Diane 35 is one of many oral contraceptives with antiandrogenic properties, which, in addition to its contraceptive action, has several other directions of action. So the drug is most often prescribed to women with manifestations of hyperandrogenism, i.e. who have increased levels of male sex hormones. This disease is often manifested by the following symptoms:

If everything is fine with your health and you just decided to switch to another type of contraception, then it is better to choose single-phase OK, for example, Yarina.

I must say that according to OK Diana 35, I met the most diverse reviews. Of course, girls write based on their own, often unsuccessful, experience, since few people write about positive experience (because of their happiness), although there are such.

Diana 35 reviews of "consumers".

More often, girls write that they want to have a baby or have already given birth on drug withdrawal. And indeed, doctors have a lot of experience in working with this drug. After a course of 4-6 months of continuous use of Diane 35, pregnancy occurs after cancellation. But it's different for everyone. Some have to take the drug for more than a year, others just a couple of months to achieve the desired result. In any case, you need to coordinate your treatment with your doctor, he must know all your chronic diseases in order to decide whether you can use this drug.

However, often girls write about Diana 35 reviews that they have side effects. Often they describe it as drug intolerance, ie. there is nausea, vomiting from the first days of admission, headaches and skin rashes. In this case, you must stop taking the pills and be sure to consult a specialist.

If you tolerate this drug well, then be sure of a positive result during its use or after its withdrawal. After all, the main thing is your desire.

Diane-35 tablets contain active ingredients cyproterone acetate and ethinylestradiol , as well as a number of additional components: lactose monohydrate, , corn starch, magnesium stearate, magnesium hydrosilicate.

The shell of the tablet consists of povidone 700000, sucrose, , magnesium hydrosilicate, glycerol, titanium dioxide, mountain glycol wax, iron oxide.

Release form

Diane-35 contraceptive pills are produced in the form of dragees, which are contained in a blister - a special calendar package of 21 pcs. It is enclosed in a cardboard pack.

Dragee light yellow, round, biconvex.

pharmachologic effect

Diane-35 is a monophasic combined oral contraceptive that has antiandrogenic, estrogenic, contraceptive, progestogen effects. This is a combination product that contains - ethinyl estradiol, as well as the antiandrogen cyproterone acetate, which demonstrates progestogenic properties.

Under the influence of the drug, the increased viscosity of the cervical mucus remains, as a result of which the process of entering the uterine cavity of spermatozoa is hampered. As a result, a contraceptive effect is noted. The substance cyproterone acetate provides blocking of androgen receptors and reduces the effects of androgenization in women, reducing the severity of sebum production, hair loss, and unwanted hair growth. Also provides treatment for diseases associated with overproduction or high sensitivity to them.

In the process of taking Diane-35 in women, the severity of acne , reduces the number of new acne. Also, the substance demonstrates progestogenic activity, inhibiting the process of ovulation.

The contraceptive effect of the drug is noted by the 14th day from the start of its use and remains for a seven-day pause in use. When using a contraceptive, the menstrual cycle normalizes, menstruation becomes less painful, the intensity of bleeding decreases and, as a result, the likelihood of iron deficiency anemia .

Pharmacokinetics and pharmacodynamics

highest concentration cyproterone acetate noted 1.6 hours after taking the dragee. Its bioavailability is 88%. In the first and second phases of elimination, the half-life of the substance cyproterone acetate is 3-4 hours and 2 days.

Ethinylestradiol after oral administration, it is rapidly absorbed, the highest concentration in the blood is observed after 1.6 hours. The bioavailability of the substance is 45%. Almost completely non-specifically binds to albumin. The half-life of the substance ethinylestradiol occurs in two phases - 1-3 hours and 1 day.

In breast milk, approximately 0.2% of the dose of cyproterone acetate and approximately 0.02% of ethinyl estradiol are determined.

Indications for use

The drug is used to prevent the onset of pregnancy in women who have symptoms androgenization (that is, the manifestation of the features of a man, provoked by the action of male sex hormones).

Also, the drug is indicated for manifestations androgenization : seborrhea, acne, mild forms , .

Contraindications

Such indications for the use of the drug Diane-35 are determined:

• the period of pregnancy and breastfeeding, suspicion of pregnancy;
• liver damage;
• pruritus, or idiopathic jaundice during pregnancy in history;
• and thromboembolism ;
• angina pectoris , ischemic transient attacks;
• Dubin-Johnson syndromes and Rotor (hereditary liver diseases);
• endometrial cancer and breast;
• disorders of fat metabolism;
• blistering dermatosis with a history of pregnancy;
• otosclerosis worsening during previous pregnancies;
• accompanied by vascular complications;
• hormone-dependent malignant diseases;
• vaginal bleeding .

Side effects of Diane-35

During the reception, such side effects of Diane-35 may appear:

• endocrine system: soreness of the mammary glands, the appearance of discharge from them, weight change;
• reproductive system: the appearance of bleeding between periods, changes in libido, changes in vaginal secretions;
• nervous system: , headaches, unstable mood;
• digestive system: vomiting, nausea;
• other manifestations: allergic manifestations, poor tolerance to contact lenses, chloasma.

These side effects in the process of taking the drug rarely develop. As a rule, negative manifestations occur in the first months of taking Diane-35, with time their severity decreases.

Many women are concerned about how Diane-35 and weight gain are related. As a rule, weight gain when using a contraceptive appears only in some cases. If a similar side effect develops, a woman needs to adjust her diet and lifestyle, as well as consult a doctor.

Diane-35 tablets, instructions for use (Method and dosage)

The provided instructions for the use of Diane-35 provide for oral administration of dragees. To ensure the necessary contraception of active substances in the body, you need to take the drug regularly.

If a woman has used any other hormonal contraceptives, before taking Diane-35, its use is stopped.

The dosage regimen of this contraceptive is the same as that of other oral contraceptives. With irregular intake of this remedy, acyclic bleeding may occur, the therapeutic and contraceptive effect may decrease.

Diana-35 calendar package contains 21 dragees. For ease of use, each dragee is marked with the day of the week on which it must be taken. It is necessary to swallow the dragee at the same time, washing down the drug with a liquid. You need to take the pills in the direction of the arrow until all the pills are taken. After completion of the reception within 7 days, you do not need to drink the drug. During these days - usually on day 2-3 - withdrawal bleeding begins. After a seven-day break, you need to start the next pack, adhering to this regimen, even if the bleeding has not stopped. That is, a woman always starts a new package of Diane-35 on the same day of the week.

Reception of a dragee needs to be begun in the first day of monthly bleeding. For convenience, you need to use the first tablet, marked with the day of the week on which the reception begins. Further dragees are taken in order.

The contraceptive effect is noted from the first day of admission, therefore, there is no need to use others.

You can start drinking Diane-35 on day 2-5 of the cycle. But at the same time, barrier contraception should be used additionally during the first 7 days of admission.

If a woman switches to Diana-35 after using any other methods of contraception, she needs to additionally consult with a gynecologist.

After an early abortion, a woman can start taking pills immediately. In this case, additional protection is not required.

After a miscarriage or spontaneous abortion, you should consult a doctor who will tell you how to take contraceptives.

If the pill was missed, then you need to take it as soon as possible, drink the next pill at the usual time. It should be taken into account that if the delay is less than 12 hours, the contraceptive effect does not decrease.

The probability of conception increases as the more pills the woman missed and the closer the gaps to the seven-day break. If you miss taking the drug for many days, you should consult your doctor.

If a woman is vomiting or diarrhea within 3-4 hours after taking the pill, it is advisable to use additional contraceptive methods.

When used for the purpose of treatment, its duration depends on the severity of the symptoms. As a rule, the medication lasts for several months. When using an acne remedy, the application period may be shorter, as the reviews indicate.

