• Instructions for use DIANE ® -35
• Composition of the drug DIANE ® -35
• Indications for the drug DIANE ® -35
• Storage conditions for the drug DIANE ® -35
• Shelf life of the drug DIANE ® -35

Release form, composition and packaging

tablets 35 mcg+2 mg: 21 pcs.
Reg. No.: 1332/95/2000/05/10/13/15 dated 01/22/2015 - Valid

Dragee beige, round, biconvex.

Excipients: lactose monohydrate, corn starch, polyvidone 25,000, magnesium stearate, sucrose, polyvidone 700,000, macrogol 6000, calcium carbonate, talc, glycerin 85%, titanium dioxide, yellow iron oxide, montanglycol wax.

21 pcs. - contour cell packaging (1) - cardboard boxes.

Description medicinal product DIANE ® -35 created in 2010 on the basis of instructions posted on the official website of the Ministry of Health of the Republic of Belarus. Update date: 06/09/2011

pharmachologic effect

Diane-35 is a low-dose monophasic oral combined estrogen-antiandrogen contraceptive drug.

The contraceptive effect of Diane-35 is carried out through complementary mechanisms, the most important of which are the suppression of ovulation and changes in the properties of cervical secretion, as a result of which it becomes impenetrable to sperm. Cyproterone acetate contained in Diana-35 is a competitive antagonist of androgen receptors, has an inhibitory effect on the synthesis of androgens in target cells and helps reduce the concentration of androgens in the blood due to its antigonadotropic effect. Cyproterone acetate inhibits the influence of androgens, which are also produced in female body. Thus it becomes possible treatment diseases caused by increased formation of androgens or increased sensitivity to these hormones.

The antigonadotropic effect of the drug is enhanced by ethinyl estradiol, which also increases the synthesis of SHBG, which helps reduce the free biologically active level of androgens in the blood. Treatment with Diane-35 leads - usually after 3-4 months of therapy - to the healing of existing acne lesions. Excessive oiliness in hair and skin usually disappears earlier. Hair loss, which often accompanies seborrhea, is also reduced. However, in women suffering from mild forms of hirsutism and, in particular, a slight increase in facial hair growth, results become visible only after several months of use.

In addition to the contraceptive effect, the combination of estrogen and progestogen has a positive effect that should be taken into account when choosing a method of birth control. The menstrual cycle becomes more regular, painful menstruation is less common, the intensity of bleeding decreases, resulting in a reduced risk of developing iron deficiency anemia.

Pharmacokinetics

Cyproterone acetate

Absorption. Cyproterone acetate taken orally is rapidly and completely absorbed. Serum Cmax of 15 ng/ml is achieved in approximately 1.6 hours. Bioavailability is approximately 88%.

Distribution. Cyproterone acetate is almost completely bound to serum albumin. Only 3.5-4.0% of total serum levels of cyproterone acetate are in free form. Ethinyl estradiol-induced increases in sex hormone binding globulin (SHBG) levels do not affect the binding of cyproterone acetate to serum proteins. The apparent V d of cyproterone acetate is approximately 986 ± 437 l.

Metabolism. Cyproterone acetate is almost completely metabolized. The main metabolite in human plasma is a 15β-hydroxyl derivative, which is formed with the participation of the CYPZA4 enzyme of the cytochrome P450 system. The clearance rate from serum is approximately 3.6 ml/min/kg.

Excretion. The content of cyproterone acetate in the blood serum undergoes a two-phase decrease, which is characterized by T1/2 of about 0.8 hours and 2.3-3.3 days. Cyproterone acetate is partially excreted in unchanged form. Metabolites of cyproterone acetate are excreted in urine and bile in a ratio of 1:

• 2 with T 1/2 about 1.8 days.

Equilibrium concentration. The pharmacokinetics of cyproterone acetate is not affected by the level of SHBG in the blood serum. As a result daily intake of the drug, the level of substances in the serum increases approximately 2.5 times, and the equilibrium concentration is achieved in the second half of the course.

Ethinyl estradiol

Absorption. After oral administration, ethinyl estradiol is absorbed quickly and completely. Serum Cmax of approximately 71 pg/ml is achieved in 1.6 hours. During absorption and first passage through the liver, ethinyl estradiol is extensively metabolized, resulting in its oral bioavailability averaging about 45%, with significant individual differences observed within 20-65%.

Distribution. Ethinyl estradiol is almost completely (98%), although nonspecific, bound to albumin. Ethinyl estradiol induces the synthesis of GSPC. The apparent V d of ethinyl estradiol is 2.8-8.6 l/kg.

Metabolism. Ethinyl estradiol undergoes presystemic conjugation in the mucosa small intestine and in the liver. Ethinyl estradiol is primarily metabolized by aromatic hydroxylation, resulting in the formation of a variety of hydroxylated and methylated metabolites, presented both as free metabolites and as conjugates with glucuronic and sulfuric acids. The rate of metabolic clearance of ethinyl estradiol varies from 2.3 to 7.0 ml/min/kg.

Excretion. The content of ethinyl estradiol in the blood serum undergoes a two-phase decrease, characterized by T1/2 of about 1 hour and 10-20 hours, respectively. It is not excreted from the body unchanged. Ethinyl estradiol metabolites are excreted by the kidneys and liver in a ratio of 4:

• 6 s T 1/2 about 24 hours.

Equilibrium concentration. Steady-state concentration is reached approximately in the second half of the treatment cycle, when the drug level in the blood serum is 60% higher compared to a single dose.

Indications for use

• contraception (prevention of unwanted pregnancy) in women with androgenization phenomena;
• treatment of androgen-dependent diseases in women, such as acne, especially common forms and forms accompanied by seborrhea, inflammation or nodule formation (papular-pustular acne, nodular cystic acne), androgenetic alopecia and mild forms of hirsutism.

Dosage regimen

For oral administration. Taking Diane-35 should be regular to achieve the necessary therapeutic effectiveness and contraceptive effect. Previously used hormonal contraceptives should be discontinued. The dosage regimen for Diane-35 is similar to that for most other combined oral contraceptives, so general guidelines for use must be taken into account. When taken correctly and regularly, combined oral contraceptives have high contraceptive reliability, with a “method failure” rate of no more than 1% per year. Irregular use of Diane-35 can lead to intermenstrual bleeding and worsen the therapeutic and contraceptive effectiveness of the drug.

The pills should be taken in the order indicated on the package, every day at approximately the same time, with a small amount of water. Take one tablet per day continuously for 21 days. Each subsequent package begins after a 7-day break, during which withdrawal bleeding (menstrual-like bleeding) is observed. It usually begins 2-3 days after taking the last pill and may not end until you start taking a new package.

How to start taking Diane-35

- in the absence of taking any hormonal contraceptives in the previous month.

Reception of Diane-35 begins on the first day of the menstrual cycle (i.e. on the first day menstrual bleeding). It is allowed to start taking it on days 2-5 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 taking the pills from the first package.

- when switching from combined hormonal contraceptives (combined oral contraceptives, vaginal ring, transdermal patch).

It is preferable to start taking Diane-35 the day after taking the last hormone-containing pill from the previous package, but in no case later than the next day after the usual 7-day break in taking (for drugs containing 21 pills) or after taking the last hormone-free pill (for preparations containing 28 tablets per package). When switching from a vaginal ring or transdermal patch, it is preferable to start taking Diane-35 on the day the ring or patch is removed, but in no case later than the day when the next ring or patch was to be applied.

- when switching from contraceptives containing only gestagens (mini-pills, injectable forms, implant), or a gestagen-releasing intrauterine device (IUD).

A woman can switch from the mini-pill to Diana-35 on any day (without a break), from an implant or IUD with progestogen - on the day of its removal, from the injection form - from the day when the next injection would have been given. In all cases, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the pill.

- after an abortion in the first trimester of pregnancy.

A woman can start taking the drug immediately. If this condition is met, the woman does not need additional contraceptive protection.

- after childbirth or abortion in the second trimester of pregnancy.

A woman should be advised to start taking the drug 21-28 days after childbirth or abortion in the second trimester of pregnancy. If use is started later, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the pill. However, if a woman has already been sexually active, pregnancy should be excluded before starting Diane-35 or she must wait until her first menstruation.

Taking missed pills

If the delay in taking the pill is less than 12 hours, contraceptive protection is not reduced. A woman should take the pill as soon as possible, and the next pill should be taken at the usual time.

If the delay in taking the pill is more than 12 hours, contraceptive protection may be reduced. In this case, you can be guided by the following two basic rules:

• Taking the pills should never be interrupted for more than 7 days.
• 7 days of continuous administration of the pills are required to achieve adequate suppression of the hypothalamic-pituitary-ovarian system. Accordingly, the following advice can be given if the delay in taking the pill is more than 12 hours (the interval since the last pill was taken is more than 36 hours):

- first week of taking the drug.

A woman should take the last pill she missed as soon as she remembers (even if this means taking two pills at the same time). The next pill is taken at the usual time. Additionally, a barrier method of contraception (for example, a condom) should be used for the next 7 days. If sexual intercourse took place during the week before missing the pills, the possibility of pregnancy must be taken into account.

The more tablets are missed, and the closer they are to a break in taking active substances, the greater the likelihood of pregnancy.

- second week of taking the drug.

A woman should take the last pill she missed as soon as she remembers (even if this means taking two pills at the same time). The next pill is taken at the usual time. Provided that the woman took the pill correctly during the 7 days preceding the first missed pill, there is no need to use additional contraceptive measures. Otherwise, as well as if you miss two or more pills, you must additionally use barrier methods of contraception (for example, a condom) for 7 days.

- third week of taking the drug.

The risk of decreased reliability is inevitable due to the upcoming break in taking the pill.

A woman must strictly adhere to one of the following two options. Moreover, if in the 7 days preceding the first missed pill, all pills were taken correctly, there is no need to use additional contraceptive methods.

1. The woman should take the last missed pill as soon as possible (even if this means taking two pills at the same time). The next pill is taken at the usual time, until the pills from the current package run out. Next pack should start right away.
Withdrawal bleeding is unlikely until the second pack is finished, but spotting or discharge may occur. breakthrough bleeding while taking the pills.

2. A woman can also stop taking pills from the current package. She should then take a break for 7 days, including the day she missed the pills, and then start taking a new pack.

If a woman misses taking the pill and then does not have withdrawal bleeding during the break from taking the pill, pregnancy must be ruled out.

Tips for gastrointestinal disorders

In severe gastrointestinal disorders, absorption of the drug may be incomplete. In this case, additional contraceptive measures should be taken.

If a woman vomits within 3-4 hours after taking Diane-35 tablets, you should follow the advice regarding skipping the tablets. If a woman does not want to change the normal regimen of taking the drug, she should take, if necessary, an additional tablet (or several tablets) from another package.

Duration of use

For the purpose of contraception, the drug is taken for a long time.

When treating hyperandrogenic conditions, the duration of use is determined by the severity of the disease and the effectiveness of treatment. As a rule, treatment should be carried out over several months. When treating acne and seborrhea, the effect usually occurs earlier than when treating hirsutism or alopecia.

After the symptoms disappear, it is recommended to take Diane-35 for at least another 3-4 months. If a relapse occurs several weeks or months after completion of the course, Diane-35 can be re-treated. In this case, the possibility of early resumption of Diane-35 therapy should be considered.

Changing the start day of the menstrual cycle

In order to delay the onset of menstruation, a woman should continue taking pills from the new Diane-35 package immediately after all the pills from the previous one have been taken, without interruption. The pills from this new package can be taken for as long as the woman wishes (until the package runs out). While taking the drug from the second package, a woman may experience spotting or breakthrough uterine bleeding. You should resume taking Diane-35 from a new package after the usual 7-day break.

