ingestion is completely absorbed, the absolute bioavailability - 88%. After ingestion 1 tablet 35 Diane Cmax serum (15 ng / ml) reached after 1.6 hours. The observed decrease of its biphasic serum characterized T1 / 2 of 0.8 and 2.3 hours of the day. Total serum Cl - 3.6 ml / min / kg. Cyproterone acetate is almost entirely bound to plasma albumin, in free form is approximately 3.5-4.0% of the total blood concentration. Since the nonspecific binding proteins, changes in binding globulin sex hormones (SHBG) did not affect the pharmacokinetics of cyproterone acetate. It is metabolized by hydroxylation and conjugation, the main metabolite in human plasma - 15 & beta-hydroxy derivative. Some of the dose is excreted unchanged in the bile. Most of the dose is excreted as metabolites in the urine or bile in the ratio of 3: 7. The metabolites are eliminated from plasma with a T1 / 2 of 1.7 days.

Ethinyl estradiol. Once inside quickly and completely absorbed. In the process of absorption and "first pass" through the liver, a large part of the ethinyl estradiol is metabolized, resulting in reduction in bioavailability and its variability at intake. After ingestion 1 tablet Diane-35 in serum Cmax (80 pg / ml) is achieved in 1.7 hours. Nonspecifically binds to serum albumin. Only 2% of ethinyl estradiol is in a free state in plasma. Apparent volume of distribution is approximately 5 l / kg, the rate of metabolic clearance of plasma - about 5 ml / min / kg. Decrease in serum concentration of ethinyl estradiol is the first phase of the biphasic characterized T1 / 2 1-2 h, a second -. Approximately 20 h unchanged from the body is not displayed. Ethinylestradiol metabolites are excreted in urine and bile in a ratio of 4: 6.

In nursing mothers about 0.02% of the daily dose of ethinyl estradiol can enter the body of the child with breast milk.

Acceptance of other drugs may affect the systemic bioavailability of ethinyl estradiol. However, interaction with high doses of vitamin C have been identified.

Ethinyl estradiol increases the hepatic synthesis of SHBG and corticoid binding globulin (CBG) during continuous administration. However, the level of SHBG induction depends on the chemical structure and the assigned dose progestogen simultaneously. While taking Diane-35 SHBG concentrations in serum increased from about 100 to 300 nmol / L, and serum concentration of CBG increased from about 50 to 95 mcg / mL.

Description of the pharmacological actions:

Cyproterone acetate inhibits the influence of androgens which are also produced in the female body. Thus, it becomes possible to treat diseases caused by increased formation of androgens or by increased sensitivity of these hormones.

While taking Diane-35 is reduced increased activity of the sebaceous glands, which plays an important role in the occurrence of acne and seborrhea. After 3-4 months of therapy it usually leads to the disappearance of existing scars. Excessive oiliness of hair and skin disappears earlier. It also reduces hair loss, often accompanied by seborrhea. Therapy of Diane-35 in women of reproductive age reduces the clinical manifestations of mild forms of hirsutism (including increased hair growth on the face), but the effect of treatment can be expected after only a few months of use.

In addition to the anti-androgenic effect, cyproterone acetate has a pronounced progestogenic activity. The contraceptive effect of Diane-35 is due to various factors, the most important of which are inhibition of ovulation and changes in cervical mucus secretion. In addition to the contraceptive effect, a combination of estrogen and progestogen is having a positive impact on non-contraceptive health, which should be considered when choosing a method of birth control. The cycle is more regular and less painful menstruation occur, thereby reducing the risk of iron deficiency anemia.

Testimony:

• contraception in women with androgenization events
  
• treatment of androgen-dependent diseases in women: acne, especially common forms and shapes, accompanied by seborrhea, inflammation or nodule formation (papulopustular acne, nodulocystic acne), androgenetic alopecia and mild forms of hirsutism.
  

Contraindications:

Formulations estrogen / gestagen should not be applied if a combination comprising any of the conditions listed below. If any of these conditions develop for the first time in patients receiving the drug should be immediately repealed:

• thrombosis (venous and arterial) and thromboembolism present or in history (including deep vein thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular accident)
  
• state prior thrombosis (including transient ischemic attack, angina) currently or history
  
• diabetes with vascular complications
  
• the presence of serious or multiple risk factors for venous or arterial thrombosis
  
• jaundice or severe liver disease at present or in history (until liver function tests have not come back to normal)
  
• liver tumors (benign or malignant) currently or history
  
• hormone-dependent cancers identified genital or suspicion of breast or they
  
• vaginal bleeding of unknown origin
  
• pregnancy or suspected it
  
• lactation
  
• hypersensitivity to any of Diane-35 components.
  