Overdose

There is no evidence of a serious overdose of the drug. When taking large doses of Diane-35, nausea and vomiting may occur, as well as slight bleeding from the vagina, which occurs mainly in young women and girls. Symptomatic therapy is practiced.

Interaction

Before starting Diane-35, a woman should inform the doctor about all the drugs she is taking.

Terms of sale

You can buy Diana-35 by prescription.

Storage conditions

Keep out of reach of children, store at a temperature not exceeding 30 °C.

Best before date

You can store the product for 5 years.

special instructions

If any of the risk factors are present, the likely risk and expected benefit should be carefully determined before starting the drug. There is evidence of an increase in the incidence of thrombosis and thromboembolism with the use of oral contraceptives. An increase in the severity and frequency of migraine is likely with this method of contraception. There is evidence of a possible increase in the likelihood of developing cervical cancer, but this relationship has not been clearly proven.

Women with a tendency to develop chloasma should not stay in the sun for a long time while taking oral contraceptives.

Women with diabetes need constant supervision of a specialist during the period of use of Diane-35.

It should be borne in mind that the use of Diane-35 may affect the results of laboratory tests.

In the first months of use, menstrual bleeding may be irregular. Sometimes there may be no withdrawal bleeding during the period of a break in taking the tablets.

With prolonged use of the Diane-35 contraceptive, a woman should be examined by a gynecologist every 6 months.

It should be borne in mind that pregnancy after the withdrawal of the drug can occur almost immediately. If a woman suspects that she has become pregnant while withdrawing the contraceptive, she should contact a specialist.

Does not affect the ability to drive vehicles.

Diana-35 analogues

Coincidence in the ATX code of the 4th level:

Analogues of this contraceptive - drugs Belluna-35 , Erica-35 , . The choice of the most suitable remedy should be carried out by the doctor individually.

children

Use in adolescents is carried out only after the onset menarche.

With antibiotics

When taking tetracyclines, ampicillins and for seven days after the abolition of such antibiotics, it is necessary to use additional barrier contraception.

During pregnancy and lactation

Diane-35 is contraindicated in pregnancy and breastfeeding.

Dosage form

Compound

One dragee contains

active substances: cyproterone acetate 2.0 mg

ethinylestradiol 0.035 mg,

excipients: lactose monohydrate, corn starch, povidone 25000, talc, magnesium stearate,

dragee shell: sucrose, povidone 700,000, macrogol 6000, calcium carbonate, talc, 85% glycerin, titanium dioxide (E171), iron oxide yellow (E172), motaglycolic wax.

Description

Round, biconvex beige dragees

Pharmacotherapeutic group

Sex hormones and modulators of the reproductive system. Antiandrogens. Antiandrogens and estrogens. Cyproterone and estrogens

ATX code G03HB01

Pharmacological properties

Pharmacokinetics

Cyproterone acetate Absorption

Orally administered cyproterone acetate is rapidly and completely absorbed. The maximum serum concentration of 15 ng / ml is reached after about 1.6 hours. Bioavailability is about 88%.

Distribution

Cyproterone acetate binds almost completely to serum albumin. Only 3.5-4.0% of the total serum level of cyproterone acetate is in the free form. The ethinylestradiol-induced increase in the level of sex hormone-binding globulin (SHBG) does not affect the binding of cyproterone acetate to serum proteins. The apparent volume of distribution of cyproterone acetate is approximately 986 ± 437 liters.

Metabolism

Cyproterone acetate is almost completely metabolized.

The main metabolite in human plasma is the 15ß-hydroxyl derivative, which is formed with the participation of the CYP 3A4 enzyme of the cytochrome P450 system. The rate of clearance from blood serum is approximately 3.6 ml / min / kg.

breeding

Equilibrium concentration

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

Ethinylestradiol Absorption

After oral administration, ethinylestradiol is absorbed rapidly and completely. The maximum concentration in blood serum, equal to approximately 71 pg / ml, is reached in 1 hour and 40 minutes. During absorption and the first passage through the liver, ethinylestradiol is extensively metabolized, resulting in its oral bioavailability averaging about 45%, with significant individual differences ranging from 20-65%.

Distribution

Ethinylestradiol is almost completely (98%), although non-specific, associated with albumin. Ethinylestradiol induces the synthesis of SHBG. The apparent volume of distribution of ethinylestradiol is 2.8-8.6 l/kg.

Metabolism

Ethinylestradiol undergoes presystemic conjugation in the mucosa of the small intestine and in the liver. Ethinylestradiol is primarily metabolized by aromatic hydroxylation, producing a variety of hydroxylated and methylated metabolites, 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.

breeding

Metabolites of ethinylestradiol are excreted by the kidneys and liver in a ratio of 4:6 with a half-life of about 24 hours.

Equilibrium concentration

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

Pharmacodynamics

The sebaceous-hair complex, consisting of the sebaceous gland and the hair follicle, is an androgen-sensitive component of the skin. Acne and seborrhea are due in part to sebaceous gland dysfunction, which may result from androgen hypersensitivity or elevated plasma androgen levels. Both active substances of Diane® 35 have a positive therapeutic effect.

Cyproterone acetate, contained in Diane 35, is a competitive androgen receptor antagonist, has an inhibitory effect on androgen synthesis in target cells and helps to reduce the concentration of androgens in the blood due to its antigonadotropic effect.

The antigonadotropic effect of the drug is enhanced by ethinyl estradiol, which also increases the synthesis of SHBG, which helps to reduce the free biologically active level of androgens in the blood.

Treatment with Dianeâ 35 leads - usually after 3-4 months of therapy - to the healing of existing acne lesions. Excessive oiliness of hair and skin, as a rule, disappears earlier. Androgen-dependent hair loss is also reduced. However, in women suffering from hirsutism, the results become visible only after a few months of use.

Cyproterone acetate is also a potent progestogen with a contraceptive effect when used in combination with ethinyl estradiol. This effect is based on the interaction of the central and peripheral mechanisms, the most important of which should be considered the suppression of ovulation and changes in the properties of the cervical secret. In addition, as a result of morphological and enzymatic changes in the endometrium, extremely unfavorable conditions for implantation arise.

Contraceptive protection begins on the first day of taking the drug.

Indications for use

Treatment of moderate and severe androgen-dependent forms of acne (without seborrhea or accompanied by seborrhea) and / or hirsutism in women of reproductive age.

For the treatment of acne, Diane® 35 should be used when topical or systemic antibiotic treatment is not effective.

Since Diane® 35 is also a hormonal contraceptive, it should not be used in combination with other hormonal contraceptives (see section "Contraindications").

Dosage and administration

Dianeâ 35 prevents ovulation and thus has a contraceptive effect. Patients taking Diane® 35 should not use additional hormonal contraceptives, as this leads to an overdose of hormones and is not necessary for effective contraceptive action.

For the same reason, Diane® 35 should not be used by women who wish to become pregnant.

Reception Dianeâ 35 should be regular to achieve the required therapeutic efficacy and the required contraceptive protection.

Mode of application

For oral administration.

The pills should be taken in the order indicated on the package, every day at about the same time with a little water. Take one tablet per day continuously for 21 days. Reception of each next pack begins after a 7-day break, during which withdrawal bleeding (menstrual-like bleeding) is observed. It usually starts 2-3 days after taking the last pill and may not end before the start of a new package. Contraceptive protection starts from the first day of taking the dragee and also lasts for 7 days when the drug is not taken. Simultaneous use of hormonal contraceptives should be discontinued.