In order to postpone the start of menstruation to another day of the week, a woman should shorten the next break in taking the pills by as many days as she wants. The shorter the interval, the higher the risk that she will not have withdrawal bleeding and, in the future, will have spotting bloody issues and breakthrough bleeding while taking the second pack (as well as when she would like to delay the onset of menstruation).

Additional information for special categories of patients

Children and teenagers. The drug Diane-35 is indicated only after the onset of menarche.

Elderly patients. Not applicable. The drug Diane-35 is not indicated for women after menopause.

Patients with liver disorders. Diane-35 is contraindicated in women with severe liver disease until liver function tests return to normal.

Patients with kidney disorders. Diane-35 has not been specifically studied in patients with renal impairment. Available data do not suggest changes in treatment in these patients.

Side effects

The following undesirable effects have been described in women taking Diane-35, and their relationship with the drug has been neither confirmed nor refuted:

• often (=1/100) nausea, abdominal pain, weight gain, headache, depressed mood, mood changes, soreness and tension of the mammary glands;
• infrequently (=1/1000,<1/100) vomiting, diarrhea, fluid retention, migraine, decreased libido, enlarged mammary glands, rash, urticaria;
• rarely (<1/1000) poor tolerance to contact lenses, hypersensitivity reactions, weight loss, increased libido, vaginal discharge, breast discharge, erythema nodosum, erythema multiforme.

The following serious side effects have been observed in women using combined oral contraceptives:

• venous thromboembolic disorders;
• arterial thromboembolic disorders;
• cerebrovascular disorders;
• stroke;
• arterial hypertension;
• hypertriglyceridemia;
• impaired glucose tolerance or effects of peripheral insulin resistance;
• liver tumors (benign and malignant);
• liver dysfunction;
• chloasma;
• in women with hereditary angioedema, exogenous estrogens can provoke or aggravate the symptoms of this disease;
• the appearance or worsening of conditions whose connection with the use of combined oral contraceptives has not been proven: jaundice and/or itching associated with cholestasis; formation of gallstones; porphyria; systemic lupus erythematosus; hemolytic uremic syndrome; chorea; herpes during pregnancy; hearing loss associated with otosclerosis, Crohn's disease and ulcerative colitis, cervical cancer
• a very small increase in the incidence of breast cancer diagnosis in women using combined oral contraceptives. Because breast cancer is less common in women under 40 years of age, the excess rate is small relative to the overall risk of developing breast cancer. The cause-and-effect relationship with the use of combined oral contraceptives is not known.

Contraindications for use

Preparations containing a combination of estrogen/progestins should not be used if any of the conditions listed below are present. If any of these conditions develop for the first time while taking the drug, the drug should be discontinued immediately.

• the presence of thrombosis/thromboembolism (venous and arterial) currently or in history (for example, deep vein thrombosis, pulmonary embolism, myocardial infarction) or cerebrovascular disorders);
• the presence or history of conditions preceding thrombosis (for example, transient ischemic attacks, angina pectoris);
• history of migraine with focal neurological symptoms;
• diabetes mellitus with vascular complications;
• the presence of severe or multiple risk factors for venous or arterial thrombosis;
• pancreatitis with severe hypertriglyceridemia currently or in history;
• severe liver disease until liver function tests return to normal;
• the presence or history of liver tumors (benign or malignant);
• identified or suspected hormone-dependent malignant diseases (for example, genital organs or mammary glands);
• vaginal bleeding of unknown origin;
• pregnancy or suspicion of it;
• lactation period;
• hypersensitivity to any of the components of the drug.

special instructions

Overdose

No serious side effects have been reported following overdose.

Symptoms: nausea, vomiting and, in young girls, minor vaginal bleeding.

Treatment: there is no specific antidote;

Symptomatic treatment should be carried out.

Drug interactions

The interaction of estrogen/progestagen combinations, like Diana-35 with other drugs (drugs that induce liver enzymes, some antibiotics), can lead to breakthrough bleeding and/or a decrease in the contraceptive effectiveness of the drug. While taking such drugs, a woman should additionally use a barrier method of contraception in addition to Diana-35 or choose another method of contraception. While taking medications that affect microsomal enzymes, and for 28 days after their discontinuation, you should additionally use a barrier method of contraception. While taking antibiotics (with the exception of rifampicin and griseofulvin) and for 7 days after their discontinuation, you should additionally use a barrier method of contraception. If the period of using the barrier method of protection against unwanted pregnancy ends later than the pill in the package, you need to move on to the next package of Diane-35 ® without the usual break in taking the pill.

Substances affecting the effectiveness of Diane-35 (liver enzyme inducers and antibiotics). Medicines that reduce the contraceptive effectiveness of the drug include drugs that induce liver enzymes and antibiotics.

Induction of liver enzymes (increased liver metabolism). The use of drugs that induce microsomal liver enzymes can lead to an increase in the clearance of sex hormones. Such medicines include:

• phenytoin, barbiturates, primidone, carbamazepine and rifampicin;
• There are also suggestions for oxcarbazepine, topiramate, felbamate, ritonavir and griseofulvin and products containing St. John's wort.

In addition, HIV proteases (eg, ritonavir) and non-nucleoside reverse transcriptase inhibitors (eg, nevirapine), and combinations thereof, may potentially increase hepatic metabolism.

Effect on enterohepatic circulation. According to some clinical studies, certain antibiotics (for example, penicillins and tetracyclines) may reduce the intrahepatic circulation of estrogens, thereby lowering the concentration of ethinyl estradiol.

Effect of estrogen/progestogen combinations on other drugs. Estrogen/progestagen combinations, like Diana-35, can affect the metabolism of other drugs, leading to an increase (for example, cyclosporine) or a decrease (for example, lamotrigine) in their concentrations in blood plasma and tissues.

Contacts for inquiries

BAYER VR LLC, representative office, (Republic of Belarus)

Indications for use

Contraception in women with androgenization phenomena;

Treatment of androgen-dependent diseases in women: acne, especially common forms and forms accompanied by seborrhea, inflammation or nodule formation (papular-pustular acne, nodular cystic acne), androgenetic alopecia and mild forms of hirsutism.

Release form

tablets 35 mcg + 2 mg; blister 21, cardboard pack 1;
Compound
Dragee 1 dragee
cyproterone acetate 2 mg
ethinyl estradiol 0.035 mg
excipients: lactose monohydrate - 31.115 mg; corn starch - 18 mg; povidone - 2.1 mg; magnesium hydrosilicate (talc) - 1.65 mg; magnesium stearate - 0.1 mg
shell: sucrose - 19.371 mg; povidone 700000 - 0.189 mg; macrogol 6000 - 2.148 mg; calcium carbonate - 8.606 mg; magnesium hydrosilicate (talc) - 4.198 mg; titanium dioxide - 0.274 mg; glycerol - 0.137 mg; mountain glycolic wax - 0.05 mg; iron (II) oxide - 0.027 mg
21 pcs in a blister with a calendar scale; 1 blister in a box.

Pharmacodynamics

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

While taking Diane®-35, the increased activity of the sebaceous glands, which plays an important role in the occurrence of acne and seborrhea, decreases. After 3–4 months of therapy, this usually leads to the disappearance of the existing rash. Excessive oiliness in hair and skin disappears even earlier. Hair loss, which often accompanies seborrhea, is also reduced. Therapy with Diane®-35 in women of reproductive age reduces the clinical manifestations of mild forms of hirsutism (including increased growth of facial hair), however, the effect of treatment should be expected only after several months of use.

Along with the antiandrogenic effect, cyproterone acetate has pronounced gestagenic activity. The contraceptive effect of Diane®-35 is due to various factors, the most important of which are inhibition of ovulation and changes in the secretion of cervical mucus. In addition to the contraceptive effect, the combination of estrogen and progestogen has positive non-contraceptive health effects that should be taken into account when choosing a method of birth control. The cycle becomes more regular, painful menstruation is less frequent, resulting in a reduced risk of iron deficiency anemia.

Pharmacokinetics

Cyproterone acetate. When taken orally, it is completely absorbed, absolute bioavailability is 88%. After oral administration of 1 tablet Diane®-35, Cmax in serum (15 ng/ml) is achieved after 1.6 hours. After this, a two-phase decrease in its level in serum is observed, characterized by T1/2 of 0.8 hours and 2.3 days. Total Cl from serum - 3.6 ml/min/kg. Cyproterone acetate is almost completely bound to plasma albumin; in free form it is approximately 3.5–4.0% of the total concentration in the blood. Since protein binding is nonspecific, changes in sex hormone binding globulin (SHBG) levels do not affect the pharmacokinetics of cyproterone acetate. Metabolized by hydroxylation and conjugation, the main metabolite in human plasma is the 15β-hydroxyl derivative. Some of the dose is excreted unchanged in bile. Most of the dose is excreted in the form of metabolites in urine or bile in a ratio of 3:7. Metabolites from plasma are eliminated with T1/2 of 1.7 days.

Ethinyl estradiol. After oral administration, it is quickly and completely absorbed. During absorption and “first pass” through the liver, a significant part of ethinyl estradiol is metabolized, which causes a decrease in bioavailability and its variability when taken orally. After oral administration of 1 tablet Diane®-35, Cmax in blood serum (80 pg/ml) is achieved after 1.7 hours. It binds nonspecifically to serum albumin. Only 2% of ethinyl estradiol is found in the plasma in a free state. The apparent volume of distribution is approximately 5 l/kg, the rate of metabolic clearance from plasma is approximately 5 ml/min/kg. The decrease in the concentration of ethinyl estradiol in the blood serum is biphasic; the first phase is characterized by T1/2 1–2 hours, the second - approximately 20 hours. It is not excreted unchanged from the body. Ethinyl estradiol 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 be passed into the baby's body through breast milk.

Taking other drugs may affect the systemic bioavailability of ethinyl estradiol. However, no interaction with high doses of vitamin C has been identified.

Ethinyl estradiol increases the hepatic synthesis of SHBG and corticoid binding globulin (CBG) during continuous use. However, the degree of SHBG induction depends on the chemical structure and dose of the simultaneously administered progestogen. While taking Diane®-35, the serum SHBG concentration increases from approximately 100 to 300 nmol/l, and the serum concentration of DSG increases from approximately 50 to 95 mcg/ml.

Use during pregnancy

Diane®-35 should not be taken during pregnancy or suspected pregnancy, as well as during breastfeeding.

Other special occasions at reception

If liver dysfunction occurs, temporary discontinuation of Diane-35 may be required until laboratory parameters normalize. Recurrent cholestatic jaundice, which develops for the first time during pregnancy or previous use of sex hormones, requires discontinuation of combined oral contraceptives.

Contraindications for use

Preparations containing a combination of estrogen/progestogen should not be used if any of the conditions listed below are present. If any of these conditions develop for the first time while taking the drug, the drug should be discontinued immediately:

Thrombosis (venous and arterial) and thromboembolism currently or in history (including deep vein thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular disorders);
- conditions preceding thrombosis (including transient ischemic attacks, angina) currently or in history;
- diabetes mellitus with vascular complications;
- the presence of severe or multiple risk factors for venous or arterial thrombosis;
- jaundice or severe forms of liver disease currently or in history (until liver tests return to normal);
- liver tumors (benign or malignant) currently or in history;
- identified or suspected hormone-dependent malignant diseases of the genital organs or mammary glands;
- vaginal bleeding of unknown origin;
- pregnancy or suspicion of it;
- period of breastfeeding;
- hypersensitivity to any of the components of Diane®-35.