Diane-35 is not applicable in men.

Application of pregnancy and breastfeeding:

Diane-35 should not be taken during pregnancy or suspected it, and during lactation.

Side effect:

In rare cases, it may be bloating, breast tenderness, the allocation of them secret headache, migraine, changes in libido, depressed mood, poor tolerance of contact lenses, nausea, vomiting, changes in vaginal secretion, various skin reactions, fluid retention, weight change, hypersensitivity reactions sometimes - chloasma, especially in women with a history of chloasma during pregnancy.

Drug Interactions:

Drug interactions that result in increased clearance of sex hormones can lead to breakthrough uterine bleeding and reduce the contraceptive reliability. It has been found in respect of hydantoins, barbiturates, primidone, carbamazepine and rifampicin have also suspicion of oxcarbazepine, topiramate, felbamate and griseofulvin. While receiving rifampicin and for 28 days after its cancellation in addition to Diane-35 should use a barrier method of contraception (eg condom). If concomitant use of the drug began in the late reception Diane-35 package, the next pack should be started without the usual break at the reception. The mechanism of this interaction is based on the induction of these drugs in liver enzymes.

Contraceptive reliability is reduced when taking antibiotics such as ampicillin and tetracycline. This mechanism of action has not been elucidated.

Women treated with any of the above-mentioned short course of drugs in addition to Diane-35 should temporarily use a barrier method of contraception at the time of concomitant drug administration and for 7 days after their cancellation.

Women receiving these drugs long course, should be encouraged to other (non-hormonal) method of contraception (eg condom).

Dosage and administration:

Inside, a small amount of water every day about the same time of day, in the order indicated on the package. Take 1 tablet a day, continuously for 21 days. Reception following each package begins after a 7-day break, during which there is withdrawal bleeding (bleeding menstrualnopodobnoe). It usually starts on day 2-3 after the last pills and may not end before you start taking a new package.

Diane-35 must be taken regularly to achieve the desired contraceptive and therapeutic effects. Receive Mode Diane-35 is similar to the standard mode of reception of most of the combined oral contraceptives. The irregular intake of Diane-35 can lead to intermenstrual bleeding and reduce the therapeutic effect and contraceptive reliability.

Medical examinations. Before the start of the application of Diane-35 she will need to undergo a thorough general medical and gynecological examination (including breast examination and cytological examination of cervical mucus), exclude pregnancy. In addition, to exclude blood coagulation disorders.

In the case of long-term use of the drug is necessary every 6 months to carry out preventive control testing. It should warn the woman that Diane-35 does not protect against HIV infection (AIDS) or any other sexually transmitted diseases through!

Reception Diane-35 begin:

• Without taking any hormonal contraceptive use in the preceding month. Reception Diane-35 begins on the first day of the menstrual cycle (ie the first day of menstrual bleeding). Shall start receiving 2-5 days of the menstrual cycle, but in this case it is recommended to additionally use a barrier method of contraception during the first 7 days of tablet-taking from the first package
  
• The transition from a combined oral contraceptive. Preferably start taking Diane-35 on the day after taking the last active pills from the previous package, but in any case not later than the day after the usual 7-day break (for products containing 21 pills) or after the last inactive pills (for products containing 28 pills in the package)
  
• The transition from contraceptives containing only progestin (mini-pill, injectable form, the implant). A woman can go to the mini-pill Diane-35 on any day (without a break), with the implant - the date of its removal from the injection mold - the day when the next injection should have to be made. In all cases, you must use an additional barrier method of contraception during the first 7 days of tablet
  
• After the abortion I trimester of pregnancy. The woman may start taking the drug immediately. Subject to this condition the woman does not need extra contraceptive protection
  
• After delivery or abortion in the II trimester of pregnancy. Women should be advised to start taking the drug on day 21-28 after delivery or abortion in the II trimester of pregnancy. If the reception is started later, you must use an additional barrier method of contraception during the first 7 days of tablet-taking. If a woman has been sexually active, before you start taking Diane-35 pregnancy must be excluded or must wait for the first menstrual period.
  

Admission missed pills. If the delay in receiving the drug was less than 12 hours, contraceptive protection is not reduced. The woman should take pills as soon as possible, should be taken at the usual time.

If the delay in taking pills made more than 12 hours, contraceptive protection may be reduced. It is possible to be guided by the following two basic rules:

• Receiving the drug should never be interrupted for more than 7 days
  
• Required 7 days of continuous tablet-taking in order to achieve adequate suppression of the hypothalamic-pituitary-ovarian regulation.
  