Medical examination / doctor's consultation

Before starting the use of the drug, it is recommended to conduct a complete general medical examination (including measurement of body weight, blood pressure, examination of the heart, legs and skin, urinalysis for diabetes, liver tests if necessary), a gynecological examination is also necessary (including examination of the mammary glands and cytological examination of cervical mucus taken from the vaginal part of the cervix and cervix), a detailed family medical history should be taken to determine diseases requiring treatment and possible risks. It is necessary to exclude pregnancy. When using the drug, it is recommended to conduct control examinations every six months.

Disorders of the blood coagulation system should be ruled out if blood relatives had thromboembolic complications (eg, deep vein thrombosis, stroke, heart attack) at an early age. It should also be noted that taking oral contraceptives does not protect against HIV infection (AIDS) and other sexually transmitted diseases.

How to start taking Dianeâ 35

In the absence of taking any hormonal contraceptives in the previous month

Dianeâ 35 is started on the first day of the menstrual cycle (i.e. the first day of menstrual bleeding). It is allowed to start taking on the 2nd-5th day 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.

Women with amenorrhea can start taking the drug immediately after being prescribed by a doctor; in this case, the day of taking the first dragee corresponds to the first day of the menstrual cycle, and then the reception continues as recommended.

When switching from combined hormonal contraceptives (combined oral contraceptive, vaginal ring, transdermal patch)

It is preferable to start taking Dianea 35 the next 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 preparations 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 Dianeâ 35 on the day the last ring or patch of the cycle pack is removed, but in no case later than the day when the next ring or patch should have been applied.

When switching from contraceptives containing only gestagens (mini-pili, injectable forms, implant), or a progestogen-releasing intrauterine system (IUD).

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

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 on the 21-28th day after childbirth or abortion in the second trimester of pregnancy. If the reception is started later, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the pills. However, if the woman has already been sexually active, pregnancy should be ruled out before Diane 35 is started, or the first menstruation should be waited for.

Application duration

The duration of taking Diane® 35 is determined by the severity of the disease and the effectiveness of the treatment. In the treatment of acne and seborrhea, the effect usually occurs earlier than in the treatment of hirsutism. After the intensity of symptoms decreases, it is recommended to take Diane-35 for at least another 3 or 4 cycles.

In case of no effect on therapy or in case of insufficient effect on treatment

Severe acne or seborrhea for at least six months or

Hirsutism for at least 12 months

concomitant administration of Dianeâ-35 and Androkur® 10 mg tablets or Androkur® 50 mg tablets should be considered or, which is more preferable, reconsider the method of treatment.

When the symptoms of androgenization subside, but contraceptive action is still required, the use of a low-dose oral contraceptive should be switched to. In the event of recurrence of androgenic symptoms, it is possible to resume therapy with Dianeâ-35.

In the case of resuming the use of Diane® 35 (after a break between doses of the drug for 4 weeks or more), an increased risk of developing venous thromboembolism should be taken into account (see section "Special Instructions").

Taking missed pills

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

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

Reception of a dragee should never be interrupted, more than for 7 days.

7 days of continuous tablet intake 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 was more than 12 hours (the interval from the moment the last pill was taken was more than 36 hours):

First week of taking the drug

The woman should take the last missed tablet as soon as she remembers (even if it means taking two tablets at the same time). The next dragee is taken at the usual time. Additionally, a barrier method of contraception (such as a condom) must be used for the next 7 days. If sexual intercourse took place within a week before skipping the dragee, it is necessary to take into account the likelihood of pregnancy.

The more pills 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

The woman should take the last missed tablet as soon as she remembers (even if it means taking two tablets at the same time). The next dragee is taken at the usual time.

Provided that the woman has taken the pill correctly within 7 days preceding the first missed pill, there is no need to use additional contraceptive measures. Otherwise, as well as skipping 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 a decrease in reliability is inevitable due to the upcoming break in taking pills.

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

1. A woman should take the last missed pill as soon as possible (even if it means taking two pills at the same time). The next dragee is taken at the usual time until the dragees 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 or breakthrough bleeding may occur while taking the pills.

2. A woman can also stop taking the dragee from the current package. Then she should take a break for 7 days, including the day she skipped the dragee, and then start taking a new package.

If a woman misses taking the pills, and then during the break in taking the pills she does not have withdrawal bleeding, pregnancy should be excluded. No withdrawal bleeding

In the absence of withdrawal bleeding, the drug should be discontinued until pregnancy has been ruled out.

Tips for intermenstrual bleeding

It is absolutely necessary to continue taking Diane-35 in case of intermenstrual bleeding. Small bleeding usually stops spontaneously or disappears within 4 to 5 days - as well as intermenstrual bleeding of the same intensity as menstruation (breakthrough bleeding) - as a result of additional simultaneous use of 25 - 50 mcg of ethinyl estradiol (i.e. not after taking the last dragee from Diane's package -35).

If breakthrough bleeding persists or recurs, a thorough evaluation, including curettage, should be performed to rule out an organic cause.

The above also applies to spotting that occurs at irregular intervals over several consecutive cycles or occurs for the first time after long-term use of Diane-35. In such cases, bleeding is usually the result of organic changes, and not the action of the drug.

Tips for gastrointestinal disorders

With severe vomiting or diarrhea, the absorption of the active substances 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 the Diane® 35 dragee, it is necessary to focus on the advice regarding skipping the dragee. 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.

Liver disease

In the case of viral hepatitis, drugs such as Diane-35 should not be used until about six months after recovery (when liver tests return to normal).

Elderly patients

Diane® 35 is contraindicated in women with severe liver disease until liver function tests return to normal Patients with renal impairment

Diane® 35 has not been specifically studied in patients with impaired renal function. Available data do not suggest a change in treatment in these patients.

Side effects

All women taking Diane® 35 have an increased risk of developing thromboembolism.

Additional factors may increase the risk (smoking, arterial hypertension, blood clotting disorders or lipid metabolism disorders, obesity, varicose veins, previous phlebitis and thrombosis), see section "Special Instructions".

For information on other side effects such as liver tumors, cervical cancer and breast cancer, see the "Special Instructions" section. The following undesirable effects have been described in women taking Diane® 35 and their relationship with the drug has not been confirmed or refuted:

Often (≥1/100)

Nausea, abdominal pain

Weight gain

Headache, depressed mood, mood changes

Soreness and tension of the mammary glands, intermenstrual bleeding

Uncommon (≥1/1000,<1/100)

Vomiting, diarrhea

Fluid retention

Migraine

Decreased libido

Breast enlargement

Rash, hives, chloasma (appearance of age spots on the face)

Rarely (<1/1000)

Hypersensitivity reactions

Poor tolerance to contact lenses

Thromboembolism

Weight loss

Increased libido

Vaginal discharge, discharge from the mammary glands

Erythema nodosum, erythema multiforme

Post-marketing data:

Increase in blood pressure

The following serious side effects described in the "Special Instructions" section have been reported in women using Diane® 35:

Venous thromboembolic disorders

Arterial thromboembolic disorders

Cerebrovascular disorders

Arterial hypertension

Hypertriglyceridemia

Impaired glucose tolerance or effects of peripheral insulin resistance

Liver tumors (benign and malignant)

Liver dysfunction

Chloasma

The appearance or worsening of the following conditions, the relationship of which with the use of combined oral contraceptives has not been reliably established: jaundice and / or itching associated with cholestasis; the formation of stones in the gallbladder; porphyria; systemic lupus erythematosus; hemolytic uremic syndrome; chorea of ​​Sydenham (small chorea), herpes of pregnant women; hearing loss associated with otosclerosis, Crohn's disease and ulcerative colitis, cervical cancer

In women with hereditary angioedema, provoking or exacerbating symptoms of the disease under the influence of exogenous estrogens

The frequency of breast cancer diagnosis is slightly increased among women taking oral contraceptives. Since breast cancer is rare in women under 40 years of age, the increase in the number of diagnoses is small in relation to the overall risk of developing this disease. Detailed information is contained in the section "Special Instructions" and "Contraindications".

