Diane-35, pills, 21 pcs.

Composition

Active ingredients:

ethinyl estradiol 35 mcg and ciproterone acetate 2 mg;

Auxiliary substances:

lactose monohydrate,

corn starch,

polyvidone 25 000,

magnesium stearate,

sucrose,

polyvidone 700 000,

macrogol 6000,

calcium carbonate precipitated,

talc,

glycerol 85%,

titanium dioxide,

iron oxide yellow,

iron oxide red,

montaglycol wax

Pharmacological action

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

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

Against the background of taking Diane-35, the increased activity of the sebaceous glands decreases, which plays an important role in the occurrence of acne and seborrhea. After 3-4 months of therapy, this usually leads to the disappearance of the existing rash. Excessive greasiness 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 hirsutism; however, the effect of treatment should be expected only after several months of use.

Along with the above-described antiandrogenic effect of ciproterone acetate, it also has a pronounced progestogenic effect.

The contraceptive effect of Diana-35 is based on the interaction of various factors, the most important of which are inhibition of ovulation and changes in the secretion of cervical mucus.

The cycle becomes more regular, painful menstruation is less frequent, the intensity of bleeding decreases, and as a result, the risk of iron deficiency anemia decreases.

Pharmacokinetics

of Ciproterone Acetate

Suction

After taking Diane-35 ciproterone acetate, it is completely absorbed from the gastrointestinal tract. Bioavailability – 88%. After oral administration of 1 tablet of Diane-35, Cmax is reached in 1.6 hours and is 15 ng / ml.

Distribution

of Ciproterone acetate is almost completely bound to plasma albumin, approximately 3.5-4.0% is in the free state. Since protein binding is non-specific, changes in the level of sex steroid binding globulin (SHBG) do not affect the pharmacokinetics of ciproterone acetate. Up to 0.2% of the ciproterone acetate dose is excreted in breast milk.

Metabolism and elimination

The pharmacokinetics of ciproterone acetate are biphasic, with T1 / 2 being 0.8 hours and 2.3 days, respectively, for the first and second phases. Total plasma clearance is 3.6 ml / min / kg. Biotransformed by hydroxylation and conjugation, the main metabolite is a 15b-hydroxyl derivative. It is mainly excreted in the form of metabolites in the urine and bile in a ratio of 1: 2, a small part-in unchanged form with bile. T1 / 2 for metabolites of ciproterone acetate is 1.8 days.

Ethinyl Estradiol

Suction

After taking Diane-35, ethinyl estradiol is rapidly and completely absorbed from the gastrointestinal tract. In the process of absorption and “first passage” through the liver, ethinyl estradiol undergoes intensive metabolism, which causes a bioavailability of approximately 45%, and its significant individual variability. After oral administration of 1 tablet of Diane-35, Cmax is approximately 80 pg / ml and is reached in 1.7 hours.

Distribution

Binding to proteins (albumin) blood plasma content is high (2% is in free form in plasma). The Vd is approximately 5 l / kg. Up to 0.02% of the ethinyl estradiol dose is excreted in breast milk. Ethinyl Estradiol increases hepatic synthesis of SHBPS and CSG (corticosteroid-binding globulin) during continuous administration. During treatment with Diane-35, the serum SHBP concentration increases from approximately 100 nmol / L to 300 nmol/L and the serum CSG concentration increases from approximately 50 mcg / ml to 95 mcg/ml.

Metabolism and elimination

The pharmacokinetics of ethinyl estradiol are biphasic, with a T1 / 2 of 1-2 hours (alpha phase) and approximately 20 hours (beta phase), respectively. Plasma clearance is about 5 ml/min/kg. Ethinyl Estradiol is excreted from the body in the form of metabolites; about 40% – in the urine,60% – in the bile.

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 / papular-pustular acne, nodular-cystic acne/), androgenic alopecia and mild forms of hirsutism.

Contraindications

• thrombosis and thromboembolism, including history (deep venous thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular disorders);
• state prior thrombosis (including transient ischemic attack, angina);
• diabetes mellitus complicated by microvascular complications;
• the presence of a severe or multiple risk factors for venous or arterial thrombosis;
• disease or severe violations of liver function;
• liver tumors (including in the anamnesis);
• hormone-dependent malignant tumors including tumors of the breast or genital organs (including in the anamnesis);
• uterine bleeding of unknown etiology;
• pancreatitis (including in history), if it was accompanied by severe hypertriglyceridemia;
• 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.

Side effects

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

On the part of the reproductive system: in rare cases-intermenstrual bleeding, changes in vaginal secretions, changes in libido.

From 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 of contact lenses, allergic reactions, the appearance of pigmented spots on the face (chloasma).