Diane®-35 is not used in men.

Side effects

From the endocrine system: in rare cases - engorgement, soreness, enlargement of the mammary glands and discharge from them, change in body weight.

From the reproductive system: in rare cases - intermenstrual bleeding, changes in vaginal secretion, changes in libido.

From the side of the central nervous system: in rare cases - headache, migraine, decreased mood.

From the digestive system: in rare cases - nausea, vomiting.

Other: in very rare cases - poor tolerance to contact lenses, allergic reactions, the appearance of age spots on the face (chloasma).

The listed side effects may develop in the first few months of taking Diane-35 and usually decrease over time.

Directions for use and doses

Inside, with a small amount of water, every day at approximately the same time of day, in the order indicated on the package. Take 1 tablet per day, continuously for 21 days. Each subsequent package begins after a 7-day break, during which withdrawal bleeding (menstrual-like bleeding) is observed. It usually begins 2-3 days after taking the last pill and may not end until you start taking a new package.

Diane®-35 must be taken regularly to achieve the required contraceptive and therapeutic effects. The regimen for taking Diane®-35 is similar to the standard regimen for most combined oral contraceptives. Irregular use of Diane®-35 can lead to intermenstrual bleeding and reduce the therapeutic effect and contraceptive reliability.

Medical examinations. Before starting to use Diane®-35, a woman is recommended to undergo a thorough general medical and gynecological examination (including examination of the mammary glands and cytological examination of cervical mucus) and exclude pregnancy. In addition, disorders of the blood coagulation system should be excluded.

In case of long-term use of the drug, it is necessary to carry out preventive control examinations every 6 months. A woman should be warned that Diane®-35 does not protect against HIV infection (AIDS) or any other sexually transmitted disease!

Start taking Diane®-35:

If you have not taken any hormonal contraceptives in the previous month. Taking Diane-35 begins on the first day of the menstrual cycle (i.e., on the first day of menstrual bleeding). It is possible to start taking it on days 2–5 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 taking pills from the first package;

When switching from combined oral contraceptives. It is preferable to start taking Diane®-35 the day after taking the last active tablet from the previous package, but in no case later than the next day after the usual 7-day break (for preparations containing 21 tablets) or after taking the last inactive tablet (for drugs containing 28 tablets per package);

When switching from contraceptives containing only gestagens (mini-pills, injection forms, implant). A woman can switch from the mini-pill to Diana®-35 on any day (without a break), from the implant - on the day of its removal, from the injection form - from the day when the next injection would have been given. In all cases, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the pill;

After an abortion in the first trimester of pregnancy. A woman can start taking the drug immediately. If this condition is met, the woman does not need additional contraceptive protection;

After childbirth or abortion in the second trimester of pregnancy. A woman should be advised to start taking the drug 21–28 days after childbirth or abortion in the second trimester of pregnancy. If use is started later, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the pill. If a woman has already been sexually active, before starting Diane®-35, pregnancy should be excluded or she must wait until her first menstruation.

Taking missed pills. If the delay in taking the drug is less than 12 hours, contraceptive protection is not reduced. A woman should take the pill as soon as possible, the next one should be taken at the usual time.

If the delay in taking the pill is more than 12 hours, contraceptive protection may be reduced. In this case, you can be guided by the following two basic rules:

The drug should never be interrupted for more than 7 days;

7 days of continuous administration of the pill are required to achieve adequate suppression of hypothalamic-pituitary-ovarian regulation.

If the delay in taking the pill is more than 12 hours (the interval from the moment you took the last pill is more than 36 hours), the following advice can be given.

The first and second weeks of taking the drug

A woman should take the last pill she missed as soon as possible (even if this means taking two pills at the same time). The next pill is taken at the usual time. Additionally, a barrier method of contraception (such as a condom) should be used for the next 7 days. If sexual intercourse took place within a week before missing the pills, the possibility of pregnancy must be taken into account. The more pills you miss, and the closer this skip is to the 7-day break in taking pills, the higher the risk of pregnancy.

Third week of taking the drug

A woman should take the last pill she missed as soon as possible (even if this means taking two pills at the same time). The next pill is taken at the usual time. Additionally, a barrier method of contraception (such as a condom) should be used for the next 7 days. In addition, taking pills from a new package should be started as soon as the current package is finished, i.e. nonstop. Most likely, the woman will not experience withdrawal bleeding until the end of the second pack, but she may experience spotting or breakthrough uterine bleeding on the days she takes the pill.

If a woman misses taking a pill, and then does not have withdrawal bleeding during the first normal interval without taking the drug, it is necessary to exclude pregnancy.

If a woman has vomited within 4 hours of taking the pill, absorption may not be complete and additional contraceptive measures should be taken. In these cases, you should follow the recommendations when skipping pills.

Changing the start day of the menstrual cycle

In order to delay the onset of menstruation, a woman should continue taking pills from the new Diane®-35 package immediately after taking all the pills from the previous one, without interruption. The pills from this new package can be taken for as long as the woman wishes (until the package runs out). While taking the drug from the second package, a woman may experience spotting or breakthrough uterine bleeding. You should resume taking Diane®-35 from a new pack after the usual 7-day break.

In order to postpone the start of menstruation to another day of the week, a woman should be advised to shorten the next break in taking the pills by as many days as she wants. The shorter the interval, the higher the risk that there will be no withdrawal bleeding and that there will be spotting and breakthrough bleeding in the future while taking the second package (the same as in the case when she would like to delay the onset of menstruation).

Duration of use

For the purpose of contraception, the drug is taken for a long time.

When treating hyperandrogenic conditions, the duration of use is determined by the severity of the disease. After symptoms disappear, it is recommended to take Diane®-35 for at least another 3-4 months. If a relapse is detected several weeks or months after completion of the course, Diane®-35 can be re-treated.

Overdose

No serious side effects have been reported following overdose.

Symptoms: nausea, vomiting, minor vaginal bleeding (in young girls).

Treatment: symptomatic. There is no specific antidote.

Interactions with other drugs

Drug interactions that increase the clearance of sex hormones may lead to breakthrough uterine bleeding or decreased contraceptive reliability. This was found for hydantoins, barbiturates, primidone, carbamazepine and rifampicin; oxcarbazepine, topiramate, felbamate and griseofulvin are also suspected. While taking rifampicin and for 28 days after its discontinuation, in addition to Diana®-35, a barrier method of contraception (for example, a condom) should be used. If the concomitant administration of the drug is started at the end of taking a package of Diane®-35, the next package should be started without the usual break in administration. The mechanism of this interaction is based on the induction of liver enzymes by these drugs.

Contraceptive reliability is reduced when taking antibiotics such as ampicillin and tetracyclines. The mechanism of this action is not clear.

Women receiving any of the above-mentioned short-course drugs in addition to Diana®-35 should temporarily use a barrier method of contraception while taking the drugs concomitantly and for 7 days after their discontinuation.

Women receiving these drugs for a long course should be advised to use other (non-hormonal) methods of contraception (for example, a condom).

Precautions for use

If any of the conditions/risk factors listed below currently exist, the potential risks and expected benefits of treatment should be carefully weighed in each individual case and discussed with the woman before she decides to start taking the drug. If any of these conditions or risk factors worsen, intensify, or appear for the first time, a woman should consult her doctor, who may decide whether to discontinue the drug.

Diseases of the cardiovascular system

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

Venous thromboembolism (VTE), in the form of deep vein thrombosis and/or pulmonary embolism, can develop during the use of all combined oral contraceptives. The estimated incidence of VTE in women taking oral contraceptives with low-dose estrogen (less than 50 mcg ethinyl estradiol) is up to 4 per 10,000 women per year, compared with 0.5 to 3 per 10,000 women per year in women not using oral contraceptives. However, the incidence of VTE occurring with combined oral contraceptives is less than that associated with pregnancy (6 per 10,000 pregnant women per year).

In women taking combined oral contraceptives, extremely rare cases of thrombosis of other blood vessels, such as the renal, hepatic, mesenteric, veins and retinal arteries, have been described. The connection of these cases with the use of combined oral contraceptives has not been proven.

A woman should stop taking the drug and consult a doctor if symptoms of venous or arterial thrombosis or cerebrovascular disorders develop, which may include: unilateral leg pain and/or swelling; sudden severe chest pain, with or without radiation to the left arm; sudden shortness of breath; sudden attack of coughing; any unusual, severe, prolonged headache; increased frequency and severity of migraines; sudden partial or complete loss of vision; diplopia; slurred speech or aphasia; dizziness; collapse with/or without partial seizure; weakness or very significant loss of sensation that suddenly appears 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 increases:
- with age;
- in smokers (with an increase in the number of cigarettes or an increase in age, the risk further increases, especially in women over 35 years of age);

In the presence of:
- family history (i.e. venous or arterial thromboembolism ever in close relatives or parents at a relatively young age);
- obesity (body mass index more than 30 kg/m2);
- dislipoproteinemia;
- arterial hypertension;
- diseases of the heart valves;
- atrial fibrillation;
- prolonged immobilization, major surgery, any leg surgery or major trauma.

In these situations, it is advisable to stop using combined oral contraceptives (in the case of planned surgery, at least 4 weeks before it) and not to resume use for 2 weeks after the end of immobilization.

The increased risk of thromboembolism in the postpartum period should be taken into account.

Circulatory abnormalities may also 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 risk of thrombosis.

Biochemical parameters that may indicate susceptibility to thrombosis include activated protein C resistance, hyperhomocysteinemia, antithrombin III deficiency, protein C deficiency, protein S deficiency, and the presence of antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant).

It should be taken into account that the risk of thrombosis during pregnancy is higher than when taking combined oral contraceptives.

Some epidemiological studies have reported an increased risk of cervical cancer with long-term use of combined oral contraceptives. Its connection with the use of combined oral contraceptives has not been proven. Controversy remains about the extent to which these cases are related to sexual behavior and other factors such as the human papillomavirus.

A meta-analysis of 54 epidemiological studies demonstrated that there is a slightly increased relative risk (RR=1.24) of developing breast cancer diagnosed in women who were using combined oral contraceptives at the time of the study. Its connection with the use of combined oral contraceptives has not been proven. The observed increased risk may be a consequence of earlier diagnosis of breast cancer in women using combined oral contraceptives.

In rare cases, the development of liver tumors has been observed during the use of sex steroids. The appearance of severe pain in the abdomen or signs of intra-abdominal bleeding, liver enlargement should be taken into account when making a differential diagnosis.

Other states

Although slight increases in blood pressure have been described in many women taking combined oral contraceptives, clinically significant increases have rarely been reported. The relationship between taking combined oral contraceptives and arterial hypertension has not been established. However, if persistent hypertension develops while taking them, it is advisable to discontinue these drugs and begin treatment for hypertension. Reception can be continued if normal blood pressure values ​​are achieved with the help of antihypertensive therapy.

The following conditions develop or worsen both during pregnancy and when taking combined oral contraceptives, but their relationship with taking combined oral contraceptives has not been proven: jaundice and/or itching associated with cholestasis; formation of gallstones; porphyria; systemic lupus erythematosus; hemolytic uremic syndrome; chorea minor (Sydenham disease); herpes during pregnancy; hearing loss associated with otosclerosis.

Acute or chronic liver dysfunction may require discontinuation of combined oral contraceptives until liver function tests return to normal. Recurrent cholestatic jaundice, which develops for the first time during pregnancy or previous use of sex steroids, requires discontinuation of combined oral contraceptives.

Although combined oral contraceptives may have an effect on insulin resistance and glucose tolerance, there is usually no need to adjust the dosage of glucose-lowering medications in diabetic patients taking these medications. However, women with diabetes should be closely monitored by a physician while taking combined oral contraceptives.