Action on breast tissue

Sex hormones have an effect on breast tissue, as they probably increase its sensitivity to the effects of other carcinogenic factors. Sex hormones are really just one of various possible risk factors unrelated to oral contraceptive use. In epidemiological studies that have analyzed the possible association between the use of hormonal contraceptives and the development of breast cancer, it was not possible to unequivocally answer the question whether this disease is indeed more common before middle age in women who use contraceptives for a long time starting at a young age.

Also, while taking combined oral contraceptives, an increase in endogenous depression and epilepsy was noted.

If a significant increase in symptoms is observed in women suffering from hirsutism, other causes should be considered in the differential diagnosis (androgen-producing tumor, fermentopathy in the adrenal cortex).

Deviation of indicators of clinical biochemical analysis from the norm Erythrocyte sedimentation rate may increase without the presence of a disease. There have been cases of increased levels of copper and iron in the blood serum, as well as cases of increased activity of leukocyte alkaline phosphatase.

Other metabolic functions

Rare disorders of folic acid and tryptophan metabolism may occur.

With regular use, Dianeâ 35 has a contraceptive effect due to its composition. Irregular use of Dianeâ 35 may lead to menstrual irregularities. Regularity in taking Diane 35 is very important both for preventing menstrual irregularities and for preventing pregnancy (because cyproterone acetate may affect the developing baby).

Contraindications

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

Hypersensitivity to any of the components of the drug

Combined use with other hormonal contraceptives

Current or history of venous thrombosis (eg, deep vein thrombosis, pulmonary embolism)

Having a personal or family history of known idiopathic venous thromboembolism (VTE) in which there is a family history of VTE in a sibling or parent at a relatively early age)

Current or history of arterial thrombosis (eg, myocardial infarction) or previous disorders (eg, angina pectoris and transient ischemic attacks)

Cerebrovascular disorders at present or in history

The presence of pronounced or multiple risk factors for the development of venous or arterial thrombosis (see section "Special Instructions"), for example:

Diabetes mellitus with vascular complications

Severe arterial hypertension

Severe dyslipoproteinemia

Hereditary or acquired predisposition to venous or arterial thromboembolism (eg, resistance to activated protein C (APC resistance), deficiency of antithrombin III, protein C, protein S, hyperhomocysteinemia, and antiphospholipid antibodies (anticardiolipin antibodies and lupus anticoagulant)

sickle cell anemia

Severe liver disease, including disorders of the excretory system such as Dubin-Johnson and Rotor syndrome until liver function tests return to normal

Liver tumors (benign or malignant) at present or in history

Unexplained vaginal bleeding

Migraine with a history of focal neurological symptoms

Smoking

Identified or suspected hormone-dependent malignant diseases (for example, genital or mammary glands)

History of idiopathic jaundice in pregnancy, severe pruritus or herpes in pregnancy, worsening of otosclerosis during previous pregnancies

Desired pregnancy, pregnancy and breastfeeding period

Dianeâ 35 does not apply to men.

Drug Interactions

Effects of other drugs on Diane â 35

Interaction with drugs that induce microsomal liver enzymes is possible, which may contribute to an increase in the clearance of sex hormones and lead to breakthrough bleeding and / or a decrease in the contraceptive effectiveness of the drug.

While taking these drugs, the woman should additionally use a barrier method of contraception in addition to Diane® 35 or choose another method of contraception. In this case, the barrier method of contraception should be used during the period of concomitant use of drugs and within 28 days after their withdrawal.

If the period of use of the barrier method of protection ends later than the tablets in the package, you need to move on to the next package of Dianeâ 35 without the usual break in taking the tablets.

Substances that increase the clearance of Dianeâ 35 (reducing the effectiveness due to the induction of liver enzymes), for example:

barbiturates, rifampicin and antiepileptic drugs (such as barbexaclone, carbamazepine, phenytoin, primidone); there are also suggestions for oxcarbazepine, topiramate, felbamate, griseofulvin and preparations containing St. John's wort.

Substances with different effects on the clearance of Dianeâ 35

When used concomitantly with Diane® 35, many HIV/HCV protease inhibitors and non-nucleoside reverse transcriptase inhibitors may increase or decrease plasma levels of estrogens or progestins. These changes may in some cases be relevant.

Effects of estrogen/progestogen combinations on other drugs

Estrogen/progestogen combinations like Diane 35 may interfere with the metabolism of certain other drugs, resulting in increased (eg, cyclosporine) or decreased (eg, lamotrigine) plasma and tissue concentrations.

It may be necessary to adjust the dose of hypoglycemic drugs, given the effect on glucose tolerance.

Other interactions

Laboratory tests

Taking drugs like Dianeâ 35 may affect the results of some laboratory tests, including liver, kidney, thyroid, adrenal function, plasma transport protein levels, such as corticosteroid-binding globulin and lipid/lipoprotein fractions, carbohydrate metabolism, coagulation parameters, and fibrinolysis. However, these changes usually do not go beyond the limits of normal values.

A woman should be warned that Diana® 35 should not be used in addition to other hormonal contraceptives. These drugs must be discontinued before starting treatment with Diane 35.

special instructions

Precautions and Warnings

Diane® 35 contains the progestogen cyproterone acetate and the estrogen ethinyl estradiol and is used for 21 days of the monthly cycle. The drug has a composition similar to other combined oral contraceptives.

Application duration

The time to relief of the symptoms of the disease is at least three months. The attending physician should conduct regular examinations to determine the need for continued treatment.

If any of the conditions / risk factors listed below are currently present, then the potential risk and expected benefit 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 or appear for the first time, the woman should consult her doctor. The doctor needs to decide when to stop the drug.

· Circulatory disorders

Patients taking Diane® 35 have an increased risk of developing venous thromboembolism (VTE) compared to women not taking this drug. The greatest additional risk of VTE occurs during the first year of taking Diane-35 or when taking it again, as well as when switching to this drug after a break in taking at least one month. Venous thromboembolism can be fatal in 1-2% of cases.

The results of epidemiological studies indicate that the incidence of VTE among users of Dianeâ 35 is 1.5-2 times higher than in women using combined hormonal contraceptives containing levonorgestrel and may be similar to the risk while taking combined hormonal contraceptives containing desogestrel / gestodene / drospirenone.

There is a possibility that among women using the drug Diane® 35, there may be patients with a congenital increased risk of developing cardiovascular diseases, for example, associated with polycystic ovary syndrome.

In addition, data from epidemiological studies indicate a relationship between the use of hormonal contraceptives and an increased risk of arterial thromboembolism, such as myocardial infarction and transient ischemic attacks.

In women taking combined oral contraceptives, extremely rare cases of thrombosis of other blood vessels, such as hepatic, mesenteric, renal, cerebral arteries and veins, as well as retinal vessels, have been described.

Symptoms of venous or arterial thrombosis or cerebrovascular disorders may include:

unusual unilateral pain and / or swelling in the leg, sudden sharp pain in the chest, regardless of radiating to the left arm, sudden attack of coughing, any unusual, severe or prolonged headache, sudden partial or complete loss of vision, diplopia, impaired speech or loss of speech, dizziness, loss of consciousness or fainting with or without a local epileptic seizure, weakness or severe numbness, suddenly occurring on one side of the body or one part of the body, movement disorders, symptoms of an "acute abdomen".

The risk of developing venous thromboembolic disorders increases:

With age

If there is a family history (venous thromboembolism in close relatives or parents at a relatively young age). If a hereditary predisposition is known or suspected, a woman should consult a doctor to decide on the possibility of taking a hormonal contraceptive.