These side effects may develop in the first few months of taking Diane-35 and usually decrease with time.

Interaction

Interaction of oral contraceptives with other medications can lead to breakthrough bleeding and / or reduced contraceptive reliability. The following types of interaction have been reported in the literature.

Effects on hepatic metabolism: the use of drugs that induce microsomal liver enzymes may 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 preparations containing St. John’s wort.

Effects on iohepatic circulation: Some antibiotics (such as penicillins and tetracycline) have been shown to reduce the iohepatic circulation of estrogens, thereby lowering the concentration of ethinyl estradiol.

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

When taking antibiotics (such as ampicillins and tetracyclines) and for 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 Diana-35 without the usual break in taking pills. Oral combined contraceptives can affect the metabolism of other drugs (including cyclosporine), which leads to changes in their concentration in plasma and tissues.

How to take it, course of administration and dosage

Dragee Diana-35 should be taken orally in the order indicated on the package, every day at about the same time, with a small amount of water. Take one tablet a day continuously for 21 days. Taking the next package begins after a 7-day break in taking pills, during which withdrawal bleeding usually occurs. Bleeding usually begins 2-3 days after taking the last tablet and may not end until the start of taking a new package.

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

After the symptoms have eased, 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 pills, treatment with Diana-35 can be resumed. If signs of androgenization recur after discontinuation of treatment, consideration should be given to resuming Diane-35 earlier.

How to start receiving Diana-35

• In the absence of taking any hormonal contraceptives in the previous month. Use of 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 pills for 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 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 drugs containing 21 tablets). When switching from progestogen-only contraceptives (“mini-pills”, injectable forms, implants) or from a progestogen-releasing intrauterine contraceptive. A woman can switch from “mini-pili” to Diana-35 on any day (without a break), from an implant or intrauterine contraceptive with a progestogen-on the day of its removal, from an injectable form-from the day when 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 pills.
• 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 giving birth or having an abortion in the second trimester of pregnancy. It is recommended to start taking the drug on 21-28 days after delivery 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 pills. However, if a woman has already had sexual activity, pregnancy should be excluded before taking Diana-35 or it is necessary to wait for the first menstruation.

Taking missed pills

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

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

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

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

Accordingly, the following tips can be given if the delay in taking pills is more than 12 hours (the interval from the moment of taking the last pill is more than 36 hours)::

* First week of taking the drug

A woman should take the last missed pill as soon as she remembers (even if it means taking two pills at the same time). The next tablet 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 during the week before skipping pills, it is necessary to take into account the probability of pregnancy. The more pills missed, and the closer they are to a break in taking active substances, the more likely pregnancy is.

* Second week of taking the drug

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

Provided that the woman took the pills 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 reduced reliability is inevitable due to the upcoming break in taking pills.

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

If a woman has missed taking pills, and then during a break in taking pills, she does not have withdrawal bleeding, it is necessary to exclude pregnancy.

Recommendations for vomiting and diarrhoea If a woman has had vomiting or diarrhoea within 4 hours of taking active pills, 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 day of the beginning of the menstrual cycle To delay the onset of menstruation, a woman should continue taking pills from the new package of Diana-35 immediately after taking all the pills from the previous one, without a break in reception. Pills from this new package can be taken as long as the woman wants (until the package is finished). Against the background of taking the drug from the second package, a woman may experience spotting or breakthrough uterine bleeding. Resume taking Diane-35 from the new pack after the usual 7-day break.

In order to move the day of the beginning of menstruation to another day of the week, a woman should be advised to shorten the next break in taking pills for 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.

Overdose

No serious overdose violations were reported.

Symptoms that may occur with an overdose: nausea, vomiting, spotting or metrorrhagia.

There is no specific antidote, and symptomatic treatment should be performed.

Special instructions

If any of the conditions / risk factors listed below are currently present, then the potential risk and expected benefit of treating Diana-35 should be carefully weighed on a case-by-case basis and discussed with the woman before she decides to start taking the drug. If any of these conditions or risk factors become more severe, worsen, or first appear, a woman should consult with her doctor, who may decide whether to discontinue the medication.

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 medications. The approximate incidence of VTE among women taking low-dose oral contraceptives (

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

• with age
• , smokers (with an increase in the number of cigarettes or an increase in age, the risk increases further, especially in women over 35 years of age).

  :

• family history (i. e. venous or arterial thromboembolism ever in close relatives or parents at a relatively young age); in the case of hereditary predisposition, the woman should be assessed appropriately skilled for the solution of the question about the possibility of using combined oral contraceptives;
• obesity (body mass index more than 30 kg/m );
• dyslipoproteinemia;
• hypertension;
• migraine;
• diseases of heart valves;
• atrial fibrillation;
• prolonged immobilization, major surgery, any surgery to the legs or major injury. 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 resume taking them 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. An increased risk of postpartum thromboembolism should be considered. Peripheral circulatory disorders can also occur with diabetes mellitus, systemic lupus erythematosus, hemolytic uremic syndrome, chronic inflammatory bowel diseases (Crohn’s disease or ulcerative colitis) and sickle cell anemia.

