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

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

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

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.

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.

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:

in the presence of:

Contraindications

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.

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