Prolonged immobilization, major surgery, any leg surgery, or major trauma. In these situations, it is advisable to stop the use of combined oral contraceptives (in the case of a planned operation, at least four weeks before it) and not resume taking within two weeks after the end of immobilization. If Diane® 35 has not been discontinued in advance, antithrombotic therapy should be considered.

The risk of developing arterial thromboembolic complications or cerebrovascular disorders 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 old. Women over 35 years old who want to use Dianeâ 35 are strongly advised to stop smoking).

Dyslipoproteinemia

Obesity (body mass index over 30 kg/m2)

arterial hypertension

Migraine

valvular heart disease

atrial fibrillation

If there is a family history (arterial thrombosis in close relatives or parents at a relatively young age). If a hereditary predisposition is known or suspected, a woman should consult a doctor to decide on the possibility of taking a hormonal contraceptive.

Circulatory disturbances may also be noted:

with diabetes mellitus, systemic lupus erythematosus, hemolytic uremic syndrome, chronic inflammatory bowel diseases (Crohn's disease or ulcerative colitis) and sickle cell anemia.

An increased risk of developing thromboembolism in the postpartum period should be taken into account (see section "Pregnancy and lactation").

An increase in the frequency and severity of migraine during the use of Diana® 35 (which may precede cerebrovascular disorders) may be grounds for immediate discontinuation of these drugs.

Women taking Diana 35 should be specifically instructed to contact their doctor if possible symptoms of thrombosis appear. Diane 35 should be discontinued if thrombosis is suspected or confirmed. Given the teratogenic effect of anticoagulants (coumarin series), appropriate methods of contraception should be used.

Arterial thromboembolic processes can be life-threatening or fatal.

Consideration should be given to the possibility of an increased synergistic risk of thrombosis in women with a combination of several risk factors or a higher severity of one of the risk factors.

In such cases, the increased risk may be greater than just the combined risk when all factors are considered.

Diane 35 should not be prescribed in case of a negative risk/benefit ratio (see section "Contraindications").

Tumors

The most significant risk factor for developing cervical cancer is a viral infection - persistent human papilloma (HPV). There are reports of a slight increase in the risk of developing cervical cancer with long-term use of combined oral

contraceptives, but there is conflicting evidence about the extent to which this may be due to other factors, including the frequency of cervical examination and sexual behavior, including the use of barrier methods of contraception.

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. The increased risk gradually disappears within 10 years after stopping these drugs. Due to the fact that breast cancer is rare in women under 40 years of age, the increase in the number of breast cancer diagnoses in women currently taking combined oral contraceptives or who have recently taken it is insignificant in relation to the overall risk of developing this disease. Its relationship with the use of combined oral contraceptives has not been proven. The observed increase in risk may be due to earlier diagnosis of breast cancer in women using combined oral contraceptives, the biological effects of combined oral contraceptives, or a combination of both factors. In women who have ever used combined oral contraceptives, earlier stages of breast cancer are detected than in women who have never used them.

In rare cases, against the background of the use of combined oral contraceptives, the development of benign liver tumors and, in even more rare cases, the development of malignant liver tumors was observed. In some cases, liver tumors can lead to life-threatening intra-abdominal bleeding. In the event of severe pain in the upper abdomen, liver enlargement, or signs of intra-abdominal bleeding, a liver tumor should be considered in the differential diagnosis.

Malignant tumors can be life-threatening or fatal.

Other conditions

In women with hypertriglyceridemia (or a family history of this condition), there may be an increased risk of developing pancreatitis while taking combined oral contraceptives.

Although a slight increase in blood pressure has been described in many women taking combined oral contraceptives or Diane® 35, clinically significant increases have been rare. However, if a persistent, clinically significant increase in blood pressure develops during Dianeâ 35, Dianeâ 35 should be discontinued and treatment of arterial hypertension initiated. Reception Diane 35 can be continued if normal blood pressure values ​​are achieved with the help of antihypertensive therapy.

The following conditions observed during pregnancy may also appear or worsen when taking combined oral contraceptives: jaundice and / or itching associated with cholestasis; the formation of stones in the gallbladder; porphyria; systemic lupus erythematosus; hemolytic uremic syndrome; chorea; herpes of pregnant women; hearing loss associated with otosclerosis. However, the relationship between the development of these conditions and the use of combined oral contraceptives has not been proven.

In women with hereditary angioedema, exogenous estrogens may provoke or exacerbate the symptoms of this disease.

In the presence of acute or chronic liver dysfunction, it is necessary to decide whether to stop taking Dianeâ 35 until the liver function returns to normal. With the development of recurrent cholestatic jaundice, which develops for the first time during pregnancy or previous use of sex hormones, Diane® 35 should be discontinued.

Although combined oral contraceptives may affect insulin resistance and glucose tolerance, there is no need to change the therapeutic regimen in diabetic patients using low-dose combined oral contraceptives (<0,05 мг этинилэстрадиола). Тем не менее, женщины с сахарным диабетом должны тщательно наблюдаться во время приема комбинированных пероральных контрацептивов.

Against the background of the use of combined oral contraceptives, manifestations of Crohn's disease and ulcerative colitis were observed.

Women with a tendency to chloasma while taking Dianeâ 35 should avoid prolonged exposure to the sun and exposure to ultraviolet radiation.

Reduced efficiency

The contraceptive effectiveness of Diane 35 may be reduced by skipping pills, gastrointestinal disturbances, or co-administration of certain drugs.

irregular bleeding

While taking all combined oral contraceptives, irregular bleeding (spotting or breakthrough bleeding) may occur, especially during the first months of use.

Some women may not develop withdrawal bleeding during the 7-day break from taking the pills. If Dianeâ-35 was taken according to the instructions given in the Dosage and Administration section, it is unlikely that the woman is pregnant. However, if Diane was not taken as directed before the first withdrawal bleeding occurred, or if there are no consecutive withdrawal bleedings, pregnancy should be ruled out before continuing with the drug.

One tablet of Dianeâ-35 contains 31 mg of lactose monohydrate and 19 mg of sucrose. Patients with rare hereditary disorders such as galactose or fructose intolerance, lactase deficiency, glucose-galactose malabsorption or sucrase-isomaltase deficiency should not take Diane-35.

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

Pregnancy and lactation

It is necessary to exclude pregnancy. Dianeâ 35 is contraindicated during pregnancy. If pregnancy is detected while taking the drug, you should immediately stop taking it.

Dianeâ 35 is also contraindicated during lactation, since cyproterone acetate may be excreted in milk. About 0.2% of the dose taken by the mother can be delivered to the newborn, which corresponds to a dose of about 1 µg/kg. 0.02% of the daily dose of ethinylestradiol taken by the mother can enter the body of a newborn with breast milk during established lactation.

Preclinical safety data for ethinylestradiol

The toxicity profile of ethinylestradiol is well understood. There are no preclinical data that supplement the information on the safety of ethinylestradiol specified in other sections of the instructions for medical use of the drug.

Cyproterone acetate Systemic toxicity

Data from standard preclinical toxicity studies with repeated use of cyproterone acetate do not indicate a specific risk to humans.

Embryotoxicity/teratogenicity

Embryotoxicity studies with a combination of both active substances of the drug do not indicate the presence of teratogenic effects at the stage of organogenesis before the development of the external genital organs.

Taking high doses of cyproterone acetate in the hormone-sensitive phase of genital differentiation leads to the appearance of female sexual characteristics in male fetuses. Monitoring of newborn boys whose mothers took cyproterone acetate during pregnancy did not reveal the development of any female sexual characteristics in them. However, taking Dianeâ 35 is contraindicated during pregnancy.

