Cyproterone + Ethinylestradiol (Cyproteronum + Aethinyloestradiolum)

Pharmacodynamics Pharmacokinetics Indications Carefully Contraindications Dosing and Administration Side effects
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Clinical and pharmacological group: & nbsp

Androgens, antiandrogens

"Estrogens, gestagens, their homologues and antagonists"

Included in the formulation
  • MODELL® PIUR
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    • АТХ:

    G.03.H.B.01   Ciproterone and estrogen

    Pharmacodynamics:

    Monophasic combined contraceptive drug with antiandrogenic activity. It blocks the androgen receptors, inhibits the pituitary secretion of gonadotropic hormones. The mechanism of action is due to the anti-androgenic drug of the steroid structure - cyproterone acetate and oral estrogen preparation - ethinyl estradiol included in its composition.

    Ciproterone has the ability to compete with the receptors of natural male sex hormones, androgens (testosterone, dihydroepiandrosterone, androstenedione, etc.), formed in small amounts in the body of women, mainly in the adrenal glands, ovaries and skin. By blocking the androgen receptors in target organs, it reduces the phenomenon of androgenization in women (due to disruption of the processes mediated by hormone-receptor complexes at the level of the main intracellular mechanisms).Along with anti-androgenic properties, it possesses gestagenic activity that mimics the properties of the hormone of the yellow body.

    Cyproterone, like other drugs with gestagenic activity, inhibits the secretion of the pituitary gland by gonadotropic hormones and inhibits ovulation, which determines its contraceptive effect.

    Ethinyl estradiol strengthens the central and peripheral effects of cyproterone on ovulation, retains a high viscosity of the cervical mucus, which makes it difficult to penetrate the spermatozoon into the uterine cavity and helps to ensure a reliable contraceptive effect.

    Pharmacokinetics:

    Cyproterone. After oral administration, it is slowly absorbed from the digestive tract. The maximum concentration in the plasma is reached after 3-4 hours. The final half-life is about 38 hours. Cyproterone is metabolized in the liver. The main metabolite, 15β-hydroxyciproterone, possesses antiandrogenic activity. About 35% of the dose is excreted in the urine in the form of free and conjugated metabolites. The rest is excreted with feces.

    Ethinyl estradiol. When taken orally ethinyl estradiol quickly and completely absorbed. Maximum concentration in blood plasma, approximately 71 pg / ml, is achieved after 1.6 hours. During the absorption and first passage through the liver, the metabolism of ethinyl estradiol occurs, resulting in a bioavailability of about 45% when ingested.

    It binds to albumin (approximately 98%) and induces an increase in the concentration of globulin, which binds the sex hormones in the blood plasma. The equilibrium concentration is achieved in the second half of the intake cycle, when the concentration of the active substance in the blood serum is 60% higher compared with a single dose.

    Ethinyl estradiol undergoes presystemic conjugation, both in the mucosa of the small intestine and in the liver. Metabolized mainly by aromatic hydroxylation, with a large number of hydroxylated and methylated metabolites, both free and conjugates with glucuronides and sulfates. The clearance rate from plasma is 2.37 ml / min / kg.

    The concentration of ethinyl estradiol in serum is reduced in 2 phases with a half-life approximately 1 hour and 10-20 hours, respectively. Ethinylestradiol is not excreted from the body in an unchanged form, its metabolites are excreted by the kidneys and through the intestine in a ratio of 4: 6. Half-life metabolites is approximately 24 hours.

    Indications:

    Contraception in women with androgenation phenomena. Treatment of androgen-dependent diseases in women: moderate acne (especially common forms and shapes, accompanied by seborrhea, inflammation or formation of papulopustular or nodulocystic acne), androgenetic alopecia and mild forms of hirsutism.

    ICD-10

    XII.L20-L30.L21   Seborrheic dermatitis

    XII.L60-L75.L64   Androgenic alopecia

    XII.L60-L75.L68.0   Hirsutism

    XII.L60-L75.L70   Acne

    XXI.Z30-Z39.Z30.0   General advice and advice on contraception

    Contraindications:

    Hypersensitivity, pregnancy, liver failure, congenital hyperbilirubinemia (Gilbert syndrome, Dubin-Johnson and Rotor), liver tumors (hemangioma, liver cancer), thromboembolism (including history and an increased risk of its development), cerebrovascular disease (ischemic stroke, hemorrhagic stroke), coronary heart disease (severe), hypertension, atherosclerosis, heart disease, myocarditis,diabetes mellitus, retinopathy, angiopathy, sickle cell anemia, breast and endometrial cancer, fat metabolism disorders, idiopathic jaundice or pruritus during a former pregnancy, otosclerosis with worsening during pregnancy, age over 40 years, hyperprolactinaemia.