An increase in the frequency and severity of migraines during the use of combined oral contraceptives (which may precede cerebrovascular disorders) may be a reason for immediate discontinuation of these drugs. * Tumors There have been reports of some increased risk of cervical cancer with long-term use of combined oral contraceptives. The association with the use of combined oral contraceptives has not been proven.

There are still contradictions about the extent to which these findings are related to screening for cervical pathology or sexual behavior (more rarely, the use of barrier methods of contraception). The most significant risk factor for developing cervical cancer is persistent papilloma, a viral infection.

It also found that there was 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 discontinuation of these medications. Its association with the use of combined oral contraceptives has not been proven. The observed increased risk may also be a consequence of earlier breast cancer diagnosis in women using combined oral contraceptives. Women who have ever used combined oral contraceptives are more likely to develop early-stage breast cancer than women who have never used them. In rare cases, the use of combined oral contraceptives resulted in the development of liver tumors, which in some cases led to life-threatening intra-abdominal bleeding. If there is severe abdominal pain, enlarged liver, or signs of intra-abdominal bleeding, this should be taken into account when making a differential diagnosis.

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

Although a small increase in blood pressure has been reported in many women taking combined oral contraceptives, clinically significant increases have rarely been observed. However, if a persistent, clinically significant increase in blood pressure develops while taking combined oral contraceptives, these medications should be discontinued and treatment for hypertension should be initiated.

The use of combined oral contraceptives can be continued if normal blood pressure values are achieved with the help of antihypertensive therapy.

The following conditions have been reported to develop or worsen both during pregnancy and with combined oral contraceptives, but their association with combined oral contraceptives has not been proven: jaundice and/or pruritus associated with cholestasis; gallstone formation; porphyria; systemic lupus erythematosus; hemolytic uremic syndrome; Sydenham’s chorea; herpes of pregnancy; hearing loss associated with otosclerosis. There are also cases of Crohn’s disease and ulcerative colitis associated with the use of combined oral contraceptives.

Sometimes chloasma can develop, especially in women with a history of chloasma in pregnant women. Women with a tendency to chloasma should avoid prolonged exposure to the sun and exposure to ultraviolet radiation while taking combined oral contraceptives. Acute or chronic liver function disorders may require discontinuation of combined oral contraceptives until liver function indicators return to normal. Relapse of cholestatic jaundice, which first developed 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 suffering from hirsutism has recently developed symptoms or is significantly pronounced, a differential diagnosis should be made to identify the possible cause of the disease (androgen-producing tumor, adrenal enzyme deficiency).

Laboratory TESTSTHE use of combined oral contraceptives may affect the results of certain laboratory tests, including liver, kidney, thyroid, and adrenal function, plasma transport protein levels, carbohydrate metabolism, coagulation, and fibrinolysis parameters. Changes usually do not exceed the limits of normal values.

Effects on the menstrual cycle While taking combined oral contraceptives, irregular bleeding (spotting spotting or breakthrough bleeding) may occur, especially during the first months of use. Therefore, any irregular bleeding should only be evaluated after an adjustment period of approximately three cycles. If irregular bleeding recurs or develops after previous regular cycles, a thorough examination should be performed to rule out malignancies or pregnancy.

Some women may not develop withdrawal bleeding during a break from taking pills. If combined oral contraceptives were taken as directed, it is unlikely that the woman is pregnant. However, if previously combined oral contraceptives were taken on an irregular basis or if there are no consecutive withdrawal bleeds, pregnancy should be excluded before continuing the drug.

Medical examinationsbefore starting the use of the drug Diana-35, a woman is recommended to undergo a thorough general medical and gynecological examination (including breast examination and cytological examination of cervical secretions), to exclude pregnancy. In addition, violations 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 such as Diana-35 do not protect against HIV infection (AIDS) and other sexually transmitted diseases!

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

Form of production

Dragees

Storage conditions

At a temperature not exceeding 30°C. Keep out of reach of children.

Shelf

life is 5 years. Do not use after the expiration date!

Active ingredient

Ciproterone, Ethinyl Estradiol

Conditions of release from pharmacies

By prescription

Dosage form

of dragees

Purpose

For women of childbearing age, For adults as prescribed by a doctor

Indications

Hirsutism, Contraception, Acne, Seborrhea

Weight

Weight: 15 gr.