Diane-35, 2 mg+0.035 mg 21 pcs

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

The cyproterone acetate contained in Diane-35 inhibits the effect of androgens, which are also produced in the female body. This makes it possible to treat diseases caused by an increased production of androgens or specific sensitivity to these hormones.

Diane-35 reduces the increased activity of sebaceous glands, 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 the hair and skin disappears even earlier. Hair loss, which often accompanies seborrhea, is also reduced. Diane-35 therapy in women of reproductive age reduces the clinical manifestations of mild forms of hirsutism; however, the effect of treatment should be expected only after several months of use.

In addition to the antiandrogenic effect described above, cyproterone acetate also has a pronounced gestagenic effect.

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

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

Cyproterone acetate

Absorption

After taking Diane-35, cyproterone acetate is completely absorbed from the gastrointestinal tract. Bioavailability is 88%. After oral administration of 1 tablet of Diane-35, the Cmax is reached after 1.6 h and is 15 ng/ml.

Distribution

Cyproterone acetate is almost completely bound to plasma albumin, approximately 3.5-4.0% is free. Since binding to proteins is non-specific, changes in the level of globulin binding sex steroids (GSSB) do not affect the pharmacokinetics of cyproterone acetate. Up to 0.2% of the dose of cyproterone acetate is excreted with breast milk.

Metabolism and excretion

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

Ethinylestradiol

Intake

Ethinylestradiol is quickly and completely absorbed from the gastrointestinal tract after administration of Diane-35. During absorption and “first passage” through the liver, ethinylestradiol undergoes intensive metabolism, which leads to a bioavailability of about 45%, and its significant individual variability. After ingestion of 1 tablet of Diane-35, Cmax is approximately 80 pg/mL and is reached after 1.7 h.

Distribution

The binding to plasma proteins (albumin) is high (2% is free in plasma). Vd is approximately 5 l/kg. Up to 0.02% of the dose of ethinylestradiol is excreted in breast milk. Ethinylestradiol increases hepatic synthesis of HSPC and CRC (corticosteroid-binding globulin) during continuous administration. During treatment with Diane-35, the serum concentration of HSPC increases from approximately 100 nmol/L to 300 nmol/L and the serum concentration of CRC increases from approximately 50 µg/mL to 95 µg/mL.

Metabolism and excretion

The pharmacokinetics of ethinylestradiol are biphasic, with a T1/2 of 1-2 h (α-phase) and approximately 20 h (β-phase), respectively. Plasma clearance is about 5 ml/min/kg. Ethinylestradiol is excreted from the body as metabolites; about 40% is excreted in the urine, 60% in the bile.

Indications

Acne, Hirsutism, Contraception

Contraception in women with androgenization phenomena; androgen-dependent diseases in women: acne (especially its pronounced forms accompanied by seborrhea, inflammatory phenomena with formation of nodules /papule-pustular acne, nodular-cystic acne/), androgenic alopecia and mild forms of hirsutism.

Active ingredient

Cyproterone, Ethinylestradiol

Composition

Active ingredients:

Ethinylestradiol 35 mcg and ciproterone acetate 2 mg;

Associate Ingredients:

Lactose monohydrate,

Corn starch,

Polividone 25,000,

magnesium stearate,

sucrose,

polyvidone 700,000,

macrogol 6000,

calcium carbonate precipitated,

talc,

glycerol 85%,

titanium dioxide,

iron oxide yellow,

iron oxide red,

monoglycol wax

How to take, the dosage

Diane-35 supplements should be taken orally in the order shown on the package, at about the same time every day, with a little water. One tablet per day is taken continuously for 21 days. The next package is taken after a 7-day break in the intake of the pills, during which you usually have a bleeding withdrawal. Bleeding usually begins 2 to 3 days after taking the last dose and may not end until the next dose.

The duration of administration depends on the severity of the symptoms of androgenism as well as their response to treatment. Generally, treatment should be continued for several months. Acne and seborrhea usually respond earlier than hirsutism or alopecia.

After symptoms subside, it is recommended that you take Diane-35 for at least 3-4 more cycles. If a relapse occurs in a few weeks or months after stopping the dragee, Diane-35 treatment can be resumed. If signs of androgenization recur after stopping treatment, 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.
  The intake of Diane-35 starts on the first day of the menstrual cycle (i.e. the first day of menstrual bleeding). It is allowed to start taking it on the 2nd-5th menstrual cycle, but in this case it is recommended to use an additional barrier method of contraception during the first 7 days of taking tablets 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 day after the usual 7-day break (for products containing 21 tablets).
  When changing from a contraceptive containing only gestagens (“mini-pills”, injectable forms, implant) or from a gestagen-releasing intrauterine device.
  A woman may change from a “mini-pill” to Diane-35 on any day (without a break), from an implant or intrauterine device with a gestagen – on the day of its removal, from an injectable form – from the day when the next injection would 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 delivery or abortion in the second trimester of pregnancy. It is recommended that the drug be started 21 to 28 days after childbirth or a second trimester abortion. If intake is started later, it is necessary to use additionally a barrier method of contraception during first 7 days of taking tablets. However, if a woman has already been sexually active, pregnancy must be ruled out or the first menstrual period must be awaited before taking Diane-35.

