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Active ingredients
Ziproterone + Ethinyl Estradiol
Release form
Dragee
Composition
Active ingredient: Tsiproteron (Cyproterone) + Ethinyl estradiol (Ethinylestradiol) Concentration of the active substance (mg): Cyproterone acetate - 2 mg, ethinyl estradiol - 0.035 mg
Pharmacological effect
The combined low-dose monophasic oral contraceptive with anti-androgenic effect, containing estrogen - ethinyl estradiol and anti-androgen with gestagen activity - cyproterone acetate. Cyproterone acetate, which is contained in Diane-35, inhibits the effect of androgens, which are also produced in the female body. Thus, it becomes possible to treat diseases caused by increased formation of androgens or specific sensitivity to these hormones. Against the background of taking Diane-35, the enhanced activity of the sebaceous glands, which plays an important role in the occurrence of acne and seborrhea, is reduced. After 3-4 months of therapy, this usually leads to the disappearance of the existing rash. Excessive oily hair and skin disappears even earlier. Hair loss that 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. Along with the above-described antiandrogenic effect, cyproterone acetate also has a pronounced gestagenic effect. Diane-35's contraceptive effect 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, less frequent painful menstruation, decreases the intensity of bleeding, resulting in reduced risk of glands deficiency anemia.
Pharmacokinetics
Cyproterone acetate Absorption After receiving Diane-35, cyproterone acetate is completely absorbed from the gastrointestinal tract. Bioavailability - 88%. After ingestion of 1 dragee Diane-35 Cmax is achieved in 1.6 h and amounts to 15 ng / ml. The distribution of Ciproterone acetate is almost completely bound to plasma albumin, approximately 3.5-4.0% is in a free state. Since protein binding is nonspecific, changes in the level of the globulin that binds sex steroids (GSPS) do not affect the pharmacokinetics of cyproterone acetate.With breast milk, up to 0.2% of the dose of cyproterone acetate is released. Metabolism and elimination The pharmacokinetics of cyproterone acetate are biphasic, T1 / 2 is 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 the 15β-hydroxyl derivative. It is derived mainly in the form of metabolites with urine and bile in the ratio of 1: 2, a small part - unchanged with bile. T1 / 2 for metabolites of cyproterone acetate is 1.8 days. Ethinyl estradiol Absorption 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 is extensively metabolized, which causes a bioavailability of approximately 45%, and its significant individual variability. After ingestion of 1 dragee Diane-35 Cmax is approximately 80 pg / ml and is achieved after 1.7 hours. The distribution of high blood plasma protein concentration (albumin) (2% is in plasma in free form). Vd is approximately 5 L / kg. With breast milk, up to 0.02% of ethinyl estradiol is excreted. Ethinyl estradiol increases hepatic synthesis of SHBG and CGC (corticosteroid-binding globulin) during continuous administration. With Diane-35 treatment, the serum SSG concentration increases from approximately 100 nmol / L to 300 nmol / L and the serum concentration of CSG increases from approximately 50 μg / ml to 95 μg / ml. Metabolism and excretion of ethinyl estradiol biphasic pharmacokinetics, with T1 / 2 1 -2 h (α phase) and approximately 20 h (β phase), respectively. Plasma clearance is about 5 ml / min / kg. Ethinyl estradiol is excreted in the form of metabolites; about 40% - with urine, 60% - with bile.
Indications
Contraception in women with androgenization. Treatment of androgen-dependent diseases in women, such as 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.
Contraindications
Thrombosis and thromboembolism, cerebrovascular disorders, identified acquired or hereditary susceptibility to venous or arterial thrombosis, including resistance to activated protein C, antithrombin III deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinemia,presence of a high risk of venous or arterial thrombosis, migraine with focal neurological symptoms, pancreatitis from severe hypertriglyceridemia, diabetes with vascular complications, hepatic failure, and severe liver disease, severe and / or acute renal failure, liver tumors (benign or malignant), identified hormone malignant neoplasms (including genital organs or mammary glands) or suspicion of them, bleeding from the vagina of unknown origin, pregnancy or suspicion of it, breastfeeding, hypersensitivity or intolerance to any of the components of the drug, hereditary lactose intolerance.
Precautionary measures
Do not exceed recommended doses.
Use during pregnancy and lactation
Diane-35 is contraindicated for use during pregnancy and lactation.