Genotoxicity and carcinogenicity

The results of standard basic tests for cyproterone acetate genotoxicity were negative. However, additional tests showed that cyproterone acetate has the ability to form DNA adducts, which leads to increased DNA repair in rat and monkey liver cells, as well as freshly isolated human hepatocytes, while the level of DNA adducts was extremely low in dog liver cells.

The formation of adducts with DNA developed with systemic exposure, presumably expected at the recommended dosages of cyproterone acetate. With the introduction of cyproterone acetate in vivo in female rats, an increase in the frequency of focal, possibly preneoplastic, foci with changes in cellular enzymes was observed, and an increase in the frequency of mutations in transgenic mice carrying a bacterial gene as a target for mutation.

During the clinical use of the drug and in epidemiological studies, there was no increase in the incidence of liver tumors in humans. In studies on rodents, no carcinogenic properties of the drug were found. However, it must be kept in mind that sex steroids can stimulate the growth of some hormone-dependent tumors and tissues. In general, according to existing data, there are no contraindications regarding the use of Dianeâ 35 in humans, provided that the instructions for its use and recommended doses are observed.

Additional information for special categories of patients Children and adolescents

Dianeâ 35 is indicated only after the onset of menarche.

Elderly patients

Not applicable. Dianeâ 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

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 HEALTHCARE PROFESSIONALS

Diane-35 - official * instructions for use

INSTRUCTIONS
(information for specialists)
on the 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 dragees of light yellow color

Pharmacotherapeutic group
Contraceptive (estrogen + antiandrogen)

ATX code O03HB01

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 the suppression of ovulation and the change in the properties of the cervical secret, as a result of which it becomes impermeable to spermatozoa.

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

Against the background of 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 of hair and skin disappears even earlier. It also reduces hair loss, which often accompanies seborrhea. Diane-35 therapy in women of reproductive age reduces the clinical manifestations of mild forms of hirsutism (in particular, increased facial hair growth); however, the effect of the treatment should be expected only after several months of use. Along with the antiandrogenic effect described above, cyproterone acetate also has a pronounced progestogenic effect.

Pharmacokinetics

Cyproterone acetate

Absorption. When administered orally, cyproterone acetate is completely absorbed over a wide dose range. After ingestion of Diane-35 dragees, the maximum concentration (Cmax) of cyproterone acetate in serum, equal to 15 ng / ml, is reached 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. In the free form is only about 3.5-4% of the total concentration of blood serum. The increase in SHBG induced by ethinylestradiol 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 the 15P-hydroxyl derivative.

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

equilibrium concentration. Since protein binding is not specific, changes in the level of sex steroid-binding globulin (SHBG) do not affect the pharmacokinetics of cyproterone acetate. During cycle treatment, the maximum equilibrium concentration of cyproterone acetate in serum is reached in the second half of the cycle.

Ethinylestradiol

Absorption. After oral administration, ethinylestradiol is rapidly and completely absorbed. The maximum concentration (Cmax) in the blood serum, equal to approximately 71 pg / ml, is reached in 1.6 hours. During absorption and the first passage through the liver, ethinylestradiol is metabolized, as a result of which its oral bioavailability averages about 45%.

Distribution. Ethinylestradiol is almost completely (approximately 98%), although non-specifically bound to albumin. Ethinylestradiol induces the synthesis of SHPS. The apparent volume of distribution of ethinylestradiol is 2.8-8.6 l/kg.

Metabolism. Ethinylestradiol undergoes presystemic conjugation both in the small intestine mucosa and in the liver. The main metabolic pathway is aromatic hydroxylation. The rate of clearance from blood plasma is 2.3-7 ml / min / kg.

Withdrawal. The decrease in the concentration of ethinylestradiol 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. Metabolites of ethinylestradiol are excreted in the urine and bile in a ratio of 4:6 with an elimination half-life of about 24 hours.

equilibrium concentration. The equilibrium concentration is reached 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 in the presence of any of the conditions listed below. If any of these conditions develop for the first time while taking the drug, the drug should be immediately discontinued.

• Thrombosis (venous and arterial) and thromboembolism at present or in history (including deep vein thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular disorders).
• Conditions preceding thrombosis (including transient ischemic attacks, angina pectoris) at present or in history.
• Migraine with a history of focal neurological symptoms
• Diabetes mellitus with vascular complications.
• Multiple or severe risk factors for venous or arterial thrombosis, including valvular heart disease, cardiac arrhythmias, cerebrovascular disease or coronary artery disease; uncontrolled arterial hypertension.
• Pancreatitis with severe hypertriglyceridemia at present or in history.
• Severe liver disease (until liver function tests return to normal).
• Liver tumors (benign or malignant) at present 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 are currently present, then the potential risk and expected benefit of using combined oral contraceptives should be carefully weighed in each individual case:

• Risk factors for thrombosis and thromboembolism: smoking; thrombosis, myocardial infarction or cerebrovascular accident at a young age in any of the immediate relatives; obesity; dyslipoproteinemia (eg, hypertension; migraine; valvular heart disease; abnormal heart rhythms, 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 disease
• Diseases that first arose or worsened during pregnancy or against the background of previous use of sex hormones (for example, jaundice, cholestasis, gallbladder disease, otosclerosis with hearing loss

Pregnancy and lactation
Diane-35 is not prescribed during pregnancy and lactation. 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.

Dosage and administration
Dragee Diane-35 should be taken orally in the order indicated on the package, every day at about the same time, with a little water. Take one tablet per day continuously for 21 days. The next pack is started after a 7-day break in taking the pills, during which withdrawal bleeding usually occurs. Bleeding usually starts 2-3 days after taking the last pill and may not end before starting a new pack.

The duration of administration depends on the severity of the symptoms of androgenization, as well as on 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 the pills, Diane-35 treatment can be resumed. In case of recurrence of signs of androgenization after discontinuation of treatment, the possibility of an earlier resumption of Diane-35 should be considered.

How to start taking Diane-35

• In the absence of taking any hormonal contraceptives in the previous month.
  Reception 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 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 the pills from the first package.
• When switching from other combined oral contraceptives.
  It is preferable to start taking Diane-35 the next 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-pili", injectable forms, implant) or from a progestogen-releasing intrauterine contraceptive.
  A woman can switch from a “mini-pill” to Diana-35 on any day (without a break), from an implant or an intrauterine contraceptive with a progestogen - on the day it is removed, from an injection form - from the day the next injection should have been made. In all cases, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the dragee.
• 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 on the 21-28th day after childbirth or abortion in the second trimester of pregnancy. If the reception is started later, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the pills. However, if a woman has already had a sexual life, pregnancy should be excluded before taking Diane-35, or it is necessary to wait for the first menstruation.

Taking missed pills

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

If the delay in taking the pill was 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 intake of dragees 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 was more than 12 hours (the interval from the moment the last pill was taken was more than 36 hours):

First week of taking the drug

The woman should take the last missed tablet as soon as she remembers (even if it means taking two tablets at the same time). The next dragee is taken at the usual time. Additionally, a barrier method of contraception (such as a condom) must be used for the next 7 days. If sexual intercourse took place within a week before skipping the dragee, the likelihood of pregnancy should be considered. The more pills 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

The woman should take the last missed tablet as soon as she remembers (even if it means taking two tablets at the same time). The next dragee is taken at the usual time.

Provided that the woman has taken the pill correctly within 7 days preceding the first missed pill, there is no need to use additional contraceptive measures. Otherwise, as well as skipping 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 a decrease in reliability is inevitable due to the upcoming break in taking pills.

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

1. The woman should take the last missed tablet as soon as she remembers (even if it means taking two tablets at the same time). The next dragee is taken at the usual time until the dragees 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 pills.
2. A woman can also stop taking pills from the current package. Then she should take a break for 7 days, including the day she skipped the dragee, and then start taking a new pack.