Missed dragees

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

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

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

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

The following advice may be given accordingly if the delay in taking the dragee is more than 12 hours (the interval since the last dragee was taken is more than 36 hours):

– First week of taking the drug

The woman should take the last missed dragee as soon as she remembers (even if that means taking two dragees at the same time). The next pill is taken at the usual time. Additionally, a barrier method of contraception (such as a condom) should be used for the next 7 days. If sexual intercourse took place during the week before skipping the pills, it is necessary to consider the possibility of pregnancy. The more the pills are missed, and the closer they are to a break in the active ingredient, the greater the chance of pregnancy.

– Second week of taking the medication

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

As long as the woman has taken the dragee correctly in the 7 days preceding the first missed dragee, no additional contraceptive measures are necessary. Otherwise, and if two or more pills are missed, additional barrier methods of contraception (e.g., a condom) should be used for 7 days.

– The third week of taking the drug

The risk of decreased reliability is inevitable because of the impending interruption in taking the pills.

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

1. Woman should take the last missed dragee as soon as she remembers (even if it means taking two dragees at the same time). The next jelly should be taken at the usual time until the jelly from the current pack is finished. The next pack should be started immediately. Bleeding cancellation is unlikely until the second pack is finished, but mucous discharge and breakthrough bleeding may occur while taking the dragee.
2. Women may also stop taking the dragee from the current pack. She should then take a break for 7 days, including the day she missed the dragee, and then start a new pack.

If a woman missed the dragee and then has no bleeding cancellation during the break in the dragee, pregnancy should be ruled out.

Recommendations for vomiting and diarrhea
If a woman has had vomiting or diarrhea within 4 hours of taking active pills, absorption may not be complete and additional contraceptive measures should be taken. In these cases, the recommendations for skipping the dragee should be followed.

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

In order to postpone the day her period starts to another day of the week, a woman should be advised to shorten the nearest break in taking the drag by as many days as she wants. The shorter the interval, the higher the risk that she won’t have a bleeding withdrawal and will subsequently have masticatory discharge and breakthrough bleeding while taking the second pack (just like when she would like to delay the start of her period.

Interaction

Interactions between oral contraceptives and other medications may result in breakthrough bleeding and/or decreased contraceptive reliability. The following types of interactions have been reported in the literature.

Influence on hepatic metabolism: the use of drugs that induce hepatic microsomal enzymes may lead to increased clearance of sex hormones. These drugs include: phenytoin, barbiturates, primidone, carbamazepine, rifampicin; there is also speculation about oxcarbazepine, topiramate, felbamate, ritonavir and griseofulvin and drugs containing St John’s wort.

Influence on intestinal-hepatic circulation: Some antibiotics (e.g., penicillins and tetracyclines) may decrease intestinal-hepatic circulation of estrogen, thereby decreasing the concentration of ethinylestradiol, according to separate studies.

When taking drugs that affect microsomal enzymes, and for 28 days after their withdrawal, an additional barrier method of contraception should be used.

When taking antibiotics (such as ampicillins and tetracyclines) and for 7 days after their withdrawal, an additional barrier method of contraception should be used. If the period of using a barrier method of contraception ends later than the pills in the package, you should proceed to the next package of Diane-35 without the usual break in the intake of pills. Oral combined contraceptives may affect the metabolism of other drugs (including cyclosporine), which leads to changes in their concentrations in plasma and tissues.

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Special Instructions

If any of the conditions/risk factors listed below are currently present, the potential risks and expected benefits of Diane-35 treatment should be carefully weighed on an individual basis and discussed with the woman before she decides to start taking the drug. If any of these conditions or risk factors worsen, intensify, or first appear, the woman should consult her physician, who can decide if the drug should be discontinued.

Cardiovascular disease
There is evidence of an increased incidence of venous and arterial thrombosis and thromboembolism (such as deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke) with combined oral contraceptives.

The risk of venous thromboembolism (VTE) is highest in the first year of use. The 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 more cigarettes or increased age, the risk further increases, especially in women over 35);

  in the presence of:

• family history (ie.е. venous or arterial thromboembolism ever in a close relative or parent at a relatively young age; if there is a hereditary predisposition, the woman should be seen by an appropriate specialist to decide whether to take combined oral contraceptives;
• dislipoproteinemia;
• arterial hypertension;
• migraine;
• heart valve disease;
• atrial fibrillation;
• prolonged immobilization, major surgery, any leg surgery, or extensive trauma. In these situations, it is advisable to discontinue the combined oral contraceptive (if surgery is planned, at least four weeks prior to surgery) and not to resume 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 thromboembolism in the postpartum period should be considered. Peripheral circulatory disorders may also occur in diabetes mellitus, systemic lupus erythematosus, hemolytic uremic syndrome, chronic inflammatory bowel disease (Crohn’s disease or nonspecific ulcerative colitis) and sickle cell anemia.