In women with hypertriglyceridemia or a family history of hypertriglyceridemia, an increased risk of developing pancreatitis while taking combined oral contraceptives cannot be excluded.

Women prone to chloasma should avoid prolonged sun exposure and exposure to UV radiation while taking combined oral contraceptives.

If symptoms have recently developed or become significantly worse in women suffering from hirsutism, other causes, such as androgen-producing tumor, congenital adrenal dysfunction, should be considered in the differential diagnosis.

Laboratory tests

Taking combined oral contraceptives may affect the results of some laboratory tests, including liver, kidney, thyroid, adrenal function, plasma transport protein levels, carbohydrate metabolism, coagulation and fibrinolysis parameters. Changes usually do not go beyond normal values.

There was no effect on the ability to drive a car or operate machinery.

Special instructions for use

While taking a combination of estrogen/progestins, irregular bleeding (spotting or breakthrough bleeding) may occur, especially during the first months of use. Therefore, any irregular bleeding should be assessed only after an adaptation period of approximately 3 cycles.

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

In some women, withdrawal bleeding may not develop during a break from taking the pill. If the drug is taken as directed, it is unlikely that the woman is pregnant. However, if the pills were taken irregularly before or, conversely, if there are no 2 menstrual-like bleedings in a row, pregnancy should be excluded before continuing to take the drug.

Storage conditions

List B.: At a temperature not exceeding 30 °C.

Best before date

ATX classification:

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Catad_pgroup Combined oral contraceptives

The most physiological contraceptive that preserves the quality of sexual life. For the treatment of heavy and/or prolonged menstrual bleeding without organic pathology.
INFORMATION IS PROVIDED STRICTLY
FOR HEALTH PROFESSIONALS

Diane-35 - official* instructions for use

*registered by the Ministry of Health of the Russian Federation (according to grls.rosminzdrav.ru)

INSTRUCTIONS
(information for specialists)
on medical use of the drug

Registration number P No. 012240/01

Tradename
Diane-35®

Dosage form
Dragee

Compound
Each dragee contains:
Active substances: 2 mg cyproterone acetate and 0.035 mg ethinyl estradiol.
Excipients: lactose monohydrate, corn starch, povidone, magnesium stearate, sucrose, povidone 700000, polyethylene glycol (macrogol 6000), calcium carbonate, talc, glycerol, titanium dioxide, iron (II) oxide, mountain glycol wax.

Description
Round, biconvex, light yellow dragees

Pharmacotherapeutic group
Contraceptive (estrogen + antiandrogen)

ATX codeО03НВ01

Pharmacological properties

Pharmacodynamics

Diane-35 is a low-dose monophasic oral combined estrogen-antiandrogen contraceptive drug.

The contraceptive effect of Diane-35 is carried out through complementary mechanisms, the most important of which include suppression of ovulation and changes in the properties of cervical secretion, as a result of which it becomes impenetrable to sperm.

In women taking combined oral contraceptives, the menstrual cycle becomes more regular, painful menstruation is less frequent, and the intensity of bleeding decreases, resulting in a reduced risk of iron deficiency anemia. In addition, there is evidence that the risk of developing endometrial and ovarian cancer is reduced.

While taking Diane-35, the increased activity of the sebaceous glands, which plays an important role in the occurrence of acne and seborrhea, decreases. After 3-4 months of therapy, this usually leads to the disappearance of the existing rash. Excessive oiliness in hair and skin disappears even earlier. Hair loss, which often accompanies seborrhea, is also reduced. Therapy with Diane-35 in women of reproductive age reduces the clinical manifestations of mild forms of hirsutism (in particular, increased growth of facial hair); however, the effect of treatment should be expected only after several months of use. Along with the above-described antiandrogenic effect, cyproterone acetate also has a pronounced gestagenic effect.

Pharmacokinetics

Cyproterone acetate

Absorption. When taken orally, cyproterone acetate is completely absorbed over a wide dose range. After oral administration of Diane-35 tablets, the maximum concentration (Cmax) of cyproterone acetate in serum, equal to 15 ng/ml, is achieved after 1.6 hours. The absolute bioavailability of cyproterone acetate is almost complete (88% of the dose). Distribution.

Cyproterone acetate binds exclusively to serum albumin. Only about 3.5-4% of the total concentration of blood serum is found in free form. The increase in SHPS induced by ethinyl estradiol does not affect the binding of cyproterone acetate to serum proteins. The average apparent volume of distribution is 986±437 l

Metabolism. Cyproterone acetate is metabolized in two ways, including hydroxylation and conjugation. The main metabolite in human plasma is a 15P-hydroxyl derivative.

Excretion. Some of the dose is excreted unchanged in bile. Most of the dose is excreted as metabolites in urine or bile in a 1:2 ratio. Metabolites from plasma are eliminated with a half-life of 1.8 days.

Equilibrium concentration. Since protein binding is not specific, changes in sex steroid binding globulin (SHBG) levels do not affect the pharmacokinetics of cyproterone acetate. During cyclic treatment, the maximum steady-state serum concentration of cyproterone acetate is achieved in the second half of the cycle.

Ethinyl estradiol

Absorption. After oral administration, ethinyl estradiol is rapidly and completely absorbed. The maximum concentration (Cmax) in the blood serum, equal to approximately 71 pg/ml, is achieved in 1.6 hours. During absorption and first passage through the liver, ethinyl estradiol is metabolized, resulting in its bioavailability when taken orally averaging about 45%.

Distribution. Ethinyl estradiol is almost completely (approximately 98%), although nonspecifically, bound by albumin. Ethinyl estradiol induces the synthesis of GSPC. The apparent volume of distribution of ethinyl estradiol is 2.8-8.6 l/kg.

Metabolism. Ethinyl estradiol undergoes presystemic conjugation, both in the mucosa of the small intestine and in the liver. The main route of metabolism is aromatic hydroxylation. The clearance rate from blood plasma is 2.3-7 ml/min/kg.

Excretion. The decrease in the concentration of ethinyl estradiol in the blood serum is biphasic; the first phase is characterized by a half-life of about 1 hour, the second - 10-20 hours. It is not excreted from the body unchanged. Ethinyl estradiol metabolites are excreted in urine and bile in a ratio of 4:6 with a half-life of about 24 hours.

Equilibrium concentration. Equilibrium concentration is achieved during the second half of the treatment cycle

Indications for use

Contraception in women with androgenization phenomena.

Treatment of androgen-dependent diseases in women, such as acne, especially common forms and forms accompanied by seborrhea, inflammation or nodule formation (papular-pustular acne, nodular-cystic acne); androgenetic alopecia and mild forms of hirsutism.

Contraindications

Diane-35 should not be used if you have any of the conditions listed below. If any of these conditions develop for the first time while taking the drug, the drug should be discontinued immediately.

• Thrombosis (venous and arterial) and thromboembolism currently or in history (including deep vein thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular disorders).
• Conditions preceding thrombosis (including transient ischemic attacks, angina) currently or in history.
• History of migraine with focal neurological symptoms
• Diabetes mellitus with vascular complications.
• Multiple or severe risk factors for venous or arterial thrombosis, including heart valve disease, heart rhythm disturbances, cerebrovascular disease or coronary artery disease; uncontrolled arterial hypertension.
• Pancreatitis with severe hypertriglyceridemia, currently or in history.
• Severe liver disease (until liver function tests return to normal).
• Liver tumors (benign or malignant) currently or in history.
• Identified hormone-dependent malignant diseases (including genital organs or mammary glands) or suspicion of them.
• Vaginal bleeding of unknown origin.
• Pregnancy or suspicion of it.
• Breastfeeding period.
• Hypersensitivity to any of the components of the drug Diane-35

Carefully

If any of the conditions/risk factors listed below currently exist, the potential risks and expected benefits of combined oral contraceptives should be carefully weighed in each individual case:

• Risk factors for the development of thrombosis and thromboembolism: smoking; thrombosis, myocardial infarction or cerebrovascular accident at a young age in one of the immediate family; obesity; dyslipoproteinemia (eg, hypertension; migraine; heart valve disease; cardiac arrhythmias, prolonged immobilization, major surgery, major trauma
• Other diseases in which peripheral circulatory disorders may occur: diabetes mellitus; systemic lupus erythematosus; hemolytic uremic syndrome; Crohn's disease and ulcerative colitis; sickle cell anemia; as well as phlebitis of superficial veins
• Hypertriglyceridemia
• Liver diseases
• Diseases that first appeared or worsened during pregnancy or against the background of previous use of sex hormones (for example, jaundice, cholestasis, gallbladder disease, otosclerosis with hearing impairment

Pregnancy and lactation
Diane-35 is not prescribed during pregnancy and breastfeeding. If pregnancy is detected while taking Diane-35, the drug should be discontinued immediately. Cyproterone acetate is excreted in milk, so the use of Diane-35 is contraindicated during lactation

Directions for use and doses
Dragee Diane-35 should be taken orally in the order indicated on the package, every day at approximately the same time, with a small amount of water. Take one tablet per day continuously for 21 days. The next package begins after a 7-day break from taking the pills, during which withdrawal bleeding usually occurs. Bleeding usually begins 2-3 days after taking the last pill and may not stop until you start taking a new package.

The duration of use depends on the severity of androgenization symptoms, as well as their response to treatment. As a rule, treatment should be continued for several months. With acne and seborrhea, the response usually occurs earlier than with hirsutism or alopecia.

After the symptoms have subsided, it is recommended to take Diane-35 for at least 3-4 more cycles. If a relapse occurs a few weeks or months after stopping taking the pills, treatment with Diane-35 can be resumed. If signs of androgenization recur after stopping treatment, the possibility of earlier resumption of Diane-35 should be considered.

How to start taking Diane-35

• If you have not taken any hormonal contraceptives in the previous month.
  Taking Diane-35 begins on the first day of the menstrual cycle (i.e., on the first day of menstrual bleeding). It is allowed to start taking it at 2-5 menstrual cycles, but in this case it is recommended to additionally use a barrier method of contraception during the first 7 days of taking pills from the first package.
• When switching from other combined oral contraceptives.
  It is preferable to start taking Diane-35 the day after taking the last active tablet from the previous package, but in no case later than the next day after the usual 7-day break (for preparations containing 21 tablets).
  When switching from contraceptives containing only gestagens (mini-pills, injectable forms, implant) or from a gestagen-releasing intrauterine contraceptive.
  A woman can switch from the “mini-pill” to Diana-35 on any day (without a break), from an implant or intrauterine contraceptive with gestagen - on the day of its removal, from the injection form - from the day when the next injection would have been given. In all cases, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the pill.
• After an abortion in the first trimester of pregnancy.
  A woman can start taking the drug immediately. If this condition is met, the woman does not need additional contraceptive protection.
• After childbirth or abortion in the second trimester of pregnancy. It is recommended to start taking the drug 21-28 days after childbirth or abortion in the second trimester of pregnancy. If use is started later, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the pill. However, if a woman has already been sexually active, pregnancy should be excluded before starting Diane-35 or she must wait until her first menstruation.

Taking missed pills

If the delay in taking the drug is less than 12 hours, contraceptive protection is not reduced. A woman should take a pill as soon as possible, and the next one should be taken at the usual time.

If the delay in taking the pill is more than 12 hours, contraceptive protection may be reduced. In this case, you can be guided by the following two basic rules:

The drug should never be interrupted for more than 7 days.

7 days of continuous administration of the pills are required to achieve adequate suppression of hypothalamic-pituitary-ovarian regulation.