If the delay in taking pills made more than 12 hours (interval from the receipt of the last pills for more than 36 h), the following advice can be given.

The first and second week of taking the drug

The woman should take the last missed pills as soon as possible (even if this means taking two pills at once). Next take the pills at the usual time. In addition to be used a barrier method of contraception (eg a condom) for the next 7 days. If intercourse took place during the week before skipping pills, you need to take into account the chance of pregnancy. The more pills missed and the closer this pass to the 7-day break in taking pills, the higher the risk of pregnancy.

The third week of taking the drug

The woman should take the last missed pills as soon as possible (even if this means taking two pills at once). Next take the pills at the usual time. In addition to be used a barrier method of contraception (eg a condom) for the next 7 days. Furthermore, dragees reception of a new package to be started as soon as the current package, i.e. nonstop. It is likely that the woman will not be withdrawal bleeding until the end of the second pack, but she may experience spotting or breakthrough uterine bleeding in the days of tablet-taking.

If a woman misses pills, and then to the first normal-free dosing interval it does not have withdrawal bleeding, pregnancy must be excluded.

Recommendations in case of vomiting

If a woman has to vomit within 4 hours after administration of dragees, absorption may not be complete and additional contraceptive must be taken measures. In these cases, you should be guided by the recommendations by skipping pills.

Changing the date of the beginning of the menstrual cycle

In order to delay the onset of menstruation, the woman should continue taking pills from a new pack of Diane-35 immediately after taking all the pills from the previous one, without a break in the reception. Drops of this new packaging may be taken for as long as the woman wants (as long as the packaging is not finished). Against the background of the drug from the second package, women may experience spotting or breakthrough uterine bleeding. Reactivate reception Diane-35 should be from a new package after the usual 7-day break.

In order to move the first day of menstruation to another day of the week, the woman should be advised to shorten the next break in taking pills for as many days, as much as she wants. The shorter the interval, the higher the risk that there will be withdrawal bleeding will continue to spotting and breakthrough bleeding while taking second pack (just as when she wanted to delay the onset of menses).

Duration of treatment

In order to take contraceptive medication for a long time.

In the treatment of hyperandrogenic conditions of reception duration determined by the severity of the disease. After the disappearance of the symptoms it is recommended to take Diane-35 for at least another 3-4 months. In case of relapse after a few weeks or months after completion of therapy can be carried out re-Diane-35.

Overdose:

No serious side effects have been reported in overdose.

Symptoms include nausea, vomiting, slight vaginal bleeding (young girls).

Treatment: symptomatic. No specific antidote.

Precautionary measures:

If any of the conditions / risk factors mentioned below are currently available, you should carefully weigh the potential risks and expected benefits of treatment in each individual case and discussed with the woman before she decides to start taking the drug. In the case of aggravation, or amplification of the first manifestations of any of these conditions or risk factors, the woman should consult with your doctor, who can decide whether to cancel the drug.

Diseases of the cardiovascular system

Several epidemiological studies have revealed a slight increase in the incidence of venous and arterial thrombosis and thromboembolism while taking combined oral contraceptives.

Venous thromboembolism (VTE) in a deep vein thrombosis and / or pulmonary embolism may develop during use of combined oral contraceptives. The approximate incidence of VTE in women taking oral contraceptives with low estrogen dose (less than 50 micrograms ethinylestradiol) is up to 4 per 10,000 women per year compared to 0.5-3 per 10,000 women per year in women not using oral contraceptives. However, the incidence of VTE developing while taking combined oral contraceptives, is less than the rate associated with pregnancy (6 per 10,000 pregnant women per year).

In women taking combined oral contraceptives are described in very rare cases of thrombosis, other blood vessels, eg renal, hepatic, mesenteric, veins and arteries of the retina. The relationship of these cases with taking combined oral contraceptives has not been proved.

Women need to stop taking the drug and seek medical advice in the development of venous or arterial thrombosis symptoms or cerebrovascular disorders, which can include: unilateral leg pain and / or swelling sudden severe pain in the chest, radiating to the left arm or without irradiation sudden shortness of breath sudden attack cough any unusual, severe, prolonged headache strengthening of the frequency and severity of migraine sudden partial or complete loss of vision diplopia slurred speech or aphasia dizziness, collapse with / or without partial seizure weakness or very marked numbness suddenly appeared on one side or in one part of the body movement disorders symptoms of "acute abdomen".