An increase in the frequency and severity of migraines during 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 some increased risk of cervical cancer with long-term use of combined oral contraceptives. The association with taking combined oral contraceptives has not been proven.

There remains controversy about the extent to which these findings are related to screening for cervical abnormalities or to patterns of sexual behavior (less frequent use of barrier methods of contraception). The most significant risk factor for 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 have used combined oral contraceptives. The increased risk gradually disappears over a 10-year period after stopping these drugs. Its association with the use of combined oral contraceptives has not been proven. The observed increase in risk may also be a consequence of earlier diagnosis of breast cancer in women using combined oral contraceptives. Women who have ever used combined oral contraceptives are detected earlier stages of breast cancer than women who have never used them. In rare cases, development of liver tumors has been observed during combined oral contraceptive use, which in some cases has led to life-threatening intra-abdominal bleeding. If severe abdominal pain, liver enlargement or signs of intra-abdominal bleeding occur, this should be considered in the differential diagnosis.

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

While small increases in blood pressure have been described in many women taking combined oral contraceptives, clinically significant increases have rarely been reported. However, if persistent, clinically significant increases in blood pressure develop while taking combined oral contraceptives, these medications should be discontinued and treatment for hypertension should be initiated.

The combined oral contraceptives may be continued if normal blood pressure values are achieved with hypotensive therapy.

The following conditions have been reported to develop or worsen both during pregnancy and while taking combined oral contraceptives, but their association with taking 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. Cases of Crohn’s disease and nonspecific ulcerative colitis have also been described with combined oral contraceptives.

Sometimes chloasma may develop, especially in women with a history of pregnancy chloasma. Women who are prone to chloasma while taking combined oral contraceptives should avoid prolonged sun exposure and exposure to ultraviolet radiation. Acute or chronic liver dysfunction may require withdrawal of combined oral contraceptives until liver function values return to normal. A recurrence of cholestatic jaundice that developed for the first time during pregnancy or previous use of sex hormones requires discontinuation of the combined oral contraceptives.

While 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 (

If a woman with hirsutism has recent or significant symptoms, a differential diagnosis should be made to identify a possible cause of the disease (androgen-producing tumor, adrenal enzyme deficiency).

Laboratory tests
The use of combined oral contraceptives may affect several laboratory tests, including liver, kidney, thyroid and adrenal function, plasma transport proteins, carbohydrate metabolism, coagulation and fibrinolysis parameters. The changes usually do not go beyond normal values.

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

Some women may not develop withdrawal bleeding during a break in the drags. If the combined oral contraceptives have been taken as directed, it is unlikely that the woman is pregnant. However, if the combined oral contraceptives have been taken irregularly before, or if there have not been two consecutive bleeding withdrawals, pregnancy must be ruled out before continuing the medication.

Medical examinations
Before starting Diane-35, a woman is recommended to undergo a thorough general medical and gynecological examination (including breast examination and cytological examination of cervical secretion), to rule out pregnancy. In addition, disorders of the blood clotting system should be excluded.

In case of long-term use of the drug, follow-up examinations should be performed every 6 months.

Warn women that Diane-35 does not protect against HIV infection (AIDS) or other sexually transmitted diseases!

The effect on the ability to drive and operate machinery.
Not identified.

Contraindications

• thrombosis and thromboembolism, including anamnesis (deep vein thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular disorders);
• states 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 marked liver dysfunction;
• liver tumors (includingч.
• hormone dependent malignant tumours including breast or genital tumours (including anamnesis);
• uterine bleeding of unclear etiology;
• pancreatitis (including anamnesis).
• pancreatitis (including anamnesis) if accompanied by severe hypertriglyceridemia;
• presence of a history of migraine accompanied by focal neurological symptoms;
• pregnancy (breastfeeding);
• pregnancy or suspected pregnancy;
• high sensitivity to the components of the drug.

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Side effects

Endocrine system disorders: in rare cases – engorgement, soreness, increase in mammary glands and discharge from them, changes in body weight.

The sexual system: in rare cases – intermenstrual bleeding, changes in the vaginal secretion, changes in libido.

CNS disorders: in rare cases – headache, migraine, decreased mood.

Digestive system disorders: in rare cases – nausea, vomiting.

Others: in very rare cases – poor tolerance of contact lenses, allergic reactions, appearance of pigment spots on the face (chloasma).

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

Overdose

Serious abnormalities have not been reported in overdose.

Symptoms that may be seen in overdose: nausea, vomiting, mucous bloody discharge or metrorrhagia.

There is no specific antidote, symptomatic treatment should be given.

Similarities

Chloe