Accordingly, the following advice can be given if the delay in taking the pill is more than 12 hours (the interval since the last pill was taken is more than 36 hours):

First week of taking the drug

A woman should take the last pill she missed as soon as she remembers (even if this means taking two pills at the same time). The next pill is taken at the usual time. Additionally, 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 missing the pills, the possibility of pregnancy must be taken into account. The more tablets are missed, and the closer they are to a break in taking active substances, the greater the likelihood of pregnancy.

Second week of taking the drug

A woman should take the last pill she missed as soon as she remembers (even if this means taking two pills at the same time). The next pill is taken at the usual time.

Provided that the woman took the pill correctly during the 7 days preceding the first missed pill, there is no need to use additional contraceptive measures. Otherwise, as well as if you miss two or more pills, you must additionally use barrier methods of contraception (for example, a condom) for 7 days.

Third week of taking the drug

The risk of decreased reliability is inevitable due to the upcoming break in taking the pill.

A woman must strictly adhere to one of the following two options. Moreover, if in the 7 days preceding the first missed pill, all pills were taken correctly, there is no need to use additional contraceptive methods.

1. A woman should take the last pill she missed as soon as she remembers (even if this means taking two pills at the same time). The next pill is taken at the usual time, until the pills from the current package run out. The next pack should be started immediately. Withdrawal bleeding is unlikely until the second pack is finished, but spotting and breakthrough bleeding may occur while taking the pill.
2. A woman can also stop taking pills from the current package. She should then take a break for 7 days, including the day she missed the pills, and then start taking a new pack.

If a woman misses taking the pill and then does not have withdrawal bleeding during the break from taking the pill, pregnancy must be ruled out.

Recommendations in case of vomiting and diarrhea
If a woman has vomiting or diarrhea within 4 hours of taking active tablets, absorption may not be complete and additional contraceptive measures should be taken. In these cases, you should follow the recommendations when skipping pills.

Changing the start day of the menstrual cycle
In order to delay the onset of menstruation, a woman should continue taking pills from the new Diane-35 package immediately after taking all the pills from the previous one, without interruption. The pills from this new package can be taken for as long as the woman wishes (until the package runs out). While taking the drug from the second package, a woman may experience spotting or breakthrough uterine bleeding. You should resume taking Diane-35 from a new pack after the usual 7-day break.

In order to postpone the start of menstruation to another day of the week, a woman should be advised to shorten the next break in taking the pills by as many days as she wants. The shorter the interval, the higher the risk that she will not have withdrawal bleeding, and will continue to have spotting and breakthrough bleeding while taking the second pack (just as if she wanted to delay the onset of menstruation.

Side effect
When taking combined oral contraceptives, irregular bleeding (spotting or breakthrough bleeding) may occur, especially during the first months of use. Other undesirable effects have been observed in women while taking combined oral contraceptives.

Organ system	Often (≥1/100)	Uncommon (≥1/1000 and ≤1/100)	Rarely (≤1/1000)
Organ of vision			intolerance to contact lenses
Gastrointestinal tract	nausea, abdominal pain	vomiting, diarrhea
The immune system			hypersensitivity reactions
General symptoms	weight gain		Weight loss
Metabolism		fluid retention
Nervous system	headache	migraine
Psychiatric disorders	decreased mood, mood swings	decreased libido	increased libido
Reproductive system and mammary glands	breast pain, breast engorgement	mammary hypertrophy	vaginal discharge, breast discharge
Skin and subcutaneous tissues		rash, hives	Erythema nodosum, multiforme

As with other combined oral contraceptives, in rare cases the development of thrombosis and thromboembolism is possible (see also “Special Instructions”).

Overdose
No serious adverse events have been reported following overdose. Symptoms that may occur in case of overdose: nausea, vomiting, spotting or metrorrhagia. There is no specific antidote; symptomatic treatment should be carried out.

Interaction with other drugs
Interaction of oral contraceptives with other drugs may lead to breakthrough bleeding and/or decreased contraceptive reliability. The following types of interactions have been reported in the literature.

Effect on hepatic metabolism: the use of drugs that induce microsomal liver enzymes can lead to an increase in the clearance of sex hormones. Such drugs include: phenytoin, barbiturates, primidone, carbamazepine, rifampicin; There are also suggestions for oxcarbazepine, topiramate, felbamate, ritonavir and griseofulvin and products containing St. John's wort.

Effect on enterohepatic circulation: According to individual studies, some antibiotics (for example, penicillins and tetracyclines) may reduce the enterohepatic circulation of estrogens, thereby lowering the concentration of ethinyl estradiol.

While taking medications that affect microsomal enzymes, and for 28 days after their discontinuation, you should additionally use a barrier method of contraception.

While taking antibiotics (such as ampicillins and tetracyclines) and for 7 days after their discontinuation, you should additionally use a barrier method of contraception. If the period of using the barrier method of protection ends later than the pill in the package, you need to move on to the next package of Diane-35 without the usual break in taking the pill. Oral combined contraceptives may affect the metabolism of other drugs (including cyclosporine), which leads to changes in their concentrations in plasma and tissues.

special instructions
If any of the conditions/risk factors listed below currently exist, the potential risks and expected benefits of treatment with Diane-35 should be carefully weighed in each individual case and discussed with the woman before she decides to start taking the drug. If any of these conditions or risk factors worsen, intensify, or appear for the first time, a woman should consult her doctor, who may decide whether to discontinue the drug.

Diseases of the cardiovascular system
There is evidence of an increased incidence of venous and arterial thrombosis and thromboembolism (such as deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke) when taking combined oral contraceptives.

The risk of developing venous thromboembolism (VTE) is greatest in the first year of taking such drugs. Estimated incidence of VTE among women taking low-dose oral contraceptives (The risk of thrombosis (venous and/or arterial) and thromboembolism increases:

• with age
• in smokers (with increasing number of cigarettes or increasing age, the risk further increases, especially in women over 35 years of age); if there is:
• family history (i.e., venous or arterial thromboembolism ever in close relatives or parents at a relatively young age); in case of hereditary predisposition, the woman should be examined by an appropriate specialist to decide on the possibility of taking combined oral contraceptives;
• obesity (body mass index more than 30 kg/m);
• dyslipoproteinemia;
• arterial hypertension;
• migraine;
• heart valve diseases;
• atrial fibrillation;
• prolonged immobilization, major surgery, any leg surgery or major trauma. In these situations, it is advisable to stop using combined oral contraceptives (in the case of planned surgery, at least four weeks before it) and not to resume use for two weeks after the end of immobilization.

The possible role of varicose veins and superficial thrombophlebitis in the development of venous thromboembolism remains controversial. The increased risk of thromboembolism in the postpartum period should be taken into account. Peripheral circulatory disorders may also occur in diabetes mellitus, systemic lupus erythematosus, hemolytic uremic syndrome, chronic inflammatory bowel disease (Crohn's disease or ulcerative colitis) and sickle cell anemia. An increase in the frequency and severity of migraine during use of combined oral contraceptives (which may precede cerebrovascular events) may be grounds for immediate discontinuation of these drugs. Tumors There have been reports of a slight increase in the risk of developing cervical cancer with long-term use of combined oral contraceptives. The connection with the use of combined oral contraceptives has not been proven. Controversy remains regarding the extent to which these findings are related to screening for cervical pathology or to sexual behavior (lower use of barrier methods of contraception). The most significant risk factor for developing cervical cancer is persistent papilloma viral infection.

It was also found that there is a slightly increased relative risk of developing breast cancer diagnosed in women who used combined oral contraceptives. The increased risk gradually disappears within 10 years of stopping these drugs. Its connection with the use of combined oral contraceptives has not been proven. The observed increased risk may also be a consequence of earlier diagnosis of breast cancer in women using combined oral contraceptives. Women who have ever used combined oral contraceptives are diagnosed with earlier stages of breast cancer than women who have never used them. In rare cases, during the use of combined oral contraceptives, the development of liver tumors has been observed, which in some cases led to life-threatening intra-abdominal bleeding. If severe abdominal pain, liver enlargement, or signs of intra-abdominal bleeding occur, this should be taken into account when making a differential diagnosis.

Other states
Women with hypertriglyceridemia (if there is a family history of this condition) may have an increased risk of developing pancreatitis while taking combined oral contraceptives.

Although slight increases in blood pressure have been described in many women taking combined oral contraceptives, clinically significant increases have rarely been reported. However, if a persistent, clinically significant increase in blood pressure develops while taking combined oral contraceptives, these drugs should be discontinued and treatment of hypertension should be initiated. Taking combined oral contraceptives can be continued if normal blood pressure values ​​are achieved with antihypertensive therapy.

The following conditions have been reported to develop or worsen both during pregnancy and while taking combined oral contraceptives, but their relationship with taking combined oral contraceptives has not been proven: jaundice and/or pruritus associated with cholestasis; formation of gallstones; porphyria; systemic lupus erythematosus; hemolytic uremic syndrome; chorea; herpes during pregnancy; hearing loss associated with otosclerosis. Cases of Crohn's disease and ulcerative colitis have also been described during the use of combined oral contraceptives.

Chloasma can sometimes develop, especially in women with a history of pregnancy chloasma. Women prone to chloasma should avoid prolonged exposure to the sun and ultraviolet radiation while taking combined oral contraceptives. Acute or chronic liver dysfunction may require discontinuation of combined oral contraceptives until liver function tests return to normal. Recurrence of cholestatic jaundice, which developed for the first time during pregnancy or previous use of sex hormones, requires discontinuation of combined oral contraceptives.

Although combined oral contraceptives may have an effect on insulin resistance and glucose tolerance, there is no need to change the therapeutic regimen in diabetic patients using low-dose combined oral contraceptives (If a woman with hirsutism has had recent or severe symptoms, treatment should be A differential diagnosis was carried out to identify the possible cause of the disease (androgen-producing tumor, deficiency of adrenal enzymes).

Laboratory tests
Taking combined oral contraceptives may affect the results of some laboratory tests, including liver, kidney, thyroid, adrenal function, plasma transport protein levels, carbohydrate metabolism, coagulation and fibrinolysis parameters. Changes usually do not go beyond normal values.

Effect on the menstrual cycle
While taking combined oral contraceptives, irregular bleeding (spotting or breakthrough bleeding) may occur, especially during the first months of use. Therefore, any irregular bleeding should be assessed only after an adaptation period of approximately three cycles. If irregular bleeding recurs or develops after previous regular cycles, careful evaluation should be performed to rule out malignancy or pregnancy.

Some women may not develop withdrawal bleeding during a break from taking the tablets. If combined oral contraceptives are taken as directed, the woman is unlikely to be pregnant. However, if combined oral contraceptives have not been taken regularly before or if there are no consecutive withdrawal bleeds, pregnancy should be ruled out before continuing to take the drug.

Medical examinations
Before starting to use the drug Diane-35, a woman is recommended to undergo a thorough general medical and gynecological examination (including examination of the mammary glands and cytological examination of cervical secretions) and exclude pregnancy. In addition, disorders of the blood coagulation system should be excluded.

In case of long-term use of the drug, it is necessary to conduct control examinations every 6 months.

A woman should be warned that drugs like Diane-35 do not protect against HIV infection (AIDS) and other sexually transmitted diseases!

Impact on the ability to drive a car and equipment.
Not found.

Release form
Dragee. 21 tablets per blister made of PVC and aluminum foil. The blister along with instructions for use is placed in a cardboard box

Storage conditions
At a temperature not higher than 30°C. Keep out of the reach of children.

Best before date
5 years. Do not use after expiration date!

Conditions for dispensing from pharmacies
On prescription.