If a woman misses taking the pills, and then during the break in taking the pills she does not have withdrawal bleeding, pregnancy should be excluded.

Recommendations in case of vomiting and diarrhea
If a woman has had vomiting or diarrhea up to 4 hours after taking active pills, absorption may not be complete and additional contraceptive measures should be taken. In these cases, you should be guided by the recommendations when skipping the dragee.

Changing the start date of the menstrual cycle
In order to delay the onset of menstruation, a woman should continue taking the pills from the new Diane-35 package immediately after taking all the pills from the previous one, without interrupting the intake. Dragees 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. Resume taking Diane-35 from a new pack should be after the usual 7-day break.

In order to move the day of the onset of menstruation to another day of the week, a woman should be advised to shorten the next break in taking 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 have spotting and breakthrough bleeding during the second pack (as well as when she would like to delay the onset of her period.

Side effect
When taking combined oral contraceptives, irregular bleeding (spotting or breakthrough bleeding) may occur, especially during the first months of use. Against the background of taking combined oral contraceptives in women, other undesirable effects were observed.

Organ system	Often (≥1/100)	Uncommon (≥1/1000 and ≤1/100)	Rare (≤1/1000)
Organ of vision			contact lens intolerance
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 tissue		rash, hives	erythema nodosum, multiforme

As with other combined oral contraceptives, in rare cases, thrombosis and thromboembolism may develop (see also "Special Instructions").

Overdose
Serious violations in case of overdose have not been reported. Symptoms that may occur in overdose include nausea, vomiting, spotting or metrorrhagia. There is no specific antidote, symptomatic treatment should be carried out.

Interaction with other drugs
Interactions of oral contraceptives with other medicinal products may result in breakthrough bleeding and/or reduced contraceptive reliability. The following types of interaction 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. These 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 separate studies, some antibiotics (eg penicillins and tetracycline) can reduce the enterohepatic circulation of estrogens, thereby lowering the concentration of ethinyl estradiol.

While taking drugs that affect microsomal enzymes, and within 28 days after their withdrawal, you should additionally use a barrier method of contraception.

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

special instructions
If any of the conditions / risk factors listed below are currently present, then the potential risk and expected benefit 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, worsen, or first appear, the woman should consult her physician, 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 highest in the first year of taking these drugs. Approximate incidence of VTE among women taking low-dose oral contraceptives (The risk of thrombosis (venous and / or arterial) and thromboembolism is increased:

• 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 old); in the presence of:
• family history (i.e. venous or arterial thromboembolism ever in close relatives or parents at a relatively young age); in the case of a 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 over 30 kg/m);
• dyslipoproteinemia;
• arterial hypertension;
• migraine;
• heart valve disease;
• atrial fibrillation;
• prolonged immobilization, major surgery, any operation on the legs, or major trauma. In these situations, it is advisable to stop the use of combined oral contraceptives (in the case of a planned operation, at least four weeks before it) and not resume taking within two weeks after the end of immobilization.

The question of the possible role of varicose veins and superficial thrombophlebitis in the development of venous thromboembolism remains controversial. An increased risk of thromboembolism in the postpartum period should be taken into account. Peripheral circulatory disorders can 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 the use of combined oral contraceptives (which may precede cerebrovascular disorders) 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 relationship with the use of combined oral contraceptives has not been proven. Controversy remains as to 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 papillomavirus infection.

It has also been 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 after stopping these drugs. Its relationship with the use of combined oral contraceptives has not been proven. The observed increase in risk may also be due to earlier diagnosis of breast cancer in women using combined oral contraceptives. In women who have ever used combined oral contraceptives, earlier stages of breast cancer are detected than in women who have never used them. In rare cases, against the background of the use of combined oral contraceptives, the development of liver tumors was observed, which in some cases led to life-threatening intra-abdominal bleeding. In the event of severe pain in the abdomen, liver enlargement, or signs of intra-abdominal bleeding, 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 increase the risk of developing pancreatitis while taking combined oral contraceptives.

Although a slight increase in blood pressure has been described in many women taking combined oral contraceptives, clinically significant increases have been rare. However, if a persistent, clinically significant increase in blood pressure develops while taking combined oral contraceptives, these drugs should be discontinued and treatment of arterial 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 when taking combined oral contraceptives, but their relationship with taking combined oral contraceptives has not been proven: jaundice and / or itching associated with cholestasis; the formation of stones in the gallbladder; porphyria; systemic lupus erythematosus; hemolytic uremic syndrome; chorea; herpes of pregnant women; hearing loss associated with otosclerosis. Cases of Crohn's disease and ulcerative colitis have also been described with the use of combined oral contraceptives.

Occasionally, chloasma may develop, especially in women with a history of chloasma of pregnancy. Women with a tendency to chloasma while taking combined oral contraceptives should avoid prolonged exposure to the sun and exposure to ultraviolet radiation. Acute or chronic liver dysfunction may require the withdrawal of combined oral contraceptives until liver function returns 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 symptoms of recent or severe symptoms, there should be a differential diagnosis was made to identify a 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 the boundaries of 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, evaluation of any irregular bleeding should be done only after an adaptation period of approximately three cycles. If irregular bleeding recurs or develops after previous regular cycles, a thorough examination should be carried out to exclude malignant neoplasms or pregnancy.

Some women may not develop withdrawal bleeding during the pill break. If combined oral contraceptives were taken as directed, it is unlikely that the woman is pregnant. However, if combined oral contraceptives have been taken irregularly before, or if there are no consecutive withdrawal bleedings, pregnancy should be excluded before continuing to take the drug.

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

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

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

Influence on the ability to drive a car and machinery.
Not found.

Release form
Dragee. 21 tablets in a PVC and aluminum foil blister. 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 the expiration date!

Terms of dispensing from pharmacies
On prescription.

Manufacturer
Bayer Schering Pharma AG, manufactured 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.

Monophasic low-dose oral contraceptive containing cyproterone acetate - a progestogen with a pronounced antiandrogenic effect.

DIANA 35 - "Gold standard" in the treatment of androgen-dependent diseases in women:

• It relieves acne, especially common forms and forms accompanied by seborrhea, inflammation or the formation of nodules (papular-pustular acne, nodular cystic acne), androgenetic alopecia and mild forms of hirsutism. reduces skin greasiness.
• Well tolerated

INSTRUCTIONS FOR USE

Composition and form of release
coated dragees:
1 dragee contains ethinylestradiol 35 mcg and cyproterone acetate 2 mg; 21 pcs. packaged.

pharmachologic effect
Diane-35 is a combined low-dose monophasic oral contraceptive with an antiandrogenic effect, containing an estrogen - ethinyl estradiol and an antiandrogen with progestogenic activity - cyproterone acetate.

Cyproterone acetate contained in Diana-35 inhibits the influence of androgens, which are also produced in the female body. Thus, it becomes possible to treat diseases caused by increased production of androgens or specific sensitivity to these hormones.

Against the background of the reception, 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 of hair and skin disappears even earlier. It also reduces hair loss, which often accompanies seborrhea. Therapy of women of reproductive age reduces the clinical manifestations of mild forms of hirsutism; however, the effect of the treatment should be expected only after several months of use.

Cyproterone acetate also has a pronounced progestogenic effect.

The contraceptive effect is based on the interaction of various factors, the most important of which are the inhibition of ovulation and changes in the secretion of cervical mucus. The cycle becomes more regular, painful periods are less often observed, the intensity of bleeding decreases, as a result of which the risk of iron deficiency anemia decreases.