The risk of thrombosis (venous and / or arterial) and thromboembolism is increased:

• with age
  
• Smokers (with the number of cigarettes or increasing age the risk further increases, especially in women over 35 years old)
  

in the presence of:

• Family history (ie venous or arterial thromboembolism ever in close relatives or parents at a relatively young age)
  
• Obesity (body mass index over 30 kg / m2)
  
• dislipoproteinemia
  
• Hypertension
  
• Diseases of the heart valves
  
• Atrial fibrillation
  
• 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 contraceptive (in case the intended operation of at least 4 weeks before it), resuming the reception and for 2 weeks after the immobilization.

It is necessary to take into account the increased risk of thromboembolism during the postpartum period.

Circulatory disorders also may occur in diabetes mellitus, systemic lupus erythematosus, hemolytic uremic syndrome, chronic inflammatory bowel disease (Crohn's disease or ulcerative colitis) and sickle cell anemia.

Adequate treatment of these diseases can reduce the associated risks of thrombosis.

Biochemical parameters, which may indicate a predisposition to thrombosis include resistance to activated protein C, hyperhomocysteinemia, antithrombin III deficiency, protein C deficiency, protein deficiency of the S, the presence of antiphospholipid antibodies (cardiolipin antibodies, lupus anticoagulant).

Keep in mind that the risk of thrombosis during pregnancy is higher than when taking combined oral contraceptives.

Tumors

Some epidemiological studies have reported an increased risk of cervical cancer in long-term use of combined oral contraceptives. His connection with the intake of combined oral contraceptives has not been proved. Contradictions persist as to the extent to which these cases are related to the characteristics of sexual behavior and other factors such as human papilloma virus.

A meta-analysis of 54 epidemiological studies showed that there is a slightly increased relative risk (RR = 1,24) of breast cancer diagnosed in women who are at the time of the study were used combined oral contraceptives. His connection with the intake 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 using combined oral contraceptives.

In rare cases during treatment with sex steroids observed the development of liver tumors. The emergence of severe pain in the abdomen or signs of intra-abdominal bleeding, liver enlargement should be considered in the differential diagnosis.

other conditions

Although a slight increase in blood pressure have been reported in many women taking COCs, clinically relevant increases were rare. The relationship between the intake of combined oral contraceptives and hypertension has not been established. However, if at the time of their admission develops resistant hypertension, it is advisable to cancel these drugs and begin treatment of hypertension. The reception can be continued, if using antihypertensive treatment achieved normal blood pressure values.

The following states develop or worsen both during pregnancy and while taking combined oral contraceptives, but their relationship with the intake of combined oral contraceptives has not been proven: jaundice and / or pruritus associated with cholestasis formation of stones in the gallbladder porphyria, systemic lupus erythematosus, hemolytic uremic syndrome chorea (a disease Sydenham) herpes pregnant hearing loss associated with otosclerosis.

Acute or chronic disturbances of liver function may require discontinuation of combined oral contraceptives as long as liver function tests have not returned to normal. Recurrent cholestatic jaundice, which develops for the first time during pregnancy or previous use of sex steroids, requires discontinuation of COCs.

Although COCs may have an effect on the resistance of tissues to insulin and glucose tolerance, there is usually no need to adjust the dose of hypoglycemic agents in diabetic patients taking these drugs. However, women with diabetes should be under close medical supervision while taking combined oral contraceptives.

Women with hypertriglyceridemia, or having information about her family history can not be excluded increased risk of pancreatitis when using combined oral contraceptives.

Women with a tendency to chloasma while taking combined oral contraceptives should avoid prolonged exposure to sunlight and UV radiation.

If women suffering from hirsutism, symptoms have recently developed or significantly strengthened, in the differential diagnosis should take into account other factors such as the androgen-producing tumors, congenital adrenal hyperplasia.

Laboratory tests

Admission combined oral contraceptives can affect the results of certain lab tests, including liver function tests, kidney, thyroid, adrenal, levels of transport proteins in the plasma, carbohydrate metabolism, coagulation and fibrinolysis parameters. Changes do not usually go beyond the normal range.

Effects on ability to drive and operate machinery is not mentioned.

Special instructions:

While taking estrogen / progestogen combinations may experience irregular bleeding (spotting or breakthrough bleeding), especially during the first months of use. Therefore, evaluation of any irregular bleeding should be performed only after a period of adaptation of approximately 3 cycles.

If irregular bleeding recur or develop after previous regular cycles, it should be considered non-hormonal causes and implemented adequate diagnostic measures to exclude malignancy or pregnancy. These may include diagnostic curettage.

In some women withdrawal bleeding may not develop during a break in taking pills. If the drug is taken according to directions, it is unlikely that the woman is pregnant. However, if taken before dragees irregularly or, conversely, if there are no two consecutive menstrualnopodobnoe bleeding to continue taking the drug should be excluded pregnancy.