Manufacturer
Bayer Schering Pharma AG, produced by Schering GmbH & Co. Productions KG, Germany
Bayer Schering Pharma AG, manufactured by Schering GmbH & Co. Products KG, Germany

Additional information can be obtained at: 107113 Russia, Moscow, 3rd Rybinskaya st., 18, building 2.

Oral contraceptive pills are currently considered one of the most reliable methods of contraception. They contain hormones that can prevent conception. "Diane-35" is a hormonal complex contraceptive that has an additional antiandrogenic effect. The drug is used not only to prevent unwanted pregnancy, but also to treat certain pathological conditions. Analogues of “Diana-35” should be selected by a specialist.

Description of the drug

Recently, an increasing number of women are choosing hormonal contraceptives in the form of oral tablets to protect against unwanted pregnancy. Taking into account the individual characteristics of the female body, you can choose the optimal remedy from this pharmacological group.

The most popular are combined monophasic drugs, the representative of which is Diane-35. Analogs of the drug can be structural (based on active components) or have a similar mechanism of action.

This drug contains two active ingredients:

• ethinyl estradiol (35 mcg);
• (2 mg).

The first component is a synthetic analogue of the natural hormone estradiol. Cyproterone, a synthetic derivative of the hormone progesterone, which has an antiandrogenic effect, is responsible for the gestagenic effect.

Thanks to the complex effect of the two substances, the ovulation process is stopped and sperm permeability is reduced due to changes in the structure of the mucous secretion.

Antiandrogenic contraceptives

Analogues of Diana-35 with an antiandrogenic effect are suitable for girls and women facing the problem of hyperandrogenism. The pathological condition occurs against the background of increased levels of male hormones, the following symptoms develop:

• seborrhea;
• hair growth on the cheeks, abdomen, mammary glands;
• changes in the menstrual cycle;
• problems with pregnancy, infertility;
• excess weight.

To treat pathology and normalize, gynecologists recommend that many patients take contraceptives based on two hormones. "Diane-35" is one of the most effective drugs in this category. The contraceptive effect occurs on the 14th day after starting the medication.

Structural analogues of Diana-35 (with an antiandrogenic effect) can also affect the synthesis of sex hormones. Estrogens contained in contraceptives reduce the level of testosterone in the blood serum. They suppress the production of male hormone in the ovaries (by suppressing the secretion of estrogens in combination with progesterone. The duration of treatment with hormonal contraceptives with antiandrogenic action is at least 6 menstrual cycles.

How to choose an analogue of “Diana-35”

Based on the composition, choosing a substitute for the original drug will not be difficult. Pharmaceutical companies offer a fairly large number of hormonal contraceptives in tablets containing several active ingredients. Some may be two or three phase. In such preparations, the concentration of the hormone estrogen will gradually increase towards the middle of the menstrual cycle.

The following contraceptives are considered the most effective:

1. "Janine."
2. "Logest".
3. "Erika-35".
4. "Belara."
5. "Jess."
6. "Belluna-35".
7. "Chloe."
8. "Tri-Mercy."

Any contraceptive medication should be prescribed to a woman only by a doctor after an examination. In order to select the optimal remedy, it is necessary to undergo laboratory tests and ultrasound of the pelvic organs. And after starting therapy, the woman is recommended to undergo a re-examination after 3 months.

If side effects occur, you should contact a specialist who will select the optimal drugs - analogues of Diana-35. The instructions for each hormonal contraceptive contain a list of pathological conditions for which it is prohibited to take this medicine.

Hormonal tablets "Jess"

Reviews from women about the popular analogue of the drug “Diana-35” confirm the high effectiveness of the drug. Gynecologists often recommend that girls take them not only for contraception, but also for the treatment of acne.

Jess tablets have a similar mechanism of action and are low-dose. But according to reviews, it is not advisable to take a contraceptive on your own. Both doctors and patients note that without a preliminary blood test for hormone levels, taking the medication can cause a lot of unpleasant side effects.

If oral contraception is not selected correctly, the skin may suffer, acne may appear, body weight may increase, and periodic attacks of nausea, dizziness and vomiting are also possible.

The drug "Janine"

Some analogues of Diana-35 may have a similar mechanism of therapeutic action and at the same time not be the same in composition as the original. The drug “Zhanine” has antiandrogenic properties. Birth control pills are a low-dose monophasic drug. They use substances such as ethinyl estradiol and dienogest (a derivative of nortestosterone) as active ingredients.

Reviews about the drug can often be heard from young nulliparous girls. It is this remedy that is predominantly prescribed by specialists in this category of patients. The drug is well tolerated by the body, rarely provokes excess weight gain, and significantly improves the condition of hair and nails.

Reviews of tablets "Chloe"

Any analogues of Diana-35 have both advantages and disadvantages. In cases where a girl starts taking a hormonal drug without prior examination, the likelihood of developing side effects increases significantly.

Thus, reviews of women and doctors warn about the development of some unpleasant symptoms while taking Chloe tablets. Most often, this condition occurs when the rules for selecting hormonal contraceptives are not followed.

Doctors recommend that some girls take the drug “Chloe” to normalize the menstrual cycle, eliminate signs of PMS, and skin rashes. And if the drug was prescribed correctly, a positive result should be observed after a month of taking the contraceptive.

Some girls, by the way, talk about such a pleasant side effect caused by the drug as breast enlargement. In addition, Chloe can really help get rid of acne and improve the functioning of the sebaceous glands.

Contraceptive "Tri-Mercy"

According to experts, they are easy to use. The effectiveness of such tablets is 99%. Many substitutes for the drug Diane-35 contain minimal doses of hormones.

New generation analogues can be three-phase, that is, the concentration of hormonal substances in them changes throughout the entire cycle. This allows you to maintain the normal rhythm of the menstrual cycle and not disrupt hormonal levels.

Oral contraceptive "Tri-Mercy" refers to combined three-phase medications. It uses desogestrel and ethinyl estradiol as active ingredients. The package contains three strips of tablets of different colors:

1. The yellow pills contain 0.035 mg ethinyl estradiol and 0.050 mg desogestrel.
2. The red tablets contain 0.030 mg of ethinyl estradiol and an increased amount of desogestrel - 0.100 mg.
3. In white pills, the concentration of ethinyl estradiol is also maintained at 0.30 mg, and desogestrel is increased to 0.150 mg.

"Diana-35" or "Tri-Mercy"?

Many girls face this choice. It should be borne in mind that doctors do not recommend choosing hormonal contraceptives on your own. The optimal remedy is selected by a specialist after collecting the patient’s medical history and laboratory test results.

The gynecologist takes into account the nature of menstruation, the duration of the cycle, the tendency to premenstrual pain, and the development of the mammary glands in order to choose the right oral contraceptives.

Drugs with antiandrogenic effects and contraception are suitable for many women. Diane-35 also causes virtually no side effects. Cheaper analogues are not always well tolerated and can provoke the development of some undesirable consequences:

• swelling of the legs;
• dizziness;
• odor intolerance;
• intermenstrual bleeding;
• weight gain;
• nausea.

Tri-Mercy is a fairly inexpensive and effective contraceptive. The cost of tablets is 820-880 rubles. Many women who have taken this drug talk about its positive effect on their skin condition. Tri-Mercy causes side effects extremely rarely.

Birth control pills "Belara"

"Belara" is another popular antiandrogenic hormonal drug. The tablets contain the same amount of hormones in the composition, that is, the drug is monophasic, like some other analogues of Diana-35.

Manufacturer: Schering AG (Schering AG) Germany

ATC code: G03HB01

Farm group:

Release form: Solid dosage forms. Dragee.

General characteristics. Compound:

Active ingredients: 2 mg of cyproterone acetate and 0.035 mg of ethinyl estradiol.
Excipients: lactose monohydrate - 31.115 mg, corn starch
- 18,000 mg, povidone - 2,100 mg, talc - 1,650 mg, magnesium stearate - 0,100 mg.
shell composition: sucrose - 19.371 mg, povidone 700000 - 0.189 mg, polyethylene glycol (macrogol 6000) - 2.148 mg, calcium carbonate - 8.606 mg, talc
- 4.198 mg, glycerol - 0.137 mg, titanium dioxide - 0.274 mg, iron (II) yellow oxide - 0.027 mg, mountain glycol wax - 0.050 mg.

Description. Round biconvex dragees of light yellow color.

Pharmacological properties:

Pharmacodynamics. Diane-35 is a low-dose monophasic oral combined estrogen-antiandrogen contraceptive drug.
The contraceptive effect of Diane-35 is carried out through complementary mechanisms, the most important of which include suppression of ovulation and changes in the properties of cervical secretion, as a result of which it becomes impenetrable to sperm.
In women taking combined oral contraceptives, the menstrual cycle becomes more regular, painful menstruation is less common, and the intensity decreases, resulting in a reduced risk. In addition, there is evidence that the risk of developing and is reduced.
While taking Diane-35, the increased activity of the sebaceous glands, which plays an important role in the occurrence of acne and seborrhea, decreases. After 3-4 months of therapy, this usually leads to the disappearance of the existing rash. Excessive oiliness in hair and skin disappears even earlier. Hair loss, which often accompanies seborrhea, is also reduced. Therapy with Diane-35 in women of reproductive age reduces the clinical manifestations of mild forms of hirsutism (in particular, increased growth of facial hair); however, the effect of treatment should be expected only after several months of use.
Along with the above-described antiandrogenic effect, cyproterone acetate also has a pronounced gestagenic effect.

Pharmacokinetics. . Cyproterone acetate
Absorption. When taken orally, cyproterone acetate is completely absorbed over a wide dose range. After oral administration of Diane-35 tablets, the maximum concentration (Cmax) of cyproterone acetate in serum, equal to 15 ng/ml, is achieved after 1.6 hours. The absolute bioavailability of cyproterone acetate is almost complete (88% of the dose).
Distribution.
Cyproterone acetate binds exclusively to serum albumin. Only about 3.5-4% of the total concentration of blood serum is found in free form. The increase in SHPS induced by ethinyl estradiol does not affect the binding of cyproterone acetate to serum proteins. The average apparent volume of distribution is 986±437 l

Metabolism. Cyproterone acetate is metabolized in two ways, including hydroxylation and conjugation. The main metabolite in human plasma is a 15P-hydroxyl derivative.
Excretion. Some of the dose is excreted unchanged in bile. Most of the dose is excreted as metabolites in urine or bile in a 1:2 ratio. Metabolites from plasma are eliminated with a half-life of 1.8 days.
Equilibrium concentration. Since protein binding is not specific, changes in sex steroid binding globulin (SHBG) levels do not affect the pharmacokinetics of cyproterone acetate. During cyclic treatment, the maximum steady-state serum concentration of cyproterone acetate is achieved in the second half of the cycle.

Ethinyl estradiol
Absorption. After oral administration, ethinyl estradiol is rapidly and completely absorbed. The maximum concentration (Cmax) in the blood serum, equal to approximately 71 pg/ml, is achieved in 1.6 hours. During absorption and first passage through the liver, ethinyl estradiol is metabolized, resulting in its bioavailability when taken orally averaging about 45%.
Distribution. Ethinyl estradiol is almost completely (approximately 98%), although nonspecifically, bound by albumin. Ethinyl estradiol induces the synthesis of GSPC. The apparent volume of distribution of ethinyl estradiol is 2.8-8.6 l/kg.
Metabolism. Ethinyl estradiol undergoes presystemic conjugation, both in the mucosa of the small intestine and in the liver. The main route of metabolism is aromatic hydroxylation. The clearance rate from blood plasma is 2.3-7 ml/min/kg.
Excretion. The decrease in the concentration of ethinyl estradiol in the blood serum is biphasic; the first phase is characterized by a half-life of about 1 hour, the second - 10-20 hours. It is not excreted from the body unchanged. Ethinyl estradiol metabolites are excreted in urine and bile in a ratio of 4:6 with a half-life of about 24 hours.
Equilibrium concentration. Equilibrium concentration is achieved during the second half of the treatment cycle.