Indications
Contraception in women with androgenization phenomena;
Androgen-dependent diseases in women: acne (especially their pronounced forms, accompanied by seborrhea, inflammatory phenomena with the formation of nodes), androgenetic alopecia and mild forms of hirsutism.

contraceptive effect
Can be used for long-term contraception as the first choice, especially in women with acne, seborrhea, oily skin and excessive hairiness (hirsutism). If it is necessary to enhance the antiandrogenic effect, it can be combined with Androkur 10®. Before prescribing Diane-35® for contraception, there is no need for a special examination that differs from the usual examination before prescribing combined oral contraceptives. Medical examination of women taking Diana-35® is also carried out according to the usual scheme.


Therapeutic effect
Due to the antiandrogenic properties of Diana-35®. Clinically, the antiandrogenic effect is manifested in the elimination of acne, a decrease in the secretion of the sebaceous glands, an improvement in hair growth on the head, and a decrease in hair growth in androgen-dependent zones.

Dosage and administration
Diane-35 is taken orally 1 tablet per day. Dragees are taken without chewing and washed down with a small amount of liquid, at the same time, preferably after breakfast or dinner.

Reception begins on the 1st day of the cycle, using pills of the corresponding day of the week from the calendar package. After the end of taking all 21 pills from the calendar package, a break is made for 7 days, during which menstrual bleeding occurs. After 28 days from the start of taking the drug (21 days of admission and 7 days off), i.e. on the same day of the week as at the beginning of the course, continue taking the drug from the next package.

After abortion in the first trimester of pregnancy a woman can start taking the drug immediately. In this case, the woman does not need additional methods of contraception.

After childbirth or abortion in the second trimester of pregnancy taking the drug Diane-35 should be started on the 21-28th day. If the reception is started later, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the pills.

Missed dragee the woman should take it as soon as possible, the next pill is taken at the usual time. If the delay is less than 12 hours, the reliability of contraception does not decrease. If the delay in taking the pills was more than 12 hours, the reliability of contraception may be reduced. It should be borne in mind that the intake of dragees should never be interrupted for more than 7 days, and that 7 days of continuous intake of dragees are required to achieve adequate suppression of the function of the hypothalamic-pituitary-ovarian system.

If the delay in taking Diana 35 tablets was more than 12 hours (the interval from the moment of taking the last tablet is more than 36 hours) during the first and second weeks of taking the drug, then the woman should take the last missed tablet as soon as possible, as soon as she remembers (even if this means taking two pills at the same time). The next dragee is taken at the usual time. Additionally, you should use a barrier method of contraception for the next 7 days.

If the delay in taking the pill was more than 12 hours (the interval from the moment of taking the last pill is more than 36 hours) during the third week of taking the drug, then the woman should take the last missed pill as soon as she remembers (even if this means taking two pills at the same time ). The next dragee is taken at the usual time. In addition, taking pills from a new package should be started as soon as the current package is over, i.e. nonstop. The woman is most likely not to have withdrawal bleeding until the end of the second pack, but she may experience spotting or breakthrough bleeding on the days she takes the pills.

If a woman has had vomiting within 3 to 4 hours after taking Diana-35, absorption of the active substances may be incomplete. In this case, it is necessary to focus on the recommendations when skipping the dragee.

To delay the onset of menstruation, the woman should continue taking the pills from the new package immediately after all the pills from the previous one have been taken, without interruption in the reception. Dragees 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. Resume taking Diane-35 from a new package should be after the usual 7-day break.

To move your period to another day of the week, a woman should shorten the next break in taking Diane-35 dragees for as many days as she wants. The shorter the interval, the higher the risk that she will not have withdrawal bleeding and will have further spotting and breakthrough bleeding during the second pack (just as she would like to delay her period).

At treatment of hyperandrogenic conditions the duration of admission is determined by the severity of the disease. After the disappearance of symptoms, it is recommended to take Diana -35 for at least another 3-4 months. In the event of a relapse a few weeks or months after the completion of the course, repeated therapy can be performed.

Side effect
From the endocrine system: in rare cases - engorgement, soreness, enlargement of the mammary glands and discharge from them, changes in body weight.
From the reproductive system: in rare cases - intermenstrual bleeding, changes in vaginal secretions, 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).

These side effects may develop in the first few months of use and usually decrease over time.

Contraindications
- thrombosis and thromboembolism, incl. in history (deep vein thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular disorders);
- conditions preceding thrombosis (including transient ischemic attacks, angina pectoris);
- diabetes mellitus complicated by microangiopathies;
- the presence of severe or multiple risk factors for venous or arterial thrombosis;
- diseases or severe violations of the liver;
- liver tumors (including history);
- hormone-dependent malignant tumors, incl. tumors of the breast or genital organs (including history);
- uterine bleeding of unknown etiology;
- pancreatitis (including history), if it was accompanied by severe hypertriglyceridemia;
- the presence of a history of migraine, which was accompanied by focal neurological symptoms;
- lactation (breastfeeding);
- pregnancy or suspicion of it;
- Hypersensitivity to the components of the drug.

special instructions
Before starting the use of Diana 35, it is necessary to conduct a general medical examination (including the mammary glands and a cytological examination of cervical mucus), exclude pregnancy, disorders of the blood coagulation system. With prolonged use, preventive control examinations should be carried out every 6 months.

If risk factors are present, the potential risk and expected benefit of therapy should be carefully assessed and discussed with the woman before she decides to start taking Diana 35. If any of these conditions or risk factors worsen, or the first manifestation of any of these conditions or risk factors may require discontinuation of the drug .

The patient should be warned that with the development of symptoms of venous or arterial thrombosis, you should immediately consult a doctor. These symptoms include unilateral leg pain and/or swelling; sudden severe chest pain with or without radiating to the left arm; sudden shortness of breath; sudden onset of coughing; any unusual, severe, prolonged headache; increased frequency and severity of migraine; sudden partial or complete loss of vision; diplopia; slurred speech or aphasia; dizziness; collapse with/without partial seizure; weakness or very significant loss of sensation that suddenly appeared on one side or in one part of the body; movement disorders; symptom complex "acute" abdomen.

The relationship between taking combined oral contraceptives and arterial hypertension has not been established. If persistent arterial hypertension occurs, Diane-35 should be canceled and appropriate antihypertensive therapy prescribed. Reception of a contraceptive can be continued with the normalization of blood pressure.

If abnormal liver function occurs, temporary withdrawal may be required until laboratory parameters return to normal. Recurrent cholestatic jaundice that develops for the first time during pregnancy or previous use of sex hormones requires discontinuation of combined oral contraceptives.

Women with a tendency to chloasma while taking combined oral contraceptives should avoid prolonged exposure to the sun and exposure to ultraviolet radiation. If symptoms in women with hirsutism have developed recently or have increased significantly, other causes, such as an androgen-producing tumor, congenital adrenal dysfunction, should be considered in the differential diagnosis.

While taking Diane-35, irregular bleeding (spotting or breakthrough bleeding) can sometimes occur, especially during the first months of therapy. Therefore, any irregular bleeding should only be assessed after an adaptation period to Diana 35 of approximately 3 cycles. If irregular bleeding recurs or develops after previous regular cycles, then non-hormonal causes should be considered and adequate diagnostic measures taken to exclude malignant neoplasms or pregnancy. These may include diagnostic curettage.

In some cases, withdrawal bleeding may not develop during a break in taking the dragee. In case of irregular intake of pills or in the absence of two menstrual-like bleeding in a row, pregnancy should be excluded before continuing to take the drug.

drug interaction
With simultaneous use with inducers of microsomal hepatic enzymes (hydantoins, barbiturates, primidone, carbamazepine and rifampicin; and possibly with oxcarbazepine, topiramate, felbamate and griseofulvin), the clearance of ethinylestradiol and cyproterone increases, which can lead to breakthrough uterine bleeding or reduce the reliability of contraception . With simultaneous use with ampicillins and tetracyclines, the contraceptive reliability of Diane-35 is reduced.