    Efficacy and safety of use in children have not been studied.

    Carefully:

    Diseases of the liver and gallbladder, epilepsy, depression, ulcerative colitis, uterine fibroids, mastopathy, chorea, tetany, porphyria, multiple sclerosis, varicose veins, tuberculosis, kidney disease, adolescence (without regular ovulatory cycles).

    Pregnancy and lactation:

    Category of recommendations for FDA is not defined. Contraindicated in pregnancy (before the therapy, women should undergo general medical and gynecological examination, the condition for the initiation of therapy is the absence of pregnancy). For the duration of treatment, breastfeeding should be stopped (penetrates into breast milk).

    Dosing and Administration:

    Inside 1 tablet a day, starting from the first day of the cycle (1 day of the cycle is 1 day of menstruation).Dragee is taken without chewing, washed down with a small amount of liquid. The time of reception does not matter, but the subsequent reception should be made at the same selected hour, preferably after breakfast or dinner. Duration of admission - 21 days, 7 days break.

    Treatment of phenomena of androgenization, as a rule, is long and requires many months of therapy (after the disappearance of the symptoms of the disease requires an additional 3-4 cycles). If a relapse occurs, a repeat course of therapy is possible. At low efficacy for 6 months of treatment of severe forms of acne or seborrhea, or 12 months of treatment with alopecia and hirsutism, cyproterone may be added to therapy. In the case of missing the reception to be taken in preparation for the next 12 hours. At the reception range over 36 hours is not guaranteed reliable contraceptive effect (it should be started to continue reception of the packaging in order to prevent the onset of premature menstruation associated with the cessation of drug administration). During this period it is recommended to use other non-hormonal methods of contraception (except for the Knaus-Ogino calendar method, as well as the temperature measurement method).

    Side effects:

    Headache, gastralgia, nausea, vomiting, breast engorgement, weight gain, changes in libido, decreased mood, intermenstrual bleeding, eyelid edema, skin rash, conjunctivitis, visual impairment, hearing loss, thrombophlebitis, thromboembolism, generalized itching, jaundice. With prolonged use - chloasma.

    Overdose:

    Symptoms, which can occur during an overdose: nausea, vomiting, vaginal bleeding.

    Treatment: There is no specific antidote, treatment is symptomatic.

    Interaction:

    Barbiturates, some antiepileptic drugs (carbamazepine, phenytoin) are able to enhance the metabolism of the steroid hormones that make up the drug.

    Reduction of the effective concentration is observed with simultaneous use with certain antibiotics (ampicillin, rifampicin), which is associated with a change in the microflora in the intestine.

    It may be necessary to correct the dosage regimen for hypoglycemic agents.

    Special instructions:

    It is possible to change the results of skin allergic tests, decrease the concentration of LH and FSH. In connection with the fact that the contraceptive effect is fully manifested by the 14th day from the beginning of admission,in the first 2 weeks it is recommended to additionally apply non-hormonal methods of contraception. Does not affect the course of puberty during the formation of a normal menstrual cycle (young and young women, if necessary, can use oral contraceptives of this type). The appointment after childbirth is recommended not earlier than the first normal menstrual cycle will pass. In cases of intermenstrual bleeding during the 3 weeks of taking the drug, the course should not be discontinued (as a rule, mild bleeding passes by itself). In the absence of bleeding in the period of 7-day interval between taking the drug, treatment should not continue until exclusion of suspicion of pregnancy.

    Before starting treatment and every 6 months of use of the drug, a general medical and gynecological examination (including breast examination) is recommended. Treatment should be stopped immediately after pregnancy, the development of migraine headaches (if they were not previously), the appearance of early signs of phlebitis or phlebotrombosis (unusual pain or bloating of the veins on the legs), with jaundice, visual impairment,cerebrovascular disorders, stinging pain of unclear etiology during breathing or coughing, pain and chest tightness, increasing blood pressure, and 3 months before the planned pregnancy and approximately 6 weeks before the planned surgical intervention, with prolonged immobilization. With diarrhea and vomiting, the contraceptive effect is reduced (without stopping the drug, it is necessary to use additional non-hormonal methods of contraception).

    Smoking women taking hormonal contraceptive drugs have an increased risk of developing vascular diseases with serious consequences (myocardial infarction, stroke). The risk increases with age and depending on the number of cigarettes smoked (especially in women over 30 years of age).

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