Indications for use:

Contraception in women with androgenization phenomena.
Treatment of androgen-dependent diseases in women, such as, especially common forms and forms accompanied by seborrhea, inflammation or the formation of nodules (papular-pustular acne, nodular-cystic acne); and mild forms of hirsutism.

Important! Get to know the treatment

Directions for use and dosage:

To achieve a therapeutic effect and provide the necessary contraception, Diane-35 should be taken regularly. If any other hormonal contraceptive drug was used before starting Diane-35, its use should be discontinued. The dosage regimen for Diane-35 coincides with the dosage regimen for most oral contraceptives. Thus, the rules for taking other oral contraceptives apply to taking Diane-35. Irregular use of Diane-35 can lead to intermenstrual bleeding, a decrease in the therapeutic effect and contraceptive effectiveness. When used correctly, the Perl index is approximately 1.
Dragee Diane-35 should be taken orally in the order indicated on the package, every day at approximately the same time, with a small amount of water. Take one tablet per day continuously for 21 days. The next package begins after a 7-day break from taking the pills, during which withdrawal bleeding usually occurs. Bleeding usually begins 2-3 days after taking the last pill and may not stop until you start taking a new package.
How to start taking Diane-35
. If you have not taken any hormonal contraceptives in the previous month.
Taking Diane-35 begins on the first day of the menstrual cycle (i.e., on the first day of menstrual bleeding).
It is allowed to start taking it on days 2-5 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 taking the pills from the first package.
. When switching from other combined oral contraceptives, vaginal ring or contraceptive patch.
It is preferable to start taking Diane-35 the day after taking the last hormonal pill from the previous package, but in no case later than the next day after the usual 7-day break (for drugs containing 21 pills) or after taking the last inactive pill (for drugs containing 28 tablets per package).
Taking Diane-35 should begin on the day the vaginal ring or patch is removed, but no later than the day when a new ring is to be inserted or a new patch is applied.
. When switching from contraceptives containing only gestagens (mini-pills, injection forms, implant), or from a gestagen-releasing intrauterine therapeutic system (Mirena).
You can switch from the mini-pill to Diana-35 on any day (without a break), from an implant or intrauterine contraceptive with gestagen - on the day of its removal, from the injection form - from the day when the next injection is due. In all cases, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the pill.
. After an abortion in the first trimester of pregnancy.
A woman can start taking the drug immediately - on the day of the abortion. If this condition is met, the woman does not need additional contraceptive protection.
. After childbirth or abortion in the second trimester of pregnancy.
You should start taking the drug no earlier than 21-28 days after birth in the absence of breastfeeding or after an abortion in the second trimester of pregnancy. If you start taking it later, you must use an additional barrier method of contraception during the first 7 days of taking the pill. However, if a woman has already been sexually active, before starting Diane-35 it is necessary to exclude pregnancy or wait until her first menstruation.
Taking missed pills
If the delay in taking the drug is less than 12 hours, contraceptive protection is not reduced. A woman should take a pill as soon as possible, and the next one should be taken at the usual time.
If the delay in taking the pill is more than 12 hours, contraceptive protection may be reduced. The more tablets you miss, and the closer the missed tablet is to the 7-day break in taking the tablets, the greater the likelihood of pregnancy.
In this case, you can be guided by the following two basic rules:
. The drug should never be interrupted for more than 7 days.
. To achieve adequate suppression of hypothalamic-pituitary-ovarian regulation, 7 days of continuous use of the pill are required.
Accordingly, the following advice can be given if the delay in taking the pill is more than 12 hours (the interval since the last pill was taken is more than 36 hours):
. First week of taking the drug
A woman should take the last pill she missed as soon as she remembers (even if this means taking two pills at the same time). The next pill is taken at the usual time. Additionally, 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 missing the pills, the possibility of pregnancy must be taken into account.
. Second week of taking the drug
A woman should take the last pill she missed as soon as she remembers (even if this means taking two pills at the same time). The next pill is taken at the usual time.
Provided that the woman took the pill correctly during the 7 days preceding the first missed pill, there is no need to use additional contraceptive measures. Otherwise, as well as if you miss two or more pills, you must additionally use barrier methods of contraception (for example, a condom) for 7 days.
. Third week of taking the drug
The risk of pregnancy increases due to the upcoming break in taking the tablets, however, if during the 7 days preceding the first missed tablet all tablets were taken correctly, there is no need to use additional contraceptive methods.
1. A woman should take the last pill she missed as soon as she remembers (even if this means taking two pills at the same time). The next pills are taken at the usual time, until the pills from the current package run out. The next pack should be started immediately. Withdrawal bleeding is unlikely until the second pack is finished, but spotting and breakthrough bleeding may occur while taking the pill.
2. A woman can also stop taking pills from the current package. She should then take a break for 7 days, including the day she missed the pills, and then start taking a new pack.
If a woman misses taking a pill and then does not have withdrawal bleeding during a break in taking it, pregnancy must be ruled out.
Recommendations in case of vomiting and diarrhea
In case of vomiting or diarrhea within 4 hours after taking the pills, absorption may not be complete; accordingly, additional measures must be taken to protect against unwanted pregnancy. In such cases, you should follow the above recommendations when skipping pills.
Changing the start day of the menstrual cycle
In order to delay the onset of menstruation, a woman should continue taking pills from the new Diane-35 package immediately after taking all the pills from the previous one, without interruption. The pills from this new package can be taken for as long as the woman wishes (until the package runs out). While taking the drug from the second package, a woman may experience spotting or breakthrough uterine bleeding. You should resume taking Diane-35 from a new pack after the usual 7-day break.
In order to postpone the start of menstruation to another day of the week, a woman should be advised to speed up the next break in taking the pill by as many days as she wants. The shorter the interval, the higher the risk that she will not have withdrawal bleeding, and will continue to have spotting and breakthrough bleeding while taking the second package (just as in the case when she would like to delay the onset of menstruation.
Duration of use
The duration of taking the pills depends on the severity of androgenization symptoms and response to treatment. Basically, treatment is carried out over several months. The response to treatment for acne and seborrhea usually occurs faster than the response to treatment for hirsutism or alopecia.
It is recommended to take the drug for at least 3 to 4 courses after the signs of the disease disappear. In case of relapse of the disease several weeks or months after stopping taking the pills, treatment with Diane-35 can be resumed. If you resume taking the drug (after a break of four weeks or more), the increased risk of VTE should be taken into account (see also the section “Special instructions” and “With caution”).
Additional information for certain patient groups
Children and teenagers.
The drug Diane-35 is indicated only after the onset of menarche. Elderly patients
Not applicable. The drug Diane-35 is not indicated after menopause. Patients with liver disorders
The drug Diane-35 is contraindicated in women with severe liver disease until liver function indicators return to normal. See also section "Contraindications".
Patients with kidney disorders
Diane-35 has not been specifically studied in patients with renal impairment. Available data do not suggest changes in treatment in these patients.

Features of application:

If any of the conditions/risk factors listed below currently exist, the potential risks and expected benefits of treatment with Diane-35 should be carefully weighed in each individual case and discussed with the woman before she decides to start taking the drug. If any of these conditions or risk factors worsen, intensify, or appear for the first time, a woman should consult her doctor, who may decide whether to discontinue the drug.
. Diseases of the cardiovascular system
There is evidence of an increased incidence of venous and arterial thrombosis and thromboembolism (such as myocardial infarction) when taking combined oral contraceptives.
The risk of developing venous thromboembolism (VTE) is greatest in the first year of taking such drugs. An increased risk is present after initial use of combined oral contraceptives or resumption of use of the same or different combined oral contraceptives (after a dosing interval of 4 weeks or more). Data from a large prospective study involving 3 groups of patients indicate that this increased risk is primarily present during the first 3 months.
The overall risk of venous thromboembolism (VTE) in patients taking low-dose combined oral contraceptives (< 50 мкг этинилэстрадиола) в два-три раза выше, чем у пациентов, которые не принимают комбинированные пероральные контрацептивы, не беременны, и он остается более низким по сравнению с риском беременности и родов.
Very rarely, VTE can cause disability or death.
Venous thromboembolism (VTE), manifesting as deep vein or pulmonary embolism, can occur with the use of any combined oral contraceptives.
It is extremely rare that when using combined oral contraceptives, thrombosis of other blood vessels occurs, for example, veins or arteries of the liver, mesenteric, renal, brain or retina. There is no general consensus regarding the relationship between the occurrence of these events and the use of combined oral contraceptives.
Symptoms of deep vein thrombosis (DVT) include swelling on one side of the leg or along a vein in the leg, pain or tenderness in the leg only when standing or walking, a feeling of warmth in the leg, redness or discoloration of the skin on the leg.
Symptoms of pulmonary embolism (PEA) include: sudden, unexplained or rapid breathing; sudden, including with blood; sharp chest pain that may get worse with deep breaths; sense of anxiety; strong; fast or irregular heartbeat. Some of these symptoms (eg, shortness of breath, cough) are nonspecific and may be misinterpreted as signs of more or less severe events (eg, respiratory tract infection).
Arterial thromboembolism can lead to stroke, vascular occlusion, or myocardial infarction. Symptoms of a stroke include: sudden weakness or loss of feeling in the face, arm or leg, especially on one side of the body, sudden confusion, problems with speech and comprehension; sudden loss of vision in one or both eyes; sudden disturbance in gait, dizziness, loss of balance or coordination; sudden, severe or prolonged for no apparent reason; loss of consciousness or fainting with or without an epileptic seizure. Other signs of vascular occlusion: sudden pain, swelling and mild blue discoloration of the extremities, acute abdomen.
Symptoms of myocardial infarction include: pain, discomfort, pressure, heaviness, a feeling of squeezing or fullness in the chest, arm, or under the breastbone; discomfort radiating to the back, cheekbone, larynx, arm, stomach; cold sweat, or dizziness, severe weakness, or shortness of breath; fast or irregular heartbeat.
Arterial thromboembolism can be fatal.
The risk of thrombosis (venous and/or arterial) and thromboembolism increases:
. with age
. in smokers (with increasing number of cigarettes or increasing age, the risk further increases, especially in women over 35 years of age);
in the presence of:
. family history (i.e., venous or arterial thromboembolism ever in close relatives or parents at a relatively young age); in case of hereditary predisposition, the woman should be examined by an appropriate specialist to decide on the possibility of taking combined oral contraceptives;
. obesity (body mass index more than 30 kg/m2);
. dyslipoproteinemia;
. arterial hypertension;
. migraine;
. heart valve diseases;
. atrial fibrillation;
. prolonged immobilization, major surgery, any leg surgery or major trauma. In these situations, it is advisable to stop using combined oral contraceptives (in the case of planned surgery, at least four weeks before it) and not to resume use for two weeks after the end of immobilization.
The question of the possible role of varicose veins and superficial ones in the development of venous thromboembolism remains controversial.
The increased risk of thromboembolism in the postpartum period should be taken into account.
Peripheral circulatory disorders can also be observed in diabetes mellitus, systemic lupus erythematosus, hemolytic uremic syndrome, chronic inflammatory bowel diseases (Crohn's disease or) and.
An increase in frequency and severity during the use of combined oral contraceptives (which may precede cerebrovascular events) may be grounds for immediate discontinuation of these drugs.
Biochemical indicators indicating a hereditary or acquired predisposition to venous or arterial thrombosis include the following: resistance to activated protein C, antithrombin III deficiency, protein C deficiency, protein S deficiency, antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant).
When assessing the benefit/risk ratio, the physician should consider that adequate treatment of the disease may reduce the associated risk of thrombosis and that the risk associated with pregnancy is greater than the risk associated with taking low-dose combined oral contraceptives (<0,05 мг этинилэстрадиола).
. Tumors
There are reports of a slight increase in the risk of cervical development with long-term use of combined oral contraceptives. The connection with the use of combined oral contraceptives has not been proven. It remains controversial to what extent these findings are associated with cervical pathology or with characteristics of sexual behavior (less frequent use of barrier methods of contraception). The most significant risk factor for development is persistent papilloma viral infection.
A meta-analysis of 54 epidemiological studies found that there is a slightly increased relative risk of developing breast cancer diagnosed in women currently taking combined oral contraceptives (relative risk 1.24). The increased risk gradually disappears within 10 years of stopping these drugs.
Because it is rare in women under 40 years of age, the increase in breast cancer diagnoses in women currently or recently taking combined oral contraceptives is small relative to the overall risk of the disease. Its connection with the use of combined oral contraceptives has not been proven. The observed increased risk may also be a consequence of earlier diagnosis of breast cancer in women using combined oral contraceptives. Women who have ever used combined oral contraceptives are diagnosed with earlier stages of breast cancer than women who have never used them.
In rare cases, during the use of combined oral contraceptives, development was observed, which in some cases led to life-threatening intra-abdominal bleeding. This should be taken into account when making a differential diagnosis in the event of severe abdominal pain, liver enlargement, or signs of intra-abdominal bleeding.
. Other states
In women with hypertriglyceridemia, while taking combined oral contraceptives (if there is a family history of this condition), there may be an increased risk of developing.
Although slight increases in blood pressure have been described in many women taking combined oral contraceptives, clinically significant increases have rarely been reported. However, if a persistent, clinically significant increase in blood pressure develops while taking combined oral contraceptives, these drugs should be discontinued and treatment should be initiated. Taking combined oral contraceptives can be continued if normal blood pressure values ​​are achieved with antihypertensive therapy.
The following conditions have been reported to develop or worsen both during pregnancy and while taking combined oral contraceptives, but their relationship with COC use has not been proven: jaundice and/or pruritus associated with cholestasis; formation of gallstones; ; ; hemolytic uremic syndrome; Sydenham; herpes during pregnancy; hearing loss associated with otosclerosis. Cases of Crohn's disease and ulcerative colitis have also been described during the use of combined oral contraceptives.
Chloasma can sometimes develop, especially in women with a history of pregnancy chloasma. Women with a tendency to chloasma should avoid prolonged exposure to the sun and exposure to ultraviolet radiation while taking COCs.
Acute or chronic liver dysfunction may require discontinuation of COCs until liver function tests return to normal. Recurrence of cholestatic jaundice, which developed for the first time during pregnancy or previous use of sex hormones, requires discontinuation of COC use.
Although combined oral contraceptives may have an effect on insulin resistance and glucose tolerance, there is no need to change the therapeutic regimen in diabetic patients using low-dose COCs (<0,05 мг этинилэстрадиола). Тем не менее, женщины с сахарным диабетом во время приема КОК должны тщательно наблюдаться.
If a woman with hirsutism has recent or severe symptoms, a differential diagnosis should be made to identify the possible cause of the disease (androgen-producing tumor, adrenal enzyme deficiency).