Dosage and administration
Diane-35 dragee 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 dragee a day continuously for 21 days.
Side effects
Mood swings, depression / depressed mood, migraine, nausea, pain in milk stores, uterine bleeding, decrease or loss of libido.
Overdose
Symptoms: nausea, vomiting, slight vaginal bleeding (in girls). Treatment: symptomatic therapy is carried out. There is no specific antidote.
Interaction with other drugs
With the simultaneous use of Diane-35 with inducers of microsomal liver enzymes (hydantoins, barbiturates, primidone, carbamazepine and rifampicin; and also, possibly, with oxcarbazepine, topimate, felbamate and griseofulvin), the clearance of ethinyl estradiol, aspirame, celbamate and griseofulvin) increases the clearance of ethinyl estradiol, aspirame, celbamate and griseofulvin), increases the clearance of ethinyl estradiol, aspirame, cypalbamate and griseofulvin) increases the clearance of ethinyl estradiol, aspirame, cypalbamate and griseofulvin) increases the clearance of ethinyl estradiol, aspirame, celbamate and griseofulvin) increases the clearance of ethinyl estradiol, aspirame, celbamate and griseofulvin), increases the clearance of ethynyl estradiol, aspirame, celbamate and griseofulvin. reducing the reliability of contraception. When used simultaneously with ampicillins and tetracyclines, the contraceptive reliability of Diane-35 is reduced.
special instructions
Before starting to use Diane-35, it is necessary to conduct a general medical examination (including the mammary glands and cytological examination of cervical mucus), to exclude pregnancy, disorders of the blood coagulation system.With long-term use of the drug, prophylactic follow-up examinations should be carried out every 6 months. If there are risk factors, the potential risk and expected benefits of therapy should be carefully evaluated and discussed with the woman before she decides to start taking the drug. When weighting, amplification, or the first manifestation of any of these conditions or risk factors, you may need to cancel the drug. The approximate frequency of venous thromboembolism (VTE) when taking oral contraceptives with a low dose of estrogen (less than 50 μg of ethinyl estradiol) is up to 4 per 10,000 women per year compared with 0.5–3 per 10,000 women who do not take oral contraceptives. At the same time, the frequency of VTE when taking combined oral contraceptives is less than the frequency of VTE associated with pregnancy (6 per 10,000 pregnant women per year). The patient should be warned that if symptoms of venous or arterial thrombosis develop, you should immediately consult a doctor. These symptoms include unilateral pain in the leg and / or swelling; sudden severe chest pain radiating to the left hand or without irradiation; sudden shortness of breath; sudden coughing up any unusual, severe, prolonged headache; increased frequency and severity of migraine; sudden partial or complete loss of vision; diplopia; inarticulate speech or aphasia; dizziness; collapse with / without partial seizure; weakness or a very significant loss of sensitivity, suddenly appearing 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 anti-hypertensive therapy should be prescribed. Intake of contraceptive can be continued with the normalization of blood pressure. In case of abnormal liver function, it may be necessary to temporarily cancel Diane-35 until the laboratory parameters normalize. Recurrent cholestatic jaundice, which develops for the first time during pregnancy or previous sex hormones, requires the discontinuation of combined oral contraceptives. Although combined oral contraceptives affect insulin resistance and glucose tolerance, it is usually not necessary to correct the dose of sugar-lowering drugs in sugar patients who need sugar to correct them. .Nevertheless, this category of patients should be under close medical supervision. Women with a tendency to chloasma while taking combined oral contraceptives should avoid prolonged exposure to the sun and exposure to ultraviolet radiation. If women with hirsutism develop symptoms recently or have significantly increased, during the differential diagnosis should take into account other causes, such as androgen-producing tumor, congenital dysfunction of the adrenal cortex. Against the background of taking D In occasional 35s, irregular bleeding (spotting or breakthrough bleeding) may occur, especially during the first months of therapy. Therefore, any irregular bleeding should be assessed only after an adaptation period of approximately 3 cycles. If irregular bleeding recurs or develops after previous regular cycles, non-hormonal causes should be considered and adequate diagnostic measures should be taken to exclude malignant neoplasms or pregnancy. They may include diagnostic curettage. In some cases, withdrawal bleeding may not develop during a break in taking the pills. In case of irregular pills or in the absence of two menstrual bleeding in a row, pregnancy should be excluded before continuing to take the drug.