Laboratory tests
Taking combined oral contraceptives may affect the results of some laboratory tests, including liver, kidney, thyroid, adrenal function, plasma transport protein levels, carbohydrate metabolism, coagulation and fibrinolysis parameters. Changes usually do not go beyond normal values.

Effect on the menstrual cycle
While taking combined oral contraceptives, irregular bleeding (spotting or breakthrough bleeding) may occur, especially during the first months of use. Therefore, any irregular bleeding should be assessed only after an adaptation period of approximately three cycles.
If irregular bleeding recurs or develops after previous regular cycles, careful evaluation should be performed to rule out malignancy or pregnancy.
Some women may not develop withdrawal bleeding during a break from taking the tablets. If combined oral contraceptives are taken as directed, the woman is unlikely to be pregnant. However, if combined oral contraceptives have not been taken regularly before or if there are no consecutive withdrawal bleeds, pregnancy should be ruled out before continuing to take the drug.

Medical examinations
Before starting to use the drug Diane-35, a woman is recommended to undergo a thorough general medical and gynecological examination (including examination of the mammary glands and cytological examination of cervical mucus) and exclude pregnancy. In addition, disorders of the blood coagulation system should be excluded.
In case of long-term use of the drug, it is necessary to carry out control examinations regularly (approximately every 6 months).
A woman should be warned that drugs like Diane-35 do not protect against (AIDS) and other sexually transmitted diseases!

Impact on the ability to drive a car and equipment.
Not found.

Side effects:

Side effects that have been reported while taking COCs, but whose connection with taking the drug has not been confirmed or refuted.

Organ system Common (>1/100) Uncommon (>1/1000 and<1/100) Редко (<1/1000)
Organ of vision intolerance
contact lenses
Gastrointestinal nausea, pain, vomiting,
tract in the abdomen
Immune system reaction
hypersensitivity
General symptoms weight gain Weight loss
Metabolism fluid retention
Nervous system headache migraine
Psychiatric decreased mood, decreased libido increased libido
mood swing disorders
Reproductive system pain in the mammary glands, breast hypertrophy Vaginal discharge
and mammary glands, engorgement of the mammary glands, discharge from the mammary glands
Skin and
subcutaneous tissue rash,
erythema multiforme

The following serious adverse events have been reported in women using combined oral contraceptives. These adverse events are discussed in the “Special Instructions” section:
. Venous thromboembolic disorders
. Arterial thromboembolic disorders
. Stroke
. Hypertension
. Hypertriglyceridemia
. Changes in glucose tolerance or effect on peripheral insulin resistance
. Liver tumors (benign and malignant)
. Impaired liver function parameters
. Chloasma
. In women with hereditary angioedema, exogenous estrogens may cause or worsen symptoms of angioedema.
. The onset or worsening of conditions for which the connection with the use of combined oral contraceptives is not indisputable: jaundice and/or itching associated with cholestasis; formation of gallstones; porphyria; systemic lupus erythematosus; ; chorea; herpes during pregnancy; hearing loss associated with otosclerosis; Crohn's disease; ulcerative colitis; cervical cancer.
The incidence of breast cancer diagnosis in women using oral contraceptives is increased only slightly. Breast cancer is rarely observed in women under 40 years of age, the excess incidence is insignificant in relation to the overall risk of breast cancer. The cause-and-effect relationship between the occurrence of breast cancer and the use of COCs has not been established. For more information, see the “Contraindications” and “Special Instructions” sections.

Interaction with other drugs:

Interaction of oral contraceptives with other drugs may lead to breakthrough bleeding and/or decreased contraceptive effectiveness. Women taking these drugs should temporarily use barrier methods of contraception in addition to Diane-35, or choose another method of contraception. The following types of interactions have been reported in the literature.
Effect on hepatic metabolism: the use of drugs that induce liver microsomal enzymes can lead to an increase in the clearance of sex hormones. Such drugs include: phenytoin, barbiturates, primidone, carbamazepine, rifampicin; There are also suggestions for oxcarbazepine, topiramate, felbamate, griseofulvin and preparations containing St. John's wort. HIV protease inhibitors (eg, ritonavir) and non-nucleoside reverse transcriptase inhibitors (eg, nevirapine) and combinations thereof also have the potential to affect hepatic metabolism.
Effect on enterohepatic circulation: According to individual studies, some antibiotics (eg penicillins and tetracycline) may reduce the enterohepatic circulation of estrogens, thereby lowering the concentration of ethinyl estradiol.
While taking medications that affect microsomal enzymes, and for 28 days after their discontinuation, you should additionally use a barrier method of contraception.
While taking antibiotics (excluding rifampicin and griseofulvin) and for 7 days after their discontinuation, you should additionally use a barrier method of contraception. If the period of using the barrier method of protection ends later than the pill in the package, you need to move on to the next package of Diane-35 without the usual break in taking the pill. Oral combination contraceptives may affect the metabolism of other drugs, resulting in increased (eg cyclosporine) or decreased (eg lamotrigine) plasma and tissue concentrations.

Other forms of interaction
The use of drugs such as Diane-35 may affect the results of some laboratory tests, including biochemical parameters of the liver, plasma protein concentrations (for example, corticosteroid binding globulin, lipid/lipoprotein fractions, parameters of hemostasis and fibrinolysis, carbohydrate metabolism). These changes usually remain within normal physiological values.

Contraindications:

Diane-35 should not be used if you have any of the conditions listed below. If any of these conditions develop for the first time while taking the drug, the drug should be discontinued immediately.
. Thrombosis (venous and arterial) and thromboembolism currently or in history (including deep vein thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular disorders).
. Conditions preceding thrombosis (including transient ischemic attacks) currently or in history.
. History of migraine with focal neurological symptoms.
. Diabetes mellitus with vascular complications.
. Multiple or severe risk factors for venous or heart disease, including damage to the valvular apparatus of the heart, cardiac arrhythmia, cerebrovascular disease or coronary artery disease; uncontrolled arterial hypertension.
. Pancreatitis with severe hypertriglyceridemia, currently or in the future
medical history.
. Severe (until liver function tests return to normal).
. Liver tumors (benign or malignant) currently or in history.
. Identified hormone-dependent malignant diseases (including genital organs or mammary glands) or suspicion of them.
. Vaginal bleeding of unknown origin.
. Pregnancy or suspicion of it.
. Breastfeeding period.
. Hypersensitivity to any of the components of the drug Diane-35.
. Carefully
If any of the conditions/risk factors listed below currently exist, the potential risks and expected benefits of combined oral contraceptives should be carefully weighed in each individual case:
. Risk factors for the development of thrombosis and thromboembolism: smoking; thrombosis, myocardial infarction or cerebrovascular accident at a young age in one of the immediate family; ; dyslipoproteinemia (eg, hypertension; migraine; heart valve disease; cardiac arrhythmias, prolonged immobilization, major surgery, major trauma)
. Other diseases in which peripheral circulatory disorders may occur: ; systemic lupus erythematosus; hemolytic uremic syndrome; Crohn's disease and ulcerative colitis; sickle cell anemia; as well as superficial veins
. Hypertriglyceridemia
. Liver diseases
. Diseases that first appeared or worsened during pregnancy or against the background of previous use of sex hormones (for example, jaundice, gallbladder disease, with hearing impairment, porphyria, herpes of pregnant women, Sydenham's chorea)

Pregnancy and lactation
Diane-35 is not prescribed during pregnancy and breastfeeding.
If pregnancy is detected while taking Diane-35, the drug should be discontinued immediately. Cyproterone acetate is excreted in milk, so the use of Diane-35 is contraindicated during lactation.

Overdose:

No serious adverse events have been reported following overdose. Symptoms that may occur in case of overdose: nausea, vomiting, spotting or metrorrhagia.
There is no specific antidote; symptomatic treatment should be carried out.

Storage conditions:

At a temperature not higher than 30°C. Keep out of the reach of children. Shelf life: 5 years. Do not use after expiration date!

Vacation conditions:

On prescription

Package:

Dragee. 21 tablets per blister made of PVC and aluminum foil. The blister along with instructions for use is placed in a cardboard box.